Antecedent and persistent symptoms in COVID-19 and other respiratory illnesses: Insights from prospectively collected data in the BRACE trial

Ellie McDonald; Laure F Pittet; Simone E Barry; Marc Bonten; John Campbell; Julio Croda; Mariana G Croda; Margareth Pretti Dalcolmo; Andrew Davidson; Fernando F de Almeida E Val; Glauce Dos Santos; Kaya Gardiner; Grace Gell; Amanda Gwee; Ann Krastev; Marcus Vinícius Guimaraes Lacerda; Michaela Lucas; David J Lynn; Laurens Manning; Nick McPhate; Kirsten P Perrett; Jeffrey J Post; Cristina Prat-Aymerich; Lynne E Quinn; Peter C Richmond; Nicholas J Wood; Nicole L Messina; Nigel Curtis; BRACE Trial Consortium Group

doi:10.1016/j.jinf.2024.106267

Antecedent and persistent symptoms in COVID-19 and other respiratory illnesses: Insights from prospectively collected data in the BRACE trial

J Infect. 2024 Nov;89(5):106267. doi: 10.1016/j.jinf.2024.106267. Epub 2024 Sep 6.

Authors

Ellie McDonald¹, Laure F Pittet², Simone E Barry³, Marc Bonten⁴, John Campbell⁵, Julio Croda⁶, Mariana G Croda⁷, Margareth Pretti Dalcolmo⁸, Andrew Davidson⁹, Fernando F de Almeida E Val¹⁰, Glauce Dos Santos¹¹, Kaya Gardiner¹², Grace Gell¹³, Amanda Gwee¹⁴, Ann Krastev¹⁵, Marcus Vinícius Guimaraes Lacerda¹⁶, Michaela Lucas¹⁷, David J Lynn¹⁸, Laurens Manning¹⁹, Nick McPhate²⁰, Kirsten P Perrett²¹, Jeffrey J Post²², Cristina Prat-Aymerich²³, Lynne E Quinn²⁴, Peter C Richmond²⁵, Nicholas J Wood²⁶, Nicole L Messina²⁷, Nigel Curtis²⁸; BRACE Trial Consortium Group

Affiliations

¹ Infectious Diseases Group, Murdoch Children's Research Institute, Parkville, Victoria, Australia. Electronic address: [email protected].
² Infectious Diseases Group, Murdoch Children's Research Institute, Parkville, Victoria, Australia; Department of Paediatrics, The University of Melbourne, Parkville, Victoria, Australia; Immunology, Vaccinology, Rheumatology and Infectious Diseases Unit, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland. Electronic address: [email protected].
³ Department of Thoracic Medicine, Royal Adelaide Hospital, Adelaide, South Australia, Australia; Precision Medicine Theme, South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia. Electronic address: [email protected].
⁴ ECRAID, European Clinical Research Alliance on Infectious Diseases, Utrecht, the Netherlands; Julius Center for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht University, the Netherlands. Electronic address: [email protected].
⁵ Exeter Collaboration for Academic Primary Care, University of Exeter Medical School, Exeter, United Kingdom. Electronic address: [email protected].
⁶ Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT, USA; Fiocruz Mato Grosso do Sul, Fundação Oswaldo Cruz, Campo Grande, Brazil; Universidade Federal de Mato Grosso do Sul, Campo Grande, Brazil. Electronic address: [email protected].
⁷ Universidade Federal de Mato Grosso do Sul, Campo Grande, Brazil. Electronic address: [email protected].
⁸ Centro de Referência Professor Hélio Fraga, ENSP/FIOCRUZ (Fundação Oswaldo Cruz), Rio de Janeiro, Brazil. Electronic address: [email protected].
⁹ Melbourne Children's Trial Centre, Murdoch Children's Research Institute, Parkville, Victoria, Australia. Electronic address: [email protected].
¹⁰ Tropical Medicine Foundation Dr Heitor Vieira Dourado, Brazil. Electronic address: [email protected].
¹¹ Centro de Referência Professor Hélio Fraga, ENSP/FIOCRUZ (Fundação Oswaldo Cruz), Rio de Janeiro, Brazil. Electronic address: [email protected].
¹² Infectious Diseases Group, Murdoch Children's Research Institute, Parkville, Victoria, Australia; Research Operations, The Royal Children's Hospital Melbourne, Parkville, Victoria, Australia. Electronic address: [email protected].
¹³ Infectious Diseases Group, Murdoch Children's Research Institute, Parkville, Victoria, Australia. Electronic address: [email protected].
¹⁴ Department of Paediatrics, The University of Melbourne, Parkville, Victoria, Australia; Infectious Diseases, Royal Children's Hospital Melbourne, Parkville, Victoria, Australia; Antimicrobials Group, Murdoch Children's Research Institute, Parkville, Victoria, Australia. Electronic address: [email protected].
¹⁵ Infectious Diseases Group, Murdoch Children's Research Institute, Parkville, Victoria, Australia. Electronic address: [email protected].
¹⁶ Fundação de Medicina Tropical Dr Heitor Vieira Dourado, Manaus, Brazil; Instituto Leônidas & Maria Deane, Oswaldo Cruz Foundation Ministry of Health, Manaus, Brazil; University of Texas Medical Branch, Galveston, TX, USA. Electronic address: [email protected].
¹⁷ Department of Immunology, Pathwest, Queen Elizabeth II Medical Centre, Nedlands, Western Australia, Australia; Department of Immunology, Perth Children's Hospital, Nedlands, Western Australia, Australia; Department of Immunology, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia; School of Medicine, University of Western Australia, Perth, Western Australia, Australia. Electronic address: [email protected].
¹⁸ Precision Medicine Theme, South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia; Flinders Health and Medical Research Institute, Flinders University, Bedford Park, South Australia, Australia. Electronic address: [email protected].
¹⁹ School of Medicine, University of Western Australia, Perth, Western Australia, Australia; Department of Infectious Diseases, Fiona Stanley Hospital, Murdoch, Western Australia, Australia; Wesfarmers Centre for Vaccines and Infectious Diseases, Telethon Kids Institute, Nedlands, Western Australia, Australia. Electronic address: [email protected].
²⁰ Infectious Diseases Group, Murdoch Children's Research Institute, Parkville, Victoria, Australia. Electronic address: [email protected].
²¹ Department of Paediatrics, The University of Melbourne, Parkville, Victoria, Australia; Department of Allergy and Immunology, Royal Children's Hospital Melbourne, Parkville, Victoria, Australia; Population Allergy Group, Murdoch Children's Research Institute, Parkville, Victoria, Australia. Electronic address: [email protected].
²² Department of Infectious Diseases, Prince of Wales Hospital, Randwick, New South Wales, Australia; School of Clinical Medicine, University of New South Wales, Sydney, New South Wales, Australia. Electronic address: [email protected].
²³ ECRAID, European Clinical Research Alliance on Infectious Diseases, Utrecht, the Netherlands; Julius Center for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht University, the Netherlands. Electronic address: [email protected].
²⁴ Exeter Clinical Trials Unit, Faculty of Health and Life Sciences, University of Exeter, St Luke's Campus, Heavitreee Road, Exeter, UK. Electronic address: [email protected].
²⁵ School of Medicine, University of Western Australia, Perth, Western Australia, Australia; Wesfarmers Centre for Vaccines and Infectious Diseases, Telethon Kids Institute, Nedlands, Western Australia, Australia; Department of Immunology and General Paediatrics, Perth Children's Hospital, Nedlands, Western Australia, Australia. Electronic address: [email protected].
²⁶ Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia; National Centre for Immunisation Research and Surveillance of Vaccine Preventable Disease, Westmead, New South Wales, Australia; Sydney Children's Hospital Network, Westmead, New South Wales, Australia. Electronic address: [email protected].
²⁷ Infectious Diseases Group, Murdoch Children's Research Institute, Parkville, Victoria, Australia; Department of Paediatrics, The University of Melbourne, Parkville, Victoria, Australia. Electronic address: [email protected].
²⁸ Infectious Diseases Group, Murdoch Children's Research Institute, Parkville, Victoria, Australia; Department of Paediatrics, The University of Melbourne, Parkville, Victoria, Australia; Infectious Diseases, Royal Children's Hospital Melbourne, Parkville, Victoria, Australia. Electronic address: [email protected].

