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Journal Article Systematic Review Meta-Analysis Ppublish 1 citation

PubMed: 42663308 DOI: 10.3310/GJMA0602

Individual Participant Data Meta-Analysis (IPDMA) of long-term COVID-19 outcomes in a systematic review-informed, international, multidisciplinary database.

Health Soc Care Deliv Res 14(29):1-160

Authors: Myzoon Ali, Marian C Brady, Pauline Campbell, Scott Rooney, Linda Williams, Lorna Paul, Helen Mason, Sarkis Manoukian, Charlie Chung, Mark Barber, Claire McGoldrick, Andrew Smith, Neil Basu, Manish Patel, Kathryn VandenBerg, Aikaterini Papadopoulou, Azza Abdelaal, Samuel Jk Abraham, Alaa Abu Sayf, Jane Agergaard, Motaz Alawna, Sergiu Albu, Laurent Alric, Paulette Andino, Jakub Antczak, Alexander Arutyunov, Aylin Ayyıldız, Ellena Badrick, Pınar Yalcin Bahat, Tala Ballouz, Clara Balsano, Matteo Bassetti, Mariana Bendersky, Danilo Berton, Fausto Biancari, Bjorn Blomberg, Gianluca Em Boari, Silvia Bonetti, Mohammad Bosaeed, Benoit Bouteleux, Salvatore Brugaletta, Mikhail Bychinin, Ina Callebaut, Stephen J Carter, Michal Chudzik, Julien Coelho, Mario Cornejo-Giraldo, Stefania Costi, Gilles Darcis, David R Darley … and 93 other authors

Affiliations

  • School of Nursing, Community and Public Health, Glasgow Caledonian University, Glasgow, UK.
  • School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, UK.
  • School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, UK.
  • Usher Institute, The University of Edinburgh, Edinburgh, UK.
  • Yunus Centre for Social Business and Health, Glasgow Caledonian University, Glasgow, UK.
  • AHP Stroke Strategic Lead/Long COVID Rehabilitation Lead/Consultant Occupational Therapist, NHS Lothian, Lothian, UK.
  • Department of Medicine for the Elderly, Monklands District General Hospital, Airdrie, UK.
  • Department of Infectious Diseases, University Hospital Monklands, NHS Lanarkshire, UK.
  • Department of Respiratory Medicine, University Hospital Wishaw, Wishaw, UK.
  • School of Infection & Immunity, University of Glasgow, Glasgow, UK.
  • Clinical Pathology Department, Assiut University, Assiut, Egypt.
  • Faculty of Medicine, University of Yamanashi, Yamanashi, Japan.
  • Department of Pulmonary & Critical Care Medicine, Henry Ford Health, Detroit, MI, USA.
  • Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark.
  • Department of Health Sciences, Faculty of Graduate Studies, The Arab American University, Palestine.
  • Institut Guttmann, Institut Universitari de Neurorehabilitació adscrit a la UAB, Barcelona, Spain.
  • Universitat Autónoma de Barcelona, Bellaterra (Cerdanyola del Vallès), Barcelona, Spain.
  • Internal Medicine and Digestive Department, Rangueil Hospital Toulouse University, Toulouse, France.
  • Instituto Nacional del Torax, Chile.
  • Department of Neurology, Jagiellonian University Medical College, Krakow, Poland.
  • NJSC Asfendiyarov Kazakh National Medical University, and National Institute of Health Named After Academician S. Avdalbekyan, Almaty, Kazakhstan.
  • Department of Physical Medicine and Rehabilitation, Çam and Sakura City Hospital, Istanbul, Turkey.
  • Bradford Institute for Health Research, Bradford Teaching Hospitals NHS Foundation Trust, Bradford, West Yorkshire, UK.
  • Department of Obstetrics and Gynecology, Health Sciences University, Istanbul Kanuni Sultan Suleyman Training and Research Hospital, Istanbul, Turkey.
  • Epidemiology, Biostatistics and Prevention Institute (EBPI), University of Zurich, Zurich, Switzerland.
  • Department of Life, Health and Environmental Sciences-MESVA, School of Emergency-Urgency Medicine, University of L'Aquila, L'Aquila, Italy.
  • University of Genoa, Policlinico San Martino Hospital, IRCCS, Genoa, Italy.
  • Laboratorio de Anatomía Viviente, UBACyT - Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.
  • Universidade Federal do Rio Grande do Sul Hospital de Clinicas de Porto Alegre, Porto Alegre, Brazil.
  • Department of Medicine, South Karelia Central Hospital, University of Helsinki, Lappeenranta, Finland.
  • Department of Clinical Science, University of Bergen & Haukeland University Hospital, Norway.
  • Internal Medicine, Montichiari Hospital, ASST Spedali Civili Brescia, University of Brescia, Italy.
  • Internal Medicine, Manerbio Hospital ASST del Garda, Italy.
  • College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia.
  • Cabinet Resp'Air, Talence, France.
  • Hospital Clinic, Instituto de Investigaciones Biomedicas August pi i Sunyer (IDIBAPS), University of Barcelona, and CIBER-CV: Biomedical Research Networking Center in Cardiovascular Diseases, Barcelona, Spain.
  • Federal Research Clinical Center of Specialized Types of Medical Care and Medical Technologies of the FMBA of Russia, ICU, Moscow, Russia.
  • Department of Anesthesiology and Intensive Care Unit, Jessa Hospital, Hasselt, Belgium; Faculty of Medicine and Life Sciences, Hasselt University, Diepenbeek, Belgium; Limburg Clinical Research Center, Hasselt, Belgium.
  • Department of Kinesiology, Indiana University Bloomington, Bloomington, IN, USA.
  • Department of Internal Medicine and Geriatric Cardiology, Medical Centre of Postgraduate Education, Medical University of Lodz, Lodz, Poland.
  • CHU Bordeaux, Service Universitaire de Médecine du sommeil, Bordeaux, France; University Bordeaux, SANPSY, CNRS, Bordeaux, France.
  • Hospital Nacional CASE-EsSalud Arequipa, Peru.
  • Azienda USL - IRCCS di Reggio Emilia (Italy); Department of Surgery, Medicine, Dentistry and Morphological Sciences with Transplant Surgery, Oncology and Regenerative Medicine Relevance, University of Modena and Reggio Emilia, Modena, Italy.
  • Infectious Diseases Department, Liège University Hospital, Liège, Belgium.
  • Department of Thoracic Medicine, St Vincent's Hospital Sydney, Sydney, NSW, Australia.

