A nurse treats a coronavirus patient in an ICU. Image from Scripps video

Patients with severe COVID-19 disease who develop respiratory failure have malfunctions in their immune systems that distinguish them from other such patients, according to a new study.

The findings could help doctors develop new ways to prevent and treat this life-threatening complication researchers said.

The Cedars-Sinai study, published Dec. 16 in the journal Cell Reports, focused on acute respiratory distress syndrome – known as ARDS. The sudden-onset respiratory failure can occur when the lungs’ lining is damaged by illness or injury.

ARDS causes fluid to accumulate in the lungs and also causes air sacs in the lungs to collapse, impeding breathing and lowering the oxygen level in the blood.

Although most COVID-19 patients have mild respiratory illness, about 20% become seriously ill and require hospitalization due to pneumonia. That can progress to ARDS and systemic inflammation, according to recent research.

ARDS is associated with poorer outcomes, including death or lasting lung damage.

“Because ARDS has such serious consequences for coronavirus patients, it is critical that we understand why it happens and what we can do to treat it,” said Peter Chen, MD, professor of Medicine and director of the Division of Pulmonary and Critical Care Medicine at Cedars-Sinai. “That is why we did this research.”

The research team analyzed the immune systems of 17 COVID-19 patients – five with moderate coronavirus disease, six with ARDS and six who were recovering from ARDS – and compared these patients against three people without COVID-19.

They looked at the “transcription process,” which is how genes transfer their instructions to proteins that construct a cell’s chemical processes, in so-called peripheral blood mononuclear cells.

This category includes various types of highly specialized immune cells that fight infections.

The investigators uncovered a range of distinctive defects in the transcription processes of peripheral blood mononuclear cells in the ARDS patients, as compared with the other subjects in the study.

These defects appeared in cells in both of the body’s immune systems: the “innate immune system,” which initially responds to viruses and bacteria; and the “adaptive immune system,” which kicks in later.

The defects also affected how the body switched between innate and adaptive immunity.

“Our study supports the concept that COVID-19, and especially severe cases that have progressed to ARDS, is characterized by multifaceted impairment of the body’s regulation of immune responses,” said Helen Goodridge, Ph.D, associate professor of Biomedical Sciences and Medicine at Cedars-Sinai.

Future research using larger sample sizes is needed to further delineate the transcriptional landscape of immune cells in different ARDS populations, according to the study team.

In the meantime, Goodridge said, the implications of the findings are clinically relevant. They indicate that treatment of patients with ARDS arising from COVID-19 infections may require a targeted approach instead of broad, immunosuppressive therapy.

– City News Service

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