A large staggered cohort study from primary care patients in the UK, Spain, and Estonia finds that COVID-19 vaccination consistently reduced the risk of long-COVID symptoms. The study is published in The Lancet Respiratory Medicine.
The study used the World Health Organization’s (WHO) definition of post COVID condition, or long COVID, as new or persisting symptoms 3 months after infection that cannot be explained by alternative causes. The WHO recognizes 25 long COVID symptoms, including fatigue, shortness of breath, and cognitive dysfunction.
In total, more than 10 million vaccinated people and 10 million unvaccinated people from each of the three countries and four databases were compared, and effectiveness of vaccination with either ChAdOx1 (AstraZeneca) and BNT162b2 (Pfizer-BioNTech) was assessed.
"For each database and country, we created four study cohorts, with each of them representing a specific stage of the national vaccination campaign rollout," the authors explained. "We defined long COVID as having at least one record of any of the pre-defined symptoms between 90 and 365 days after the date of a PCR-positive test or clinical diagnosis of COVID-19, with no record of that symptom 180 days before SARS-CoV-2 infection."
VE of 29% to 52% for long COVID
Across all four staggered cohorts in all three countries, vaccination was associated with a lowered risk of developing long COVID. And a slightly stronger preventative effect was seen for the first dose of BNT162b2 than for ChAdOx1, the authors said.
Vaccine efficacy (VE) against long COVID ranged from 29% to 52%.
The hazard ratio (HR) for long COVID symptoms in people vaccinated with a first dose of any COVID-19 vaccine were 0.54 (95% confidence interval [CI], 0.44 to 0.67) and, 0.48 (0.34 to 0.68) for the UK cohorts. In Spain the HR was 0.71 (0.55 to 0.91), and in Estonia the HR was 0.59 (0.40 to 0.87).
To our knowledge, this is the first multinational study assessing population-level vaccine effectiveness to prevent long COVID symptoms.
"To our knowledge, this is the first multinational study assessing population-level vaccine effectiveness to prevent long COVID symptoms," the authors concluded. "These findings were robust to multiple sensitivity analyses and various definitions of long COVID, including different duration of symptoms and clinically diagnosed long COVID in a secondary analysis."
Several recent studies have shown varying VE for COVID-19 vaccines against long COVID, including a recent meta-analysis which showed a 69% VE when three doses of vaccine were used.
In other long COVID research, in Switzerland, among those who remained outpatients during their first SARS-CoV-2 infection, women reported long-COVID symptoms more often than men (40.5% vs 25.5%).
However, there was no different rates between the sexes among long COIVD patients that had required hospitalization.
"The reasons for the differential impact of sex and gender in outpatients vs hospitalized patients can only be hypothesized, but might be attributed to the substantial differences in baseline characteristics between hospitalized patients and outpatients,” the authors said.
Hospitalized patients were significantly older, with more comorbidities, and had cardiovascular risk factors.
