Nature - Long COVID after breakthrough SARS-CoV-2 infection by Al-Aly et al, 2022

Abstract

The post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection—also referred to as Long COVID—have been described, but whether breakthrough SARS-CoV-2 infection (BTI) in vaccinated people results in post-acute sequelae is not clear.

In this study, we used the US Department of Veterans Affairs national healthcare databases to build a cohort of 33,940 individuals with BTI and several controls of people without evidence of SARS-CoV-2 infection, including contemporary (n = 4,983,491), historical (n = 5,785,273) and vaccinated (n = 2,566,369) controls.

At 6 months after infection, we show that, beyond the first 30 days of illness, compared to contemporary controls, people with BTI exhibited a higher risk of death (hazard ratio (HR) = 1.75, 95% confidence interval (CI): 1.59, 1.93) and incident post-acute sequelae (HR = 1.50, 95% CI: 1.46, 1.54), including cardiovascular, coagulation and hematologic, gastrointestinal, kidney, mental health, metabolic, musculoskeletal and neurologic disorders.

The results were consistent in comparisons versus the historical and vaccinated controls.

Compared to people with SARS-CoV-2 infection who were not previously vaccinated (n = 113,474), people with BTI exhibited lower risks of death (HR = 0.66, 95% CI: 0.58, 0.74) and incident post-acute sequelae (HR = 0.85, 95% CI: 0.82, 0.89).

Altogether, the findings suggest that vaccination before infection confers only partial protection in the post-acute phase of the disease; hence, reliance on it as a sole mitigation strategy may not optimally reduce long-term health consequences of SARS-CoV-2 infection.

The findings emphasize the need for continued optimization of strategies for primary prevention of BTI and will guide development of post-acute care pathways for people with BTI.

https://www.nature.com/articles/s41591-022-01840-0

 

Prof Amitava Banerjee, professor in clinical data science and cardiologist summarises on Twitter:

 

0.85 seems very 'partial'.

My own n=1 indicates that despite three jabs and having Covid already another bout of Covid can leave you feeling garbage for six weeks. But I am not complaining. At seven weeks I am not too bad.

 

I am glad to hear you are feeling a bit better

 

I am sorry you've caught it twice, @Jonathan Edwards
Hope next week will be even better.

The Washington Post has an article about the study:
Vaccines may not prevent many symptoms of long covid, study suggests

quotes:
“This was disappointing,” said Ziyad Al-Aly, lead author and chief of research and development service at VA Saint Louis Health Care System. “I was hoping to see that vaccines offer more protection, especially given that vaccines are our only line of defense nowadays.”

...

“We failed in our health messaging that death is not the only serious outcome of a covid-19 infection,” Putrino said. “. . . I’m very concerned that what this is going to do is lead us into a continuation of this mass-disabling event we are seeing with long covid.”

 

Interesting that in their analysis, vaccination reduces the risk of pulmonary, coagulation and hematologic symptoms by about 50%, but other symptoms, including fatigue, much less. Maybe the symptoms that were reduced more are related to acute Covid severity and the others aren't.

I suspect fatigue is under-reported in this data though, because they only report 2% at six months — not a surprise as the data came from health records.

 

Also worth noting, since this shows quite a lot lower protection than other studies, that the average age of the patients with breakthrough infections was about 63 after adjustments. So these results might not be that applicable to the general population. We already know vaccines are a lot less protective in older age groups, so not a huge surprise if they are less protective against post-Covid symptoms too.

They do mention that it is a VA study, but seems like it would have been valuable to include the average age up front.

[Edit: Changed age from 70 to 63, I was looking at a stratified analysis, not the main one.]

 

And the breakthrough infection group was 89% men, so that would probably skew the results significantly as well, since we know women are more likely to have ME-like LC symptoms.

[Edit: Fixed percentage, I was looking at a stratified analysis, not the main one.]

 

Twitter thread from Ziyad Al-Aly, one of the researchers behind the study:

 

Continued:

 

Washington Post article, 25th May 2022
Vaccines may not prevent many symptoms of long covid, study suggests

 

I know that Washington Post gift links have not worked in the past for some folks on here, but here's a gift link (no paywall for 14 days) for those who can access it this way - https://wapo.st/3zlU1xN

 

They just posted a preprint for a follow up using the same data set, this time on post-Covid sequela after reinfections:

Outcomes of SARS-CoV-2 Reinfection

First infection with SARS-CoV-2 is associated with increased risk of acute and post-acute death and sequelae in the pulmonary and extrapulmonary organ systems. However, whether reinfection adds to the risk incurred after the first infection is not clear. Here we use the national health care databases of the US Department of Veterans Affairs to build a cohort of people with first infection (n = 257,427), reinfection (2 or more infections, n = 38,926), and a non-infected control group (n = 5,396,855) to estimate risks and 6-month burdens of all-cause mortality, hospitalization, and a set of pre-specified incident outcomes.

We show that compared to people with first infection, reinfection contributes additional risks of all-cause mortality, hospitalization, and adverse health outcomes in the pulmonary and several extrapulmonary organ systems (cardiovascular disorders, coagulation and hematologic disorders, diabetes, fatigue, gastrointestinal disorders, kidney disorders, mental health disorders, musculoskeletal disorders, and neurologic disorders); the risks were evident in those who were unvaccinated, had 1 shot, or 2 or more shots prior to the second infection; the risks were most pronounced in the acute phase, but persisted in the post-acute phase of reinfection, and most were still evident at 6 months after reinfection.

Compared to non-infected controls, assessment of the cumulative risks of repeated infection showed that the risk and burden increased in a graded fashion according to the number of infections. The constellation of findings show that reinfection adds non-trivial risks of all-cause mortality, hospitalization, and adverse health outcomes in the acute and post-acute phase of the reinfection. Reducing overall burden of death and disease due to SARS-CoV-2 will require strategies for reinfection prevention.

Preprint

 

I think the headline is that the risk of post-Covid sequela is higher after a second infection than a first one. So risk for Long Covid is higher after a reinfection, not lower as many have assumed.

Risk of at least one sequela (excess over control group):

• 1st infection: 8%
• 2nd infection: 23%
• 3rd infection: 36%

Seems like the general pattern is similar for most symptoms or sequela groups when looked at individually, some show an even more pronounced increase (e.g. fatigue, gastro issues).

Lots of caveats on this one though:

• Study was on US Veterans, average age 61-66, 88-91% male, 82-91% unvaccinated. This cohort is definitely different from the general population.
• Slightly higher risk for unvaccinated or single vaccinated than double vaccinated.
• Data was from medical records, likely underestimates symptoms like fatigue, cognitive issues, etc.
• They only counted reinfections within seven months of the first infection.
• Not clear how many reinfections were Omicron, Delta or earlier.
  

 

Marvel at the wisdom of Graded Infection Therapy, where it is believed that every infection protects more than the next.

I'm about 99% sure that this will be a thing for a while, deniers will latch on to anything and actually promote the idea that repeated infections offer the most protection. Not named GIT, of course, the problem is with the name, though. But contrarian ideas are what contrarians promote, so I'd be very surprised if we didn't go through this phase at least in several countries.

 

After thinking about this, I think the study is more likely measuring a significant number of late positives on PCR tests (like a second positive test 6 weeks later from the same infection) rather than only re-infections. And if late positives are associated with post-Covid symptoms, which seems like a reasonable possibility (more difficulty clearing the virus or more viral RNA hanging around could be correlated with post-Covid symptoms), then these results are not going to be valid.

https://twitter.com/user/status/1539306169537134592