Postacute Sequelae of SARS-CoV-2 Infection in the Pre-Delta, Delta, and Omicron Eras

Jul 17, 2024The New England journal of medicine

Long-term effects after COVID-19 infection during the Pre-Delta, Delta, and Omicron periods

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Abstract

The cumulative incidence of postacute sequelae of SARS-CoV-2 infection decreased from 10.42 events per 100 persons in the pre-delta era to 7.76 events per 100 persons in the omicron era among unvaccinated individuals.

Cumulative incidence of postacute sequelae decreased by 2.66 events per 100 persons when comparing the omicron to the pre-delta era.
Among vaccinated individuals, cumulative incidence of postacute sequelae was lower at 3.50 events per 100 persons during the omicron era compared to 5.34 events per 100 persons in the delta era.
Vaccinated persons had a significantly lower risk of postacute sequelae compared to unvaccinated persons, with a difference of 4.18 events per 100 persons during the delta era.
Decomposition analyses indicated that 28.11% of the decrease in postacute sequelae events during the omicron era was associated with changes in the virus and other temporal effects, while 71.89% was attributed to vaccinations.
Despite the decrease, the risk of postacute sequelae remained substantial among vaccinated individuals infected during the omicron era.

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BACKGROUND: Postacute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC) can affect many organ systems. However, temporal changes during the coronavirus disease 2019 (Covid-19) pandemic, including the evolution of SARS-CoV-2, may have affected the risk and burden of PASC. Whether the risk and burden of PASC have changed over the course of the pandemic is unclear.

METHODS: We used health records of the Department of Veterans Affairs to build a study population of 441,583 veterans with SARS-CoV-2 infection between March 1, 2020, and January 31, 2022, and 4,748,504 noninfected contemporaneous controls. We estimated the cumulative incidence of PASC at 1 year after SARS-CoV-2 infection during the pre-delta, delta, and omicron eras of the Covid-19 pandemic.

RESULTS: Among unvaccinated persons infected with SARS-CoV-2, the cumulative incidence of PASC during the first year after infection was 10.42 events per 100 persons (95% confidence interval [CI], 10.22 to 10.64) in the pre-delta era, 9.51 events per 100 persons (95% CI, 9.26 to 9.75) in the delta era, and 7.76 events per 100 persons (95% CI, 7.57 to 7.98) in the omicron era (difference between the omicron and pre-delta eras, -2.66 events per 100 persons [95% CI, -2.93 to -2.36]; difference between the omicron and delta eras, -1.75 events per 100 persons [95% CI, -2.08 to -1.42]). Among vaccinated persons, the cumulative incidence of PASC at 1 year was 5.34 events per 100 persons (95% CI, 5.10 to 5.58) during the delta era and 3.50 events per 100 persons (95% CI, 3.31 to 3.71) during the omicron era (difference between the omicron and delta eras, -1.83 events per 100 persons; 95% CI, -2.14 to -1.52). Vaccinated persons had a lower cumulative incidence of PASC at 1 year than unvaccinated persons (difference during the delta era, -4.18 events per 100 persons [95% CI, -4.47 to -3.88]; difference during the omicron era, -4.26 events per 100 persons [95% CI, -4.49 to -4.05]). Decomposition analyses showed 5.23 (95% CI, 4.97 to 5.47) fewer PASC events per 100 persons at 1 year during the omicron era than during the pre-delta and delta eras combined; 28.11% of the decrease (95% CI, 25.57 to 30.50) was attributable to era-related effects (changes in the virus and other temporal effects), and 71.89% (95% CI, 69.50 to 74.43) was attributable to vaccines.

CONCLUSIONS: The cumulative incidence of PASC during the first year after SARS-CoV-2 infection decreased over the course of the pandemic, but the risk of PASC remained substantial even among vaccinated persons who had SARS-CoV-2 infection in the omicron era. (Supported by the Department of Veterans Affairs.).

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Postacute Sequelae of SARS-CoV-2 Infection in the Pre-Delta, Delta, and Omicron Eras

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