SALT LAKE CITY — Doctors have learned a lot about COVID-19 since the pandemic began. Those who now regularly treat patients with severe infection are reporting not just respiratory problems, but serious complications throughout patients’ bodies.
Some have kidney failure. A smaller share have heart issues, including younger adults who were considered to have little risk. Some have serious digestive issues or liver problems consistent with hepatitis. Some suffer strokes, even patients in their 30s, 40s and 50s.
Children, many under age 5, occasionally show up with a constellation of troublesome symptoms that resemble Kawasaki disease, all related to inflammation and starting with fever higher than 101 degrees Fahrenheit that lasts for days. They may have rash, bright red eyes and swollen hands, feet and glands. Some have heart complications. The syndrome makes them critically ill.
And some symptoms are just odd. Patients with “silent hypoxia” may have no complaints about shortness of breath while their blood oxygen level hovers around 60% to 70% — above 94% is normal — alarming doctors, who say the brain is not appropriately signaling that the patient is in trouble.
All told, the U.S. death toll from COVID-19 is roughly equivalent to two attacks on the Twin Towers every week, multiple sources note.
As America reopens, she needs to know what she’s dealing with and not drop her guard or become less vigilant in avoiding this highly infectious virus. While most with COVID-19 will skate by with few or no symptoms, in severe cases the virus ravages its victims and sometimes kills.
How it begins
Several months into this unprecedented global health crisis, medical experts and researchers are still learning how SARS-CoV-2, the name of the virus that causes COVID-19, spreads and harms.
It gets in through the eyes, nose or mouth, then moves to the back of the throat, which has proven to be a launching pad for the virus’ attack. Coronaviruses, including this one, have spiky proteins on their outer shell that resemble crowns (hence the name “corona”). The virus is “enveloped” or coated with lipids that are delicate, which is why hand sanitizer and soap can kill it on skin surface and why consistent vigorous hand-washing is the best defense. It rips open that envelope.
Inside the body, that same envelope helps the virus hide from the immune system. Experts at Des Moines University say enveloped viruses create longer-lasting, more complex illnesses and it’s harder to make a vaccine for them.
The spikes fit perfectly into a matching protein receptor called angiotensin-converting enzyme 2 (ACE2). ACE2 is an enzyme common on the outer surface of cells in many organs. Among other functions, it helps regulate blood pressure, wound healing and inflammation. But in COVID-19, the virus uses it to enter those cells and hijack their machinery to replicate itself.
A study in the European Heart Journal suggests men may be more prone to COVID infection because they have more ACE 2 receptors than women have.
The viral copies can infect others when those with COVID-19 cough or even exhale.
Immune system running amok
The infected individual’s immune system — charged with protecting the person from viral, bacterial and other invaders — determines what the disease will look like or if it will even be noticeable. If the innate immune system acts fast and gobbles up whatever it sees as posing danger, it’s good news.
The adaptive immune system is slower kicking in, but mops cleanup.
Some believe the innate system works faster in kids than in adults, which may explain why they are typically not sickened as much. It destroys more of their viral load early.
The immune response can be very tricky — and dangerous. You’d think a strong immune response is a good thing, but many of the sickest people are those whose body mounted an excessive response.
The immune system calls on cytokines, “messenger” proteins that help direct the immune system’s defense. Cytokines are a very important and normal part of the immune response, but only to a point, said Dr. Brandon Webb, Intermountain Healthcare infectious disease physician and chairman of Intermountain’s COVID-19 therapeutics team.
Sometime they unleash a disproportionate attack that damages not just the invading virus, but the body’s tissues. That “cytokine storm” can rage, whipping up inflammation that damages the lungs, the liver, the kidneys, blood vessels and other organs — maybe even the central nervous system. It can create blood clots throughout the body.
Dr. Peter Marshall treats patients whose symptoms are extensive. The vice chief for medical critical care and clinical associate professor at the Keck School of Medicine at the University of Southern California said they often have clotting problems in multiple organs. Depending on where they are, clots can cause strokes, heart attack, pulmonary embolism.
The cytokine storm is the main problem in a bad disease, said Marshall.
The storm rages
A cytokine storm is terrible news. It causes acute respiratory distress syndrome (ARDS), the lungs filling with fluid. ARDS is the most lethal complication in COVID-19.
Dr. Jeremy Voros, medical director of St. Mark’s Hospital emergency department, said clotting issues were discovered when doctors saw patients with discolored toes, the so-called COVID toes. Initially, they attributed it to low oxygen levels, but “have found that it looks like it’s micro clots forming in the small blood vessels and extremities.”
