Evaluation of Oropharyngeal responses to SARS-CoV-2

National Institute Of Allergy And Infectious Diseases

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Abstract

Peripheral blood, tonsil, and adenoid tissue were obtained from 110 children who underwent tonsillectomy at Childrens National Hospital in late 2020 with the goal of: 1) evaluating the incidence of infection with SARS-CoV2 infection and epidemiologic characteristics of patients; 2) comparing the immune profile of convalescent children who had COVID-19 and those with no evidence of prior COVID-19; and 3) evaluating immune responses to SARS-CoV2 in the oropharyngeal tissue compared to peripheral blood. All patients had to be PCR negative for SARS-CoV2 prior to surgery. We identified 24 with a history of SARS-CoV2 infection through serologic testing and immunostaining of Spike (S)+RBD+ B cells. Although the cohort was diverse, COVID positive patients were enriched for Hispanic and Black patients. For 11 of these patients, we knew of prior positive PCR history ranging from 25-303 days prior to surgery (mean 102 days). With high dimensional flow cytometry, we identified SARS-CoV2 antigen specific B cells derived from robust geminal center (GC) responses, with evidence of somatic hypermutation in S- and RBD-reactive immunoglobulins from CITE-Seq analyses. We also saw altered T cell populations, including reduced naive T, and increased Tfh and CD57+PD1+CD8 cells, as well as CXCR3+ T cell populations in subjects that were COVID-seropositive, suggesting prolonged changes in lymphocyte populations. These changes were most notable in the cells from the adenoids and some were not observed in peripheral blood. We further found we find robust and persistent activation of TRM cells in the oropharyngeal lymphoid tissue months following COVID-19, suggesting infection can modify immune profiles in children beyond the acute phase (in preparation).