In March, a Chinese researcher warned scientists and doctors to expect the unexpected with COVID-19.

That researcher hit it on the nose, said UAB pulmonary critical care physician Dr. Sheetal Gandotra. “We had a lot to learn about the risk factors, symptoms, course of the disease, organ systems affected and recovery. But the basic tenets of excellent critical care remain the same.”

As doctors treat COVID-19 patients with a constellation of symptoms and organ damage, researchers continue to try to determine health outcomes for virus survivors. They have no long-term studies to guide them, because the disease surfaced in China in November 2019.

Initially, COVID-19 was thought of as a respiratory disease. But now, studies show the virus spreads its deadly effects through blood clots to the brain, heart, kidneys, endothelial cells that line blood vessels and other vital organs. From looking at the damage, some researchers have said a subset of patients who contract the coronavirus may suffer long-term damage from the disease.

Autopsies of COVID victims have found that the virus attacked the lungs the most ferociously, but the pathogen was found in other vital body organs. Pathologists found that oxygen deprivation to the brain and the formation of blood clots may start early in the disease process.

A study released in May by Lancet’s eClinical Medicine found abnormal clotting in the heart, kidneys and liver, as well as the lungs, leading study authors to suggest this may be a major cause of multiple organ failure in COVID patients. The blood clotting also may account for the high number of virus patients who suffer strokes.

“Early on, there were reports of people recovering from respiratory failure and dying rapidly and unexpectedly from cardiac complications,” Gandotra said. “I can’t say that we have seen a lot of that here at UAB.

“We do, of course, have complications along the course, particularly since patients with COVID 19 who get critically ill have long hospital courses with multiple organs affected, becoming particularly susceptible to secondary infections and they do sometimes develop cardiac complications such as arrhythmias (an irregular heart rhythm) or heart failure where the heart doesn’t pump properly.

“Patients who develop those complications and those with multiple organ systems involved have a higher mortality rate,” Gandotra said.

There are about 300 studies researching the effects of COVID-19 on patients and gathering information through autopsies of virus victims.

Researchers can compare, to a certain extent, the aftereffects of COVID to its sister viruses: Middle East Respiratory Syndrome, first reported in Saudi Arabia in 2012, and Severe Acute Respiratory Syndrome, which surfaced in China in 2002. But evidence so far has not shown whether patients with COVID-19 will suffer permanent lung damage, as did about one third of the survivors of SARS and MERS.

Neurological Complications

Scientists have found that other viral infections can cause lasting neurological complications, which until recently pretty much flew under the radar as one of the effects of COVID. The 1918 flu pandemic, which killed 50,000 people worldwide and 675,000 in the U.S., was similarly associated with encephalitis, inflammation of the brain, in some patients.

Genetic material of the SARS-COV-2 virus, the technical name for the virus that causes COVID-19, has been found in spinal fluid and viral particles in the brain of COVID victims, according to studies.

Neurologic complications found in SARS and MERS patients, including muscular weakness, numbness and burning or prickling, did not occur until about two to three weeks into the course of the diseases. Other more serious complications, such as confusion and comas, also were seen in MERS patients.

Mitchell Elkind, president-elect of the American Heart Association and professor of neurology and epidemiology at Columbia University, said doctors should be “on the lookout for long-term neurocognitive problems,” including decreased concentration and memory as well as dysfunction of the peripheral nerves that lead to the “arms, legs, fingers and toes.”

A study in JAMA Neurology found that more than 36% of 214 patients in Wuhan, China, experienced neurologic symptoms during the course of their COVID-19 illness. Dizziness and headache were among the most common symptoms listed; instances of stroke and loss of taste and smell were also reported.

The Brain-Virus Connection

“I think at this point, I would say that we know something” is happening when it comes to COVID-19 and the brain,” Dr. Sherry Chou, associate professor of critical care medicine, neurology and neurosurgery at the University of Pittsburgh, said in the article. “But we definitely don’t know enough.”

Does it target the nervous system directly? Or is the brain merely a victim of the body’s reaction to the infection?

“We’re really in uncharted waters here,” Chou said, noting that most of what is known about how the virus attacks the body is still anecdotal due to its newness and the current focus on care and containment.

A study of 125 hospitalized patients with COVID reported in Lancet Psychiatry in June found that:

• 57 patients had an ischemic stroke, caused by a blood clot to the brain.
• 39 patients had an altered mental state, including encephalitis, which is brain inflammation, and encephalopathy, a disease that alters brain function.
• 10 patients had psychosis.
• 6 patients had issues akin to dementia.

“We don’t know yet if the encephalopathy is more severe with COVID-19 patents than with other viruses, but I can tell you we’ve been seeing quite a lot of it,” said neurologist Elissa Flory of the Henry Ford Foundation in Detroit. “As the number of cases increase, you will start to see not only the common manifestations but also the uncommon manifestations …  and we’re seeing them all at once, which is not something any of us have encountered in our lifetimes.”

Strokes are more common among older patients with COVID, but researchers found the altered mental states among half of the patients younger than 60.

Gandotra says she has seen patients with altered mental status. “When patients get to us in the ICUs, they usually have several reasons to have acute encephalopathy — their poor respiratory status with low oxygen numbers concurrent with other infections, or neurologic manifestations of COVID. “But it is hard to know when people get to us in the critical care unit what that is from. Certainly low oxygen numbers will alter mental states. And it is difficult for us to tell if the numbers are a manifestation of COVID,” she said.

