AntiS-RBD antibodies come from a humoral-type immune response following contact with SARS-CoV-2. Their role will be to prevent the virus, on second contact, from penetrating the cells by inhibiting its binding to the ACE2 receptor. Replication will no longer be possible and the infection will be stopped.

Brief Communication Published 29 April 2020 Bai-Zhong Liu2 na1, Hai-Jun Deng ORCID na1, Gui-Cheng Wu3,4 na1, Kun Deng5 na1, Yao-Kai Chen6 na1, Pu Liao7, Jing-Fu Qiu8, Yong Lin ORCID Xue-Fei Cai1, De-Qiang Wang1, Yuan Hu1, Ji-Hua Ren1, Ni Tang1, Yin-Yin Xu2, Li-Hua Yu2, Zhan Mo2, Fang Gong2, Xiao-Li Zhang2, Wen-Guang Tian2, Li Hu2, Xian-Xiang Zhang3,4, Jiang-Lin Xiang3,4, Hong-Xin Du3,4, Hua-Wen Liu3,4, Chun-Hui Lang3,4, Xiao-He Luo3,4, Shao-Bo Wu3,4, Xiao-Ping Cui3,4, Zheng Zhou3,4, Man-Man Zhu5, Jing Wang6, Cheng-Jun Xue6, Xiao-Feng Li6, Li Wang6, Zhi-Jie Li7, Kun Wang7, Chang-Chun Niu7, Qing-Jun Yang7, Xiao-Jun Tang8, Yong Zhang ORCID Xia-Mao Liu9, Jin-Jing Li9, De-Chun Zhang10, Fan Zhang10, Ping Liu11, Jun Yuan1, Qin Li12, Jie-Li Hu ORCID Juan Chen ORCID & …Ai-Long Huang ORCID Nature Medicine volume 26, pages 845–848 2020Cite this article 824k Accesses 5536 Citations 4038 Altmetric Metrics details Subjects AbstractWe report acute antibody responses to SARS-CoV-2 in 285 patients with COVID-19. Within 19 days after symptom onset, 100% of patients tested positive for antiviral immunoglobulin-G IgG. Seroconversion for IgG and IgM occurred simultaneously or sequentially. Both IgG and IgM titers plateaued within 6 days after seroconversion. Serological testing may be helpful for the diagnosis of suspected patients with negative RT–PCR results and for the identification of asymptomatic infections. MainThe continued spread of coronavirus disease 2019 COVID-19 has prompted widespread concern around the world, and the World Health Organization WHO, on 11 March 2020, declared COVID-19 a pandemic. Studies on severe acute respiratory syndrome SARS and Middle East respiratory syndrome MERS showed that virus-specific antibodies were detectable in 80–100% of patients at 2 weeks after symptom onset1,2,3,4,5,6. Currently, the antibody responses against SARS-CoV-2 remain poorly understood and the clinical utility of serological testing is total of 285 patients with COVID-19 were enrolled in this study from three designated hospitals; of these patients, 70 had sequential samples available. The characteristics of these patients are summarized in Supplementary Tables 1 and 2. We validated and used a magnetic chemiluminescence enzyme immunoassay MCLIA for virus-specific antibody detection Extended Data Fig. 1a–d and Supplementary Table 3. Serum samples from patients with COVID-19 showed no cross-binding to the S1 subunit of the SARS-CoV spike antigen. However, we did observe some cross-reactivity of serum samples from patients with COVID-19 to nucleocapsid antigens of SARS-CoV Extended Data Fig. 1e. The proportion of patients with positive virus-specific IgG reached 100% approximately 17–19 days after symptom onset, while the proportion of patients with positive virus-specific IgM reached a peak of approximately 20–22 days after symptom onset Fig. 1a and Methods. During the first 3 weeks after symptom onset, there were increases in virus-specific IgG and IgM antibody titers Fig. 1b. However, IgM showed a slight decrease in the >3-week group compared to the ≤3-week group Fig. 1b. IgG and IgM titers in the severe group were higher than those in the non-severe group, although a significant difference was only observed in IgG titer in the 2-week post-symptom onset group Fig. 1c, P = 1 Antibody responses against Graph of positive rates of virus-specific IgG and IgM versus days after symptom onset in 363 serum samples from 262 patients. b, Levels of antibodies against SARS-CoV-2 in patients at different times after symptom onset. c, Comparison of the level of antibodies against SARS-CoV-2 between severe and non-severe patients. The boxplots in b and c show medians middle line and third and first quartiles boxes, while the whiskers show the interquartile range IQR above and below the box. Numbers of patients N are shown underneath. P values were determined with unpaired, two-sided Mann–Whitney DataFull size imageSixty-three patients with confirmed COVID-19 were followed up until discharge. Serum samples were collected at 3-day intervals. Among these, the overall seroconversion rate was 61/63 over the follow-up period. Two patients, a mother and daughter, maintained IgG- and IgM-negative status during hospitalization. Serological courses could be followed for 26 patients who were initially seronegative and then underwent seroconversion during the observation period. All these patients achieved seroconversion of IgG or IgM within 20 days after symptom onset. The median day of seroconversion for both IgG and IgM was 13 days post symptom onset. Three types of seroconversion were observed synchronous seroconversion of IgG and IgM nine patients, IgM seroconversion earlier than that of IgG seven patients and IgM seroconversion later than that of IgG ten patients Fig. 2a. Longitudinal antibody changes in six representative patients of the three types of seroconversion are shown in Fig. 2b–d and Extended Data Fig. 2a– 2 Seroconversion time of the antibodies against Seroconversion type of 26 patients who were initially seronegative during the observation period. The days of seroconversion for each patient are plotted. b–d, Six representative examples of the three seroconversion type synchronous seroconversion of IgG and IgM b, IgM seroconversion earlier than that of IgG c and IgM seroconversion later than that of IgG c.Full size imageIgG levels in the 19 patients who underwent IgG seroconversion during hospitalization plateaued 6 days after the first positive IgG measurement Extended Data Fig. 3. Plateau IgG levels varied widely more than 20-fold across patients. IgM also showed a similar profile of dynamic changes Extended Data Fig. 4. We found no association between plateau IgG levels and the clinical characteristics of the patients Extended Data Fig. 5a–d. We next analyzed whether the criteria for confirmation of MERS-CoV infection recommended by WHO, including 1 seroconversion or 2 a fourfold increase in IgG-specific antibody titers, are suitable for the diagnosis of COVID-19 using paired samples from 41 patients. The initial sample was collected in the first week of illness and the second was collected 2–3 weeks later. Of the patients whose IgG was initially seronegative in the first week of illness, 21/41 underwent seroconversion. A total of 18 patients were initially seropositive in the first week of illness; of these, eight patients had a fourfold increase in virus-specific IgG titers Extended Data Fig. 6. Overall, 29/41 of the patients with COVID-19 met the criteria of IgG seroconversion and/or fourfold increase or greater in the IgG investigate whether serology testing could help identify patients with COVID-19, we screened 52 suspected cases in patients who displayed symptoms of COVID-19 or abnormal radiological findings and for whom testing for viral RNA was negative in at least two sequential samples. Of the 52 suspected cases, four had virus-specific IgG or IgM in the initial samples Extended Data Fig. 7. Patient 3 had a greater than fourfold increase in IgG titer 3 days after the initial serology testing. Interestingly, patient 3 also tested positive for viral infection by polymerase chain reaction with reverse transcription RT–PCR between the two antibody measurements. IgM titer increased over three sequential samples from patient 1 1 was defined as positive and S/CO ≤ 1 as of IgG and IgM against SARS-CoV-2To measure the level of IgG and IgM against SARS-CoV-2, serum samples were collected from the patients. All serum samples were inactivated at 56 °C for 30 min and stored at −20 °C before testing. IgG and IgM against SARS-CoV-2 in plasma samples were tested using MCLIA kits supplied by Bioscience Co. approved by the China National Medical Products Administration; approval numbers 20203400183IgG and 20203400182IgM, according to the manufacturer’s instructions. MCLIA for IgG or IgM detection was developed based on a double-antibody sandwich immunoassay. The recombinant antigens containing the nucleoprotein and a peptide from the spike protein of SARS-CoV-2 were conjugated with FITC and immobilized on anti-FITC antibody-conjugated magnetic particles. Alkaline phosphatase conjugated anti-human IgG/IgM antibody was used as the detection antibody. The tests were conducted on an automated magnetic chemiluminescence analyzer Axceed 260, Bioscience according to the manufacturer’s instructions. All tests were performed under strict biosafety conditions. The antibody titer was tested once per serum sample. Antibody levels are presented as the measured chemiluminescence values divided by the cutoff S/CO. The cutoff value of this test was defined by receiver operating characteristic curves. Antibody levels in the figures were calculated as log2S/CO + 1.Performance evaluation of the SARS-CoV-2-specific IgG/IgM detection assayThe precision and reproducibility of the MCLIA kits were first evaluated by the National Institutes for Food and Drug Control. Moreover, 30 serum samples from patients with COVID-19 showing different titers of IgG range and IgM range were tested. Each individual sample was tested in three independent experiments, and the coefficient of variation CV was used to evaluate the precision of the assay. Finally, 46 serum samples from patients with COVID-19 were assessed using different batches of the diagnostic kit for SARS-CoV-2-specific IgG or IgM antibody; reproducibility was calculated based on the results from two batch of antigens from SARS-CoV and SARS-CoV-2Two recombinant SARS-CoV nucleocapsid N proteins from two different sources Sino Biological, cat. no. 40143-V08B; Biorbyt, cat. no. orb82478, the recombinant S1 subunit of the SARS-CoV spike Sino Biological, cat. no. 40150-V08B1 and the homemade recombinant N protein of SARS-CoV-2 were used in a chemiluminescence enzyme immunoassay CLEIA, respectively. The concentration of antigens used for plate coating was μg ml−1. The dilution of alkaline phosphatase conjugated goat anti-human IgG antibody was 12,500. Five serum samples from patients with COVID-19 and five serum samples from healthy controls were diluted 150 and tested using CLEIA assays. The binding ability of antibody to antigen in a sample was measured in relative luminescence analysesContinuous variables are expressed as the median IQR and were compared with the Mann–Whitney U-test. Categorical variables are expressed as numbers % and were compared by Fisher’s exact test. A P value of < was considered statistically significant. Statistical analyses were performed using R software, version approvalThe study was approved by the Ethics Commission of Chongqing Medical University ref. no. 2020003. Written informed consent was waived by the Ethics Commission of the designated hospital for emerging infectious SummaryFurther information on research design is available in the Nature Research Reporting Summary linked to this article. Data availabilityRaw data in this study are provided in the Supplementary Dataset. Additional supporting data are available from the corresponding authors on request. All requests for raw and analyzed data and materials will be reviewed by the corresponding authors to verify whether the request is subject to any intellectual property or confidentiality obligations. Source data for Fig. 1 and Extended Data Figs. 1 and 5 are available V. M. et al. Viral shedding and antibody response in 37 patients with Middle East respiratory syndrome coronavirus infection. Clin. Infect. Dis. 62, 477–483 2016.CAS PubMed Google Scholar Li, G., Chen, X. & Xu, A. Profile of specific antibodies to the SARS-associated coronavirus. N. Engl. J. Med. 349, 508–509 2003.Article Google Scholar Hsueh, P. R., Huang, L. M., Chen, P. J., Kao, C. L. & Yang, P. C. Chronological evolution of IgM, IgA, IgG and neutralisation antibodies after infection with SARS-associated coronavirus. Clin. Microbiol. Infect. 10, 1062–1066 2004.Article Google Scholar Park, W. B. et al. Kinetics of serologic responses to MERS coronavirus infection in humans, South Korea. Emerg. Infect. Dis. 21, 2186–2189 2015.Article CAS Google Scholar Drosten, C. et al. Transmission of MERS-coronavirus in household contacts. N. Engl. J. Med. 371, 828–835 2014.Article Google Scholar Meyer, B., Drosten, C. & Muller, M. A. Serological assays for emerging coronaviruses challenges and pitfalls. Virus Res. 194, 175–183 2014.Article CAS Google Scholar Tang, Y. W., Schmitz, J. E., Persing, D. H. & Stratton, C. W. The laboratory diagnosis of COVID-19 infection current issues and challenges. J. Clin. Microbiol. 2020.Zou, L. et al. SARS-CoV-2 viral load in upper respiratory specimens of infected patients. N. Engl. J. Med. 382, 1177–1179 2020.Article Google Scholar Download referencesAcknowledgementsWe thank Yang and Kwan for critical reviewing of the manuscript. This work was supported by the Emergency Project from the Science & Technology Commission of Chongqing and a Major National S&T Program grant 2017ZX10202203 and 2017ZX10302201 from the Science & Technology Commission of informationAuthor notesThese authors contributed equally Quan-Xin Long, Bai-Zhong Liu, Hai-Jun Deng, Gui-Cheng Wu, Kun Deng, Yao-Kai and AffiliationsKey Laboratory of Molecular Biology on Infectious Diseases, Ministry of Education, Chongqing Medical University, Chongqing, ChinaQuan-Xin Long, Hai-Jun Deng, Yong Lin, Xue-Fei Cai, De-Qiang Wang, Yuan Hu, Ji-Hua Ren, Ni Tang, Jun Yuan, Jie-Li Hu, Juan Chen & Ai-Long HuangYongchuan Hospital Affiliated to Chongqing Medical University, Chongqing, ChinaBai-Zhong Liu, Yin-Yin Xu, Li-Hua Yu, Zhan Mo, Fang Gong, Xiao-Li Zhang, Wen-Guang Tian & Li HuChongqing University Three Gorges Hospital, Chongqing, ChinaGui-Cheng Wu, Xian-Xiang Zhang, Jiang-Lin Xiang, Hong-Xin Du, Hua-Wen Liu, Chun-Hui Lang, Xiao-He Luo, Shao-Bo Wu, Xiao-Ping Cui & Zheng ZhouChongqing Three Gorges Central Hospital, Chongqing, ChinaGui-Cheng Wu, Xian-Xiang Zhang, Jiang-Lin Xiang, Hong-Xin Du, Hua-Wen Liu, Chun-Hui Lang, Xiao-He Luo, Shao-Bo Wu, Xiao-Ping Cui & Zheng ZhouThe Third Hospital Affiliated to Chongqing Medical University, Chongqing, ChinaKun Deng & Man-Man ZhuDivision of Infectious Diseases, Chongqing Public Health Medical Center, Chongqing, ChinaYao-Kai Chen, Jing Wang, Cheng-Jun Xue, Xiao-Feng Li & Li WangLaboratory Department, Chongqing People’s Hospital, Chongqing, ChinaPu Liao, Zhi-Jie Li, Kun Wang, Chang-Chun Niu & Qing-Jun YangSchool of Public Health and Management, Chongqing Medical University, Chongqing, ChinaJing-Fu Qiu, Xiao-Jun Tang & Yong ZhangThe Second Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaXia-Mao Liu & Jin-Jing LiWanzhou People’s Hospital, Chongqing, ChinaDe-Chun Zhang & Fan ZhangBioScience Co. Ltd, Chongqing, ChinaPing LiuChongqing Center for Disease Control and Prevention, Chongqing, ChinaQin LiAuthorsQuan-Xin LongYou can also search for this author in PubMed Google ScholarBai-Zhong LiuYou can also search for this author in PubMed Google ScholarHai-Jun DengYou can also search for this author in PubMed Google ScholarGui-Cheng WuYou can also search for this author in PubMed Google ScholarKun DengYou can also search for this author in PubMed Google ScholarYao-Kai ChenYou can also search for this author in PubMed Google ScholarPu LiaoYou can also search for this author in PubMed Google ScholarJing-Fu QiuYou can also search for this author in PubMed Google ScholarYong LinYou can also search for this author in PubMed Google ScholarXue-Fei CaiYou can also search for this author in PubMed Google ScholarDe-Qiang WangYou can also search for this author in PubMed Google ScholarYuan HuYou can also search for this author in PubMed Google ScholarJi-Hua RenYou can also search for this author in PubMed Google ScholarNi TangYou can also search for this author in PubMed Google ScholarYin-Yin XuYou can also search for this author in PubMed Google ScholarLi-Hua YuYou can also search for this author in PubMed Google ScholarZhan MoYou can also search for this author in PubMed Google ScholarFang GongYou can also search for this author in PubMed Google ScholarXiao-Li ZhangYou can also search for this author in PubMed Google ScholarWen-Guang TianYou can also search for this author in PubMed Google ScholarLi HuYou can also search for this author in PubMed Google ScholarXian-Xiang ZhangYou can also search for this author in PubMed Google ScholarJiang-Lin XiangYou can also search for this author in PubMed Google ScholarHong-Xin DuYou can also search for this author in PubMed Google ScholarHua-Wen LiuYou can also search for this author in PubMed Google ScholarChun-Hui LangYou can also search for this author in PubMed Google ScholarXiao-He LuoYou can also search for this author in PubMed Google ScholarShao-Bo WuYou can also search for this author in PubMed Google ScholarXiao-Ping CuiYou can also search for this author in PubMed Google ScholarZheng ZhouYou can also search for this author in PubMed Google ScholarMan-Man ZhuYou can also search for this author in PubMed Google ScholarJing WangYou can also search for this author in PubMed Google ScholarCheng-Jun XueYou can also search for this author in PubMed Google ScholarXiao-Feng LiYou can also search for this author in PubMed Google ScholarLi WangYou can also search for this author in PubMed Google ScholarZhi-Jie LiYou can also search for this author in PubMed Google ScholarKun WangYou can also search for this author in PubMed Google ScholarChang-Chun NiuYou can also search for this author in PubMed Google ScholarQing-Jun YangYou can also search for this author in PubMed Google ScholarXiao-Jun TangYou can also search for this author in PubMed Google ScholarYong ZhangYou can also search for this author in PubMed Google ScholarXia-Mao LiuYou can also search for this author in PubMed Google ScholarJin-Jing LiYou can also search for this author in PubMed Google ScholarDe-Chun ZhangYou can also search for this author in PubMed Google ScholarFan ZhangYou can also search for this author in PubMed Google ScholarPing LiuYou can also search for this author in PubMed Google ScholarJun YuanYou can also search for this author in PubMed Google ScholarQin LiYou can also search for this author in PubMed Google ScholarJie-Li HuYou can also search for this author in PubMed Google ScholarJuan ChenYou can also search for this author in PubMed Google ScholarAi-Long HuangYou can also search for this author in PubMed Google ScholarContributionsConceptualization was provided by The methodology was developed by P. Liu, and Investigations were carried out by and The original draft of the manuscript was written by and Review and editing of the manuscript were carried out by and Funding acquisition was performed by and Resources were provided by P. Liao, . and provided authorsCorrespondence to Jie-Li Hu, Juan Chen or Ai-Long declarations Competing interests The authors declare no competing interests. Additional informationPeer review information Saheli Sadanand was the primary editor on this article and managed its editorial process and peer review in collaboration with the rest of the editorial note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional dataExtended Data Fig. 1 The performance evaluation of the SARS-CoV-2 specific IgG/IgM detection Thirty serum sample from COVID-19 patients showing different titers of IgG a range from to and IgM b range from to were tested. Each individual sample was tested in three independent experiment. CVs of titers of certain sample were calculated and presented. c,d. The correlation analysis of IgG and IgM titers serum samples from COVID-19 patients from 2 independent experiment. Forty-six serum samples from COVID-19 patients were detected using different batches of diagnostic kit for SARS-CoV-2 IgG c or IgM d antibody. Pearson correlation coefficients R are depicted in plots. For IgG, r = p = For IgM, r = p = e. The reactivity between COVID-19 patient serums N = 5 and SARS-CoV S1, N two sources and SARS-CoV-2 N protein were measured by ELISA. Serum samples from COVID-19 patients showed no cross-binding to SARS-CoV S1 antigen, while the reactivity between COVID-19 patient serums and SARS-CoV N antigen from different sources was inconsistent. Source Data Extended Data Fig. 2 Three types of Patients with a synchronous seroconversion of IgG and IgM N = 7. b. Seroconversion for IgG occurred later than that for IgMN = 5. c. Seroconversion for IgG occurred earlier than that for IgM N = 8.Extended Data Fig. 3 Dynamic changes of the SARS-CoV-2 specific course of the virus-specific IgG level in 19 patients experienced IgG titer plateau. IgG in each patient reached plateau within 6 days since IgG became Data Fig. 4 Dynamic changes of the SARS-CoV-2 specific course of the virus-specific IgM level in 20 patients experienced IgM titer plateau. IgM in each patient reached plateau within 6 days since IgM became Data Fig. 5 The association between the IgG levels at the plateau and clinical characteristics of the COVID-19 No significant difference in the IgG levels at the plateau was found between < 60 y group N = 11 and ≥ 60 y group N = 9. Unpaired, two-sided Mann-Whitney U test, p = b–d. No association was found between the IgG levels at the plateau and lymphocyte count b or CRP c or hospital stay d of the patients N = 20. Pearson correlation coefficients r and p value are depicted in plots. Source Data Extended Data Fig. 6 The assessment of MERS serological criteria for assessment of MERS serological criteria for COVID-19 confirmation were carried out in 41 patients with sequential samples. All 41 patients were classified into three groups based on IgG change from sequential samples, including 1 seroconversion, 2 fold change ≥ 4-fold in paired samples, 3 Data Fig. 7 Serology testing in identification of COVID-19 from 52 suspected of symptom onset, RT-PCR and serology testing in 4 cases developing positive IgG or/and IgM were Data Fig. 8 Serological survey in close contacts with COVID-19 cluster of 164 close contacts of known COVID-19 patients were tested by RT-PCR followed by serology testing. Serum samples were collected from these 164 individuals for antibody tests approximately 30 days after informationSource dataRights and permissionsAbout this articleCite this articleLong, QX., Liu, BZ., Deng, HJ. et al. Antibody responses to SARS-CoV-2 in patients with COVID-19. Nat Med 26, 845–848 2020. citationReceived 24 March 2020Accepted 22 April 2020Published 29 April 2020Issue Date June 2020DOI This article is cited by
