In a recent study published in Nature Medicine, researchers comprehensively assessed the risks and burdens of post-acute sequelae of coronavirus disease 2019 (PASC) in hospitalized and non-hospitalized settings for the acute phase of COVID-19 in two years post-infection.
Study: Postacute sequelae of COVID-19 at 2 years. Image Credit: DraganaGordic/Shutterstock.com
Background
Post-acute consequences of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection include elevated risks and health burdens of metabolic illnesses (dyslipidemia and diabetes), cardiovascular disease, psychiatric and neurologic problems, and gastrointestinal (GI) and renal disorders.
However, the data is primarily restricted to the first year after acute COVID-19. Addressing this research gap will provide valuable insights into the post-acute and longer-term trajectories of COVID-19 and influence post-COVID treatment recommendations.
About the study
In the present study, researchers characterized PASC risks and burdens across organ systems up to two years after acute COVID-19, which could inform care pathways and healthcare capacity planning.
The researchers used national healthcare records from the United States Veterans Affairs Department (VA) to create a group of 138,818 individuals who lived beyond the initial 30.0 days of acute infection and a group of 5,985,227 uninfected US Veterans Health Administration (VHA) users (controls).
Participants in the trial were tracked for two years to assess the hospitalization, mortality, and 80 pre-specified PASC outcome risks among hospitalized and non-hospitalized individuals.
Following acute COVID-19, the post-acute phase was classified into the following periods: 30 to 90 days, 91 to 180 days, 181 to 360 days, 361 to 540 days, and 541 to 720 days.
For baseline factors such as age, race, gender, body mass index (BMI), smoking behaviours, area deprivation index (ADI), and medical conditions, inverse probability weighting was used. A conditional modelling technique was used to perform sensitivity analyses, correcting for vaccination status and healthcare consumption throughout the follow-up period.
Furthermore, the researchers assessed the outcomes for individuals who had one or more healthcare visits during the analyzed periods.
During follow-up, the researchers additionally assessed the link between SARS-CoV-2 infections and new-onset tumors as a negative control. COVID-19 was identified using polymerase chain reaction (PCR) and SARS-CoV-2 antigen testing.
Results
The mean participant ages in the SARS-CoV-2-infected and uninfected groups were 61 years and 63 years, respectively. The proportions of females in the corresponding groups were 11% and 9.9%, respectively. Among 138,818 SARS-CoV-2-infected individuals, 20,580 were hospitalized and 118,238 were non-hospitalized during acute coronavirus disease 2019.
The median duration of follow-up in the uninfected and infected groups were 719.0 and 715.0 days, contributing to 11,181,224 and 255,119 individual-years for follow-up, respectively, and altogether, 11,436,344 individual-years for follow-up.
The increased mortality risk was non-significant beyond six months (probable risk horizon: three months to one year) post-infection among non-hospitalized individuals but remained significantly increased through two years post-infection among hospitalized individuals.
Within the PASC outcomes, 69% and 35% of outcomes turned non-significant two years post-infection among non-hospitalized and hospitalized patients, respectively, including risks of neurologic, cardiovascular, psychological, and renal outcomes.
Cumulatively, at two years, post-acute sequelae of COVID-19 contributed 80 and 643 disability-adjusted life years (DALYs) among every 1,000 individuals among non-hospitalized and hospitalized individuals, respectively; 25% and 21% of the cumulative two-year DALYs in non-hospitalized and hospitalized individuals were from the subsequent follow-up year.
The risks of PASC outcomes such as hematologic and coagulation disorders, fatigue, pulmonary diseases, musculoskeletal diseases, diabetes, and gastrointestinal disorders remained increased two years post-infection in the non-hospitalized compared to controls.
Similar results were obtained in the sensitivity analyses, indicating that the primary findings were robust. There was no relationship between COVID-19 and neoplastic incidence in the analysis periods.
Among non-hospitalized individuals, 24 PASC risks continued to remain high, including several musculoskeletal, neurologic, and gastrointestinal sequelae, indicating a longer risk horizon concerning the organs involved.
Among indiviudals hospitalized during acute COVID-19, hospitalization, death, and 50 PASC risks, denoting all organ systems, remained significantly high at two years, indicating the protracted and difficult course of recovery among individuals hospitalized during acute COVID-19.
Conclusions
Overall, the study findings showed that while the odds of several post-acute sequelae decreased and were statistically insignificant with time, the drop was less dramatic in individuals hospitalized during acute COVID-19. The findings underscore the cumulative burden of health loss caused by PASC and call for attention to the care requirements of patients suffering from long-term SARS-CoV-2 health impacts.
Population health policy must continue to prioritize measures to lower the post-acute and longer-term COVID-19 sequelae risks in SARS-CoV-2-infected individuals.
The health loss burden would not only affect patients’ life quality, but may also lead to lowered life expectancy, workforce engagement, financial productivity, and social well-being.
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