Abstract

Background: Some individuals have a persistence of symptoms following both COVID-19 (post-acute COVID-19 syndrome; PACS) and other viral infections. This study used prospectively collected data from an international trial to compare symptoms following COVID-19 and non-COVID-19 respiratory illness, to identify factors associated with the risk of PACS, and to explore symptom patterns before and after COVID-19 and non-COVID-19 respiratory illnesses.

Methods: Data from a multicentre randomised controlled trial (BRACE trial) involving healthcare workers across four countries were analysed. Symptom data were prospectively collected over 12 months, allowing detailed characterisation of symptom patterns. Participants with COVID-19 and non-COVID-19 respiratory illness episodes were compared, focussing on symptom severity, duration (including PACS using NICE and WHO definitions), and pre-existing symptoms.

Findings: Compared to those with a non-COVID-19 illness, participants with COVID-19 had significantly more severe illness (OR 7·4, 95%CI 5·6-9·7). Symptom duration meeting PACS definitions occurred in a higher proportion of COVID-19 cases than non-COVID-19 respiratory controls using both the NICE definition (2·5% vs 0·5%, OR 6·6, 95%CI 2·4-18·3) and the WHO definition (8·8% vs 3·7%, OR 2·5, 95%CI 1·4-4·3). When considering only participants with COVID-19, age 40-59 years (aOR 2·8, 95%CI 1·3-6·2), chronic respiratory disease (aOR 5·5, 95%CI 1·3-23·1), and pre-existing symptoms (aOR 3·0, 95%CI 1·4-6·3) were associated with an increased risk of developing PACS. Symptoms associated with PACS were also reported by participants in the months preceding their COVID-19 or non-COVID-19 respiratory illnesses (32% fatigue and muscle ache, 11% intermittent cough and shortness of breath).

Interpretation: Healthcare workers with COVID-19 were more likely to have severe and longer-lasting symptoms than those with a non-COVID-19 respiratory illness, with a higher proportion meeting the WHO or NICE definitions of PACS. Age, chronic respiratory disease, and pre-existing symptoms increased the risk of developing PACS following COVID-19.

Keywords: Age; COVID-19; Chronic respiratory disease; Healthcare workers; Long COVID; Multicentre study; Non-COVID-19 respiratory illness; Persistent symptoms; Post-acute COVID-19 syndrome (PACS); Pre-existing symptoms; Prospective data; Symptom duration; Symptom patterns; Symptom severity.

Publication types

Multicenter Study
Randomized Controlled Trial

MeSH terms

Adult
COVID-19* / complications
COVID-19* / epidemiology
Female
Health Personnel / statistics & numerical data
Humans
Male
Middle Aged
Post-Acute COVID-19 Syndrome*
Prospective Studies
Respiratory Tract Infections / epidemiology
Respiratory Tract Infections / virology
SARS-CoV-2*
Severity of Illness Index