Longitudinal analysis of the humoral response to SARS-CoV-2 spike RBD in convalescent plasma donors

Abstract

Héma-Québec, the blood supplier in the Province of Quebec, Canada, collects and tests convalescent plasma used in a clinical trial to determine the clinical efficacy of this product for the treatment of hospitalized COVID-19 patients. So far, we have collected 1159 plasma units from 282 COVID-19 convalescent donors. The presence of antibodies to the receptor binding domain (RBD) of SARS-CoV-2 spike protein in convalescent donors was established at the first donation. Seropositive donors were asked to donate additional plasma units every six days. Until now, 15 donors have donated at least four times and, in some cases, up to nine times. This allowed us to perform a longitudinal analysis of the persistence of SARS-CoV-2 RBD-specific antibodies in these repeat donors, with the first donation occurring 33-77 days after symptoms onset and donations up to 71-114 days after symptoms onset thereafter. In all donors, the level of antibodies remained relatively stable up to about 76 days after symptoms onset but then started to decrease more rapidly to reach, in some convalescent donors, a seronegative status within 100-110 days after symptoms onset. The decline in anti-RBD antibodies was not related to the number of donations but strongly correlated with the numbers of days after symptoms onset (r = 0.821). This suggests that de novo secretion of SARS-CoV-2 RBD antibodies by short-lived plasma cells stopped about 2-3 months after disease onset, an observation that has important implications for convalescent plasma collection and seroprevalence studies undertaken several months after the peak of infection.

Cross-sectional evaluation of humoral responses against SARS-CoV-2 Spike

“…Interestingly, anti-RBD IgM presented a stronger correlation with neutralization than IgG and IgA ( Figure S4A,C), suggesting that at least part of the neutralizing activity is mediated by IgM. The neutralization activity appears to further decrease after the resolution of symptoms as recently reported in a series of longitudinal studies on convalescent patients (Beaudoin-Bussières et al, Ibarrondo et al, 2020;Long et al, 2020;Perreault et al, 2020;Yin et al, 2020;Zhang et al, 2020). However, it remains unclear whether this reduced level of neutralizing activity would remain sufficient to protect from re-infection.…”

Functional SARS-CoV-2-specific immune memory persists after mild COVID-19

“…However, more recent studies, including our own, have examined memory time points when only LLPCs, and not short-lived PBs, are producing circulating antibodies. Our study, along with three others clearly demonstrates elevated IgG + RBD-specific plasma antibodies and neutralizing plasma are generated and maintained for at least 3 months post-SARS-CoV-2 infection 34 – 36 .…”

Longitudinal analysis of clinical serology assay performance and neutralising antibody levels in COVID19 convalescents

“…Alternatively, it is possible that the range of N epitopes recognized by sera might change with time. Whatever the explanation, it is clear that that the trajectories of antibody titres measured using assays based on recognition of the same or related antigens can differ [22][23][24][25] .…”