Persistence of IgG response to SARS-CoV-2
Authors: Els Duysburgh, Laure Mortgat, Cyril Barbezange, Katelijne Dierick, Natalie Fischer, Leo Heyndrickx, Veronik Hutse, Isabelle Thomas, Steven Van Gucht, Bea Vuylsteke, Kevin K Ariën, Isabelle Desombere
Journal: The Lancet Infectious Diseases (2020)

Little is known about the duration and protective capacity of the humoral immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In studies from Iceland1Gudbjartsson DF Norddahl GL Melsted P et al.Humoral immune response to SARS-CoV-2 in Iceland.N Engl J Med. 2020; 383: 1724-1734Crossref PubMed Scopus (714) Google Scholar and the USA,2Wajnberg A Amanat F Firpo A et al.Robust neutralizing antibodies to SARS-CoV-2 infection persist for months.Science. 2020; (published online Oct 28.)https://doi.org/10.1126/science.abd7728Crossref PubMed Scopus (805) Google Scholar antibodies against SARS-CoV-2 did not decline within 4 months after diagnosis. However, other studies have reported rapid waning of antibodies within 3–4 months.3Ibarrondo FJ Fulcher JA Goodman-Meza D et al.Rapid decay of anti-SARS-CoV-2 antibodies in persons with mild COVID-19.N Engl J Med. 2020; 383: 1085-1087Crossref PubMed Scopus (787) Google Scholar, 4Seow J Graham C Merrick B et al.Longitudinal observation and decline of neutralizing antibody responses in the three months following SARS-CoV-2 infection in humans.Nat Microbiol. 2020; 5: 1598-1607Crossref PubMed Scopus (861) Google Scholar, 5Ward H Cooke G Atchison C et al.Declining prevalence of antibody positivity to SARS-CoV-2: a community study of 365,000 adults.medRxiv. 2020; (published online Oct 27.) (preprint)https://doi.org/10.1101/2020.10.26.20219725PubMed Google Scholar Since April 22, 2020, we have been following up a representative cohort of 850 health-care workers from 17 Belgian hospitals. Participants are tested on a monthly basis for the presence of SARS-CoV-2 with quantitative RT-PCR (RT-qPCR) and for antibodies targeting S1 (spike subunit 1) protein with a commercial semi-quantitative ELISA (Euroimmun IgG; Medizinische Labordiagnostika, Lübeck, Germany), using a stringent manufacturer-defined cut-off for having a positive test result (ratio ≥1·1; NCT04373889).6Mortgat L Barbezange C Fischer N et al.SARS-CoV-2 prevalence and seroprevalence among healthcare workers in Belgian hospitals: baseline results of a prospective cohort study.medRxiv. 2020; (published online Oct 6.) (preprint)https://doi.org/10.1101/2020.10.03.20204545Google Scholar By the end of September, 2020, seven rounds of testing had been done. To assess the longevity of the humoral immune response, we recorded the duration of the presence of detectable IgG in the serum of health-care workers who were seropositive for SARS-CoV-2. At least two consecutive positive samples were needed to classify a participant as seropositive, whereas disappearance of IgG was defined as having at least two negative tests after having been classified as seropositive. Only health-care workers who attended at least four testing points and had at least two positive tests were included in this assessment. Additionally, we did in-vitro neutralisation tests on IgG-positive samples, measuring the serum titre of antibodies needed to neutralise 50% of SARS-CoV-2 (NT50). By the end of September, 2020, 81 IgG-positive health-care workers had been identified. Of these individuals, five were asymptomatic, 75 had reported mild symptoms, and one needed hospitalisation. Median follow-up was 170 (range 62–199) days. In seven (9%) health-care workers, antibodies became undetectable after intervals ranging from 107 days to 159 days from presumed onset of infection (defined by day of positive RT-qPCR test or [if not available] day of onset of symptoms or [for asymptomatic patients] day of first positive serological test minus 14 days). Among 74 (91%) health-care workers who remained seropositive, median duration of antibody persistence (defined as the time between the day IgGs were