• Otávio Santiago

Spatial Analysis of T-cell Subsets in Lungs of COVID-19 Patients

Many studies have been performed in severe COVID-19 on immune cells in the circulation and on cells obtained by bronchoalveolar lavage. Most studies have tended to provide relative information rather than a quantitative view, and it is a combination of approaches by various groups that is helping the field build a picture of the mechanisms that drive severe lung disease. Approaches employed to date have not revealed information on lung parenchymal T cell subsets in severe COVID-19.

Therefore, we sought to examine early and late T cell subset alterations in the lungs and draining lymph nodes in severe COVID-19 using a rapid autopsy protocol and quantitative imaging approaches. Here, we have established that cytotoxic CD4+ T cells (CD4 + CTLs) increase in the lungs, draining lymph nodes and blood as COVID-19 progresses. CD4 + CTLs are prominently expanded in the lung parenchyma in severe COVID-19. In contrast CD8+ T cells are not prominent, exhibit increased PD-1 expression, and no obvious increase is seen in the number of Granzyme B+ CD8+ T cells in the lung parenchyma in severe COVID-19. Based on quantitative evidence for re-activation in the lung milieu, CD4 + CTLs may be as likely to drive viral clearance as CD8+ T cells and may also be contributors to lung inflammation and eventually to fibrosis in severe COVID-19.

When hospitalized patients with acute COVID-19 were traced back to establish whether they had a previous mRNA vaccine course in the previous 3 to 6 months or had been naturally infected, the Odds Ratio supporting a protective effect of vaccination over natural infection ranged from 5 to 7 depending on the vaccine taken. However, when patients were segregated by age in those 64 and older the Odds Ratio favoring prior mRNA vaccination over natural infection rose to 19.5.

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