Immune cell dysregulation is a driver of COVID-19 severity

In one of the largest single-center COVID-19 cohort studies to date, researchers at the Icahn School of Medicine at Mount Sinai used samples collected during the peak of the pandemic in New York City to identify a key driver
of disease severity affecting COVID-19.
The findings were published in the Sept.
14 issue of the journal Science-Translational Medicine
.
Studies have shown that lung damage is linked to the loss of a type of immune cell called macrophages, which normally reside in the lungs, tissue tissue repairs, and then new macrophages rush into the lungs from the bloodstream, causing inflammation
.
Blocking the entry of inflammatory macrophages and preventing the loss of repairing lung macrophages could be a therapeutic strategy
for SARS-CoV-2 and other viral lung diseases.

Nearly three years since the beginning of the COVID-19 pandemic at the end of 2019, the virus continues to exacerbate the global health crisis
.
Although the death rate caused by the new crown virus is not high, and some people call it the big flu, because it is much more contagious than the flu, the cumulative number of deaths in three years is still quite amazing
.
Although many countries have gradually lifted epidemic prevention restrictions and mask requirements, winter is approaching, and the latest warning issued by American virus expert Fauci and the emergence of a new strain of omicron reported by Canada are still worrying
.
Understanding why some people develop severe illness after contracting SARS-CoV-2 remains a top priority
.

For the study, researchers collected blood and lung fluid samples from 583 COVID-19 patients admitted to the Health Control Group and Mount Sinai for analysis, following
these cohorts vertically.
The researchers used serum proteomics and immune cell phenotypes to compare the systemic immune response of the two groups of patients and identify underlying drivers of disease severity to assess which patients were most
at risk.
They found that the severity of COVID-19 was associated with alterations in antigen presentation characteristics and a pronounced macrophage profile in peripheral blood, and with shifts in the specialized functions of different macrophage populations in the lungs
.
They found that in patients with severe COVID-19, an increase in the number of immature bone marrow cells and activated B cells, that is, increased infiltration of inflammatory monocytes and inflammatory macrophages, not only depleted sharply by alveolar macrophages residing in lung tissue, but also altered antigen presentation characteristics, which coincided
with the influx of inflammatory monocytes and monocyte-derived macrophages.
Alveolar macrophage count correlates with patient prognosis, and alveolar macrophage numbers and function have been observed to return to homeostasis
in patients recovering from COVID-19.
The researchers say this may partly explain why older adults — who typically have fewer restorative lung macrophages that produce more inflammatory macrophages — may be more susceptible to serious disease
.
Together, these data suggest that restoring macrophage homeostasis may be a strategy
for treating COVID-19.

"Despite the development of vaccines to prevent disease, as well as therapies to treat COVID-19 and other infections, these serious viral diseases remain a major unmet need in medicine," said
Steven Chen, senior author of the study and a M.
D.
/PhD graduate at the Ikahn School of Medicine at Mount Sinai.
"Our study sought to identify drivers of disease severity and mortality to identify therapeutic strategies
that could stop the progression of severe lung viral infections.
"

The researchers emphasize that this study highlights the need to improve the measurement of patients' immune systems
.
Dr Merad said: "Immunoassays that are clinically available are very limited, which is unfortunate because understanding the composition of the immune cells circulating in the blood and the inflammatory molecules they produce can provide great information and help identify new therapies
for many different diseases.
" "Our study shows that the Immunoassay can help stratify patients based on disease drivers and identify treatment strategies tailored to those drivers
.
" "In our study, a subset of patients may benefit
significantly from the recovery of restorative lung macrophages.
The use of immunoassay research in the clinic will help make this judgment
early in the course of the disease.
"We are now following the COVID-19 cohort described in this study and will compare patients with prolonged COVID with a broad immunological spectrum of patients who are fully recovered to identify drivers and treatment strategies
for prolonged COVID.
"