As a summer wave of COVID-19 infections swells once again, a study published this week in the New England Journal of Medicine offers some positive news about the pandemic disease: Rates of long COVID have declined since the beginning of the health crisis, with rates falling from a high of 10.4 percent before vaccines were available to a low of 3.5 percent for those vaccinated during the omicron era, according to the new analysis.

The study, led by Ziyad Al-Aly, chief of research at the VA Saint Louis Health Care System, used data from a wealth of health records in the Department of Veterans Affairs. The researchers ultimately included data from over 440,000 veterans who contracted COVID-19 sometime between March 1, 2020, and January 31, 2022, as well as over 4.7 million uninfected veterans who acted as controls.

Al-Aly and colleagues divided the population into eight groups. People who were infected during the study period were divided into five groupings by the dates of their first infection and their vaccination status. The first group included those infected in the pre-delta era before vaccines were available (March 1, 2020, to June 18, 2021). Then there were vaccinated and unvaccinated groups who were infected in the delta era (June 19, 2021, to December 18, 2021) and the omicron era (December 19, 2021, and January 31, 2022). The uninfected controls made up the final three of eight groups, with the controls assigned to one of the three eras.

On the decline

In the pre-delta/pre-vaccine era, 10.42 out of 100 unvaccinated people infected developed long COVID in the year after their infection, which the researchers referred to as PASC, or postacute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In the delta era, the rate of long COVID among the unvaccinated fell slightly to 9.51 out of 100. But for the vaccinated, the rate fell much further, to 5.35 out of 100. A similar pattern was seen in the omicron era. For the unvaccinated, the rate of long COVID again fell slightly to 7.76 per 100 people, while the vaccinated saw their rate fall to 3.5 per 100.

In a secondary statistical analysis, called a decomposition analysis, the researchers found that vaccines could explain about 72 percent of the cumulative decline in long COVID rates across the eras, while era-related factors explained about 28 percent. Those era-related factors could include differences in the virus, improved treatments, and use of anti-viral medications.

Further, looking at data on the disease categories related to long COVID cases, the researchers also did an analysis finding a shift in symptoms over the eras. The researchers looked at over 10 disease categories: cardiovascular, coagulation and hematologic, fatigue, gastrointestinal, kidney, mental health, metabolic, musculoskeletal, neurologic, and pulmonary. Compared to the two earlier eras, the researchers noted an increase in gastrointestinal, metabolic, and musculoskeletal diseases involved in long COVID cases in the omicron era.

Overall, the study points to a welcomed decline in the rates of long COVID among the infected, particularly for those who are vaccinated. But, it also makes clear that long COVID isn't a thing of the past: "a substantial residual risk of PASC remains among vaccinated persons who had SARS-CoV-2 infection during the omicron era," Al-Aly and his colleagues conclude.

The study also has some limitations, leaving lingering questions for further study. One is whether the type or number of vaccines affect the risk of long COVID—that was not included in the study. The study also didn't allow researchers to assess whether repeat infections increase the burden of long COVID.