Seroprevalence of anti-SARS-CoV-2 antibodies in COVID-19 patients and healthy volunteers up to 6 months post disease onset
Patrícia Figueiredo-Campos, Birte Blankenhaus, Catarina Mota, Andreia Gomes, Marta Serrano, Silvia Ariotti, Catarina Costa, Helena Nunes-Cabaço, António M Mendes, Pedro Gaspar, M Conceição Pereira-Santos, Fabiana Rodrigues, Jorge Condeço, M Antonia Escoval, Matilde Santos, Mario Ramirez, José Melo-Cristino, J Pedro Simas, Eugenia Vasconcelos, Ângela Afonso, Marc Veldhoen, Patrícia Figueiredo-Campos, Birte Blankenhaus, Catarina Mota, Andreia Gomes, Marta Serrano, Silvia Ariotti, Catarina Costa, Helena Nunes-Cabaço, António M Mendes, Pedro Gaspar, M Conceição Pereira-Santos, Fabiana Rodrigues, Jorge Condeço, M Antonia Escoval, Matilde Santos, Mario Ramirez, José Melo-Cristino, J Pedro Simas, Eugenia Vasconcelos, Ângela Afonso, Marc Veldhoen
Abstract
SARS-CoV-2 has emerged as a human pathogen, causing clinical signs, from fever to pneumonia-COVID-19-but may remain mild or asymptomatic. To understand the continuing spread of the virus, to detect those who are and were infected, and to follow the immune response longitudinally, reliable and robust assays for SARS-CoV-2 detection and immunological monitoring are needed. We quantified IgM, IgG, and IgA antibodies recognizing the SARS-CoV-2 receptor-binding domain (RBD) or the Spike (S) protein over a period of 6 months following COVID-19 onset. We report the detailed setup to monitor the humoral immune response from over 300 COVID-19 hospital patients and healthcare workers, 2500 University staff, and 198 post-COVID-19 volunteers. Anti-SARS-CoV-2 antibody responses follow a classic pattern with a rapid increase within the first three weeks after symptoms. Although titres reduce subsequently, the ability to detect anti-SARS-CoV-2 IgG antibodies remained robust with confirmed neutralization activity for up to 6 months in a large proportion of previously virus-positive screened subjects. Our work provides detailed information for the assays used, facilitating further and longitudinal analysis of protective immunity to SARS-CoV-2. Importantly, it highlights a continued level of circulating neutralising antibodies in most people with confirmed SARS-CoV-2.
Keywords: COVID-19; SARS-CoV-2; Seroprevalence; neutralizing antibodies.
Conflict of interest statement
The authors have no commercial or financial conflict of interest.
© 2020 The Authors. European Journal of Immunology published by Wiley-VCH GmbH.
Figures
References
- Buchholz, U. J. , Bukreyev, A. , Yang, L. , Lamirande, E. W. , Murphy, B. R. , Subbarao, K. and Collins, P. L. . Contributions of the structural proteins of severe acute respiratory syndrome coronavirus to protective immunity. PNAS 2004. 101: 9804–9809.
- Deming, D. , Sheahan, T. , Heise, M. , Yount, B. , Davis, N. , Sims, A. , Suthar, M. et al., Vaccine efficacy in senescent mice challenged with recombinant SARS‐CoV bearing epidemic and zoonotic spike variants. PLoS Med. 2006. 3: e525.
- Suthar, M. S. , Zimmerman, M. , Kauffman, R. , Mantus, G. , Linderman, S. , Vanderheiden, A. , Nyhoff, L. et al., Rapid generation of neutralizing antibody responses in COVID‐19 patients. medRxiv 2020.
- Robbiani, D. F. , Gaebler, C. , Muecksch, F. , Lorenzi, J. C. C. , Wang, Z. , Cho, A. , Agudelo, M. et al., Convergent antibody responses to SARS‐CoV‐2 in convalescent individuals. Nature 2020.
- Bosch, B. J. , van der Zee, R. , de Haan, C. A. and Rottier, P. J. . The coronavirus spike protein is a class I virus fusion protein: structural and functional characterization of the fusion core complex. J. Virol. 2003. 77: 8801–8811.
- Hoffmann, M. , Kleine‐Weber, H. , Schroeder, S. , Kruger, N. , Herrler, T. , Erichsen, S. , Schiergens, T. S. et al., SARS‐CoV‐2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell 2020. 181: 271–280 e278.
