Pneumonia the most severe symptom of COVID-19

Heart problems, kidney damage, clots can occur

There’s a reason the virus that causes COVID-19 is called a novel coronavirus. Its symptoms are in particular ways unlike those caused by similar bugs.

The worst is pneumonia, the scary feeling that you can’t catch a breath. In some cases, the virus causes the lung to fill with so much fluid that a ventilator is needed to help patients breathe. Some don’t make it off the breathing machine.

In the five months since SARSCoV-2 was discovered in China, doctors and researchers have learned much about the virus and the disease it causes. But much is still based on hypotheses, educated guesses based on previous outbreaks of other diseases caused by coronaviruses, such as SARS and MERS.

Among the questions they would like answered is whether the virus helps kick the body’s immune system into such a high gear that it makes the illness worse.

They also would like to know why there are so many reports of kidney damage and heart problems, patients developing blood clots and coming down with diarrhea, even losing their senses of taste and smell.

“We’re really realizing in the last few weeks that this is very different from other viruses that we’ve dealt with,” said Dr. Luke Davis, a pulmonary specialist and associate professor of epidemiology at the Yale School of Public Health. “Coronavirus really has a pattern of illness to surprise and confound clinicians that are seeing tens of these patients every day.”

Davis said the coronavirus easily enters cells in the lungs and mucous membranes in the nose and mouth. “It turns out for this virus to do its work it really has to get inside our cells,” he said. “It starts using that factory to do its work.”

One aspect of COVID-19 is the way people start out with no symptoms, then feel feverish and achy and start to have trouble breathing. Then, suddenly they feel much worse.

“Folks can often present with just a fever and difficulty breathing and that can continue for about a week before the really severe lung issues can arise,” said Dr. Sunil Parikh, an associate professor of epidemiology at the school. “Folks who don’t do well can get severely ill over a few days. The body is responding in a robust way.

“It can be several days to a week before severe disease kicks in. What we’re learning is that you have to watch people really carefully,” he said.

That response of the body’s immune system, combined with the cellular infection, may be what causes pneumonia, when the tiny air sacs in the lungs, the alveoli, fill with fluid, preventing oxygen from getting to the body.

“Your body has two types of immune systems that work in parallel,” said Dr. Joseph Canterino, an assistant professor of medicine at the Yale School of Medicine and an infectious disease specialist at Yale New Haven Hospital. “You have an innate immune system and an adaptive immune system. They’re there all the time scouting out for invading pathogens.”

“When you have any infection anywhere in the body, your body generates an immune response … first to recruit more immune cells to that site to help fight the infection. Secondly, it dilates the blood vessels,” Canterino said.

The signals are sent out by proteins called cytokines, such as interferon and interleukin, which call in cells from the adaptive immune system.

The temperature at the site increases and the blood vessels dilate and become more permeable, allowing the infection-fighting cells to get to the site of infection. Fluid and other cells also leak out of the blood vessels and the area becomes inflamed. “That local inflammation response can spill out to the body and cause a systemic inflammation response,” Canterino said.

He said that in the sickest patients, there is a theory that there are two phases to the viral infection. The first phase involves the coronavirus itself, “invading cells, killing cells, and the innate immune system killing it off,” Canterino said.

The body begins to build antibodies to the virus, “but that can take days to weeks to build up those antibodies,” Canterino said. And how long the antibodies last differs from one infection to another. “For COVID this is still a big question,” he said. “Basically, our bodies are naïve to this infection. None of us have seen it before.”

The antibodies send out signals to attract infection-fighting cells, but there is a hypothesis that after 10 days, “when they get significantly worse, that this is caused by what is called the cytokine storm, which is this hyperinflammatory response the body is having, an exaggerated immune response to the infection that is causing more damage to the body than the virus is causing, and we really don’t understand why that is, but it has implications in treatment,” Canterino said.

“Potentially in this later stage of the infection, medication that can modulate the immune system might be better than medications that fight the virus,” he said. Otherwise, the proteins and white blood cells of the immune system will themselves fill the lungs’ air sacs.

COVID-19 tends to cause more severe breathing issues than the flu, Parikh said. “This is different from the influenza virus’ impacts on the lungs,” he said. “We don’t see this exuberant inflammatory response” in flu.

Another difference between COVID-19 and the flu is when people are contagious. “Typically in flu people are thought to be infectious right around the time they are presenting with symptoms,” Davis said. But someone infected with the coronavirus is “shedding” the virus one to three days before symptoms appear.

Without a vaccine, there is no way to stop the virus from entering cells by matching its protein to receptors on the cells. “It just matches up perfectly with the receptor on human cells and allows the virus to get in,” Davis said.

“Sometimes when there’s a bad firefight, there’s collateral damage,” Davis said. “The immune response seems to kick into high gear and make them very, very sick.”

In the worst cases, “pneumonia can progress to acute respiratory distress syndrome. That can happen in other infections, too,” Canterino said. “It’s basically this intense inflammatory response throughout the lungs. It makes ventilating these patients more difficult. That’s the main complication that we get concerned about in these patients.”

Also, “as a response to your body fighting infection … you could get kidney injury,” Canterino said. This is not unique to COVID-19. Heart problems also result from the increased strain put on the organ, but Canterino said it is unknown how much this plays a role in causing deaths or severe illness.

“For all of these issues, the challenge is figuring out what is due directly to the virus vs. what is due to medication side effects vs. what is due to comorbidities,” such as other illnesses, Parikh said. However, “we are seeing people having abnormal heart rhythms. We are seeing inflammation of the heart.”

“I think the pattern that we’re seeing with the heart dysfunction, with the kidney dysfunction is more and significant that we would see in a regular infection, so we think there’s something the virus is doing to these tissues,” Davis said. He said there is some evidence that the coronavirus “may actually be able to make its way into the brain.”

Parikh added that “we don’t know exactly what’s happening in these organs because it’s too early in the pandemic.”

While the emphasis has been on deaths, with more than 150,000 worldwide so far, COVID-19 is not a threat to most. “The big data from China showed that about 80 percent of people with the virus will get what is considered a minor infection,” Canterino said. “The majority of people who get this illness will get better, so that is encouraging. But I think if you crunch the numbers on a population level, it’s still pretty concerning.”

That’s because if 150 million people around the globe become infected with the coronavirus, that still means tens of millions of deaths.