Half of COVID survivors still had symptoms at 3 years, more reinfections amid Omicron

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Three years after COVID-19 infection, 54% of adults in a Chinese cohort still had at least one symptom, most of them mild to moderate in severity, with higher rates of reinfection and pneumonia after the emergence of the Omicron variant, shows a study published yesterday in The Lancet Respiratory Medicine.

Researchers from China-Japan Friendship Hospital in Beijing led the study of 1,359 COVID-19 patients released from Jinyintan Hospital in Wuhan from January to May 2020. The patients completed three follow-up visits at 6 months, 1 year, and 2 years after illness onset. The study period spanned the predominance of wild-type SARS-CoV-2 and the emergence of all variants up to Omicron.

At 1 year, COVID-naïve controls from two communities in Wuhan were recruited. At 2 years, the controls were matched in a 1:1 ratio with the COVID-19 patients who underwent lung function tests. At 3 years, all eligible COVID-19 survivors and controls matched at 2-year follow-up completed several face-to-face questionnaires, a 6-minute walking test (6MWT), and lab tests from February to April 2023.

Community controls and a sample of COVID-19 survivors stratified by illness severity during hospitalization underwent lung function tests. COVID-19 patients who underwent high-resolution computed tomography (CT) and had abnormal lung imaging results at 2 years were reevaluated.

Organ function recovered over time

Of the 1,359 COVID-19 survivors, 728 (54%) reported one or more mostly mild or moderate lingering symptoms at 3 years. After Omicron emerged in November 2021, relative to participants without long COVID, those with long COVID at 2 years had significantly higher rates of reinfection (76% vs 67%) and pneumonia (5% vs 2%).

Three months after Omicron infection, 126 of 204 COVID-19 survivors with long COVID at 2 years (62%) had new-onset or worsened symptoms, a significantly higher proportion than in the group without long COVID (41%) and controls (40%).

Although the organ function of survivors of COVID-19 recovered over time, those with severe long COVID symptoms, abnormal organ function, or limited mobility require urgent attention in future clinical practice and research.

The percentage wasn't significantly different between COVID-19 survivors without persistent symptoms and controls (41% vs 39%). At 3 years, reinfection was a risk factor for shortness of breath (odds ratio [OR], 1.36), anxiety or depression (OR, 1.65), and EuroQol visual analog score (β, –4·51) but not for less daily activity (OR, 0.72). The lung function of COVID-19 survivors at 3 years was comparable to that of controls.

"Although the organ function of survivors of COVID-19 recovered over time, those with severe long COVID symptoms, abnormal organ function, or limited mobility require urgent attention in future clinical practice and research," the study authors wrote.

Need for consistent long-COVID definition

In a related commentary, Ash Routen, PhD, and Kamlesh Khunti, MD, PhD, both of the University of Leicester, cautioned that the study data are from a single center in an ethnically homogenous population, with few critically ill COVID-19 survivors, and the lung function sample was small.

But they said the inclusion of matched community controls and the attempt to parse the effect of Omicron on survivors and reinfection rates were study strengths. "Unfortunately, although various outcomes were measured in uninfected controls, sequelae symptoms were not," they wrote.

"Further work is required to define what an appropriate comparator group is—should studies be constrained only to test controls without COVID-19 or include those infected by SARS-CoV-2 but unvaccinated? The answer is likely to depend on the chosen research question."

Routen and Khunti called for the provision of sufficient infrastructure to enable global longitudinal study of the epidemiologic factors of COVID-19, especially on the developmental outcomes and new-onset chronic disease in younger people.

"In the short term, outstanding research priorities include the need to improve consistency of classifications of long COVID between analyses, the inclusion of comparator groups (aligned with research questions), the use of large sample sizes for sufficient statistical power, particularly when effects might be small, and stratification of findings by potential explanatory factors (including socioeconomic status, ethnicity, COVID-19 variants, and vaccination status)," they concluded.

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