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

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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.

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Most cited references 79

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6-month consequences of COVID-19 in patients discharged from hospital: a cohort study

Chaolin Huang, Lixue Huang, Yeming Wang … (2021)

Background The long-term health consequences of COVID-19 remain largely unclear. The aim of this study was to describe the long-term health consequences of patients with COVID-19 who have been discharged from hospital and investigate the associated risk factors, in particular disease severity. Methods We did an ambidirectional cohort study of patients with confirmed COVID-19 who had been discharged from Jin Yin-tan Hospital (Wuhan, China) between Jan 7, 2020, and May 29, 2020. Patients who died before follow-up, patients for whom follow-up would be difficult because of psychotic disorders, dementia, or re-admission to hospital, those who were unable to move freely due to concomitant osteoarthropathy or immobile before or after discharge due to diseases such as stroke or pulmonary embolism, those who declined to participate, those who could not be contacted, and those living outside of Wuhan or in nursing or welfare homes were all excluded. All patients were interviewed with a series of questionnaires for evaluation of symptoms and health-related quality of life, underwent physical examinations and a 6-min walking test, and received blood tests. A stratified sampling procedure was used to sample patients according to their highest seven-category scale during their hospital stay as 3, 4, and 5–6, to receive pulmonary function test, high resolution CT of the chest, and ultrasonography. Enrolled patients who had participated in the Lopinavir Trial for Suppression of SARS-CoV-2 in China received severe acute respiratory syndrome coronavirus 2 antibody tests. Multivariable adjusted linear or logistic regression models were used to evaluate the association between disease severity and long-term health consequences. Findings In total, 1733 of 2469 discharged patients with COVID-19 were enrolled after 736 were excluded. Patients had a median age of 57·0 (IQR 47·0–65·0) years and 897 (52%) were men. The follow-up study was done from June 16, to Sept 3, 2020, and the median follow-up time after symptom onset was 186·0 (175·0–199·0) days. Fatigue or muscle weakness (63%, 1038 of 1655) and sleep difficulties (26%, 437 of 1655) were the most common symptoms. Anxiety or depression was reported among 23% (367 of 1617) of patients. The proportions of median 6-min walking distance less than the lower limit of the normal range were 24% for those at severity scale 3, 22% for severity scale 4, and 29% for severity scale 5–6. The corresponding proportions of patients with diffusion impairment were 22% for severity scale 3, 29% for scale 4, and 56% for scale 5–6, and median CT scores were 3·0 (IQR 2·0–5·0) for severity scale 3, 4·0 (3·0–5·0) for scale 4, and 5·0 (4·0–6·0) for scale 5–6. After multivariable adjustment, patients showed an odds ratio (OR) 1·61 (95% CI 0·80–3·25) for scale 4 versus scale 3 and 4·60 (1·85–11·48) for scale 5–6 versus scale 3 for diffusion impairment; OR 0·88 (0·66–1·17) for scale 4 versus scale 3 and OR 1·77 (1·05–2·97) for scale 5–6 versus scale 3 for anxiety or depression, and OR 0·74 (0·58–0·96) for scale 4 versus scale 3 and 2·69 (1·46–4·96) for scale 5–6 versus scale 3 for fatigue or muscle weakness. Of 94 patients with blood antibodies tested at follow-up, the seropositivity (96·2% vs 58·5%) and median titres (19·0 vs 10·0) of the neutralising antibodies were significantly lower compared with at the acute phase. 107 of 822 participants without acute kidney injury and with estimated glomerular filtration rate (eGFR) 90 mL/min per 1·73 m2 or more at acute phase had eGFR less than 90 mL/min per 1·73 m2 at follow-up. Interpretation At 6 months after acute infection, COVID-19 survivors were mainly troubled with fatigue or muscle weakness, sleep difficulties, and anxiety or depression. Patients who were more severely ill during their hospital stay had more severe impaired pulmonary diffusion capacities and abnormal chest imaging manifestations, and are the main target population for intervention of long-term recovery. Funding National Natural Science Foundation of China, Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, National Key Research and Development Program of China, Major Projects of National Science and Technology on New Drug Creation and Development of Pulmonary Tuberculosis, and Peking Union Medical College Foundation.

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Persistent Symptoms in Patients After Acute COVID-19

Angelo Carfì, Roberto Bernabei, Francesco Landi (2020)

This case series describes COVID-19 symptoms persisting a mean of 60 days after onset among Italian patients previously discharged from COVID-19 hospitalization.

