GenOMICC study - Looking at DNA of patients with severe illness and injury to find the genes that cause some people to become very unwell and be admitted to intensive care

Not Applicable

• Conditions: Genetics of susceptibility and mortality in life-threatening infection; Infections and Infestations

• Registration Number: ISRCTN16993428
• Lead Sponsor: Accord (United Kingdom)

Brief Summary

2021 Preprint results in https://doi.org/10.1101/2021.03.10.21252820 (added 01/06/2021) 2021 Preprint results in https://doi.org/10.1101/2021.03.04.21252931 (added 01/06/2021) 2021 Preprint results in https://www.biorxiv.org/content/10.1101/2021.04.21.440697v1 (added 01/06/2021) 2021 Results article in https://pubmed.ncbi.nlm.nih.gov/33307546/ genome-wide association study results (added 01/06/2021) 2022 Results article in https://pubmed.ncbi.nlm.nih.gov/35255492/ Critical COVID-19 results (added 31/03/2022) 2023 Results article in https://pubmed.ncbi.nlm.nih.gov/37198478/ (added 25/05/2023)

Detailed Description

Not available

Study Timeline

• Study Start: 2021-06-25
• Last Update Posted: 29 April 2024
• Study Completion: 2029-08-31

Recruitment & Eligibility

• Status: Ongoing
• Sex: All
• Target Recruitment: 40000

Inclusion Criteria

1. Patients will be recruited who:
1.1. Are deemed, in the view of the treating physician, to require continuous cardiovascular or respiratory monitoring or invasive mechanical ventilation,
1.2. AND provide appropriate consent or assent,
1.3. AND present with one of the following primary diagnoses:
2. Group 1: specific infectious syndromes in highly-selected patients
2.1.COVID-19. Confirmed or suspected COVID-19.
2.2.Influenza. Confirmed or suspected infection with influenza virus.
2.3.Secondary pneumonia. Acute pneumonia complicating confirmed infection with influenza virus.
2.4.Dengue. Confirmed or suspected infection with dengue virus.
2.5.RSV. Confirmed infection with respiratory syncytial virus.
2.6.Emerging infections. Confirmed or suspected infection with an emerging infection (see below).
3. Group 2: specific non-infectious critical illness syndromes:
3.1.Burns. Full-thickness burns covering > 20% of body surface area.
3.2.Emerging critical illness syndromes. Confirmed or suspected presence of an emerging critical illness syndrome. These are unexplained or idiosyncratic presentations of acute organ injury, or suspected reactions to therapeutic agents, including:
3.3.acute disease associated with inhalation of noxious substances or vapours, such as vaping
3.4.acute disease associated with CAR T-cell therapy
4. Group 3: extreme critical illness
4.1. Extra-corporeal life support. Requirement for continuous veno-venous extra-corporeal support for respiratory failure of any aetiology.
5. Group 4: common/nonspecific critical illness syndromes:
5.1.Cellulitis. Soft tissue infections causing systemic sepsis.
5.2.Pneumonia. Primary pneumonia of any aetiology, with radiographic changes at presentation to critical care. Pneumonia is defined as: symptoms and signs consistent with an acute lower respiratory tract infection associated with new radiographic shadowing for which there is no other explanation (eg, not pulmonary oedema or infarction). Where this illness is the primary reason for hospital admission and is managed as pneumonia, the patient is eligible for inclusion.(Harris et al, 2011). No microbiology information is required to meet this entry criterion.
5.3.Pancreatitis. Pancreatitis of any aetiology.
5.4.Emerging Infections
Emerging infections are by their nature unpredictable and present a significant challenge to the international research community. In order to ensure research preparedness, in accordance with the principles laid out by the International Severe Acute and Emerging Infection Consortium (ISARIC)(Dunning et al. 2014), patients will be recruited to this study if they have confirmed or suspected infection with a novel pathogen, a new strain of an existing pathogen, or a re-emerging known pathogen, that causes life-threatening illness. This will include the Middle East Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome (SARS), highly pathogenic strains of influenza, Ebola virus disease and other epidemics of viral haemorrhagic fever.

Exclusion Criteria

Current participant exclusion criteria as of 25/01/2023:
There are no exclusion criteria. All consenting patients can be recruited.

Previous participant exclusion criteria:
Exclusion criteria do not apply to COVID-19. All consenting COVID-19 patients will be included. For all inclusion categories apart from COVID-19, patients who are functionally limited by any comorbid illness (such as frailty, heart failure, chronic obstructive pulmonary disease (COPD), or reduced exercise tolerance of any cause) or have significant immunosuppression (such as cancer chemotherapy or acquired immune deficiency syndrome) will be excluded from this study.

Study & Design

• Study Type: Observational
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
60-day survival measured using electronic medical records post recruitment

Secondary Outcome Measures

Name	Time	Method
The genetic data from severely ill patients will be measured in comparison with the genetic data from volunteers who suffered only mild symptoms using whole genome sequencing and/or SNP arrays at one-time point to try to determine which genes might play a part in an illness progressing to critical illness