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Innate lymphoid cells and disease tolerance in SARS-CoV-2 infection.

ABSTRACT: Risk of severe COVID-19 increases with age, is greater in males, and is associated with lymphopenia, but not with higher burden of SARS-CoV-2. It is unknown whether effects of age and sex on abundance of specific lymphoid subsets explain these correlations. This study found that the abundance of ILCs decreases more than 7-fold over the human lifespan and is lower in males than in females. After accounting for age and sex, innate lymphoid cells (ILCs), but not T cells, were lower in adults hospitalized with COVID-19, independent of lymphopenia. Among SARS-CoV-2-infected adults, ILC abundance correlated inversely with odds and duration of hospitalization, and with severity of inflammation. ILCs were also uniquely decreased in pediatric COVID-19 and did not recover during follow-up. In contrast, individuals with MIS-C had depletion of both ILCs and T cells, and both cell types increased during follow-up. In both pediatric COVID-19 and MIS-C, ILC abundance correlated inversely with inflammation. Blood ILC mRNA and phenotype tracked more closely with ILCs from lung than from other organs. Importantly, blood ILCs produced amphiregulin, a protein implicated in disease tolerance and tissue homeostasis, and the percentage of amphiregulin-producing ILCs was higher in females. These results suggest that, by promoting disease tolerance, homeostatic ILCs decrease morbidity and mortality associated with SARS-CoV-2 infection, and that lower ILC abundance accounts for increased COVID-19 severity with age and in males.

SUBMITTER: Silverstein NJ

PROVIDER: S-EPMC7814851 | biostudies-literature |

REPOSITORIES: biostudies-literature

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