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.
Highlights
COVID-19, caused by the SARS-CoV-2 virus, has infected millions of individuals and caused profound morbidity and mortality worldwide
Symptoms reported beyond 30 days in the prolonged group included dyspnea, fatigue, psychataxia, and/or cough. (Note: isolated anosmia/ageusia for more than 30 days did not meet our criteria for classification into the prolonged group.) As expected, the prolonged group had higher frequencies of hospitalization and severe infection, consistent with previous studies that have shown up to 76% of hospitalized patients reported at least 1 residual symptom at 6 months after initial symptom onset [27]
We longitudinally investigate systemic cellular and humoral immunity from convalescent COVID-19 samples, comparing those with a prolonged symptom duration with those who experienced rapid symptom resolution
Summary
COVID-19, caused by the SARS-CoV-2 virus, has infected millions of individuals and caused profound morbidity and mortality worldwide. Reports have shown that SARS-CoV-2–specific T cell memory is maintained for months after initial symptom onset in convalescent PBMC samples, but the magnitude of observed T cell responses decreases over time [14, 16,17,18,19,20,21]. Numerous studies have detected increased magnitudes of IgG+ SARS-CoV-2–specific memory B cells in the blood of convalescent patients during late convalescence, suggesting that the memory B cell population is sustained in the months following acute infection [16, 18, 20, 22]. Many groups have found that SARS-CoV-2–specific antibodies, and neutralizing antibodies in particular, decrease within the first few months following initial symptom onset in many individuals [16, 18,19,20, 22,23,24]
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