‘Something we’ve never seen before’: Scientists still trying to understand baffling, unpredictable coronavirus – USA TODAY

Dr. Anthony Fauci told senators "it is without a doubt that there will be infections" in the fall and warned of more deaths without adequate response. USA TODAY

MILWAUKEE The new coronavirus has spread like wildfire, killed and spared people of all ages and all health conditions, baffled doctors, defied guidance and conventional wisdom, and produced an unprecedented array of symptoms.

There's never been a virus like it.

"This gets into every major biological process in our cells," said Nevan J. Krogan, a molecular biologist at the University of California, San Francisco, who has studied HIV, Ebola, Zika, dengue and other viruses over the past 13 years.

"At the molecular level, it's something we've never seen before, and then look at what it does to the body the long list of symptoms we've never seen that before."

As Americans debate the reopening of businesses, bars, schools and other aspects of everydaylife, it's important to understandthe virus weare up against andwhy it has sown so muchsuffering and confusion.

At first, the virus was thought to be mostlya risk to older adults and people with chronic illnesses; its primary point of attack, the lungs. Then 30- and 40-years-olds with the virus began dying of strokes. Recently,a small number of infected childrenhave died of a mysterious illness resembling Kawasaki disease.

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Symptoms of COVID-19 range from fever, coughing and shortness of breath tothe lossof smell and taste andthe angry red swelling that has come to be known as "COVID toes."Studies have found that damage fromSARS-CoV-2, the virus that causes the disease COVID-19,isn't limited to the lungs; itcan includethe heart, liver, kidneys, gastrointestinal systemand bowels.

To understand avirus' "motivation" why it does what it does keep in mind that it is aparasite. Itlives inside its humanor animal hosttaking what it needs at the expense ofthehost.

As long as itfinds hosts withoutimmunity, and as long as its ownmutations do not weakenits ability to spread and multiply,the virusthrives.

Key benchmarks of a virus are how widely it spreads and how deadly it is to those it infects.

In the five months since it was first identified in Wuhan, China, SARS-CoV-2 has infected more than 4.5 million people across the globe, killing more than 300,000.

"The thing that strikes me about the clinical aspect is the shear amount of transmissibility," said Megan Freeman, a virologist and specialist in pediatric infectious diseases at UPMC Children's Hospital of Pittsburgh.

"There are very few viruses that are more contagious than this one," agreed Mark Schleiss, an investigator for the Institute of Molecular Virology at the University of Minnesota.

A single COVID-19 patient spreads the diseaseto a median of 5.7 people, making it twice as contagiousasthe 1918 Spanish flu, according to areport in the journal Emerging Infectious Diseases.

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The rateof infection in the U.S.whatexperts are referring towhen they talkabout "flattening the curve" has slowed. Even so, thenation is still averaging about 1,000 COVID-19 deaths a day, roughly twice the number of deaths from 9/11 every week.

Thousands of theworld's best scientists have worked with remarkable speed seeking to understand the new coronavirus. They deciphered its genetic code in barely a week and have produced scores of papers suggesting possible treatments and vaccines.

"The canvas we call COVID-19 was blank 16 weeks ago," said Gregory Poland, director of Mayo Clinic's Vaccine Research Group. "We've filled in a lot of dots, but we have so much more to go."

"We don't understand HIV that well in my opinion," Krogan said, "and we've been studying that for decades."

Scientistsknow somebut not all of the reasons the new coronavirusspreads so easily. Freeman points to several factors, including one thatdistinguishes SARS-CoV-2from the virus it closely resembles, Severe Acute Respiratory Syndrome (SARS).

SARS attacks the lower respiratory system, whose job it is to pullin air from the upper respiratory system.

SARS-CoV-2, however, attacks the upper respiratory system, the pathway that allows air to travelin and out of the lungs aswe breathe. The upperairway is also the system involved when we cough.

The upper respiratory system offers a more efficient means of spreading, Freeman said.

"That's why it is more transmissible. ... When this emerged probably there was some mutation that adapted it to use the upper airway, and the upper airway has made it very successful."

A seconddifference between SARS and SARS-CoV-2involvesthebond that allows viral cells to attach to human cells andinfect them. With both viruses, this bond forms between theSpike Protein on the virus and a regiononthe outside of the human cell called the ACE-2 receptor.

Both viruses usethis bond to enter cells,but the bond is much stronger with the new coronavirus than it was with SARS. That is why many of the potential treatments so far are designed tounderminethat bond.