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IntroductionIt has been more than one year since the first reported case of the novel coronavirus disease 2019 COVID-19, which has already cost more than 2 million lives Fortunately, vaccines against severe acute respiratory syndrome coronavirus 2 SARS-CoV-2 have been developed with record-breaking speed and vaccine programs are ongoing worldwide to take the pandemic under During this expansion of research focus from treatment to prevention of COVID-19, the immune evasion mechanism and immunopathogenic nature of SARS-CoV-2 adds uncertainty to the efficacy of this global vaccination During natural infection, SARS-CoV-2 could avoid the innate antiviral response mediated by interferons IFNs via an array of possible strategies,4,5 which not only leads to viral replication and spreading but also could delay or impair the adaptive immune response including T cell and antibody The significant prevalence of SARS-CoV-2 RNA re-positive cases among discharged patients further raises the concern about the effectiveness and persistency of immune responses after natural Recent long-term follow-up surveys report significant decrease of SARS-CoV-2 antibody titers 5 to 8 months after infection,10,11,12 but its correlation with reduced capacity of SARS-CoV-2 neutralization and immune memory is still vaccination, equally important is the recovery and rehabilitation of COVID-19 Mild cases usually do not require hospitalization but may share similar long-lasting symptoms or discomforts with severe cases, which may reduce life quality after recovery from Also, cardiac magnet resonance imaging cMRI screening revealed surprisingly high prevalence of subclinical myocardial inflammation and fibrosis in recently recovered Due to the overloading of medical systems and the fear of in-hospital transmission, long-term follow-up studies of the structural and functional recovery of COVID-19-involved organs are still this prospective cohort study of recovered COVID-19 patients from Xiangyang, China, we aimed to assess long-term antibody response at 12 months after infection and comprehensively evaluate the structural and functional recovery of the lung and cardiovascular systems. We also attempted to identify potential risk factors associated with those long-term January 15 through 31 March 2020, a total of 307 patients were diagnosed with COVID-19 at Xiangyang Central Hospital, which represented of 549 cases in the downtown and of 1175 cases city-wide. During hospitalization, 12 patients succumbed to COVID-19-induced respiratory distress or lethal infection, which translated to a mortality rate of in line with the citywide mortality rate of 40/1175. All 295 survivors were invited to participate in this study and the final cohort consisted of 121 survivors including 19 recovered from severe COVID-19 Supplementary Fig. 1. Clinical procedures were performed at Xiangyang Central Hospital between 25 December 2020 and 29 January and clinical features of participantsDemographic-wise, this cohort consisted of middle-aged Chinese population with an overall comorbidity prevalence of including hypertension and diabetes as the most common preexisting conditions, which was typical for the local agricultural and industrial population with a preference of high-salt diets Table 1. The participants of this study were among the earliest confirmed COVID-19 patients with virological confirmation dates as early as January 19, 2020. Standard of care consisted of antivirals, antibiotics, immunomodulants and supplemental oxygen was given to participants following CDC guidelines Supplementary Table 1. Only 1 in this cohort received invasive ventilation Supplementary Table 1, which reflected the dismal mortality rate among critically ill patients relying on respiratory Of note, the basic characteristics of this cohort were comparable with the entire population of COVID-19 survivors treated at this hospital Supplementary Table 2.Table 1 Characteristics of participants by COVID-19 severityFull size tableAfter stratifying the cohort by severity graded according to the guideline,21 severe groups had higher ages, less females, and more comorbidities Table 1. Severe group also presented more symptoms at admission, and received more aggressive immunomodulatory therapies, supplemental oxygen, and ICU care during hospitalization Supplementary Table 1. Both severe and non-severe groups share similar lengths since symptom onset, while the severe group had shorter periods since recovery because of longer hospitalization Table 1.Long-lasting SARS-CoV-2 antibody response 1-year after infectionFirst, blood samples were screened by colloidal gold-based immunochromatographic assays GICA separately detecting IgM and IgG against At a median of 11 months post- infection, only 4% 95% CI, 2–10% participants returned positive IgM results, which included both positive and weakly positive results, while 62% 95% CI, 54–71% were IgG positive Table 1, comparing to prevalence of IgM among pre-discharge samples from the same Severe group showed higher prevalence of IgG, while the prevalence of IgM was equally low in both groups Table 1.Next, the concentration of total antibodies against the receptor-binding domain of SARS-CoV-2 spike protein RBD was quantitatively measured by chemiluminescence microparticle immunoassays CMIA.24 Although signal/cutoff S/CO ratios were lower in non-severe group, all but 1 of the results were above the positive diagnostic threshold of S/CO = when all 100 samples of unexposed individuals, which were randomly chosen from sera of in-hospital patients who had negative results from multiple PCR and serological tests for SARS-CoV-2 before and after the date of serum collection, had S/CO values participants were exposed to SARS-CoV-2 and diagnosed with COVID-19 during January to March 2020. During their COVID-19 disease courses, they have received combinations of therapies including antivirals, immunomodulatory agents, antibiotics, supplemental oxygen, and ICU outcomes of this study were immunity against SARS-CoV-2 and functional recovery of the lung and other involved organs. Immunity against SARS-CoV-2 was assessed by multiple antibody assays. The colloidal gold-based test kit gave positive, weak positive, and negative readout of anti-SARS-CoV-2 IgM and IgG separately. The quantitative chemiluminescence microparticle immunoassay for antibodies against SARS-CoV-2 RBD was performed according to manufacturer’s protocol and previous publication,24 and the results were deemed positive if the signal/cutoff S/CO ratio ≥1. For ELISA tests, results were recorded and analyzed as continuous variables and the limit of sensitivity was calculated as mean + 2 × SD of 20 serum samples negative for SARS-CoV-2 antibodies in chemiluminescence assays. Functional recovery of the lung was assessed based on 1 current CT images comparing to images taken before discharge and during earlier follow-ups, 2 pulmonary function test results, and 3 six-minute walk test results. Recovery of the heart was assessed based on ECG, echocardiogram, and cardiac MRI scans. Recovery of other potentially involved organs were assessed by laboratory tests Roche Diagnostics.Sample sizeAn initial target sample size of 108 was determined based on the assumption of a 15 ratio of severe and non-severe COVID-19 patient enrollment and α = This sample size was calculated to have 90% power to detect a 10% difference of antibody concentrations. The final sample size exceeded the target in both analysisQuantitative data were presented in violin plots with all data points shown. Patient characteristics and clinical data were summarized as incidence with prevalence or median with IQR and were assessed with Fisher’s exact test dichotomous variables or χ2 test variables with more than two categories for categorical variables and Mann–Whitney U test for continuous variables. Antibody concentrations were log-transformed before being analyzed as continuous variables. The difference of antibody concentrations between groups were assessed by the Mann–Whitney U test two groups or Kruskal–Wallis test with post hoc comparisons more than two groups. Special tests were mentioned in figure legends. Correlation was assessed by Spearman’s ρ test. Linearity between two factors was assessed by simple linear regression. Generalized linear models were used to assess factors associated with antibody titers. Analyses were performed using SPSS 26 IBM or Prism 9 GraphPad. Missing data were excluded pairwise from analyses. 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This work was supported by Xiangyang Science and Technology Bureau 2020YL10, 2020YL14, 2020YL17, and 2020YL39, National Natural Science Foundation of China 31501116, Shenzhen Science and Technology Innovation Commission JCYJ20190809100005672, Shenzhen Sanming Project of Medicine SZSM201911013, and US Department of Veterans Affairs 5I01BX001353.Author informationAuthor notesThese authors contributed equally Yan Zhan, Yufang Zhu, Shanshan Wang, Shijun Jia, Yunling Gao, Yingying LuAuthors and AffiliationsDepartment of Rehabilitation Medicine, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, Hubei, 441021, ChinaYan Zhan, Shanshan Wang, Peng Du, Hao Yu, Chang Liu & Peijun LiuDepartment of Laboratory Medicine, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, Hubei, 441021, ChinaYufang Zhu, Caili Zhou & Ran LiangDepartment of Radiology and Medical Imaging, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, Hubei, 441021, ChinaShijun Jia & Feng WuDepartment of Research Affairs, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, Hubei, 441021, ChinaYunling Gao & Jin ChengDepartment of Nephrology, Center of Nephrology and Urology, Sun Yat-sen University Seventh Hospital, Shenzhen, Guangdong, 518107, ChinaYingying Lu, Zhihua Zheng & Peng HongDepartment of Biomedical Science, Shenzhen Research Institute, City University of Hong Kong, Kowloon Tong, Hong Kong, ChinaYingying LuDepartment of Rehabilitation Medicine, Xiangzhou District People’s Hospital, Xiangyang, Hubei, 441000, ChinaDingwen SunDepartment of Rehabilitation Medicine, Gucheng People’s Hospital, Affiliated Gucheng Hospital of Hubei University of Arts and Science, Xiangyang, Hubei, 441700, ChinaXiaobo WangDivision of Quality Control, Xiangyang Central Blood Station, Xiangyang, Hubei, 441000, ChinaZhibing HouDepartment of Respiratory and Critical Care Medicine, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, Hubei, 441021, ChinaQiaoqiao Hu & Yulan ZhengDepartment of Pathology, Mount Sinai St. Luke’s Roosevelt Hospital Center, New York, NY, 10025, USAMiao CuiDepartment of Oncology, Peking University Shenzhen Hospital, Shenzhen, Guangdong, 518036, ChinaGangling TongDepartment of Dermatology, Sun Yat-sen University Seventh Hospital, Shenzhen, Guangdong, 518107, ChinaYunsheng Xu & Linyu ZhuDivision of Research and Development, US Department of Veterans Affairs New York Harbor Healthcare System, Brooklyn, NY, 11209, USAPeng HongDepartment of Cell Biology, State University of New York Downstate Health Sciences University, Brooklyn, NY, 11203, USAPeng HongAuthorsYan ZhanYou can also search for this author in PubMed Google ScholarYufang ZhuYou can also search for this author in PubMed Google ScholarShanshan WangYou can also search for this author in PubMed Google ScholarShijun JiaYou can also search for this author in PubMed Google ScholarYunling GaoYou can also search for this author in PubMed Google ScholarYingying LuYou can also search for this author in PubMed Google ScholarCaili ZhouYou can also search for this author in PubMed Google ScholarRan LiangYou can also search for this author in PubMed Google ScholarDingwen SunYou can also search for this author in PubMed Google ScholarXiaobo WangYou can also search for this author in PubMed Google ScholarZhibing HouYou can also search for this author in PubMed Google ScholarQiaoqiao HuYou can also search for this author in PubMed Google ScholarPeng DuYou can also search for this author in PubMed Google ScholarHao YuYou can also search for this author in PubMed Google ScholarChang LiuYou can also search for this author in PubMed Google ScholarMiao CuiYou can also search for this author in PubMed Google ScholarGangling TongYou can also search for this author in PubMed Google ScholarZhihua ZhengYou can also search for this author in PubMed Google ScholarYunsheng XuYou can also search for this author in PubMed Google ScholarLinyu ZhuYou can also search for this author in PubMed Google ScholarJin ChengYou can also search for this author in PubMed Google ScholarFeng WuYou can also search for this author in PubMed Google ScholarYulan ZhengYou can also search for this author in PubMed Google ScholarPeijun LiuYou can also search for this author in PubMed Google ScholarPeng HongYou can also search for this author in PubMed Google ScholarContributionsY. Zhan and conceptualized the study; Y. Zhan, and recruited patients, performed physical examinations, and abstracted historic data; Y. Zhu, and performed laboratory tests and interpreted results; and conducted sonographic and radiological examinations and interpreted results; and Y. Zheng conducted PFT and interpreted results; Y. Zhan, and conducted functional tests, assessed rehabilitation status and interpreted data; and interpreted metabolic and immunological findings; Y. Zhan, and conducted data quality checks and performed statistical analyses; Y. Zhan and wrote the manuscript. All authors read and approved the final authorsCorrespondence to Feng Wu, Yulan Zheng, Peijun Liu or Peng declarations Competing interests The authors declare no competing interests. Supplementary informationRights and permissions Open Access This article is licensed under a Creative Commons Attribution International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original authors and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit Reprints and PermissionsAbout this articleCite this articleZhan, Y., Zhu, Y., Wang, S. et al. SARS-CoV-2 immunity and functional recovery of COVID-19 patients 1-year after infection. Sig Transduct Target Ther 6, 368 2021. citationReceived 06 March 2021Revised 16 September 2021Accepted 20 September 2021Published 13 October 2021DOI KondisiPenyerta / Komorbid / Penyakit Bawaan. Klik dibawah ini untuk memilih semua Kondisi Penyerta / Komorbid / Penyakit Bawaan *. Ya Tidak. Hamil *. Ya Tidak. Diabetes *. Ya Tidak. Penyakit Jantung *. Ya Tidak. Estimates of SARS-CoV-2 Seroprevalence and Incidence of Primary SARS-CoV-2 Infections Among Blood Donors, by COVID-19 Vaccination Status — United States, April 2021–September 2022 Jefferson M. Jones, MD1; Irene Molina Manrique, MS2; Mars S. Stone, PhD3; Eduard Grebe, PhD3; Paula Saa, PhD4; Clara D. Germanio, PhD3; Bryan R. Spencer, PhD4; Edward Notari, MPH4; Marjorie Bravo, MD3; Marion C. Lanteri, PhD5; Valerie Green, MS5; Melissa Briggs-Hagen, MD1; Melissa M. Coughlin, PhD1; Susan L. Stramer, PhD4; Jean Opsomer, PhD2; Michael P. Busch, MD, PhD3 View author affiliations View suggested citationSummary What is already known about this topic? SARS-CoV-2 hybrid immunity immunity derived from both previous infection and vaccination has been reported to provide better protection than that from infection or vaccination alone. What is added by this report? By the third quarter of 2022, an estimated of persons aged ≥16 years in a longitudinal blood donor cohort had SARS-CoV-2 antibodies from previous infection or vaccination, including from infection alone and from vaccination alone; had hybrid immunity. Hybrid immunity prevalence was lowest among adults aged ≥65 years. What are the implications for public health practice? Low prevalence of infection-induced and hybrid immunity among older adults, who are at increased risk for severe disease if infected, reflects the success of public health infection prevention efforts while also highlighting the importance of this group staying up to date with recommended COVID-19 vaccination, including at least 1 bivalent dose. Altmetric Citations Views Views equals page views plus PDF downloads Changes in testing behaviors and reporting requirements have hampered the ability to estimate the SARS-CoV-2 incidence 1. Hybrid immunity immunity derived from both previous infection and vaccination has been reported to provide better protection than that from infection or vaccination alone 2. To estimate the incidence of infection and the prevalence of infection- or vaccination-induced antibodies or both, data from a nationwide, longitudinal cohort of blood donors were analyzed. During the second quarter of 2021 April–June, an estimated of persons aged ≥16 years had infection- or vaccination-induced SARS-CoV-2 antibodies, including from vaccination alone, from infection alone, and from both. By the third quarter of 2022 July–September, had SARS-CoV-2 antibodies from previous infection or vaccination, including from infection alone and from vaccination alone; had hybrid immunity. Prevalence of hybrid immunity was lowest among persons aged ≥65 years the group with the highest risk for severe disease if infected, and was highest among those aged 16–29 years Low prevalence of infection-induced and hybrid immunity among older adults reflects the success of public health infection prevention efforts while also highlighting the importance of older adults staying up to date with recommended COVID-19 vaccination, including at least 1 bivalent dose.*,† Since July 2020, SARS-CoV-2 seroprevalence in the United States has been estimated by testing blood donations 3. CDC, in collaboration with Vitalant, American Red Cross, Creative Testing Solutions, and Westat, established a nationwide cohort of 142,758 blood donors in July 2021; the cohort included persons who had donated blood two or more times in the preceding year.§ All blood donations collected during April–June 2021 were tested for antibodies against the spike S and nucleocapsid N proteins. Beginning in 2022, up to one blood donation sample per donor was randomly selected each quarter and tested using the Ortho VITROS SARS-CoV-2 Quantitative S immunoglobulin G¶ and total N antibody** tests. Both SARS-CoV-2 infection and COVID-19 vaccination result in production of anti-S antibodies, whereas anti-N antibodies only result from infection. At each donation, blood donors were asked if they had received a COVID-19 vaccine. Using vaccination history and results of antibody testing, the prevalence of the population aged ≥16 years with vaccine-induced, infection-induced, or hybrid immunity was estimated for four 3-month periods April–June 2021, January–March 2022, April–June 2022, and July–September 2022; in addition, the proportion of persons who transitioned from one immune status to another by quarter was estimated. Analysis was limited to 72,748 donors for whom it was possible to ascertain immune status during each period using their prior classification previously infected or vaccinated, antibody testing results, and their vaccination status at the time of each donation.†† The sample data were weighted to account for selection into the study cohort, for nonresponse during the four analysis periods, and for demographic differences between the blood donor population and the overall population. The weights were obtained through a combination of stratification and raking, an iterative weighting adjustment procedure 4. Rates of infection among those previously uninfected were estimated for each period by determining the percentage of anti-N–negative persons seroconverting to anti-N–positive from one 3-month period included in the study to the next. Estimates were stratified by age group 16–29, 30–49, 50–64, and ≥65 years and race and ethnicity§§ Asian, Black or African American [Black], White, Hispanic or Latino [Hispanic], and other. SAS version SAS Institute was used to compute the final weights, and R version R Foundation was used to calculate all the estimates and create the plots.¶¶ Seroprevalence and infection rates were estimated as weighted means and compared by demographic group and vaccination status using two-sided t-tests with a significance level of α = This activity was reviewed by CDC and conducted consistent with applicable federal law and CDC policy.*** During the first quarter examined April–June 2021, an estimated 95% CI = of persons aged ≥16 years had SARS-CoV-2 antibodies from previous infection or vaccination, including 95% CI = from vaccination alone, 95% CI = from infection alone, and 95% CI = from both Figure 1 Supplementary Figure 1, During January–March 2022, 95% CI = of persons aged ≥16 years had antibodies from previous infection or vaccination, including 95% CI = from vaccination alone, 95% CI = from infection alone, and 95% CI = from both. During July–September 2022, 95% CI = of persons had antibodies from previous infection or vaccination, including 95% CI = with vaccine-induced immunity alone, 95% CI = with infection-induced immunity alone, and 95% CI = with hybrid immunity. During July–September 2022, the prevalence of infection-induced immunity was 95% CI = among unvaccinated persons and 95% CI = among vaccinated persons. During July–September 2022, the lowest prevalence of hybrid immunity, 95% CI = was observed in persons aged ≥65 years, and the highest, 95% CI = in adolescents and young adults aged 16–29 years Figure 2 Supplementary Figure 2, During all periods, higher prevalences of hybrid immunity were observed among Black and Hispanic populations than among White and Asian populations Supplementary Figure 3, Among persons with no previous infection, the incidence of first infections during the study period conversion from anti-N–negative to anti-N–positive was higher among unvaccinated persons Table. From April–June 2021 through January–March 2022, the incidence of first SARS-CoV-2 infections among unvaccinated persons was compared with among vaccinated persons p< From January–March 2022 through April–June 2022, the incidence among unvaccinated persons was and was among vaccinated persons. Between April–June 2022 and July–September 2022, the incidence among unvaccinated persons was compared with among vaccinated persons p< Incidence of first SARS-CoV-2 infections was higher among younger than among older persons and was lower among Asian persons than among other racial and ethnic populations, but the differences among groups narrowed over time. Discussion Both infection-induced and hybrid immunity increased during the study period. By the third quarter of 2022, approximately two thirds of persons aged ≥16 years had been infected with SARS-CoV-2 and one half of all persons had hybrid immunity. Compared with vaccine effectiveness against any infection and against severe disease or hospitalization, the effectiveness of hybrid immunity against these outcomes has been shown to be higher and wane more slowly 2. This increase in seroprevalence, including hybrid immunity, is likely contributing to lower rates of severe disease and death from COVID-19 in 2022–2023 than during the early pandemic.