Diagnosis and Tracking of Past SARS-CoV-2 Infection in a Large Study of Vo', Italy Through T-Cell Receptor Sequencing

Gittelman, R. M.; Lavezzo, E.; Snyder, T. M.; Zahid, H. J.; Elyanow, R.; Dalai, S.; Kirsch, I.; Baldo, L.; Manuto, L.; Franchin, E.; Del Vecchio, C.; Simeoni, F.; Bordini, J.; Lore, N. I.; Lazarevic, D.; Cirillo, D. M.; Ghia, P.; Toppo, S.; Carlson, J. M.; Robins, H. S.; Tonon, G.; Crisanti, A.

Measuring the adaptive immune response after SARS-CoV-2 infection may improve our understanding of COVID-19 exposure and potential future protection or immunity. We analyzed T-cell and antibody signatures in a large population study of over 2,200 individuals from the municipality of Vo', Italy, including 70 PCR-confirmed COVID cases (24 asymptomatic, 37 symptomatic, 9 hospitalized). Blood samples taken 60 days after PCR diagnosis demonstrated 97% (68/70) of the latter subjects had a positive T-cell test result, higher than an antibody serology assay (77%; 54/70 of subjects) performed on the same samples. The depth and breadth of the T-cell response was associated with disease severity, with symptomatic and hospitalized COVID cases having significantly higher response than asymptomatic cases. In contrast, antibody levels at this convalescent time point were less informative as they did not correlate with disease severity. 45 additional suspected infections were identified based on T-cell response from the 2,220 subjects without confirmatory PCR tests. Among these, notably, subjects who reported symptoms or had household exposure to a PCR-confirmed infection presented a higher T-cell test positive rate. Taken together, these results establish that T cells are a sensitive, reliable and persistent measure of past SARS-CoV-2 infection.