Brain fog in lung covid may be due to overactive immune cells

Highly responsive immune cells in the brain, microglia, could play a role in the lack of concentration and memory loss that people with long-term Covid-19 (lung covid) sometimes suffer. The immune cells may inhibit the formation of new brain cells and of myelin, the insulating layer around nerve fibers, research in mice and Covid patients has shown.

American researchers discovered immunological similarities with the ‘brain fog’ that occurs in cancer patients after chemotherapy. She published their research as a preprint last week, it has yet to be reviewed by independent scientists.

Some people have health problems for weeks or months after an infection with SARS-Cov-2, even if it was only mild, including extreme tiredness, shortness of breath or pain. Intractable cognitive complaints are also reported. about one quarter of them has problems with attention, concentration, information processing and memory. Its cause is not yet clear.

Damaged brain cells

The Americans modified lab mice so that their lung cells had the gateway for the coronavirus (the human ACE 2 receptor), and infected them with SARS-CoV-2. In their brain tissue, they found reactive microglia for up to seven weeks in the white matter under the cerebral cortex (which contains the nerve fibers), and not in the gray matter (which contains the brain cells). Microglia clear up damaged brain cells and pathogens, but can also inhibit the formation of myelin. That seemed to be the case in the mice: the myelin layer around nerve fibers was less thick.

The researchers also saw less production of new nerve cells in the hippocampus, which is crucial for memory. The animals also had more inflammatory substances in the cerebrospinal fluid for up to seven weeks. One such substance was CLL11, which has previously been linked to cognitive decline and reduced production of brain cells in the hippocampus.

Also in nine deceased covid patients more reactive microglia in the white matter were seen in the brain tissue than in five uninfected deceased.

The effects found are not very large

Debby van Riel Erasmus MC

To find out whether the dysregulated immune system could also play a role in lung covid patients, the researchers tested whether CLL11 was present in their blood plasma. In the blood of 48 people with lung covid and cognitive problems, the amount of CLL11 was indeed slightly increased on average, compared to 15 people with lung covid complaints but without cognitive symptoms.

“A great study,” says virologist Debby van Riel of Erasmus MC in Rotterdam. “It confirms previous findings that a coronavirus infection can affect the brain.” She does, however, have a hand in hand. “It is a mouse model, the groups of people studied are small.” She would like to see more research, in better animal models and especially in humans. “The question is whether this activation of microglia and the other findings could contribute to the lung covid symptoms that people report. The effects found are not very large. The translation into what it means for patients is difficult.”

Also read: What we do know about lung covid

It is not yet clear whether the long-term complaints, also called post-acute Covid-19 syndrome (PACS), are actually caused by the corona virus. French study among more than 25,000 people showed in November 2021 that people who thought they had had Covid-19 were more likely to report persistent complaints than people who believed they had not had Covid-19. When the group was divided on the basis of proven Covid-19, demonstrated by antibodies against the coronavirus in the blood, this difference disappeared: only loss of smell was more common in people who had demonstrated Covid-19. So some symptoms may not be due to SARS-CoV-2 and must be attributed to another cause, the authors warn.

Vaccination protects

Recovery can also take longer after a serious flu infection or another viral infection, says Van Riel. “The long-term complaints reported after a corona infection partly overlap with the complaints we know from the post-viral syndrome after other viral infections.” For example, activation of microglia and less myelin has been observed after an infection with the flu virus, she says. How often this occurs has not yet been investigated. “It is very difficult to investigate what happens when an infection is no longer acute. You cannot then clearly link the findings to the presence of a pathogen.”

When asked whether vaccination protects against lung covid complaints after a corona infection, a uplifting answer in a preprint from Israel. These initial results suggest so. People who got Covid-19 after two doses of Pfizer reported long-term complaints as often as people who were not infected. That research was done when the Delta variant was worth around. Whether the Omikron variant can also cause long-term complaints is not yet known, the variant has only been with us for two months.

Also read: Covid that never ends

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