Before getting into the science and new medical discoveries about how Coronavirus truly kills (below), I’d like to first address the one thing that seems to kill more than the virus itself: human arrogance!
I confess that I don’t get easily surprised by such a thing anymore. Most people think they know it all just because someone else’s once wrote or said something that aligns with their unsubstantiated thoughts. They never research or validate such knowledge, they simply embrace it as the final truth and pass their whatever unsubstantiated understandings along as if they are now experts on the matter, adding another link to the ever-growing chain of idiocracy.
If it wasn’t for this pandemic situation and for the risk it brings upon everyone, it would be amusing and hilarious to continue watching and laughing about it, but it is not the case anymore.
Among many of the crazy things people repeat like parrots, one is so stupidly wrong that I fail to understand how they can even consider repeating it:
Why should one care about it? Because it is dangerous for the world! Not caring for such an argument would be the same as not caring if a red button says: “Nuclear Launch“, and this same person implies “It is just a red button, technically not different than ones found in elevators“. I am sure you wouldn’t respond “Cool. Press it, though!“
But, amazingly enough, if you bring all the facts and explain how wrong the person is, your arguments won’t be sufficient because they may respond with an even worst argument like this one:
This is another absurd statement I keep hearing over, and over, and over…
It is not only fundamentally wrong in all possible ways to compare those facts like that, but it is also outrageously disrespectful such a disregarding to the people has been affected by both situations! So, I lost my cool a little bit and answered the person like this:
I was mad because statistics are not mere numbers, those who died for no good reason were people that once lived among us! They had families, they used to laugh, work, play sports, watch TV, dream, travel… They used to do all the same as we all still have the chance to do. So, the picture of the sufferings those numbers paints is real, and I hate it when people make it seem banal. But, ultimately, that was a good discussion because it motivated me to research and write this article…
I strongly believe people must understand that: CORONAVIRUS KILLS, and IT KILLS A LOT. Not only that, but people must also realize that WE ARE THE AGENTS OF THE KILLING when we ignore the science behind this pandemic.
So, lets look at it, shall we?
Why Coronavirus is not a strong flu
As time pass and more we learn from the COVID-19 disease, more we understand that patients can also develop seizures and suffer from kidneys failures caused by the Coronavirus, just to name the more common ones, all that beyond the respiratory failure.
Clinicians and pathologists are struggling to understand the damage wrought by the Coronavirus as it tears through the body. They are realizing that although the lungs are ground zero, its reach can extend to many organs including the heart and blood vessels, kidneys, gut, and brain.
“COVID-19 can attack almost anything in the body with devastating consequences,” says cardiologist Harlan Krumholz of Yale University and Yale-New Haven Hospital, who is leading multiple efforts to gather clinical data on COVID-19. “Its ferocity is breathtaking and humbling.”
Understanding the rampage could help the doctors on the front lines treat the fraction of infected people who become desperate and sometimes mysteriously ill.
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).
What follows is a snapshot of the fast-evolving understanding of how the virus attacks cells around the body, especially in the roughly 5% of patients who become critically ill. Despite thousands of papers now spilling into journals and onto preprint servers every week, a clear picture is elusive, as the virus acts as no pathogen humanity has ever seen.
Without larger, prospective controlled studies that are only now being launched, scientists must pull information from small studies and case reports, often published at warp speed and not yet peer-reviewed. “We need to keep a very open mind as this phenomenon goes forward,” says Nancy Reau, a liver transplant physician who has been treating COVID-19 patients at Rush University Medical Center. “We are still learning.”
The infection begins like a flu
When an infected person expels virus-laden droplets and someone else inhales them, the SARS-CoV-2 enters the nose and throat. It finds a welcome home in the lining of the nose, according to a preprint from scientists at the Wellcome Sanger Institute and elsewhere. They found that 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, an infected person may shed copious amounts of it, especially during the first week or so. Symptoms may be absent at this point. Most of the virus’ new victims develop a fever, dry cough, sore throat, loss of smell and taste, or head and body aches, but not everyone.
If the immune system doesn’t beat back SARS-CoV-2 during this initial phase, the virus then marches down the windpipe to attack the lungs, where it can turn deadly. The thinner, distant branches of the lung’s respiratory tree end in tiny air sacs called alveoli, each lined by a single layer of cells that are also rich in ACE2 receptors.