- Wang, Q. , Zhang, Y. , Wu, L. , Niu, S. , Song, C. , Zhang, Z. , Lu, G. et al., Structural and Functional Basis of SARS‐CoV‐2 Entry by Using Human ACE2. Cell 2020. 181: 894–904 e899.
- Walls, A. C. , Park, Y. J. , Tortorici, M. A. , Wall, A. , McGuire, A. T. and Veesler, D. . Structure, Function, and Antigenicity of the SARS‐CoV‐2 Spike Glycoprotein. Cell 2020. 181: 281–292 e286.
- Amanat, F. , Stadlbauer, D. , Strohmeier, S. , Nguyen, T. H. O. , Chromikova, V. , McMahon, M. , Jiang, K. et al., A serological assay to detect SARS‐CoV‐2 seroconversion in humans. Nat. Med. 2020. 26: 1033–1036.
- Okba, N. M. A. , Muller, M. A. , Li, W. , Wang, C. , GeurtsvanKessel, C. H. , Corman, V. M. , Lamers, M. M. et al., Severe Acute Respiratory Syndrome Coronavirus 2‐Specific Antibody Responses in Coronavirus Disease Patients. Emerg. Infect. Dis. 2020. 26: 1478–1488.
- GeurtsvanKessel, C. H. , Okba, N. M. A. , Igloi, Z. , Bogers, S. , Embregts, C. W. E. , Laksono, B. M. , Leijten, L. et al., An evaluation of COVID‐19 serological assays informs future diagnostics and exposure assessment. Nat. Commun. 2020. 11: 3436.
- Stadlbauer, D. , Amanat, F. , Chromikova, V. , Jiang, K. , Strohmeier, S. , Arunkumar, G. A. , Tan, J. et al., SARS‐CoV‐2 Seroconversion in Humans: A Detailed Protocol for a Serological Assay, Antigen Production, and Test Setup. Curr Protoc Microbiol 2020. 57: e100.
- Remy, M. M. , Alfter, M. , Chiem, M. N. , Barbani, M. T. , Engler, O. B. and Suter‐Riniker, F. . Effective chemical virus inactivation of patient serum compatible with accurate serodiagnosis of infections. Clin. Microbiol. Infect. 2019. 25: 907 e907‐907 e912.
- Scott‐Taylor, T. H. , Axinia, S. C. , Amin, S. and Pettengell, R. . Immunoglobulin G; structure and functional implications of different subclass modifications in initiation and resolution of allergy. Immun Inflamm Dis 2018. 6: 13–33.
- Hsueh, P. R. , Huang, L. M. , Chen, P. J. , Kao, C. L. and Yang, P. C. . Chronological evolution of IgM, IgA, IgG and neutralisation antibodies after infection with SARS‐associated coronavirus. Clin. Microbiol. Infect. 2004. 10: 1062–1066.
- Wajnberg, A. , Amanat, F. , Firpo, A. , Altman, D. , Bailey, M. , Mansour, M. , McMahon, M. et al., SARS‐CoV‐2 infection induces robust, neutralizing antibody responses that are sTable for at least three months. medRxiv 2020. 2020.2007.2014.20151126.
- Wang, W. , Xu, Y. , Gao, R. , Lu, R. , Han, K. , Wu, G. and Tan, W. . Detection of SARS‐CoV‐2 in Different Types of Clinical Specimens. JAMA 2020.
- Blanco, J. L. , Ambrosioni, J. , Garcia, F. , Martinez, E. , Soriano, A. , Mallolas, J. and Miro, J. M. , Investigators C‐iH: COVID‐19 in patients with HIV: clinical case series. Lancet HIV 2020. 7: e314‐e316.
- Cooper, T. J. , Woodward, B. L. , Alom, S. and Harky, A. . Coronavirus disease 2019 (COVID‐19) outcomes in HIV/AIDS patients: a systematic review. HIV Med. 2020.
- Group, R. C. , Horby, P. , Lim, W. S. , Emberson, J. R. , Mafham, M. , Bell, J. L. , Linsell, L. et al., Dexamethasone in Hospitalized Patients with Covid‐19 ‐ Preliminary Report. N. Engl. J. Med. 2020.
- Klein, S. L. and Flanagan, K. L. . Sex differences in immune responses. Nat. Rev. Immunol. 2016. 16: 626–638.
- Jin, J. M. , Bai, P. , He, W. , Wu, F. , Liu, X. F. , Han, D. M. , Liu, S. and Yang, J. K. . Gender Differences in Patients With COVID‐19: Focus on Severity and Mortality. Front Public Health 2020. 8:152.