Abstract

BACKGROUND

Identifying and addressing long-term health and societal challenges after COVID-19 is a research priority.

OBJECTIVES

To create an international, multidisciplinary COVID-19 database, and synthesise long-term outcomes, predictors and costs.

DESIGN

Systematic identification of COVID-19 data sets and meta-analysis of individual participant data on long-term outcomes after COVID-19.

SETTING

Contributed data were collected in clinical, community and research settings.

INTERVENTIONS

Interventions from original studies were included as covariates in models.

DATA SOURCES

MEDLINE, Cochrane Central Register of Controlled Trials, EMBASE, Web of Science, PsycInfo ® (American Psychological Association, Washington, DC, USA), Cumulative Index to Nursing and Allied Health Literature, World Health Organization Global Index Medicus, Epistemonikos, LitCOVID; World Health Organization International Clinical Trials Registry Platform; ClinicalTrials.gov and supplementary searches for studies (November 2019-November 2021) were searched for studies on > 10 people from cohort, case-control, survey or randomised controlled trial studies, across any setting, describing validated assessment instruments, symptoms, hospitalisation, discharge destination or mortality beyond 28-days after COVID-19 onset. Data were extracted by two independent reviewers.

METHODS

Principal investigators contributed fully anonymised individual participant data. Demography, equity and symptoms were described. Assessment instruments were mapped to the International Classification of Functioning, Disability and Health. Factors associated with outcomes at 3-6 months, 9-12 months and beyond 12 months of index infection, for n > 500 individual participant data and > 1 data set were described using ratio of difference, point estimates, odds ratio and 95% confidence interval, as appropriate. The Mixed Methods Appraisal Tool described study quality; models were appraised using a Grading of Recommendations Assessment, Development and Evaluation-informed approach; heterogeneity was described using I 2.

OUTCOME MEASURES

Included overall perception of health, multidomain cognitive function, anxiety, depression, stress, post-traumatic stress disorder, fatigue, strength, walking ability, mobility, coping with daily life, breathlessness, mortality, later hospitalisation and health-related quality of life.

RESULTS

PRECIOUS collated 116 data sets from 40 countries (individual participant data = 62,849), comprising 20 randomised controlled trials, 13 case-control, 60 cohort 2 longitudinal, 1 survey and 20 other study types. Participants' median age was 58 years interquartile range (45-68); 34,185 (54.4%) were female; 158 unique symptoms and 137 unique assessment instruments were captured, predominantly describing International Classification of Function, Disability and Health-body functions. Women had poorer outcomes across 30/37 models, compared with men. In 15/37 models, pre-existing lung disease and increasing age were associated with poorer outcomes; hospitalisation, diabetes and chronic kidney disease were each associated with poorer outcomes in 8/37 models. Initial hospitalisation resulted in lower health-related quality of life that did not recover for up to 2 years after initial infection. Heterogeneity was low in 34/37 models; 22/37 models were of moderate and 11/37 were of low quality.

LIMITATIONS

Use of secondary data limits available covariates, outcomes and time points to those included in primary data sets; evidence was primarily based on high-income countries. There was a lack of data on longer-term healthcare resource use to estimate the costs to the healthcare system.

CONCLUSIONS

PRECIOUS contributes to the overall picture of long-term COVID-19 outcomes beyond the long-COVID condition and highlights poorer long-term outcomes in women and people with pre-existing comorbidities.

FUTURE WORK

Evidence gaps included healthcare resource use, isolation, loneliness, societal participation and return to work outcomes. Data are needed on the role of health inequity on long-term outcomes.

STUDY REGISTRATION

This study is registered as PROSPERO (CRD42020224323, IRAS ID: 293578).

FUNDING

This award was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme (NIHR award ref: NIHR132895) and is published in full in Health and Social Care Delivery Research; Vol. 14, No. 29. See the NIHR Funding and Awards website for further award information.

MeSH

Quality Of Life, Mortality, Stress, Physiological, Signs And Symptoms, Covid-19, Stress Disorders, Traumatic, Research, Infections