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Post-acute COVID-19 syndrome

Ani Nalbandian, Kartik Sehgal, Aakriti Gupta … (2021)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the pathogen responsible for the coronavirus disease 2019 (COVID-19) pandemic, which has resulted in global healthcare crises and strained health resources. As the population of patients recovering from COVID-19 grows, it is paramount to establish an understanding of the healthcare issues surrounding them. COVID-19 is now recognized as a multi-organ disease with a broad spectrum of manifestations. Similarly to post-acute viral syndromes described in survivors of other virulent coronavirus epidemics, there are increasing reports of persistent and prolonged effects after acute COVID-19. Patient advocacy groups, many members of which identify themselves as long haulers, have helped contribute to the recognition of post-acute COVID-19, a syndrome characterized by persistent symptoms and/or delayed or long-term complications beyond 4 weeks from the onset of symptoms. Here, we provide a comprehensive review of the current literature on post-acute COVID-19, its pathophysiology and its organ-specific sequelae. Finally, we discuss relevant considerations for the multidisciplinary care of COVID-19 survivors and propose a framework for the identification of those at high risk for post-acute COVID-19 and their coordinated management through dedicated COVID-19 clinics.

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Author and article information

Journal

Title: JAMA

Abbreviated Title: JAMA

Publisher: American Medical Association (AMA)

ISSN (Print): 0098-7484

Publication date (Electronic): October 10 2022

Affiliations

[1 ]Institute for Health Metrics and Evaluation, University of Washington, Seattle

[2 ]Department of Juridical and Economic Studies, La Sapienza University, Rome, Italy

[3 ]Department of Pulmonary Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands

[4 ]John T. Milliken Department of Internal Medicine, Washington University in St Louis, St Louis, Missouri

[5 ]Clinical Epidemiology Center, US Department of Veterans Affairs, St Louis, Missouri

[6 ]Epidemiology, Biostatistics, and Prevention Institute, University of Zürich, Zurich, Switzerland

[7 ]Wolfson Institute of Population Health, Queen Mary University of London, London, England

[8 ]Department of Pediatrics and Pediatric Infectious Diseases, I. M. Sechenov First Moscow State Medical University, Moscow, Russia

[9 ]Clinical Medicine (Pediatric Profile), I. M. Sechenov First Moscow State Medical University, Moscow, Russia

[10 ]EuroQol Research Foundation, Rotterdam, the Netherlands

[11 ]Pirogov Russian National Research Medical University, Moscow

[12 ]Research Institute for Healthcare Organization and Medical Management, Moscow Healthcare Department, Moscow, Russia

[13 ]Department of Woman and Child Health and Public Health, Agostino Gemelli University Polyclinic IRCCS, Rome, Italy

[14 ]Global Health Research Institute, Catholic University of Sacred Heart, Rome, Italy

[15 ]I. M. Sechenov First Moscow State Medical University, Moscow, Russia

[16 ]Department of Medicine, University of Washington, Seattle

[17 ]Center for Policy Impact in Global Health, Duke University, Durham, North Carolina

[18 ]Department of Surgery, Duke University, Durham, North Carolina

[19 ]Uppsala University Hospital, Uppsala, Sweden

[20 ]Pediatric Dentistry and Dental Public Health Department, Alexandria University, Alexandria, Egypt

[21 ]Rector’s Office, I. M. Sechenov First Moscow State Medical University, Moscow, Russia

[22 ]Department of Surgical Sciences, Anesthesiology, and Intensive Care Medicine, Uppsala University, Uppsala, Sweden

[23 ]Clinical Medicine (General Medicine Profile), I. M. Sechenov First Moscow State Medical University, Moscow, Russia

[24 ]Administration Department, I. M. Sechenov First Moscow State Medical University, Moscow, Russia

[25 ]Department of Public Health, Erasmus University Medical Center, Rotterdam, the Netherlands

[26 ]Applied Physiology Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran

[27 ]School of Nursing, Duke University, Durham, North Carolina

[28 ]Department of Rehabilitation Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands

[29 ]Neurorehabilitation, Rijndam Rehabilitation, Rotterdam, the Netherlands

[30 ]Department of Neurology, Medical University Innsbruck, Innsbruck, Austria

[31 ]Department of Infectious Diseases and Respiratory Medicine, Charité Medical University Berlin, Berlin, Germany

[32 ]Department of Respiratory Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands

[33 ]Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden

[34 ]Department of Public Health Surveillance and Response, National Institute for Communicable Diseases, Johannesburg, South Africa

[35 ]Department of Infectious Diseases and Respiratory Medicine, Charité University Medical Center Berlin, Berlin, Germany

[36 ]Department of Clinical Research and Tropical Medicine, Bernhard-Nocht Institute of Tropical Medicine, Hamburg, Germany

