Journal Article

SARS-CoV-2-specific T cells associate with inflammation and reduced lung function in pulmonary post-acute sequalae of SARS-CoV-2

Watson, Renée O., Neff, Charles P., Campbell, Thomas B., Jolley, Sarah E., Fontenot, Andrew P., Littlefield, Katherine M., Schneider, Jennifer M., Yamada, Eiko, Falta, Michael T., Palmer, Brent E., Zhang, Min

2022

Overview

As of January 2022, at least 60 million individuals are estimated to develop post-acute sequelae of SARS-CoV-2 (PASC) after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While elevated levels of SARS-CoV-2-specific T cells have been observed in non-specific PASC, little is known about their impact on pulmonary function which is compromised in the majority of these individuals. This study compares frequencies of SARS-CoV-2-specific T cells and inflammatory markers with lung function in participants with pulmonary PASC and resolved COVID-19 (RC). Compared to RC, participants with respiratory PASC had between 6- and 105-fold higher frequencies of IFN-γ- and TNF-α-producing SARS-CoV-2-specific CD4 + and CD8 + T cells in peripheral blood, and elevated levels of plasma CRP and IL-6. Importantly, in PASC participants the frequency of TNF-α-producing SARS-CoV-2-specific CD4 + and CD8 + T cells, which exhibited the highest levels of Ki67 indicating they were activity dividing, correlated positively with plasma IL-6 and negatively with measures of lung function, including forced expiratory volume in one second (FEV 1 ), while increased frequencies of IFN-γ-producing SARS-CoV-2-specific T cells associated with prolonged dyspnea. Statistical analyses stratified by age, number of comorbidities and hospitalization status demonstrated that none of these factors affect differences in the frequency of SARS-CoV-2 T cells and plasma IL-6 levels measured between PASC and RC cohorts. Taken together, these findings demonstrate elevated frequencies of SARS-CoV-2-specific T cells in individuals with pulmonary PASC are associated with increased systemic inflammation and decreased lung function, suggesting that SARS-CoV-2-specific T cells contribute to lingering pulmonary symptoms. These findings also provide mechanistic insight on the pathophysiology of PASC that can inform development of potential treatments to reduce symptom burden.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Biology and Life Sciences / CD4 antigen / CD8 antigen / Complications / Coronaviruses / COVID-19 / Cytokines / Dyspnea / Health aspects / Hospitalization / Humans / Immune response / Infections / Inflammation / Interleukin 6 / Lung / Lungs / Lymphocytes / Lymphocytes T / Medicine and Health Sciences / Observations / Peripheral blood / Pre-existing conditions / Proteins / Pulmonary functions / Pulmonary ventilation / Respiration / Respiratory diseases / Respiratory function / SARS-CoV-2 / Severe acute respiratory syndrome / Severe acute respiratory syndrome coronavirus 2 / Statistical analysis / T cells / Tumor Necrosis Factor-alpha / Tumor necrosis factor-α / Viral diseases / γ-Interferon