Impaired innate immunity tied to severe COVID-19

A weak innate immunity appears to play a central role in severe infections of the coronavirus disease 2019 (COVID-19), a recent study has found.

Researchers enrolled 22 healthy controls (median age 49 years, 64 percent women), 40 mild COVID-19 patients (median age 68 years, 50 percent women), and 44 severe COVID-19 patients (median age 60 years, 11 percent women). They used a variety of lab assays to phenotypically assess neutrophil and monocyte subpopulations, as well as soluble activation markers in plasma samples.

Moreover, they looked at the antimicrobial functions: phagocytosis, oxidative burst, and NETosis, a regulated form of neutrophil cell death.

Cell marker analysis revealed that in COVID-19 patients, neutrophils and monocytes displayed hallmarks of activation, with heightened expression of markers such as CD11b, elastase, lipocalin-2, and calprotectin. Of note, those with severe disease displayed an even more distinct phenotypic profile, indicating greater neutrophil activation.

Subsequent experiments further verified the disturbed distribution of cell subpopulations in COVID-19 patients. In particular, those with severe disease had heightened levels of immunosuppressive and immature neutrophils, indicating an impaired immune response.

“These findings indicate that SARS-CoV2 infection may induce an overactivation of the innate system resulting in apparition of abnormal subpopulations and exhaustion of cellular effectors,” the researchers said.

“Such dysregulation of innate responses strongly advocates for the use of systematic antibiotic and antifungal prophylaxis in severe patients and warrants further studies to assess efficacy of neutrophil-related therapeutics like elastase inhibitors and the usefulness of severity-associated markers as prognosis tools in COVID-19,” they added.