Duration of post–COVID-19 symptoms is associated with sustained SARS-CoV-2–specific immune responses
Jacob K. Files, Sanghita Sarkar, Tim R. Fram, Sushma Boppana, Sarah Sterrett, Kai Qin, Anju Bansal, Dustin M. Long, Steffanie Sabbaj, James J. Kobie, Paul A. Goepfert, Nathan Erdmann
Jacob K. Files, Sanghita Sarkar, Tim R. Fram, Sushma Boppana, Sarah Sterrett, Kai Qin, Anju Bansal, Dustin M. Long, Steffanie Sabbaj, James J. Kobie, Paul A. Goepfert, Nathan Erdmann
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Research Article COVID-19 Immunology

Duration of post–COVID-19 symptoms is associated with sustained SARS-CoV-2–specific immune responses

Abstract

A subset of COVID-19 patients exhibit post-acute sequelae of COVID-19 (PASC), but little is known about the immune signatures associated with these syndromes. We investigated longitudinal peripheral blood samples in 50 individuals with previously confirmed SARS-CoV-2 infection, including 20 who experienced prolonged duration of COVID-19 symptoms (lasting more than 30 days; median = 74 days) compared with 30 who had symptom resolution within 20 days. Individuals with prolonged symptom duration maintained antigen-specific T cell response magnitudes to SARS-CoV-2 spike protein in CD4+ and circulating T follicular helper cell populations during late convalescence, while those without persistent symptoms demonstrated an expected decline. The prolonged group also displayed increased IgG avidity to SARS-CoV-2 spike protein. Significant correlations between symptom duration and both SARS-CoV-2–specific T cells and antibodies were observed. Activation and exhaustion markers were evaluated in multiple immune cell types, revealing few phenotypic differences between prolonged and recovered groups, suggesting that prolonged symptom duration is not due to persistent systemic inflammation. These findings demonstrate that SARS-CoV-2–specific immune responses are maintained in patients suffering from prolonged post–COVID-19 symptom duration in contrast to those with resolved symptoms and may suggest the persistence of viral antigens as an underlying etiology.

Authors

Jacob K. Files, Sanghita Sarkar, Tim R. Fram, Sushma Boppana, Sarah Sterrett, Kai Qin, Anju Bansal, Dustin M. Long, Steffanie Sabbaj, James J. Kobie, Paul A. Goepfert, Nathan Erdmann

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Figure 3

Maintenance of S-protein–specific CD4+ T cell response magnitude in individuals with prolonged symptom duration.

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Maintenance of S-protein–specific CD4+ T cell response magnitude in indi...
Investigation into the upregulation of OX40 and PD-L1 in CD4+ T cells after stimulation with SARS-CoV-2 S pool. (A) Representative flow cytometry plots of a recovered and a prolonged individual at all 3 time points. (B) Comparisons of the net CD4+ T cell response magnitude between recovered (n = 29) and prolonged (n = 20) groups; significance between time points determined by paired Wilcoxon’s signed-rank test and significance between groups determined by unpaired Wilcoxon’s rank sum. (C) Comparisons of the net CD4+ T cell response magnitude made longitudinally by DPSO (n = 135 across all 3 time points); significance determined by linear mixed effects modeling. (D) Frequencies of CD4+ T cell responses meeting positivity criteria; no significance determined by Fisher’s exact. Navy = recovered group, red = prolonged group; circles = early, triangles = intermediate, squares = late. Box plots indicate median, IQR, and 95% confidence interval; significance is indicated as follows: *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001.