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Abnormally Suppressed Immunity can Cause Long COVID-19

Sandipan Talukdar |
A recent study showed that hyperactive immunity may not necessarily cause post-disease syndrome.

Hyperactive immunity has been determined as a major contributor to developing severe COVID-19 and this has been found across the world. Even after infection, hyperactive immunity has been considered a major factor in cases of long-COVID-19. However, a study published on April 22 in the journal Clinical Infectious Diseases states that an abnormally suppressed immune system rather than hyperactive immunity may be linked to long-COVID-19 rather than hyper immunity.

Long COVID-19 is attributable to the persistence of various symptoms in patients who have recovered from initial illness. The symptoms could range from fatigue, shortness of breath to mental haziness and are debilitating and last for months. Notably, these symptoms vary widely and cannot be said to be a single disease entity. Treating such cases has been difficult as there is a scarcity of knowledge about the causes of the conditions. It was hypothesised that hyper immunity may be a factor in this case as well just like in severe cases.

Based on the hypothesis, a team of researchers conducted a pilot study with Leronlimab, an antibody that gets attached to a receptor called CCR5. C-C chemokine receptor type 5, or CCR5, is a protein present on the surface of certain cells (white blood cells) involved in the immune system. The CCR5 receptor acts as a receptor for a chemokine, which again is a type of protein used in the signalling process of the immune system. The immune system involves a wide array of proteins, particular types of cells and other chemicals to generate the protective ability via cascades of signals among them.

The recent study was conducted on 55 subjects as a small pilot project. Senior author Dr Otto Yang, a professor of medicine at the University of California, Los Angeles, explained “While this was a small pilot study, it does suggest that some people with long COVID-19 may actually have underactive immune systems after recovering from COVID-19, which means that boosting immunity in those individuals could be a treatment.”

All of the participants were having the long COVID-19 syndrome and assigned randomly for receiving injections of Leronlimab or a placebo of saline water for eight weeks. The researchers tracked whether there were any changes in the 24 symptoms associated with long COVID-19 during this time. Among these symptoms, loss of smell and taste, muscle and joint pain and also brain fog were included.

The researchers began with the idea that blocking the CCR5 receptor with Leronlimab would result in a dampened activity of the hyperactive immunity, which persisted after getting rid of the initial COVID-19 infection.

However, to their surprise, the researchers found the opposite. Explaining the findings, Yang said, “We found just the opposite. Patients who improved were those who started with low CCR5 on their T cells, suggesting their immune system was less active than normal, and levels of CCR5 actually increased in people who improved. This leads to the new hypothesis that long COVID in some persons is related to the immune system being suppressed and not hyperactive and that while blocking its activity, the antibody can stabilise CCR5 expression on the cell surface leading to upregulation of other immune receptors or functions.”

The findings suggest that CCR5 plays a complex role in creating a balance of inflammatory and anti-inflammatory effects via the T cells. The T cells are specialised cells belonging to the immune system and involved in myriads of activities in providing protective ability.

However, the study is only preliminary and has been conducted on a small sample size. To reach a conclusion, larger and confirmatory studies should be conducted. Nevertheless, the study provides a new angle on the debilitating condition of long COVID-19

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