More than half of patients who were hospitalized with COVID-19 reported at least one persistent symptom 2 years post-infection, regardless of initial disease severity, researchers reported.

The most frequently reported symptoms at 2 years were fatigue and muscle weakness.

“Several cohort studies have highlighted that the health effects of COVID-19 could persist up to 1 year after acute infection, most of which had no control groups of individuals who had not contracted COVID-19 and focused only on symptomatic sequelae or respiratory outcomes,”Lixue Huang, MD, from the department of pulmonary and critical care medicine at China-Japan Friendship Hospital at Capital Medical University and the National Center for Respiratory Medicine at the National Clinical Research Center for Respiratory Diseases, Beijing, and colleagues wrote in The Lancet Respiratory Medicine. “Hence, long-term and overall health outcomes of COVID-19 are largely unknown.”

Huang and colleagues reported 2-year follow-up data from an ambidirectional, longitudinal cohort study of 1,192 patients (median age, 57 years; 46% women) who survived COVID-19 and were discharged from Jin Yin-tan Hospital between January and May 2020. Participants completed three follow-up assessments during which the researchers measured health outcomes at 6 months, 12 months and 24 months after COVID-19 symptom onset using 6-minute walking distance, laboratory tests and questionnaires about symptoms, mental health, health-related quality of life, return to work and health care use after discharge. Also included in this study were participants without COVID-19 who were age-, sex- and comorbidities-matched to determine COVID-19 survivor recovery status at 2 years.

Median follow-up after COVID-19 symptom onset was 185 days for the 6-month visit, 349 days for the 12-month visit and 685 days for the 24-month visit.

The proportion of COVID-19 survivors with at least one reported symptom declined from 68% at 6 months to 55% at 2 years (P < .0001). Fatigue or muscle weakness was the most frequently reported symptom, present in 52% of patients at 6 months.

Compared with 26% of patients with a modified British Medical Research Council (mMRC) score of at least 1 at 6 months, 14% of patients had a score of at least 1 at 2 years (P < .0001).

Researchers reported improvement in health-related quality of life in nearly all domains, especially anxiety or depression. The proportion of patients with symptoms of anxiety or depression decreased from 23% at 6 months to 12% at 2 years (P < .0001). The researchers reported a continual decline in the proportion of patients with a 6-minute walking distance less than the lower limit of normal overall and in subgroups of different initial disease severity, with 89% of 494 COVID-19 survivors returning to their original work at 2 years.

Those with long COVID symptoms at 2 years reported more mobility problems (OR = 3.81; 95% CI, 1.62-8.93), more pain or discomfort (OR = 4.42; 95% CI, 3.14-6.21) and more anxiety or depression (OR = 7.46; 95% CI, 4.12-13.52) compared with survivors without long COVID. COVID-19 survivors also reported more problems with usual activity (2% vs. < 1%), more pain or discomfort (23% vs. 5%) and anxiety or depression (12% vs. 5%) at 2 years compared with controls.

Finally, researchers observed a higher proportion of COVID-19 survivors who received higher-level respiratory support during hospitalization with lung diffusion impairment (65% vs. 36%; P = .0009), reduced residual volume (62% vs. 20%; P < .0001) and total lung capacity (39% vs. 6%; P < .0001) compared with controls.

“The COVID-19 survivors had not returned to the same health status as the general population 2 years after acute infection, so ongoing follow-up is needed to characterize the protracted natural history of long COVID; we plan to conduct yearly follow-ups in this cohort,” the researchers wrote. “The value of rehabilitation programs in mitigating the effects of long COVID and in accelerating recovery requires further exploration.”