COVID-19 vaccination within six months before first infection significantly reduces the risk of developing long COVID in adolescents by 36%, according to a comprehensive analysis of data from the Researching COVID to Enhance Recovery Initiative (RECOVER-Pediatrics) published in Vaccine. The study represents one of the most robust examinations of vaccination's protective effects against long COVID in pediatric populations to date.
Study Design and Population
The research analyzed data from 1,231 adolescents aged 12 to 17 years, including 724 vaccinated participants and 507 unvaccinated controls matched on sex, first infection date, and enrollment date. Participants were recruited from more than 60 healthcare and community settings between February 7, 2022, and November 14, 2024, during the predominance of the Omicron variant.
The study utilized caregiver-reported survey data to assess the association between vaccination status and long COVID development. Researchers defined exposure as any COVID-19 vaccine dose received within 6 months and 14 days before the first COVID-19 infection, with 86% of vaccinated participants having received at least two doses within 18 months prior to infection.
Primary Findings
Among infected adolescents, long COVID risk was 20.7% in unvaccinated participants compared to 13.3% in vaccinated participants, yielding a relative risk of 0.64 (95% CI, 0.50-0.83). For severe long COVID, the risks were 6.1% and 4.7% in unvaccinated and vaccinated groups respectively (relative risk, 0.77; 95% CI, 0.48-1.26).
The researchers defined long COVID using a weighted summary of eight associated symptoms: loss of smell/taste, body/joint pain, fatigue, post-exertional malaise, back/neck pain, cognitive difficulties, headache, and lightheadedness. Symptoms were counted if present for at least four weeks post-infection and at enrollment (at least 90 days post-infection), with a total score of 5 or greater indicating long COVID.
Mechanisms of Protection
The study identified three distinct mechanisms by which COVID-19 vaccination can reduce long COVID risk. First, vaccination prevents COVID-19 infection, indirectly lowering the risk of long COVID. Second, it can reduce infection severity, which is associated with a higher likelihood of developing long COVID. Third, vaccination may mitigate the longer-term pathophysiologic response to infection even when breakthrough infections occur.
"The COVID-19 vaccine is relatively unique in having this effect on progression to a chronic condition, despite infection," the researchers noted. "This highlights that even if infection occurs, recent vaccination still has a protective effect on LC risk."
Clinical Implications
The findings carry particular significance given the limited treatment options available for long COVID in adolescents. The researchers described long COVID as "a significant public health problem for children and adolescents, with health, educational, familial, and economic costs," noting that the condition is understudied in children, with adolescents potentially at the highest risk.
"Given the profound impact LC can have on the health and well-being of adolescents and the limited availability of treatments during this developmental stage, this supports vaccination as a strategy for preventing LC by demonstrating an important secondary prevention effect," the authors concluded.
Study Limitations and Context
The researchers acknowledged several limitations, including caregiver-reported vaccination status, which may have introduced recall bias. Additionally, they only assessed vaccinations before the first infection and focused on long COVID present at enrollment, not considering intermittent lingering symptoms or subclinical long COVID.
Prior studies have established protective effects of vaccination against long COVID in adults, but evidence in pediatric populations has been limited and sometimes conflicting. Most previous studies were electronic health records-based or only included patients from post-COVID clinics, making this RECOVER-Pediatrics analysis particularly valuable for its comprehensive community-based approach.
The authors suggested their estimate of vaccine effectiveness beyond infection prevention may be conservative, given the study's focus on persistent symptoms present at enrollment rather than the full spectrum of long COVID manifestations.