Normally, oxygen crosses the alveoli into the capillaries, tiny blood vessels that lie beside the air sacs; 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. 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.
There is a good video about this specific case in the article What Coronavirus Symptoms Look Like, Day By Day.
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 they struggle ever harder to breathe. On x-rays and computed tomography scans, their lungs are riddled with white opacities where black space — air — should be.
This is a real three-dimensional volume-rendered reconstruction that shows the distribution of the ground-glass opacities in a 41-year-old woman who presented with fever and positive polymerase chain reaction assay for the 2019 novel Coronavirus. Three representative axial thin-section chest CT images show multifocal ground-glass opacities without consolidation.
Commonly, these patients end up on ventilators. Many die. Autopsies show their alveoli became stuffed with fluid, white blood cells, mucus, and the detritus of destroyed lung cells.
Some clinicians suspect the driving force in many gravely ill patients’ downhill trajectories is a disastrous overreaction of the immune system known as a “cytokine storm,” which other viral infections are known to trigger. Cytokines are chemical signaling molecules that guide a healthy immune response; but in a cytokine storm, levels of certain cytokines soar far 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.
Some studies have shown elevated levels of these inflammation-inducing cytokines in the blood of hospitalized COVID-19 patients. “The real morbidity and mortality of this disease is probably driven by this out of proportion inflammatory response to the virus,” says Jamie Garfield, a pulmonologist who cares for COVID-19 patients at Temple University Hospital.
But others aren’t convinced. “There seems to have been a quick move to associate COVID-19 with these hyperinflammatory states. I haven’t really seen convincing data that that is the case,” says Joseph Levitt, a pulmonary critical care physician at the Stanford University School of Medicine.
He’s also worried that efforts to dampen a cytokine response could backfire. Several drugs targeting specific cytokines are in clinical trials in COVID-19 patients. But Levitt fears those drugs may suppress the immune response that the body needs to fight off the virus. “There’s a real risk that we allow more viral replication,” Levitt says.
Meanwhile, other scientists are zeroing in on an entirely different organ system that they say is driving some patients’ rapid deterioration: the heart and blood vessels.
Striking the heart
In Brescia, Italy, a 53-year-old woman walked into the emergency room of her local hospital with all the classic symptoms of a heart attack, including telltale signs in her electrocardiogram and high levels of a blood marker suggesting damaged cardiac muscles. Further tests showed cardiac swelling and scarring, and a left ventricle — normally the powerhouse chamber of the heart — so weak that it could only pump one-third its normal amount of blood. But when doctors injected dye in the coronary arteries, looking for the blockage that signifies a heart attack, they found none. Another test revealed why: The woman had COVID-19.
How the virus attacks the heart and blood vessels is a mystery, but dozens of preprints and papers attest that such damage is common. A 25 March paper in JAMA Cardiology documented heart damage in nearly 20% of patients out of 416 hospitalized for COVID-19 in Wuhan, China. In another Wuhan study, 44% of 36 patients admitted to the ICU had arrhythmias.
The disruption seems to extend to the blood itself. Among 184 COVID-19 patients in a Dutch ICU, 38% had blood that clotted abnormally, and almost one-third already had clots, according to a 10 April paper in Thrombosis Research. Blood clots can break apart and land in the lungs, blocking vital arteries — a condition known as pulmonary embolism, which has reportedly killed COVID-19 patients. Clots from arteries can also lodge in the brain, causing a stroke. Many patients have “dramatically” high levels of D-dimer, a byproduct of blood clots. “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,” says Behnood Bikdeli, a cardiovascular medicine fellow at Columbia University Medical Center.
Infection may also lead to blood vessel constriction. Reports are emerging of ischemia in the fingers and toes—a reduction in blood flow that can lead to swollen, painful digits, and tissue death.
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.
Behnood Bikdeli, Columbia University Irving Medical Center
Flooding the lungs
In the lungs, blood vessel constriction might help explain anecdotal reports of a perplexing phenomenon seen in pneumonia caused by COVID-19: Some patients have extremely low blood-oxygen levels and yet are not gasping for breath. It’s possible that at some stages of the disease, the virus alters the delicate balance of hormones that help regulate blood pressure and constricts blood vessels going to the lungs. So oxygen uptake is impeded by constricted blood vessels, rather than by clogged alveoli. “One theory is that the virus affects the vascular biology and that’s why we see these really low oxygen levels,” Levitt says.
