US researchers have found that an abnormally suppressed immune system may be to blame for long Covid-19 and not a persistently hyperactive one previously thought.In a subset of persons who recover from the initial Covid illness, various symptoms persist, such as fatigue, mental haziness, and shortness of breath, which can be debilitating and last for months.This is generally classified as long Covid, although symptoms vary widely and this syndrome is probably not a single disease entity. Limited understanding of its causes, however, makes finding ways to treat the condition particularly difficult.Many scientists have suggested that persistence of immune hyperactivity after Covid-19 is a major contributor.To explore, researchers at the University of California-Los Angeles conducted a small exploratory trial of Leronlimab - an antibody that attaches to an immune receptor called CCR5 that is involved in inflammation - on 55 people with the syndrome."While this was a small pilot study, it does suggest that some people with long Covid may actually have under-active immune systems after recovering from Covid-19, which means that boosting immunity in those individuals could be a treatment," said Dr. Otto Yang, Professor at UCLA's David Geffen School of Medicine. The study was published in the peer reviewed journal Clinical Infectious Diseases.
Participants were randomly assigned to receive weekly injections of the antibody or a saline placebo for eight weeks, over which time they tracked any changes in 24 symptoms associated with long Covid, which also included loss of smell and taste, muscle and joint pain, and brain fog.The researchers originally thought that blocking CCR5 with the antibody would dampen the activity of an overactive immune system after Covid-19 infection."But we found just the opposite," Yang said.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, Yang said.The findings "suggests a complex role for CCR5 in balancing inflammatory and anti-inflammatory effects, e.g. through T regulatory cells," although the results need to be confirmed in a larger, more definitive study.