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Coronavirus: How sick will you get?

Together, a Palo Alto couple fell ill. He recovered quickly. She didn’t. Why?

Monica and Adrian Arima both were infected by the COVID-19 virus at the same time on the same Nile River cruise, probably during a shared dinner buffet between the Egyptian cities of Aswan and Luxor. As they traveled home to Palo Alto, the couple’s early symptoms — body aches and low-grade fever — were identical.

But then, mysteriously, their experiences suddenly diverged. Monica spent 13 days at Stanford Hospital; Adrian was there for just three days. She needed extra oxygen and an experimental drug; he didn’t.

Now, weeks later, she still has a cough. He is fully recovered, healthy enough to go food shopping and do other errands. Meanwhile, two of their traveling companions — in their 70s and 80s — tested positive but never suffered symptoms.

Their experience illustrates one of the many puzzling questions raised by the lethal new disease: Why is COVID-19 so inexplicably and dreadfully selective? The difference between life and death can depend on the patient’s health and age — but not always.

To understand, scientists are scrutinizing patients’ medical histories, genomes and recoveries for any clues to explain this mystery.

“Why are some people completely asymptomatic, some have mild disease, others have severe disease but recover — and others have fatal disease? We are still trying to figure this out,” said Dr. Brian Schwartz, Vice Chief for Clinical Affairs in UC San Francisco’s Division of Infectious Diseases.

“It is a small subset of people that will go on to develop serious disease. Most will not,” he said. “We want to learn how to prevent people from developing serious disease — and if they do, figure out how to treat it the right way.”

It’s well known that death rates are higher among older people. Only 0.2% of people younger than 19 die. But for people between the ages of 60 and 69, the death rate is 3.6%. It jumps to 8% to 12.5% for those between ages 70 and 79 and 14.8% to 20% percent for those older than 80.

But there’s more to it than that. Monica Arima is age 64; her husband Adrian, at 70, is six years her senior. But she has asthma and diabetes, while his underlying health is good.

Emerging U.S. data confirms trends seen in China and Italy: Rates of serious COVID-related symptoms are higher in those with other medical problems and risk factors, such as diabetes, hypertension, chronic obstructive pulmonary disease, coronary artery disease, cerebrovascular disease, chronic renal disease and smoking. In a U.S. Centers for Disease Control report released on Tuesday, higher percentages of patients with underlying conditions were admitted to the hospital and to an ICU than patients without other health issues.

There may also be a genetic influence.

“One of the things that we’ve learned from human genetics is that there are extremes at the human phenotype distribution, and pathogen susceptibility is no different,” Stanford geneticist Carlos Bustamante told the journal Science. Stanford is part of a “COVID-19 Host Genetics Initiative,” a Finnish effort to link genetic variants associated with COVID-19 susceptibility and severity.

“There are going to be people who are particularly susceptible, and there are going to be those who are particularly resistant,” he said.

Biologically, what’s going on?

One leading theory is focused on the “doors” of a cell that permit the virus to enter. We know that the virus enters the body through epithelial cells in the respiratory tract. To get inside the cell, the virus uses a “door” — a receptor called ACE-2 (angiotensin converting enzyme 2) — on the cell’s surface.

Individual variations in this receptor could make it harder or easier for the virus to enter, cause infection and burrow deep into the lungs. In some of us, the cell “door” may open easily; in others, it may stay closed.

Or perhaps some people simply have more of these receptors on their cells. With more “doors,” the virus may enter more readily, so patients suffer worse infection and more serious disease, said Schwartz.

There’s an abundance of this ACE-2 receptor in cells in the lower lung, which may explain the high incidence of pneumonia and bronchitis in those with severe COVID-19 infection.

Once someone is infected, their immune system’s response to that infection is likely the next big decider of their fate.

Doctors are discovering that nine or 10 days into the illness, there’s a fork in the road. In most people, the immune system launches a carefully calibrated and effective response, so they recover. But in others, the immune response is too aggressive, triggering massive inflammation in what’s called a “cytokine storm.”  Immune cells are overproduced and flood into the lungs, making it hard to breathe and leading to often fatal Acute Respiratory Distress Syndrome. Those people develop sepsis, then acute kidney and heart damage. By day 20, they may be dead.

Why does the immune system misbehave? One reason may be age. As we get older, our immune response grows less accurate. It doesn’t respond as effectively, and it is not as well regulated. Genetics may also play a role.

Finally, other pre-existing illnesses seem to elevate our risk, although the precise mechanisms aren’t known.

https://www.mercurynews.com/2020/04/01/coronavirus-how-sick-will-you-get/

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