Why does COVID-19 kill some, not others? Answer may lie in human immune system

Why does COVID-19 kill some, not others? Answer may lie in human immune system
Dr. Anthony Fauci at a White House news briefing on Tuesday, March 31, 2020. “There’s something there ... that we’re missing from a pathogenesis standpoint” about the coronavirus, he told CNN.Photo: Erin Schaff / New York Times
Why does COVID-19 kill some, not others? Answer may lie in human immune system
Dr. Carolyn Calfee of UCSF, on Thursday, March 26, 2020, in San Francisco. Calif. One thing common in virtually every critical COVId-19 case, she said, is the onset of acute respiratory distress syndrome, which is characterized by fluid leaking into the lungs. That is why many victims need a ventilator to breath.Photo: Jana Asenbrennerova / Special to The Chronicle

It is scary enough that a dangerous virus is multiplying throughout the world, but one of the most frightening aspects of COVID-19 is the mysterious way it affects its victims, killing some people and leaving others with mild or no symptoms.

It is a puzzle that has baffled medical professionals and prompted a batch of studies in the Bay Area and around the world to try to figure out what is going on. The early evidence is sobering.

Infectious disease specialists increasingly believe the perplexing randomness of who gets sickest may have less to do with SARS-CoV-2, the virus that causes the disease, than it does with some people’s overly robust immune responses to the infection.

The quandary has taken on new urgenocy, given that many hard hit victims are not old or harboring pre-existing medical conditions, but young, healthy and active people. That troubling fact was highlighted this week by Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases and a member of President Trump’s coronavirus task force.

“You get so many people who do well and then some people who just, bingo, they’re on a respirator, they’re on ECMO (a life-support machine) and they’re dead,” Fauci said during an interview with CNN medical correspondent Dr. Sanjay Gupta. “I mean, the dichotomy between that, there’s something there, Sanjay, that we’re missing from a pathogenesis standpoint. And I don’t think it’s only if you’re elderly or if you have underlying conditions. There’s something else going on there that hopefully we’ll ultimately figure out.”

The death toll is, no doubt, highest among the elderly and those with underlying medical conditions, but the extreme respiratory distress that causes those deaths — inflammation, the filling of the lungs with fluid, pneumonia — seems to be less selective.

“Some of the symptoms are caused by the inflammatory response to the virus,” said Levi Garraway, chief medical officer at Genentech, which is conducting trials on a drug called Atemra, which was designed to control overactive immune responses. “The response can be a good thing, but in some cases there may be an excessive response. That can lead to its own problems.”

Most auto-immune diseases, like rheumatoid arthritis, lupus and multiple sclerosis, are the result of a hyperactive immune response. Although the causes of most autoimmune diseases are unknown, it is believed that some kind of bacteria, virus or drug tricks the body and causes white blood cells to think healthy cells are invaders and attack them.

Experts theorize that it was the strong immune system responses of victims that caused so much death during the 1918 Spanish flu pandemic, which actually killed more young, healthy 20-to 40-year-olds than anyone else.

The coronavirus spreading across the globe appears to be triggering a similar auto-immune type reaction in certain people, experts say.

Dr. Carolyn Calfee, a professor of medicine and anesthesia at UCSF, is researching those reactions and trying to understand how this coronavirus differs from other infections.

One thing common in virtually every critical case, she said, is the onset of acute respiratory distress syndrome, or ARDS, which is characterized by fluid leaking into the lungs. That is why many victims need a ventilator to breath.

Calfee, an expert on the condition, said ARDS is caused by inflammation in the lungs, similar to a burn or blister on the skin.

“Imagine what happens when you burn your arm. Well, when you have acute injury to the air sacs in your lungs, a similar thing happens,” Calfee said. “The nice clean barrier between the air sacks and the blood becomes leaky and inflames and fluids begin pouring into the lungs.”

What’s strange, she said, is how suddenly ARDS materializes in COVID-19 patients and how difficult it is to eliminate.

She said patients may experience relatively mild, flu-like symptoms for as long as a week before symptoms of ARDS begin, and it’s onset is usually sudden, without warning. And then it often requires a week to several weeks on a ventilator — an unusually long time for a patient with a respiratory illness — for patients to recover, if they do.

Calfee and her colleagues are collecting blood and lung fluid samples trying to figure out what it is about some people’s immune systems that causes them to have such severe reactions. These kinds of studies are the key for dozens of university laboratories and biological institutes around the world trying to develop medicines and a vaccine.

Dr. Melanie Ott, a senior investigator with the Gladstone Institute of Virology and Immunology, in San Francisco’s Mission Bay, said the extreme coronavirus cases are the result of a unique interaction between the virus and its human host.

Viruses such as SARS-CoV-2, she explained, are microscopic parasites that cannot reproduce or live very long outside of an animal.

“It needs to go inside and hijack the machinery, which is what makes it so dangerous because it takes the host machinery away,” Ott said. “It propagates its genome into a host cell.”

The problems begin, experts say, when the body gets confused and attacks healthy cells along with the virus-compromised organisms in the lungs, causing an out-of-control inflammatory reaction that sometimes impacts the heart and gut, too.

Microbiologists must now comb through the sequenced genomes of the virus in search of the mechanisms that provoke such a harsh human immune system response. They will scour through the microbes in inflamed and healthy tissues, examine molecules in the fluid extracted from the lungs of sick people and search for a weakness in the virus that can be exploited.

“We’re trying to predict how this virus is vulnerable by replicating the infection and the damage it causes in humans,” Ott said.

The scientists working on this case have done it before with HIV/AIDS, which was once a death sentence and is now a chronic but treatable disease, and Hepatitis C, which can now be cured in eight weeks with a drug that was approved for use in 2014.

Duplicating those success stories isn’t an easy task, said Dr. Annie Luetkemeyer, an infectious disease specialist at San Francisco General Hospital, who participated in the clinical trials for both HIV/AIDs and Hepatitis C.

“There were no coronavirus experts” before this pandemic, Luetkemeyer said. “All of us had to step up and say, ‘what am I gonna do?’ We had to become COVID experts. ... Not only have we been asked to take care of this disease that nobody has ever seen before, but also figure out how to treat it.”

It appears now that the key to unlocking the mystery of the pandemic is to figure out why a damaging immune response occurs only in some people and what COVID-19 does to cause that reaction.

“You can learn a lot from a virus,” Ott said. “The more we learn, the more we can fight.”

Peter Fimrite is a San Francisco Chronicle staff writer. Email: [email protected] Twitter: @pfimrite