As the summer wave of COVID-19 infections spreads again, The study was published this week in the New England Journal of Medicine. There is some good news about this pandemic disease: A new analysis shows that the rate of long COVID-19 has been declining since the health crisis began, dropping from a high of 10.4% before vaccines became available to a low of 3.5% in people vaccinated in the Omicron era.
The study, led by Ziyad Al Ali, principal investigator at the VA St. Louis Healthcare System, used data from the Department of Veterans Affairs’ vast medical records. Researchers ultimately included data from more than 440,000 veterans who had COVID-19 between March 1, 2020 and Jan. 31, 2022, as well as more than 4.7 million uninfected veterans as controls.
Al-Ali and his colleagues divided the subjects into eight groups. Those infected during the study period were divided into five groups according to their date of first infection and vaccination status. The first group included those infected during the pre-Delta era (March 1, 2020 to June 18, 2021), before the vaccine was available. Next, there were vaccinated and unvaccinated groups infected during the Delta era (June 19, 2021 to December 18, 2021) and the Omicron era (December 19, 2021 and January 31, 2022). Uninfected controls made up the last three of the eight groups, with controls assigned to one of the three eras.
In decline
During the Delta era/pre-vaccine era, 10.42 out of 100 unvaccinated infected individuals developed long COVID one year after infection, which researchers called PASC, or acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. During the Delta era, the rate of long COVID among unvaccinated individuals dropped slightly to 9.51 out of 100 individuals. However, in vaccinated individuals, the rate dropped more dramatically to 5.35 out of 100 individuals. A similar pattern was seen in the Omicron era. In unvaccinated individuals, the rate of long COVID again dropped slightly to 7.76 out of 100 individuals, while in vaccinated individuals, the rate dropped to 3.5 out of 100 individuals.
In a secondary statistical analysis called a decomposition analysis, the researchers found that vaccines could explain about 72% of the cumulative decline in long COVID rates across eras, and era-related factors could explain about 28%. Era-related factors could include differences in the virus, improvements in treatments, and the use of antiviral drugs.
Additionally, the researchers also conducted an analysis looking at data on disease categories associated with Long COVID cases to find changes in symptoms across eras. The researchers looked at 10 disease categories: cardiovascular, coagulation and hematology, fatigue, gastrointestinal, renal, mental health, metabolic, musculoskeletal, neurological, and pulmonary. The researchers noted an increase in gastrointestinal, metabolic, and musculoskeletal diseases associated with Long COVID cases in the Omicron era compared to the previous two eras.
Overall, the study points to a declining incidence of long COVID among infected individuals, especially those who have been vaccinated. But it also makes clear that long COVID is not a thing of the past. “A significant residual risk of PASC remains in vaccinated individuals infected with SARS-CoV-2 during the Omicron era,” Al Ali and his colleagues conclude.
The study also has several limitations that leave questions for further research. One is whether the type or number of vaccines affects the risk of long COVID-19, which the study did not include. The study also did not allow the researchers to assess whether repeated infections increase the burden of long COVID-19.
