The immunology of long COVID Abstract Long COVID is the patient-coined term for the disease entity whereby persistent symptoms ensue in a significant proportion of those who have had COVID-19, whether asymptomatic, mild or severe. Estimated numbers vary but the assumption is that, of all those who had COVID-19 globally, at least 10% have long COVID. The disease burden spans from mild symptoms to profound disability, the scale making this a huge, new health-care challenge. Long COVID will likely be stratified into several more or less discrete entities with potentially distinct pathogenic pathways. The evolving symptom list is extensive, multi-organ, multisystem and relapsing–remitting, including fatigue, breathlessness, neurocognitive effects and dysautonomia. A range of radiological abnormalities in the olfactory bulb, brain, heart, lung and other sites have been observed in individuals with long COVID. Some body sites indicate the presence of microclots; these and other blood markers of hypercoagulation implicate a likely role of endothelial activation and clotting abnormalities. Diverse auto-antibody (AAB) specificities have been found, as yet without a clear consensus or correlation with symptom clusters. There is support for a role of persistent SARS-CoV-2 reservoirs and/or an effect of Epstein–Barr virus reactivation, and evidence from immune subset changes for broad immune perturbation. Thus, the current picture is one of convergence towards a map of an immunopathogenic aetiology of long COVID, though as yet with insufficient data for a mechanistic synthesis or to fully inform therapeutic pathways. https://www.nature.com/articles/s41577-023-00904-7
The article is paywalled. According to the references, there seems to be a couple of mentions of ME/CFS.
Quite suprising to me nature has made the announcement that the article soon won't be paywalled anymore. In the meantime it can be accessed via: https://www.nature.com/articles/s41...M6vdM2K5BcWFS277sKJkeUY_MmwxvcQ3YVqNZxe2_NGE=
Thank you for the link @EndME The relationship between Long Covid and ME/CFS is discussed in a separate section: Box 3 Lessons from and for ME/CFS and the case of ‘long SARS’ It is hard to discuss or present data on long COVID without being challenged about the relationship of findings to mechanisms in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), not least by patient groups who understandably feel that their condition has endured decades of neglect in terms of biomedical research prioritization. In light of clear overlaps with long COVID, there now exists an opportunity for cross-hybridization, with much to be learnt from the long, past experience and investigations in ME/CFS, and from the new momentum of long COVID investigations over the past few years. The symptom overlap is self-evident, encompassing the key features of post-exertional fatigue, neurocognitive symptoms, dysautonomia and postural orthostatic tachycardic syndrome. A systematic review found that 25 of 29 CFS symptoms were reported by at least one long COVID study18, whereas another study compared genes common between the two conditions in a number of ways, including pathway and network analysis148. This study found common hub proteins, such as IL-6 and IL-1β, between the two conditions. Another review focused on their similarities through the link of TGFβ signalling and circadian rhythms148. There is reso nance in the post-acute viral infection symptomology across the two conditions19. ME/CFS has commonly been described as a post-viral condition that may ensue following a range of infections, including pandemic H1N1 influenza149, Varicella zoster virus150, enteroviruses and SARS-CoV-117. Overlap in the immunopathological analyses is particularly interesting. It is noteworthy that raised CCL11, which has credentials as a long COVID serum biomarker functionally linked to neurocognitive symptoms, is also a biomarker of ME/CFS151. Revisiting the ME/CFS data also raises the possibility of investigating some of the implicated biomarkers, such as CXCL10 and leptin, in more detail in long COVID152. Furthermore, the ME/CFS data set may offer a reference framework to consider a role for Epstein–Barr virus reactivation in long COVID, noting that CFS can ensue from infectious mononucleosis associated with an enhanced imprint of T cell activation153. Long SARS, caused by SARS-CoV-1 infection, is a forerunner of long COVID and thus more helpfully considered as a variant of long COVID rather than a category of ME/CFS. A study from Canada and another from Hong Kong reported findings very similar to long COVID, with many people reporting chronic fatigue and psychiatric illnesses17,154. The comparative experience and lessons were recently reviewed and summarized155. Reviewing the Toronto University HCW cohort from 2003 to 2004, and with the caveat that it may be hard to extrapolate to long COVID generally as this was a group with severe disease and who were hospitalized, it was concluded that many of the changes were permanent and irreversible, with most patients unable to return to their former occupations
Translatable as : I actually have nothing to say but I am pleased to have the opportunity to say it anyway.
But Eric Topol gave it a five star rating. https://twitter.com/user/status/1678848512749080576 As did this person (yes I know this person is controversial….) https://twitter.com/user/status/1679190293923373056 https://twitter.com/user/status/1679184065562279949
Do I detect a touch of irony? It is certainly due. I also seem to detect a trace of brown-nosing in those tweets?
I found it a good review article. It summarises the various research avenues, with commentary weighting their likely relevance or reliability. There are a lot of biomedical references and zero biopsychosocial. The initial framing in relation to long-SARS (from SARS-CoV-1) and ME/CFS was good.
Greenhalgh? Expert? At what? She wrote 3 things on LC and they weren't even good, has a long history of dismissing chronic illness. Did she read the paper? Or just glosses over the ME references that she has been dismissed with hostility for years with her pals? I guess you can say that she was one of the early ones to take LC seriously, but in some of the things she wrote she was very dismissive of anything having to do with ME. The first one I remember was completely dismissive, something about how "patients felt the fatigue was more serious than mere chronic fatigue", or whatever. This is really damn weird.
This is a good question (N presumably being the nucleocapsid protein). How does the virus (any virus) hide in a cell but also cause a reaction major enough to cause ME/CFS? Perhaps the answer isn't that the impact of the virus is conventionally pro-inflammatory, as the authors suggest here. A lot of the cytokine and chemokine evidence is very patchy and questionable. Instead, might the impact be more to do with what the virus does inside the cell to allow it to keep hidden (and perhaps prepare for occasional replication)? We've seen papers on the amazing ways intra-cellular pathogens tweak the cell function.
Professor Altmann was interviewed on New Zealand national radio. The interview is discussed here: Long Covid in the media and social media 2023 and here News from Aotearoa/New Zealand and the Pacific Islands
