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Survivors Of Severe COVID-19 With Long-Haul Respiratory Symptoms Display Enhanced Activation of Circulating T Cells

2022; Elsevier BV; Volume: 149; Issue: 2 Linguagem: Inglês

10.1016/j.jaci.2021.12.222

1097-6825

Glenda Canderan, Lyndsey M. Muehling, Alexandra Kadl, Chintan Ramani, Jeffrey M. Sturek, Catherine A. Bonham, Deborah D. Murphy, Paul Wright, Behnam Keshavarz, Jeffrey M. Wilson, Sierra Barone, Jonathan M. Irish, Judith A. Woodfolk,

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Some patients who survive severe COVID-19 develop persistent respiratory symptoms. Although increased activation of T-cells has been reported in severe acute disease, little is known about the long-term evolution of T-cells after SARS-CoV-2 infection in patients with long-haul symptoms. Circulating T-cells were tracked in a sample of a COVID-19 cohort (n=88) consisting of patients with persistent respiratory symptoms. Cells were obtained during severe acute COVID-19 illness and at 6 weeks and 6-11 months after hospital discharge. Cells were analyzed by high-dimensional immunophenotyping using spectral flow cytometry. Longitudinal changes in complex cell signatures were identified using the T-REX algorithm. Antibodies to SARS-CoV-2 proteins were assessed by ImmunoCAP assay. Patients with long-haul symptoms who were sampled at 6 weeks after hospital discharge had higher frequencies of activated (HLA-DR+CD38+) and tissue-homing (CCR5+) CD4+ and CD8+ T-cells compared to healthy subjects and patients with mild acute COVID-19. Higher numbers of terminally differentiated (CCR7-CD27-) CD8+ T-cells were also evident. T-REX identified multiple CD4+ and CD8+ T cell signatures that expanded or contracted by ≥95% up to 6 months after acute infection, including highly activated subtypes (CD3+6CD4+7CD45RA+7CD45RO+1CD38+1HLA-DR+4CD95+1T-BET+2TCF1+1KI-67+2 and CD3+6CD8+9CD45RA+6CD38+1HLA-DR+5CD95+2CCR5+2TCF1+1T-BET+6KI-67+2). Fluxes in T-cell signatures were detectable several months after acute infection, even in the presence of declining antibodies to SARS-CoV-2 proteins. Patients with long-haul respiratory symptoms after severe COVID-19 illness display activated T-cell signatures and marked immune perturbations, consistent with trafficking of T-cells with pathogenic potential and dysregulated homeostasis. Activated T-cells may contribute to airway inflammation long after acute illness resolves.