††† The prevalence of hybrid immunity is lowest in adults aged ≥65 years, likely due to higher vaccination coverage and earlier availability of COVID-19 vaccines for this age group, as well as to higher prevalences of behavioral practices to avoid infection 5. However, lower prevalences of infection-induced and hybrid immunity could further increase the risk for severe disease in this group, highlighting the importance for adults aged ≥65 years to stay up to date with COVID-19 vaccination and have easy access to antiviral medications. COVID-19 vaccine efficacy studies have reported reduced effectiveness against SARS-CoV-2 infection during the Omicron-predominant period compared with earlier periods and have shown that protection against infection wanes more rapidly than does protection against severe disease 6,7. In this study, unvaccinated persons had higher rates of infection as evidenced by N antibody seroconversion than did vaccinated persons, indicating that vaccination provides some protection against infection. The differences in incidence could also be due to systematic differences between vaccinated and unvaccinated persons in terms of the prevalence of practicing prevention behaviors such as masking and physical distancing. The relative difference in infection rates narrowed during the most recent months, possibly because of waning of vaccine-induced protection against infection in the setting of increased time after vaccination or immune evasion by the SARS-CoV-2 Omicron variant. The narrowing of difference in infection rates might also be attributable to increasing similarities in behavior among vaccinated and unvaccinated persons during late 2022 8. The findings in this report are subject to at least six limitations. First, although COVID-19 booster vaccine doses and reinfections can strengthen immunity 9,10, this analysis did not account for these effects because blood donor vaccination history did not include the number of doses received, and data on reinfections were not captured. Second, immunity wanes over time, but time since vaccination or infection was not included in the analysis 2. Third, vaccination status was self-reported, potentially leading to misclassification. Fourth, although the results were adjusted based on differences in blood donor and general population demographics, estimates from blood donors might not be representative of the general population; thus, these results might not be generalizable. Fifth, vaccinated and unvaccinated persons might differ in other ways not captured by this analysis 8, nor can causality be inferred from the results on relative infection incidence. Finally, if both vaccination and infection occurred between blood donations included in the study, the order of occurrence could not be determined, and some unvaccinated donors might have been vaccinated before infection and thus misclassified; in 2022, this was uncommon and occurred in < of donors during any 3-month period. This report found that the incidence of first-time SARS-CoV-2 infection was lower among persons who had received COVID-19 vaccine than among unvaccinated persons and that infection-induced and hybrid immunity have increased but remain lowest in adults aged ≥65 years. These adults have consistently had a higher risk for severe disease compared with younger age groups, underscoring the importance of older adults staying up to date with recommended COVID-19 vaccination, including at least 1 bivalent dose. Acknowledgments Brad Biggerstaff, Matthew McCullough, CDC; Roberta Bruhn, Brian Custer, Xu Deng, Zhanna Kaidarova, Kathleen Kelly, Anh Nguyen, Graham Simmons, Hasan Sulaeman, Elaine Yu, Karla Zurita-Gutierrez, Vitalant Research Institute; Akintunde Akinseye, Jewel Bernard-Hunte, Robyn Ferg, Rebecca Fink, Caitlyn Floyd, Isaac Lartey, Sunitha Mathews, David Wright, Westat; Jamel Groves, James Haynes, David Krysztof, American Red Cross; Ralph Vassallo, Vitalant; Sherri Cyrus, Phillip Williamson, Creative Testing Solutions; Paul Contestable, QuidelOrtho; Steve Kleinman, University of British Columbia; CDC, Vitalant Research Institute, Westat, American Red Cross, and Creative Testing Solutions staff members; blood donors whose samples were analyzed and who responded to surveys for this study. Corresponding author Jefferson M. Jones, ioe8 Center for Immunization and Respiratory Diseases, CDC; 2Westat, Rockville, Maryland; 3Vitalant Research Institute, San Francisco, California; 4American Red Cross, Washington, DC; 5Creative Testing Solutions, Tempe, authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed. * † § Blood donors who donated at least twice during the year before July 2021 were included in the cohort, because they might represent persons who were more likely to donate frequently. Among donors who donated more than once during a quarter, one sample was selected at random for testing. ¶ ** †† §§ Persons of Hispanic origin might be of any race but are categorized as Hispanic; all racial groups are non-Hispanic. ¶¶ Jackknife replication was used to compute replicate weights. Weights were adjusted for nonresponse using adjustment cells created by age category, vaccination and previous infection status, and blood collection organization Vitalant or American Red Cross. Raking was used to further adjust the weights to account for demographic differences between the blood donor population and population. The demographic variables used for raking were sex female and male, age group 16–24, 25–34, 35–44, 45–54, 55–64, and ≥65 years, and race and ethnicity Asian, Black, White, Hispanic, and other. *** 45 part 46, 21 part 56; 42 Sect. 241d; 5 Sect. 552a; 44 Sect. 3501 et seq. ††† Accessed May 25, 2023. References Rader B, Gertz A, Iuliano AD, et al. Use of at-home COVID-19 tests—United States, August 23, 2021–March 12, 2022. MMWR Morb Mortal Wkly Rep 2022;71489–94. PMID35358168 Bobrovitz N, Ware H, Ma X, et al. Protective effectiveness of previous SARS-CoV-2 infection and hybrid immunity against the Omicron variant and severe disease a systematic review and meta-regression. Lancet Infect Dis 2023;23556–67. PMID36681084 Jones JM, Stone M, Sulaeman H, et al. Estimated US infection- and vaccine-induced SARS-CoV-2 seroprevalence based on blood donations, July 2020–May 2021. JAMA 2021;3261400–9. PMID34473201 Deville J-C, Särndal C-E, Sautory O. Generalized raking procedures in survey sampling. J Am Stat Assoc 1993;881013–20. Steele MK, Couture A, Reed C, et al. Estimated number of COVID-19 infections, hospitalizations, and deaths prevented among vaccinated persons in the US, December 2020 to September 2021. JAMA Netw Open 2022;5e2220385. PMID35793085 Higdon MM, Wahl B, Jones CB, et al. A systematic review of coronavirus disease 2019 vaccine efficacy and effectiveness against severe acute respiratory syndrome coronavirus 2 infection and disease. Open Forum Infect Dis 2022;9ofac138. PMID35611346 Feikin DR, Higdon MM, Abu-Raddad LJ, et al. Duration of effectiveness of vaccines against SARS-CoV-2 infection and COVID-19 disease results of a systematic review and meta-regression. Lancet 2022;399924–44. PMID35202601 Thorpe A, Fagerlin A, Drews FA, Shoemaker H, Scherer LD. Self-reported health behaviors and risk perceptions following the COVID-19 vaccination rollout in the USA an online survey study. Public Health 2022;20868–71. PMID35717747 Sette A, Crotty S. Immunological memory to SARS-CoV-2 infection and COVID-19 vaccines. Immunol Rev 2022;31027–46. PMID35733376 Atti A, Insalata F, Carr EJ, et al.; SIREN Study Group and the Crick COVID Immunity Pipeline Consortium. Antibody correlates of protection from SARS-CoV-2 reinfection prior to vaccination a nested case-control within the SIREN study. J Infect 2022;85545–56. PMID36089104 FIGURE 1. Prevalences of vaccine-induced, infection-induced, and hybrid* immunity† against SARS-CoV-2 among blood donors aged ≥16 years — United States, April 2021–September 2022 * Immunity derived from a combination of vaccination and infection. † Ascertained by the presence of anti-spike antibodies present in both COVID-19–vaccinated and SARS-CoV-2–infected persons and anti-nucleocapsid antibodies present only in previously infected persons and self-reported history of vaccination. FIGURE 2. Prevalences of vaccine-induced, infection-induced, and hybrid* immunity† against SARS-CoV-2 among blood donors aged ≥16 years, by age group — United States, April 2021–September 2022 * Immunity derived from a combination of vaccination and infection. † Ascertained by the presence of anti-spike antibodies present in both COVID-19–vaccinated and SARS-CoV-2–infected persons and anti-nucleocapsid antibodies present only in previously infected persons and self-reported history of vaccination. TABLE. Estimated percentage* of persons infected with SARS-CoV-2 for the first time among blood donors, by analysis quarter, sociodemographic characteristics, and vaccination status — United States, April 2021–September 2022 Characteristic Period, % 95% CI Apr–Jun 2021 to Jan–Mar 2022 Jan–Mar 2022 to Apr–Jun 2022 Apr–Jun 2022 to Jul–Sep 2022 Overall Total Unvaccinated Vaccinated Age group, yrs 16–29 Total Unvaccinated Vaccinated 30–49 Total Unvaccinated Vaccinated 50–64 Total Unvaccinated Vaccinated ≥65 Total Unvaccinated Vaccinated Race and ethnicity§ Asian Total Unvaccinated Vaccinated Black or African American Total Unvaccinated Vaccinated White Total Unvaccinated Vaccinated Hispanic or Latino Total Unvaccinated Vaccinated Other and multiple races¶ Total Unvaccinated Vaccinated * Percentage of uninfected persons anti-nucleocapsid–negative in the previous 3-month period seroconverting to anti-nucleocapsid–positive. If both vaccination and infection occurred between donations included in the study, the order could not be determined, and some unvaccinated donors might have been vaccinated before infection and thus misclassified. † If donors who transitioned from no antibodies to hybrid immunity between April–June 2021 and January–March 2022 were excluded, an estimated 95% CI = of unvaccinated donors were infected. For other periods, exclusion did not substantially change results. Between January–March and April–June 2022, of persons shifted from no antibodies to hybrid immunity. Between April–June and July–September 2022, of persons shifted from no antibodies to hybrid immunity. § Persons of Hispanic or Latino Hispanic origin might be of any race but are categorized as Hispanic; all racial groups are non-Hispanic. ¶ Includes American Indian or Alaska Native and non-Hispanic persons of other races. Suggested citation for this article Jones JM, Manrique IM, Stone MS, et al. Estimates of SARS-CoV-2 Seroprevalence and Incidence of Primary SARS-CoV-2 Infections Among Blood Donors, by COVID-19 Vaccination Status — United States, April 2021–September 2022. MMWR Morb Mortal Wkly Rep 2023;72601–605. DOI MMWR and Morbidity and Mortality Weekly Report are service marks of the Department of Health and Human Services. Use of trade names and commercial sources is for identification only and does not imply endorsement by the Department of Health and Human Services. References to non-CDC sites on the Internet are provided as a service to MMWR readers and do not constitute or imply endorsement of these organizations or their programs by CDC or the Department of Health and Human Services. CDC is not responsible for the content of pages found at these sites. URL addresses listed in MMWR were current as of the date of publication. All HTML versions of MMWR articles are generated from final proofs through an automated process. 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Antibodytests may help identify past SARS-CoV-2 infection if performed two to four weeks after symptom onset. 36, 37 Antibody test results should not yet be used to infer immunity to SARS-CoV-2
. 2021 Oct;2710 doi Epub 2021 Jun 7. Sheila F Lumley 2 , Jia Wei 3 , Stuart Cox 4 , Tim James 4 , Anita Justice 4 , Gerald Jesuthasan 4 , Denise O'Donnell 3 , Alison Howarth 3 , Stephanie B Hatch 3 , Brian D Marsden 5 , E Yvonne Jones 3 , David I Stuart 3 , Daniel Ebner 6 , Sarah Hoosdally 7 , Derrick W Crook 2 , Tim E A Peto 2 , Timothy M Walker 8 , Nicole E Stoesser 2 , Philippa C Matthews 2 , Koen B Pouwels 9 , A Sarah Walker 7 , Katie Jeffery 4 Affiliations PMID 34111577 PMCID PMC8180449 DOI Free PMC article Quantitative SARS-CoV-2 anti-spike responses to Pfizer-BioNTech and Oxford-AstraZeneca vaccines by previous infection status David W Eyre et al. Clin Microbiol Infect. 2021 Oct. Free PMC article Abstract Objectives We investigated determinants of severe acute respiratory syndrome coronavirus 2 SARS-CoV-2 anti-spike IgG responses in healthcare workers HCWs following one or two doses of Pfizer-BioNTech or Oxford-AstraZeneca vaccines. Methods HCWs participating in regular SARS-CoV-2 PCR and antibody testing were invited for serological testing prior to first and second vaccination, and 4 weeks post-vaccination if receiving a 12-week dosing interval. Quantitative post-vaccination anti-spike antibody responses were measured using the Abbott SARS-CoV-2 IgG II Quant assay detection threshold ≥50 AU/mL. We used multivariable logistic regression to identify predictors of seropositivity and generalized additive models to track antibody responses over time. Results 3570/3610 HCWs were seropositive >14 days post first vaccination and prior to second vaccination 2706/2720 were seropositive after the Pfizer-BioNTech and 864/890 following the Oxford-AstraZeneca vaccines. Previously infected and younger HCWs were more likely to test seropositive post first vaccination, with no evidence of differences by sex or ethnicity. All 470 HCWs tested >14 days after the second vaccination were seropositive. Quantitative antibody responses were higher after previous infection median IQR >21 days post first Pfizer-BioNTech 14 604 7644-22 291 AU/mL versus 1028 564-1985 AU/mL without prior infection p 21 days post second Pfizer vaccination in those not previously infected, 10 058 6408-15 582 AU/mL, were similar to those after prior infection followed by one vaccine dose. Conclusions SARS-CoV-2 vaccination leads to detectable anti-spike antibodies in nearly all adult HCWs. Whether differences in response impact vaccine efficacy needs further study. Keywords Antibody; Quantitative anti-spike antibody; SARS-CoV-2; Serology; Vaccine. Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved. Figures Fig. 1 Anti-spike IgG-positive results by days since first vaccination, by prior infection status and vaccine received. Tests performed after a second dose of vaccine are not included. The number of tests performed and positive and the resulting percentage is shown under each bar. Fig. 2 The relationship between vaccine, age and probability of testing anti-spike IgG seropositive >14 days post first vaccination. Model predictions are shown using reference categories for sex and ethnicity white, female, respectively and in those without prior evidence of infection. Fig. 3 Modelled quantitative anti-spike IgG responses following first vaccination by vaccine and previous infection status. Panels A and B show responses in previously infected healthcare workers HCWs and panels C and D HCWs without evidence of previous infection. Panels A and C show data for those receiving Pfizer–BioNTech vaccine and panels B and D Oxford–AstraZeneca vaccine. Model predictions are shown at three example ages 30, 45, and 60 years. The shaded ribbon shows the 95% confidence interval. Values are plotted from 7 days prior to vaccination to illustrate baseline values models are fitted using data from 28 days prior to vaccination onwards. Fig. 4 Modelled quantitative anti-spike IgG titres following second Pfizer–BioNTech vaccination by previous infection status. Panel A shows those who were previous infected including those previously infected at baseline or testing PCR-positive between vaccines and panel B those who had no evidence of previous infection. Model predictions are shown at three example ages 30, 45, and 60 years. The shaded ribbon shows the 95% confidence interval. Data were included in each model from 7 days before the second vaccination to allow pre-vaccination levels to be fitted correctly. Similar articles Low immunogenicity to SARS-CoV-2 vaccination among liver transplant recipients. Rabinowich L, Grupper A, Baruch R, Ben-Yehoyada M, Halperin T, Turner D, Katchman E, Levi S, Houri I, Lubezky N, Shibolet O, Katchman H. Rabinowich L, et al. J Hepatol. 2021 Aug;752435-438. doi Epub 2021 Apr 21. J Hepatol. 2021. PMID 33892006 Free PMC article. Immunogenicity of COVID-19 Tozinameran Vaccination in Patients on Chronic Dialysis. Schrezenmeier E, Bergfeld L, Hillus D, Lippert JD, Weber U, Tober-Lau P, Landgraf I, Schwarz T, Kappert K, Stefanski AL, Sattler A, Kotsch K, Dörner T, Sander LE, Budde K, Halleck F, Kurth F, Corman VM, Choi M. Schrezenmeier E, et al. Front Immunol. 2021 Jun 30;12690698. doi eCollection 2021. Front Immunol. 2021. PMID 34276681 Free PMC article. Immunogenicity of the BNT162b2 COVID-19 mRNA vaccine and early clinical outcomes in patients with haematological malignancies in Lithuania a national prospective cohort study. Maneikis K, Šablauskas K, Ringelevičiūtė U, Vaitekėnaitė V, Čekauskienė R, Kryžauskaitė L, Naumovas D, Banys V, Pečeliūnas V, Beinortas T, Griškevičius L. Maneikis K, et al. Lancet Haematol. 2021 Aug;88e583-e592. doi Epub 2021 Jul 2. Lancet Haematol. 2021. PMID 34224668 Free PMC article. COVID-19 vaccines comparison of biological, pharmacological characteristics and adverse effects of Pfizer/BioNTech and Moderna Vaccines. Meo SA, Bukhari IA, Akram J, Meo AS, Klonoff DC. Meo SA, et al. Eur Rev Med Pharmacol Sci. 2021 Feb;2531663-1669. doi Eur Rev Med Pharmacol Sci. 2021. PMID 33629336 Review. SARS-CoV-2 Proteins Are They Useful as Targets for COVID-19 Drugs and Vaccines? Mohammed MEA. Mohammed MEA. Curr Mol Med. 2022;22150-66. doi Curr Mol Med. 2022. PMID 33622224 Review. Cited by Tracking Changes in Mobility Before and After the First SARS-CoV-2 Vaccination Using Global Positioning System Data in England and Wales Virus Watch Prospective Observational Community Cohort Study. Nguyen V, Liu Y, Mumford R, Flanagan B, Patel P, Braithwaite I, Shrotri M, Byrne T, Beale S, Aryee A, Fong WLE, Fragaszy E, Geismar C, Navaratnam AMD, Hardelid P, Kovar J, Pope A, Cheng T, Hayward A, Aldridge R; Virus Watch Collaborative. Nguyen V, et al. JMIR Public Health Surveill. 2023 Mar 8;9e38072. doi JMIR Public Health Surveill. 2023. PMID 36884272 Free PMC article. Impact of BNT162b2 Booster Dose on SARS-CoV-2 Anti-Trimeric Spike Antibody Dynamics in a Large Cohort of Italian Health Care Workers. Renna LV, Bertani F, Podio A, Boveri S, Carrara M, Pinton A, Milani V, Spuria G, Nizza AF, Basilico S, Dubini C, Cerri A, Menicanti L, Corsi-Romanelli MM, Malavazos AE, Cardani R. Renna LV, et al. Vaccines Basel. 2023 Feb 17;112463. doi Vaccines Basel. 2023. PMID 36851340 Free PMC article. Robust specific RBD responses and neutralizing antibodies after ChAdOx1 nCoV-19 and CoronaVac vaccination in SARS-CoV-2- seropositive individuals. Fernandes ER, Taminato M, de Souza Apostolico J, Gabrielonni MC, Lunardelli VAS, Maricato JT, Andersen ML, Tufik S, Rosa DS. Fernandes ER, et al. J Allergy Clin Immunol Glob. 2023 May;22100083. doi Epub 2023 Feb 21. J Allergy Clin Immunol Glob. 2023. PMID 36845213 Free PMC article. Durability of ChAdOx1 nCoV-19 Covishield Vaccine Induced Antibody Response in Health Care Workers. Verma A, Goel A, Katiyar H, Tiwari P, Mayank, Sana A, Khetan D, Bhadauria DS, Raja A, Khokher N, Shalimar, Singh RK, Aggarwal A. Verma A, et al. Vaccines Basel. 2022 Dec 30;11184. doi Vaccines Basel. 2022. PMID 36679930 Free PMC article. The Influence of Two Priming Doses of Different Anti-COVID-19 Vaccines on the Production of Anti-SARS-CoV-2 Antibodies After the Administration of the Pfizer/BioNTech Booster. Wolszczak Biedrzycka B, Bieńkowska A, Smolińska-Fijołek E, Biedrzycki G, Dorf J. Wolszczak Biedrzycka B, et al. Infect Drug Resist. 2022 Dec 29;157811-7821. doi eCollection 2022. Infect Drug Resist. 2022. PMID 36600955 Free PMC article. References Folegatti Ewer Aley Angus B., Becker S., Belij-Rammerstorfer S. Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2 a preliminary report of a phase 1/2, single-blind, randomised controlled trial. Lancet. 2020;396467–478. - PMC - PubMed Wajnberg A., Amanat F., Firpo A., Altman Bailey Mansour M. Robust neutralizing antibodies to SARS-CoV-2 infection persist for months. Science. 2020;3701227–1230. - PMC - PubMed GeurtsvanKessel Okba Igloi Z., Bogers S., Embregts Laksono An evaluation of COVID-19 serological assays informs future diagnostics and exposure assessment. Nat Commun. 2020;113436. - PMC - PubMed Medicines and Healthcare products Regulatory Agency . 2020. MHRA guidance on coronavirus COVID-19 Walsh Frenck Falsey Kitchin N., Absalon J., Gurtman A. Safety and immunogenicity of two RNA-based Covid-19 vaccine candidates. N Engl J Med. 2020;3832439–2450. - PMC - PubMed MeSH terms Substances LinkOut - more resources Full Text Sources Elsevier Science Europe PubMed Central PubMed Central Medical Genetic Alliance MedlinePlus Health Information Miscellaneous NCI CPTAC Assay Portal
PemeriksaanAnti SARS-CoV-2 Kuantitatif dilakukan umumnya 14 hari setelah dosis vaksin terakhir diberikan sudah terjadi serokonversi, lalu secara berkala setiap 3-6 bulan; secara berkala 3-6 bulan untuk para penyintas; dan sebelum memberikan donor plasma konvalesen. “Diharapkan antibodi dapat bertahan selama 1 tahun, namun seperti yang
