CU Anschutz Experts Break COVID-19 Effects Down by Body Part

During the months-long pandemic, healthcare providers have seen a lot of things, often on levels they have never seen before. From brain fog and loss of smell to leg clots and purple toes, what began as a mysterious pulmonary disease has shown the world that its destructive powers far transcend the lungs.

While respiratory failure remains the most serious outcome of Coronavirus Disease 2019 (COVID-19), scientists have found evidence that SARS-CoV-2 can make its way into most major systems of the body using its spike proteins to attach and invade through ACE2 (angiotensin converting enzyme 2) receptors.

Below, experts from the School of Medicine at the University of Colorado Anschutz Medical Campus, share some of the effects they’ve seen on the body, from head to toe. But they note that the information must be kept in perspective.

The limited data focus almost exclusively on the minority of infected patients who end up hospitalized with COVID-19. And with the SARS-CoV-2 virus infecting upwards of 100 million (as of Jan. 26) people worldwide since its discovery a year ago, definitive connections are sparse. The need for many randomized studies remains.

Parts of the Body

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Ken Tyler, MD

Chair, Department of Neurology

As the motherboard of the body, the Central Nervous System (CNS) can fall prey to viruses like SARS-CoV-2 in debilitating and round-about ways. Encephalopathy, or a change in mental status (delirium, agitation, depressed level of consciousness) commonly plagues seriously ill COVID-19 patients in the ICU, affecting the brain via the complex CNS circuitry.

“Those cases are probably due to all the other head-to-toe organs that are affected – think the heart, the lungs, the degree of oxygenation in the blood, the blood pressure or thrombosis and clotting.”

ICU patients can also experience inflammation of the brain, with doctors questioning whether COVID-19’s sometimes severe systemic inflammatory response (cytokine storm) also results in an inflammatory encephalitis.

More rarely, the virus can directly invade the brain and produce encephalitis. In those cases, doctors can detect viral proteins and particles in the brain tissue or viral genome in the cerebrospinal fluid. Severe encephalitis from inflammation or direct virus invasion can cause seizures, weakness, paralysis, speech impairments and coma.

Recently, connections between COVID-19 and severe psychotic disorders began emerging, and long-term cognitive effects (brain fog, difficulty concentrating) are also being reported and prompting studies.

Peripheral nerve diseases, such as Acute Disseminated Encephalomyelitis (ADEM) and Guillain–Barré syndrome (GBS), have occurred in COVID-19 patients. Other effects include muscle and nerve injury and loss of taste and smell. (CU School of Medicine Professor Diego Restrepo, PhD, is researching the olfactory connection.)

Eyes

Richard Davidson, MD

Professor, Department of Ophthalmology

Red, itchy, gunky eyes – tell-tale signs of inflammation of the conjunctiva (conjunctivitis) – periodically coincide with SARS CoV-2 infection.

“It’s thought that the virus can actually enter the body through the conjunctiva. It has not been a very common form of entry. But it’s definitely something that we always have to keep in mind when evaluating patients with conjunctivitis.”

In a small study, 15% of COVID-19 patients reported eye soreness with no signs of conjunctivitis. Another small study found severe infections in some patients’ eyes called endophthalmitis, which can steal vision. “They think that COVID may have led to infection of the cornea.”

Eye inflammation, dryness, corneal problems and even hemorrhaging have been reported in COVID-19 patients, but they are rare and could easily be caused by other issues. Data are too limited to confirm causality with these ocular effects. “But there are a lot of people looking into it.”

Lungs

Marc Moss, MD

Professor, Division of Pulmonary Sciences and Critical Care

If body parts were the cast of COVID-19, the lungs would be the star. Although the past few months have taught doctors that SARS CoV-2 far exceeds a respiratory infection, the organs responsible for life-sustaining breath remain ground zero.

COVID-19 lung infection can result in Acute Respiratory Distress Syndrome (ARDS). First identified at the University of Colorado in 1967, ARDS remains the chief cause of COVID-19 morbidity and mortality.

“ARDS is more of a systemic response where the body’s immune system sort of goes out of control and starts causing damage to other parts of the lung in addition to where the initial pneumonia or infection began.”

Relatively early in the pandemic, providers realized not all patients required mechanical ventilation, finding other means, including prone positioning, to curb pulmonary issues. About 60% of ICU patients with lung involvement require mechanical ventilation.

Providers have been enhancing their knowledge of treating both COVID-19-induced ARDS and ARDS in general and using mechanical ventilation more effectively for treatment in the future.

Heart

Michael Bristow, MD, PhD

Professor, Division of Cardiology

Few organs escape the inflammatory attack of COVID-19, including the heart. Myocarditis (inflammation of the heart) tops the list of effects on the body’s circulatory center, but other effects can occur.

“Myocarditis is probably thought to be more common than it is. We’re learning it’s pretty unusual to have something serious going on that ends up adversely affecting the heart.”

