Vaccine may limit long-COVID impact, studies show, but controlled trials needed

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Two new observational studies suggest that COVID-19 vaccination lowers long-COVID incidence and severity, although the authors of a related commentary say trials comparing vaccination with a placebo are needed. The research was published yesterday in BMJ Medicine.

Vaccine tied to double remission rate

French researchers compared the outcomes of 455 patients enrolled in a nationwide long-COVID cohort by May 2021 who had received at least one post-infection vaccine dose with those of unvaccinated controls.

By 120 days, the average number of long-COVID symptoms had declined in the vaccinated compared with the unvaccinated group (13.0 vs 14.8), and the rate of remission among the vaccinated had doubled (16.6% vs 7.5%; hazard ratio, 1.93). Long COVID also appeared to have a lesser effect on vaccinated patients' lives (average impact score, 24.3 vs 27.6).

The authors conclude, "We found that covid-19 vaccination reduced the severity of symptoms and the effect of long covid on patients' social, professional, and family lives in those who already have persistent symptoms of infection."

Vaccination reduced the severity of symptoms and the effect of long covid on patients' social, professional, and family lives.

While the results seem promising, a commentary by Frances Edwards, MBChB, and Fergus Hamilton, MBChB, both of the UK's North Bristol NHS Trust, points out that the study took place before the Delta and Omicron variant waves and that no patients were vaccinated before infection, limiting its relevance to today's pandemic landscape.

They write, "Given new and existing evidence, covid-19 vaccination is likely to have some beneficial effect on long covid through reducing case severity as well as incidence. However, estimating the size of the effect (and the effect of further vaccine doses) remains a challenge in observational data.

Edwards and Hamilton add, "While these studies are encouraging, trials comparing vaccination with placebo in patients with long covid (as defined by WHO [World Health Organization] criteria) are required to definitively recommend for or against vaccination to improve symptoms of long covid."

Review shows low evidence

The second study, a systematic review by Australian researchers, compared the effect of COVID-19 vaccination before and after infection in 16 observational studies involving 614,392 students published from January 2020 to August 2022.

Of 12 studies that reported data on vaccination before infection, 10 showed a reduced rate of long COVID (odds ratios [ORs] after one vaccine dose, 0.22 to 1.03; two doses, 0.25 to 1.00; three doses, 0.16; and any dose, 0.48 to 1.01. Five studies on vaccination after infection showed ORs of 0.38 to 0.91.

The authors, however, noted the high study heterogeneity. "The studies failed to adjust for potential confounders, such as other protective behaviours and missing data, thus increasing the risk of bias and decreasing the certainty of evidence to low," they wrote.

While these studies are encouraging, trials comparing vaccination with placebo in patients with long covid ... are required.

The study authors conclude, "More robust comparative observational studies and trials are needed, however, to clearly determine the effectiveness of vaccines in preventing and treating long covid."

Until trials compare long-COVID outcomes after vaccination versus placebo, Edwards and Hamilton say, vaccination should continue to be based on the prevention of infection, hospitalization, and death.

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