According to a news release issued by the University of Pennsylvania, a new study lead by researchers from the Perelman School of Medicine has identified the potential mechanisms that cause long COVID. The findings from this study may not only help to untangle some of the mechanisms that contribute to long COVID, but also provide biomarkers that can help clinicians diagnose patients and objectively measure their response to individual treatments, according to Maayan Levy, PhD, from the University of Pennsylvania.
Long COVID, which can be exhibited in patients through symptoms such as memory loss, brain fog, or fatigue for months or even years following a COVID-19 infection, affects nearly one in five American adults who have had COVID-19, as reported by the CDC. The University of Pennsylvania notes that extensive research into the underlying causes of long COVID is lacking, and there is a notable absence of broadly effective treatments for alleviating these persistent symptoms.
The recent study, published in the journal 'Cell' on Oct. 16, was a collaborative effort involving scientists from the University's departments of Microbiology, Pathology and Laboratory Medicine, as well as their Physical Medicine and Rehabilitation's Post COVID Assessment and Recovery Clinic. The researchers examined blood and stool samples collected from various clinical studies and small animals.
Penn Medicine noted the study was a collaborative effort, bringing together scientists from the University's departments of Microbiology, Pathology and Laboratory Medicine, as well as their Physical Medicine and Rehabilitation's Post COVID Assessment and Recovery Clinic. Their investigation focused on examining blood and stool samples collected from various clinical studies and small animals. Notably, during their investigation, researcher detected remnants of the SARS-CoV-2 virus in the stool samples of long COVID patients. This suggests that the virus can persist in the gastrointestinal (GI) tract of some patients for an extended period after the initial infection, Penn Medicine reports. Researchers discovered this leftover virus, which they call a "viral reservoir", prompts the immune system to release proteins known as interferons, which are responsible for fighting the virus. These interferons, in turn, lead to inflammation that hampers the absorption of the amino tryptophan in the GI tract.
Tryptophan is a building material for various neurotransmitters, particularly serotonin, which plays a critical role in controlling memory, sleep, digestion, wound healing, and other functions that help keep the body in balance. The researchers discovered that when ongoing viral inflammation reduces the absorption of tryptophan, it leads to a shortage of serotonin. This shortage disrupts the signals sent through the vagus nerve, which can then lead to several of the symptoms connected to long COVID, such as memory problems.
Clinicians treating long COVID patients have traditionally relied on self-reports from these individuals to assess symptom improvement. However, the researchers propose a more promising approach. By identifying biomarkers, they believe they can better match patients with treatments or clinical trials that directly target the underlying causes of their long COVID symptoms, leading to more effective progress tracking. The researchers also explored the possibility of alleviating long COVID symptoms by replenishing tryptophan or serotonin in patients with deficiencies. Their investigations in small animal models showed that restoring serotonin levels and reversing memory impairment could be achieved through treatment with serotonin precursors or selective serotonin reuptake inhibitors (SSRIs).
“Long COVID varies from patient to patient, and we don’t fully understand what causes the differences in symptoms,” said co-senior author, Christoph Thaiss, PhD, an assistant professor of Microbiology. “Our study provides a unique opportunity for further research to determine how many individuals with long COVID are affected by the pathway linking viral persistence, serotonin deficiency, and dysfunction of the vagus nerve and to uncover additional targets for treatments across the different symptoms patients experience.”
