A UCLA-led team of researchers studying the effect of the monoclonal antibody Leronlimab on protracted COVID-19 may have found a surprising clue to the puzzling syndrome, which contradicts their original hypothesis. An abnormally weakened immune system may be to blame, not persistently hyperactive as they had suspected.
The study, which was funded by Leronlimab maker CytoDyn Inc. and conducted by company-employed or consultant researchers, will be published online April 22 in the peer-reviewed journal Clinical infectious diseases.
“Although this is a small pilot study, it suggests that some people who have had COVID for a long time may actually have an underactive immune system after recovering from COVID-19, which means that strengthening immunity in these people could be a treatment,” the lead author said. Dr. Otto Yang, Professor of Medicine, Division of Infectious Diseases and Microbiology, Immunology, and Molecular Genetics at UCLA’s David Geffen School of Medicine.
COVID-19 is known to be caused by overactive immune responses against SARS-CoV-2 resulting in damage to the lungs and other organs, and sometimes what is known as a ‘cytokine storm’ that overwhelms the body. individual, which could result in serious illness and death.
In a subset of people who recover from the initial illness, various symptoms persist, such as fatigue, mental clouding, 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 unlikely to be a single disease entity. However, a limited understanding of its causes makes finding ways to treat the disease particularly difficult.
Many scientists have suggested that the persistence of immune overactivity after COVID-19 is a major contributor. Working by this theory, the researchers conducted a small exploratory trial of Leronlimab – an antibody that attaches to an immune receptor called CCR5 which is involved in inflammation – on 55 people with the syndrome.
Participants were randomly assigned to receive weekly injections of the antibody or a saline placebo for eight weeks, during which 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 the exact opposite,” Yang said. “Patients who improved were those who started with low CCR5 on their T cells, suggesting that their immune system was less active than normal, and that CCR5 levels actually increased in people who are improved. This leads to the new hypothesis that the long COVID in some people is related to the fact that the immune system is suppressed and not overactive, and that while blocking its activity, the antibody can stabilize the expression of CCR5 on the surface of cells. cells, resulting in upregulation of other immune receptors or functions. .”
The results, the researchers write, “suggest a complex role for CCR5 in balancing inflammatory and anti-inflammatory effects, for example via T-regulatory cells”, although the findings need to be confirmed in a larger, more comprehensive study. definitive.
Study co-authors are Norman Gaylis of Arthritis and Rheumatic Disease Specialties in Aventura, Florida; Angela Ritter of the Center for Advanced Research & Education in Gainesville, Georgia; Scott Kelly, Nader Pourhassan, and Christopher Recknor of CytoDyn Inc. in Vancouver, Washington; and Meenakshi Tiwary, Jonah Sacha, and Scott Hansen of Oregon Health & Science University.
Sacha, Hansen and Yang are paid consultants for CytoDyn. Gaylis is a member of the scientific board of CytoDyn with stock options.
Clinical infectious diseases
Randomized clinical/controlled trial
The title of the article
Reduced Cell Surface Levels of CCR5 and Immunosuppression in Long COVID Syndrome
Publication date of articles
Warning: AAAS and EurekAlert! are not responsible for the accuracy of press releases posted on EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.