More mRNA COVID-19 Vaccine Doses Associated with Lower Risk of Long COVID

Being fully vaccinated and boosted against COVID-19 provided the most protection against long COVID, a recent study of health care workers in Italy found.

The study, described in a research letter in JAMA, included 2560 workers at 9 Italian health care facilities between March 2020 and March 2022. All workers were tested every one or two weeks for SARS-CoV-2 infection and received a two-dose primary series of Pfizer-BioNTech’s mRNA COVID-19 vaccine in January and February 2021 followed by a booster dose in November and December.

“Having the opportunity to follow a small (2570 individuals) but very well characterized population of healthcare workers for two years we show that two and, even more so, three doses of mRNA vaccine associate with reduction of Long COVID (at least one symptom persisting over 4 weeks) prevalence,” corresponding author Maria Rescigno, PhD, Humanitas University told Contagion. “We excluded the population of hospitalized patients to evaluate the effect on less severe disease as vaccination already reduces the risk of severe disease.”

Study participants completed surveys between February and April 2022, and long COVID was defined as reporting at least one COVID-19 symptom for more than four weeks. The study excluded hospitalized patients and those whose SARS-CoV-2 infection occurred less than 28 days before the survey.

Participants were broken into groups by date of infection corresponding to variant prevalence, including those who tested positive between February and September 2020, when the wild-type variant was prevalent; those who tested positive from October 2020 to July 2021, during the Alpha wave; and those who tested positive between August 2021 and March 2022, when the Delta and Omicron variants were dominant.

“By adopting a multivariable logistic regression analysis we found that vaccination but not virus variant was associated with reduced Long COVID,” Rescigno said. “We also confirmed that women which are less prone to severe COVID disease are instead more likely to develop Long COVID.”

The study included 739 participants who tested positive for SARS-CoV-2 during the study period, including 89 of whom were asymptomatic and 229 who had long COVID.

“This research could help clinicians and health care providers to promote vaccination as it may not only protect from severe disease but also from Long COVID,” Rescigno said.

Long COVID was most common during the first wave, affecting 48.1% of participants, followed by 35.9% in the second wave and 16.5% in the third wave. Long COVID was most common in those who weren’t vaccinated, affecting 41.8%, followed by 30% of those who had received one dose of a COVID-19 vaccine, 17.4% who had two doses and 16% of those with three doses.

Long COVID also was more likely among participants with older age, higher body mass index, allergies and obstructive lung disease.

“Next steps are to monitor the evolvement of new vaccines which cover also against new variants of concern of the virus,” Rescigno said.

The study is consistent with previous research, including a study published in September in The Lancet that found that those who received a second dose of a COVID-19 vaccine were 49% less likely to develop long COVID.

The effects of long COVID are costly.

Based on May 5 estimates, more than 9.6 million people in the United States may have developed long COVID, and lost income could amount to an estimated $50 billion a year, David M. Cutler, PhD, of the Department of Economics and Kennedy School of Government at Harvard University, wrote in a related article in JAMA. Annual health care costs to treat long COVID could be around $9000 per person, he said.