The long Covid mystery has a new suspect

by The Insights

Wheezing after receiving on the treadmill. Suck in air while doing chores. Shortness of breath is one of many frightening and frustrating symptoms that can linger in Covid patients months after their initial infection. But while these symptoms were a mystery at the start of the pandemic, scientists are slowly uncovering their causes, bringing us closer to finding a cure.

In an article recently published in the European Respiratory Journal, researchers from the University of Manchester in the UK have identified a likely culprit: immune cells called monocytes. These blue-gray spongy cells float around in the bloodstream, looking for signs of trouble. When they encounter an invading pathogen, such as a bacteria or virus, they generate other crucial immune cells and alert the immune system to activate additional defenses. Monocytes are particularly important in lung damage. At the first sign of trouble, they travel to the lungs, spawning various specialized macrophages – immune cells that eat pathogens – which become the first line of immunological defense against invading germs.

But it appears that a Covid infection can really disrupt the functioning of these immune cells, meaning they “may respond abnormally to subsequent events”, says Laurence Pearmain, clinical lecturer at the University of Manchester and co-author of the article. In Covid patients with long-lasting shortness of breath after an infection, the researchers found monocytes with irregularities. Compared to healthy people, these patients had monocytes with different levels of proteins attached to them that are essential for directing cells to the lungs. These findings, the scientists say, link abnormal monocytes to long lung damage and Covid, paving the way for potential therapies to correct abnormalities or alleviate symptoms.

Pearmain and the team had good reason to suspect these cells. Other researchers had already discovered that SARS-CoV-2 affects monocytes. According to Judy Lieberman, a biologist at Harvard Medical School, in severe Covid cases, monocytes infected with the virus often die in a way that releases many alarm molecules into the body, triggering large amounts of additional inflammation. . “It’s like an anticipation loop,” she says. “Once it starts, it’s incredibly difficult to control.” These findings highlighted the potential role of dysfunctional monocytes in long Covid, as inflammation is known to contribute to some long-lasting symptoms.

Pearmain and the team decided to investigate. To understand exactly what these cells were doing during Covid and the long Covid, scientists turned to blood samples. From the summer of 2020, at several hospitals across the UK, Pearmain and the team took blood from 71 patients while they were in hospital for Covid. Over the following months, they also drew blood from 142 separate patients previously hospitalized with Covid, collecting samples during their follow-up visits.

The patients followed had had Covid about six months earlier, and at this point after an infection, Pearmain says, one would expect any immune dysfunction caused by the virus to have subsided. Yet that was not what the team saw. “It was obvious that a lot of people were still really struggling with shortness of breath, fatigue and a lot of other long Covid symptoms,” he says. More specifically, 48% of patients followed reported shortness of breath, 44% fatigue. The team had found a long Covid cohort to study – so it was time to take a closer look at their immune cells.

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