New Study – Does it Prove Long-COVID is a Huge Problem OR
Is it Just More Long-COVID Shenanigans
I’ve been meaning to write about this study for a while now, but I have unfortunately been distracted by a significant injury that requires an upcoming surgery.
I came across this study from another popular Substacker who is very insistent that Long-COVID (PASC) is a big issue and from time to time attacks other writers like Alex Berenson, for posting studies that call the frequency and severity of PASC into question. I have posted articles on such studies myself.
I wont’ mention the Substacker by name because he is doing a great deal of good in this space and we are all allowed to disagree, still get along, and work towards a better world together.
Before we proceed, if you have read my previous articles, you will know that I entirely believe PASC is a real thing, but I am very sceptical that the frequency with which we are told (by mainstream media and government) it occurs has nothing to do with physical SARS-CoV-2 infection. Previous studies reveal that much of the reported PASC may in fact be a psychosomatic condition, meaning there is no confirmed physical reason for the reported PASC symptoms. Instead, the psychological state leads to the physical symptoms.
We therefore come to the possibility that a non-trivial amount of PASC has been conjured into existence by the constant fear messaging about COVID-19 and Long-COVID by our government and media, pushing those who struggled with psychological health (diagnosed or not) before COVID-19 infection to more likely believe they have PASC. The significant impact that previous psychological health struggles (depression and anxiety) have on PASC risk has been shown in the articles I have written about before. This is not simply my opinion.
Again, this does not mean that a non-psychosomatic version of PASC doesn’t exist, it almost certainly does, as is the case with nearly all other infectious diseases. The question is, what is the risk of these 2 versions of PASC? Additionally, proper diagnostics need to be done as appropriate treatment will differ between physical and psychosomatic version of PASC.
A pre-print from Sept 2022 may shed a bit of light on this issue; however, the study is flawed, IMO.
The Study
First, let’s outline what the authors say they found, here is an excerpt.
Simply put, the authors say that low grade inflammation is present in those with PASC which resembles that seen in other conditions such as Chronic Fatigue Syndrome (CFS) and Major Depressive Disorder (MDD). CFS is complex and multifactorial in its cause; however, the strong connection with psychological struggles lead to the theory that a certain portion of CFS patients experience a psychosomatic disorder. We then enter a situation where we don’t know what came first, the psychological issues or the low-level inflammation issues because low level inflammation can cause the symptoms of CFS and MDD while the feelings that accompany chronic mental health struggles (depression, anxiety, etc.) can cause low level inflammation.
This will be different for each individual and this is why exhaustive diagnostic testing and treating patients as individuals is essential.
Back to PASC. If we want to paint PASC as a major problem that is without a doubt caused by SARS-CoV-2 infection, we don’t put ourselves on good footing comparing inflammatory markers to CFS and MDD. But again, that doesn’t mean PASC doesn’t exist.
For the PASC deniers, I do think this paper presents some information showing that PASC is in fact a real thing that may be tied to the chronic elevation of the immune system following COVID-19 recovery. However, the paper solely focuses on patients that were hospitalized for COVID-19, and specifically the Alpha variant. As with PAS from other infection diseases, we would expect the highest risk of PAS in those that had the worst symptoms. So, when a study only uses hospitalized patients, we cannot gather any useful data on the risk and frequency of PASC across the entire population.
Now let’s discuss some other critiques of the paper.
The first and major critique is that the study doesn’t use a control group of recovered COVID-19 patients that were hospitalized but never reported PASC. The paper had 3 main groups, one group had PASC with fatigue, one had PASC without fatigue, and one was a an aged and gender matched healthy control group. The 2 PASC groups were recruited from patients hospitalized with COVID-19 while the control group was recruited from hospital visitors. Yup, visitors, not patients!
This is straight up a terrible study design to the extent that it’s hard to take the findings all that seriously. Let me explain.
If one wanted to redesign this study to find out if there are any underlying inflammation issues causing PASC after COVID-19 hospitalization I would have the following groups.
· PASC group that was hospitalized for COVID-19
· Non-PASC group that was also hospitalized for COVID-19**
· PAS group that was hospitalized for another respiratory infectious disease
· Non-PAS group that was hospitalized for another respiratory infectious disease
· Age, gender, and health status matched control group that wasn’t hospitalized
If the study was designed with these groups, we would be able to determine if the underlying low-level inflammation seen in the PASC groups was the true cause of the PASC symptoms, whether this inflammation was different from any other forms of PAS, and the frequency and severity of PASC compared to other forms of PAS.
Unfortunately, the study does not include a non-PASC group that was also hospitalized for COVID-19. Because of this, we literally cannot determine if the low-level inflammation is causing PASC. Why? Because extended low-level inflammation could simply be a normal part of COVID-19 recovery regardless of whether the person has PASC or not.
With the study design as is, we have no way of making this determination, and the authors even identify this as a limitation of their study.
This kind of blows my mind. The researchers realize this limitation, so they should have tried to address this issue from the start of the study, they didn’t do so and didn’t explain the reason for the lack of such a control group. IMO, this is a fatal flaw in the study.
To further this point, the non-fatigue, less severe PASC group showed elevated inflammatory markers in a similar way to the more severe PASC group. This means we must ask whether the inflammatory markers are the actual cause of symptoms, this is a very rational question considering these results. Yet, the authors comment on this is that it’s just surprising.
Next, the control group used in the study were healthy visitors to the hospital, not people who were hospitalized for a respiratory infection. The only information we can gather from this group is what inflammation levels are expected to be in the general population of people that were NOT recovering from a respiratory viral infection. This is necessary information, but it tells us nothing about whether the elevated inflammatory markers are causing PASC, or whether it’s different from recovery from other respiratory viral infections.
Because this study design lacked a proper control group to make useful comparisons, here is the conclusion regarding the pattern of low-level inflammation in PASC patients.
So, while inflammation is elevated in PASC patients, there is no link between specific immune abnormalities and specific PASC symptoms. Gee, maybe if there had been a non-PASC control group of recovered COVID-19 patients who had also been hospitalized, some patterns may have emerged, and this could have been a useful paper to help practitioners figure out treatment options.
Finally, in the fatigue/severe PASC group, PTSD was present in 14%, 14% experienced anxiety, and 35% experienced mild to moderate depression. PTSD on its own can cause many of the reported PASC symptoms, and the authors say nothing of whether these patients experienced anxiety and depression prior to COVID-9 infection. This is very surprising since a few studies have connected previous anxiety and depression to a higher risk of reporting PASC symptoms (see my linked article above) without having any positive diagnostic testing.
Final Thoughts
Ultimately, this study provides some evidence that ongoing low-level inflammation MIGHT be one of the physical causes of PASC; however, given the design flaws in the study we cannot determine whether the low-level inflammation is the actual cause of PASC or whether it’s a normal response to COVID-19 (or even other respiratory infection) recovery, PASC or no PASC.
At best this study provides a starting point for future investigations using much better designed studies.