COVID-19: not just a respiratory disease

A team of New York health experts have described COVID-19’s effects outside the lung.

A Columbia University cardiologist has mobilised clinicians at institutions including Columbia, Harvard, Yale and Mount Sinai Hospital to review the latest findings on COVID-19’s effect on organ systems outside the lungs and provide clinical guidance for physicians.

After only a few days caring for critically ill COVID-19 patients at the start of the outbreak in New York City, Dr Aakriti Gupta realised that this was much more than a respiratory disease.

“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,” Dr Gupta said.

Deployed to the COVID intensive care units at Columbia University Irving Medical Center (CUIMC) — with little clinical guidance on the non-respiratory effects of COVID-19 — Dr Gupta decided to coalesce findings from studies that were just beginning to appear in the literature with what the physicians were learning from experience.

Dr Gupta and her colleagues organised senior co-authors and mobilised clinicians to take part. Their extensive review of COVID-19’s effects on all affected organs outside the lungs was published in the journal Nature Medicine.

“Physicians need to think of COVID-19 as a multisystem disease,” Dr Gupta said.

“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.”

Blood clots, inflammation and immune system overdrive

Haematology/oncology fellow at Beth Israel Deaconess Medical Center and Harvard Medical School Dr Kartik Sehgal said, “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, and they can have profound consequences on the patient.”

Scientists think these clotting complications may stem from the viral attack on cells that line the blood vessels. When the virus attacks blood vessel cells, inflammation increases and blood begins to form clots. These blood clots can travel all over the body and wreak havoc on organs, perpetuating a vicious cycle of thromboinflammation.

To combat clotting and its damaging effects, clinicians at Columbia are conducting a randomised clinical trial to investigate the optimal dose and timing of anticoagulation drugs in critically ill patients with COVID-19.

The untempered inflammation can overstimulate the immune system and, though doctors initially shied away from using steroids to globally suppress the immune system, a recent clinical trial has found that at least one steroid, dexamethasone, reduced deaths in ventilated patients by one-third. Randomised clinical trials are underway to target specific components of thromboinflammation and the immune system, such as interleukin-6 signalling.

“Scientists all over the world are working at an unprecedented rate towards understanding how this virus specifically hijacks the normally protective biological mechanisms,” Dr Sehgal said.

“We hope that this would help in the development of more effective, precise and safer treatments for COVID-19 in the near future.”

Effects on the heart

Clots can cause heart attacks, but the study authors explain that the virus attacks the heart in other ways.

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

The heart muscle may be damaged by systemic inflammation and the accompanying cytokine release — a flood of immune cells that normally clears up infected cells —but can spiral out of control in severe COVID-19 cases.

During the early stages of the pandemic, despite the degree of heart damage, physicians were not able to use the diagnostic and therapeutic strategies that they normally would — including heart biopsies and cardiac catheterisations — given the need to protect personnel and patients from viral transmission. This has changed as the disease prevalence in New York CIty has reduced.

Kidney failure

Another surprising finding was the high proportion of COVID-19 patients in the ICU with acute kidney damage.

The ACE2 receptor used by the virus to gain entry into the cells is found in high concentrations in the kidney and could likely be responsible for renal damage. Studies in China reported renal complications, and in New York City clinicians saw renal failure in up to 50% of patients in the ICU.

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

Data regarding long-term renal damage is currently lacking, but a significant proportion of patients will likely go on to require permanent dialysis.

CUIMC cardiology fellow Dr Mahesh Madhavan said, “Future studies following patients who experienced complications during hospitalisations for COVID-19 will be crucial.”

Neurological effects

Neurological symptoms, including headache, dizziness, fatigue and loss of smell, may occur in about one-third of patients with COVID-19. More concerning, strokes caused by blood clots occur in up to 6% of severe cases and delirium in 8–9%.

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

“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.”

Dr Madhavan added, “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.

“Despite our 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.”

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