Of course, damage does happen, likely more often in patients with underlying conditions. In addition to myocarditis the virus can directly invade the heart and damage cells.

Blood clots that are relatively common with COVID-19 also can block flow to the heart, causing heart attacks and organ damage.

Patients have reported dizziness, fatigue and higher heart rates weeks after discharge, with some concern it could be heart-damage related. “I think that’s still an open question. It can be in some cases, but it also could be a product of deconditioning from being sick for weeks.”

Kidneys

Michel Chonchol, MD

Professor, Division of Renal Disease and Hypertension

Kidney failure ranks high in terms of severe illness and death from COVID-19, evidenced in part during the early surge in New York City, when it was harder to find a dialysis machine than a respirator.

“Anywhere between 33% and 43% of all hospitalized COVID-19 patients will develop Acute Kidney Injury (AKI), and approximately half of those will require dialysis to replace their kidney function.”

Cell death, or Acute Tubular Necrosis (ATN), is the main cause of AKI, with some reports of direct SARS CoV-2 invasion of the kidney’s tubular cells. COVID-19’s huge cytokine storm also plays a role. “These patients are so sick, they have multi-organ failure, and the kidneys are one of the first organs to fail.”

Medications, including those required to manage some of the complications of mechanical ventilation, will worsen kidney problems, sometimes leading to dialysis. Risk factors include obesity, diabetes and underlying kidney disease. AKI disproportionately strikes black patients.

“Of those with AKI who require dialysis, the mortality rate is anywhere between 60% and 80%.” The death rate with AKI is not unique to COVID-19, but the high number of patients who develop AKI with the novel coronavirus is higher than the nephrology community has ever seen.

Liver GI

Michael Kriss, MD

Larissa Muething, MD

Assistant Professors, Division of Gastroenterology and Hepatology

The toxin-filtering liver often takes a COVID-19 punch, with abnormal enzyme levels occurring in about half of hospitalized patients.

“It’s actually quite common to see,” Kriss said. “It is presumed that there is probably a direct effect of the virus on the liver.” Data suggest the higher the enzyme levels, the higher the risk of severe illness and death.

It’s also possible that the liver takes a double blow in hospitalized COVID-19 patients. “It’s a little bit muddy, just because patients who are critically ill with severe COVID are on multiple medications. Those therapies potentially contribute to elevated enzyme levels.”

Generally, patients with liver involvement require no specific treatment. “The liver problem is either a consequence of your body’s immune response to the COVID or to the COVID itself, and so the treatments of COVID target those two things,” Kriss said.

The prevalence of long-term liver damage in these patients remains unclear.

SARS-CoV-2 can also infiltrate the gastrointestinal tract, causing loss of appetite, diarrhea, nausea, vomiting and abdominal pain.

“Approximately 20% of people will have some GI symptoms, and some people can present with predominantly GI symptoms,” Muething said.

Scientists have detected the virus in the GI tract and stool specimens. “We know it enters through the ACE2 receptors that are predominant in the small intestine and in the colon.”

Typically, GI manifestations are symptomatic and controllable with targeted medications.

Vascular System

Kathryn Hassell, MD

Professor, Division of Hematology

When the pandemic took hold, providers began noting a seemingly higher incidence of vascular events – including heart attacks, stroke, Deep Vein Thrombosis (DVT) and pulmonary embolism (PE) – than with other types of pneumonia or viral infections.

Multiple factors are likely behind the effect. “COVID can be a very inflammatory, very wicked, very aggravating infection that gets your immune and inflammatory systems revved up. Anytime you strongly stimulate those systems, you also stimulate the thrombotic system and enhance clotting.”

One of the ways the body fights an infected area is by creating scar tissue to contain it, an endpoint of clotting. “That’s why clot-busting therapies are sometimes used for severe lung diseases.”

Underlying vascular issues (diabetes, high blood pressure) increase the risk. Growing evidence suggests the virus can affect the vessels and the lining of the vessels (endothelial cells) themselves, further increasing risk of clots.

When arteries are involved, that can cause stroke or heart attack. In the venous system, COVID-19 can increase the risk of DVT and PE’s upwards of 20%, which has led to providers boosting the preventive dose of anticoagulants in many hospitalized patients.

Sometimes, blood flow to the toes can be compromised, causing painful red and purple toes that have earned the label of “COVID Toe.”

CU Anschutz Medical Campus

CU Anschutz Experts Break COVID-19 Effects Down by Body Part

From foggy mind to ‘COVID toe,’ observations abound, but causal evidence still lags

Parts of the Body

Ken Tyler, MD

Richard Davidson, MD

Marc Moss, MD

Michael Bristow, MD, PhD

Michel Chonchol, MD

Michael Kriss, MD

Larissa Muething, MD

Kathryn Hassell, MD

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