RESUMO
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.
RESUMO
Serological tests are important tools helping to determine previous infection with severe acute respiratory disease coronavirus 2 (SARS-CoV-2) and to monitor immune responses. The current tests are based on spike (S), the receptor binding domain (RBD), or the nucleoprotein (NP) as substrate. Here, we used samples from a high seroprevalence cohort of health care workers (HCWs) to perform a longitudinal analysis of the antibody responses using three distinct serological assays. 501 serum samples were tested using: a) a research-grade RBD and spike based tandem enzyme-linked immunosorbent assay (MS-RBD ELISA, MS-spike ELISA), b) a commercial RBD and spike based tandem ELISA (Kantaro-RBD, -spike), and c) a commercial NP-based chemiluminescent microparticle immunoassay (CMIA, Abbott Architect). Seroprevalence ranged around 28% during the early stage of the pandemic (a: 28.4% positives; b: 28.1%; c: 27.3%). Good correlation was observed between the MS and Kantaro RBD ELISAs and between the MS and Kantaro spike ELISAs. By contrast, modest correlations were observed between the Abbott Architect and both RBD and spike-based assays. A proportion of HCWs (n=178) were sampled again 3-5 months after the first time point. Although antibody levels declined in most of the positive individuals, the overall seroprevalence measured by RBD-spike based assays remained unchanged. However the seroprevalence of NP-reactive antibodies significantly declined. Lastly, we tested six samples of individuals who received two doses of SARS-CoV-2 mRNA vaccine and found that seroconversion was detected by the RBD-spike assays but - of course as expected - not the NP based assay. In summary, our results consolidate the strength of different serological assays to assess the magnitude and duration of antibodies to SARS-CoV-2.
