Abstract Long COVID is a debilitating, multisystemic illness following a SARS-CoV-2 infection whose duration may be indefinite. Over four years into the pandemic, little knowledge has been generated from clinical trials. We analyzed the information available on ClinicalTrials.gov, and found that the rigor and focus of trials vary widely, and that the majority test non-pharmacological interventions with insufficient evidence. We highlight promising trials underway, and encourage the proliferation of clinical trials for treating Long COVID and other infection-associated chronic conditions and illnesses (IACCIs). We recommend several guidelines for Long COVID trials: First, pharmaceutical trials with potentially curative, primary interventions should be prioritized, and both drug repurposing and new drug development should be pursued. Second, study designs should be both rigorous and accessible, e.g., triple-blinded randomized trials that can be conducted remotely, without participants needing to leave their homes. Third, studies should have multiple illness comparator cohorts for IACCIs such as Myalgic Encephalomyelitis (ME/CFS) and dysautonomia, and screen for the full spectrum of symptomatology and pathologies of these illnesses. Fourth, studies should consider inclusion/exclusion criteria with an eye towards equity and breadth of representation, including participants of all races, ethnicities, and genders most impacted by COVID-19, and including all levels of illness severity. Fifth, involving patient-researchers in all aspects of studies brings immensely valuable perspectives that will increase the impact of trials. We also encourage the development of efficient clinical trial designs including methods to study several therapies in parallel. https://www.sciencedirect.com/science/article/pii/S0024320524005605 (Life Sciences; open access)
I suspect that little knowledge has been generated because so much of the research papers I've seen in recent years have been BPS-based and Psychology/Psychiatric based. Didn't the US government dish out lots of money? (Over a billion dollars?) But I am yet to hear about any benefit from it and I think I read that it had mostly been spent. One thing that made me very angry while I had my worst bouts of Covid (the first two of four) was that there was no real treatment for the condition. It just seemed to be a case of take an aspirin or a paracetamol and go to bed. I don't think anything has changed. So there isn't just Long Covid to be investigated, a treatment for the actual condition itself is required to shorten the course of the disease and reduce the chance of the patient getting Long Covid in the first place.
Even worse is that most of them are redundant. They add nothing at all to hundreds have already produced. They're clones of one another and are clearly done with zero care for the massive duplication of identical wastes of effort. Even worse than that is that all those interventions have been tested and failed before, in fact formed the first line of treatments deployed for LC. Despite evidence against. But they're testing them again! It's insane. Haven't read beyond and the abstract seems sensible and needed, but damn does medicine have fundamental issues to deal with here. I'm talking about needing an intervention. In the "we need to sit down with you and explain calmly and explicitly just how deeply you have fucked us and need to make a radical change in behavior, intent and motivation" and they need to accept it and commit to radical change.
Ah, reading it a bit and noticed the authors. Definitely needed and sensible. IMO the most important: From trials and research. Although the research so far has validated decades of controversy our way, it hasn't made an impact, but more importantly hasn't actually added anything that wasn't known on day 1. At least not that I'm aware of.
Does not seem to mention the issue of blinding for non-pharmacological interventions and that in these cases objective outcomes such as actigraphy or employment should be used (alongside symptom questionnaires). I think this is much more important than including under-represented populations or measuring all possible comorbidities. They write for example:
They also write: I disagree with this. These findings are not robust enough to be used as endpoints in clinical trials.
I've not read the paper. Frustrating that this point re the need for objective outcome measures in unblinded / unblindable trials is not highlighted let alone mentioned. Disappointing. "It is therefore imperative that clinical trials comprehensively screen Long COVID participants for and track the full spectrum of symptoms and comorbid conditions. This also involves screening for less studied pathologies, such as connective tissue disorders [12,61,63] and spinal conditions [12]; mast cell activation disorders [12] and environmental sensitivities [16,48]; neuroendocrine dysfunction [64]; gastrointestinal issues [16,48], sleep disorders [16,48], lymphatic issues [16,48]; and reproductive health conditions [65]" No mention of immunological disorders like CVID? That a miss. Also, as the symptoms are akin to those with people with active infections, its a bit remiss to not mention this or that infections also need to be included in screening. As an aside: The patients with ME I see making progress and recovering their health (at least to some degree) all have taken some form of longer term antimicrobials. Why this happens we don't know but surely that message is getting through to researchers / clinics? It hasn't been in the past.
I'm curious about the common portrayal of work status/hours and walking tests as "objective". They are quantifiable (e.g. speed and distance walked using traditional actimetry or accelerometer-based wearables) in a way that questionnaires are not but no-one should mistake them for truly objective measures. If we are being intellectually honest then we also have to acknowledge that work status and walking tests are also dependent on a number of human factors like motivation and effort and there may be placebo effects involved with these as well. This is not in any way a defence of psychological pseudoresearch. If people who are being assessed as being significantly better as a result of QoL questionnaires are not returning to work or education and cannot walk any farther, as in PACE, that is a grave problem for those trials. But nonetheless they are not "objective" in the sense that a red blood cell count is objective.
