Studies Suggest Biological Factors That May Contribute to Long COVID

Jan. 9, 2024
Changes in the mitochondria of the muscle could be attributable to long COVID-related fatigue

A pair of studies published in Nature Communications suggest certain clinical features that may lead to long COVID in patients.

The first study, published on Jan. 3, concerned patient reported outcomes in 590 patients with post-acute sequelae of SARS-CoV-2 (PASC), or long COVID, which is described as “symptoms [that] linger after the acute (first 4 weeks) phase of illness” or new symptoms patients experience after acute infections. These patients, who were hospitalized for COVID-19 from May 5, 2020 to March 19, 2021, were not vaccinated against the disease at the time of illness.

Overall, 52% of the participants of the study had symptoms lasting 3 months after the acute phase of infection. Long COVID (PASC) was “seen more often in female patients, those with longer hospital stays, and those with multiple comorbidities. The main factors associated with PASC were chronic pulmonary disease…and chronic neurologic disorder.” Blood studies of the patients with PASC showed that they “had lower receptor binding domain and spike antibody (Ab) titers on day 1 of the study,” demonstrating that “higher SARS-CoV-2 viral burden and lower Ab titers during the acute phase are associated with both the physical predominant deficit as well as the multidomain deficit PRO clusters.”

Additionally, the study found that use of remdesivir and steroids in the inpatient period “was not associated with a decrease in PASC prevalence.” The authors conclude that there is a benefit to “measuring immune responses during the acute phase for the early identification of patients at high risk for PASC” in order to facilitate “testing and monitoring of targeted PASC prevention and treatment.”

The second study, published on Jan. 4 and performed by investigators from Amsterdam University Medical Center, specifically concerned itself with finding the root cause of post-exertional malaise – defined as “extreme fatigue after physical or mental exertion” – in long COVID patients. The researchers “induced post-exertional malaise in a cohort of 25 patients with long COVID and 21 controls who had recovered from mild COVID, taking blood and skeletal muscle biopsies before and after a maximal exercise test.”

According to senior study author Rob Wust, PhD, the research indicated “various abnormalities in the muscle tissue of the patients,” specifically that “the mitochondria of the muscle, also known as the energy factories of the cell, function less well and…produce less energy.” Heart and lung function remained “normal” among long COVID patients during the study, which suggests that “the muscles play a significant role in post-exertional malaise.”

The authors of the study advise tailoring exercise regimens specifically for patients with long COVID. Lead author Brent Appelman, MS, a PhD candidate at Amsterdam UMC, advises patients to “guard their physical limits and not…exceed them.”

CIDRAP has the news release.