ABSTRACT
T-cell recognition of antigenic peptides presented by HLA molecules at the cell surface is critical for mounting an efficient adaptive immune response during acute viral infection such as COVID-19 caused by SARS-CoV-2. Recent data suggest that the depth of peptide coverage and the breadth of T cells that are able to respond are both important parameters associated with disease outcome. Strong T-cell responses against SARS-CoV-2 have also been reported in unexposed individuals, pointing to a possible role of heterologous immunity. In this study, we performed immunosequencing of the TCR CDR3beta region in a large cohort of 116 alloHSCT recipients and their corresponding healthy donors collected prior to the emergence of SARS-CoV-2. We used bioinformatics analyses and a large database of about 150,000 SARS-CoV-2 specific T-cell sequences in order to investigate the composition of the TCR repertoire regarding the presence of SARS-CoV-2 specific clonotypes in unexposed subjects among the more than 3.5 million CDR3beta sequences that we retrieved by immunosequencing. We also performed peptide binding predictions based on the reference proteome of the virus and by using the HLA class I high resolution typing data of the 116 patients. We could show that every individual is equipped with a large and diverse repertoire of clonotypes sharing their CDR3beta sequence with a SARS-CoV-2 specific T cell. Furthermore, the composition of the anti-SARSCoV- 2 repertoire was very similar among individuals, in healthy donors but also in the context of immune reconstitution in recipients, despite significant differences previously reported when accounting for the whole repertoire or for CMV-specific clonotypes only. In addition, each individual had the potential to cover a diverse repertoire of SARS-CoV-2 derived peptides (i.e., a few thousands strong and weak binders), but, interestingly, some interindividual differences were observed when only accounting for a strong affinity level of binding.
ABSTRACT
Aim: Evaluate the kinetics of antibody, plasmablasts (PB) and memory B cells (MBCs) from day 7 up to 8 months following mild COVID-19 Methods: This observational study enrolled 31 RT-PCR confirmed acute mild COVID-19 patients longitudinal followed ups at six visits: 0, +7, +14 +28, +56 and +200 days post onset of symptoms (dpos). Antibodies against S1 domain of the spike and N (nucleocapside) proteins of SARSCoV- 2 were evaluated using ELISA, while neutralization was quantified by a commercially available surrogate (sVNT) assay. Specific PB and MBC were assessed by ELISPOT Results: During mild COVID-19, anti-S1, anti-N as well as neutralizing antibodies were elicited during the first 3 weeks pos, reached a peak between 20-30 dpos and decayed slowly, however 80% of patients had detectable neutralizing antibodies at +200 dpos. S1-specific IgA and IgM PB reached their peak around +14 days while IgG slow increased. All patients developed anti-S1 IgG MBCs by one month that peaked at 49 dpos and remained stable up to 245dpos;anti-N IgG MBCs kinetics was similar but their magnitude was reduced. We next correlated humoral with cellular immune responses and found that anti-S1 IgG and IgA titers at visits +14 and +28 days correlated with plasmablast, while there was a poor correlation between antibody titers and MBCs at visit +56 days that was lost at visit +200 days Conclusion: Mild COVID-19 elicits early and long lasting neutralizing antibodies Antigen-specific PB correlated with early antibody titers, while specific MBCs frequencies were stable and independent of antibody titers up to 245 dpos.