If COVID-19 targets blood vessels, that could also help explain why patients with pre-existing damage to those vessels, for example from diabetes and high blood pressure, face a higher risk of serious disease. Recent Centers for Disease Control and Prevention (CDC) data on hospitalized patients in 14 U.S. states found that about one-third had chronic lung disease — but nearly as many had diabetes, and fully half had pre-existing high blood pressure.
Mangalmurti says she has been “shocked by the fact that we don’t have a huge number of asthmatics” or patients with other respiratory diseases in HUP’s ICU. “It’s very striking to us that risk factors seem to be vascular: diabetes, obesity, age, hypertension.”
Scientists are struggling to understand exactly what causes cardiovascular damage. The virus may directly attack the lining of the heart and blood vessels, which, like the nose and alveoli, are rich in ACE2 receptors. Or perhaps lack of oxygen, due to the chaos in the lungs, damages blood vessels. Or a cytokine storm could ravage the heart as it does other organs.
“We’re still at the beginning,” Krumholz says. “We really don’t understand who is vulnerable, why some people are affected so severely, why it comes on so rapidly … and why it is so hard [for some] to recover.”
The worldwide fears of ventilator shortages for failing lungs have received plenty of attention. Not so a scramble for another type of equipment: dialysis machines. “If these folks are not dying of lung failure, they’re dying of renal failure,” says neurologist Jennifer Frontera of New York University’s Langone Medical Center, which has treated thousands of COVID-19 patients. Her hospital is developing a dialysis protocol with different machines to support additional patients. The need for dialysis may be because the kidneys, abundantly endowed with ACE2 receptors, present another viral target.
According to one preprint, 27% of 85 hospitalized patients in Wuhan had kidney failure. Another reported that 59% of nearly 200 hospitalized COVID-19 patients in China’s Hubei and Sichuan provinces had protein in their urine, and 44% had blood; both suggest kidney damage. Those with acute kidney injury (AKI), were more than five times as likely to die as COVID-19 patients without it, the same Chinese preprint reported.
“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,” says Hongbo Jia, a neuroscientist at the Chinese Academy of Sciences’s Suzhou Institute of Biomedical Engineering and Technology and a co-author of that study.
Viral particles were identified in electron micrographs of kidneys from autopsies in one study, suggesting a direct viral attack. But kidney injury may also be collateral damage. Ventilators boost the risk of kidney damage, as do antiviral compounds including remdesivir, which is being deployed experimentally in COVID-19 patients. Cytokine storms also can dramatically reduce blood flow to the kidney, causing often-fatal damage. And pre-existing diseases like diabetes can increase the chances of kidney injury. “There is a whole bucket of people who already have some chronic kidney disease who are at higher risk for acute kidney injury,” says Suzanne Watnick, chief medical officer at Northwest Kidney Centers.
Buffeting the brain
Another striking set of symptoms in COVID-19 patients centers on the brain and central nervous system. Frontera says neurologists are needed to assess 5% to 10% of Coronavirus patients at her hospital. But she says that “is probably a gross underestimate” of the number whose brains are struggling, especially because many are sedated and on ventilators.
Frontera has seen patients with the brain inflammation encephalitis, with seizures, and with a “sympathetic storm,” a hyperreaction of the sympathetic nervous system that causes seizure-like symptoms and is most common after a traumatic brain injury. Some people with COVID-19 briefly lose consciousness. Others have strokes. Many report losing their sense of smell. And Frontera and others wonder whether in some cases, infection depresses the brain stem reflex that senses oxygen starvation. This is another explanation for anecdotal observations that some patients aren’t gasping for air, despite dangerously low blood oxygen levels.
ACE2 receptors are present in the neural cortex and brain stem, says Robert Stevens, an intensive care physician at Johns Hopkins Medicine. But it’s not known under what circumstances the virus penetrates the brain and interacts with these receptors. That said, the Coronavirus behind the 2003 severe acute respiratory syndrome (SARS) epidemic — a close cousin of today’s culprit — could infiltrate neurons and sometimes caused encephalitis.
On 3 April, a case study in the International Journal of Infectious Diseases, from a team in Japan, reported 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.
But other factors could be damaging the brain. For example, a cytokine storm could cause brain swelling, and the blood’s exaggerated tendency to clot could trigger strokes. The challenge now is to shift from conjecture to confidence, at a time when staff is focused on saving lives, and even neurologic assessments like inducing the gag reflex or transporting patients for brain scans risk spreading the virus.
