BackgroundDynamics of humoral immune responses to SARS-CoV-2 antigens following infection suggests an initial decay of antibody followed by subsequent stabilization. We aim to understand the longitudinal humoral responses to SARS-CoV-2 nucleocapsid (N) protein and spike (S) protein and to evaluate their correlation to clinical symptoms among healthcare workers (HCW). MethodsIn this cross-sectional longitudinal cohort study done in two phases over four months, HCW underwent serial qualitative serology testing for anti-N antibody, quantitative MSH-ELISA to detect Receptor Binding Domain and full-length S reactive antibodies and completed online surveys about COVID-19 related symptoms and healthcare/community exposure. ResultsAnti-N antibody positivity was 27% and anti-S positivity was 28% in Phase 1. In Phase 2 anti-S titres were higher in symptomatic than in asymptomatic positive subjects in Phase 1. Marginally higher titers were seen in asymptomatic compared to the symptomatic positive subgroup in Phase 2. A positive correlation was noted between age, number and duration of symptoms, and Phase 1 anti-S antibody titre. A strong correlation was observed between Phase 1 titers and decay of anti-S antibody titres between the two phases. Significant correlation with rate of decay was also noted with fever, GI symptoms, and total number and duration of COVID-19 symptoms. ConclusionsHigher initial anti-S antibody titres were associated with larger number and longer duration of symptoms as well as faster decay during the two time points. Key PointsO_ST_ABSQuestionC_ST_ABSWhat is the decay rate of neutralizing antibodies among SARS-CoV-2 infected healthcare workers? FindingsIn this cohort study that included 178 healthcare workers, over a 4-month period following the COVID-19 pandemic, participants had an initial rise in anti-nucleocapsid (N) and anti-spike (S) antibodies, which was followed by decay and stabilization of the titres. Significant correlation with rate of decay was noted with the symptomatic participants. MeaningA strong correlation is observed in the decay of anti-S antibody titres based on symptomology, thus eluding to the fact that continued recommendations for infection protection and COVID-19 vaccine campaigns are necessary.