Apparent risks of postural orthostatic tachycardia syndrome diagnoses after COVID-19 vaccination and SARS-Cov-2 Infection, 2022, Kwan et al

[SNT Gatchaman]

Apparent risks of postural orthostatic tachycardia syndrome diagnoses after COVID-19 vaccination and SARS-Cov-2 Infection
Kwan, Alan C.; Ebinger, Joseph E.; Wei, Janet; Le, Catherine N.; Oft, Jillian R.; Zabner, Rachel; Teodorescu, Debbie; Botting, Patrick G.; Navarrette, Jesse; Ouyang, David; Driver, Matthew; Claggett, Brian; Weber, Brittany N.; Chen, Peng-Sheng; Cheng, Susan

Postural orthostatic tachycardia syndrome (POTS) was previously described after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection; however, limited data are available on the relation of POTS with Coronavirus Disease 2019 (COVID-19) vaccination.

Here we show, in a cohort of 284,592 COVID-19-vaccinated individuals, using a sequence–symmetry analysis, that the odds of POTS are higher 90 days after vaccine exposure than 90 days before exposure; we also show that the odds for POTS are higher than referent conventional primary care diagnoses but lower than the odds of new POTS diagnosis after SARS-CoV-2 infection.

Our results identify a possible association between COVID-19 vaccination and incidence of POTS. Notwithstanding the probable low incidence of POTS after COVID-19 vaccination, particularly when compared to SARS-Cov-2 post-infection odds, which were five times higher, our results suggest that further studies are needed to investigate the incidence and etiology of POTS occurring after COVID-19 vaccination.

Link | PDF

 

[Hutan]

In Nature Cardiovascular Research, authors are associated with
Department of Cardiology, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Department of Medicine, Division of Infectious Diseases, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Department of Medicine, Division of Cardiovascular Medicine, Brigham and Women’s Hospital, Boston, MA, USA.

So, that's some pretty main-stream and influential entertainment of the idea of POTS occurring after an immunological challenge.

POTS is now known as one of many possible features of post-acute COVID-19 syndromes that can develop after SARS-CoV-2 infection

The data suggests that having Covid-19 results in much worse odds than having the vaccine. I suspect the data gets pretty messy, with asymptomatic infections, and infections +vaccination, and the authors acknowledge that in a lengthy Limitations section. Note, that these odds are for out-patient data, so the before and after odds can be compared to each other but I don't think that they tell us about the absolute risk of developing POTS.

I had more commentary, but I've run out of energy to properly read and understand the study, and can't hold thoughts, so I'll leave it there.

 

[DokaGirl]

Hi @Hutan,

You've summed up my communication and cognition problems in a nut shell here:

"I had more commentary, but I've run out of energy to properly read and understand the study, and can't hold thoughts, so I'll leave it there."

Re the study, thanks for your analysis of this. It does seem like it would be difficult and indeed messy to sift out cause and effect.

ETA: Speaking of energy to properly understand, I don't know how to quote just a small bit of a Member's comments. So, this my attempt to try to get that figured out.

 

[SNT Gatchaman]

News and Views commentary on this paper from Svetlana Blitshteyn and Artur Fedorowski

The risks of POTS after COVID-19 vaccination and SARS-CoV-2 infection: it’s worth a shot (Nature Cardiovascular Research, Dec 2022)

Despite these limitations, the study by Kwan et al is of major importance to POTS research and patient care for several reasons. First, it undeniably establishes POTS and dysautonomia in general as adverse events after vaccination that should be recognized and investigated as other well-accepted post-vaccination syndromes, such as Guillain–Barre syndrome and acute disseminated encephalomyelitis. Second, it clearly demonstrates that POTS and POTS-associated comorbidities occur more frequently after COVID vaccination than before, and much more frequently than myocarditis, which, despite increasing at a higher rate after vaccination, remains a rare post-vaccination complication. Consequently, POTS and POTS-associated conditions may be among the most common adverse events after COVID-19 vaccination. Third, it reaffirms that POTS occurs at a high rate after SARS-CoV-2 infection and is likely one of the major phenotypes of PASC. Fourth, the rate of new-onset POTS diagnoses is more than five times higher following natural SARS-CoV-2 infection than after COVID-19 vaccination.

 

[SNT Gatchaman]

Note that an issue has been raised around the 5.3x odds ratio of POTS between infection-only and vaccine-only cohorts.



It's centred on the study design as summarised in their figure 3. This shows odds being calculated for the vaccination-only cohort, pre- and post- intervention: for both POTS diagnoses and Common Primary Care diagnoses. Then an odds ratio is calculated between these diagnoses, for the vaccination group.

For the infection group, odds have not been expressed in this graphic, and what is labelled as "OR 5.35" would seem to be a post-intervention incidence ratio for POTS.



Obviously this is not a randomised trial - the two groups self-selected whether they would or would not have vaccination (with infection being under neither subject or investigator control). So their background rates might well be expected to be different. The findings that pre-intervention the POTS incidence was a little under 5x are now being highlighted as very close to the 5.3x, as summarised in the abstract.

Perhaps people that chose no-vaccine had existing conditions or related reasons that associated with a higher rate of POTS development (pre- and post- infection). I note that the infection-only group had zero new EDS diagnoses, pre- or post- (vs 6.68 & 7.73 /100K for the vaccinated group). Does this mean that they already had EDS, so couldn't be newly diagnosed within the 90 days pre-intervention?

 

[Jonathan Edwards]

In Nature Cardiovascular Research, authors are associated with
Department of Cardiology, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Department of Medicine, Division of Infectious Diseases, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Department of Medicine, Division of Cardiovascular Medicine, Brigham and Women’s Hospital, Boston, MA, USA.

So, that's some pretty main-stream and influential entertainment of the idea of POTS occurring after an immunological challenge.

Is it?
I had never heard of Nature Cardiovascular Research and rather suspect it is yet another important-sounding clone journal designed specifically to sound good.
I no longer have any faith that big USA university hospital names mean anything.
I guess in a sense this is the mainstream now and yes it may be influential but that does not mean it isn't just empty cans jangling in the breeze.

I have not gone through in detail but I am pretty sure nothing can be concluded from this sort of study in which ascertainment bias is likely to be huge.

The Blitshteyn piece shows just how hyped things like this get.

 

[SNT Gatchaman]

I've highlighted the EDS and mast cell disorder figures in the tables of the two groups. Zero for both is suspicious and I can imagine have either as a pre-existing diagnosis might affect the individual's decision to vaccinate.

 

[Jonathan Edwards]

Interesting. I am more and more confused by this. It seems that the people who were vaccinated had ten times as many diagnoses of everything? So not exactly matched.