Estimated Global Proportions of Individuals With Persistent Fatigue, Cognitive, and Respiratory Symptom Clusters Following Symptomatic COVID-19 in 2020 and 2021

Abstract

Importance: Some individuals experience persistent symptoms after initial symptomatic SARS-CoV-2 infection (often referred to as Long COVID).

Objective: To estimate the proportion of males and females with COVID-19, younger or older than 20 years of age, who had Long COVID symptoms in 2020 and 2021 and their Long COVID symptom duration.

Design, setting, and participants: Bayesian meta-regression and pooling of 54 studies and 2 medical record databases with data for 1.2 million individuals (from 22 countries) who had symptomatic SARS-CoV-2 infection. Of the 54 studies, 44 were published and 10 were collaborating cohorts (conducted in Austria, the Faroe Islands, Germany, Iran, Italy, the Netherlands, Russia, Sweden, Switzerland, and the US). The participant data were derived from the 44 published studies (10 501 hospitalized individuals and 42 891 nonhospitalized individuals), the 10 collaborating cohort studies (10 526 and 1906), and the 2 US electronic medical record databases (250 928 and 846 046). Data collection spanned March 2020 to January 2022.

Exposures: Symptomatic SARS-CoV-2 infection.

Main outcomes and measures: Proportion of individuals with at least 1 of the 3 self-reported Long COVID symptom clusters (persistent fatigue with bodily pain or mood swings; cognitive problems; or ongoing respiratory problems) 3 months after SARS-CoV-2 infection in 2020 and 2021, estimated separately for hospitalized and nonhospitalized individuals aged 20 years or older by sex and for both sexes of nonhospitalized individuals younger than 20 years of age.

Results: A total of 1.2 million individuals who had symptomatic SARS-CoV-2 infection were included (mean age, 4-66 years; males, 26%-88%). In the modeled estimates, 6.2% (95% uncertainty interval [UI], 2.4%-13.3%) of individuals who had symptomatic SARS-CoV-2 infection experienced at least 1 of the 3 Long COVID symptom clusters in 2020 and 2021, including 3.2% (95% UI, 0.6%-10.0%) for persistent fatigue with bodily pain or mood swings, 3.7% (95% UI, 0.9%-9.6%) for ongoing respiratory problems, and 2.2% (95% UI, 0.3%-7.6%) for cognitive problems after adjusting for health status before COVID-19, comprising an estimated 51.0% (95% UI, 16.9%-92.4%), 60.4% (95% UI, 18.9%-89.1%), and 35.4% (95% UI, 9.4%-75.1%), respectively, of Long COVID cases. The Long COVID symptom clusters were more common in women aged 20 years or older (10.6% [95% UI, 4.3%-22.2%]) 3 months after symptomatic SARS-CoV-2 infection than in men aged 20 years or older (5.4% [95% UI, 2.2%-11.7%]). Both sexes younger than 20 years of age were estimated to be affected in 2.8% (95% UI, 0.9%-7.0%) of symptomatic SARS-CoV-2 infections. The estimated mean Long COVID symptom cluster duration was 9.0 months (95% UI, 7.0-12.0 months) among hospitalized individuals and 4.0 months (95% UI, 3.6-4.6 months) among nonhospitalized individuals. Among individuals with Long COVID symptoms 3 months after symptomatic SARS-CoV-2 infection, an estimated 15.1% (95% UI, 10.3%-21.1%) continued to experience symptoms at 12 months.

Conclusions and relevance: This study presents modeled estimates of the proportion of individuals with at least 1 of 3 self-reported Long COVID symptom clusters (persistent fatigue with bodily pain or mood swings; cognitive problems; or ongoing respiratory problems) 3 months after symptomatic SARS-CoV-2 infection.

Conflict of interest statement

Conflict of Interest Disclosures: Drs Bobkova, Munblit, and Svistunov and Mss Gamirova, Shikhaleva, and Spiridonova reported receiving grants and contracts paid to Sechenov University from the British Embassy in Moscow for the StopCOVID Cohort: Clinical Characterisation of Russian Patients 2020-2021. Dr Haagsma reported receiving grants from the EuroQol Foundation. Dr Lipcsey reported receiving grants from and having contracts with Hjärt-Lungfonden (Swedish Heart Lung Foundation) and being a member of data and safety monitoring boards for the PROFLO and COVID-19 Hyperbaric Oxygen randomized clinical trials. Dr Munblit reported receiving grants paid to Sechenov University from the Russian Foundation for Basic Research and the UK Research and Innovation/National Institute for Health Research; receiving personal fees from Merck Sharp & Dohme and Bayer; and having unpaid leadership positions as co-chair of the International Severe Acute Respiratory and Emerging Infection Consortium Global Pediatric Long COVID Working Group and co-lead of the PC-COS (Post-COVID Condition Core Outcomes) Project. Dr Petersen reported being on the board of the Faroese National Data Protection Authority and receiving equipment, materials, drugs, medical writing, gifts, or other services from Beijing Wantai Biological Pharmacy Enterprise Co Ltd. Dr Puhan reported receiving support from the University of Zurich Foundation and the Department of Health, Canton of Zurich. Dr Flaxman reported having stock options in Agathos Ltd and receiving personal fees from Janssen, Swiss Re, Merck for Mothers, and Sanofi. Ms Fullman reported receiving personal fees from the World Health Organization and receiving funding from Gates Ventures. No other disclosures were reported.

Figures

Figure 1.. Analytical Flowchart of Estimation Process for Long COVID Symptom Clusters

ICU indicates intensive care unit. The 3 Long COVID symptom clusters were persistent fatigue with bodily pain or mood swings; cognitive problems; or ongoing respiratory problems and were self-reported 3 months after SARS-CoV-2 infection in 2020 and 2021.

Figure 2.. Proportion of Individuals Who Survived Symptomatic SARS-CoV-2 Infection and Who Experienced at Least 1 of the 3 Long COVID Symptom Clusters in 2020 and 2021

The proportion estimates with the 95% uncertainty intervals appear in eTables 14-15 in Supplement 1.