Global Prevalence of Post-Acute Sequelae of COVID-19 (PASC) or Long COVID: A Meta-Analysis and Systematic Review

Abstract

ImportanceAs SARS-CoV-2 pervades worldwide, considerable focus has been placed on the longer lasting health effects of the virus on the human host and on the anticipated healthcare needs.ObjectiveThe primary aim of this study is to examine the prevalence of post-acute sequelae of COVID-19 (PASC), commonly known as long COVID, across the world and to assess geographic heterogeneities through a systematic review and meta-analysis. A second aim is to provide prevalence estimates for individual symptoms that have been commonly reported as PASC, based on the existing literature.Data SourcesPubMed, Embase, and iSearch for preprints from medRxiv, bioRxiv, SSRN, and others, were searched on July 5, 2021 with verification extending to August 12, 2021.Study SelectionStudies written in English that consider PASC (indexed as ailments persisting at least 28 days after diagnosis or recovery for SARS-CoV-2 infection) and that examine corresponding prevalence, risk factors, duration, or associated symptoms were included. A total of 40 studies were included with 9 from North America, 1 from South America, 17 from Europe, 11 from Asia, and 2 from other regions.Data Extraction and SynthesisData extraction was performed and separately cross-validated on the following data elements: title, journal, authors, date of publication, outcomes, and characteristics related to the study sample and study design. Using a random effects framework for meta-analysis with DerSimonian-Laird pooled inverse-variance weighted estimator, we provide an interval estimate of PASC prevalence, globally, and across regions. This meta-analysis considers variation in PASC prevalence by hospitalization status during the acute phase of infection, duration of symptoms, and specific symptom categories.Main Outcomes and MeasuresPrevalence of PASC worldwide and stratified by regions.ResultsGlobal estimated pooled PASC prevalence derived from the estimates presented in 29 studies was 0.43 (95% confidence interval [CI]: 0.35, 0.63), with a higher pooled PASC prevalence estimate of 0.57 (95% CI: 0.45, 0.68), among those hospitalized during the acute phase of infection. Females were estimated to have higher pooled PASC prevalence than males (0.49 [95% CI: 0.35, 0.63] versus 0.37 [95% CI: 0.24, 0.51], respectively). Regional pooled PASC prevalence estimates in descending order were 0.49 (95% CI: 0.21, 0.42) for Asia, 0.44 (95% CI: 0.30, 0.59) for Europe, and 0.30 (95% CI: 0.32, 0.66) for North America. Global pooled PASC prevalence for 30, 60, 90, and 120 days after index test positive date were estimated to be 0.36 (95% CI: 0.25, 0.48), 0.24 (95% CI: 0.13, 0.39), 0.29 (95% CI: 0.12, 0.57) and 0.51 (95% CI: 0.42, 0.59), respectively. Among commonly reported PASC symptoms, fatigue and dyspnea were reported most frequently, with a prevalence of 0.23 (95% CI: 0.13, 0.38) and 0.13 (95% CI: 0.09, 0.19), respectively.Conclusions and RelevanceThe findings of this meta-analysis suggest that, worldwide, PASC comprises a significant fraction (0.43 [95% CI: 0.35, 0.63]) of COVID-19 tested positive cases and more than half of hospitalized COVID-19 cases, based on available literature as of August 12, 2021. Geographic differences appear to exist, as lowest to highest PASC prevalence is observed for North America (0.30 [95% CI: 0.32, 0.66]) to Asia (0.49 [95% CI: 0.21, 0.42]). The case-mix across studies, in terms of COVID-19 severity during the acute phase of infection and variation in the clinical definition of PASC, may explain some of these differences. Nonetheless, the health effects of COVID-19 appear to be prolonged and can exert marked stress on the healthcare system, with 237M reported COVID-19 cases worldwide as of October 12, 2021.Key PointsQuestionAmong those infected with COVID-19, what is the global and regional prevalence of post-acute sequelae COVID-19 (PASC)?FindingsGlobally, the pooled PASC prevalence estimate was 0.43, whereas the pooled PASC prevalence estimate for patients who had to be hospitalized due to COVID-19 was 0.57. Regionally, estimated pooled PASC prevalence from largest to smallest effect size were 0.49 for Asia, 0.44 for Europe, and 0.30 for North America. Global pooled PASC prevalence for 30, 60, 90, and 120 days after index date were estimated to be 0.36, 0.24, 0.29, and 0.51, respectively. Among commonly reported PASC symptoms, fatigue and dyspnea were reported most frequently, with a prevalence of 0.23 and 0.13.MeaningIn follow-up studies of patients with COVID-19 infections, PASC was common both globally and across geographic regions, with studies from Asia reporting the highest prevalence.

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“…COVID-19 can cause long-term illness and disability, 1 , 2 , 3 which is increasingly appreciated as a major global challenge. 4 , 5 Various case definitions are currently in use—long COVID refers to symptoms that continue or develop beyond 4 weeks after the start of acute COVID-19, 6 whereas post-COVID condition refers to symptoms 3 months from initial infection and lasting at least 2 months.…”

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“…As reported elsewhere, our hospitalized cases had a higher prevalence and severity of PCC than ambulatory cases, 12,14,20 with female sex and increasing age also associated with higher PCC risk. 9,12,15,16,25,[32][33][34] We could not properly assess the impact of vaccination as few of our participants had been vaccinated at the time of their COVID-19. Lasting post-COVID-19 symptoms disrupt work life with 8% to 73% indicating they were unable to return to previous full-time work 3 to 8 months after acute COVID-19 4,11,35 .…”

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“…Seropositivity in these subjects had been estimated at 4.6% in the USA (ranging from 1.1% to 14.2%) [31]. Between the ages of 18 to 44 years, about four to five cases are undiagnosed for every diagnosed case of COVID-19 [31,32]. There is a general sequel rate of 0.30-0.43 and 0.52 among those requiring hospitalization [32].…”

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