A large UK study in BMJ suggests that COVID-19 vaccination after infection lowers the odds of persistent symptoms, with a 12.8% initial decline after the first dose and an 8.8% drop after the second—although the long-term effects are unclear.
Published this week, the observational study included 28,356 participants aged 18 to 69 years in the Office for National Statistics COVID-19 Infection Survey who had received one or more doses of the AstraZeneca/Oxford adenovirus vector or the Pfizer/BioNTech or Moderna mRNA vaccines after COVID-19 infection.
The team, led by researchers from the Office for National Statistics, monitored participants from Feb 3 to Sep 5, 2021, to identify those with COVID-19 infections and symptoms lasting at least 12 weeks. The study period spanned the emergence and dominance of the SARS-CoV-2 Delta variant but preceded the emergence of Omicron.
Participants answered survey questions and underwent COVID-19 polymerase chain reaction (PCR) testing once weekly for 1 month and then monthly for a year or longer, and those in households in which a household contact had tested positive for COVID-19 were asked to provide monthly blood samples for SARS-CoV-2 antibody testing.
Average participant age was 46 years, 55.6% were women, and 88.7% were White. Follow-up was a median of 141 days after the first COVID-19 vaccine dose for all participants and 67 days after the second dose for the 83.8% who received both doses.
Lower odds of long COVID after first dose
Among the 28,356 participants, 23.7% reported long COVID symptoms of any severity once or more during follow-up. One vaccine dose was tied to an initial 12.8% reduction in the likelihood of long COVID, followed by increases and decreases (0.3% weekly; 95% confidence interval [CI], -0.6% to 1.2%).
A second vaccine dose was linked to an initial 8.8% (95% CI, -14.1% to -3.1%) reduction in the risk of lingering symptoms, declining 0.8% per week (95% CI, -1.2% to -0.4%) thereafter. The results didn't differ by sociodemographic factors, health status, hospital admission for the initial infection, vaccine type, or time from diagnosis to vaccination.
Of all participants, 16.7% reported that long COVID symptoms limited their ability to participate in activities at least once during follow-up. A first vaccine dose was tied to an initial 12.3% (95% CI, −19.5% to −4.5%) reduction in the chances of activity-limiting long COVID effects (0.9% per week; 95% CI, −0.2% to 1.9%) until receipt of a second dose. A second dose was linked to an initial 9.1% decline (95% CI, −15.6% to −2.1%) in the likelihood of activity-limiting long COVID, followed by a 0.5% reduction per week (95% CI, −1.0% to 0.05%) until the last follow-up.
The risk of long COVID after a first dose of COVID-19 vaccine fell over time from infection, at 24.8%, 16.5%, and 4.8% for participants who received their first dose 9, 12, and 15 months after diagnosis.
The likelihood of experiencing most symptoms, as well as more than three or five symptoms at once, declined after each vaccination, with the largest reductions in loss of smell (−12.5%), loss of taste (−9.2%), and poor sleep (−8.8%). After the second dose, the largest declines occurred in fatigue (−9.7%), headache (−9.0%), and poor sleep (−9.0%).
The probability of experiencing most individual symptoms and more than three or five symptoms at once fell after the first dose. Trends were mostly positive between the first and second doses, but most returned to a declining or flat trend after the second.
Clear explanation 'still lacking'
"People with long COVID who experience dysregulation of the immune system may benefit from autoimmune processes being 'reset' by vaccination (although whether this is long lasting remains to be established), while any residual viral reservoir may also be destroyed by the antibody response," the authors wrote.
While the observational nature of the study precludes establishment of causality, "vaccination may contribute to a reduction in the population health burden of long COVID," they concluded.
In a related editorial, Manoj Sivan, MD, of the University of Leeds in England; Trisha Greenhalgh, MD, of the University of Oxford; Ruairidh Milne, MBBS, of the University of Southampton; and Brendan Delaney, BMBCh, of Imperial College London, said the results show that vaccination is likely to avert long COVID in only a low percentage of patients.
"A clear explanation for how vaccines might reduce the multisystem manifestations of long COVID is still lacking," they wrote. "Particularly for people already well past the stage of systemic inflammatory responses, and those with end organ damage from COVID-19, such as lung fibrosis."
While the benefits of vaccination outweigh the potential risks and is particularly important for long-COVID patients, Sivan and colleagues said that much remains unknown about the effects of recurrent infection or booster doses and the long-term prognosis.