Abstract
We describe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cell responses, soluble markers of inflammation, and antibody levels and neutralization capacity longitudinally in 70 individuals with PCR-confirmed SARS-CoV-2 infection. Participants represent a spectrum of illness and recovery, including some with persistent viral shedding in saliva and many experiencing post-acute sequelae of SARS-CoV-2 infection (PASC). T cell responses remain stable for up to 9 months. Whereas the magnitude of early CD4+ T cell immune responses correlates with severity of initial infection, pre-existing lung disease is independently associated with higher long-term SARS-CoV-2-specific CD8+ T cell responses. Among participants with PASC 4 months following coronavirus disease 2019 (COVID-19) symptom onset, we observe a lower frequency of CD8+ T cells expressing CD107a, a marker of degranulation, in response to Nucleocapsid (N) peptide pool stimulation, and a more rapid decline in the frequency of N-specific interferon-γ-producing CD8+ T cells. Neutralizing antibody levels strongly correlate with SARS-CoV-2-specific CD4+ T cell responses.
Highlights
Most people generate detectable and durable severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific CD4+ and CD8+ T cell responses following natural infection (Braun et al, 2020; Breton et al, 2021; Dan et al, 2021; Grifoni et al, 2020; Peng et al, 2020; Rydyznski Moderbacher et al, 2020; Sekine et al, 2020; Zhou et al, 2020)
We measured SARS-CoV-2-specific T cell responses, soluble markers of inflammation, antibody levels and neutralization capacity, and viral RNA in saliva longitudinally up to 8.9 months following infection in a diverse group of 70 individuals with PCR-confirmed SARS-CoV-2 infection with varying degrees of initial disease severity and post-acute sequelae of SARS-CoV-2 infection (PASC) in northern California enrolled in the Long-Term Impact of Infection with Novel Coronavirus (LIINC) cohort (Peluso et al, 2021)
Whereas the magnitude of the early CD4+ T cell immune response is determined by the severity of initial infection, pre-existing lung disease was significantly associated
Summary
Most people generate detectable and durable severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific CD4+ and CD8+ T cell responses following natural infection (Braun et al, 2020; Breton et al, 2021; Dan et al, 2021; Grifoni et al, 2020; Peng et al, 2020; Rydyznski Moderbacher et al, 2020; Sekine et al, 2020; Zhou et al, 2020). Current understanding of the factors associated with the magnitude and long-term persistence of the cellular immune response and its relationship to clinical outcomes, humoral responses, and soluble markers of inflammation remain limited. Few studies have investigated inflammatory responses in carefully curated PASC cohorts or in those with prolonged viral RNA shedding To address these issues, we measured SARS-CoV-2-specific T cell responses, soluble markers of inflammation, antibody levels and neutralization capacity, and viral RNA in saliva longitudinally up to 8.9 months following infection in a diverse group of 70 individuals with PCR-confirmed SARS-CoV-2 infection with varying degrees of initial disease severity and PASC in northern California enrolled in the Long-Term Impact of Infection with Novel Coronavirus (LIINC) cohort (Peluso et al, 2021). Whereas the magnitude of the early CD4+ T cell immune response is determined by the severity of initial infection (participants requiring hospitalization or intensive care), pre-existing lung disease was significantly associated
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