Risk of Long COVID Has Declined, Largely Due to Vaccination

While the risk of developing long COVID after a SARS-CoV-2 infection remains a persistent threat, it decreased significantly over the course of the COVID-19 pandemic. The decline is largely attributed to vaccination against COVID-19, according to a new study published in New England Journal of Medicine (NEJM).¹

Ziyad Al-Aly, MD

Image credit: Washington University School of Medicine in St. Louis.

Ziyad Al-Aly, MD, a clinical epidemiologist with Washington University School of Medicine in St. Louis and a nephrologist at John J. Cochran Veterans Hospital in St. Louis, said the declining rates of long COVID is a rare occasion of good news regarding COVID-19.² However, he emphasized that long COVID remains a challenge.

Presentation and Prevalence of Long COVID

Long COVID, or postacute sequelae of SARS-CoV-2 (PASC), affects many organ systems, and the risk of developing PASC increases with the severity of infection and the presence of preexisting conditions. The list of reported symptoms of long COVID is extensive and varied, including fatigue, headache, nausea, trouble with sleep, low and high blood pressure, depression, and brain fog.³ People who experience brain fog describe it as forgetfulness and the inability to think clearly, focus attention, or find the right words in a conversation.⁴

An estimated 17 million (6.9%) adults in the US currently had long COVID, according to data from the Medical Expenditure Panel Survey (MEPS) Household Component.⁵ The data were published in JAMA in June. Overall, females were more likely to develop long COVID compared with males (8.6% vs 5.1%), and Hispanic and White adults had higher rates of long COVID than Asian and Black adults.

Echoing the results of the new NEJM study, the analysis of MEPS data found older adults had lower rates of long COVID than midlife adults owing to lower rates of COVID-19 and high rates of booster shots.⁵ Young adults also had lower rates of long COVID compared with midlife adults, which the researchers had attributed to being healthier in general.

Declining Rates of Long COVID Due to Vaccination

Al-Aly and colleagues¹ used the Veterans Affairs Health Care System databases to include 441,583 veterans in 5 cohorts: no vaccination and COVID-19 in the pre-delta era (206,011), no vaccination and COVID-19 during delta (54,002), vaccination and COVID during delta (56,260), no vaccination and COVID-19 during omicron (40,367), and vaccination and COVID-19 during omicron (84,943). The researchers also selected control cohorts of people without COVID-19 infection in the pre-delta era (2,300,313), the delta era (1,174,003), and the omicron era (1,274,199). All individuals in the cohorts with COVID-19 were followed for 1 year to understand the risk and burden of PASC.

For individuals who were not vaccinated, the cumulative incidence of PASC a year after COVID-19 infection was 10.42 events per 100 persons (95% CI, 10.22-10.54) in the pre-delta period, 9.51 events per 100 persons (95% CI, 9.26-9.75) in the delta era, and 7.76 events per 100 persons (95% CI, 7.57-7.98) in the omicron era. At 1 year, the cumulative incidence of PASC was lower among vaccinated people compared with unvaccinated people during the delta and omicron eras. There were 5.34 events per 100 person (95% CI, 5.10-5.58) during the delta era and 3.50 events per 100 persons (95% CI, 3.31-3.71) during the omicron era among the vaccinated individuals.

“You can see a clear and significant difference in risk during the delta and omicron eras between the vaccinated and unvaccinated,” Al-Aly, who is also director of the Clinical Epidemiology Center at the VA St. Louis Health Care System and head of the research and development service, said in a statement.² “So, if people think COVID is no big deal and decide to forgo vaccinations, they’re essentially doubling their risk of developing long COVID.”

Decomposition analyses to understand the contribution of the era and the vaccines on changes in cumulative incidence of PASC found that 71.89% of the decrease of PASC events per 100 persons at 1 year was attributable to the vaccines, and 28.11% was attributable to the era, such as changes in the virus.¹ Al-Aly noted that each variant of the virus “has its own fingerprint,” with different symptoms, such as the original virus hitting the respiratory system harder, while omicron was associated with an increase in diseases and illnesses related to metabolic function and the gastrointestinal system.²

Among the study's limitations was the population, which consisted mostly of older White men, which might mean the findings are not representative of the general population.¹ Also, it is possible that individuals with undiagnosed COVID-19 were misclassified as noninfected controls. In addition, because they did not balance the cohorts at the time of vaccination, some vaccinated persons may have been misclassified as unvaccinated, which would underestimate the benefit of the vaccines.

“We cannot let our guard down,” Al-Aly said.² “This includes getting annual COVID vaccinations because they are the key to suppressing long COVID risk. If we abandon vaccinations, the risk is likely to increase.”

References

1. Xie Y, Choi T, Al-Aly Z. Postacute sequelae of SARS-CoV-2 infection in the pre-delta, delta, and omicron eras. N Eng J Med. doi:10.1056/NEJMoa2403211

2. Risk of long COVID declined over course of pandemic. News release. Washington University in St. Louis. July 17, 2024. Accessed July 17, 2024.

3. Derman C. COVID-19 never truly goes away: long COVID’s debilitating symptoms uproots lives. HCPLive®. March 13, 2024. Accessed July 17, 2024. https://www.hcplive.com/view/covid-19-never-truly-goes-away-long-covids-debilitating-symptoms-uproots-lives

4. Katella K. Long COVID brain fog: what it is and how to manage it. Yale Medicine. May 29, 2024. Accessed July 17, 2024. https://www.yalemedicine.org/news/how-to-manage-long-covid-brain-fog

5. Fang Z, Arhnsbrak R, Rekito A. Evidence mounts that about 7% of US adults have had long COVID. JAMA. 2024;332(1):5-6. doi:10.1001/jama.2024.11370