. 2021 Mar 19;594e03149-20. doi Print 2021 Mar 19. Affiliations PMID 33483360 PMCID PMC8092751 DOI Free PMC article Quantitative Measurement of Anti-SARS-CoV-2 Antibodies Analytical and Clinical Evaluation Victoria Higgins et al. J Clin Microbiol. 2021. Free PMC article Abstract The severe acute respiratory syndrome coronavirus 2 SARS-CoV-2 is the causative agent of coronavirus disease 2019 COVID-19. Molecular-based testing is used to diagnose COVID-19, and serologic testing of antibodies specific to SARS-CoV-2 is used to detect past infection. While most serologic assays are qualitative, a quantitative serologic assay was recently developed that measures antibodies against the S protein, the target of vaccines. Quantitative antibody determination may help determine antibody titer and facilitate longitudinal monitoring of the antibody response, including antibody response to vaccines. We evaluated the quantitative Roche Elecsys anti-SARS-CoV-2 S assay. Specimens from 167 PCR-positive patients and 103 control specimens were analyzed using the Elecsys anti-SARS-CoV-2 S assay on the cobas e411 Roche Diagnostics. Analytical evaluation included assessing linearity, imprecision, and analytical sensitivity. Clinical evaluation included assessing clinical sensitivity, specificity, cross-reactivity, positive predictive value PPV, negative predictive value NPV, and serial sampling from the same patient. The Elecsys anti-SARS-CoV-2 S assay exhibited its highest sensitivity at 15 to 30 days post-PCR positivity and exhibited no cross-reactivity, a specificity and PPV of 100%, and an NPV between and at ≥14 days post-PCR positivity, depending on the seroprevalence estimate. Imprecision was 30, 0 to 14, and ≥14 days post-PCR positivity for the quantitative Roche Elecsys anti-SARS-CoV-2 S assay using serum or plasma samples collected from 167 patients confirmed SARS-CoV-2 positive within the previous 0 to 73 days. FIG 2 Anti-SARS-CoV-2 antibody response by days post-PCR positivity in five patients as measured by the quantitative Roche Elecsys anti-SARS-CoV-2 S assay. Similar articles Anti-SARS-CoV-2 IgM improves clinical sensitivity early in disease course. Higgins V, Fabros A, Wang XY, Bhandari M, Daghfal DJ, Kulasingam V. Higgins V, et al. Clin Biochem. 2021 Apr;901-7. doi Epub 2021 Jan 19. Clin Biochem. 2021. PMID 33476578 Free PMC article. Analytical and Clinical Evaluation of the Automated Elecsys Anti-SARS-CoV-2 Antibody Assay on the Roche cobas e602 Analyzer. Chan CW, Parker K, Tesic V, Baldwin A, Tang NY, van Wijk XMR, Yeo KJ. Chan CW, et al. Am J Clin Pathol. 2020 Oct 13;1545620-626. doi Am J Clin Pathol. 2020. PMID 32814955 Free PMC article. Head-to-Head Comparison of Two SARS-CoV-2 Serology Assays. Merrill AE, Jackson JB, Ehlers A, Voss D, Krasowski MD. Merrill AE, et al. J Appl Lab Med. 2020 Nov 1;561351-1357. doi J Appl Lab Med. 2020. PMID 32717056 Free PMC article. [SARS-CoV-2 and Microbiological Diagnostic Dynamics in COVID-19 Pandemic]. Erensoy S. Erensoy S. Mikrobiyol Bul. 2020 Jul;543497-509. doi Mikrobiyol Bul. 2020. PMID 32755524 Review. Turkish. Performance of Elecsys Anti-SARS CoV-2 Roche and VIDAS Anti-SARS CoV-2 Biomérieux for SARS-CoV-2 Nucleocapsid and Spike Protein Antibody Detection. Inés RM, Gabriela HTM, Paula CM, Magdalena TM, Jimena A, Salome KB, Javier AJ, Sebastián B, Lorena S, Adrián DL, Elisa R, Mauricio B, Tersita BM, Verónica GS, Beatriz IM. Inés RM, et al. EJIFCC. 2022 Aug 8;332159-165. eCollection 2022 Aug. EJIFCC. 2022. PMID 36313907 Free PMC article. Review. Cited by Association between reactogenicity and immunogenicity after BNT162b2 booster vaccination a secondary analysis of a prospective cohort study. Jorda A, Bergmann F, Ristl R, Radner H, Sieghart D, Aletaha D, Zeitlinger M. Jorda A, et al. Clin Microbiol Infect. 2023 May 25S1198-743X2300252-5. doi Online ahead of print. Clin Microbiol Infect. 2023. PMID 37244466 Free PMC article. Variation in antibody titers determined by Abbott and Roche Elecsys SARS-CoV-2 assays in vaccinated healthcare workers. Nakai M, Yokoyama D, Sato T, Sato R, Kojima C, Shimosawa T. Nakai M, et al. Heliyon. 2023 Jun;96e16547. doi Epub 2023 May 22. Heliyon. 2023. PMID 37235203 Free PMC article. Anti-N SARS-CoV-2 assays for evaluation of natural viral infection. Gaeta A, Angeloni A, Napoli A, Pucci B, Cinti L, Roberto P, Colaiacovo F, Berardelli E, Farina A, Antonelli G, Anastasi E. Gaeta A, et al. J Immunol Methods. 2023 Jul;518113486. doi Epub 2023 May 6. J Immunol Methods. 2023. PMID 37156408 Free PMC article. Humoral Immune Response Following SARS-CoV-2 mRNA Vaccination and Infection in Pediatric-Onset Multiple Sclerosis. Breu M, Lechner C, Schneider L, Tobudic S, Winkler S, Siegert S, Baumann M, Seidl R, Berger T, Kornek B. Breu M, et al. Pediatr Neurol. 2023 Jun;14319-25. doi Epub 2023 Mar 2. Pediatr Neurol. 2023. PMID 36966598 Free PMC article. SARS-CoV-2-reactive antibody waning, booster effect and breakthrough SARS-CoV-2 infection in hematopoietic stem cell transplant and cell therapy recipients at one year after vaccination. Piñana JL, Martino R, Vazquez L, López-Corral L, Pérez A, Chorão P, Avendaño-Pita A, Pascual MJ, Sánchez-Salinas A, Sanz-Linares G, Olave MT, Arroyo I, Tormo M, Villalon L, Conesa-Garcia V, Gago B, Terol MJ, Villalba M, Garcia-Gutierrez V, Cabero A, Hernández-Rivas JÁ, Ferrer E, García-Cadenas I, Teruel A, Navarro D, Cedillo Á, Sureda A, Solano C; Spanish Hematopoietic Stem Cell Transplantation and Cell Therapy Group GETH-TC. Piñana JL, et al. Bone Marrow Transplant. 2023 May;585567-580. doi Epub 2023 Feb 28. Bone Marrow Transplant. 2023. PMID 36854892 Free PMC article. References Carter LJ, Garner LV, Smoot JW, Li Y, Zhou Q, Saveson CJ, Sasso JM, Gregg AC, Soares DJ, Beskid TR, Jervey SR, Liu C. 2020. Assay techniques and test development for COVID-19 diagnosis. ACS Cent Sci 6591–605. doi - DOI - PMC - PubMed Van Caeseele P, Bailey D, Forgie SE, Dingle TC, Krajden M, COVID-19 Immunity Task Force. 2020. SARS-CoV-2 COVID-19 serology implications for clinical practice, laboratory medicine and public health. CMAJ 192E973–E979. doi - DOI - PMC - PubMed Deeks JJ, Dinnes J, Takwoingi Y, Davenport C, Spijker R, Taylor-Phillips S, Adriano A, Beese S, Dretzke J, Ferrante di Ruffano L, Harris IM, Price MJ, Dittrich S, Emperador D, Hooft L, Leeflang MM, Van den Bruel A, Cochrane COVID-19 Diagnostic Test Accuracy Group. 2020. Antibody tests for identification of current and past infection with SARS-CoV-2. Cochrane Database Syst Rev 6CD013652. doi - DOI - PMC - PubMed Long Q-X, Liu B-Z, Deng H-J, Wu G-C, Deng K, Chen Y-K, Liao P, Qiu J-F, Lin Y, Cai X-F, Wang D-Q, Hu Y, Ren J-H, Tang N, Xu Y-Y, Yu L-H, Mo Z, Gong F, Zhang X-L, Tian W-G, Hu L, Zhang X-X, Xiang J-L, Du H-X, Liu H-W, Lang C-H, Luo X-H, Wu S-B, Cui X-P, Zhou Z, Zhu M-M, Wang J, Xue C-J, Li X-F, Wang L, Li Z-J, Wang K, Niu C-C, Yang Q-J, Tang X-J, Zhang Y, Liu X-M, Li J-J, Zhang D-C, Zhang F, Liu P, Yuan J, Li Q, Hu J-L, Chen J, et al. 2020. Antibody responses to SARS-CoV-2 in patients with COVID-19. Nat Med 26845–848. doi - DOI - PubMed Kofler N, Baylis F. 2020. Ten reasons why immunity passports are a bad idea. Nature 581379–381. doi - DOI - PubMed MeSH terms Substances LinkOut - more resources Full Text Sources Atypon Europe PubMed Central PubMed Central Other Literature Sources scite Smart Citations Medical Genetic Alliance MedlinePlus Health Information Miscellaneous NCI CPTAC Assay Portal
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Intepretasihasil rapid test antibodi: anti SARS-CoV-2 non reaktif. Alo Dokter, ijin bertanya. Pada Webinar “Rapid Test COVID-19 di Layanan Primer" yang dibawakan oleh narasumber Prof. Dr. dr. Aryati, MS, Sp.PK (K). Dilampirkan, contoh Pelaporan Hasil rapid test antibodi Non Reaktif dan Reaktif.

. 2022 Jan;941388-392. doi Epub 2021 Aug 31. Affiliations PMID 34415572 PMCID PMC8426838 DOI Free PMC article Correlation between a quantitative anti-SARS-CoV-2 IgG ELISA and neutralization activity Ramona Dolscheid-Pommerich et al. J Med Virol. 2022 Jan. Free PMC article Abstract In the current COVID-19 pandemic, a better understanding of the relationship between merely binding and functionally neutralizing antibodies is necessary to characterize protective antiviral immunity following infection or vaccination. This study analyzes the level of correlation between the novel quantitative EUROIMMUN Anti-SARS-CoV-2 QuantiVac ELISA IgG and a microneutralization assay. A panel of 123 plasma samples from a COVID-19 outbreak study population, preselected by semiquantitative anti-SARS-CoV-2 IgG testing, was used to assess the relationship between the novel quantitative ELISA IgG and a microneutralization assay. Binding IgG targeting the S1 antigen was detected in 106 samples using the QuantiVac ELISA, while 89 samples showed neutralizing antibody activity. Spearman's correlation analysis demonstrated a strong positive relationship between anti-S1 IgG levels and neutralizing antibody titers rs = p < High and low anti-S1 IgG levels were associated with a positive predictive value of for high-titer neutralizing antibodies and a negative predictive value of for low-titer neutralizing antibodies, respectively. These results substantiate the implementation of the QuantiVac ELISA to assess protective immunity following infection or vaccination. Keywords COVID-19; ELISA; SARS-CoV-2; microneutralization. © 2021 The Authors. Journal of Medical Virology Published by Wiley Periodicals LLC. Conflict of interest statement Sandra Saschenbrecker and Katja Steinhagen are employed by EUROIMMUN Medizinische Labordiagnostika AG, a manufacturer of diagnostic reagents and co‐owner of a patent application pertaining to the detection of antibodies to the SARS‐CoV‐2 S1 antigen. Katja Steinhagen is designated as an inventor. The other authors declare that there are no conflict of interests. Figures Figure 1 Correlation between quantitative ELISA and microneutralization assay. Binding anti‐SARS‐CoV‐2 S1 IgG was determined quantitatively using the QuantiVac ELISA and titers of neutralizing antibodies were determined using the CPE reduction NT assay n = 123. Neutralization titers correspond to reciprocal plasma dilutions protecting 50% of the wells at incubation with 100 TCID50 of SARS‐CoV‐2. Samples with a cytopathic effect CPE equal or similar to the negative control are depicted on the y‐axis. Dotted and dashed lines indicate borderline and positivity cut‐offs, respectively. r s, Spearman rank‐order correlation coefficient Similar articles Inference of SARS-CoV-2 spike-binding neutralizing antibody titers in sera from hospitalized COVID-19 patients by using commercial enzyme and chemiluminescent immunoassays. Valdivia A, Torres I, Latorre V, Francés-Gómez C, Albert E, Gozalbo-Rovira R, Alcaraz MJ, Buesa J, Rodríguez-Díaz J, Geller R, Navarro D. Valdivia A, et al. Eur J Clin Microbiol Infect Dis. 2021 Mar;403485-494. doi Epub 2021 Jan 6. Eur J Clin Microbiol Infect Dis. 2021. PMID 33404891 Free PMC article. SARS-CoV-2 Serologic Assays in Control and Unknown Populations Demonstrate the Necessity of Virus Neutralization Testing. Rathe JA, Hemann EA, Eggenberger J, Li Z, Knoll ML, Stokes C, Hsiang TY, Netland J, Takehara KK, Pepper M, Gale M Jr. Rathe JA, et al. J Infect Dis. 2021 Apr 8;22371120-1131. doi J Infect Dis. 2021. PMID 33367830 Free PMC article. A highly specific and sensitive serological assay detects SARS-CoV-2 antibody levels in COVID-19 patients that correlate with neutralization. Peterhoff D, Glück V, Vogel M, Schuster P, Schütz A, Neubert P, Albert V, Frisch S, Kiessling M, Pervan P, Werner M, Ritter N, Babl L, Deichner M, Hanses F, Lubnow M, Müller T, Lunz D, Hitzenbichler F, Audebert F, Hähnel V, Offner R, Müller M, Schmid S, Burkhardt R, Glück T, Koller M, Niller HH, Graf B, Salzberger B, Wenzel JJ, Jantsch J, Gessner A, Schmidt B, Wagner R. Peterhoff D, et al. Infection. 2021 Feb;49175-82. doi Epub 2020 Aug 21. Infection. 2021. PMID 32827125 Free PMC article. Quantitative SARS-CoV-2 Serology in Children With Multisystem Inflammatory Syndrome MIS-C. Rostad CA, Chahroudi A, Mantus G, Lapp SA, Teherani M, Macoy L, Tarquinio KM, Basu RK, Kao C, Linam WM, Zimmerman MG, Shi PY, Menachery VD, Oster ME, Edupuganti S, Anderson EJ, Suthar MS, Wrammert J, Jaggi P. Rostad CA, et al. Pediatrics. 2020 Dec;1466e2020018242. doi Epub 2020 Sep 2. Pediatrics. 2020. PMID 32879033 Recent Developments in SARS-CoV-2 Neutralizing Antibody Detection Methods. Banga Ndzouboukou JL, Zhang YD, Fan XL. Banga Ndzouboukou JL, et al. Curr Med Sci. 2021 Dec;4161052-1064. doi Epub 2021 Dec 21. Curr Med Sci. 2021. PMID 34935114 Free PMC article. Review. Cited by Impact of Health Workers' Choice of COVID-19 Vaccine Booster on Immunization Levels in Istanbul, Turkey. Ören MM, Canbaz S, Meşe S, Ağaçfidan A, Demir ÖS, Karaca E, Doğruyol AR, Otçu GH, Tükek T, Özgülnar N. Ören MM, et al. Vaccines Basel. 2023 May 3;115935. doi Vaccines Basel. 2023. PMID 37243039 Free PMC article. Development and validity assessment of ELISA test with recombinant chimeric protein of SARS-CoV-2. Fernandez Z, de Arruda Rodrigues R, Torres JM, Marcon GEB, de Castro Ferreira E, de Souza VF, Sarti EFB, Bertolli GF, Araujo D, Demarchi LHF, Lichs G, Zardin MU, Gonçalves CCM, Cuenca V, Favacho A, Guilhermino J, Dos Santos LR, de Araujo FR, Silva MR. Fernandez Z, et al. J Immunol Methods. 2023 May 11;519113489. doi Online ahead of print. J Immunol Methods. 2023. PMID 37179011 Free PMC article. Dynamics of Antibody Responses after Asymptomatic and Mild to Moderate SARS-CoV-2 Infections Real-World Data in a Resource-Limited Country. Sayabovorn N, Phisalprapa P, Srivanichakorn W, Chaisathaphol T, Washirasaksiri C, Sitasuwan T, Tinmanee R, Kositamongkol C, Nimitpunya P, Mepramoon E, Ariyakunaphan P, Woradetsittichai D, Chayakulkeeree M, Phoompoung P, Mayurasakorn K, Sookrung N, Tungtrongchitr A, Wanitphakdeedecha R, Muangman S, Senawong S, Tangjittipokin W, Sanpawitayakul G, Nopmaneejumruslers C, Vamvanij V, Auesomwang C. Sayabovorn N, et al. Trop Med Infect Dis. 2023 Mar 23;84185. doi Trop Med Infect Dis. 2023. PMID 37104311 Free PMC article. Convalescent Plasma Treatment of Patients Previously Treated with B-Cell-Depleting Monoclonal Antibodies Suffering COVID-19 Is Associated with Reduced Re-Admission Rates. Ioannou P, Katsigiannis A, Papakitsou I, Kopidakis I, Makraki E, Milonas D, Filippatos TD, Sourvinos G, Papadogiannaki M, Lydaki E, Chamilos G, Kofteridis DP. Ioannou P, et al. Viruses. 2023 Mar 15;153756. doi Viruses. 2023. PMID 36992465 Free PMC article. Characterisation of the Antibody Response in Sinopharm BBIBP-CorV Recipients and COVID-19 Convalescent Sera from the Republic of Moldova. Ulinici M, Suljič A, Poggianella M, Milan Bonotto R, Resman Rus K, Paraschiv A, Bonetti AM, Todiras M, Corlateanu A, Groppa S, Ceban E, Petrovec M, Marcello A. Ulinici M, et al. Vaccines Basel. 2023 Mar 13;113637. doi Vaccines Basel. 2023. PMID 36992221 Free PMC article. References Krammer F, Simon F. Serology assays to manage COVID‐19. Science. 2020;3681060‐1061. - PubMed Lee CY, Lin RTP, Renia L, Ng LFP. Serological approaches for COVID‐19 Epidemiologic perspective on surveillance and control. Front Immunol. 2020;11879. - PMC - PubMed Theel ES, Slev P, Wheeler S, Couturier MR, Wong SJ, Kadkhoda K. The role of antibody testing for SARS‐CoV‐2 is there one? J Clin Microbiol. 2020;5858. - PMC - PubMed Zost SJ, Gilchuk P, Case JB, et al. Potently neutralizing and protective human antibodies against SARS‐CoV‐2. Nature. 2020;584443‐449. - PMC - PubMed Rogers TF, Zhao F, Huang D, et al. Isolation of potent SARS‐CoV‐2 neutralizing antibodies and protection from disease in a small animal model. Science. 2020;369956‐963. - PMC - PubMed Publication types MeSH terms Substances LinkOut - more resources Full Text Sources Europe PubMed Central Ovid Technologies, Inc. PubMed Central Wiley Medical Genetic Alliance Miscellaneous NCI CPTAC Assay Portal Everyonewho has symptoms that are consistent with COVID-19 and people with known high-risk exposures to SARS-CoV-2 should be tested for SARS-CoV-2 infection. Such testing should employ either a nucleic acid amplification test (NAAT) or an antigen test to detect SARS-CoV-2. Testing may also be used for screening, determining the length of a . 2021 Dec;93126813-6817. doi Epub 2021 Aug 5. Affiliations PMID 34314037 PMCID PMC8427121 DOI Free PMC article The dynamics of quantitative SARS-CoV-2 antispike IgG response to BNT162b2 vaccination Shun Kaneko et al. J Med Virol. 2021 Dec. Free PMC article Abstract Vaccination for SARS-CoV-2 is necessary to overcome coronavirus disease 2019 COVID-19. However, the time-dependent vaccine-induced immune response is not well understood. This study aimed to investigate the dynamics of SARS-CoV-2 antispike immunoglobulin G IgG response. Medical staff participants who received two sequential doses of the BNT162b2 vaccination on days 0 and 21 were recruited prospectively from the Musashino Red Cross Hospital between March and May 2021. The quantitative antispike receptor-binding domain RBD IgG antibody responses were measured using the Abbott SARS-CoV-2 IgGII Quant assay cut off ≥50 AU/ml. A total of 59 participants without past COVID-19 history were continuously tracked with serum samples. The median age was 41 22-75 years, and 14 participants were male The median antispike RBD IgG and seropositivity rates were 0 AU/ml, AU/ml, AU/ml, 18, AU/ml, and 0%, 0%, and 100% on days 0, 3, 14, and 28 after the first vaccination, respectively. The antispike RBD IgG levels were significantly increased after day 14 from vaccination p < The BNT162b2 vaccination led almost all participants to obtain serum antispike RBD IgG 14 days after the first dose. Keywords COVID-19; SARS-Cov-2; mRNA vaccine; quantitative antispike RBD IgG. © 2021 Wiley Periodicals LLC. Conflict of interest statement The authors declare that there are no conflict of interests. Figures Figure 1 Dynamics of SARS‐CoV‐2 antispike RBD IgG response after vaccination. A Schema of the schedule for vaccination and blood test. B Antispike RBD IgG titer AU/ml and seropositive rate of antispike RBD IgG and antinucleocapsid IgG in a time‐dependent manner. RBD, receptor‐binding domain Similar articles Evaluation of Humoral Immune Response after SARS-CoV-2 Vaccination Using Two Binding Antibody Assays and a Neutralizing Antibody Assay. Nam M, Seo JD, Moon HW, Kim H, Hur M, Yun YM. Nam M, et al. Microbiol Spectr. 2021 Dec 22;93e0120221. doi Epub 2021 Nov 24. Microbiol Spectr. 2021. PMID 34817223 Free PMC article. Healthcare Workers in South Korea Maintain a SARS-CoV-2 Antibody Response Six Months After Receiving a Second Dose of the BNT162b2 mRNA Vaccine. Choi JH, Kim YR, Heo ST, Oh H, Kim M, Lee HR, Yoo JR. Choi JH, et al. Front Immunol. 2022 Jan 31;13827306. doi eCollection 2022. Front Immunol. 2022. PMID 35173736 Free PMC article. Evaluation of Seropositivity Following BNT162b2 Messenger RNA Vaccination for SARS-CoV-2 in Patients Undergoing Treatment for Cancer. Massarweh A, Eliakim-Raz N, Stemmer A, Levy-Barda A, Yust-Katz S, Zer A, Benouaich-Amiel A, Ben-Zvi H, Moskovits N, Brenner B, Bishara J, Yahav D, Tadmor B, Zaks T, Stemmer SM. Massarweh A, et al. JAMA Oncol. 2021 Aug 1;781133-1140. doi JAMA Oncol. 2021. PMID 34047765 Free PMC article. Evaluation of the SARS-CoV-2 Antibody Response to the BNT162b2 Vaccine in Patients Undergoing Hemodialysis. Yau K, Abe KT, Naimark D, Oliver MJ, Perl J, Leis JA, Bolotin S, Tran V, Mullin SI, Shadowitz E, Gonzalez A, Sukovic T, Garnham-Takaoka J, de Launay KQ, Takaoka A, Straus SE, McGeer AJ, Chan CT, Colwill K, Gingras AC, Hladunewich MA. Yau K, et al. JAMA Netw Open. 2021 Sep 1;49e2123622. doi JAMA Netw Open. 2021. PMID 34473256 Free PMC article. Review of SARS-CoV-2 Antigen and Antibody Testing in Diagnosis and Community Surveillance. Nerenz RD, Hubbard JA, Cervinski MA. Nerenz RD, et al. Clin Lab Med. 2022 Dec;424687-704. doi Clin Lab Med. 2022. PMID 36368790 Free PMC article. Review. No abstract available. Cited by Higher Immunological Response after BNT162b2 Vaccination among COVID-19 Convalescents-The Data from the Study among Healthcare Workers in an Infectious Diseases Center. Skrzat-Klapaczyńska A, Kowalska JD, Paciorek M, Puła J, Bieńkowski C, Krogulec D, Stengiel J, Pawełczyk A, Perlejewski K, Osuch S, Radkowski M, Horban A. Skrzat-Klapaczyńska A, et al. Vaccines Basel. 2022 Dec 15;10122158. doi Vaccines Basel. 2022. PMID 36560567 Free PMC article. Measurements of Anti-SARS-CoV-2 Antibody Levels after Vaccination Using a SH-SAW Biosensor. Cheng CH, Peng YC, Lin SM, Yatsuda H, Liu SH, Liu SJ, Kuo CY, Wang RYL. Cheng CH, et al. Biosensors Basel. 2022 Aug 4;128599. doi Biosensors Basel. 2022. PMID 36004995 Free PMC article. Relationship between changes in symptoms and antibody titers after a single vaccination in patients with Long COVID. Tsuchida T, Hirose M, Inoue Y, Kunishima H, Otsubo T, Matsuda T. Tsuchida T, et al. J Med Virol. 2022 Jul;9473416-3420. doi Epub 2022 Mar 8. J Med Virol. 2022. PMID 35238053 Free PMC article. The Comparability of Anti-Spike SARS-CoV-2 Antibody Tests is Time-Dependent a Prospective Observational Study. Perkmann T, Mucher P, Perkmann-Nagele N, Radakovics A, Repl M, Koller T, Schmetterer KG, Bigenzahn JW, Leitner F, Jordakieva G, Wagner OF, Binder CJ, Haslacher H. Perkmann T, et al. Microbiol Spectr. 2022 Feb 23;101e0140221. doi Epub 2022 Feb 23. Microbiol Spectr. 2022. PMID 35196824 Free PMC article. References Guan WJ, Ni ZY, Hu Y, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. 2020;382181708‐1720. - PMC - PubMed Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID‐19 in Wuhan, China a retrospective cohort study. Lancet. 2020;395102291054‐1062. - PMC - PubMed Zheng Z, Peng F, Xu B, et al. Risk factors of critical & mortal COVID‐19 cases a systematic literature review and meta‐analysis. J Infect. 2020;8116. - PMC - PubMed Hu Y, Sun J, Dai Z, et al. Prevalence and severity of corona virus disease 2019 COVID‐19 a systematic review and meta‐analysis. J Clin Virol. 2020;127104371. - PMC - PubMed World Health Organization . Coronavirus disease COVID‐19. Situation report. Accessed, May 17th, MeSH terms Substances LinkOut - more resources Full Text Sources Europe PubMed Central Ovid Technologies, Inc. PubMed Central Wiley Medical Genetic Alliance MedlinePlus Health Information Miscellaneous NCI CPTAC Assay Portal

Sumber Kementerian Kesehatan RI. Panduan teknis pelayanan Rumah Sakit pada masa adaptasi kebiasaan baru.. ALUR DAN ZONASI COVID-19.. Sumber: Kementerian Kesehatan RI.

