Besides being more infectious than MERS and similar diseases, COVID-19 has turned the alarm on because in a large proportion of cases it caused severe lesions in the lungs and many other organs. Most authors agree that viral sepsis worsens the prognosis of coronavirus, causing damage in multiple organs in a cascade of inflammation.
The main mechanisms of multiple organ injury include (1):
In the professional tenure, research has shown that skilled nurses are treating many patients and working long extended hours sometimes without an adequate break therefore could not remember accurate information when updating patient records. In the Nursing & Midwifery Council (NMC) Code Of Conduct it is a requirement for nurses to perform their duties and maintained accurate record keeping of their interventions, the Care Quality Commission (CQC) It is one of the assessment criteria under the Key Line of Enquiries (KLOE) base their inspection on the following key points:
- Direct cytotoxicity: The virus can directly affect the infected tissue and cause damage to healthy cells.
- Dysregulation of the renin-angiotensin-aldosterone system (RAAS): This system regulates blood pressure, and different body tissues have receptors to one of these hormones. Thus, dysregulation causes damage to many organs.
- Dysregulation of the immune response: The virus changes the way our body responds to pathogens. It changes the behavior of white blood cells and causes severe inflammation.
- Endothelial injury: The endothelium is the inner lining of the blood vessels. Inflammation causes damage to this structure, which is found throughout the body. The endothelium has many functions and triggers thrombus formation in response to inflammatory injury.
- Are we responsive to our patient’/resident’s needs?
- Tissue fibrosis: Sustained damage in tissues causes fibrosis. This is a thickening of the tissue similar to a scar. Healthy cells are replaced by this thickened tissue devoid of any function. Organ function is affected when fibrosis affects a large portion of the tissue.
But how does multi-organ damage increase the mortality of these patients? Is it possible to die from COVID-19 due to organ damage outside of the lungs? In this article, we will review the damage caused in different body systems and how it affects mortality risk.[cz_image css_position=”relative;display: table;margin:0 auto” id=”cz_62135″ image=”2036″]
Respiratory system
We should naturally start in the respiratory system, where COVID-19 usually starts. The lungs are vulnerable to the disease, especially in children who have a higher proportion of angiotensin receptors (ACE2). The virus needs them to enter the cell, but they also protect the lung from damage. Both contradicting functions are triggered at the same time, initiating a vicious cycle of damage and repair. In the end, this continuous damage causes fibrosis in the lungs. Additionally, there’s an active inflammatory process combined with thrombosis that causes respiratory failure.
Circulatory system
In the circulatory system, the most important mechanism of disease is endothelial dysfunction. As noted above, the endothelium releases substances and has essential functions. It is found all over the body, and endothelial problems affect the blood vessels and many organs simultaneously.
ACE2 is also found in the arteries and veins. Thus, COVID-19 reaches those tissues and cause damage. There’s an alteration in the blood flow, vasoconstriction, and inflammation inside the arteries. Then, in response to inflammation, platelets start to build up clots causing micro and macro-thrombosis.
Thrombosis events in COVID-19 increase the risk of mortality. These thrombi may migrate into the lungs or the heart and cause infarction of either tissue. Additionally, the heart can also be directly affected by COVID-19. The virus causes cardiomegaly, fibrosis, and degeneration of the heart muscle. All of this increases the risk of heart disease, especially in patients with pre-existing cardiovascular disease.
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Urogenital system
The kidneys also display ACE2 and become another target of COVID-19. The virus causes direct injury in the kidneys, destroying the tissue that filters the blood. This is evident in patients who urinate blood and those who lose proteins through the urine. There is intense inflammation in the kidneys, and we can even find edema (liquid retention) in computed tomography.
The course of kidney injury varies, and some patients develop a life-threatening acute injury that requires dialysis. There’s a higher expression of ACE2 in the male genitalia compared to women, which might partly explain why males have a higher COVID-19 fatality than women.
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Gastrointestinal system
COVID-19 patients commonly have nausea, vomiting, diarrhea, and abdominal pain. Such symptoms are associated with gastrointestinal dysfunction caused by the virus. This is clearly mediated by an abundance of ACE2 in epithelial cells of the intestines. ACE2 aids with amino acid absorption in the intestines, but it increases morbidity and mortality risk during coronavirus infections. It is also the reason why coronavirus has a fecal-oral transmission instead of limiting to respiratory droplets.
