“If people think COVID is no big deal and decide to forgo vaccinations, they’re essentially doubling their risk of developing long COVID,” wrote investigators.
Vaccination dramatically reduced the risk of developing post-acute sequelae of severe acute respiratory syndrome SARS-CoV-2 infection (PASC), or long COVID, according to new research published in the New England Journal of Medicine.1
Although PASC still remains a concern past the end-date of the official public health emergency, the risk declined substantially throughout the pandemic. Researchers at Washington University School of Medicine found that vaccination is likely responsible for about 70% of this decrease; the other 30% is thought to be due to factors such as changes in the virus itself, better detection of
Key Takeaways
“The research on declining rates of long COVID marks the rare occasion when I have good news to report regarding this virus,” said Ziyad Al-Aly, MD, senior study author, clinical epidemiologist at Washington University and global leader in COVID-19 research, in a news release.2 “The findings also show the positive effects of getting vaccinated.”
In conducting the current study, investigators sought to understand whether the risk and burden of PASC changed throughout the pandemic alongside the evolution of the SARS-CoV-2 virus and other temporal shifts.
Investigators drew upon health records of the Department of Veterans Affairs to recruit 441,583 veterans with SARS-CoV-2 infection between March 1, 2020, and January 31, 2022, as well as 4,748,504 noninfected contemporaneous controls. Estimates of cumulative incidence of long COVID were made 1 year after SARS-CoV-2 infection spanning cases from the pre-delta, delta, and omicron eras of the COVID-19 pandemic.
Participants were divided into 6 total groups, including unvaccinated persons with pre-delta in 2020, during which vaccines were not available; the delta variant in 2021; and the omicron variant in 2022. The remaining groups included vaccinated persons with the delta variant, and vaccinated persons with the omicron variant.
Health outcomes were grouped into categories based on the body system they affected, including cardiovascular, coagulation, hematologic, fatigue, gastrointestinal, kidney, mental health, metabolic, musculoskeletal, neurologic, and pulmonary.
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Overall, findings elicited a significant drop in the likelihood of PASC over the course of the pandemic. Whereas cases of PASC peaked at 10.42 per 100 persons (95% CI, 10.22 to 10.64) among unvaccinated persons during the pre-delta era, they decreased to 3.50 per 100 persons (95% CI, 3.31 to 3.71) among vaccinated persons during the omicron era.
However, investigators noticed an important trend: vaccinated persons had a lower cumulative incidence of PASC at 1 year than unvaccinated persons. This difference translated to 4.18 less PASC events per 100 per persons during the delta era (95% CI, −4.47 to −3.88) and 4.26 less events per 100 persons during the omicron era (95% CI, −4.49 to −4.05).
Further, decomposition analyses showed 5.23 (95% CI, 4.97 to 5.47) less PASC events per 100 persons at 1 year after infection during the omicron era than during the pre-delta and delta eras combined. The same analyses showed that era-related effects and the impact of vaccines attributed to 28.11% (95% CI, 25.57 to 30.50) and 71.89% (95% CI, 69.50 to 74.43) of the decrease in PASC events, respectively. “These findings suggest that vaccine uptake will be key to maintaining the lower cumulative incidence of PASC relative to earlier phases of the pandemic,” wrote investigators.
Sensitivity analyses conducted to challenge the robustness of investigators’ findings found consistent results with those of main analyses.
“You can see a clear and significant difference in risk during the delta and omicron eras between the vaccinated and unvaccinated,” said Al-Aly.2 “So, if people think COVID is no big deal and decide to forgo vaccinations, they’re essentially doubling their risk of developing long COVID.”
But even with the decline and vaccination’s protection against PASC, investigators highlighted a residual risk for
“That’s 3 to 4 vaccinated individuals out of 100 getting long COVID,” said Al-Aly.2 “Multiplied by the large numbers of people who continue to get infected and reinfected, it’s a lot of people. This remaining risk is not trivial. It will continue to add an already staggering health problem facing people across the world.”
Other results demonstrated that while the risk of most complications across disease categories decreased, there were elevated risks of gastrointestinal, metabolic, and musculoskeletal disorders during the omicron era than during the pre-delta and delta eras combined. This suggests that there may be a shift in the characteristics of PASC due to virus variants, the effects of vaccination, and other changes over time.
“It’s really good news that the risk has declined,” concluded Al-Aly.2 “But we know millions of people have long COVID, and millions more will continue to get long COVID. We need to double down on our efforts to understand it so we can prevent suffering and treat affected individuals.”
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