Global Prevalence of Long COVID, its Subtypes and Risk factors: An Updated Systematic Review and Meta-Analysis, 2025, Hou et al.

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 I2 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.

https://www.medrxiv.org/content/10.1101/2025.01.01.24319384v1

 

I don't understand how this paper has defined long covid.

"Our inclusion criteria are as follows: (1) human study population with confirmed COVID-19 diagnosis through polymerase chain reaction (PCR) test, antibody test, or a clinical diagnosis; (2) index date of first test/diagnosis, date of hospitalization, discharge date, date of clinical recovery/negative test, or date of symptom occurrence; (3) outcome must include prevalence, risk factors, duration, or symptoms of long COVID; and (4) the follow-up time was at
least two months after the index date. The definition of long COVID from the World Health Organization (WHO) was applied in criteria (4)."

The WHO definition is: "The continuation or development of new symptoms 3 months after the initial SARS-CoV-2 infection, with these symptoms lasting for at least 2 months with no other explanation."

The authors then state: "For this systematic review, long COVID is defined as at least one new or persisting symptom during the follow-up time."

I'm confused. Can anybody make sense of this?