- 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.

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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