Therapeutic trials for long COVID-19: A call to action from the interventions taskforce of the RECOVER initiative 2023 Bonilla et al

Although most individuals recover from acute SARS-CoV-2 infection, a significant number continue to suffer from Post-Acute Sequelae of SARS-CoV-2 (PASC), including the unexplained symptoms that are frequently referred to as long COVID, which could last for weeks, months, or even years after the acute phase of illness. The National Institutes of Health is currently funding large multi-center research programs as part of its Researching COVID to Enhance Recover (RECOVER) initiative to understand why some individuals do not recover fully from COVID-19.

Several ongoing pathobiology studies have provided clues to potential mechanisms contributing to this condition. These include persistence of SARS-CoV-2 antigen and/or genetic material, immune dysregulation, reactivation of other latent viral infections, microvascular dysfunction, and gut dysbiosis, among others. Although our understanding of the causes of long COVID remains incomplete, these early pathophysiologic studies suggest biological pathways that could be targeted in therapeutic trials that aim to ameliorate symptoms. Repurposed medicines and novel therapeutics deserve formal testing in clinical trial settings prior to adoption. While we endorse clinical trials, especially those that prioritize inclusion of the diverse populations most affected by COVID-19 and long COVID, we discourage off-label experimentation in uncontrolled and/or unsupervised settings.

Here, we review ongoing, planned, and potential future therapeutic interventions for long COVID based on the current understanding of the pathobiological processes underlying this condition. We focus on clinical, pharmacological, and feasibility data, with the goal of informing future interventional research studies.

Open access, https://www.frontiersin.org/articles/10.3389/fimmu.2023.1129459/full

 

Lots of mentions of ME/CFS.

Thought this was less than ideal, my bolding.

"Post exertional malaise (PEM), also called “crash,” has been clinically defined as an increase in fatigue, pain, cognitive dysfunction, and flu-like illness after physical exertion, mental activities, or stressful events (146, 147). A recent meta-analysis found that PEM is 10.4 times more likely to be associated with ME/CFS (148). Therefore, PEM has been considered the hallmark for diagnosing ME/CFS (146–148). Some patients with long COVID experience similar clinical PEM symptoms. In a pre-print manuscript, investigators described a cohort of 105 patients from the Stanford long COVID clinic with symptoms greater than six months; they found that fatigue, PEM, and brain fog were the predominant and severe symptoms of which 43% were diagnosed with ME/CFS (149). PEM can be mitigated by energy conservation activities known as ‘pacing’ (resting, decreasing stress or overstimulation) (150). A supervised activity program may involve brief walking (~5 minutes), stretching/limb and spine active range of motion, participation in personal or instrumental activities of living, or reading for 5-10 minutes. The duration of these activities is then slowly increased. This method may allow careful introduction of aerobic exercise to prevent deconditioning (cycling, tai chi, yoga or aquatic exercises). For all patients, the goal of this individualized activity program is to regain functional independence, resume participation in life roles, and restore of quality of life"