Last month, Sherry Chou, a neurologist at the University of Pittsburgh Medical Center, began to organize a worldwide consortium that now includes 50 centers to draw neurological data from care patients already receive. The early goals are simple: Identify the prevalence of neurologic complications in hospitalized patients and document how they fare. Longer term, Chou and her colleagues hope to gather scans, lab tests, and other data to better understand the virus’s impact on the nervous system, including the brain.
Chou speculates about a possible invasion route: through the nose, then upward and through the olfactory bulb — explaining reports of a loss of smell — which connects to the brain. “It’s a nice sounding theory,” she says. “We really have to go and prove that.”
Most neurological symptoms “are reported from colleague to colleague by word of mouth,” Chou adds. “I don’t think anybody, and certainly not me, can say we’re experts.”
Reaching the gut
In early March, a 71-year-old Michigan woman returned from a Nile River cruise with bloody diarrhea, vomiting, and abdominal pain. Initially doctors suspected she had a common stomach bug, such as Salmonella. But after she developed a cough, doctors took a nasal swab and found her positive for the novel Coronavirus. A stool sample positive for viral RNA, as well as signs of colon injury seen in an endoscopy, pointed to a gastrointestinal (GI) infection with the Coronavirus, according to a paper posted online in The American Journal of Gastroenterology (AJG).
Her case adds to a growing body of evidence suggesting the new Coronavirus, like its cousin SARS, can infect the lining of the lower digestive tract, where the crucial ACE2 receptors are abundant. Viral RNA has been found in as many as 53% of sampled patients’ stool samples. And in a paper in press at Gastroenterology, a Chinese team reported finding the virus’ protein shell in gastric, duodenal, and rectal cells in biopsies from a COVID-19 patient. “I think it probably does replicate in the gastrointestinal tract,” says Mary Estes, a virologist at Baylor College of Medicine.
“Recent reports suggest up to half of patients, averaging about 20% across studies, experience diarrhea,” says Brennan Spiegel of Cedars-Sinai Medical Center in Los Angeles, co-editor-in-chief of AJG. GI symptoms aren’t on CDC’s list of COVID-19 symptoms, which could cause some COVID-19 cases to go undetected, Spiegel, and others say. “If you mainly have fever and diarrhea, you won’t be tested for COVID,” says Douglas Corley of Kaiser Permanente, Northern California, co-editor of Gastroenterology.
The presence of the virus in the GI tract raises the unsettling possibility that it could be passed on through feces. But it’s not yet clear whether stool contains intact, infectious virus, or only RNA and proteins. To date, “We have no evidence” that fecal transmission is important, says Coronavirus expert Stanley Perlman of the University of Iowa. CDC says that based on experiences with SARS and with the virus that causes Middle East respiratory syndrome, another dangerous cousin of the new Coronavirus, the risk from fecal transmission is probably low.
The intestines are not the end of the disease’s march through the body. For example, up to one-third of hospitalized patients develop conjunctivitis — pink, watery eyes — although it’s not clear that the virus directly invades the eye. Other reports suggest liver damage: More than half of COVID-19 patients hospitalized in two Chinese centers had elevated levels of enzymes indicating injury to the liver or bile ducts. But several experts told Science that direct viral invasion isn’t likely the culprit. They say other events in a failing body, like drugs or an immune system in overdrive, are more likely driving the liver damage.
Conclusion, so far…
This map of the devastation that COVID-19 disease can inflict on the body is still just a sketch. It will take years of painstaking research to sharpen the picture of its reach, and the cascade of cardiovascular and immune effects it might set in motion. As science races ahead, from probing tissues under microscopes to testing drugs on patients, the hope is for treatments more wily than the virus that has stopped the world in its tracks.
Meanwhile, people, we all have the responsibility to stop those who insist on comparing Coronavirus with flu or minimize its risks. COVID-19 is a very serious, highly contagious, and deadly disease. And, even for those who manage to survive it, or are lucky enough to catch it and suffer mild or no symptoms, those people should be seriously concerned about their health for the future, and yet careful because it is not proven reinfections aren’t possible and, it is not discarded if cured individuals are exempted from carrying on the virus, thus keep spreading it.
It is everyone’s responsibility to know all that and educate others. So, please, share this article, make your comments below, and lets keep everyone safe by spreading information that has science behind it, not pure beliefs and hopes.