Wheezing after receiving on the treadmill. Swallowing air while doing housework. Difficulty breathing is one of the many frightening and frustrating symptoms that can persist in covid patients months after the initial infection. But while these symptoms were a mystery at the start of the pandemic, scientists are slowly unraveling their causes, bringing us closer to finding a treatment.
In a recently published article in the European respiratory magazine, researchers at the University of Manchester in the UK identified a likely culprit: immune cells known as monocytes. These soft, blue-gray cells float around in your bloodstream looking for signs of trouble. When they encounter an invading pathogen, such as a bacterium or virus, they generate other crucial immune cells and alert the immune system to activate additional defenses. Monocytes are particularly important during lung injury. At the first sign of trouble, they move to the lungs and spawn several specialized macrophages (immune cells that feed on pathogens) that become the first line of immune defense against invading germs.
But it appears that a covid infection can really mess with the functioning of these immune cells, meaning that “they may respond abnormally to subsequent events,” says Laurence Pearmain, a clinical professor at the University of Manchester and a co-author on the paper. 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 attached proteins that are critical for directing cells to the lungs. These results, the scientists say, link abnormal monocytes to prolonged Covid and lung injury, paving the way for possible therapies to correct the abnormalities or alleviate symptoms.
Pearmain and the team had good reason to be suspicious of these cells. Other researchers had already discovered that SARS-CoV-2 affects monocytes. According to Judy Lieberman, a biologist at Harvard Medical School, in cases of severe covid, virus-infected monocytes often die in a way that releases many alarm molecules into the body. causing large amounts of additional inflammation. “It’s like a forward feeding loop,” she says. “Once this gets going, it’s incredibly difficult to control.” These results pointed to the potential role of dysfunctional monocytes in prolonged covid, as inflammation is known to contribute to some long-lasting symptoms.
Pearmain and the team decided to investigate. To find out exactly what these cells were doing during Covid and prolonged Covid, the scientists turned to blood samples. Starting in the summer of 2020, at various hospitals in the UK, Pearmain and team drew blood from 71 patients during their covid hospitalizations. Over the next few months, they also collected blood from 142 separate patients previously hospitalized for Covid, collecting samples during their follow-up visits.
The patients followed up had had Covid about six months earlier, and at this point after an infection, Pearmain says, any immune dysfunction caused by the virus would be expected to have subsided. However, this was not what the team was looking at. “It was obvious that a lot of people were still battling shortness of breath, fatigue, and many of the other long-term symptoms of covid,” she says. Specifically, 48 percent of the patients being followed reported shortness of breath, 44 percent fatigue. The team had found a long cohort of Covid to study, so it was time to take a closer look at their immune cells.
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