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

Abstract

Abstract Importance As 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. Objective The 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 Sources PubMed, 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 Selection Studies 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 Synthesis Data 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 Measures Prevalence of PASC worldwide and stratified by regions. Results Global 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 Relevance The 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 Points Question Among those infected with COVID-19, what is the global and regional prevalence of post-acute sequelae COVID-19 (PASC)? Findings Globally, 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. Meaning In 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.