Axcella Makes Progress Against Long COVID as New Symptoms Emerge


Long COVID, whose technical name is post-acute sequelae of SARS-CoV-2 infection (PASC), describes symptoms of COVID-19 that persist at least four weeks after infection. According to two recent studies from the Journal of the American Medical Association, 10 to 30% of people with COVID-19 reported at least one persistent symptom up to six months after infection, which qualifies as Long COVID. 

New research is revealing more about this chronic condition and potential avenues to treat it.

Axcella’s Experimental Drug Improves Mental and Physical Fatigue

Cambridge, Massachusetts-based Axcella Therapeutics reported topline results from the Phase IIa trial of AXA1125 in patients with fatigue related to Long COVID. In the study, 41 patients were enrolled and received either 67.8 grams per day of AXA1125 or a matched placebo in two divided doses for 28 days, with a one-week safety follow-up.

Endpoints included phosphocreatine recovery time following moderate exercise as assessed by 31P-magnetic resonance spectroscopy, which was used to evaluate mitochondrial function. Clinically relevant endpoints include self-reported mental and physical fatigue as evaluated by the Chalder Fatigue Questionnaire, a 6-minute walk test and serum lactate levels.

Patients receiving the drug had improvements in all measures of mental and physical fatigue. They were highly statistically significant and clinically relevant compared to the placebo cohort. The researchers noted the phosphocreatine recovery time in all patients was significantly higher and had a higher degree of variability than previously seen in the literature.

“These findings support the hypothesis that there is significant mitochondrial dysfunction in these patients but limits the utility of this parameter in a clinical trial,” the company noted.

Because Long COVID is so new and so relatively understudied, there were no standard endpoints. However, based on the results, the company plans to talk to U.K. and U.S. regulators about how to get the drug authorized for Long COVID. 

“We believe we have already demonstrated in just a month of dosing a profound effect,” Axcella CEO Bill Hinshaw said. 

The drug was originally designed to fight muscle weakness and fatigue linked to nonalcoholic steatohepatitis (NASH), a form of fatty liver disease. It appears to have a positive impact on mitochondrial function, bioenergetics and inflammation.

3 Categories of Long COVID

New research suggests there are three different forms of Long COVID, with each category having its own symptoms. One category includes neurological symptoms like fatigue, “brain fog” and headache.

This appears to occur in people who contracted the Alpha and Delta variants, according to a study out of King’s College London. These were more common during the first wave.

The second category is defined by respiratory issues, such as shortness of breath and chest pain. These are also associated with the first wave of the pandemic and suggest lung damage.

The third group comes with a wide range of symptoms, which include muscle ache and pain, changes in skin and hair and heart palpitations. These are associated with all variants.

The researchers evaluated 1,459 people living with Long COVID who were part of the Zoe Health study. They all reported symptoms at least 12 weeks after infection.

Claire Steves, Ph.D., clinical lead author from King’s College London, said, “These data show clearly that post-COVID syndrome is not just one condition, but appears to have several subtypes. Understanding the root causes of these subtypes may help in finding treatment strategies. Moreover, these data emphasize the need for Long COVID services to incorporate a personalized approach sensitive to the issues of each individual.”

New Symptoms of Long COVID

Another study out of the U.K., this one published in Nature Medicine, evaluated 500,000 adults with Long COVID. Researchers found a broader range of symptoms, including hair loss, difficulty ejaculating, reduced libido, vertigo, problems urinating, anorexia and hot flashes. These are classified as “emerging” symptoms associated with Long COVID, and there are 15 of them.

“My reaction to the study would be ‘yeah, sounds about right,’” Amy Proal, Ph.D., a microbiologist at PolyBio Research Foundation who studies chronic conditions, told Insider. “The chronic consequences of this virus are immense when you start to actually account for these symptoms.”

Catching COVID-19 Twice Increases Long-Term Health Risks

As immunity from previous infections and vaccines wanes, more people are catching COVID-19 a second time. This is exacerbated by the highly infectious Omicron subvariants, BA.4 and BA.5. Although these infections tend to be mild, data is suggesting that catching the virus a second time can increase long-term health risks, particularly due to Long COVID.

In a not yet peer-reviewed study of U.S. veterans, a second infection “contributes to additional risks of all-cause mortality, hospitalization and adverse health outcomes,” and appears to increase the risk for diabetes, fatigue and mental health disorders. In the study, people who caught COVID-19 a second time were at 2.5 times greater risk of developing heart or lung disease and having blood clotting problems.

“The additive risk is really not trivial, not insignificant,” Dr. Ziyad Al-Aly, M.D., a clinical epidemiologist at Washington University in St. Louis and chief of research and development at the Veterans Affairs St. Louis Healthcare System said. 

Persistent Loss of Smell from COVID-19 Associated with Cognitive Impairment

A research study out of Argentina analyzed 766 adults ages 55-95. Researchers followed the subjects for one year and conducted a series of physical, cognitive and neuropsychiatric tests. Of the group, 88.4% had COVID-19 infections and 11.6% were controls. Clinical evaluations found functional memory impairment in two-thirds of the people who had COVID-19 infections. They found that persistent loss of smell was a significant predictor of cognitive impairment, while severity of the initial COVID-19 infection wasn’t.

“The more insight we have into what causes or at least predicts who will experience the significant long-term cognitive impact of COVID-19 infection, the better we can track it and begin to develop methods to prevent it,” Gabriela Gonzalez-Aleman, Ph.D., professor at Pontificia Universidad Catolica Argentina, Buenos Aires said. 

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