No Causal Effects Detected in COVID-19 and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Two Sample Mendelian Randomi.. (Xu et al, 2023)

[Consul]

No Causal Effects Detected in COVID-19 and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Two Sample Mendelian Randomization Study

Abstract

New clinical observational studies suggest that Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a sequela of COVID-19 infection, but whether there is an exact causal relationship between COVID-19 and ME/CFS remains to be verified. To investigate whether infection with COVID-19 actually causes ME/CFS, this paper obtained pooled data from the Genome Wide Association Study (GWAS) and analyzed the relationship between COVID susceptibility, hospitalization and severity of COVID and ME/CFS, respectively, using two-sample Mendelian randomization (TSMR). TSMR analysis was performed by inverse variance weighting (IVW), weighted median method, MR-Egger regression and weighted mode and simple mode methods, respectively, and then the causal relationship between COVID-19 and ME/CFS was further evaluated by odds ratio (OR). Eventually, we found that COVID-19 severity, hospitalization and susceptibility were all not significantly correlated with ME/CFS (OR:1.000,1.000,1.000; 95% CI:0.999–1.000, 0.999–1.001, 0.998–1.002; p = 0.333, 0.862, 0.998, respectively). We found the results to be reliable after sensitivity analysis. These results suggested that SARS-CoV-2 infection may not significantly contribute to the elevated risk of developing CFS, and therefore ME/CFS may not be a sequela of COVID-19, but may simply present with symptoms similar to those of CFS after COVID-19 infection, and thus should be judged and differentiated by physicians when diagnosing and treating the disease in clinical practice.

https://www.mdpi.com/1660-4601/20/3/2437

 

[Atlas]

If I understood correctly they are using self-reported diagnosis as a way to classify who has ME/CFS?

Wouldn't this invalidate the results, because most people with post Covid consider themselves Long Covid patients and not ME/CFS patients?

Likewise even with official diagnoses I expect many doctors would prefer to give a PASC/Long Covid diagnosis to their patients because it is taken more seriously.


It doesn't appear that this paper is considering everyone post-covid who matches ME/CFS criteria, it only seems to be looking for a link between Covid and people who have been self-diagnosed (and/or diagnosed?) with ME/CFS.

If that's the case, all that it appears to prove is that Long Covid patients don't want to be identified as ME/CFS patients...

 

[Murph]

It's pretty rare I completely can't understand something. Usually I can grasp something and fill in the gaps. But this is leaving me completely muddled.

1. My best guess on what a mendelian randomisation is, is that they compare genetic susceptibility to covid to the outcome mecfs. the idea being that using genetic suscpetibility avoids some confounders in the data that might explain why some people werer more likely to *actually* get covid.
2. The self-report data on mecfs outcomes they use appears to be from 2018. Before covid. If my understand of what a mendelian randomisation *is* is right, how does that help?
3. Are they aware that men are more likely to get covid but women are more likely to get long covid. It doesn't seem to account for that anywhere.

 

[Atlas]

The self-report data on mecfs outcomes they use appears to be from 2018.

I noticed that and it confused me too. I didn't have the energy to go and look at the data in depth, but assumed that maybe that data was for ruling out reverse causality, and there must have been more ME/CFS diagnoses in the other dataset.

But whatever they did, as far as I can tell it doesn't appear to be clearly explained.