Myalgic Encephalomyelitis/Chronic Fatigue Syndrome After SARS-CoV-2 Infection, 2024, Unger et al

Key Points

Question Does prevalence of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)–like illness differ between individuals with an acute infection–like index illness who are COVID-19 positive or negative?

Findings In this cohort study of 4378 participants, the weighted prevalence of ME/CFS-like illness was 4.5% or less at 3 to 12 months after the index illness in the COVID-19–positive and COVID-19–negative groups, with no significant differences in odds of ME/CFS-like illness.

Meaning The findings suggest that ME/CFS-like illness following an acute infection–like index illness does not vary by COVID-19 test result.


Abstract

Importance Chronic symptoms reported following an infection with SARS-CoV-2, such as cognitive problems, overlap with symptoms included in the definition of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

Objective To evaluate the prevalence of ME/CFS-like illness subsequent to acute SARS-CoV-2 infection, changes in ME/CFS symptoms through 12 months of follow-up, and the association of ME/CFS symptoms with SARS-CoV-2 test results at the acute infection–like index illness.

Design, Setting, and Participants This prospective, multisite, longitudinal cohort study (Innovative Support for Patients with SARS-CoV-2 Infections Registry [INSPIRE]) enrolled participants from December 11, 2020, to August 29, 2022. Participants were adults aged 18 to 64 years with acute symptoms suggestive of SARS-CoV-2 infection who received a US Food and Drug Administration–approved SARS-CoV-2 test at the time of illness and did not die or withdraw from the study by 3 months. Follow-up surveys were collected through February 28, 2023.

Exposure COVID-19 status (positive vs negative) at enrollment.

Main Outcome and Measures The main outcome was the weighted proportion of participants with ME/CFS-like illness based on the 2015 Institute of Medicine clinical case definition using self-reported symptoms.

Results A total of 4378 participants were included in the study. Most were female (3226 [68.1%]). Mean (SD) age was 37.8 (11.8) years. The survey completion rates ranged from 38.7% (3613 of 4738 participants) to 76.3% (1835 of 4738) and decreased over time. The weighted proportion of participants identified with ME/CFS-like illness did not change significantly at 3 through 12 months of follow-up and was similar in the COVID-19–positive (range, 2.8%-3.7%) and COVID-19–negative (range, 3.1%-4.5%) groups. Adjusted analyses revealed no significant difference in the odds of ME/CFS-like illness at any time point between COVID-19–positive and COVID-19–negative individuals (marginal odds ratio range, 0.84 [95% CI, 0.42-1.67] to 1.18 [95% CI, 0.55-2.51]).

Conclusions and Relevance In this prospective cohort study, there was no evidence that the proportion of participants with ME/CFS-like illness differed between those infected with SARS-CoV-2 vs those without SARS-CoV-2 infection up to 12 months after infection. A 3% to 4% prevalence of ME/CFS-like illness after an acute infection–like index illness would impose a high societal burden given the millions of persons infected with SARS-CoV-2.

Open access: https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2821459

 

An article:

Research finds no difference in chronic fatigue syndrome prevalence caused by COVID-19, other illnesses

 

Another article in US News:

COVID-19 Won't Raise Odds for Chronic Fatigue Syndrome: Study

The news outlets are picking up the press release, more of these articles may come.

 

Surprising result.

The controls had an infectious disease as well ('Our study design required an acute infection prompting COVID-19 testing') so that may explain the lack of difference between the groups. Nonetheless, the prevalence of ME/CFS-like illness was quite low, as the authors note:

 

Study took place from 2020-2022 (ending August 2022).

What are the odds that a lot of the people who didn’t test positive for covid were false negatives? (Based on time range). I know I had to get tested three times when I first got COVID before the test came out positive.

It’s not exactly like there was a high rate of other illnesses going around pre-2023.

Additionally given the suprisingly low rate in both groups, I’d note a rather high non-response rate. Is it possible people who’s lives were derailed by developing ME were much less likely to respond?

 

Press release:
https://www.eurekalert.org/news-releases/1052033

 

“Our findings suggest that ME/CFS may follow several precipitating events (acute COVID-19 illness, other acute infections, or life disruptions due to the COVID-19 pandemic) but that regardless of reason or exact percentages, there will be millions affected who will seek care.”

Frustrating. I wonder whether the originally submitted manuscript had this or whether it was suggested in the review process.

 

It’s a pity they didn’t have another control group who hadn’t requested a test which might have better clarified the effect of having an infection.

 

I think peer review should have led to emphasis of the following, in limitations —

But now everyone is picking up that likelihood of ME/CFS is the same following any infection, which is simply unsupportable.

In fact there have been data to suggest that a negative Covid PCR test at the time someone has Covid is associated with increased risk of LC. We need studies to use advanced techniques to more reliably demonstrate viral history.

Eg SARS-CoV-2–Specific Immune Responses in Patients With Postviral Syndrome After Suspected COVID-19 (2023, Neurology - Neuroimmunology Neuroinflammation) —

And Divergent adaptive immune responses define two types of long COVID (2023, Frontiers in Immunology) —

 

The amount of bad studies in medicine is absurd. And as usual they get a lot more press. The CDC continues to be inept and the profession generally appears incapable of learning much about issues that doesn't interest them.

 

On further review, I think I got sidetracked by how it's being reported. This is actually pretty much expected, COVID is creating far more cases because it became so prevalent and ran through the population like a wildfire several times, but there's nothing special about it and that all points to the immune reaction as being the problem, at least for ME/CFS.

So this finds that about 3% of people with an acute infection-like illness meet case definition for ME/CFS at 12 months. It's actually huge. Infections are common and this result is holding up solidly. There are now multiple corroborations that as a general statement of fact, it is true that following an acute infection, there is a small but significant percentage, 3-4%, who will develop a highly disabling chronic illness that meets case definition for ME/CFS, of which 3/4 are too ill to work and function normally.

The reporting and how the paper is written is atrocious and generally blatant propaganda, but it does include the important takeaway:

The press is reporting it under the same framing as the abstract: COVID likely doesn't cause Long Covid. This is how the paper is written to be interpreted, and it hides the major takeaway that this isn't a potential "high societal burden", it's already there in many studies. I've seen several headlines like this, all different ways of saying roughly this.

The pattern where significant findings from major institutions continue to be hidden in plain sight is disturbing. The NIH intramural study did find interesting leads, but it got entirely sidetracked by the awful effort preference thing. Here the conclusion is disturbing, but it's instead presented in just the right way that sounds like minimizing, but actually confirms the overall picture of ME/CFS and how it relates to Long Covid and infections in general.

This has to take into account that many long haulers don't have ME/CFS, but do have significant symptoms, so the overall burden of illness is immense. It becomes clear that reigning in infections will have major societal and economic benefits, including higher government revenue and lower taxes. The investment is worth it, and there's almost zero chance that it happens. Instead we'd rather do nothing about it, even though it's more expensive and worse in every way. What a weird people we are.