The Path To Shortening Long COVID May Go Through Gut

For reasons that aren’t entirely clear, long COVID is associated with diminished microbial diversity in the gut and a decrease in several healthful strains of bacteria, such as Bifidobacterium adolescentis. Researchers are now exploring whether therapies that aimed at reviving a beleaguered gut microbiome’s profile might be an avenue for treating long COVID.

Last week researchers at The Chinese University of Hong Kong reported positive results for microbiome-modifying therapy in the journal The Lancet Infectious Diseases. Although randomized and double blinded, the study was conducted at a single center and so must be interpreted with some caution.

Long COVID is also called long-haul COVID, post-COVID-19 conditions and chronic COVID. The technical term is post-acute sequelae of SARS-CoV-2 (PASC). Some research suggests that the proportion of people who develop long COVID after the initial infection has decreased. The National Center for Health Statistics reported in September 2023 that 6.9% of those who have had COVID-19 had had long COVID, according to the 2022 National Health Interview Survey.

Joint first authors Raphaela I. Lau, Ph.D., and Qi Su and colleagues tested a preparation that included three strains of bacteria — Bifidobacterium adolescentis, Bifidobacterium bifidum and Bifidobacterium longum — and three compounds that encourage the growth of healthful bacteria: galacto-oligosaccharides, xylo-oligosaccharides and resistant dextrin. The study subjects were people had at least one of 14 long COVID symptoms for four weeks or more after a confirmed infection with SARS-CoV-2 (the virus that causes COVID-19) by either a PCR test or a rapid antigen test. Between June 2021 and August 2022, the researchers randomly assigned 463 patients to either take a placebo (vitamin C) twice daily or the bacteria-prebiotic preparation. The primary end point was the alleviation of long COVID symptoms by six months; alleviation was defined as a reduction in the severity of symptoms leading to an improvement The symptoms were measured by responses to a questionnaire commonly used in the research long COVID symptoms. After drop outs, withdrawals and loss to follow-up, the study had 204 people in the treatment group and 199 in the placebo group.

Results reported by Lau and Su and colleagues showed that those assigned to the treatment group fared than those assigned to the placebo group on all 14 long COVID symptoms. Here are the results by proportion of patient whose long COVID symptoms were relieved:

The researchers also analyzed fecal samples. The bacteria diversity was higher in the treatment group than in the placebo group. Their measurements also showed greater numbers of certain species (Bifidobacterium pseudocatenulatum and Bifidobacterium longum) and lesser numbers of others (Klebsiella pneumoniae, Klebsiella variicola and Parabacteroides merdae). They also found some association between the decreases in some symptoms with the bacteria; for example, Bifidobacterium adolescentis was positively associated with alleviation in fatigue.

“We found that SIMO1 led to improved gut microbiota composition by promoting the abundance of beneficial bacteria associated with [long COVID] such as those of the Klebsiella genus,” Lau and Su and colleagues wrote in the discussion section of the study. But they note that their analysis of cytokines didn’t show any difference between the treatment and placebo groups, so there are still unanswered questions about how improving the gut’s microbiota would ease long COVID symptoms.

Lau and Su also note one of the ob with researching long COVID: The symptoms are common ones and having many causes so teasing out the effect of a particular treatment and its effects.