COVID-19: A ferocious killer from brain to toe

As the number of confirmed cases of COVID-19 surges past 2.2 million globally and deaths surpass 150,000, clinicians and pathologists worldwide are trying to understand the damage brought by the coronavirus.

The health experts are realizing that although lungs are attacked initially, the virus can reach can to many organs including the heart and blood vessels, kidneys, gut, and brain. A cardiologist Harlan Krumholz of Yale University and Yale-New Haven Hospital said that the disease can attack almost anything in the body with devastating consequences.

Understanding the ferocity of the deadly disease could help the doctors on the frontline treat the fraction of the infected patients. Does a dangerous, newly observed tendency to blood clotting transform some mild cases into life-threatening emergencies? Is an overzealous immune response behind the worst cases, suggesting treatment with immune-suppressing drugs could help? What explains the startlingly low blood oxygen that some physicians are reporting in patients who nonetheless are not gasping for breath? “Taking a systems approach may be beneficial as we start thinking about therapies,” says Nilam Mangalmurti, a pulmonary intensivist at the Hospital of the University of Pennsylvania (HUP).

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What follows is the study of the virus’s attack in the body of the 5% of the patients who become critically ill. This virus acts as no pathogen humanity has ever seen and scientists need to pull information from small studies and case reports.

When an infected person expels virus-laden droplets and someone else inhales them, the novel coronavirus, called SARS-CoV-2, enters the nose and throat and finds a welcome home in the lining of the nose. The cells there are rich in a cell-surface receptor called angiotensin-converting enzyme 2 (ACE2). Throughout the body, the presence of ACE2, which normally helps regulate blood pressure, marks tissues vulnerable to infection, because the virus requires that receptor to enter a cell. Once inside, the virus hijacks the cell’s machinery, making myriad copies of itself and invading new cells.

As the virus multiplies, the body may produce a copious amount of it in the first week, when symptoms may be absent in the person. The victim may develop a fever, dry cough, sore throat, loss of smell and taste, or head and body aches.

In the case of a low immune system, the virus reaches the windpipe and attacks the alveoli air sacs in the lungs. Oxygen crosses the alveoli into the capillaries, the oxygen is then carried to the rest of the body. But as the immune system wars with the invader, the battle itself disrupts this healthy oxygen transfer.

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Front-line white blood cells release inflammatory molecules called chemokines, which in turn summon more immune cells that target and kill virus-infected cells, leaving a stew of fluid and dead cells—pus—behind. This is the underlying pathology of pneumonia, with its corresponding symptoms: coughing; fever; and rapid, shallow respiration.

Some COVID-19 patients recover, sometimes with no more support than oxygen breathed in through nasal prongs. But others deteriorate, often quite suddenly, developing a condition called acute respiratory distress syndrome (ARDS). Oxygen levels in their blood plummet and the patients find it hard to breathe often succumbing to the ventilators and some may die even.

Other than the lungs, the SARS-CoV-2 or the body’s response to it also affects other organs of the body. The heart and blood vessels, for example, are affected by the virus, although how it attacks them is a mystery. Several preprints and papers have confirmed that damage does occur, a paper shared by JAMA Cardiology disclosed heart damage in approximately 20% of the patients out of 416 admitted for Covid-19 in Wuhan, China.

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Another study in Wuhan showed that 44% of the patients out of 36 admitted in the ICU had arrhythmias. Behnood Bikdeli, a cardiovascular medicine fellow at Columbia University Medical Center says that: “The more we look, the more likely it becomes that blood clots are a major player in the disease severity and mortality from COVID-19.” Blood clots are dangerous as they might break apart and land in the lungs, consequently blocking vital arteries- causing a condition called pulmonary embolism, which has killed Covid-19 patients, clots can also lodge in the brain and causing a stroke in the patient.

If it is supposed that COVID-19-19 affects the blood vessels, it could help explain why people with prior damage to those vessels, for example by diabetes or high blood pressure, are at a higher risk of catching this disease.

However, scientists are struggling to understand what causes the cardiovascular damage as there are a couple of theories that are yet to be proven: the virus may directly attack the lining of the heart and the blood vessels, which are rich in ACE2 receptors; or due to chaos in the lungs, there is lack of oxygen and this damages the lungs; or a cytokine storm could ravage the heart as it does so with other organs.

Along with the apparent need for ventilators in hospitals for COVID-19 patients, there is also a fear of shortage of other machines like the dialysis machine because kidney failure is a huge threat to these patients.

A neurologist from New York University’s Langone Medical Center, which has treated thousands of COVID-19 patients, Jennifer Frontera says that: “If these folks are not dying of lung failure, they’re dying of renal failure.” The demand for dialysis is perhaps because the kidneys are another vital target since the ACE2 receptors are abundantly present over there. As per a preprint, 27% of 85 hospitalized patients in Wuhan had kidney failure.

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As a neuroscientist at the Chinese Academy of Sciences’ Suzhou Institute of Biomedical Engineering and Technology explain: “The lung is the primary battle zone. But a fraction of the virus possibly attacks the kidney. And as on the real battlefield, if two places are being attacked at the same time, each place gets worse.”

There are a lot of people who already suffer from some sort of chronic kidney disease and are at higher risk for acute kidney injury, moreover, there are various other factors during the treatment for COVID-19 which increases this risk, hence the need for dialysis machines.

The Covid-19 virus also affects the brain and central nervous system, doctors have reported that patients show brain inflammation encephalitis, seizures, “sympathetic storm,” a hyper reaction of the sympathetic nervous system that causes seizure-like symptoms and is most common after a traumatic brain injury, some lose consciousness whilst others have a stroke.

The SARS coronavirus in 2003, was able to infiltrate neurons and sometimes caused encephalitis, a study from a team in Japan found traces of new coronavirus in the cerebrospinal fluid of a COVID-19 patient who developed meningitis and encephalitis, suggesting it, too, can penetrate the central nervous system.

It is also suggested that the novel coronavirus can infect the lining of the lower digestive tract, where ACE2 receptors are abundant, causing gastrointestinal infections. Viral RNA has been found in as many as 53% of sampled patients’ stool samples. however, gastrointestinal infections are not on CDC’s list of symptoms of Covid-19, which could lead to some cases being undetected.

There are other complications caused in COVID-19 pateints as well such as conjuctivitis or liver damage and research is still ongoing as to the devastation this virus truly causes and it would take several years to fully unravel the mysteries associated with this novel coronavirus.

 

 

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