In the United Kingdom, there are currently 138,000 confirmed patients with coronavirus,causing 18,738 deaths. Whilst the disease may be mild in the majority of patients, asignificant proportion of patients require intensive care therapy and a ventilator due tolung injury. In addition to lung injury/failure (acute respiratory distress syndrome(ARDS)), around 50% of patients admitted to intensive care develop acute kidney injury(AKI) (requiring advanced support via haemofiltration) and multi-organ failure.It is unclear why patients suffering from COVID-19 develop such severe lung injury(requiring life support or ventilation) or indeed why patients develop other organdysfunction such as kidney injury. The investigators hypothesis that this may due to anover-reaction of the immune system particularly in the lungs. This then results in therelease of various mediators and biological messengers which can be pushed into the bloodbloodstream (exacerbated by positive pressure generated by the ventilator). Thesemediators then travel, via the blood, to other organs such as the kidney where they causeinflammation and injury of cells, resulting in organ failure.The investigators would like to apply their well-established laboratory methods tofurther the scientific community's knowledge of this severe and deadly viral conditionand we hope that this would lead to the development of medication that would treat thisdeadly virus.
COVID-19 is a highly contagious virus, causing a global health emergency. A significant
number (~17%) of hospitalised patients become severely unwell and require admission to an
intensive care unit (ICU) due to lung failure (acute respiratory distress syndrome
(ARDS)) and multi-organ failure (MOF). Sadly, 51.8% of COVID-ARDS patients develop kidney
failure, which has a markedly increased risk of dying (61%). We have learned that kidney
failure starts several days after lung failure, which suggest an initial viral "attack"
on the lungs followed by kidney involvement several days later.
Cytokines are "signalling" molecules made by cells, which in healthy individuals help
fight disease. It was initially thought that in COVID-19, lung cells release excessive
cytokines (i.e. cytokine storm), which then cause kidney injury and MOF. However,
research has demonstrated that cytokine levels in blood are actually very low and not
enough to explain the extent of organ injury in COVID-19. This perhaps explains why
treatment strategies aimed at specifically damping down the action of these particular
cytokines in COVID-19 have failed. Consequently, there remains no cure for COVID-19 MOF,
and whilst treatments such as steroids, manage symptoms, have a general anti-inflammatory
effect and improve mortality, 30% of intensive care patients still die. Therefore, urgent
research is needed to improve scientific knowledge of this condition and identify new
therapies.
Microvesicles (MVs) are extremely small particles released by cells and carry various
chemicals including cytokines, from inside the cell, packaged securely and safely within
membranes (cellular envelopes). These vesicles act as 'postmen' delivering chemical
messengers (e.g. cytokines) between cells and are important in various diseases where
inflammation is implicated. The investigators have demonstrated that MVs have a
fundamental role in the development of organ failure in laboratory models of non-COVID
ARDS but the investigators do not yet know the role of these vesicles in the development
of ARDS/MOF in COVID-19.
The investigators hypothesise that during COVID-19 infection of the lung, significant
numbers of MVs are released within the lung (especially in severe COVID-19), which then
"transmit" signals and inflammation to other organs via the bloodstream, causing organs
to fail. Furthermore, as chemical messengers (e.g. cytokines) are hidden inside these
vesicles, they are not measured by standard laboratory techniques and may explain why
there are low cytokine levels in blood. This may also clarify why treatments inhibiting
circulating cytokines (not hidden in vesicle membranes) have failed.
To explore these ideas, the group aim to investigate MVs in blood and urine of ICU
patients with severe COVID-19 (20mls blood (1 1/3 tablespoons); 10ml urine (3/4
tablespoon)). The investigators intend to examine which chemicals are present in these
tiny vesicles and to relate this information to the clinical progress or otherwise of
patients. These data will help the scientific community understand the chemical systems
involved in severe COVID-19, tell us the significance of MVs and whether blocking MV
signalling could lead to new treatments for COVID-19. Furthermore, analysis of these MVs
may allow the investigators to identify patients who are likely to become seriously ill,
which would help in planning treatment.
Other: no intervention-mechanistic study
no intervention-mechanistic study
Inclusion Criteria:
- Male and female patients aged 18-90 years;
- Patients diagnosed with COVID-19 and without COVID-19 (control purposes);
- Patients who have developed evidence of organ injury failure (requiring oxygen).
Exclusion Criteria:
- Patients who are under the age of 18;
- Refusal to consent/gain assent;
- Presence of an advanced directive to withhold or to withdraw life-sustaining
treatment;
- Moribund patient likely to die within 24 hours.
Chelsea and Westminster Hospital NHS Foundation Trust
London, United Kingdom
Imperial College NHS Trust
London, United Kingdom