During the recovery phase, the mental states of patients are closely monitored as sedation is discontinued.

“Medical staff check to see if patients are regaining their mental status or are in an appropriately wakeful stage, following commands and starting to interact. If not, we pursue additional evaluation to identify potential causes which can be a CT to the head or MRI or EEG,” Gandotra said.

“Certainly it seems that COVID can affect the brain, and we are waiting to better understand the how and why. There are many sequelae of COVID-19 and acute encephalopathy is just one of them and can be due to a variety of underlying causes,” she said. Sequelae is a pathological condition resulting from a disease, injury or trauma.

Research Into Treatments

Research has found two drugs to aid in fighting COVID, Remdesivir, believed to inhibit the virus from replicating itself, and dexamethasone, an anti-inflammatory drug.

Monday, UAB announced that one vaccine candidate researched on mice at the university has shown positive preclinical results. The research on AdCOVID was done in collaboration with Altimmune, a biopharmaceutical company in Maryland.

The virus learning curve extends from research to COVID intensive care units. UAB epidemiologist Dr. Jodie Dionne-Odom said recently that the hospital is learning more about how to take care of COVID patients.

There were 102 virus patients at UAB on Sunday. More than two-thirds of hospitalized coronavirus patients usually need ventilators to breathe. While intensive care units at some hospitals across the nation have maxed out, Dionne-Odom said UAB creates capacity for the virus patients.

“But every bed for a COVID patient could be for someone who has suffered a heart attack or stroke,” she said.

UAB this week implemented its surge plan, which will turn one waiting room into a 10-bed acute care COVID care area and move the emergency waiting room.

Gandotra, a pulmonary critical care physician, is among the doctors on UAB’s frontline who treat patients in the COVID ICU. Critically ill patients who require ventilation spend an average of two weeks on a ventilator, and their hospital stay can be much longer, she said.

Patients who develop respiratory manifestations of COVID-19, such as severe pneumonia or in the most severe form, acute respiratory distress syndrome, often require mechanical ventilation.

“Patients are attached to the machine via a plastic tube that passes into the mouth and through the vocal cords to the trachea. The machine pumps oxygen into the lungs. This machine is a type of life support.

“Ventilated patients are often not conscious. They need sedation to be comfortable while we manage their breathing with the ventilator. Many patients are placed in a prone position on their stomachs, which helps with oxygenation. They are turned daily.”

“Some patients with COVID-19 never need to receive ICU-level care. They’re usually in the hospital (rather than home) because of new oxygen needs,” Gandotra said. “Usually, the patients who do not have a worsening course and do not require critical care will have a shorter hospital course and, we think, faster recovery, though reports suggest symptoms can still linger for weeks or longer.”

After their release from the hospital, COVID patients continue to be monitored by pulmonary and/or infectious disease doctors.

“They have had long-term hospital courses with COVID, and we expect them to have long-term problems, such as weakness, shortness of breath and fatigue for weeks to months afterward,” Gandotra said. “They may continue to have difficulties with their physical function, finding it challenging to return to their pre-COVID critical illness lifestyle.”

When the virus struck last March, pulmonary critical care physicians at UAB added extra teams to care for COVID patients, as well as providing care for critically ill patients in ICUs.

Gandotra worked 7 a.m.-7 p.m., seven days a week from March through June, and then had nonclinical time to work on research and administrative issues and to prepare an education curriculum for doctors pursuing subspecialty training.

In the COVID Ward 

Gandotra’s day with COVID patients begins by reviewing health records, then seeing and evaluating patients with a team made up of nurse practitioners, nurses, respiratory therapists and doctors pursuing more training to create a plan of action for the day.

“Along the way, we’ll discuss care with any consulting teams either during their rounds in the unit or by phone afterward.

“We make it a point for someone on the team to talk to each patient’s family during the day. Sometimes, if a patient’s clinical condition is particularly tenuous, multiple times a day,” she said. “We have family meetings as needed, mostly by phone on conference calls and when possible or necessary in person. We try and make sure that families understand the clinical condition of their loved one, whether they are worsening, improving or staying the same.

“We have many difficult conversations, asking about decisions. For example whether their loved one would want dialysis if they are developing acute renal failure, and how long they’d accept life support for, particularly if things are not improving,” Gandotra said.

“The goal is always to provide care that is in line with the patient’s wishes, and we do our best to ensure that the ICU care and interventions will ultimately still fulfill the patient’s desired quality of life.”

She says the most stunning thing about the COVID ICU, aside from the sheer number of critically ill patients requiring multiple forms of life support from the same disease process at the same time, is “the absence of families and personal effects.”

“There is no one at bedside to tell me about their loved ones. The medical staff serve as people’s families,” she said.

Families can see COVID patients electronically, via video calls.

“These nurses are the best. I have seen them wash a patient’s hair before families see them so the patients can look their best even at this … one of the worst times of their lives.”

Gandotra said it is striking to most doctors how fast research has moved to find and implement treatments.

“We balance the risk versus benefit,” she said “The treatment should ideally improve the outcome, and we do not want to inadvertently cause harm by implementing therapies that haven’t been well-studied — at least as well as they can be during a pandemic.”