Study provides further evidence that immune cell dysregulation is a driver of COVID-19 severity

Oct. 4, 2022
Maintenance of reparative lung macrophages may be a viable therapeutic strategy for the treatment of SARS-CoV-2 and other inflammatory lung diseases.

Researchers at the Icahn School of Medicine at Mount Sinai, using samples collected during the peak of the pandemic in New York City, have identified a key driver of COVID-19 disease severity.

The findings, published in the September 14 edition of Science Translational Medicine, suggest that lung damage is linked to the loss of immune cells called macrophages that normally reside in the lung and organize tissue repair, followed by an influx of new macrophages from the blood into the lung that cause inflammation. Blocking the entry of inflammatory macrophages and preventing the loss of reparative lung resident macrophages may be a therapeutic strategy for treating SARS-CoV-2 and other viral lung diseases

Nearly three years since the start of the COVID-19 pandemic in late 2019, the virus continues to fuel a worldwide health crisis. 

In the study, blood and lung fluid samples of healthy controls and 583 COVID-19 patients admitted to Mount Sinai were collected as part of the Health System’s COVID-19 Biobank. The cohorts were longitudinally followed from March through December 2020.

The investigators used serum proteomics and immune cell phenotyping to compare the two groups' systemic immune responses and identify potential disease severity drivers that could predict which patients were most at risk and guide new treatment protocols. They found that COVID-19 severity was linked to a shift in the specialized functions of different macrophage populations in the lung. This may partly explain why older adults, who have fewer reparative lung resident macrophages to start with and can produce more inflammatory blood-derived macrophages, may be predisposed to severe disease, say the researchers.  

Mount Sinai release on Newswise