Symptoms of COVID-19 routinely persist beyond the acute phase of infection and have implications for health-associated functioning and quality of life, according to a systematic review published in JAMA Network Open.

Researchers searched the PubMed and Web of Science databases for studies examining persistent symptoms of COVID-19 between January 1, 2020, and March 11, 2021. They defined persistent symptoms as those lasting at least 60 days after diagnosis, symptom onset, or hospitalization, or at least 30 days from recovery or hospital discharge.

A total of 45 studies reporting 84 clinical signs from 9751 total participants were included. Participants were mostly men (54.0%), and 30 of 45 studies reported mean or median ages of 60 and younger. The persistence of at least 1 symptom at last follow-up was reported in 16 studies whose participants mostly included previously hospitalized patients.


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The median frequency of persistence of at least 1 symptom was 72.5% (interquartile range [IQR], 55-80). The most frequently occurring individual symptoms were shortness of breath or dyspnea occurring in 26 studies with a median frequency of 36.0% (IQR, 27.6-50.0), fatigue or exhaustion occurring in 25 studies with a median frequency of 40.0% (IQR, 31-57), and sleep disorders or insomnia occurring in 8 studies with a median frequency of 29.4% (IQR, 24.4-33.0).

Heterogeneity in study design and quality was high among the included studies, which according to the study authors, “had implications for interpretation and often limited direct comparability and combinability.” Some of the reported design differences were patient selection criteria, patient characteristics, time zero definitions and follow-up lengths, and definitions of outcomes and illness severity.

Further study limitations included a limited ability to address the duration of symptoms, the percentage of symptoms that were resolved, and the long-term trajectory of quality of life and function. There also were limited data on persistence based on initial severity, and few studies examined history or baseline prevalence of similar symptoms and prevalence in similar groups without COVID-19.

According to the researchers, the results from the review revealed, “COVID-19 symptoms frequently persist beyond the acute phase of infection, but there is a need to standardize designs and improve study quality.” The study authors added, “The designs of studies reported to date preclude making precise risk estimates about many long-term outcomes, particularly by patient or disease characteristic, but they suggest that the problem of persistent symptoms is substantial.”

Reference

Nasserie T, Hittle M, Goodman SN. Assessment of the frequency and variety of persistent symptoms among patients with COVID-19: a systematic review. JAMA Netw Open. 2021;4(5):e2111417. doi:10.1001/jamanetworkopen.2021.11417