Having gastrointestinal symptoms by itself does not increase the risk of mortality. However, studies show that patients with such symptoms have a longer duration of the disease. In some cases, acute and very severe gastrointestinal symptoms may also suggest a life-threatening problem. Patients with sudden and very severe abdominal pain could have a mesenteric infarction, similar to cardiac infarction, but this time the thrombus is found in the arteries of the intestines. Obstruction of the blood flow causes necrosis of the intestinal cells, with severe acute abdominal pain and a high risk of mortality. Hemorrhages in the abdominal cavity are also a possibility in these patients, causing similar abdominal pain symptoms.
Besides the intestines, COVID-19 may also affect liver function. It triggers inflammation in the liver with patchy necrosis in some cases. The virus often increases transaminase levels in the blood because liver cells start to die and release their enzymes into the bloodstream. Additionally, there is hepatic congestion and increasing bilirubin levels that worsen the problem.
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Nervous system
There are ACE2 receptors in the olfactory bulb cells, which is why many patients with COVID-19 experience a sudden loss of gustation and olfaction. The olfactory bulb is the usual entry point to the brain. Another entry point would be through the vascular endothelium through infected leukocytes that reach the central nervous system. That is why many patients with coronavirus experience constant headaches, and some of them may report visual impairments and experience confusion.
There is apparently no direct infection in neurons and brain tissue, but the virus can invade the cerebrospinal fluid and cause meningoencephalitis. In such cases, there is cerebral edema that may lead to neuronal degeneration. Intracranial hemorrhages may also develop in these patients, with life-threatening consequences.
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Causes of death in hospitalized patients
After years of fighting COVID-19 and its comorbidities, we have gathered evidence about the leading causes of death in hospitalized patients. Why would a coronavirus-infected patient die in the hospital despite having medical attention all around? According to the evidence, here’s a list of the most common causes of death and how they relate to multi-organ failure (2):
- Hypoxia and respiratory failure: Naturally, respiratory failure is one of the leading causes of death in COVID-19 patients. Even with the aid of mechanical ventilation, it is sometimes difficult to keep the patient adequately oxygenated. Besides lung toxicity and inflammation, damage to the endothelium reduces the blood flow to the lungs. The blood is not sufficiently oxygenated, and the patient starts developing neurological changes followed by acid-base imbalances that ultimately cause multi-organ failure and death. Fatal respiratory failure is more common in patients with a history of pulmonary embolism, active smokers, and chronic obstructive pulmonary disease.
- Pulmonary embolism: Endothelial dysfunction favors thrombi formation, which migrates to different parts of the body. There are very small arteries in the heart, the lungs, the abdominal mesentery, and other tissues. A dislodged thrombus obstructs the arteries and causes necrosis in the tissue when it stops receiving oxygen and nutrients. Pulmonary embolism is more common in patients with a history of stroke, ischemic heart disease, and blood clotting abnormalities.
- Sepsis and septic shock: Sepsis is a systemic inflammatory state triggered by severe infection. It causes changes in the circulatory system, impairments in circulation, and leakage of substances outside the blood vessels. Sepsis takes the inflammatory state to all organs simultaneously, causing weakening of the heart, blood pressure drops, progressive failure of the kidneys, liver, and lungs, and very high mortality risk. Many patients who died from septic shock had hypertension and other cardiovascular problems before getting infected with COVID-19.
- Bacterial superinfection: Besides coronavirus, aggressive Staphylococcus bacteria and other microorganisms can cause overlapped pneumonia. Multiple organisms can cause severe infection and worsen the prognosis of the patient. There are cases of toxic megacolon and fulminant colitis with severe intestinal hemorrhage and a very high mortality rate in coronavirus patients.
Throughout these years, we have understood that coronavirus goes beyond the reach of the common cold and influenza. Through ACE2 enzymes, it reaches a wide variety of tissues causing direct or indirect damage in multiple organs simultaneously. Despite having medical attention, mortality in hospitalized patients usually responds to multi-organ failure with highly complex management. In other cases, an unexpected event such as thrombus formation or fulminant colitis may worsen the prognosis and cause a very high mortality risk.
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