Postacute Sequelae of SARS-CoV-2 Infection in the Pre-Delta, Delta, and Omicron Eras, 2024, Ziyad Al-Aly, M.D et al

Abstract

BACKGROUND
Postacute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC) can affect many organ systems. However, temporal changes during the coronavirus disease 2019 (Covid-19) pandemic, including the evolution of SARS-CoV-2, may have affected the risk and burden of PASC. Whether the risk and burden of PASC have changed over the course of the pandemic is unclear.

METHODS
We used health records of the Department of Veterans Affairs to build a study population of 441,583 veterans with SARS-CoV-2 infection between March 1, 2020, and January 31, 2022, and 4,748,504 noninfected contemporaneous controls. We estimated the cumulative incidence of PASC at 1 year after SARS-CoV-2 infection during the pre-delta, delta, and omicron eras of the Covid-19 pandemic.

RESULTS
Among unvaccinated persons infected with SARS-CoV-2, the cumulative incidence of PASC during the first year after infection was 10.42 events per 100 persons (95% confidence interval [CI], 10.22 to 10.64) in the pre-delta era, 9.51 events per 100 persons (95% CI, 9.26 to 9.75) in the delta era, and 7.76 events per 100 persons (95% CI, 7.57 to 7.98) in the omicron era (difference between the omicron and pre-delta eras, −2.66 events per 100 persons [95% CI, −2.93 to −2.36]; difference between the omicron and delta eras, −1.75 events per 100 persons [95% CI, −2.08 to −1.42]). Among vaccinated persons, the cumulative incidence of PASC at 1 year was 5.34 events per 100 persons (95% CI, 5.10 to 5.58) during the delta era and 3.50 events per 100 persons (95% CI, 3.31 to 3.71) during the omicron era (difference between the omicron and delta eras, −1.83 events per 100 persons; 95% CI, −2.14 to −1.52). Vaccinated persons had a lower cumulative incidence of PASC at 1 year than unvaccinated persons (difference during the delta era, −4.18 events per 100 persons [95% CI, −4.47 to −3.88]; difference during the omicron era, −4.26 events per 100 persons [95% CI, −4.49 to −4.05]). Decomposition analyses showed 5.23 (95% CI, 4.97 to 5.47) fewer PASC events per 100 persons at 1 year during the omicron era than during the pre-delta and delta eras combined; 28.11% of the decrease (95% CI, 25.57 to 30.50) was attributable to era-related effects (changes in the virus and other temporal effects), and 71.89% (95% CI, 69.50 to 74.43) was attributable to vaccines.

CONCLUSIONS
The cumulative incidence of PASC during the first year after SARS-CoV-2 infection decreased over the course of the pandemic, but the risk of PASC remained substantial even among vaccinated persons who had SARS-CoV-2 infection in the omicron era. (Supported by the Department of Veterans Affairs.)

LINK

 

Surprised that the very first iteration of the virus caused more long covid than the delta-era one, which if i recall correctly, caused more severe acute illness.

But overall this matches my prior which is that as the virus mutates to cause less serious illness, there's a lower rate of long covid. 3.5% chance of long covid for a vaccinated person these days seems credible.

 

Quote from study:
This study has several limitations. The study population consisted predominantly of older White men. The eligibility criteria, including demographic characteristics, coexisting conditions, and vaccination rates, may not be representative of the general population.

Would be nice if the same study could be done on other demographics.

 

Press release:

Risk of long COVID declined over course of pandemic
Drop attributed mostly to vaccination but remaining risk still significant

https://medicine.wustl.edu/news/risk-of-long-covid-declined-over-course-of-pandemic/

 

I think viral mutations can go in either direction of severity and don't inevitably become more benign. After all ancestral SARS-CoV-2 mutated into existence at the outset. The paper looks to be implying vaccination as the major factor.

From Cliff Rosen's editorial Viral Variants, Vaccinations, and Long Covid — New Insights (2024, New England Journal of Medicine) —

(On the day President Biden again contracts Covid, nearly two years after declaring the pandemic over.)

 

What is the prognosis of repeated Covid infections, mild, moderate and severe 5+ years from now. That's concerning too.

https://covid19.nih.gov/news-and-stories/rapid-progression-dementia-following-covid-19

 

Interesting study, and one that shows just how valuable some of these large databases can be for research. Looks like they carefully considered a great many potentially confounding variables. What would also have been useful, rather than just treating vaccination as a binary would have been to determine how the incidence of long COVID was affected by 1st & 2nd & booster doses of vaccine (& looking at vaccine type might also have been interesting). Also curious that there was "a lower risk of sequelae in most disease categories but a higher risk of gastrointestinal, metabolic, and musculoskeletal disorders during the omicron era than during the pre-delta and delta eras combined".

Even the "low" incidence in the vaccinated in the Omicron era still strikes me as an alarmingly high level of suffering. Absurd that transmission mitigations and measures to encourage vaccine uptake have been abandoned so readily.

 

Long COVID puzzle pieces are falling into place – the picture is unsettling

https://theconversation.com/long-co...g-into-place-the-picture-is-unsettling-233759

 

Thanks for posting the link. I saw this story earlier and was disappointed that although this story mentions post-exertional malaise it never mentions ME/CFS.

The mention of PEM is even linked to the CDC website for ME/CFS. But the article itself never mentions the illness.

Maybe it's due to editorial choices for this news outlet? Because I've seen interviews with the author (Dr. Ziyad Al-Aly ) and he has mentioned ME/CFS often.

Here's a section from the transcript of the recent Washington Post Live event on Long Covid:

source =

https://www.washingtonpost.com/wash.../25/transcript-long-covid-where-things-stand/

 

The cumulative DALY impact for fatigue seems rather low compared to other outcomes:

 

Correspondence in NEJM commenting on & critiquing this study today with responses from the authors (p1658+):

https://www.nejm.org/doi/pdf/10.1056/NEJMc2411213