There could be some genetic predisposition to clotting. A test called the D dimer measurement indicates propensity to form clots. Treatment has included aggressive clot prevention for COVID-19 patients in intensive care.
A blood test can measure cytokine levels and determine if there’s a storm. Some drugs have been shown to tame cytokine storms in other illnesses, though it’s not yet clear if they work well against the COVID-19 version.
In the cytokine storm, some patients experience high blood pressure in the lung that causes heart weakness and failure, according to Dr. Joseph Khabbaza, pulmonary and critical care physician at Cleveland Clinic.
ACE2 receptors are tricky, too, both blessing and curse in COVID-19. While they let the virus in, they also help regulate the immune system, so those with more ACE2 receptors are believed to be less likely to have an over-the-top response.
And here’s something else that at first blush seems to make no sense: Doctors sometimes tamp down a patient’s immune system to calm the cytokine storm. So while being immune-compromised because of illness or from immune-suppression drugs puts one at greater risk from COVID, that weakened immune may prevent a cytokine storm.
Symptoms: weird vs. expected
The classic symptoms of COVID-19 are fever, dry cough and body aches.
Far less expected by those used to respiratory infections was the complete loss of sense of smell and taste some patients experience. The senses return if the patient recovers.
Patients complain of dire fatigue, the kind that makes someone stop and rest when climbing a few stairs. “And then we hook them up to our monitors and find they have an oxygen level of 80%, which is very low,” said Voros. Yet the patients are, atypically, not short of breath, so the disease didn’t catch their attention early.
Voros said doctors are very familiar with how to manage respiratory infections, but “for whatever reason, this disease is behaving differently than those other conditions.” Early on, when patients showed up with oxygen levels drifting as low as 70%, doctors were being very aggressive and putting patients on a ventilator. Over time, they saw that often didn’t make much difference in raising oxygen level. Putting patients on their stomachs, called proning, did, he said. With COVID, that makes a difference early on.
Some patients still require a ventilator or heart-lung machine.
Acute respiratory disease syndrome (ARDS) is responsible for a very large portion of the deaths from COVID-19. Lungs are supposed to stretch to fill, but with ARDS, the lungs fill with fluid and aren’t as stretchy. Proning allows more oxygen to get in.
Severe inflammation in the lungs makes one vulnerable to bacterial pneumonia. Add to that kidney failure and you’re really sick, Voros said. You might also develop a pulmonary embolism because of the clotting risk factors “and suddenly, you’re much sicker because you have these additional complications.”
The virus can directly attack both heart and kidney. It can create irregular heart rhythms that may cause cardiac arrest.
“They seem to be doing really well as far as respiratory status goes, and then suddenly they develop a cardiac issue that seems out of proportion to their respiratory issues,” Mitchell Elkind, a Columbia University neurologist and president-elect of the American Heart Association, recently told The Washington Post. “This seems to be out of proportion to their lung disease, which makes people wonder about that direct effect.”
Doctors suspect the high degree of kidney failure is related to the multi-organ failure and sepsis seen with other viruses, too, but Marshall said it’s more prevalent among patients with COVID. Patients may require dialysis, which may be temporary.
Many patients experience gastrointestinal symptoms, possibly because the digestive system has many ACE2 receptors.
Seriously ill patients may become confused or delirious. Doctors don’t think the virus is infecting the central nervous system, Marshall said, but rather the cytokine storm may be contributing to sepsis and the body’s response may contribute to confusion. He said they wonder about small seizures that aren’t readily seen. Another possibility is small clots in the tiny blood vessels of the brain.
Treating COVID-19 requires strategy and balancing risks.
The cytokine storm can damage the lungs, which can trigger more cytokines and immune and inflammatory cells to run amok, causing blood pressure to drop.
ACE2 receptors help lower blood pressure, so trying to block the receptor to prevent viral entry can send blood pressure spiraling, increasing risk of heart failure and kidney injuries, as well as more damaging inflammation.
Trying to lessen the cytokine storm by muting the immune response can unfortunately lower the chance of killing the virus.
And there are, of course, many unknowns when it comes to this coronavirus.
Experts aren’t even positive if people who never show symptoms but are infected can infect others or what causes some people to be more infectious, so-called “super spreaders.”
WEBMD said that on autopsy and biopsy, SARS-CoV-2 viral particles were detectable not just in the nasal passage and throat or in organs, but also in tears and stool. What that means in terms of infecting others isn’t known.
The virus has even been detected in semen, raising the specter of sexual transmission, though it has not been proven to occur.