COVID shots moderately effective against postacute sequelae

COVID-19 vaccination appears to be moderately effective at preventing lingering symptoms following SARS-CoV-2 infection, and this effectiveness may increase with the number of doses administered, according to a meta-analysis.

Pooled data from nonrandomized interventional studies showed that receipt of at least one dose of COVID-19 vaccine had a vaccine effectiveness (VE) of 41 percent (95 percent confidence interval [CI], 27.8–51.7) against post-COVID-19 condition, defined as the continuation or development of new symptoms assessed 3 months or later after SARS-CoV-2 infection. [Clin Microbiol Infect 2025;31:1961-1971]

VE notably rose with each subsequent vaccine dose: 19.1 percent after one dose, 43.2 percent after two doses, and 70 percent after three doses.

In subgroup analyses, VE against post-COVID-19 condition was higher in older individuals (>60 years: 41 percent) than in children (<18 years: 26 percent) who received at least one dose. VE was also higher during the pre-Omicron period (32.1 percent) than during the Omicron period (20.9 percent) for individuals who received two doses.

For the secondary outcome of long COVID, defined as continuation or development of new symptoms 4 weeks after SARS-CoV-2 infection, VE was 34.1 percent.

Sensitivity analyses indicated no influence of risk of bias and effect measure.

“This systematic review and meta-analysis provides a comprehensive and contemporary overview of the efficacy and effectiveness of COVID-19 vaccination in preventing post-COVID-19 condition and long COVID,” the investigators said.

They emphasized the relevance of the findings, saying that current COVID-19 vaccination strategies—which focus on preventing death and severe illness in older adults and specific risk groups—are too narrow and must be expanded to include the prevention of postacute sequelae.

Post-COVID-19 condition or long COVID, which also affects the young and healthy populations, can have a significant public health and economic burden, the investigators pointed out. This justifies a broader immunization strategy.

“SARS-CoV-2 continues to circulate and can infect people. It is estimated that between 5 percent and 10 percent of people infected with SARS-CoV-2 develop long-term symptoms after the acute phase of COVID-19,” they said.

A total of 89 nonrandomized intervention studies were included in the meta-analysis. The pooled population comprised roughly 5.7 million participants. Most studies included adults from the general population, and some involved specific populations such as healthcare workers, veterans, and children/adolescents. Severity of acute SARS-CoV-2 infection in study participants ranged from mild to severe in most studies, and a few focused on outpatients or hospitalized patients.

The investigators highlighted the need for additional research to determine the duration of protection of COVID-19 vaccines against postacute sequelae, define risk groups, and evaluate the VE of regular booster vaccinations given before or after infections, “as most people have acquired hybrid immunity against SARS-CoV-2 by now.”