A new study explores interactions between airway cells and immune cells at the molecular level to identify why some people are at risk for severe COVID-19 while others are not.
There is a lot of evidence that SARS-CoV-2, the new coronavirus, affects people differently. About 80% of those with SARS-CoV-2 experience a clinically mild version of COVID-19, which means they get better without going to the hospital.
Risk factors for severe disease include being male, older, and having underlying health conditions, among other factors.
What drives these risk factors is not entirely clear.
Some experts have suggested that an excessive immune reaction in response to the virus is at the heart of damage to the lungs and other parts of the body that people with severe COVID-19 experience.
Writing in Biotechnology natureScientists at the Digital Health Center of the Berlin Institute of Health (BIH) and the Charité – Universitätsmedizin in Berlin in Germany attempted to discover the molecular actions that underpin these excessive immune reactions.
Professor Roland Eils, president and founding director of the Digital Health Center, is one of the study’s five main authors.
To determine how different cells interact and communicate with each other, the multidisciplinary research team performed a single-cell RNA sequencing analysis of upper and lower respiratory tract samples from 19 people in the hospital with COVID-19 and five volunteers. without the new coronavirus.
In total, the scientists analyzed 160,528 individual cells.
Of the 19 people with COVID-19, eight had moderate illness, the authors write, while they classified 11 as critical. Two people died from the disease.
In participants with COVID-19, the team observed a three-fold increase in gene expression of angiotensin-converting enzyme 2 (ACE2), which encodes the receptor that the new coronavirus uses to bind to cells during infection.
“It is interesting to note that in the case of COVID-19, the interferon signaling protein, which is actually the central defense strategy of the immune system against viral infections, contributes to epithelial cells producing more ACE2 and therefore , become more vulnerable to viral infection, “Professor Irina Lehmann, director of the BIH Molecular Epidemiology Research Group and one of the study’s lead authors, explains.
“In COVID-19, the immune system helps the virus infect more cells, thereby amplifying the disease,” he continues.
The team then identified the specific subsets of immune and epithelial cells that were present in the samples and found proinflammatory cell types that may be causing cell death in the lungs.
“Especially in seriously ill patients, we see that an overreactive immune system drives destruction of lung tissue. This may explain why these patients are more severely affected by the infection than patients in whom the immune system reacts appropriately. ”
– Prof. Roland Eils, corresponding author
Professor Leif-Erik Sander, another of the study’s lead authors, also evaluates the findings:
“These results suggest that our treatments in patients with COVID-19 should not only target the virus itself, but also consider therapies that restrict the immune system, such as those now used with dexamethasone, possibly even early in disease, prevent the immune system from overreacting. “
Specifically, the researchers suggest that attacking the proinflammatory pathways “CCR1 and / or CCR5 could suppress immune hyperactivation.”
The team acknowledges that their study has some shortcomings. Due to the relatively low number of people with COVID-19 requiring hospital care in Germany, the study was not large enough to look at the influences of age, gender, and underlying health conditions on the results.
The researchers also were unable to include people who had mild COVID-19 and who did not require hospital care.
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