last detected and the day of presumed onset of infection) is currently 168·5 (range 62–199) days. 71 (96%) of 74 health-care workers have already had antibodies for 90 days or more and 67 (91%) have had them for 120 days or more (appendix p 1). Among the 74 seropositive health-care workers, 61 (82%) had neutralising antibodies in their most recent IgG-positive serum sample. Of note, of the 13 individuals with no detectable neutralising antibodies, eight had weak neutralising antibody titres (NT50 55–100) and five had no measurable neutralising antibody titres from the start. Since antibodies specific for SARS-CoV-2 were only assessed for S1 protein, and because S1-specific cross-reactivity of prepandemic serum samples from patients infected with common cold human coronaviruses has been described,7Okba NMA Müller MA Li W et al.Severe acute respiratory syndrome coronavirus 2-specific antibody responses in coronavirus disease patients.Emerg Infect Dis. 2020; 26: 1478-1488Crossref PubMed Scopus (1090) Google Scholar, 8Lassaunière R Frische A Harboe Z et al.Evaluation of nine commercial SARS-CoV-2 immunoassays.medRxiv. 2020; (published online April 10.) (preprint)https://doi.org/10.1101/2020.04.09.20056325Google Scholar an explanation could be that these five individuals are false-positive for SARS-CoV-2 antibodies. For as long as correlates of protection are not well defined, measuring anti-S1 IgG is an acceptable biomarker that probably slightly overestimates true seropositivity. Follow-up of our cohort will continue at least until April, 2021. Based on data currently available, a rapid decline of SARS-CoV-2 IgG seropositivity or neutralising capacity has not been seen. It must be stressed that, compared with other studies, we used a stringent cut-off value for having a positive test result and a conservative definition for seroconversion. Our findings accord with earlier observations of antibody persistence after infection with severe acute respiratory syndrome coronavirus or Middle East respiratory syndrome coronavirus.9Murchu EO Byrne P Walsh KA et al.Immune response following infection with SARS-CoV-2 and other coronaviruses: a rapid review.Rev Med Virol. 2020; (published online Sept 23.)https://doi.org/10.1002/rmv.2162Google Scholar The importance of neutralising antibodies in long-term immunity against SARS-CoV-2 remains to be determined. This online publication has been corrected. The first corrected version first appeared at thelancet.com/infection on December 18, 2020 and the second on January 27, 2021. This online publication has been corrected. The first corrected version first appeared at thelancet.com/infection on December 18, 2020 and the second on January 27, 2021. We declare no competing interests. We thank the hospitals, health-care workers, and hospital study coordinators for their participation in this study; and laboratory technicians and administrative staff of Sciensano (Brussels, Belgium) and the Institute of Tropical Medicine (Antwerp, Belgium) for their support in study implementation. Download .pdf (.08 MB) Help with pdf files Supplementary appendix Correction to Lancet Infect Dis 2020; published online Dec 17. https://doi.org/10.1016/S1473-3099(20)30943-9Duysburgh E, Mortgat L, Barbezange C, et al. Persistence of IgG response to SARS-CoV-2. Lancet Infect Dis 2020; published online Dec 17. https://doi.org/10.1016/S1473-3099(20)30943-9—In the final paragraph of this Comment, reference 8 was cited instead of reference 9. This correction has been made to the online version as of Dec 19, 2020, and will be made to the printed version. Full-Text PDF Correction to Lancet Infect Dis 2021; 21: 163–64Duysburgh E, Mortgat L, Barbezange C, et al. Persistence of IgG response to SARS-CoV-2. Lancet Infect Dis 2021; 21: 163–64—In this Comment, the penultimate author's name is Kevin K Ariën, and Kevin K Ariën and Isabelle Desombere have shared last authorship. These corrections have been made as of Jan 27, 2021. Full-Text PDF