What is this study about?

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Death from critical illness is strongly affected by genetics

Susceptibility to infection, including sepsis and influenza is known very strongly genetically determined. There are strong reasons to believe the same is true for COVID-19.

In critical illness, a complex cascade of immune signals leads to failure of critical organ systems and death. These events are often not specific to a particular type of infection - they can happen to any patient with a severe infection. Although we know that susceptibility to a particular bug, such as the influenza virus, SARS-CoV-2 (the coronavirus that causes COVID-19), or a bacteria like Staphylococcus aureus, is genetic, it is harder to tell if there are specific genes that alter a patient's chance of survival once they are already desperately sick with sepsis. But we do know that the immune system plays a key role in causing organ failure in sepsis, and in other forms of critical illness. Genetic differences have a very strong impact on immune function.

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How to look for answers

There are millions of DNA sequence differences between any pair of humans. Any of these could be important in determining the outcome in sepsis. Finding the ones that matter requires us to look at DNA from huge numbers of patients. We need to look at DNA from thousands of people in order to find robust genetic associations with outcomes. This is urgent, because if we can achieve it then we may be able to find treatments that will ultimately save lives.

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Inclusion Criteria: COVID-19

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Should the primary diagnosis be covid (proven or suspected) there are no exclusion criteria.

 

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Inclusion Criteria: Non-Covid-19 patients

                          

*Influenza

*Secondary pneumonia

*Dengue

*RSV

*Confirmed or suspected infection with an emerging infection

*Burns (full thickness covering >20% of body surface)

*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:

•             confirmed or suspected multisystem inflammatory syndrome temporally associated with COVID-19

•             acute disease associated with inhalation of noxious substances or vapours, such as "vaping"

•             acute disease associated with CAR T-cell therapy

*Extra-corporeal life support

*Cellulitis

*Pneumonia

*Pancreatitis

*Life-threatening complications of vaccines. In addition to the critical illness inclusion criteria, patients will be recruited who have potentially life-threatening complications of vaccines against SARS-CoV-2. Note that since these complications are all potentially life-threatening, patients will be eligible even if they are not admitted to a continuous monitoring/critical care area. This will include confirmed or suspected:

• Cerebral venous sinus thrombosis

• Deep vein thrombosis/pulmonary embolism

• Other thrombotic events, with or without thrombocytopaenia

• Neuroinflammatory disorders including Guillain-Barre syndrome

• Anaphylaxis

• Vasculitis

• Other potentially life-threatening suspected complications of vaccine

 

Exclusion Criteria: Non-Covid-19 patients

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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).

 

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Link to GenOMICC study protocol

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Flowchart