Ao longo da pandemia de Covid-19, muitos nomes que não costumavam fazer parte da nossa vida se tornaram comuns. Boa parte dessas palavras novas são semelhantes e até parecem sinônimos, mas se referem a conceitos diferentes. Entender exatamente o que quer dizer cada novo termo da pandemia é importante para evitar a propagação de informações falsas ou incompletas. A diretora do Laboratório de Biotecnologia Viral do Instituto Butantan, Soraia Attie Calil Jorge, explica alguns desses conceitos e mostra por que é tão importante entendê-los. Vírus x Bactérias Vírus seres que dependem de outros para se reproduzir, ou seja, que precisam infectar células humanas, de plantas e até de bactérias para dar origem a seus descendentes. Não possuem células por isso se discute se são seres vivos ou não, apenas material genético e proteína. Às vezes, levam consigo parte da membrana da célula que infectaram; por isso, existem vírus envelopados e vírus não-envelopados, sendo que o envelopado é aquele que passou a ter em sua formação parte da membrana da célula invadida. Quando entram em nosso corpo, rompendo a membrana para se multiplicar, geralmente estouram nossas células, causando sua lise dissolução. Bactéria organismos mais independentes do que os vírus. São células que possuem material genético e diversos mecanismos para se desenvolver e multiplicar, sem precisar de outra célula. Por mais que algumas sejam prejudiciais ao nosso corpo, existem certas bactérias em nosso organismo que são benéficas e não causam doença alguma, geralmente fornecem substâncias importantes ou regulam parte do nosso metabolismo. Coronavírus X SARS-CoV-2 X Covid-19 Coronavírus nome dado a uma extensa família de vírus que se assemelham. Muitos deles já nos infectaram diversas vezes ao longo da história da humanidade. Dentro dessa família há vários tipos de coronavírus, inclusive os chamados SARS-CoVs a síndrome respiratória aguda grave, conhecida pela sigla SARS, que há alguns anos começou na China e se espalhou para países da Ásia, também é causada por um coronavírus. SARS-CoV-2 vírus da família dos coronavírus que, ao infectar humanos, causa uma doença chamada Covid-19. Por ser um microrganismo que até pouco tempo não era transmitido entre humanos, ele ficou conhecido, no início da pandemia, como “novo coronavírus”. Covid-19 doença que se manifesta em nós, seres humanos, após a infecção causada pelo vírus SARS-CoV-2. Prevalência x Incidência Prevalência visão geral de uma doença, ou seja, quantos casos ou mortes aquela doença provocou em sua totalidade. No Brasil, já temos mais de 21 milhões de casos e mais de 588 mil mortes por Covid-19, então esse número equivale à prevalência da doença. Incidência é um indicador mais fechado, que não olha em âmbito geral para uma doença, mas traça um recorte em determinado período de tempo. Em agosto, o Brasil registrou a menor incidência mensal de mortes por Covid-19 em 2021, com pouco mais de 24 mil óbitos. Mortalidade x Letalidade Mortalidade É o tanto de pessoas que adoeceram e morreram em relação a toda a população de uma região. Tem relação com um cenário geral, como a totalidade de mortos por determinada doença em uma população inteira durante uma pandemia, epidemia ou surto. Letalidade está ligada ao patógeno o vírus SARS-CoV-2, no caso e avalia o número de mortes em relação às pessoas que apresentam a doença ativa, e não em relação à população toda. Em outras palavras, mede a porcentagem de pessoas infectadas que evoluem para óbito. O SARS-CoV-2 não tem uma alta letalidade 2,9%, pois muitas pessoas que contraem o vírus ficam assintomáticas, às vezes sem nem mesmo saber que estão infectadas.

dokterdengan infeksi SARS-CoV-2 dapat berdasarkan kriteria berikut: 1. Berdasarkan gejala (symptom-based strategy) Asimtomatik dan tanpa imunokompromais berat: o >10 hari setelah pasien dinyatakan positif dengan tes diagnostik virus SARS-CoV-2 Simtomatik ringan hingga sedang, dan tanpa imunokompromais berat: o >10 hari sejak gejala muncul pertama

- Seperti diketahui, orang yang sudah pernah terinfeksi Covid-19 akan memiliki kekebalan tubuh atau antibodi terhadap serangan virus SARS-CoV-2 penyebab Covid-19 di masa depan. Namun, seberapa besar kekebalan tubuh orang yang pernah terpapar Covid-19?Mengenai persoalan ini, Dokter Spesialis Patologi Klinik Primaya Hospital Bekasi Barat dan Bekasi Timur, dr Muhammad Irhamsyah SpPK MKes angkat bicara. Irhamsyah menjelaskan bahwa terdapat metode pemeriksaan kekebalan tubuh manusia terhadap Covid-19 melalui pemeriksaan Antibodi SARS-CoV-2 kuantitatif. Baca juga Daftar 5 Kelompok Prioritas Vaksinasi Covid-19 Tahap Kedua, dari Guru hingga Pedagang Pemeriksaan Antibodi SARS-CoV-2 suatu pemeriksaan untuk mendeteksi suatu protein yang disebut antibodi, khususnya antibodi spesifik terhadap SARS-CoV-2 ini."Pemeriksaan ini dapat dilakukan pada orang-orang yang sudah pernah terinfeksi Covid-19, orang yang sudah mendapatkan vaksinasi, serta dapat digunakan untuk mengukur antibodi pada donor plasma konvalesen yang akan ditransfusikan,” kata Irhamsyah. Cara kerja pemeriksaan kuantitatif antibodi ECLIA Dijelaskan dr Irhamsyah, prinsip pemeriksaan kuantitatif antibodi spesifik SARS-CoV-2 ini menggunakan pemeriksaan laboratorium imunoserologi pada sebuah alat automatik autoanalyzer. Alat automatik ini dipergunakan untuk mendeteksi antibodi terhadap SAR-CoV-2. Pemeriksaan ini biasa disebut dengan Electro Chemiluminescence Immunoasssay ECLIA. ECLIA akan mendeteksi, mengikat, serta mengukur antibodi netralisasi. Sebagai informasi, antibodi netralisasi adalah antibodi yang dapat berikatan spesifik pada bagian struktur protein spike SARS-CoV-2. Protein spike adalah protein berbentuk paku yang tersebar di permukaan virus Covid-19, sebelum virus Covid-19 memasuki sel-sel pada tubuh kita dengan menggunakan label-label yang berikatan spesifik dengan antibodi netralisasi tersebut. Adapun, jenis sampel yang dapat digunakan dalam pemeriksaan ini yaitu sampel serum dan plasma dengan cara diambil darah vena. Journal Emergency Radiology Article Title: Qualitative and quantitative chest CT parameters as predictors of specific mortality in COVID-19 patients doi: 10.1007/s10140-020-01867-1 Figure Lengend Snippet: A 70-year-old man admitted to the emergency department with cough and fever from 1 week, with positive RT-PCR nasal-pharyngeal swab for SARS-CoV-2, who died 13 days Dear Editor,The Coronavirus disease 2019 COVID-19 pandemic has caused over 670 million cases and million deaths worldwide, many of which are attributed to cardiovascular complications. Virus-induced endothelial damage, endothelial barrier dysfunction, thrombosis, and cytokine storm are implicated in heart and multi-organ failure. The prognosis is worsened by comorbidities, including diabetes and arterial hypertension, characterized by an inflammatory and pro-thrombotic milieu and upregulation of total and glycosylated Angiotensin-Converting Enzyme 2 ACE2 in pericytes represent a preferential target of SARS-CoV-2 These perivascular cells preserve vascular integrity through physical and paracrine crosstalk with capillary endothelial cells. Pericyte dysfunction and detachment favor the SARS-CoV-2 to spread from the bloodstream and damage the infection starts with the engagement of the Spike S-protein with its cellular ACE-2 and CD147 receptors. Due to the homology with human proteins, the S-protein also acts as a natural ligand activating the ERK1/2 MAPK signaling pathway in cardiac Some evidence suggests that the S-protein, CD147, cyclophilin, and MAPK axis are essential in triggering the cytokine However, an in vivo demonstration of the S-protein’s direct damaging effect on cardiac pericytes is present study investigated the acute effects of intravenously injected S-protein on the heart microvasculature of otherwise healthy mice. Moreover, we analyzed the expressional changes caused by the S-protein in primary cultures of human cardiac pericytes using bulk RNA-Sequencing. Finally, the RNA-Sequencing data were cross-referenced with single-nuclei sn-RNA-Sequencing datasets of COVID-19 patients’ hearts to determine how expressional changes after SARS-CoV-2 infection overlap with those caused by the S-protein healthy CD1 mice 6 male, 6 female were randomized to receive either 10 µg endotoxin-free S-protein resuspended in 100 µL sterile PBS or PBS only, intravenously. They were culled three days later for molecular and histological analyses Fig. 1a. S-protein immunoreactive levels in the circulation were like those reported in COVID-19 patients early after infection and before seroconversion ± ng/mL.7 Immunohistochemistry of the hearts demonstrated that the S-protein, although not altering the capillary density, increased the fraction that expresses ICAM-1, an adhesion molecule implicated in leucocyte-endothelial interactions Fig. 1b and remarkably reduced the pericyte density, coverage, and viability Fig. 1c–e. SARS-CoV-2 can trigger direct or indirect activation of all three complement Here, we show that the in vivo administration of S-protein increased complement-activated C5a protein levels in peripheral blood and the heart Fig. 1f, g. Moreover, the S-protein increased the heart’s abundance of CD45+ immune cells ± cells/mm2 vs. ± cell/mm2 in PBS-treated mice, specifically Ly6G/6C+ neutrophils/monocytes Fig. 1h and F4/80+ macrophages Fig. 1i. Leucocytes can crawl along pericyte processes to enlarged gaps between adjacent pericytes in an ICAM-1-dependent manner during inflammation. Controls for immunohistochemistry stainings are provided in Supplementary Fig. 1a–i Injection of S-protein in vivo in mice. a Experimental design of the in vivo study in mice. b Representative immunofluorescence images of mice hearts showing capillaries IB4, green and activated endothelium ICAM-1, red. Bar graphs summarize the quantitative analysis of capillaries positive for ICAM-1, expressed as a percentage of total vessels. c Representative immunofluorescence images showing capillaries IB4, green and pericytes PDGFRβ, red. Bar graphs summarize the quantitative analysis of pericyte density. d Representative immunofluorescence images showing longitudinal capillaries IB4, green covered by pericytes PDGFRβ, red. Bar graphs report the quantitative analysis of pericyte coverage. e Representative immunofluorescence images of mice hearts showing endothelial cells IB4, green, pericytes PDGFRβ, red, and TUNEL-positive nuclei apoptotic nuclei, magenta. Bar graphs report the quantification of TUNEL+ pericytes. f Measurement of C5a in mice plasma using ELISA. g Immunohistochemistry/DAB staining and a bar graph showing the accumulation of the activated complement factor C5a in the mice hearts. Nuclei are shown in blue Haematoxylin. The graph reports the integrated optical density IOD values. Representative immunofluorescence images of mice hearts showing the presence of neutrophils/monocytes h—Ly6G/6 C, green and macrophages i—F4/80, green. Cardiomyocytes are labeled with α-Sarcomeric Actin red. Bar graphs report the density of Ly6G/6 C+ neutrophils/monocytes and F4/80+ macrophages. In all immunofluorescence images, DAPI labels nuclei in blue. For all images, the scale bar is 50 μm. For all analyses, n = 6 per group. All data are presented as individual values and means ± SEM. Statistical tests after a normality test, an unpaired t-Test was applied. j–l RNA-Sequencing analysis of human cardiac pericytes challenged with the S-protein in vitro. n = 3 patients. j Experimental design and volcano plot showing transcripts differentially expressed in S-protein-treated nM human cardiac pericytes vs. PBS vehicle-treated pericytes. The terms of the most relevant genes were reported. k Bar graph indicating all differentially expressed KEGG pathways. l Bar graphs indicating the most relevant differentially expressed Reactome pathways. FDR = false discovery rate. Genes were considered differentially expressed for FDR ≤ m–p Sn-RNA-Sequencing analysis of pericytes from COVID-19 patients’ hearts. n = 22 COVID patients, n = 25 controls. m Plots show the ordering of pericytes in pseudo-time. The starting point of pseudo-time is from the pericytes of healthy donors. n A heatmap summarizing the mean expression of normalized unique molecular identifiers UMIs of genes in the modules resulting from the pseudo-time analysis. o A volcano plot showing fold-change of module expression COVID-19 compared to healthy donors and enrichment significance of each module and differentially expressed genes from bulk RNA-Sequencing comparing PBS-vehicle and Spike. p A plot summarising overlapped/similar Reactome and Gene Ontology terms overrepresented in each module and differentially expressed genes in bulk RNA-Sequencing. q Schematic summarizing major findings and candidate mechanisms underpinning the S-protein damaging action. Left panel We provide novel evidence that S-protein alone can damage the heart microvasculature of otherwise healthy mice. On one side, the S-protein acts as a ligand activating intracellular pericyte signaling, which results in pericyte detachment, death, and decreased vascular coverage, thus disrupting the coronary microcirculation. On the other, the S-protein triggers endothelial activation ICAM-1+ endothelial cells, resulting in increased homing of leukocytes to the heart and accumulation of activated complement protein C5a. Right panel A comparison between the expressional changes induced by the S-protein in primary human cardiac pericytes in vitro and single-nuclei sn-RNA-Sequencing pseudo-time trajectories analysis in pericytes extracted from the heart of deceased COVID-19 patients revealed overlapping expressional responses as indicated. These findings suggest that at least some of the in vivo effects of SARS-CoV-2 on human cardiac pericytes may be due to the modulation of inflammatory and epigenetic pathways triggered by the S-protein interaction with its cell surface receptors. The drawing was created with size imageTo further validate the theory of the S-protein acting as a direct transcriptomic influencer, we added it or the PBS vehicle to human primary cardiac pericytes in vitro for 48 h. RNA-Sequencing analysis indicated the differential modulation of 309 RNA transcripts, with 201 genes being up-regulated and 108 genes down-regulated by the S-protein at FDR < Fig. 1j. KEGG pathway analysis showed an overrepresentation of inflammatory pathways, for example, TNF, IL-17, and NF-kappa B signaling pathways, cytokine-cytokine receptor interaction, and cell adhesion molecules CAMs. Moreover, there was an enrichment for pathways associated with infectious diseases, including Legionellosis, Pertussis, Malaria, Herpes virus, and Epstein-Barr virus infection Fig. 1k. An overview of the pathway analysis based on the Reactome database further pinpointed the transcriptional induction of cytokine signaling pathways, such as IL-10, IL-4, and IL-13 signaling and Toll-like receptor cascade Fig. 1l and Supplementary Fig. S2, and the downregulation of pathways implicated in histone deacetylation and methylation and chromatin modification, and RNA polymerase-related mechanisms controlling promoter opening and clearance, transcription, and chain elongation Fig. 1l and Supplementary Fig. S2. The analysis of modulated biological processes confirmed the upregulation of cellular responses to stress and the downregulation of homeostatic responses associated with healing and angiogenesis processes Supplementary Fig. S3. A comprehensive list of regulated pathways is provided in Supplementary Dataset to dissect clinically relevant targets further, we cross-interrogated the transcriptional landscape of pericytes exposed in vitro to the recombinant S-protein and pericytes from the hearts of COVID-19 patients. Additionally, we employed a pseudo-time inference approach to probe individual genes’ expression dynamics along with the progression of the disease. To this aim, we extracted pericytes from the integrated Seurat, R object downloaded from Delorey et al., 20219 using marker genes followed by a pseudo-time analysis of pericytes collected from the heart of COVID-19 patients Fig. 1m. The pseudo-time analysis allowed the identification of pericyte genes that are differential and co-expressed along the trajectory. This resulted in the recognition of 37 gene clusters Fig. 1n. Next, to identify common signals between ex vivo and in vivo datasets, we tested for the overrepresentation of expressional changes in pericytes exposed to S-protein and gene clusters in the human heart. We observed that seven gene clusters 1, 2, 6, 13, 15, 20, and 27, FDR < significantly overlapped with the expressional changes observed in pericytes exposed to the S-protein experiment Fig. 1o. Cluster 15 was enriched for cytokine-related pathways, metallothioneins, and regulation of histone acetylation, while clusters 1, 6 and 27 were overrepresented for extracellular matrix organization, elastic fibre formation, and integrin cell surface interactions Fig. 1p and Supplementary Dataset 2. Studies have reported that COVID-19 can cause cardiovascular complications due to impaired extracellular matrix organisation and reduced elastic fibre levels, potentially leading to blood These findings suggest a convergence of signals that proteins of the virion envelope mediate at least part of the transcriptional changes induced by the virus in the hearts of infected people. Therefore, some of the in vivo effects of SARS-CoV-2 on human cardiac pericytes may be attributable to the interaction between the S-protein and the host’s transcriptomic program modulating inflammatory and epigenetic we performed drug target enrichment analysis using the LINCS L1000CDS and DrugBank databases. This analysis allowed us to identify drugs that reverse the expressional changes induced by the S-protein in pericytes Supplementary Dataset 3 and 4. Among the top fifty compounds, we found a prevalence of anti-tumoral, pro-apoptotic, anti-viral, anti-inflammatory and anti-thrombotic drugs, some of which have already been trialed in COVID-19 patients. Although more research is needed to determine if pharmacological interference with the signaling emanating from the S-protein can alleviate COVID-19 outcomes, these data suggest a competitive effect of anti-inflammatory and anti-tumoral drugs. In addition, several compounds like Quercetin or ubiquitin-conjugating enzyme inhibitors may help moderate inflammation by eliminating S-Protein-induced senescent summarized in Fig. 1q provide novel evidence of the SARS-CoV-2 S-protein’s direct pathogenic action on cardiac pericytes and the heart’s microvasculature. It is plausible that the harmful effects observed in healthy mice three days after a single systemic injection of the S-protein might be intensified in the presence of cardiovascular risk factors and prolonged exposure. These possibilities merit further investigation. Moreover, we showed that the S-protein modifies the transcriptional program of human cells to the virus’ advantage. This new information could have significant implications for the treatment of COVID-19, for instance, using anti-S-protein engineering approaches to protect vascular cells. Data availabilityThe article’s data can be obtained as reasonably required from the corresponding author. The main datasets underlying transcriptomic analyses are provided as supplementary datasets Dataset 1–4. The bulk RNA-Seq raw data have been deposited in NCBI’s Gene Expression Omnibus and are accessible through GEO Series accession number N. et al. Glycated ACE2 receptor in diabetes open door for SARS-COV-2 entry in cardiomyocyte. Cardiovasc. Diabetol. 20, 99 2021.Article PubMed PubMed Central Google Scholar Sardu, C. et al. Could Anti-Hypertensive Drug Therapy Affect the Clinical Prognosis of Hypertensive Patients With COVID-19 Infection? 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The SARS-CoV-2 Spike protein disrupts human cardiac pericytes function through CD147 receptor-mediated signalling a potential non-infective mechanism of COVID-19 microvascular disease. Clin. Sci. 135, 2667–2689 2021.Article CAS Google Scholar Afzali, B., Noris, M., Lambrecht, B. N. & Kemper, C. The state of complement in COVID-19. Nat. Rev. Immunol. 22, 77–84 2022.Article CAS PubMed Google Scholar Delorey, T. M. et al. COVID-19 tissue atlases reveal SARS-CoV-2 pathology and cellular targets. Nature 595, 107–113 2021.Article CAS PubMed PubMed Central Google Scholar Shi, S. et al. Association of Cardiac Injury With Mortality in Hospitalized Patients With COVID-19 in Wuhan, China. JAMA Cardiol. 