Genomic, Proteomic, and Phenotypic Biomarkers of COVID-19 Severity: Protocol for a Retrospective Observational Study
Year: 2023
Type: article
Abstract: BACKGROUND: Health organizations and countries around the world have found it difficult to control the spread of COVID-19. To minimize the future impact on the UK National Health Service and improve patient care, there is a pressing need to identify individuals who are at a higher risk of being hospitalized because of severe COVID-19. Early targeted work was successful in identifying angiotensin-converting enzyme-2 receptors and type II transmembrane serine protease dependency as drivers of severe infection. Although a targeted approach highlights key pathways, a multiomics approach will provide a clearer and more comprehensive picture of severe COVID-19 etiology and progression. OBJECTIVE: The COVID-19 Response Study aims to carry out an integrated multiomics analysis to identify biomarkers in blood and saliva that could contribute to host susceptibility to SARS-CoV-2 and the development of severe COVID-19. METHODS: The COVID-19 Response Study aims to recruit 1000 people who recovered from SARS-CoV-2 infection in both community and hospital settings on the island of Ireland. This protocol describes the retrospective observational study component carried out in Northern Ireland (NI; Cohort A); the Republic of Ireland cohort will be described separately. For all NI participants (n=519), SARS-CoV-2 infection has been confirmed by reverse transcription-quantitative polymerase chain reaction. A prospective Cohort B of 40 patients is also being followed up at 1, 3, 6, and 12 months postinfection to assess longitudinal symptom frequency and immune response. Data will be sourced from whole blood, saliva samples, and clinical data from the electronic care records, the general health questionnaire, and a 12-item general health questionnaire mental health survey. Saliva and blood samples were processed to extract DNA and RNA before whole-genome sequencing, RNA sequencing, DNA methylation analysis, microbiome analysis, 16S ribosomal RNA gene sequencing, and proteomic analysis were performed on the plasma. Multiomics data will be combined with clinical data to produce sensitive and specific prognostic models for severity risk. RESULTS: An initial demographic and clinical profile of the NI Cohort A has been completed. A total of 249 hospitalized patients and 270 nonhospitalized patients were recruited, of whom 184 (64.3%) were female, and the mean age was 45.4 (SD 13) years. High levels of comorbidity were evident in the hospitalized cohort, with cardiovascular disease and metabolic and respiratory disorders being the most significant (P<.001), grouped according to the International Classification of Diseases 10 codes. CONCLUSIONS: This study will provide a comprehensive opportunity to study the mechanisms of COVID-19 severity in recontactable participants. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/50733.
Source: JMIR Research Protocols
DOI: 10.2196/50733
Authors: Andrew English, Darren McDaid, Seodhna M Lynch, Joseph McLaughlin, Eamonn Cooper, Benjamin Wingfield, Martin Kelly, Manav Bhavsar, Victoria McGilligan, Rachelle E Irwin, Magda Bucholc, Shu-Dong Zhang, Priyank Shukla, Taranjit Singh Rai, Anthony J Bjourson, Elaine Murray, David S Gibson, Colum Walsh
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $1,900
Funders: Brain and Behavior Research Foundation, American Foundation for Suicide Prevention, Klingenstein Third Generation Foundation, University of Minnesota, National Alliance for Research on Schizophrenia and Depression, Children's Hospital Foundation, EU Joint Programme – Neurodegenerative Disease Research, Department for the Economy, Universitätsmedizin Göttingen, Amsterdam University Medical Centers, National Institute for Health and Care Research, Department of Health and Social Care, King's College London, Science Foundation Ireland, Public Health Agency, Universiteit Leiden, ZonMw, Vrije Universiteit Amsterdam, Bundesministerium für Bildung und Forschung, Generalitat de Catalunya, Ege Üniversitesi, Ministero della Salute, Alberta Children's Hospital Foundation, GGZ inGeest, Rivierduinen, Ministero dell’Istruzione, dell’Università e della Ricerca, Türkiye Bilimsel ve Teknolojik Araştırma Kurumu, Ministerio de Ciencia e Innovación, Leids Universitair Medisch Centrum, Universitair Medisch Centrum Groningen, Gratama Stichting, National Healthcare Group, Siemens Healthineers, Branch Out Neurological Foundation, National Institutes of Health, University of Texas MD Anderson Cancer Center, University of California, San Francisco, NIHR Maudsley Biomedical Research Centre, Medical Research Council, National Health and Medical Research Council, Instituto de Salud Carlos III, European Regional Development Fund, National Center for Mental Health, National Institute of Mental Health, National Cancer Institute, National Institute of Neurological Disorders and Stroke, National Institute of Biomedical Imaging and Bioengineering, National Institute of Child Health and Human Development, National Center for Research Resources
Awards: G1035381911, G1054454475, A Cross-Sectional and Longitudinal Functional MRI Study of Adolescent Depression, Brain imaging study of twins, First-Line Management of Youth Depression, G1564270761, ENIGMA-SD: Understanding Sex Differences in Global Mental Health through ENIGMA, G1825629232, JPND Verbundprojekt BRIDGET: Bildgebung, Kognition, Demenz und Next Generation Sequencing - Ein interdisziplinärer Ansatz zur Analyse und Identifikation von Risikofaktoren und protektiven Faktoren neurodegenerativer Erkrankungen, G1980987201, G2076520454, Diagnostico diferencial de primeros episodios psicóticos basado en datos funcionales y estructurales de conectividad cerebral, G2446878227, G2464543338, G277641092, G293715275, G297749360, G3212302888, The Metabolic Basis of Cancer-Related Fatigue, G344542073, G3506393344, G3559709381, G3637121363, G365276949, Ailevi Depresyon Yükü Taşıyan Genç Erişkin Riskli Kadınlarda Negatif Uyaranın İşlenmesinin Nöral İzdüşümleri: Depresif Anneleri ile Karşılaştırılması ve HPA Ekseninin Nöronal İşlev Üzerine Olan Etkisi, G3700221019, G3805357451, G3990375104, G4457840320, The Roles of Inflammatory and Glutamatergic Processes in the Neurodevelopmental Mechanisms Underlying Adolescent Depression, G4604642625, G5177134401, G5452741828, G5628238840, G5652653302, Genetics of brain structure and function, Fronto-limbic Connectivity in Adolescents with MDD, G5888468584, G5923802800, Neurodevelopmental risk factors for depression from childhood to early adulthood, ENIGMA Center for Worldwide Medicine, Imaging & Genomics, G6221874794, NMR Imaging and Spectroscopy, Antidepressant drugs effect on the gender-dependent development of depressive behavior induced by early neuroinflammatory hit: a multitask approach from mice to patients, Neuroimmune Mechanisms of Recovery from Comorbid Depression and Chronic Pain, G69671276, Utilidad de las máquinas de aprendizaje automático para la predicción del diagnóstico en pacientes con un primer episodio psicotico, G7034736287, G7051567, G7190573489, Neural predictors of treatment response in youth depression, G836522160, A global alliance to unlock brain mechanisms influencing suicidal behaviors through the ENIGMA Consortium, G9000228748, e:Med Nachwuchsgruppe PreNeSt - Untersuchung von Hirnnetzwerken durch nicht-invasive transkraniale Magnetstimulation zur Therapieoptimierung bei affektiven Störungen, Cancer Center Support Grant, Glutamatergic Modulators for Rapid and Sustained Antidepressant Effect, Psychobiological Mechanisms Underlying the Association Between Early Life Stress and Depression Across Adolescence, G906719305, G943946881
OpenAlex ID: W4388523918