Repeated Hand Grip Strength is an Objective Marker for Disability and Severity of Key Symptoms in Post-COVID ME/CFS (preprint)

Post-COVID Syndrome (PCS) refers to a diverse array of symptoms that persist beyond 3 months of the acute phase of a SARS-CoV-2 infection. The most frequent symptom is fatigue, which can manifest both mentally and physically. In this study, handgrip strength (HGS) parameters were determined as an objective measure of muscle fatigue and fatigability. HGS parameters were correlated with other fre-quent symptoms among 144 female PCS patients suffering from fatigue, exertional intolerance, and cognitive impairment. Seventy-eight patients met the Canadian Consensus Criteria (CCC) for post-infectious myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). The severity of disa-bility and key symptoms were evaluated utilizing self-reported questionnaires. Notably, patients di-agnosed with ME/CFS exhibited a higher overall severity of symptoms, including lower physical func-tion (p < 0.001), a greater degree of disability (p < 0.001), more severe fatigue (p < 0.001), post-exertional malaise (p < 0.001), and autonomic dysfunction (p = 0.004). While HGS was similarly impaired in both PCS and ME/CFS patients, the associations between HGS and the severity of symptoms and disability revealed striking differences. We observed significant correlations of HGS parameters with physical function across all patients, but with the key symptoms PEM, fatigue, cog-nitive impairment, and autonomic dysfunction in ME/CFS patients only. This points to a common mechanism for these symptoms in the ME/CFS subtype, distinct from that in other types of PCS. Further HGS provides an objective marker of disease severity in ME/CFS.

Symptom persistence and biomarkers in post-COVID-19/chronic fatigue syndrome - results from a prospective observational cohort (preprint)

IntroductionPost-COVID-19 syndrome (PCS) is characterized by a wide range of symptoms, predominantly fatigue and exertional intolerance. While disease courses during the first year post infection have been repeatedly described, little is known about long-term health consequences. MethodsWe assessed symptom severity and various biomarkers at three time points post infection (3-8 months (mo), 9-16mo, 17-20mo) in 106 PCS patients with moderate to severe fatigue and exertional intolerance. A subset of patients fulfilled diagnostic criteria of myalgic encephalomyelitis/chronic fatigue syndrome (PCS-ME/CFS) based on the Canadian Consensus Criteria. ResultsWhile PCS-ME/CFS patients showed persisting symptom severity and disability up to 20mo post infection, PCS patients reported an overall health improvement. Inflammatory biomarkers equally decreased in both groups. Lower hand grip force at onset correlated with symptom persistence especially in PCS-ME/CFS. DiscussionDebilitating PCS may persist beyond 20mo post infection, particularly in patients fulfilling diagnostic criteria for ME/CFS.

Post-COVID syndrome is associated with capillary alterations, macrophage infiltration and distinct transcriptomic signatures in skeletal muscles (preprint)

The SARS-CoV-2 pandemic not only resulted in millions of acute infections worldwide, but also caused innumerable cases of post-infectious syndromes, colloquially referred to as long COVID. Due to the heterogeneous nature of symptoms and scarcity of available tissue samples, little is known about the underlying mechanisms. We present an in-depth analysis of skeletal muscle biopsies obtained from eleven patients suffering from enduring fatigue and post-exertional malaise after an infection with SARS-CoV-2. Compared to two independent historical control cohorts, patients with post-COVID exertion intolerance had fewer capillaries, thicker capillary basement membranes and increased numbers of CD169+ macrophages. SARS-CoV-2 RNA could not be detected in the muscle tissues, but transcriptomic analysis revealed distinct gene signatures compared to the two control cohorts, indicating immune dysregulations and altered metabolic pathways. We hypothesize that the initial viral infection may have caused immune-mediated structural changes of the microvasculature, potentially explaining the exercise-dependent fatigue and muscle pain.