"You always want to target the Achilles' heel of the virus, something the virus does not have the luxury of changing too much" explained Maria Elena Bottazzi, a professor of pediatrics at Baylor College of Medicineand co-developer of a potential SARS vaccine that is going to be tested on SARS-CoV-2.

Althoughpublic health leaders compared the new coronavirus to seasonal flu early on, coronaviruses have a special feature that separates them from other viruses likeflu. Theyhave their ownproofreading system that helps limit mistakes in theirgenetic code known as mutations.

"Flu viruses make six and a half times more mistakes than coronaviruses do," Freemansaid.

Even as the spread of the virus slows in the United States, some researchers fear what will happen if major outbreaks hitpoorer, densely populated cities in Africa.

"Look at the problems we've had," Poland warned. "Now amplify that through areas that have civil wars, that have corruption, that have scarce resources. That's a humanitarian disaster in the making."

The virus' skill at spreading poses one challenge; what it does inside the human body poses another.

Much of what scientists have learned so far about the new coronavirus suggests that it is aremarkabledestroyer at both the micro and macro levels, decimatingindividual cells andentireorgans.

At the molecular level, the virus disrupts some of the mostfundamental functions of life: cell division; the systemcells use to talk with one another; and their abilitytomake proteins.

The proteins ourbodies make help uscarry out almost every human action from eating and walkingto breathing and thinking.

Once a person ingests the new coronavirus, it enters the lungs and directly infects the air sacs, the microscopic workhorses that take in the air we breathe. In serious cases, the air sacs fillwith fluid, leaving less and less room for oxygen. This is a feature of what is known asCOVID-19 pneumonia.

The pneumoniacan lead to Acute Respiratory Distress Syndrome, a severe breathing condition that deprivesthe vital organs of oxygen.

A healthy blood oxygen level is usually between 95% and 100%. Below 90% is low. Some COVID-19 patients have been found to have blood oxygen levels below 65%.

As the air sacs are infected and damaged, this triggersthe immune system, which can lead to a dangerous condition calleda cytokine storm. In a cytokine storm, the immune system goes into overdrive andwinds up killing both healthy and diseased cells.

One of the most subtle and deadlyoffshoots of low blood oxygen is a condition called silent hypoxia.

As described by emergency room doctor Richard Levitan in a commentary inThe New York Times, silenthypoxia allows patients to develop low blood oxygen levels without realizing the problem until it dips intodangerous territory. Theybreathe faster to compensate for the lack of oxygenbut are unaware they arebreathing faster.

Levitan suggested that people can bypass long waits for coronavirustests,usinga simple devicecalleda pulse oximeteras an early warning system for detecting COVID-19 pneumonia.The device, which fits over your finger, measures blood oxygen levels, and can be boughtat pharmacies without prescription for about $30.

Unfortunately, SARS-CoV-2 does not restrictits damage to the lungs.

The virus also causes blood clots, which haveled to people in their 30s and 40s dying from strokes.

And then there are the recent cases in New York and Paris of childrenwith COVID-19 who develop symptoms closely resemblingKawasaki disease. The diseasebegins with a rash and fever, inflames blood vessels, andeventually can damage the coronary arteries that deliver blood to the heart.

"What is it about COVID-19 that it produces Kawasaki disease?" said Schleiss, at the University of Minnesota, who estimates he has seen more than 1,000 Kawasaki cases in his medical career.

"I don't think SARS-CoV-2 is a cause of Kawasaki disease, but it is the cause of something very similar."

Every few weeks, SARS-CoV-2 seems to reveal new and disturbing oddities.

A recent studyfrom China published in the journal JAMA Network Open, reported finding the new coronavirus in the semen of six of 38 infected men, raising concern that it may be possible to transmit the virus through sexual contact.

The virus also hasbeen found in patientstool samples and untreated wastewater. The Centers for Disease Control and Prevention has reported that standard methods atwastewater treatment plants should be effectiveenough to protect workers.

Such discoveries, however, raisefundamental questions, as we try to return toour old lives. Have we yet determined all of the ways the virus can spread from one person to another? Are there activities that may poserisks we have not anticipated?

At the University of California, San Francisco, Krogan said it will be important to examine the genetic scripts of both those who suffer severe cases of COVID-19and those who getmild or no disease at all.

"There are 30-year-olds and some of them are asymptomatic and others are on respirators. What the hell is that all about?"

Follow Mark Johnson on Twitter: @majohnso

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