Doctors Share COVID-19 Effects Outside The Lung

Despite a substantial body of evidence regarding the non-respiratory impact of COVID-19 on some patients, it’s still considered a respiratory disease. Doctors from Columbia University Irving Medical Center are sharing information that sheds light on the effects of the virus on the body’s other organs and systems.

It didn’t take long for Dr. Aakriti Gupta to recognize that COVID-19, the virus caused by SARS-CoV-2, was apparently not just another respiratory virus. He’d been caring for critically ill COVID-19 patients right from the beginning of New York City’s outbreak and saw some unusual and unexpected effects.

“I was on the front lines right from the beginning. I observed that patients were clotting a lot, they had high blood sugars even if they did not have diabetes, and many were experiencing injury to their hearts and kidneys,” says Gupta. He was one of the first Columbia cardiologists to go to work in the COVID intensive care units at Columbia University Irving Medical Center.

When the pandemic fully hit the US in early March, we didn’t know much about the virus. We certainly had little information regarding the non-respiratory effects. It was in the midst of this intense time that Dr. Gupta thought to review and coordinate findings from research studies which were just starting to turn up in research journals. He then compared what he’d learned with what the Columbia physicians were learning on the front lines.

Gupta got together with the chair of medicine at Columbia’s Vagelos College of Physicians and Surgeons, Donald Landry, MD, PhD, CUIMC cardiology fellow Mahesh Madhavan, MD and Kartik Sehgal, MD, who is a hematology/oncology fellow at Beth Israel Deaconess Medical Center/Harvard Medical School. This group then extended the team to include clinicians at Columbia, Harvard, Yale and Mount Sinai Hospital. These clinicians reviewed the latest available findings regarding COVID-19’s impact on organ systems outside the lungs.

The purpose was to offer clinical guidance for physicians treating COVID-19 patients. Theirs was the first extensive review of the effects of the virus on organs and systems outside the lungs. It was published in the journal Nature Medicine.

“Physicians need to think of COVID-19 as a multisystem disease,” Gupta says. “There’s a lot of news about clotting but it’s also important to understand that a substantial proportion of these patients suffer kidney, heart, and brain damage, and physicians need to treat those conditions along with the respiratory disease.”

Unusual Inflammation, Unexpected Clotting and Uncontrolled Immune Responses

“In just the first few weeks of the pandemic, we were seeing a lot of thrombotic complications, more than what we would have anticipated from experience with other viral illnesses,” says Sehgal, “and they can have profound consequences on the patient.”

The unexpected complications in clotting could be a result of how the virus attacks the cells lining the blood vessels. As blood vessel cells come under COVID-19 attack, there is an increase in inflammation. Various sized blood clots begin to form, which can make their way through the body damaging organs and creating a dangerous cycle of thromboinflammation.

Some of the co-authors of this review are involved with a randomized clinical trial in which the timing of anti-coagulation drugs, along with their optimal dose, are being tested in COVID-19 patients with critical symptoms. The hope is that the anti-coagulants will help stave off the clotting and prevent its damaging effects.

A dangerous effect of unmitigated inflammation is an overstimulation of the body’s immune system. Early in the treatment of COVID-19, doctors were reluctant to use steroids in an effort to suppress the immune system. That may change based in the results of a clinical trial in which the steroid dexamethasone was found to reduce death among ventilated patients by one-third. There are also randomized clinical trials underway which target specific components of thromboinflammation and the immune system. One of those is interleukin-6 signaling.

“Scientists all over the world are working at an unprecedented rate towards understanding how this virus specifically hijacks the normally protective biological mechanisms. We hope that this would help in the development of more effective, precise, and safer treatments for COVID-19 in the near future,” says Sehgal.

Matters of the Heart

We know blood clots can cause heart attacks. Less well-understood are the other ways that COVID-19 attacks the heart.

“The mechanism of heart damage is currently unclear, as the virus has not been frequently isolated from the heart tissue in autopsy cases,” says Gupta.

One possible mechanism may be related to what’s called a cytokine storm. The damage may occur when the heart muscle is damaged by systemic inflammation and a flood of immune cells (cytokines) is released. In healthy individuals, that release would clean up damaged or infected cells. In severe COVID-19 cases, it often explodes into uncontrolled cytokine release, causing organ and organ system damage.


Because of the risks posed to medical personnel and patients by COVID-19 early in the pandemic, doctors couldn’t take advantage of therapeutic and diagnostic tools like heart catheterizations and biopsies. As the severity of the pandemic has receded and the prevalence of the disease has subsided in New York, doctors have begun to return to their normal courses of diagnosis and treatment for hearts damaged by the virus.

Surprises in the Kidney

Acute kidney damaged in a significant number of COVID-19 patients also surprised the doctors. This may be the result of the high concentration of ACE2 receptors in the kidney. This receptor is the path by which the virus gets into cells. While Chinese studies reported some renal complications, ICU doctors in New York City saw renal failure in up to 50 percent of ICU patients.

“About 5 to 10% of patients needed dialysis. That’s a very high number,” Gupta says.

Doctors are concerned that a large number of COVID-19 patients with serious to critical symptoms may need permanent dialysis if they survive.

“Future studies following patients who experienced complications during hospitalizations for COVID-19 will be crucial,” notes Madhavan.

Brain Oddities

While symptoms like loss of smell, headaches, fatigue and dizziness seem to be common in about a third of patients, there is a more serious concern. Delirium seems to be occurring in 8 to 9 percent of severely ill patients and blood clots may be causing strokes in up to 6 percent of patients.

“COVID-19 patients can be intubated for two to three weeks; a quarter require ventilators for 30 or more days,” Gupta says.

“These are very prolonged intubations, and patients need a lot of sedation. ‘ICU delirium’ was a well known condition before COVID, and the hallucinations may be less an effect of the virus and more an effect of the prolonged sedation.”

“This virus is unusual and it’s hard not to take a step back and not be impressed by how many manifestations it has on the human body,” says Madhavan.

“Despite subspecialty training as internists, it’s our job to keep all organ systems in mind when caring for the patients in front of us. We hope that our review, observations, and recommendations can help other clinicians where cases are now surging.”

It’s true that the overwhelming majority of people who get infected with SARS-CoV-2 will suffer no symptoms or mild symptoms. Some 99.7 percent of all who are infected will survive, according to new CDC measures.

But for a very small number of patients who suffer serious to critical symptoms, COVID-19 is more than just a “bad seasonal flu.” It could be the cause of serious, lasting and often surprising side- and after-effects.

Let’s hope it continues to mutate toward a weaker strain and that we find better treatments for the virus. The fewer serious, severe and critical cases we see, the better.

Keep the faith and keep after it!

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Journal Reference – Aakriti Gupta, Mahesh V. Madhavan, Kartik Sehgal, Donald W. Landry, et al., Extrapulmonary manifestations of COVID-19. Nature Medicine, 2020; DOI: 10.1038/s41591-020-0968-3

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