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

Abstract

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.).

Figure 1. Study Cohorts.

T0 for persons in the coronavirus disease 2019 (Covid-19) cohorts was defined as the date of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. T0 for persons in the control cohorts was assigned according to the distribution of T0 in the Covid-19 cohorts. VA denotes Veterans Affairs.

Figure 2. Cumulative Incidence of Postacute Sequelae of SARS-CoV-2 Infection (PASC) in the Pre-Delta, Delta, and Omicron Eras According to Vaccination Status.

Shown is the cumulative incidence of PASC at 1 year after SARS-CoV-2 infection among unvaccinated persons during the pre-delta, delta, and omicron eras and among vaccinated persons during the delta and omicron eras. Also shown are selected comparisons (presented as differences on the absolute scale) within and between the cohorts. 𝙸 bars indicate 95% confidence intervals.

Figure 3. Decomposition Analyses of the Influence of Pandemic Era and Vaccines on PASC.

Shown in Panel A is the cumulative incidence of PASC at 1 year after SARS-CoV-2 infection in the omicron and pre-delta cohorts (top), the absolute reduction in the cumulative incidence in the omicron cohort as compared with the pre-delta cohort (middle), and the percentage of the reduction in the cumulative incidence that was attributable to era-related effects (e.g., changes in the characteristics of SARS-CoV-2) and vaccines (bottom). Shown in Panel B is the cumulative incidence of PASC at 1 year in the omicron and delta cohorts (top), the absolute reduction in the cumulative incidence in the omicron cohort as compared with the delta cohort (middle), and the percentage of the reduction that was attributable to era-related effects and vaccines (bottom). Shown in Panel C is the cumulative incidence of PASC at 1 year in the omicron cohort and the pre-delta and delta cohorts combined (top), the absolute reduction in the cumulative incidence in the omicron cohort as compared with the pre-delta and delta cohorts combined (middle), and the percentage of the reduction that was attributable to era-related effects and vaccines (bottom). Data include all the vaccinated and unvaccinated persons in the study. 𝙸 bars indicate 95% confidence intervals.

Figure 4. Disability-Adjusted Life-Years Due to PASC in the Pre-Delta, Delta, and Omicron Eras According to Vaccination Status.

Shown in Panel A are cumulative disability-adjusted life-years (DALYs) due to PASC per 100 persons from 30 days to 1 year after infection among unvaccinated persons during the pre-delta, delta, and omicron eras and among vaccinated persons during the delta and omicron eras. Shaded areas indicate 95% confidence intervals. Shown in Panel B are DALYs due to PASC per 100 persons at 1 year among unvaccinated persons during the pre-delta, delta, and omicron eras and among vaccinated persons during the delta and omicron eras and selected comparisons (presented as differences on the absolute scale) within and between the cohorts. 𝙸 bars indicate 95% confidence intervals.