5, 802–810 2020.Article PubMed PubMed Central Google Scholar Download referencesAcknowledgementsThe authors wish to acknowledge the members of the University of Bristol COVID-19 Emergency Research Group UNCOVER for their scientific support. Drawings were generated with work was supported by the British Heart Foundation BHF project grant “Targeting the SARS-CoV-2 S-protein binding to the ACE2 receptor to preserve human cardiac pericytes function in COVID-19” PG/20/10285 to and European Commission H2020 CORDIS project COVIRNA project/id/101016072 to and and BHF Chair award CH/15/1/31199 to In addition, it was supported by a grant from the National Institute for Health Research NIHR Biomedical Research Centre at University Hospitals Bristol NHS Foundation Trust and the University of Bristol. is a postdoctoral researcher supported by the Heart Research UK translational project grant “Targeting pericytes for halting pulmonary hypertension in infants with congenital heart disease” RG2697/21/23 to and is an investigator of the Wellcome Trust 106115/Z/14/Z.Author informationAuthor notesThese authors contributed equally Elisa Avolio, Prashant K SrivastavaAuthors and AffiliationsBristol Medical School, Translational Health Sciences, University of Bristol, Bristol, UKElisa Avolio, Michele Carrabba, Christopher T. W. Tsang, Yue Gu, Anita C. Thomas & Paolo MadedduNational Heart & Lung Institute, Imperial College, London, UKPrashant K. Srivastava, Jiahui Ji & Costanza EmanueliSchool of Biochemistry, University of Bristol, Bristol, UKKapil Gupta & Imre BergerAuthorsElisa AvolioYou can also search for this author in PubMed Google ScholarPrashant K. SrivastavaYou can also search for this author in PubMed Google ScholarJiahui JiYou can also search for this author in PubMed Google ScholarMichele CarrabbaYou can also search for this author in PubMed Google ScholarChristopher T. W. TsangYou can also search for this author in PubMed Google ScholarYue GuYou can also search for this author in PubMed Google ScholarAnita C. ThomasYou can also search for this author in PubMed Google ScholarKapil GuptaYou can also search for this author in PubMed Google ScholarImre BergerYou can also search for this author in PubMed Google ScholarCostanza EmanueliYou can also search for this author in PubMed Google ScholarPaolo MadedduYou can also search for this author in PubMed Google research conception and design. manuscript writing. histological analyses of mice hearts. cellular and molecular biology experiments. transcriptomic analyses in pericytes. in vivo procedures with mice. production and provision of Spike protein. funding, supervision of transcriptomic studies, and manuscript editing. funding provision. study supervision. All authors data interpretation and manuscript revision. All authors approved the authorship and the final version of the manuscript for authorCorrespondence to Paolo declarations Competing interests The authors declare no competing interests. Ethics declarations The animal study was covered by a license from the British Home Office PPL 1377882 and complied with EU Directive 2010/63/EU. Procedures were carried out according to the principles in the Guide for the Care and Use of Laboratory Animals The Institute of Laboratory Animal Resources, 1996. Termination was conducted according to humane methods outlined in the Guidance on the Operation of the Animals Scientific Procedures Act 1986 Home Office 2014. The collection of human patients’ cardiac waste tissue was covered by the ethical approval number 15/LO/1064 from the North Somerset and South Bristol Research Ethics Committee. Patients gave informed written consent. Supplementary informationRights and permissions Open Access This article is licensed under a Creative Commons Attribution International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original authors and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit Reprints and PermissionsAbout this articleCite this articleAvolio, E., Srivastava, Ji, J. et al. Murine studies and expressional analyses of human cardiac pericytes reveal novel trajectories of SARS-CoV-2 Spike protein-induced microvascular damage. Sig Transduct Target Ther 8, 232 2023. citationReceived 11 January 2023Revised 28 April 2023Accepted 08 May 2023Published 02 June 2023DOI
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Pemeriksaanini dilakukan untuk mendeteksi respon kekebalan tubuh (abtibodi) secara kuantitatif terhadap visrus SARS-CoV-2. Pemeriksaan ini digunakan untuk melihat titer antibodi yang merepresentasikan kekebalan terhadap terhadap SARS-Cov_2 pada penyintas COVID-19, individu yang sudah mendapatkan vaksinasi COVID-19 maupun individu yang akan
Loading metrics Open Access Peer-reviewed Research Article Michael Tu, Jordan Cheng, Fang Wei, Feng Li, David Chia, Omai Garner, Sukantha Chandrasekaran, Richard Bender, Charles M. Strom , David T. W. Wong Development and validation of a quantitative, non-invasive, highly sensitive and specific, electrochemical assay for anti-SARS-CoV-2 IgG antibodies in saliva Samantha H. Chiang, Michael Tu, Jordan Cheng, Fang Wei, Feng Li, David Chia, Omai Garner, Sukantha Chandrasekaran, Richard Bender, Charles M. Strom x Published July 1, 2021 Figures AbstractAmperial™ is a novel assay platform that uses immobilized antigen in a conducting polymer gel followed by detection via electrochemical measurement of oxidation-reduction reaction between H2O2/Tetrametylbenzidine and peroxidase enzyme in a completed assay complex. A highly specific and sensitive assay was developed to quantify levels of IgG antibodies to SARS-CoV-2 in saliva. After establishing linearity and limit of detection we established a reference range of 5 standard deviations above the mean. There were no false positives in 667 consecutive saliva samples obtained prior to 2019. Saliva was obtained from 34 patients who had recovered from documented COVID-19 or had documented positive serologies. All of the patients with symptoms severe enough to seek medical attention had positive antibody tests and 88% overall had positive results. We obtained blinded paired saliva and plasma samples from 14 individuals. The plasma was analyzed using an EUA-FDA cleared ELISA kit and the saliva was analyzed by our Amperial™ assay. All 5 samples with negative plasma titers were negative in saliva testing. Eight of the 9 positive plasma samples were positive in saliva and 1 had borderline results. A CLIA validation was performed as a laboratory developed test in a high complexity laboratory. A quantitative non-invasive saliva based SARS-CoV-2 antibody test was developed and validated with sufficient specificity to be useful for population-based monitoring and monitoring of individuals following vaccination. Citation Chiang SH, Tu M, Cheng J, Wei F, Li F, Chia D, et al. 2021 Development and validation of a quantitative, non-invasive, highly sensitive and specific, electrochemical assay for anti-SARS-CoV-2 IgG antibodies in saliva. PLoS ONE 167 e0251342. Chandrabose Selvaraj, Alagappa University, INDIAReceived January 14, 2021; Accepted April 25, 2021; Published July 1, 2021Copyright © 2021 Chiang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are Availability Data is available on figshare DW is supported by U54HL119893, UCLA Keck Foundation Research Award Program. SC is supported by F30DE027615. This study was partially funded by Liquid Diagnostics, LLC LD. The funder provided reimbursement to MT as a paid consultant. This author contributed to this study by performing some experiments and in manuscript preparation. He did not contribute to the decision to publish, data collection or interests CS in an unpaid CEO of LD. CS, MT, RB, and DW are equity holders in LD. LD is the exclusive license holder for the Amperial™ technology from the University of California and hopes to commercialize products based on this technology. This does not alter our adherence to PLOS ONE policies on sharing data an materials. IntroductionA novel corona virus, severe acute respiratory syndrome coronavirus 2 SARS-CoV-2, has caused a global pandemic causing major disruptions world-wide [1]. Multiple high-throughput PCR based tests have been developed that are reasonably sensitive and specific, however the same cannot be said for antibody testing, prompting The Center for Disease Control CDC to issue guidelines entitled “Interim Guidelines for COVID-19 Antibody Testing” [2]. This publication describes the variability of in-home antibody tests and the lack of specificity required to make home-based antibody testing a valuable tool for epidemiologic surveillance. Having a reliable self-collection antibody test may be of enormous help in epidemiologic studies of background immunity, testing symptomatic individuals without RNA based testing during their acute illness, and screening health care providers and first responders to establish prior COVID-19 infection. Such a test may also be valuable in following vaccinated patients to assess the kinetics of anti-SARS-CoV-2 antibody production following inoculation. Multiple serological tests based on serum or plasma have been developed and marketed, with ELISA and lateral flow methods predominating. However, many methods suffer from low sensitivities and specificities [2–6]. Antibodies begin appearing in the first week following the development of symptoms. IgG, IgM, and IgA are detectable with IgA appearing somewhat earlier than IgG and IgM. Most patients seroconvert by 2 weeks following symptoms. Unlike IgA and IgM, IgG persists for several months following infection [7–9]. In a published study of 1,797 Icelandic individuals recovered from qPCR documented COVID-19 disease, 91% were IgG seropositive and antibody levels remained stable for 4 months after initial symptoms [10]. Notably of individuals quarantined due to exposure but untested for virus, with negative qPCR results, tested positive for IgG antibodies. Of 18,609 patients who were both unexposed and asymptomatic, the seropositivity rate was [11]. Since health care systems are burdened with care for COVID-19 patients, having a test that does not require phlebotomy would be extremely beneficial. To that end, investigations have been carried out using home finger prick blood sampling and even some home blood spot testing lateral flow strips [5–7]. However, home finger stick is invasive and not acceptable to some individuals, and requires a health care professional to administer the test to vulnerable individuals such as the elderly and children. In addition, home blood collection tests are less accurate than phlebotomy, with specificities less than 98%. In a low prevalence disease, the positive predictive value for a test with 98% specificity is less than 50% [7, 11]. Saliva is an oral fluid that is obtained easily and non-invasively. Proteomic studies show that the immunoglobulin profile in saliva is nearly identical to that of plasma [12]. Therefore, saliva is an excellent medium for COVID-19 antibody measurement. There are several commercially available collection devices to facilitate saliva collection, stabilization of IgG, and transport. A recently published study demonstrated excellent correlation between levels of COVID-19 antibodies in serum and saliva [13]. In order to be useful in population-based screening and to determine individual immunity in exposed populations, a SARS-CoV-2 antibody test must be highly specific because of the low seroprevalence rate in the population [2, 14]. In addition, the ability to quantify antibody levels is important for vaccine development and in monitoring for waning immunity [2, 14]. The only published saliva based assay for SARS-CoV-2 antibodies had only 89% sensitivity with 98% specificity [13], leading to a positive predictive value of only 49% in a population with a 2% prevalence of COVID-19 exposure. Our goal was to develop a non-invasive saliva based quantitative test for COVID-19 antibodies with exquisite sensitivity. We reviewed existing literature to find the SARS-CoV-2 antigen domain with the highest specificity and the ability to distinguish between the COVID-19 virus and other related Coronaviruses. The S1 domain is the most specific in terms of cross reactivity with other Corona and other respiratory viruses. As recombinant S1 antigen is readily available from at least 2 vendors, we chose the S1 antigen for our assay development. Levels of IgM and IgA deteriorate rapidly following recovery from COVID-19 infection; IgG levels remain detectable for several weeks to months [10]. Since the intended use of our assay is for population-based screening and vaccine efficacy monitoring, we chose to assay IgG only. The Amperial™ technology, formerly known as Electric Field Induced Release and Measurement EFIRM™, is a novel platform capable of performing quantitation of target molecules in both blood and saliva [15]. The device works by immobilizing capture moieties on the surface of an electrode structure for capturing target analytes and then quantifying the target analyte through electrochemically measuring oxidation-reduction between a hydrogen peroxide and tetramethylbenzidine substrate and peroxidase enzyme in a completed assay sandwich. The assay takes place on electrodes packaged in the format of a traditional 96-well microtiter plate, making the assay technique highly compatible and scalable with existing lab liquid handling instruments. We developed quantitative Amperial™ assays for IgG, IgM, and IgA antibodies to the S1 spike protein antigen of SARS-CoV-2. This test is highly sensitive >88% and specific > for patients with COVID-19 infections and correlates well with plasma ELISA analysis. The unique assay described in this article is completely non-invasive, allows home-collection, is quantitative, and has shown no false positives in 667 unexposed individuals, leading to a specificity of at least The assay has strong utility for clinical laboratories as it does not require purification/extraction of the saliva specimen, but the sample can simply be pipetted out of the collection device, diluted, and pipetted to the assay plate. The turnaround time of the assay is also fast, requiring less than 1 hour for a complete assay to be run. The widespread use of this test may be of great value in identifying individuals with prior exposure to SARS-CoV-2, to follow patients longitudinally to determine the kinetics of diminishing antibody concentration, and may be of special value in the longitudinal monitoring of vaccinated individuals to assess continued serologic immunity. Materials and methodsThe schematic of the Amperial™ SARS-CoV-2 IgG antibody is shown in Fig 1. The principle of the Amperial™ platform is that a biomolecule in this case SARS-CoV-2 Spike protein S1 antigen is added to a liquid pyrrole solution that is then pipetted into the bottom of microtiter wells containing a gold electrode at the bottom of each well. After the solution is added to each well, the plate is placed into the Amperial™ Reader and subjected to an electric current leading to polymerization. This procedure results in each well becoming coated with a conducting polymer gel containing the S1 antigen. Following the polymerization, diluted saliva, plasma, or serum is added to the well. Specific anti-S1 antibodies bind to the S1 antigen in the polymer. After rigorous washing procedures, the bound antibody is detected by using biotinylated anti-human IgG and then the signal is amplified by a standard streptavidin / horseradish peroxidase reaction that produces an electric current measured by the Amperial™ Reader in the nanoampere nA scale. The instrument is capable of accurately measuring current in the picoampere pA range, so the measurement is well within the ability of the instrument [13, 14, 16, 17]. The measurement of current rather than optical absorbance, as is done in the typical ELISA, has two important advantages over standard ELISA. Firstly, it allows precise quantitation of the amount of bound antibody and secondly, the measurement of current rather than optical absorbance allows increased sensitivity. Since antibody levels in saliva are lower than in plasma [13, 16], this increased sensitivity is crucial. The precise details of the assay are described in the next paragraph. COVID-19 Spike-1 Antigen Sanyou-Bio, Shanghai, China was diluted to a concentration of μg / mL, added to each well of the microtiter plate, and co-polymerized with pyrrole Sigma-Aldrich, St. Louis, MO onto the bare gold electrodes by applying a cyclic square wave electric field at 350 mV for 1 second and 1100 mV for 1 second. In total, polymerization proceeded for 4 cycles of 2 seconds each. Following this electro-polymerization procedure, 6 wash cycles were performed using 1x PBS with Tween-20 PBS-T using a 96-channel Biotek 405LS plate washer programmed to aspirate and dispense 400 μL of solution per cycle. Following the application of the polymer layer, 30 μL of saliva diluted at a 110 ratio in Casein/PBS Thermo-Fisher, Waltham, MA was pipetted into each well and incubated for 10 minutes at room temperature. Unbound components were removed by performing 6 wash cycles of PBS-T using the plate washer. Biotinylated anti-human IgG secondary antibody Thermofisher, Waltham, MA at a stock concentration of mg / mL was diluted 1500 in Casein/PBS and 30 μL pipetted to the surface of each well and incubated for 10 minutes at room temperature followed by 6 wash cycles using PBS-T. Subsequently, 30 μL of Poly-HRP80 Fitzgerald Industries, Acton, MA at a stock concentration of 2 μg / mL was diluted 125 in Casein/PBS, added to the wells, and incubated at 10 minutes at room temperature. Following a final wash using 6 cycles of PBS-T, current generation is accomplished by pipetting 60 μL of 1-Step Ultra TMB Thermofisher, Waltham, MA to the surface of the electrode and placing the plate into the Amperial™ reader where current is measured at -200 mV for 60 seconds. The current in nA is measured 3 times for each well. The process for reading the entire 96 well plate requires approximately 3 minutes. Plasma quantitative Amperial™ assay for SARS-CoV-2 IgG The protocol is similar to the Amperial™ SARS-CoV-2 IgG antibody for saliva samples. Following the application of the polymer layer, 30 μL of plasma diluted at a 1100 ratio in Casein/PBS Thermo-Fisher, Waltham, MA was pipetted into each well and incubated for 10 minutes at room temperature. The standard curve for plasma contains the following points 300 ng / ml, 150 ng / ml, 75 ng / ml, ng / ml, ng / ml, and 0 ng / ml. Plasma SARS-CoV-2 ELISA assay We purchased FDA EUA ELISA kits EUROIMMUN Anti-SARS-CoV-2 ELISA Assay for detection of IgG antibodies EUROIMMUN US, Mountain Lakes, NJ, Product ID EI 2606–9601 G, Lot E2001513BK. We processed samples exactly as described in the package insert. Human subjects Volunteers, with prior positive qPCR tests for COVID-19 infection or positive antibody tests using currently available FDA EUA-cleared antibody tests were consented via a written consent. Subjects enrolled were all over the age of 18. Subject participants responded to a questionnaire regarding severity of symptoms, onset of symptoms, and method of diagnosis UCLA IRB 06-05-042. Severity of symptoms were self-graded on the following 7-point scale 0 Asymptomatic 1 Mild Barely noticed, perhaps slight fever and cough 2 Moderate felt moderately ill but did not need to seek medical care 3 Sought medical Care but was not admitted to hospital 4 Hospitalized 5 Admitted to ICU 6 Placed on Ventilator A set of 13 paired saliva and plasma samples were provided by the Orasure™ Company. Saliva collection All COVID-19 samples were obtained using the Orasure™ FDA-cleared saliva collection device and used according to manufacturer instructions. The Orasure™ collection device consists of an absorbent pad on the end of a scored plastic wand. The individual places the pad between cheek and gum for a period of 2–5 minutes. Subsequently the wand and pad are placed into a tube containing transport medium, the top of the stick is broken off, and the tube is sealed for transport. The sealed tube is placed into a zip-lock bag and shipped by any standard method. According to the package insert, samples are stable at ambient temperature for 21 days see results below and Orasure™ website. An alternate sample collection method involves the individual swabbing the pad 4 times in the gingival tooth junction prior to placing the pad between the cheek and gum. This method has been shown to improve IgG yield in some patients with low antibody levels personal communication with Orasure Technologies, Inc.. Participant recruitment method Positive samples determined either through a positive SARS-CoV-2 viral test or antibody test were acquired beginning May 2020 to July 2020 via the described Orasure™ Oral Fluid Collection Device Kit previous described. Subjects were