ABSTRACT
From April 2020 through May 2021 in Padova Province 3395 COVID-19 recovered patients were recruited as potential convalescent plasma donors and tested for SARS-CoV-2 antibodies. Since January 2021 COVID-19 vaccination campaign began in Italy, the impact of vaccination on antibody levels and suspect vaccine breakthrough infections in these subjects were investigated. Post-vaccination anti-Sars-Cov-2 antibody level in 54 previously infected subjects had an exponential increase compared to pre-vaccination level regardless of the number of vaccine doses. However after 100 days from vaccination SARS-CoV-2 antibody level tends to decline. Post-vaccination primary infections were detected in 15 cases, with 3 possible breakthrough infections after a full vaccination course. In these cases, antibody response after infection was present but weaker than the one of subjects vaccinated after natural infection. A trend toward stronger antibody response was observed with increasing distance between natural infection and vaccination. Additionally, 2 cases of asymptomatic reinfections are also discussed.
ABSTRACT
In viral diseases T cells exert a prominent role in orchestrating the adaptive immune response and yet a comprehensive assessment of the T-cell repertoire, compared and contrasted with antibody response, after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is currently lacking. A prior population-scale study of the municipality of Vo', Italy, conducted after the initial SARS-CoV-2 outbreak uncovered a high frequency of asymptomatic infected individuals and their role in transmission in this town. Two months later, we sampled the same population's T-cell receptor repertoire structure in terms of both diversity (breadth) and frequency (depth) to SARS-CoV-2 antigens to identify associations with both humoral response and protection. For this purpose, we analyzed T-cell receptor and antibody signatures from over 2,200 individuals, including 76 PCR-confirmed SARS-CoV-2 cases (25 asymptomatic, 42 symptomatic, 9 hospitalized). We found that 97.4% (74/76) of PCR confirmed cases had elevated levels of T-cell receptors specific for SARS-CoV-2 antigens. The depth and breadth of the T-cell receptor repertoire were both positively associated with neutralizing antibody titers; helper CD4+ T cells directed towards viral antigens from spike protein were a primary factor in this correlation. Higher clonal depth of the T-cell response to the virus was also significantly associated with more severe disease course. A total of 40 additional suspected infections were identified based on T-cell response from the subjects without confirmatory PCR tests, mostly among those reporting symptoms or having household exposure to a PCR-confirmed infection. Taken together, these results establish that T cells are a sensitive, reliable and persistent measure of past SARS-CoV-2 infection that are differentially activated depending on disease morbidity.