[37 ]Department of Epidemiology, Harvard University, Boston, Massachusetts

[38 ]Department of Medical Sciences, Uppsala University, Uppsala, Sweden

[39 ]Duke Global Health Institute, Duke University, Durham, North Carolina

[40 ]Russian Medical Academy of Continuous Professional Education, Ministry of Healthcare of the Russian Federation, Moscow

[41 ]Isfahan Cardiovascular Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran

[42 ]National Heart and Lung Institute, Imperial College London, London, England

[43 ]ZA Bashlyaeva Children’s Municipal Clinical Hospital, Moscow, Russia

[44 ]Department of Public Health, Institute of Tropical Medicine, Antwerp, Belgium

[45 ]Friedman School of Nutrition Science and Policy, Tufts University, Boston, Massachusetts

[46 ]Department of Occupational Medicine and Public Health, Faroese Hospital System, Torshavn, Faroe Islands

[47 ]Centre of Health Science, University of Faroe Islands, Torshavn

[48 ]Department of Epidemiology, Johns Hopkins University, Baltimore, Maryland

[49 ]Department of Internal Medicine, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh

[50 ]Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy

[51 ]Department of Surgical Sciences, Hedenstierna Laboratory, Uppsala University, Uppsala, Sweden

[52 ]School of Population and Public Health, University of British Columbia, Vancouver, Canada

[53 ]Hospital Universitario de La Princesa, Madrid, Spain

[54 ]Centro de Investigación Biomédica en Red Enfermedades Respiratorias (Center for Biomedical Research in Respiratory Diseases Network), Madrid, Spain

[55 ]Department of Global Health and Social Medicine, Harvard University, Boston, Massachusetts

[56 ]Nursing and Midwifery Department, Seed Global Health, Boston, Massachusetts

[57 ]German Center for Lung Research, Berlin

[58 ]Department of Family Medicine and Community Health, Duke University, Durham, North Carolina

[59 ]Department of Political Science, University of Washington, Seattle

[60 ]Center for Statistics and the Social Sciences, University of Washington, Seattle

[61 ]Department of Applied Mathematics, University of Washington, Seattle

[62 ]Department of Health Metrics Sciences, School of Medicine, University of Washington, Seattle

[63 ]Department of Global Health, University of Washington, Seattle

[64 ]Postgraduate Program in Epidemiology, Federal University of Rio Grande do Sul, Porto Alegre, Brazil

[65 ]School of Public Health, University of Queensland, Brisbane, Australia

[66 ]National Center for Disease Control and Public Health, Tbilisi, Georgia

[67 ]School of Public Health, Queensland Centre for Mental Health Research, Wacol, Australia

[68 ]Department of Maternal and Child Nursing and Public Health, Federal University of Minas Gerais, Belo Horizonte, Brazil

[69 ]West Moreton Hospital Health Services, Queensland Centre for Mental Health Research, Wacol, Australia

[70 ]Clinical Epidemiology and Public Health Research Unit, Burlo Garofolo Institute for Maternal and Child Health, Trieste, Italy

[71 ]Department of Health Policy and Management, Keio University, Tokyo, Japan

[72 ]Department of Global Health Policy, University of Tokyo, Tokyo, Japan

[73 ]Department of Internal Medicine, Federal University of Minas Gerais, Belo Horizonte, Brazil

[74 ]Centre of Telehealth, Federal University of Minas Gerais, Belo Horizonte, Brazil

[75 ]Policy and Epidemiology Group, Queensland Centre for Mental Health Research, Wacol, Australia

[76 ]Department of Social and Behavioral Sciences, School of Public Health, Yale University, New Haven, Connecticut

[77 ]Evans School of Public Policy and Governance, University of Washington, Seattle

[78 ]Cochrane South Africa, South African Medical Research Council, Cape Town

[79 ]HIV and Other Infectious Diseases Research Unit, South African Medical Research Council, Durban

[80 ]Department of Orthopedic Surgery, Duke University, Durham, North Carolina

Article

DOI: 10.1001/jama.2022.18931

PubMed ID: 36215063

SO-VID: 7eaf5a10-e346-435e-a9e1-b165663ff283

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

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Abstract

Importance

Objective

Design, Setting, and Participants

Exposures

Main Outcomes and Measures

Results

Conclusions and Relevance

Related collections

Novel Coronavirus Disease COVID-19

Most cited references 79

6-month consequences of COVID-19 in patients discharged from hospital: a cohort study

Persistent Symptoms in Patients After Acute COVID-19

Post-acute COVID-19 syndrome

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Journal

Affiliations

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Comment on this article

Similar content 37

Cited by 222

Most referenced authors 1,832