recruited into the study via electronic correspondence during the early stages of the COVID-19 pandemic in regions affected by COVID-19 California, Illinois, New York, New Jersey. Subjects are all over the age of 18. Subjects are not representative of the general population. Samples collected pre-2012 were used as controls. Saliva was collected from healthy individual volunteers at meetings of the American Dental Association between 2006 and 2011. Consent was obtained under IRB approval UCLA IRB 06-05-042. Both male and females, mostly non-smokers, 18–80 years of age, and differing ethnicities were included. All subjects were consented prior to collection. Each subject expectorated ~ 5 mL of whole saliva in a 50cc conical tube set on ice. The saliva was processed within 1/2 hour of collection. Samples were spun in a refrigerated centrifuge at 2600 X g for 15 minutes at 4°C. The supernatant cell-free saliva was then pipetted into two-2 mL cryotubes and μL Superase-In Ambion, Austin, TX was added as a preservative. Each tube was inverted to mix. The samples were frozen in dry ice and later stored in -80°C. Sample size and statistical methods Due to the nature of the pandemic and the evolving nature of EUA diagnostics during the early phases of the pandemic, no power calculations were performed for study size but instead the FDA/EUA recommendation of 30 subjects was followed. For components of work that required comparisons between groups, student’s T-test was conducted. p value, corresponds to a 95% confidence or p value, corresponds to 99% confidence. Data analysis performed was using GraphPad Prism Results Linearity Fig 2 demonstrates the dynamic range and linearity of the assay. In these experiments varying amounts of monoclonal human anti-S1 IgG was added to a saliva sample from a healthy volunteer and subjected to the assay. Fig 2 shows a range of to 6 ng/ml. The Y-axis shows nano-amperage measured nA. The X-axis represents spike-in concentrations of IgG. The assay begins to become saturated at about 3 ng / ml. Fig 3 shows dilutions down to ng / ml to ng / ml and shows linearity in that range. This allows us to create a standard curve containing the following points 3 ng / ml, ng / ml, ng / ml, ng / ml, ng / ml, and 0 ng / ml. Fig 2. Dynamic range and linear range of Amperial™ anti-Spike S1 IgG Amount of spike in anti-SARS-CoV-2 IgG in ng / ml. Y-axis Normalized current in nA. Panel A 0–5 ng / ml Panel B ng / ml. Inhibition assay In order to demonstrate the specificity for the assay on actual clinical samples, we used the saliva from 3 recovered patients who had high levels of SARS-CoV-2 antibodies and added exogenous S1 antigen in varying amounts prior to analysis on the Amperial™ assay. The exogenous S1 antigen should compete for binding sites and therefore extinguish the nA signal. Fig 3 shows the results of this experiment. The red, purple, and green represent 3 different patients. The X-axis demonstrates increasing concentration of exogenous S1 added to the saliva before subjecting it to the assay. As shown, saliva pre-incubated with S1 antigen extinguishes the detectable IgG signal proportionately, therefore demonstrating the specificity of the assay to S1 antigen in clinical samples. Matrix effects Since we are be comparing samples collected by various methods, it is vital to determine if any significant matrix effects could interfere with data interpretation. We examined the 3 different collection methods used in this study Expectoration/centrifugation, Orasure™ without swabbing and Orasure™ with swabbing. Two methods of collection using the Orasure™ Oral Fluid Collection Device were tested. The first method non-swabbing collects saliva by placing an absorbent pad into the lower gum area for 2–5 minutes and then placing the saturated collection pad into a preservative collection tube. The second method swabbing adds the step of first gently rubbing the collection pad along gum line, between the gum and cheek, 5 times, before placing the device in the lower gum area for 2–5 minutes, and then immersing the saturated collection pad into the collection tube. Healthy donors n = 5 collected their saliva using these two different methods. The control pre-2012 samples were collected with an expectoration protocol for whole saliva collection falcon tubes, processing centrifuge, stabilization, and storage. Five samples collected by each of the 3 methods and were analyzed in duplicate. The results are shown in Fig 4 under the heading “No spike in.” There are no differences among 3 sample types. We then added monoclonal human anti-S1 IgG to each sample and again ran them in duplicate Fig 4 above caption Spike-in ng / ml IgG. A non-parametric Student t-test was performed with no significant differences between any of the collection methods. Stability The Orasure™ collector is an FDA-cleared device for the analysis of anti-HIV IgG. The package insert describes a 21-day stability at ambient temperature. We wished to establish the stability of anti-COVID-19 IgG using this collector. Passive whole saliva was collected from four healthy individuals using 50 mL falcon tubes and spiked with anti-Spike S1 IgG to reach a final concentration of 300 ng / ml. Aliquots of mL of saliva were placed into 50 mL tubes and then the sponge of the Orasure™ collector was submerged into the saliva for five minutes and processed as described in Methods. The collected saliva was then aliquoted into PCR tubes and left at ambient temperature 21°C for 0, 1, 3, 7, and 14 days before storage at -80°C. After 14 days, samples were thawed and assayed using the anti-Spike S1 IgG Amperial™ assay to assess stability. At 14 days, 95% of the original signal remained, demonstrating the 14-day stability of anti-SARS-CoV-2 antibodies collected in Orasure™ containers see Fig 5. Fig 5. Stability study performed on spike-in of SARS-CoV-2 IgG into healthy saliva specimen using two different methods a research SOP which involves expectoration into a falcon tube and the Orasure™ Oral Fluid collection device.The collect saliva was aliquoted and left at ambient temp for 0, 1, 3, 7, 14 days. Results were normalized relative to the measured assay signal of a sample at day 0. Results show that the sample is stable with no significant degradation for up to 14 days. Specificity and reference range Once we established no significant differences between the tube collection method and the Orasure™ collector method, we analyzed a series of 667 samples collected between 2006 and 2009 at the annual meeting of the American Dental Association. Scatter plots of these data for both nA and ng / ml are shown in Fig 6A and 6B. We established the mean and standard deviation for both raw nA values and concentration in ng / ml. In order to maximize specificity, we selected a reference range > 5 SD above the mean. A 5 sigma level would lead to a specificity of In fact, we have never seen a healthy sample above the 5 sigma level. As will be seen, the sensitivity of the assay remains greater than 88% even with this rigorous specificity. Fig 6. Healthy reference range of Amperial™ saliva anti-SARS-CoV-2 IgG assay of 667 unexposed subjects in A normalized current ΔnA with mean = and cutoff = and B concentration ng / ml with mean = and cutoff = Recovered COVID-19 patients Fig 7 displays the scatter plot for 667 healthy controls and 34 volunteer patients who recovered from COVID-19 infection. All patients were a minimum of 14 days post onset of symptoms and some patients were as many as 15 weeks post symptoms. The 5 sigma cutoff is shown by the green dotted line. A more detailed discussion of the recovered patients appears in the following section. The data show that all healthy patients are negative and 30 of the 34 recovered patients are positive. These data demonstrate a sensitivity of 88% and a specificity of > It is important to note that not all recovered patients have detectable antibody [10] so the 4 patients with undetectable antibody may be biologically negative and not the result of lack of sensitivity of the assay. Fig 8 demonstrates the relationship of anti-S1 IgG levels to severity of symptoms. Table 1 is a tabular summary of these data. All patients who had severity indexes ≥3 sought medical attention, admitted to hospital, admitted to ICU, on ventilator had positive antibody levels. Although 4 patients with mild symptoms had antibody levels in the normal range, both asymptomatic patients had appreciable antibody levels. These patients were close contacts of more severely affected patients. The highest antibody level recorded is severity index level 2 patient moderate symptoms, did not seek medical care. It is important to note that both asymptomatic patients had easily detectable antibody levels in saliva, suggesting this test may be useful in general population screening. Paired saliva and plasma samples We obtained 14 paired, blinded plasma and saliva samples. The plasma was analyzed by an FDA EUA-cleared ELISA test purchased from EUROIMMUN see Methods. The saliva samples, collected in Orasure™ buffer, were analyzed by the Amperial™ assay described in Methods. After unblinding, we discovered 8 recovered COVID patients and 5 healthy patients in this series. All 5 healthy patients were negative in both the saliva and plasma assays. In 7 of the 8 recovered patients, both plasma and saliva tests were positive. There was one sample with a discrepancy between saliva and plasma, with the plasma positive and the saliva in the indeterminate range. The EUROIMMUNE ELISA assay is a semi-quantitative assay and yields an absorbance ratio rather than a quantity. Fig 9 demonstrates the relationship between the saliva quantitative results and plasma absorbance ratio for the paired plasma and saliva samples. There is a clear relationship between the 2 levels, with the higher plasma absorbance ratios associated with higher saliva quantitation. Fig 9. COVID-19 antibody level in paired saliva and plasma of COVID-19 n = 8 subjects in a blinded randomized antibodies level are measured by EUROIMMUN ELISA reported in ratio proportion of OD of calibrator to OD of sample and saliva antibodies are measured by Amperial™ in pg / ml. Green dashed line indicates 5 SD reference range cutoff of Amperial™ test and red dashed line is reference range for EUROIMMUN ELISA. developed a research quality assay to quantify anti-SARS-CoV-2 IgG levels in plasma see Methods. We analyzed the 13 plasma samples using this assay. The results of this experiment are shown in Fig 10. Panel A shows a log / log plot of plasma versus saliva levels showing a clustering with high plasma levels associated with high saliva levels. Panel B shows the box plot of these values, demonstrating that plasma levels are approximately 50X those of saliva. This observation explains the necessity for an extremely sensitive assay such as the Amperial™ assay in order to detect antibodies in saliva. Of note, the publication regarding saliva SARS-CoV-2 IgG detection reports levels of 25–60 mcg / ml, 1000 times less sensitive than our assay. Fig 10. Relationship of plasma anti-SARS-CoV-2 IgG levels to saliva levels measured by Amperial™ assays.A Panel A shows a log / log plot of plasma versus saliva levels showing a clustering of the positive values with high plasma levels associated with high saliva levels on the Amperial™ platform. B Box plot of COVID-19 n = 8 and healthy n = 5 subjects demonstrating that the normalized plasma levels are approximately 50X those of saliva. Longitudinal tracking of antibody levels Three of our volunteers supplied samples at weekly intervals so we could determine the stability of their antibody levels. Results appear in Fig 11. The 5 standard deviation cutoff is again shown with the dashed green line. All 3 patients continued to have detectable levels for more than 12 weeks, with the longest interval of 15 weeks. All tests were positive in all patients and antibody levels in all 3 patients remained clearly positive during the time interval studied. Patients C1 and C3 seem to have a rise in antibody level between 11 and 12 weeks post initial symptoms followed by a return to baseline level. Patient C2 might also have had a spike in antibody levels at 10 weeks. This may be result of the amnestic B-cell population becoming established. There is insufficient data at this time to determine if this is a generalized pattern. CLIA evaluation We performed a full CLIA laboratory developed test evaluation for the Amperial™ COVID-19 IgG Antibody test. The validation assayed 72 unaffected patients and 30 recovered patients and demonstrated 100% sensitivity and specificity. The intra-assay and inter-assay variability were and respectively. DiscussionWe have developed an exquisitely specific, sensitive, non-invasive saliva based quantitative assay for anti-SARS-CoV-2 IgG antibodies. Our goal was to create a quantitative assay with sufficient positive predictive value to be useful to inform individuals regarding previous infection with COVID-19. By establishing a reference range of 5 sigma above than the mean we have a theoretical analytical specificity of We plan to repeat the analysis of all positive samples to further increase analytical specificity. Since our test is non-invasive with home-collection we can also offer repeat testing on a second sample to further increase specificity. These procedures will minimize the false positives due to purely technical issues. There is still the possibility of biological false positives, however, due to cross reactivity with other infectious or environmental agents. The S1 antigen appears to be specific for SARS-CoV-2 [2, 3, 10] and in our series of 667 samples collected prior to 2019 we observed no false positive results. We cannot predict the eventual clinical specificity of this assay. At a minimum, the specificity is 667 / 668 or assuming the next control sample tested would be a false positive, but the specificity is likely to be higher. Our current sensitivity is 100% for patients with symptoms severe enough to seek medical care. For all patients, including mildly asymptomatic patients, our clinical sensitivity is 88%. Since the Amperial™ assay only requires 6 μL of collection fluid, several assays can be performed from the same sample. This allows all positives to be repeated to confirm the positive results and further increase the specificity of the assay. We will offer testing of a second, independent sample for all patients testing positive. Since saliva collection is easily be performed at home, obtaining a second sample is not difficult. For any laboratory test, the PPV is proportional to the prevalence of positivity in the population. A recent study demonstrated a prevalence of between to 6% in Britain [17]. Using the minimum specificity of and a prevalence of 6% the Amperial™ saliva assay would have a minimum PPV of 96%. In contrast, a published saliva antibody detection assay reported a specificity of 98% with a similar sensitivity 89%. This specificity leads to PPV of only 69% making it an ineffective tool for population screening. Our data demonstrate that the Imperial™ assay is appropriate for longitudinal screening of antibody levels, a particular utility in vaccine trials and in population monitoring following mass immunization. Since this assay is quantitative and levels appear to be stable with time, patients may be monitored from home at frequent intervals. If antibodies raised in response to vaccination do not include IgG antibodies to S1 antigen, it is easy to rapidly develop Amperial™ antibody tests to any antigen. This requires adding the new antigen to the pyrrole solution and does not require significant alteration of assay conditions. A particular advantage of this assay is convenience. The Orasure™ collector is simple and easy to use and does not require professional monitoring for adequate collection. Home collection relieves the burden to an already stressed health care system. Vulnerable populations such as children and the elderly can be guided through the collection process by parents or other adults. It is possible to obtain repeat samples to confirm positives and to perform longitudinal testing since the only requirement for testing is shipping the collecting kit. The Amperial™ IgG test is plate-based and high-throughput. An entire plate is easily processed in 2 hours, leading to rapid turnaround time once the sample enters the laboratory. There is no pre-processing of the sample required; samples are taken directly from the collection vial and placed into the assay. With standard liquid handlers, the assay may be easily automated allowing for extremely high-throughput since the Amperial™ reader is only required for the polymerization step of less than a minute at the beginning of the assay and 3 minutes for the measurement phase at the end of the assay. Published data [13] and our own demonstrate a correlation between blood results and saliva results indicating that the IgG present in saliva is most likely derived from the plasma through filtration. Our data shows that saliva IgG levels are approximately 50-fold less than those in plasma necessitating a highly sensitive assay in order to detect the IgG levels in saliva. There is some discussion in the literature of the role antibody testing may have in managing the COVID-19 epidemic. Alter and Seder published an editorial in the New England Journal of Medicine arguing, “Contrary to recent reports suggesting that SARS-CoV-2 RNA testing alone, in the absence of antibodies, will be sufficient to track and contain the pandemic, the cost, complexity, and transient nature of RNA testing for pathogen detection render it an incomplete metric of viral spread at the population level. Instead, the accurate assessment of antibodies during a pandemic can provide important population-based data on pathogen exposure, facilitate an understanding of the role of antibodies in protective immunity, and guide vaccine development [14]”. ConclusionIn this article, we describe the development of a non-invasive, home collection based, exquisitely specific, and acceptably sensitive test for the presence of anti-SARS-CoV-2 antibodies in saliva. This may be an important tool in controlling the pandemic and facilitating and understanding of the role of antibody production in COVID-19 immunity. Longitudinal monitoring of anti-SARS-CoV-2 IgG levels could also play a valuable role in vaccine development and deployment by allowing longitudinal quantitative assessment of antibody levels. If the presence of detectable anti-COVID-19 IgG is shown to be an indicator of immunity to reinfection, measurement of these antibodies could allow individuals to safely return to work, school and community. The Amperial™ SARS-CoV-2 assay fulfills the requirements for all of these applications. References1. Guan W, Ni Z, Hu Y, Liang W, Ou C, He J, et al. Clinical Characteristics of Coronavirus Disease 2019 in China. New Eng J Med. 2020 Apr;382181708–20. pmid32109013 View Article PubMed/NCBI Google Scholar 2. Interim Guidelines for COVID-19 Antibody Testing. Center for Disease Control and Prevention. 2020 Aug 1. [Cited 2020 Nov 5] 3. Hoffman T, Nissen K, Krambach J, Ronnberg B, Akaberi D, Esmaeilzadeh , et al. Evaluation of a COVID-19 IgM and IgG rapid test; an efficient tool for assessment of past exposure to SARS-CoV-2. Infection Ecology and Epidemiology. 2020 Jan 1;1011754538. pmid32363011 View Article PubMed/NCBI Google Scholar 4. 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Hettegger P, Huber J, Pabecker K, Soldo R, Kegler U, Nöhammer C, et al. High similarity of IgG antibody profiles in blood and saliva opens opportunities for saliva based serology. PLoS ONE. 2019 Jun 20;146e0218456. pmid31220138 View Article PubMed/NCBI Google Scholar 13. Isho B, Abe KT, Zuo M, Jamal A, Rathod B, Wang J, et al. Persistence of serum and saliva antibody responses to SARS-CoV-2 spike antigens in COVID-19 patients. Sci Immunol. 2020 Oct 8;552eabe5511. pmid33033173 View Article PubMed/NCBI Google Scholar 14. Alter G, Seder R. The power of Antibody-Based Surveillance. N Engl J Med. 2020 Oct 29;383181782–1784. pmid32871061 View Article PubMed/NCBI Google Scholar 15. Wei F, Patel P, Liao W, Chaudhry K, Zhang L, Arellano-Garcia M, et al. Electrochemical Sensor for Multiplex Biomarkers Detection. Clinical Cancer Research. 2009;15 4446–4452. pmid19509137 View Article PubMed/NCBI Google Scholar 16. 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PemeriksaanAntibodi Kuantitatif adalah tes yang dilakukan untuk mengukur jumlah antibodi IgG SARS-CoV-2. Tujuan Pemeriksaan. Mengetahui dan memonitor respon imun terhadap vaksin. Mengetahui tingkat antibodi untuk menentukan apakah seseorang dapat melakukan donor plasma kepada pasien covid yang membutuhkan; Sampel pemeriksaan Petugas memeriksa beberapa sampel PCR COVID-19 ilustrasi. JAKARTA - Pendistribusian vaksin SARS-CoV-2 alias Covid-19 tengah berlangsung. Di tengah kondisi itu, banyak pertanyaan bermunculan terkait seberapa besar kekebalan tubuh seseorang yang pernah terpapar Covid-19. Menurut Muhammad Irhamsyah, dokter spesialis patologi di Klinik Primaya Hospital Bekasi Barat dan Bekasi Timur, ada metode untuk memeriksanya. Kekebalan tubuh terhadap Covid-19 bisa diketahui melalui tes antibodi SARS-CoV-2 kuantitatif. "Pemeriksaan ini dapat dilakukan pada orang-orang yang pernah terinfeksi Covid-19, orang yang sudah mendapatkan vaksinasi, serta dapat digunakan untuk mengukur antibodi pada donor plasma konvalesen yang akan ditransfusikan," ujar Irhamsyah. Tes mendeteksi protein yang disebut antibodi, khususnya antibodi spesifik terhadap SARS-CoV-2. Prinsipnya menggunakan pemeriksaan laboratorium imunoserologi pada sebuah alat automatik autoanalyzer untuk mendeteksi antibodi itu. Pemeriksaan ini biasa disebut dengan ECLIA Electro chemiluminescence immunoassay. ECLIA mendeteksi, mengikat, serta mengukur antibodi netralisasi, yaitu antibodi yang berikatan spesifik pada struktur protein Spike SARS-CoV-2. Protein itu terdapat pada permukaan virus Covid-19 sebelum memasuki sel-sel pada tubuh. Pengukuran menggunakan label-label yang berikatan spesifik dengan antibodi netralisasi. Jenis sampel yang digunakan yakni sampel serum dan plasma. BACA JUGA Ikuti News Analysis News Analysis Isu-Isu Terkini Perspektif Klik di Sini Tesantibodi kuantitatif untuk covid-19 ini dilakukan agar dapat mengetahui jumlah antibodi yang spesifik yang ada didalam tubuh. Antibodi tersebut dapat dikatakan dengan SARS-COV-2, kemudian tes ini juga dapat menunjukan hasil dari respon kekebalan tubuh seseorang terhadap virus sars-cov-2 ini. Tes Serologi Covid-19