- Wenham, C. , Smith, J. and Morgan, R. , Gender, Group C‐W . COVID‐19: the gendered impacts of the outbreak. Lancet 2020. 395: 846–848.
- Laffont, S. , Rouquie, N. , Azar, P. , Seillet, C. , Plumas, J. , Aspord, C. and Guery, J. C. . X‐Chromosome complement and estrogen receptor signaling independently contribute to the enhanced TLR7‐mediated IFN‐alpha production of plasmacytoid dendritic cells from women. J. Immunol. 2014. 193: 5444–5452.
- Klein, S. L. , Hodgson, A. and Robinson, D. P. . Mechanisms of sex disparities in influenza pathogenesis. J. Leukoc. Biol. 2012. 92: 67–73.
- Gudbjartsson, D. F. , Helgason, A. , Jonsson, H. , Magnusson, O. T. , Melsted, P. , Norddahl, G. L. , Saemundsdottir, J. et al., Spread of SARS‐CoV‐2 in the Icelandic Population. N. Engl. J. Med. 2020. 382: 2302–2315.
- Behrens, G. M. , Cossmann, A. , Stankov, M. V. , Schulte, B. , Streeck, H. , Foerster, R. , Bosnjak, B. et al., Strategic anti‐SARS‐CoV‐2 serology testing in a low prevalence pandemic: The COVID‐19 Contact (CoCo) Study in health care professionals. medRxiv 2020. 2020.2008.2006.20169250.
- Pollan, M. , Perez‐Gomez, B. , Pastor‐Barriuso, R. , Oteo, J. , Hernan, M. A. , Perez‐Olmeda, M. , Sanmartin, J. L. et al., Prevalence of SARS‐CoV‐2 in Spain (ENE‐COVID): a nationwide, population‐based seroepidemiological study. Lancet 2020.
- Stringhini, S. , Wisniak, A. , Piumatti, G. , Azman, A. S. , Lauer, S. A. , Baysson, H. , De Ridder, D. et al., Seroprevalence of anti‐SARS‐CoV‐2 IgG antibodies in Geneva, Switzerland (SEROCoV‐POP): a population‐based study. Lancet 2020. 396: 313–319.
- Long, Q. X. , Liu, B. Z. , Deng, H. J. , Wu, G. C. , Deng, K. , Chen, Y. K. , Liao, P. et al., Antibody responses to SARS‐CoV‐2 in patients with COVID‐19. Nat. Med. 2020. 26: 845–848.
- Addetia, A. , Crawford, K. H. , Dingens, A. , Zhu, H. , Roychoudhury, P. , Huang, M. , Jerome, K. R. et al., Neutralizing antibodies correlate with protection from SARS‐CoV‐2 in humans during a fishery vessel outbreak with high attack rate. medRxiv 2020. 2020.2008.2013.20173161.
- Grifoni, A. , Weiskopf, D. , Ramirez, S. I. , Mateus, J. , Dan, J. M. , Moderbacher, C. R. , Rawlings, S. A. et al., Targets of T Cell Responses to SARS‐CoV‐2 Coronavirus in Humans with COVID‐19 Disease and Unexposed Individuals. Cell 2020. 181: 1489–1501 e1415.
- Braun, J. , Loyal, L. , Frentsch, M. , Wendisch, D. , Georg, P. , Kurth, F. , Hippenstiel, S. et al., Presence of SARS‐CoV‐2 reactive T cells in COVID‐19 patients and healthy donors. medRxiv 2020. 2020.2004.2017.20061440.
- Gangaev, A. , Ketelaars, S. L. C. , Patiwael, S. , Dopler, A. , Isaeva, O. I. , Hoefakker, K. , De Biasi, S. et al., Profound CD8 T cell responses towards the SARS‐CoV‐2 ORF1ab in COVID‐19 patients. Researchsquare 2020.
- Le Bert, N. , Tan, A. T. , Kunasegaran, K. , Tham, C. Y. L. , Hafezi, M. , Chia, A. , Chng, M. H. Y. et al., SARS‐CoV‐2‐specific T cell immunity in cases of COVID‐19 and SARS, and uninfected controls. Nature 2020.
- Oguntuyo, K. Y. , Stevens, C. S. , Hung, C. ‐. T. , Ikegame, S. , Acklin, J. A. , Kowdle, S. S. , Carmichael, J. C. et al., Quantifying absolute neutralization titers against SARS‐CoV‐2 by a standardized virus neutralization assay allows for cross‐cohort comparisons of COVID‐19 sera. medRxiv 2020. 2020, 2008.2013.20157222.
Source: PubMed