A study yesterday in the New England Journal of Medicine from long-COVID researchers at Washington University School of Medicine in St. Louis shows the risk of long COVID has decreased over time, most likely due to the impact of vaccination.
"We had a hunch that things have changed during the pandemic after the initial couple years, which were brutal," said Ziyad Al-Aly, MD, senior author of the study, in an interview. "But a hunch is not data. This study now shows COVID is dynamic, and I was pleasantly surprised by how much vaccines made a dent in preventing long COVID."
Al-Aly is the chief of research and development at the VA St. Louis Health Care System and a clinical epidemiologist at Washington University in St. Louis.
As with his prior work, Al-Aly and colleagues mined data from the Veteran's Affairs (VA) health system to look at the risk of developing long COVID over the past 4 years. The study involved data on 441,583 veterans with SARS-CoV-2 infections and more than 4.7 million uninfected veterans, with accompanying health records from March 1, 2020, through January 31, 2022.
The study assessed long-COVID symptoms 1-year post COVID-19 infection in one of five groups: unvaccinated veterans infected with either the original strain in 2020, the Delta variant in 2021, or the Omicron variant in 2022, and vaccinated veterans infected with either the Delta variant or Omicron variant.
1 in 10 infected with original strain had long COVID
The highest risk of developing long COVID was seen among patients infected with the original strain of the virus, when no vaccines were available. Those case-patients had a cumulative incidence of long COVID symptoms 1-year post infection of 10.42 per 100 people (95% confidence interval [CI], 10.22 to 10.64), or 10.4%.
Among the unvaccinated, long-COVID prevalence dropped with each subsequent variant, to 9.51 events per 100 people (95% CI, 9.26 to 9.75) in the Delta era and to 7.76 events per 100 people (95% CI, 7.57 to 7.98) in the Omicron era.
Overall, vaccinated VA patients had significantly lower incidences of long COVID. Among vaccinated patients, the cumulative incidence of long COVID symptoms at 1 year was 5.34 events per 100 people (95% CI, 5.10 to 5.58) during the Delta era and 3.50 events per 100 people (95% CI, 3.31 to 3.71) during the Omicron era.
Despite the significant reduction, Al-Aly warned that 3.5 people developing long COVID out of every 100 infected still poses a significant public health threat as the pandemic wanes. He said the findings are of particular interest during the current summer surge of virus activity, which sees many Americans being reinfected with the virus.
"Every time you get COVID is a chance to get long COVID," Al-Aly said.
Vaccination plays biggest role in reducing risk
In decomposition analyses, researchers found that 28.11% (95% CI, 25.57% to 30.50%) of the decrease in long COVID incidence was attributable to variant strain-related effects and that 71.89% (95% CI, 69.50% to 74.43%) was attributable to COVID-19 vaccines.
"The lion's share of the reduction is attributed to vaccination, with a 30% reduction to viral characteristics over time," said Al-Aly.
The lion's share of the reduction is attributed to vaccination.
Of note, Al-Aly said the study did not assess what role booster vaccines played in preventing long COVID. For the study, being vaccinated meant completing just the initial series of mRNA vaccines. He said the role of boosters in offering further long-COVID protection is an important question.
In an editorial on the study, Clifford Rosen, MD, from the MaineHealth Institute for Research in Scarborough, Maine, writes, "What are the messages from this study? First, vaccinations can prevent many but not all cases of long Covid. Second, viral variants influence the risk of PASC [post-acute sequelae of SARS-CoV-2 infection]. Third, the study suggests that new cases of PASC may continue unabated, owing to a potentially greater prevalence of metabolic dysfunction and its associated coexisting conditions among persons infected during the omicron era."
He adds, "Changes in the clinical presentation of long COVID are a function of 'points in time' and must be considered in any future trial or study design, as well as in clinical assessments."
