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

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.).

Mortality in Patients Hospitalized for COVID-19 vs Influenza in Fall-Winter 2023-2024.

This cohort study evaluates the risk of death in patients hospitalized for COVID-19 or seasonal influenza following the emergence of the JN.1 variant in winter 2023.

Solving the puzzle of Long Covid.

Long Covid provides an opportunity to understand how acute infections cause chronic disease.

Long-term outcomes following hospital admission for COVID-19 versus seasonal influenza: a cohort study.

BACKGROUND: Previous comparative analyses of people admitted to hospital for COVID-19 versus influenza evaluated the risk of death, hospital readmission, and a narrow set of health outcomes up to 6 months following infection. We aimed to do a comparative evaluation of both acute and long-term risks and burdens of a comprehensive set of health outcomes following hospital admission for COVID-19 or seasonal influenza. METHODS: For this cohort study we used the health-care databases of the US Department of Veterans Affairs to analyse data from 81 280 participants admitted to hospital for COVID-19 between March 1, 2020, and June 30, 2022, and 10 985 participants admitted to hospital for seasonal influenza between Oct 1, 2015, and Feb 28, 2019. Participants were followed up for up to 18 months to comparatively evaluate risks and burdens of death, a prespecified set of 94 individual health outcomes, ten organ systems, overall burden across all organ systems, readmission, and admission to intensive care. Inverse probability weighting was used to balance the baseline characteristics. Cox and Poisson models were used to generate estimates of risk on both the relative scale and absolute scale as the event rate and disability-adjusted life-years (DALYs) per 100 persons. FINDINGS: Over 18 months of follow-up, compared to seasonal influenza, the COVID-19 group had an increased risk of death (hazard ratio [HR] 1·51 [95% CI 1·45-1·58]), corresponding to an excess death rate of 8·62 (95% CI 7·55-9·44) per 100 persons in the COVID-19 group versus the influenza group. Comparative analyses of 94 prespecified health outcomes showed that COVID-19 had an increased risk of 68·1% (64 of 94) pre-specified health outcomes; seasonal influenza was associated with an increased risk of 6·4% (six of 94) pre-specified health outcomes, including three out of four pre-specified pulmonary outcomes. Analyses of organ systems showed that COVID-19 had a higher risk across all organ systems except for the pulmonary system, the risk of which was higher in seasonal influenza. The cumulative rates of adverse health outcomes across all organ systems were 615·18 (95% CI 605·17-624·88) per 100 persons in COVID-19 and 536·90 (527·38-544·90) per 100 persons in seasonal influenza, corresponding to an excess rate of 78·72 (95% CI 66·15-91·24) per 100 persons in COVID-19. The total number of DALYs across all organ systems were 287·43 (95% CI 281·10-293·59) per 100 persons in the COVID-19 group and 242·66 (236·75, 247·67) per 100 persons in the seasonal influenza group, corresponding to 45·03 (95% CI 37·15-52·90) higher DALYs per 100 persons in COVID-19. Decomposition analyses showed that in both COVID-19 and seasonal influenza, there was a higher burden of health loss in the post-acute than the acute phase; and comparatively, except for the pulmonary system, COVID-19 had a higher burden of health loss across all other organ systems than seasonal influenza in both the acute and post-acute phase. Compared to seasonal influenza, COVID-19 also had an increased risk of hospital readmission (excess rate 20·50 [95% CI 16·10-24·86] per 100 persons) and admission to intensive care (excess rate 9·23 [6·68-11·82] per 100 persons). The findings were consistent in analyses comparatively evaluating risks in seasonal influenza versus COVID-19 by individuals' respective vaccination status and in those admitted to hospital during the pre-delta, delta, and omicron eras. INTERPRETATION: Although rates of death and adverse health outcomes following hospital admission for either seasonal influenza or COVID-19 are high, this comparative analysis shows that hospital admission for COVID-19 was associated with higher long-term risks of death and adverse health outcomes in nearly every organ system (except for the pulmonary system) and significant cumulative excess DALYs than hospital admission for seasonal influenza. The substantial cumulative burden of health loss in both groups calls for greater prevention of hospital admission for these two viruses and for greater attention to the care needs of people with long-term health effects due to either seasonal influenza or SARS-CoV-2 infection. FUNDING: US Department of Veterans Affairs.

Three-year outcomes of post-acute sequelae of COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes post-acute sequelae of coronavirus disease 2019 (COVID-19) (PASC) in many organ systems. Risks of these sequelae have been characterized up to 2 years after infection, but longer-term follow-up is limited. Here we built a cohort of 135,161 people with SARS-CoV-2 infection and 5,206,835 controls from the US Department of Veterans Affairs who were followed for 3 years to estimate risks of death and PASC. Among non-hospitalized individuals, the increased risk of death was no longer present after the first year of infection, and risk of incident PASC declined over the 3 years but still contributed 9.6 (95% confidence interval (CI): 0.4-18.7) disability-adjusted life years (DALYs) per 1,000 persons in the third year. Among hospitalized individuals, risk of death declined but remained significantly elevated in the third year after infection (incidence rate ratio: 1.29 (95% CI: 1.19-1.40)). Risk of incident PASC declined over the 3 years, but substantial residual risk remained in the third year, leading to 90.0 (95% CI: 55.2-124.8) DALYs per 1,000 persons. Altogether, our findings show reduction of risks over time, but the burden of mortality and health loss remains in the third year among hospitalized individuals.

Long COVID science, research and policy.

Long COVID represents the constellation of post-acute and long-term health effects caused by SARS-CoV-2 infection; it is a complex, multisystem disorder that can affect nearly every organ system and can be severely disabling. The cumulative global incidence of long COVID is around 400 million individuals, which is estimated to have an annual economic impact of approximately $1 trillion-equivalent to about 1% of the global economy. Several mechanistic pathways are implicated in long COVID, including viral persistence, immune dysregulation, mitochondrial dysfunction, complement dysregulation, endothelial inflammation and microbiome dysbiosis. Long COVID can have devastating impacts on individual lives and, due to its complexity and prevalence, it also has major ramifications for health systems and economies, even threatening progress toward achieving the Sustainable Development Goals. Addressing the challenge of long COVID requires an ambitious and coordinated-but so far absent-global research and policy response strategy. In this interdisciplinary review, we provide a synthesis of the state of scientific evidence on long COVID, assess the impacts of long COVID on human health, health systems, the economy and global health metrics, and provide a forward-looking research and policy roadmap.