Performance, Dynamic Change and Clinical Relevance of SARS-CoV-2 Antibody Responses

Background: Although reports suggest that most individuals with COVID-19 develop detectable antibodies post infection, the kinetics, durability, and relative differences between IgM and IgG responses beyond the first few weeks after symptom onset remain poorly understood.  Methods: Within a large, well-phenotyped, diverse, prospective cohort of subjects with and without SARS-CoV-2 PCR-confirmed infection and historical controls derived from cohorts with high prevalence of viral coinfections and samples taken during prior flu seasons, we measured SARS-CoV-2 serological responses (both IgG and IgM) using commercially available assays. We calculated sensitivity and specificity, relationship with disease severity and mapped the kinetics of antibody seropositivity and antibody levels over time using generalised additive models. Findings: We analysed 1,001 samples from 752 subjects, 327 with confirmed SARS-CoV-2 (29.7% with severe disease) spanning a period of 90 days from symptom onset. Sensitivity was lower (44.1-47.1%) early ( 80% after 10 days. IgM positivity increased earlier than IgG-targeted assays but positivity peaked between day 32 and 38 post onset of symptoms and declined thereafter, a dynamic that was confirmed when antibody levels were analysed, with more rapid decline observed with IgM. Early (<10 days) IgM but not IgG levels were significantly higher in those who subsequently developed severe disease (signal / cut-off 4.20 (0.75-17.93) versus 1.07 (0.21-5.46), P=0.048). Interpretation: This study suggests that post-infectious antibody responses in those with confirmed COVID-19 begin to decline relatively early post infection and suggests a potential role for higher IgM levels early in infection predicting subsequent disease severity.    Funding: Science Foundation Ireland (grant number 20/COV/0305). W. T. is supported from the European Union’s Horizon 2020 Research and Innovation Programme under the Marie Sklodowska-Curie (grant number 666010). Antibody assays were provided by Abbott Diagnostics. Declaration of Interests: Patrick W. G. Mallon has received honoraria and/or travel grants from Gilead Sciences, MSD, Bristol Myers Squibb and ViiV Healthcare. Willard Tinago – no conflicts declared. Alejandro Abner Garcia Leon – no conflicts declared. Kathleen McCann – no conflicts declared. Grace Kenny – no conflicts declared. Padraig McGettrick – no conflicts declared. Sandra Green – no conflicts declared. Rosanna Inzitiari – no conflicts declared. Aoife Cotter – no conflicts declared. Stefano Savinelli – no conflicts declared. Eoin R Feeney has received honoraria and/or travel grants from Gilead Sciences, Abbvie, MSD, Vidacare and ViiV Healthcare. Peter Doran – no conflicts declared. Ethics Approval Statement: All subjects provide written, informed consent and the study is approved by local and national research ethics committees