Global Prevalence of Long COVID, its Subtypes and Risk factors: An Updated Systematic Review and Meta-Analysis

Abstract

Importance: Updated knowledge regarding the global prevalence of long COVID (or post-COVID-19 condition), its subtypes, risk factors, and variations across different follow-up durations and geographical regions is necessary for informed public health recommendations and healthcare delivery.

Objective: The primary objective of this systematic review is to evaluate the global prevalence of long COVID and its subtypes and symptoms in individuals with confirmed COVID-19 diagnosis, while the secondary objective is to assess risk factors for long COVID in the same population.

Data sources: Studies on long COVID published from July 5, 2021, to May 29, 2024, searched from PubMed, Embase, and Web of Science were used for this systematic review. Supplemental updates to the original search period were made.

Study selection: There were four inclusion criteria: (1) human study population with confirmed COVID-19 diagnosis; (2) appropriate index diagnosis date; (3) outcome must include either prevalence, risk factors, duration, or symptoms of long COVID; and (4) follow-up time of at least two months after the index date. The exclusion criteria were: (1) non-human study population; (1) case studies or reviews; (2) studies with imaging, molecular, and/or cellular testing as primary results; (3) studies with specific populations such as healthcare workers, residents of nursing homes, and/or those living in long-term care facilities; and (4) studies that did not meet the sample size threshold needed to estimate overall prevalence with margin of error of 0.05.

Data extraction and synthesis: Two screeners independently performed screenings and data extraction, and decision conflicts were collectively resolved. The data were pooled using a random-effects meta-analysis framework with a DerSimonian-Laird inverse variance weighted estimator.

Main outcomes and measures: The primary estimand (target population parameter of interest) was the prevalence of long COVID and its subtypes among individuals with confirmed COVID-19 diagnoses, and the secondary estimand was effect sizes corresponding to ten common risk factors of long COVID in the same population.

Results: A total of 442 studies were included in this mega-systematic review, and 429 were meta-analyzed for various endpoints, avoiding duplicate estimates from the same study. Of the 442 studies, 17.9% of the studies have a high risk of bias. Heterogeneity is evident among meta-analyzed studies, where the I ² statistic is nearly 100% in studies that estimate overall prevalence. Global estimated pooled prevalence of long COVID was 36% among COVID-19 positive individuals (95% confidence interval [CI] 33%-40%) estimated from 144 studies. Geographical variation was observed in the estimated pooled prevalence of long COVID: Asia at 35% (95% CI 25%-46%), Europe at 39% (95% CI 31%-48%), North America at 30% (95% CI 24%-38%), and South America at 51% (95% CI 35%-66%). Stratifying by follow-up duration, the estimated pooled prevalence for individuals with longer follow-up periods of 1 to 2 years (47% [95% CI 37%-57%]) compared to those with follow-up times of less than 1 year (35% [95% CI 31%-39%]) had overlapping CI and were therefore not statistically distinguishable. Top five most prevalent long COVID subtypes among COVID-19 positive cases were respiratory at 20% (95% CI 14%-28%) estimated from 31 studies, general fatigue at 20% (95% CI 18%-23%) estimated from 121 studies, psychological at 18% (95% CI 11%-28%) estimated from 10 studies, neurological at 16% (95% CI 8%-30%) estimated from 23 studies, and dermatological at 12% (95% CI 8%-17%) estimated from 10 studies. The most common symptom based on estimated prevalence was memory problems estimated at 11% (95% CI 7%-19%) meta-analyzed from 12 studies. The three strongest risk factors for long COVID were being unvaccinated for COVID-19, pre-existing comorbidity, and female sex. Individuals with any of these risk factors had higher odds of having long COVID with pooled estimated odds ratios of 2.34 (95% CI 1.49-3.67) meta-analyzed from 6 studies, 1.59 (95% CI 1.28-1.97) from 13 studies, and 1.55 (95% CI 1.25-1.92) from 22 studies, respectively.

Conclusions and relevance: This study shows long COVID is globally prevalent in the COVID-19 positive population with highly varying estimates. The prevalence of long COVID persists over extended follow-up, with a high burden of symptoms 1 to 2 years post-infection. Our findings highlight long COVID and its subtypes as a continuing health challenge worldwide. The heterogeneity of the estimates across populations and geographical regions argues for the need for carefully designed follow-up with representative studies across the world.

Figure 1.

PRISMA Flow Diagram. Additional study characteristics such as cohort type, region, and status of all included studies are listed in the box in the bottom left.

Figure 2.

Panel 2A shows global coverage amongst the 33 studies included in meta-analysis by Chen et al. [17]. Panel 2B shows global coverage amongst the 429 studies included in this current meta-analysis. Countries with greater than ten studies are marked with circles indicating the exact number of studies. The lack of studies in the grey areas shows the lack of representation in global datasets and the information gap. The change from 2A to 2B shows that except Africa and Oceania, considerable literature has emerged in the past three years in other parts of the world.

Figure 3.

Forest plot for pooled long COVID prevalence, corresponding 95% confidence intervals and number of contributing studies stratified by hospitalization status, geographical regions, follow-up time, biological sex, and age groups.

Figure 4.

Forest plot for pooled odds ratio estimates for long COVID associated with nine risk factors with corresponding 95% confidence intervals and the number of contributing studies.

Figure 5.

Examination of heterogeneity by boxplot of overall long COVID prevalence, neurological, psychological, cardiovascular, respiratory, musculoskeletal, dermatological, gastrointestinal, and general fatigue subtype prevalence. Potential sources of true etiological heterogeneity versus study-induced heterogeneity are listed.