. 2021 Aug 18;599e0028821. doi Epub 2021 Aug 18. Affiliations PMID 34260272 PMCID PMC8373017 DOI Free PMC article Performance of the Abbott SARS-CoV-2 IgG II Quantitative Antibody Assay Including the New Variants of Concern, VOC 202012/V1 United Kingdom and VOC 202012/V2 South Africa, and First Steps towards Global Harmonization of COVID-19 Antibody Methods Emma English et al. J Clin Microbiol. 2021. Free PMC article Abstract In the initial stages of the severe acute respiratory syndrome coronavirus 2 SARS-CoV-2 COVID-19 pandemic, a plethora of new serology tests were developed and introduced to the global market. Many were not evaluated rigorously, and there is a significant lack of concordance in results across methods. To enable meaningful clinical decisions to be made, robustly evaluated, quantitative serology methods are needed. These should be harmonized to a primary reference material, allowing for the comparison of trial data and improved clinical decision making. A comprehensive evaluation of the new Abbott IgG II anti-SARS-CoV-2 IgG method was undertaken using CLSI-based protocols. Two different candidate primary reference materials and verification panels were assessed with a goal to move toward harmonization. The Abbott IgG II method performed well across a wide range of parameters with excellent imprecision < and was linear throughout the positive range tested to 38,365 AU/ml. The sensitivity based on ≥14-day post-positive reverse transcription-PCR [RT-PCR] samples and specificity were to and to 100%, respectively. The candidate reference materials showed poor correlation across methods, with mixed responses noted in methods that use the spike protein versus the nucleocapsid proteins as their binding antigen. The Abbott IgG II anti-SARS-CoV-2 measurement appears to be the first linear method potentially capable of monitoring the immune response to natural infection, including from new emerging variants. The candidate reference materials assessed did not generate uniform results across several methods, and further steps are needed to enable the harmonization process. Keywords COVID-19; SARS-CoV-2; analytical performance; antibody assay; evaluation; harmonization; serology; variants. Figures FIG 1 Linearity of method over the complete working range of the Abbott IgG II assay using a range of dilutions of a high positive mean, 38,365 AU/ml in the Abbott diluent. Dash-dot line indicates the identity line. The darker dotted line represents the 95% likelihood asymmetrical CI of the slope. FIG 2 Cohen’s kappa concordance analysis of the assays and overall all samples included agreement of results given as percent. Equivocal results were considered negative. FIG 3 Representative examples of the quantitative immune response in three different variants of the SARS-CoV-2 virus, including the “UK” and “South Africa” variants. The days post-PCR do not necessarily correlate to the day of onset of symptoms or the day of hospitalization. FIG 4 Comparison graphs of the values obtained for the Technopath positive panel with different methods A Abbott IgG II versus DiaSorin Liaison XL; B Abbott IgG II versus EDI; C Abbott IgG II quantitative S versus Abbott IgG qualitative R. Only the Abbott quantitative assay showed linearity r2 = and was plotted against DiaSorin, quadratic r2 = A, EDI, 4-PL r2 = B, and Abbott qualitative, 4-PL r2 = C. FIG 5 Dilution of NIBSC working standard 20/162 using the Abbott diluent. Dash-dot line indicates the identity line. The darker dotted line represents the 95% likelihood asymmetrical CI of the slope. Similar articles Clinical and analytical evaluation of the Abbott AdviseDx quantitative SARS-CoV-2 IgG assay and comparison with two other serological tests. Maine GN, Krishnan SM, Walewski K, Trueman J, Sykes E, Sun Q. Maine GN, et al. J Immunol Methods. 2022 Apr;503113243. doi Epub 2022 Feb 16. J Immunol Methods. 2022. PMID 35181288 Free PMC article. SARS-CoV-2 Antibody Testing in Health Care Workers A Comparison of the Clinical Performance of Three Commercially Available Antibody Assays. Allen N, Brady M, Carrion Martin AI, Domegan L, Walsh C, Houlihan E, Kerr C, Doherty L, King J, Doheny M, Griffin D, Molloy M, Dunne J, Crowley V, Holmes P, Keogh E, Naughton S, Kelly M, O'Rourke F, Lynagh Y, Crowley B, de Gascun C, Holder P, Bergin C, Fleming C, Ni Riain U, Conlon N; PRECISE Study Steering Group. Allen N, et al. Microbiol Spectr. 2021 Oct 31;92e0039121. doi Epub 2021 Sep 29. Microbiol Spectr. 2021. PMID 34585976 Free PMC article. A Qualitative Comparison of the Abbott SARS-CoV-2 IgG II Quant Assay against Commonly Used Canadian SARS-CoV-2 Enzyme Immunoassays in Blood Donor Retention Specimens, April 2020 to March 2021. Abe KT, Rathod B, Colwill K, Gingras AC, Tuite A, Robbins NF, Orjuela G, Jenkins C, Conrod V, Yi QL, O'Brien SF, Drews SJ. Abe KT, et al. Microbiol Spectr. 2022 Jun 29;103e0113422. doi Epub 2022 Jun 2. Microbiol Spectr. 2022. PMID 35652636 Free PMC article. Efficacy of frontline chemical biocides and disinfection approaches for inactivating SARS-CoV-2 variants of concern that cause coronavirus disease with the emergence of opportunities for green eco-solutions. Rowan NJ, Meade E, Garvey M. Rowan NJ, et al. Curr Opin Environ Sci Health. 2021 Oct;23100290. doi Epub 2021 Jul 3. Curr Opin Environ Sci Health. 2021. PMID 34250323 Free PMC article. Review. Recapping the Features of SARS-CoV-2 and Its Main Variants Status and Future Paths. Ortega MA, García-Montero C, Fraile-Martinez O, Colet P, Baizhaxynova A, Mukhtarova K, Alvarez-Mon M, Kanatova K, Asúnsolo A, Sarría-Santamera A. Ortega MA, et al. J Pers Med. 2022 Jun 18;126995. doi J Pers Med. 2022. PMID 35743779 Free PMC article. Review. Cited by The changing profile of SARS-CoV-2 serology in Irish blood donors. Coyne D, Butler D, Meehan A, Keogh E, Williams P, Carterson A, Hervig T, O'Flaherty N, Waters A. Coyne D, et al. Glob Epidemiol. 2023 Dec;5100108. doi Epub 2023 Apr 21. Glob Epidemiol. 2023. PMID 37122774 Free PMC article. Mix-and-match COVID-19 vaccines trigger high antibody response after the third dose vaccine in Moroccan health care workers. Amellal H, Assaid N, Akarid K, Maaroufi A, Ezzikouri S, Sarih M. Amellal H, et al. Vaccine X. 2023 Aug;14100288. doi Epub 2023 Mar 25. Vaccine X. 2023. PMID 37008956 Free PMC article. Impact of MERS-CoV and SARS-CoV-2 Viral Infection on Immunoglobulin-IgG Cross-Reactivity. AlKhalifah JM, Seddiq W, Alshehri MA, Alhetheel A, Albarrag A, Meo SA, Al-Tawfiq JA, Barry M. AlKhalifah JM, et al. Vaccines Basel. 2023 Feb 26;113552. doi Vaccines Basel. 2023. PMID 36992136 Free PMC article. Dynamics of Anti-S IgG Antibodies Titers after the Second Dose of COVID-19 Vaccines in the Manual and Craft Worker Population of Qatar. Bansal D, Atia H, Al Badr M, Nour M, Abdulmajeed J, Hasan A, Al-Hajri N, Ahmed L, Ibrahim R, Zamel R, Mohamed A, Pattalaparambil H, Daraan F, Chaudhry A, Oraby S, El-Saleh S, El-Shafie SS, Al-Farsi AF, Paul J, Ismail A, Al-Romaihi HE, Al-Thani MH, Doi SAR, Zughaier SM, Cyprian F, Farag E, Farooqui HH. Bansal D, et al. Vaccines Basel. 2023 Feb 21;113496. doi Vaccines Basel. 2023. PMID 36992080 Free PMC article. Quantification of Severe Acute Respiratory Syndrome Coronavirus 2 Binding Antibody Levels To Assess Infection and Vaccine-Induced Immunity Using WHO Standards. Pernet O, Balog S, Kawaguchi ES, Lam CN, Anthony P, Simon P, Kotha R, Sood N, Hu H, Kovacs A. Pernet O, et al. Microbiol Spectr. 2023 Feb 14;111e0370922. doi Epub 2023 Jan 23. Microbiol Spectr. 2023. PMID 36688648 Free PMC article. References Worldometer. 2021. COVID-19 coronavirus pandemic. Dover, DE, USA. Accessed 10 January 2021. World Health Organization. 2021. Weekly epidemiological update on COVID-19 – 16 March 2021. World Health Organization, Geneva, Switzerland. Krammer F. 2020. SARS-CoV-2 vaccines in development. Nature 586516–527. - DOI - PubMed Department of Health and Social Care. 2021. UK COVID-19 vaccines delivery plan. Department of Health and Social Care, London, United Kingdom. Khoury DS, Wheatley AK, Ramuta MD, Reynaldi A, Cromer D, Subbarao K, O'Connor DH, Kent SJ, Davenport MP. 2020. Measuring immunity to SARS-CoV-2 infection comparing assays and animal models. Nat Rev Immunol 20727–738. - DOI - PMC - PubMed Publication types MeSH terms Substances LinkOut - more resources Full Text Sources Atypon Europe PubMed Central PubMed Central Medical Genetic Alliance MedlinePlus Health Information Miscellaneous NCI CPTAC Assay Portal
PRDABERI BANTUAN PEMERIKSAAN ANTI SARS COV-2 KEPADA PELAYAN PUBLIK. 75163923. IQPlus, (17/03) - PT Prodia Widyahusada Tbk (Kode saham: PRDA) memberikan bantuan pemeriksaan COVID-19 kepada lebih dari 3.800 orang pelayan publik yang berada di wilayah DKI Jakarta, Lampung dan Pangkal Pinang pada tanggal 22-27 Februari 2021.
Evaluation of Three Quantitative Anti-SARS-CoV-2 Antibody Immunoassays Sabine Chapuy-Regaud et al. Microbiol Spectr. 2021. Free PMC article Abstract The severe acute respiratory syndrome coronavirus 2 SARS-CoV-2 emerged in December 2019 and caused a dramatic pandemic. Serological assays are used to check for immunization and assess herd immunity. We evaluated commercially available assays designed to quantify antibodies directed to the SARS-CoV-2 Spike S antigen, either total Wantaï SARS-CoV-2 Ab ELISA or IgG SARS-CoV-2 IgG II Quant on Alinity, Abbott, and Liaison SARS-CoV-2 TrimericS IgG, Diasorin. The specificities of the Wantaï, Alinity, and Liaison assays were evaluated using 100 prepandemic sera and were 98, 99, and 97%, respectively. The sensitivities of all three were around 100% when tested on 35 samples taken 15 to 35 days postinfection. They were less sensitive for 150 sera from late infections >180 days. Using the first WHO international standard NIBSC, we showed that the Wantai results were concordant with the NIBSC values, while Liaison and Alinity showed a proportional bias of and 7, respectively. The results of the 3 immunoassays were significantly globally pairwise correlated and for late infection sera P < They were correlated for recent infection sera measured with Alinity and Liaison P < However, the Wantai results of recent infections were not correlated with those from Alinity or Liaison. All the immunoassay results were significantly correlated with the neutralizing antibody titers obtained using a live virus neutralization assay with the SARS-CoV-2 strain. These assays will be useful once the protective anti-SARS-CoV-2 antibody titer has been determined. IMPORTANCE Standardization and correlation with virus neutralization assays are critical points to compare the performance of serological assays designed to quantify anti-SARS-CoV-2 antibodies in order to identify their optimal use. We have evaluated three serological immunoassays based on the virus spike antigen that detect anti-SARS-CoV-2 antibodies a microplate assay and two chemiluminescent assays performed with Alinity Abbott and Liaison Diasorin analysers. We used an in-house live virus neutralization assay and the first WHO international standard to assess the comparison. This study could be useful to determine guidelines on the use of serological results to manage vaccination and treatment with convalescent plasma or monoclonal antibodies. Keywords COVID; SARS-CoV-2; binding antibodies; immunoassay; neutralizing antibodies. Conflict of interest statement The authors declare no conflict of interest. Figures FIG 1 Distribution of the results. A Wantaï, B Liaison, and C Alinity assays according to patient groups. Black lines = median of each group. Red lines = manufacturer’s negative/positive threshold. Zero 0 values in the Liaison negative group n = 92, the Liaison late infection group n = 15, the Alinity negative group n = 14, and the Alinity late infection group n = 7 are not shown. FIG 2 ROC curves for Wantaï black line, Liaison green line and Alinity red line. Gray line y = x. The AUROCs were Wantaï 95% CI to Liaison 95% CI to and Alinity 95% CI to indicating their capacity to accurately detect anti-SARS-CoV-2 antibodies. FIG 3 Quantification of anti-SARS-CoV-2 antibodies relative to the NIBSC international standard. Serial dilutions of the NIBSC 20/136 standard were assayed with the A Wantaï, B Liaison, and C Alinity assay. Neutralizing antibodies NAb were also determined with a live method D. The black line represents the regression line and the dashed lines its 95% CI. The dashed red line represents the y = x line. AU arbitrary units. BAU binding antibody unit. The equations were y = x − slope 95% CI to y-intercept 95% CI − to for Wantaï; y = x − slope 95% CI to y-intercept 95% CI − to for Liaison; y = x - slope 95% CI to y-intercept 95% CI − to for Alinity and y = x + slope 95% CI to y-intercept 95% CI − to for NAb titers. FIG 4 Correlation between the immunoassay results. Pairwise distribution of the Wantaï, Liaison, and Alinity assays values for all positive results A to C, recent infections D to F, and late infections G to I. When the Spearman rank coefficient r indicated a significant correlation, the regression line was drawn. Dashed lines 95% CI limits. FIG 5 Immunoassays results and neutralizing antibody titers. Distribution of the Wantaï, Liaison, and Alinity assay values and the NAb titers for all positive results A to C The NAb titers were determined in a live virus neutralization assay using the B strain. Spearman’s rank coefficients r and their P value are indicated. The box extends from the 25th to 75th percentiles and whiskers from minimal to maximal values. Similar articles Performance evaluation of three automated quantitative immunoassays and their correlation with a surrogate virus neutralization test in coronavirus disease 19 patients and pre-pandemic controls. Jung K, Shin S, Nam M, Hong YJ, Roh EY, Park KU, Song EY. Jung K, et al. J Clin Lab Anal. 2021 Sep;359e23921. doi Epub 2021 Aug 8. J Clin Lab Anal. 2021. PMID 34369009 Free PMC article. Inference of SARS-CoV-2 spike-binding neutralizing antibody titers in sera from hospitalized COVID-19 patients by using commercial enzyme and chemiluminescent immunoassays. Valdivia A, Torres I, Latorre V, Francés-Gómez C, Albert E, Gozalbo-Rovira R, Alcaraz MJ, Buesa J, Rodríguez-Díaz J, Geller R, Navarro D. Valdivia A, et al. Eur J Clin Microbiol Infect Dis. 2021 Mar;403485-494. doi Epub 2021 Jan 6. Eur J Clin Microbiol Infect Dis. 2021. PMID 33404891 Free PMC article. Serological Assays for Assessing Postvaccination SARS-CoV-2 Antibody Response. Mahmoud SA, Ganesan S, Naik S, Bissar S, Zamel IA, Warren KN, Zaher WA, Khan G. Mahmoud SA, et al. Microbiol Spectr. 2021 Oct 31;92e0073321. doi Epub 2021 Sep 29. Microbiol Spectr. 2021. PMID 34585943 Free PMC article. Overview of Neutralization Assays and International Standard for Detecting SARS-CoV-2 Neutralizing Antibody. Liu KT, Han YJ, Wu GH, Huang KA, Huang PN. Liu KT, et al. Viruses. 2022 Jul 18;1471560. doi Viruses. 2022. PMID 35891540 Free PMC article. Review. Recent Developments in SARS-CoV-2 Neutralizing Antibody Detection Methods. Banga Ndzouboukou JL, Zhang YD, Fan XL. Banga Ndzouboukou JL, et al. Curr Med Sci. 2021 Dec;4161052-1064. doi Epub 2021 Dec 21. Curr Med Sci. 2021. PMID 34935114 Free PMC article. Review. Cited by Diagnostic performance of four lateral flow immunoassays for COVID-19 antibodies in Peruvian population. Calderon-Flores R, Caceres-Cardenas G, Alí K, De Vos M, Emperador D, Cáceres T, Eca A, Villa-Castillo L, Albertini A, Sacks JA, Ugarte-Gil C. Calderon-Flores R, et al. PLOS Glob Public Health. 2023 Jun 2;36e0001555. doi eCollection 2023. PLOS Glob Public Health. 2023. PMID 37267241 Free PMC article. Correlation of Postvaccination Fever With Specific Antibody Response to Severe Acute Respiratory Syndrome Coronavirus 2 BNT162b2 Booster and No Significant Influence of Antipyretic Medication. Tani N, Ikematsu H, Goto T, Gondo K, Inoue T, Yanagihara Y, Kurata Y, Oishi R, Minami J, Onozawa K, Nagano S, Kuwano H, Akashi K, Shimono N, Chong Y. Tani N, et al. Open Forum Infect Dis. 2022 Sep 23;910ofac493. doi eCollection 2022 Oct. Open Forum Infect Dis. 2022. PMID 36267253 Free PMC article. Current immunoassays and detection of antibodies elicited by Omicron SARS-CoV-2 infection. Migueres M, Chapuy-Regaud S, Miédougé M, Jamme T, Lougarre C, Da Silva I, Pucelle M, Staes L, Porcheron M, Diméglio C, Izopet J. Migueres M, et al. J Med Virol. 2023 Jan;951e28200. doi Epub 2022 Oct 17. J Med Virol. 2023. PMID 36207814 Free PMC article. SARS-CoV-2 anti-spike antibodies after a fourth dose of COVID-19 vaccine in adult solid-organ transplant recipients. Perrier Q, Lupo J, Gerster T, Augier C, Falque L, Rostaing L, Pelletier L, Bedouch P, Blanc M, Saint-Raymond C, Boignard A, Bonadona A, Noble J, Epaulard O. Perrier Q, et al. Vaccine. 2022 Oct 19;40446404-6411. doi Epub 2022 Sep 6. Vaccine. 2022. PMID 36184404 Free PMC article. Can the COVID-19 Pandemic Improve the Management of Solid Organ Transplant Recipients? Del Bello A, Marion O, Izopet J, Kamar N. Del Bello A, et al. Viruses. 2022 Aug 24;1491860. doi Viruses. 2022. PMID 36146666 Free PMC article. Review. 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\n\n\n anti sars cov 2 kuantitatif
ABSTRACT Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the cause of severe acute respiratory syndrome known as Coronavirus Disease 2019 (COVID-19). The main protease receptor (Mpro) is the main part of the characteristic formation of the Corona virus (SARS-CoV-2). Bioactive lipid compounds (Arachidonic Acid, Eicosapentaenoic
2SARS Cov 2) ini dapat menyerang seluruh kelompok usia termasuk ibu dan neonatus. Risiko infeksi neonatal melalui transmisi vertikal dari ibu dan bayi ataupun melalui ASI masih belum dapat disimpulkan dan membutuhkan penelitian lebih lanjut. Sehingga menyebabkan ada banyak variasi dalam cara merawat bayi baru lahir dan cara menyusui (8). Intheir Viewpoint on Interpreting Diagnostic Tests for SARS-CoV-2 Sethuraman and colleagues may have left out a major player of the humoral immune response against respiratory viruses, and that is IgA. By now there are a number of publications which demonstrate a clear-cut IgA anti-SARS-CoV-2 response (1-3).
DeskripsiProduk Kit Tes Cepat 2019nCov Ag. Kit Antibodi Penetralisir SARS-Cov-2 Ketika seseorang tertular COVID-19, respons imun pejamu dapat diukur dengan adanya antibodi penetralisir.Antibodi penetralisir mencegah interaksi antara virus SARS-CoV-2 dan reseptor pada sel manusia, sehingga memberikan kekebalan pada pasien.
Parapeneliti mencoba menemukan banyak cara efektif melawan penyebaran virus corona baru. Menurut sebuah penelitian baru-baru ini, antibodi dalam sampel yang dikumpulkan dari pasien yang terinfeksi SARS-CoV (menyebabkan penyakit SARS) selama wabah pada 2003, telah secara efektif dan berhasil menetralkan infeksi SARS-CoV-2 dalam sel yang dibiakkan. F1sbNi.