Studies note higher risk of death, impaired health up to 2 years after COVID infection

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A pair of new studies describe the risks associated with long COVID, with one showing a significantly elevated risk of death among patients who required hospitalization and another finding an increased risk of health problems, functional limitations, and worse well-being after 1 year.

A 'substantial cumulative burden'

Researchers from the Veterans Affairs Saint Louis Health Care System followed 138,818 US veterans (20,580 of them hospitalized and 118,238 not hospitalized) during their COVID-19 infections and 5,985,227 of their uninfected peers for 2 years to estimate their risk of death and 80 long-COVID symptoms.

The study was published yesterday in Nature Medicine.

The average age of the COVID-19 group was 60.9 years, and 11.4% were women. In the control group, the average age was 62.8 years, and 9.9% were women. Median follow-up time was 715 days in the infected group and 719 in the control group.

The increased risk of death was not significant beyond 6 months after infection among nonhospitalized veterans but was significantly elevated through 2 years in those admitted to the hospital. A total of 69% and 35% of the 80 long-COVID signs and symptoms became nonsignificant 2 years after infection in nonhospitalized and hospitalized veterans, respectively.

Among hospitalized veterans, risks at 2 years after infection remained increased for 65% of long-COVID signs and symptoms, including those involving the cardiovascular (57%), coagulation and hematologic (80%), endocrine (100%), gastrointestinal (82%), renal (75%), musculoskeletal (75%), neurologic (60%), pulmonary (100%) systems and for mental health symptoms (38%).

The findings suggest that the risk horizon... is further prolonged among hospitalized individuals—highlighting the importance of reducing risk of hospitalization among people with SARS-CoV-2 infection."

At 2 years, long COVID had cumulatively contributed 80.4 and 642.8 disability-adjusted life years (DALYs) per 1,000 people in nonhospitalized and hospitalized veterans, respectively. Of the cumulative 2-year DALYs, 25.3% and 21.3% in nonhospitalized and hospitalized participants were from year 2.

"While risks of many sequelae declined 2 years after infection, the substantial cumulative burden of health loss due to PASC [postacute sequelae of COVID-19] calls for attention to the care needs of people with long-term health effects due to SARS-CoV-2 infection," the study authors wrote.

"The findings suggest that the risk horizon for postacute sequelae after SARS-CoV-2 infection is prolonged even among nonhospitalized individuals and is further prolonged among hospitalized individuals—highlighting the importance of reducing risk of hospitalization among people with SARS-CoV-2 infection," they added.

Persistent symptoms, new-onset conditions

For the second paper, Robert Koch Institute researchers in Germany conducted a multicenter study on adult COVID-19 patients' health 1 to 1.5 years after their 2020 infections compared with uninfected controls.

Participants in the four regions of the country most affected by COVID-19 in 2020 completed baseline and follow-up questionnaires on recurrent or persistent health problems, new-onset diseases, health-related quality of life, subjective health, and subjective memory impairment from October 2021 to January 2022.

The findings were published yesterday in BMC Public Health.

Of 4,817 participants, 350 (7.3%) had COVID-19 at baseline, and 4,467 were uninfected at baseline or during follow-up. The average age was 49.8 years, slightly more than half were women, 17% were obese, more than a third had an underlying illness, less than 10% were aged 75 or older, and 6 were hospitalized due to COVID-19, but none required intensive care.

Infected participants more often reported 7 of 18 recurrent or persistent symptoms at follow-up, including impaired smell or taste (12.8% vs 3.4%; odds ratio [OR], 4.11), shortness of breath (23.0% vs 9.5%; OR, 3.46), pain with breathing (4.7% vs 1.9%; OR, 2.36), fatigue (36.9% vs 26.1%; OR, 1.76), leg weakness (12.8% vs 7.8%; OR, 1.93), muscle or joint pain (21.9% vs 15.1%; OR, 1.53), and cough (30.8% vs 24.8%; OR, 1.34).

Post-COVID patients also were more likely to report 3 of 6 groups of new-onset diseases, including those of the liver or kidneys (2.7% vs 0.9%; OR, 3.70), lung (3.2% vs 1.1%; OR, 3.50), and cardiovascular or metabolic (6.5% vs 4.0%; OR, 1.68) systems.

The results point to considerable long-term impact of SARS-CoV-2 infection on health and well-being among adults with a mainly mild course of acute infection.

The absence of all 18 studied health problems was less likely among participants with COVID-19 at baseline (45.9%) than among uninfected participants (60.0%). A multivariable ordinal regression analysis revealed a significant link between infection and a higher number of persistent health problems (OR, 1.83).

Compared with uninfected participants, those with COVID-19 had significantly higher odds of reporting poor subjective health (19.3% vs 13.0%; OR, 1.91), memory impairment (25.7% vs 14.3%; OR, 2.27), and worse average fatigue and physical function scores.

The results "point to considerable long-term impact of SARS-CoV-2 infection on health and well-being among adults with a mainly mild course of acute infection," the authors concluded. "Harnessing high-quality population-based epidemiological and health care research on long COVID is necessary to guide the planning and implementation of effective preventive and health care services."

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