Accumulating research suggests reinfections with SARS-CoV-2 increase the likelihood of developing long COVID, the horrific post-acute syndrome with indefinite duration and a panoply of neurological, autoimmune, and physical conditions.
Moreover, the risk of developing long COVID incrementally increases with each reinfection, according to a study that found this cumulative effect continues in up to three reinfections.1
“We started seeing patients coming back to the clinic, saying they have been infected, vaccinated, and are super-immune. They don’t have to worry about reinfection,” said study co-author Ziyad Al-Aly, MD, a researcher in the Clinical Epidemiology Center in Veteran Affairs St. Louis Health Care System. “We decided to look at this — is reinfection totally inconsequential, specifically when it comes to long COVID? The answer is, it is not inconsequential.”
Comparing a group who had been reinfected, some multiple times, to those who had not been reinfected, “[the results] specifically showed that two infections are worse than one and three infections are worse than two,” Al-Aly noted. “Don’t interpret this as the second infection is more severe than the first. What we’re saying is that cumulatively, the adverse health effects from two infections are worse than only one; the adverse health effects from three infections are worse than two. Reinfection remains consequential (as a risk for long COVID) at least up to three infections.”
“Compared to people with no reinfection, people who had reinfection exhibited increased risks of all-cause mortality, hospitalization, and several prespecified outcomes,” Al-Aly and colleagues concluded. “The risks were evident in those who were unvaccinated and had one vaccination or two or more vaccinations before reinfection.”
The authors of a different study projected that the number of long COVID cases is expected to increase as SARS-CoV-2 reinfections become more frequent.
“A possible link between SARS-CoV-2 reinfections and the consequent higher likelihood of long COVID becomes crucial as the COVID-19 pandemic is now waning amid widespread relaxation of social distancing and other restrictions, causing many people to become infected multiple times,” the authors noted. “Some studies have shown an increased risk of long COVID after SARS-CoV-2 reinfection even in vaccinated individuals. … [However], evidence is accumulating to support vaccination, both pre- and post-SARS-CoV-2 infection, as a preventive strategy to reduce the risk of long COVID.”2
The Protective Effect
One such study in adults in Sweden found that COVID-19 vaccination before initial SARS-CoV-2 infection is protective against long COVID in a stepwise fashion: 21% for one dose, 59% for two doses, and 73% for three or more doses.3 The authors of an accompanying editorial said the study shows that COVID-19 vaccines “have a clear and clinically important protective effect against post-COVID-19 condition[s].”4
The population study in Sweden looked at 589,722 people age 18 years or older who had COVID-19 between Dec. 27, 2020, to Feb. 9, 2022. Individuals who had received at least one dose of a COVID-19 vaccine before infection were considered vaccinated. The primary outcome was a clinical diagnosis of post-COVID conditions (PCC).3
Of 299,692 vaccinated individuals with COVID-19, 1,201 (0.4%) had a diagnosis of long COVID during follow-up, compared with 4,118 (1.4%) of 290,030 unvaccinated individuals.
“COVID-19 vaccination with any number of doses before infection was associated with a reduced risk of PCC, with a vaccine effectiveness of 58%,” the authors reported. “Of the vaccinated individuals, 21,111 received one dose only, 205,650 received two doses, and 72,931 received three or more doses.”
Again, there was protection across all groups, but those who had received three or more vaccine doses had a 73% reduced risk of long COVID.
“The results of this study suggest a strong association between COVID-19 vaccination before infection and reduced risk of receiving a diagnosis of PCC,” the authors concluded.
In addition to the obvious benefits revealed, the study also serves to confirm the existence of long COVID, which some have questioned given the variety of symptoms and the absence of diagnostic biomarkers, the authors of the accompanying editorial observed. The findings also underscore the importance of vaccines for future pandemics.
“Future pandemic preparedness plans should continue to prioritize prompt manufacture, evaluation, and distribution of vaccines, and mass vaccination to reduce a pandemic’s impact on health,” the editorial authors noted. “Although vaccines have adverse effects, including some that are rare but can lead to considerable disability, the benefits of vaccination for both individuals and populations far outweigh the risks.”4
While the Swedish study looked at an adult population, vaccine protection before the first infection intuitively implies some benefit for children.
A meta-analysis5 of recent studies estimated that 1% to 3% of children have one or more long COVID symptoms after SARS-CoV-2 infection, said Anna Yousaf, MD, a CDC medical offer at the Centers for Disease Control and Prevention (CDC).
“The CDC estimates that over 65 million children in the U.S. have had SARS-CoV-2 infection since January 2023, meaning there’s the potential for thousands of children in the U.S. to have post-COVID conditions,” Yousaf said. “Data in adults show that COVID-19 vaccination prior to SARS-CoV-2 infection does reduce the likelihood of post-COVID conditions. There’s very little data on COVID-19 vaccination in children in post-COVID conditions.”
Using an existing CDC database, Yousaf and colleagues studied 622 children ages 5 to 17 years. Twenty-eight children had long COVID, and 594 controls did not develop the condition.
“The outcome of interest was an estimate of the odds of one or more post-COVID condition, one or more respiratory post-COVID condition symptom, or one or more non-respiratory post-COVID condition symptom in COVID-19-vaccinated children compared to unvaccinated children,” Yousaf said. “We found that mRNA COVID-19 vaccination prior to SARS-CoV-2 omicron variant infection appeared to be protective against post-COVID conditions in children, with a 34% reduced likelihood of one or more post-COVID conditions, a 47% reduced likelihood of respiratory post-COVID conditions, and a 48% reduced likelihood of two or more post-COVID condition symptoms. These data support COVID-19 vaccination for children.”
Unfortunately, COVID-19 vaccine uptake is low across all age ranges, but the potential that it could prevent or reduce the effect of long COVID could be leveraged in future immunization campaigns.
“[These findings may] encourage increased pediatric vaccine uptake in a population that typically does not experience severe COVID-19 illness,” Yousaf said.
REFERENCES
- Bowe B, Xie Y, Al-Aly Z. Acute and postacute sequelae associated with SARS-CoV-2 reinfection. Nat Med 2022;28:2398-2405.
- Boufidou F, Medic S, Lampropoulou V, et al. SARS-CoV-2 reinfections and long COVID in the post-omicron phase of the pandemic. Int J Mol Sci 2023;24:12962.
- Lundberg-Morris L, Leach S, Martikainen J, et al. Covid-19 vaccine effectiveness against post-covid-19 condition among 589,722 individuals in Sweden: Population based cohort study. BMJ 2023;383:e076990.
- Sivan M, Ormerod M, Maini R. Does timely vaccination help prevent post-viral conditions? BMJ 2023;383:2633.
- Morello R, Martino L, Buonsenso D. Diagnosis and management of post-COVID (long COVID) in children: A moving target. Curr Opin Pediatr 2023;35:184-192.
Accumulating research suggests reinfections with SARS-CoV-2 increase the likelihood of developing long COVID, the horrific post-acute syndrome with indefinite duration and a panoply of neurological, autoimmune, and physical conditions. Moreover, the risk of developing long COVID incrementally increases with each reinfection, according to a study that found this cumulative effect continues in up to three reinfections.
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