Mild Covid-19 Linked to Increased Inflammation in Cells Months Later, Study Finds

In new research out Monday, scientists say they’ve found evidence that our immune system appears more prone to inflammation and other metabolic changes in the aftermath of even a mild case of covid-19. More research will be needed to understand how these changes could be linked to post-covid symptoms, however.

Researchers are continuing to gather clues about the nature of infection from the SARS-CoV-2 coronavirus and how it can affect us months after the initial illness has passed. Inflammation is a key aspect of how our bodies respond to infection from germs like the coronavirus. In some cases of covid-19, though, the immune response becomes a double-edged sword, causing self-inflicted damage throughout the body. Survivors of severe covid-19, in particular, often experience a variety of persistent symptoms, some of which have been linked to ongoing immune dysfunction. But while the risk of long-term symptoms, commonly known as long covid, may be highest for severe cases, studies have found that some people with initially mild illness can experience similar problems.

This new study, published in the journal Mucosal Immunology, attempts to shed light on the immune changes that might be happening in milder covid-19 cases. It was conducted by scientists at the Karolinska Institute in Sweden, as well as the Helmholtz Center Munich and the Technical University of Munich in Germany. They collected blood samples from 68 people previously diagnosed with mild covid and compared them to people without covid; the samples were collected three to five months after infection, as well as a year later.

The scientists specifically focused on people’s macrophages, important white blood cells that detect foreign invaders, alert other immune cells to the infection, and even swallow germs whole. They prodded these macrophages into action by exposing them to mock signals of an infection, then took measurements of how they reacted, which included seeing which genes were being actively turned on.

At the three to five month mark, the macrophages of those with mild covid behaved noticeably different on average than those who had never been exposed to the coronavirus, the researchers found. Specifically, they released greater amounts of molecules known to be involved in causing inflammation.

“We can show that the macrophages from people with mild covid-19 exhibit an altered inflammatory and metabolic expression for three to five months post-infection,” said study author Craig Wheelock, a lecturer at Karolinska’s department of Medical Biochemistry and Biophysics, in a statement. “Even though the majority of these people did not have any persistent symptoms, their immune system was more sensitive than that of their healthy counterparts.”

The study has some caveats. For one, it’s based on a relatively small sample size, though the addition of a control group does lend more credibility. It’s also not clear how relevant these findings are to our understanding of long covid, since those patients weren’t being explicitly studied. The authors do note that about 16% of the people in their mild covid group reported persistent symptoms at the three to five month mark, which had dropped to zero people a year later. Interestingly enough, the inflammatory changes seen in these people’s macrophages also appeared to fade away 12 months later.

Perhaps more important is that long covid is suspected to be caused by one or more of several different mechanisms, so even confirming a connection between post-covid inflammation and people’s lingering symptoms may still not explain every single case. Ideally, though, this kind of research may someday point us to better treatments for at least some patients. The team, for their part, hope to keep digging deeper and to include even more groups of people for comparison.

“We would like to do a corresponding study in which we involve both people with severe covid-19 and people without covid-19 but who have another kind of respiratory disease, such as influenza,” said co-author Julia Esser-von Bieren, research group leader at the Helmholtz Center Munich and the Technical University of Munich. “We’ll then examine if what inflicts covid-19 patients also inflicts those with, say, seasonal influenza.”