How COVID-19 kills? Frankly, we know little. The cunning, stubborn virus acts like no pathogen modern science has ever seen. Although the lungs are ground zero, doctors and scientists are realising that it is attacking its human host with devastating ferocity—from the brain to the toes, and the heart and blood vessels, kidneys, gut in between. Here’s a snapshot of what we know so far, based on publicly available data and studies/reports, some published at warp speed and not yet peer reviewed at the time of publication. Wait for research to sharpen the picture.
Don C: The Coronavirus Family’s new don—a cousin of SARS of 2003. Codenamed SARS-CoV-2, he began small in Wuhan in December 2019 and quickly became the world leader (like most Chinese products). With a diameter of 75 to 160 nanometers (a good face mask can hold him off) and a continuous linear single-stranded RNA (genetic material of viruses), he is lightweight—around 0.85 attograms, or about one millionth of a trillion gram (70 billion of him makes a person sick, which is about 0.0000005 gram). But he packs a killer punch. Like all things underworld, he is a parasite; needs a host to survive and procreate (the abundant human species plays perfect surrogate mother and wet nurse). Known weakness is soapwater/disinfectant that breaks down his biological suit: the fatty shell protecting his protein/RNA (imagine a hen’s egg). His primary murder weapon is COVID-19. Relies on stealth; a cough, sneeze or touch makes the fleet-footed killer change location instantly, constantly—“Don ko pakadna mushkil hi nahi, namumkin hai!”
Protein Shake: Like any wily criminal enlisting a hardworking but unacknowledged insider for clandestine access into a protected setup, Don C uses a cell protein called angiotensin-converting enzyme II, or ACE-2, which sits next to human cells and whose task is to regulate blood pressure of various organs, head to toe. He latches onto this protein and uses it as a gateway into the cell, where he rapidly makes a bunch of little progeny, and the host cell dies. Other proteins play a role too. Like the transmembrane serine protease 2 (TMPRSS2), a receptor-class gene that encodes a protein and whose biological function is yet unknown. The job becomes easier for Don C if both receptors are present in the same cell.
Go For A Nosedive: Don C enters the oral airway through the nose—behind your beautiful face sits the mucous membranes, nasal passages, sinuses. Say, if you touched a contaminated surface and ran your hands over your nose, or if an infected, ‘unmasked’ person talks to you up-close. Oral fluids contain about seven million SARS-CoV-2 copies per ml, and one minute of loud speaking generates more than 1,000 virus-containing droplets that remain airborne for eight minutes or longer, especially in enclosed environments. Well, Don C rides those projectiles and finds a welcome home in the inner lining of the nose (mucus-producing goblet cells and ciliated cells) that contains ACE-2 and TMPRSS2. He reproduces rapidly. The hijacked cells release interferons, a signaling protein that activates anti-viral defence of nearby cells, which in turn sets off the immune system alarm. Stormtroopers, the body’s soldiers, are scrambled and if they don’t beat back the gangster here, he slides down the trachea to the lungs and the oesophagus to the gut. Invisibly, of course!
Liquid+Oxygen=Lungs: Don C does to the lungs what Ajit became famous for—“Isko liquid oxygen me daal do. Liquid ise jeene nahi dega aur oxygen ise marne nahi dega.” The lungs have microscopic air pockets, called alveoli, like holes in sponges, for the gas exchange: inhale oxygen, exhale CO2. They have two types of cells, or pneumocytes. Type I helps in the gas swap. Type II produces a layer of goo—surfactant—that keeps the alveoli from sticking when it collapses/expands, like a bellow. Don C targets Type II that has the ACE-2 receptor, and triggers an inflammatory response and the body sends out Stormtroopers. But the troops go berserk. The body suffers an auto-immune disorder: a “cytokine storm”. Cytokines are chemical signaling molecules that guide an immune response. In a storm, cytokine levels soar beyond what’s needed, and immune cells start to attack healthy tissues. Blood vessels leak, blood pressure drops, clots form, and catastrophic organ failure can ensue. Your alveoli starts filling up with fluid—pus and debris from the fighting. Fluid accumulates in the interstitial space too, the gap between your cells. Your lungs are drowning to death. You are intubated to a ventilator for oxygen support. That’s pneumonia, acute respiratory distress syndrome et al.
Kidney Binned: Devoid of fresh oxygenated blood, the kidneys will fail. They will need dialysis because the body’s filters, abundantly endowed with ACE-2 receptors, present another Don C target. Ventilators boost the risk of kidney damage, as do antiviral medicines. Cytokine storms can dramatically reduce blood flow to the kidney, causing renal failure. And pre-existing diseases like diabetes can increase the chances of kidney injury.
Stomach This: Don C slides down the foodpipe to the stomach, also a rich source of ACE-2. The classic COVID-19 symptoms—diarrhoea, vomiting, abdominal pain—are believed to be the don’s misdoings in the gastrointestinal tract. Similarly, ACE-2’s presence in the liver and bile ducts makes these organs vulnerable too. Plus, lack of oxygen will inflame the liver. Other events in a failing body, like drugs or an immune system in overdrive, can damage the liver.
Bheja Fry: Don C can infiltrate the brain’s neurons/the central nervous system, much like his cousin SARS from 2003 could. He may cause meningitis and encephalitis, while blood clots can trigger strokes. A cytokine storm can provoke brain swelling. It’s not clear how Don C enters the brain. ACE-2 plays handyman, perhaps. Our top floor is endowed with this enzyme. Some believe he travels up the nose through the olfactory bulb—which explains a loss of smell that Don C’s victims experience.
Eyes, Toes In The Ballroom: Don C may cause conjunctivitis—red, watery eyes—though it’s not clear if he directly invades the eye. Besides, blood vessel constriction can cause ischemia in the fingers and toes—a reduction in blood flow that can lead to swollen, painful digits and tissue death. Reports also suggest a man’s testes are loaded with ACE-2 receptors, which raises the possibility of the don giving a kick in the groin. Does he really like to hang out down there? Picture abhi baki hain!
The Plumbing Leaks: The don goes into Dharmendra mode—“Main tera khoon pee jaunga”. In the lungs, oxygen transfers from the alveoli to the capillaries (tiny blood vessels that lie beside the air sacs). But a cytokine storm triggers blood clots, which break apart and land in the lungs, blocking vital arteries. Don C may directly attack the lining of blood vessels, which are rich in ACE-2 receptors. Lack of oxygen, from the chaos in the lungs, can damage blood vessels/alter oxygen uptake. Some COVID-19 patients record extremely low blood-oxygen levels and yet not gasp for breath. The blood vessels become inflamed throughout the body, causing vasculitis—a form of which, seen in kids, is the Kawasaki disease. Patients with pre-existing damage to those vessels (from diabetes and high blood pressure) face higher risk of serious disease.
Kill Dill: Your heart has abundant ACE-2 and the don loves it. Low oxygen can collapse your heart from a cardiac arrest and clots from arteries block it, especially the left ventricle—powerhouse chamber of our blood pump. Or a cytokine storm could ravage the heart as it does other organs.
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Text curated by Rituparna Kakoty
