Abstract
ABSTRACTThe coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) has now caused over 2 million deaths worldwide and continues to expand. Currently, much is unknown about functionally neutralizing human antibody responses and durability to SARS-CoV-2 months after infection or the reason for the discrepancy in COVID-19 disease and sex. Using convalescent-phase sera collected from 101 COVID-19-recovered individuals 21 to 212 days after symptom onset with 48 additional longitudinal samples, we measured functionality and durability of serum antibodies. We also evaluated associations of individual demographic and clinical parameters with functional neutralizing antibody responses to COVID-19. We found robust antibody durability out to 6 months, as well as significant positive associations with the magnitude of the neutralizing antibody response and male sex and in individuals with cardiometabolic comorbidities.IMPORTANCE In this study, we found that neutralizing antibody responses in COVID-19-convalescent individuals vary in magnitude but are durable and correlate well with receptor binding domain (RBD) Ig binding antibody levels compared to other SARS-CoV-2 antigen responses. In our cohort, higher neutralizing antibody titers are independently and significantly associated with male sex compared to female sex. We also show for the first time that higher convalescent antibody titers in male donors are associated with increased age and symptom grade. Furthermore, cardiometabolic comorbidities are associated with higher antibody titers independently of sex. Here, we present an in-depth evaluation of serologic, demographic, and clinical correlates of functional antibody responses and durability to SARS-CoV-2 which supports the growing literature on sex discrepancies regarding COVID-19 disease morbidity and mortality, as well as functional neutralizing antibody responses to SARS-CoV-2.
Highlights
The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) has caused over 2 million deaths worldwide and continues to expand
COVID-19 convalescent plasma (CP) donors were enrolled in this study
In-depth serological, clinical, and demographic correlates of durable and protective functional antibodies in individuals who have recovered from COVID-19 have not been well described
Summary
The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) has caused over 2 million deaths worldwide and continues to expand. Longevity of serum antibodies to SARS-CoV-2 S protein after vaccination as well as natural infection has been studied out to 3 months, during which time IgG, IgM, and IgA levels to most SARS-CoV-2 antigens peak and begin to decline [16, 18,19,20], as plasmablast and short-lived plasma cell responses wane. We add to growing evidence of sex disparities in neutralizing antibody responses previously seen up to 114 days post-symptom onset in predominantly urban areas [23,24,25,26,27,28] Our data support these findings out to 6 months postinfection in a previously uncharacterized cohort in a semiurban and rural population in North Carolina. We further define demographic and clinical correlates of the magnitude and durability of both binding and functional antibody responses to SARS-CoV-2
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