Elevated risk of new-onset chronic fatigue syndrome/myalgic encephalomyelitis up to four years after SARS-CoV-2 infection 2025 Hadidchi et al.

[Jaybee00]

Background​

Fatigue is a common sequela of SARS-CoV-2 infection, with many COVID-19 patients subsequently developing chronic fatigue syndrome and myalgic encephalomyelitis (CFS/ME). Long-term associations between COVID-19, new-onset CFS/ME, and other independent predictors such as vaccination for SARS-CoV-2, re-infection, and blood biomarkers at time of infection remain unclear. This study investigated the incidence and independent predictors of developing new-onset CFS/ME up to 4 years post SARS-CoV-2 infection in comparison to COVID− controls.

Methods​

This retrospective analysis conducted within the Montefiore Health System from February 1, 2020, to January 12, 2024 included adults without a prior diagnosis of fatigue or CFS/ME who were hospitalized for COVID-19 (n = 10,667), not hospitalized for COVID-19 (n = 25,409), and non-COVID-19 controls (n = 111,301). The observation time was between 30 days and 4 years post index date. The outcome was new-onset CFS/ME. Multivariate adjusted hazard ratios (HR) with 95% confidence intervals were calculated, assessing risk posed by SARS-CoV-2 infection, re-infection, and vaccination. Whether abnormal levels of aspartate aminotransferase, creatinine, D-dimer, lactate dehydrogenase, ferritin, hemoglobin, platelets, neutrophil/lymphocyte ratio, and temperature during hospitalization were associated with future CFS/ME risk was examined.

Results​

Compared to COVID− controls, the risk of developing new-onset CFS/ME was higher among both COVID-19 hospitalized (adjusted HR = 1.46 [1.07, 1.99]) and non-hospitalized patients (1.56 [1.25, 1.93]). Females (1.54 [1.27, 1.89]), patients with liver disease (1.61 [1.29, 2.00]), autoimmune disorders (1.57 [1.18, 2.08]), and anxiety disorders (1.35 [1.04, 1.74]) were more likely to develop CFS/ME (p < 0.05). Re-infection with SARS-CoV-2 was not associated with increased risk of incident CFS/ME. COVID-19 vaccination status during the initial phase of the rollout (prior to 2022) was associated with an increased risk of new-onset CFS/ME (p < 0.05). None of the blood biomarkers during acute COVID-19 were associated with new-onset CFS/ME risk (p > 0.05).

Conclusion​

SARS-CoV-2 infection is associated with an increased risk of new-onset CFS/ME, independent of hospitalization status. Females, and individuals with autoimmune and anxiety disorders were more susceptible. These findings highlight the need for ongoing surveillance and management of fatigue-related symptoms in COVID-19 survivors.

Elevated risk of new-onset chronic fatigue syndrome/myalgic encephalomyelitis up to four years after SARS-CoV-2 infection - Journal of Translational Medicine

Background Fatigue is a common sequela of SARS-CoV-2 infection, with many COVID-19 patients subsequently developing chronic fatigue syndrome and myalgic encephalomyelitis (CFS/ME). Long-term associations between COVID-19, new-onset CFS/ME, and other independent predictors such as vaccination for...

translational-medicine.biomedcentral.com

CFS/ME? The new style?

 

[mariovitali]

Liver disease, again

 

[Hutan]

Female:male ratio reported is quite low: 3 women to 2 men. 61% women: 39% men.

Lots of questions.

Were the 'non-Covid-19 controls' really so by 2024? I would have thought a large proportion of them would have been infected. Possibly, many people who were not infected by that time had some distinctive characteristics.

I'd want to look at the assumptions about reinfection too. Probably not many people were having subsequent infections recorded in the health system in the later years.

COVID-19 vaccination status during the initial phase of the rollout (prior to 2022) was associated with an increased risk of new-onset CFS/ME (p < 0.05).

Not sure what that means, but it doesn't really sound as though they found that vaccination was unequivocally protective, as reported by some other studies.

 

[EndME]

Also note that the reported onset of CFS/ME following Covid is fairly low (and perhaps somewhat more realistic than what has been seen elsewhere but there's no way of knowing whether "CFS/ME" here reflects our understanding of "ME/CFS" for example layed out in the CCC). Out of 36,076 Covid positive cases 171 (0.47%) developed CFS/ME and out of 111,301 Covid "negative" cases 336 (0.30%) developed CFS/ME. The difference in percentages here might also easily be driven by additional factors (positive Covid cases being more likely to see a physician). I don't think we have any idea what a diagnosis of "CFS/ME" taken from EHR actually means here and we've seen in the past how misleading those can often be. Maybe the people given a diagnosis of "CFS/ME" are actually those that have MS and those that have "ME/CFS" were given a diagnosis of "FND"?

Given how small these differences as well as other differences mentioned in the studies are and given that there are no long-term follow-ups, results may easily be driven by confounding factors. For example all you'd need is one single physician with an interest in liver disease and ME/CFS that diagnoses both more often than the average physician to drive a "liver disease and ME/CFS association" in the context of this study.

I think this is a good illustration that studies of the above type don't make much sense because you're sample size has to a priori be so large that any subsequent differences may be driven by methodological problems that subsequentially arise from the necessity of a massive sample size.

It might be interesting to know where exactly the CFS/ME cases are coming from. 171 respectively 336 cases is not a lot. So supposedly it's very possible that these results are just be driven by a handful of physicians and how they use diagnostic codes related to "CFS/ME" rather than having anything to do with actual ME/CFS.

 

[Hutan]

I think this is a good illustration that studies of the above type don't make much sense because you're sample size has to a priori be so large that any subsequent differences may be driven by methodological problems that subsequentially arise from the necessity of a massive sample size.

So true. We see it over and over again. Even in sample sizes that aren't quite 'massive'.

It might be interesting to know where exactly the CFS/ME cases are coming from. 171 respectively 336 cases is not a lot.

It would be interesting. I guess provisions around data privacy mean we can't know.

 

[Peter T]

Looking at the article I don’t seem to find what criteria were used for diagnosing ME/CFS (or CFS/ME as the authors called it). I am a bit slow on the up take today, but were they just relying on treating doctors to use their own choice of criteria when diagnosing?

I was wondering about the spread of onset delays following the acute Covid episode, but my brain is just not allowing me to make much sense of the article.

 

[EndME]

Looking at the article I don’t seem to find what criteria were used for diagnosing ME/CFS (or CFS/ME as the authors called it). I am a bit slow on the up take today, but were they just relying on treating doctors to use their own choice of criteria when diagnosing?

I was wondering about the spread of onset delays following the acute Covid episode, but my brain is just not allowing me to make much sense of the article.

Yes no specific criteria, just looking at electronic health records. Looks like the codes "Chronic fatigue syndrome (52702003) and/or Postviral fatigue syndrome (51771007)" were then flagged as CFS/ME.

It's probably likely that with the emergence of Long-Covid certain physicians don't use those codes anymore and instead just use codes related to LC even when say patients would meet an ME/CFS diagnosis according to stringent criteria.

 

[BrightCandle]

Yes no specific criteria, just looking at electronic health records. Looks like the codes "Chronic fatigue syndrome (52702003) and/or Postviral fatigue syndrome (51771007)" were then flagged as CFS/ME.

It's probably likely that with the emergence of Long-Covid certain physicians don't use those codes anymore and instead just use codes related to LC even when say patients would meet an ME/CFS diagnosis according to stringent criteria.

I can't even get my GP to write down my symptoms let alone code them correctly. The digital records are a gross underestimate because I know my records would never be caught by any of them and I am not unique in this level of patient gaslighting and dismissal.