How long COVID is defined and measured affects prevalence estimation

In a recent study posted to the medRxiv* preprint server, researchers evaluated the prevalence of long coronavirus disease (COVID) symptoms, functional disabilities, symptoms, and pathological alterations among adults and children ≥12 weeks post-acute COVID 2019 (COVID-19).

Long COVID has been established as an adverse outcome of SARS-CoV-2 infections that affects the routine activities of many individuals and refers to the development or persistence of COVID-19 symptoms after the acute COVID-19 phase. 

​​​​​​​Study: Systematic review of the prevalence of Long Covid. ​​​​​​​Image Credit: metamorworks / Shutterstock

About the study

Researchers examined long-term COVID prevalence in the present systematic review and meta-analysis in order to inform policy-making and resource planning.

The team searched English publications in databases such as Embase, MEDLINE, Cochrane CENTRAL, the Cochrane COVID-19 study register, ClinicalTrials.gov, PubMed, medRxiv preprint server, World Health Organization (WHO)’s ICTRP (international clinical trials registry platform) and the global research on COVID-19 databases between January 1, 2020, and November 2, 2021.

Studies comprising ≥100 individuals without critical illness with study designs such as cohort (prospective and retrospective), case-control, and cross-sectional were included. The study groups comprised community residents, outpatients, institutionalized groups such as the military or schools, hospitalized patients, and patient panels or support groups.

For subgroup analyses, studies with ≥50 participants were included. Two independent reviewers screened the studies, and any disagreements between the two were solved by another reviewer. The primary study outcome was long COVID development, defined as the presence of ≥1 COVID-19 symptom, functional disability, or associated pathological change 12 weeks post-acute COVID-19.

The risk of bias was assessed based on a modified Newcastle-Ottawa scale, and subgroup analyses were performed. Long COVID prevalence was estimated based on the cumulative incidence of ≥1 or the most commonly reported persistent symptom or pathological change. The I² statistic was used to calculate study heterogeneity.

Heterogeneity was also assessed by stratifying individuals in the predetermined subgroups: type of outcome type (symptom, functional status, pathology), locations (Europe, North America, China, mixed or other), sample population source (outpatients, hospital inpatients, healthcare workers, communities, outpatients), follow-up durations, study designs, confirmed COVID-19 diagnosis, and other domains for bias risks. In addition, individuals were stratified based on the WHO clinical progression scale severity scores. Finally, random-effects modeling was used for the meta-analysis.

Results

In the initial data search, 11,518 study records were found. After duplicate removal and screening of the titles and abstracts, 457 studies whose full text was available were further assessed for eligibility. By hand-searching, an additional nine studies were found, and a total of 130 publications with 120 discrete studies were included for the final analysis. 

Of the included studies, 24 were conducted in China, 66 in Europe, 14 in North America, and 16 in other nations. The participants were recruited from communities, outpatient settings, social media, and healthcare institutions.

Follow-up periods varied between 12 weeks and >1 year. The bias risk was low in very few studies. Almost all (except one) subgroup and complete analyses had I² values ≥ 90.0%, indicative of significant heterogeneity, with prevalence estimates of persistent COVID-19 symptoms ranging from 0% to 93%. Studies utilizing regular healthcare data showed a tendency to report lower long COVID prevalence than those utilizing self-reported records.

However, studies including systematic investigations or persistent pathology among the study participants during follow-up assessments showed a tendency to report the highest prevalence estimates. Studies comprising hospitalized COVID-19 patients had higher prevalence estimates compared to those involving COVID-19 patients residing in community settings. The studies with the least bias risks reported long COVID prevalence estimates ranging from 3.0% to 37.0%.

The prevalence of incomplete recovery to full fitness/health after ≥12 weeks of acute COVID-19 ranged between 8.0% and 70.0%, and a 31% prevalence was reported for lower quality of life. The most commonly reported symptoms of long COVID were fatigue, breathing difficulties, sleep disturbances, itching or tingling sensations, and muscle/joint pain. In addition, pulmonary, cardiovascular and neurological pathologies were most commonly reported.

The wide variations in prevalence estimates were because of differing long COVID definitions, severity thresholds for affecting routine activities, study population sources, study design used, the definition of the initial SARS-CoV-2 infection, symptom assessment method, and the number of symptoms assessed. Among studies including case-control comparisons, significant considerations about the study methodology for selecting control individuals were observed, including difficulties in determining SARS-CoV-2-naive individuals.

Overall, the study findings showed that the assessment method affects prevalence estimates of long COVID. Looking at the extensive global impact of COVID-19, a considerable COVID-19 burden is likely to be present even after considering highly conservative prevalence estimates, especially among nations with high SARS-CoV-2 transmission in community settings. Further research must be conducted, including the impact of COVID-19 vaccinations on the prevalence of long COVID-19.

*Important notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Written by

Pooja Toshniwal Paharia

Dr. based clinical-radiological diagnosis and management of oral lesions and conditions and associated maxillofacial disorders.