Broadway star Nick Cordero has lost his over-three-month battle with COVID-19 at the age of 41. Cordero's Broadway credits include "Waitress," "Rock of Ages," "A Bronx Tale," and "Bullets Over Broadway."
Many have been following the roller coaster ride that has been Cordero's medical course through the posts of his wife Amanda Kloots. A previously healthy Cordero fell ill on March 20, with an initial diagnosis of pneumonia. After two negative tests, a third was positive for COVID-19. He was admitted from the emergency department on March 30 and was intubated on a ventilator on April 1.
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"Since then has [sic] he has suffered an infection that caused his heart to stop, he needed resuscitation, he had two mini strokes, went on ECMO, went on dialysis, needed surgery to remove an ECMO cannula that was restricting blood flow to his leg, a fasciotomy to relieve pressure on the leg, an amputation of his right leg, an MRI to further investigate brain damage, several bronchial sweeps to clear out his lungs, a septic infection causing septic shock, a fungus in his lungs, holes in his lungs, a tracheostomy, blood clots, low blood count and platelet levels, and a temporary pacemaker to assist his heart."
On May 1, he was taken off sedation but did not regain consciousness until May 13. Although he was able to respond slightly with his eyes, he remained immobile. His lung damage was so severe that that it was likely that Nick would need a double lung transplant, "in order to live the kind of life that I know my husband would want to live."
On July 5, Kloots once again took to Instagram to say: "God has another angel in heaven now. My darling husband passed away this morning. He was surrounded in love by his family, singing and praying as he gently left this earth." Cordero is also survived by his one-year-old son, Elvis.
Complications of COVID-19
SARS-CoV-2 has indeed turned out to be a "novel" coronavirus. Those afflicted can be completely asymptomatic, have mild "flu-like" symptoms, or can have severe illness that leads to protracted, complicated courses that may ultimately be fatal.
The most common symptoms of COVID-19 (which may appear 2-14 days after viral exposure) include:
- Fever or chills
- Cough
- Shortness of breath or difficulty breathing
- Fatigue
- Muscle or body aches
- Headache
- New loss of taste or smell
- Sore throat
- Congestion or runny nose
- Nausea or vomiting
- Diarrhea
According to the CDC, approximately one-sixth of COVID-19 patients will have complications, including some that are life-threatening. The complications of COVID-19 are diverse and can affect nearly every organ in the body. The mechanism of these problems is complex and may involve several factors.
Cytokine Storm
Some researchers are finding that COVID-19 complications may be caused by a dysregulation of the body's immune response. This leads to a proliferation of inflammatory cells and cytokines which can result in tissue damage.
"Cytokine storm" is a general term applied to a maladaptive immune response to infection or other stimuli. Loss of regulation causes the usually helpful immune response to spiral out of control, killing healthy tissue and leading to organ failure. A found that COVID-19 patients have higher levels of expression of the cytokines IL-1β, IFN-γ, IP-10, and MCP-1. In addition, there are "elevated levels of Tѻý cell-secreted cytokines (such as IL-4 and IL-10), which inhibit the inflammatory response." The levels appear to be highest in the sickest patients.
Cytokines are small proteins made by both immune and non-immune system cells that have either a stimulatory or inhibitory effect on the immune system. Examples of cytokines are interleukins, interferons, tumor necrosis factors, and colony-stimulating factors. Cytokines modulate the balance between humoral and cell-based immune responses, and they regulate the maturation, growth, and responsiveness of specific cell populations. In addition, some cytokines enhance or inhibit the action of other cytokines in complex ways.
Pulmonary Complications
Pneumonia seems to be the most frequent, serious manifestation of COVID-19 infection. It is characterized by cough, fever, dyspnea (shortness of breath), and bilateral infiltrates on chest x-ray, radiographically similar to other viral pneumonias. Severe pneumonia is associated with severe dyspnea, respiratory distress, tachypnea (rapid breathing >30 breaths/min), and hypoxia (low oxygenation saturation- SpO2- less than 90% on room air). Fever may or may not be present.
Cytokine storm is believed to be an important factor in the development of adult respiratory distress syndrome (ARDS) in COVID patients. In ARDS, fluid builds up inside the tiny air sacs of the lungs, and surfactant breaks down. Loss of surfactant, the foamy substance that keeps the lungs fully expanded, prevents the lungs from filling properly and decreasing the amount of oxygen in the body. In some cases of ARDS, the lung tissue may scar and become stiff. However, this may not be the case in COVID-19.
Sepsis and Multiorgan Failure
Sepsis is "a life-threatening organ dysfunction caused by a dysregulated host response to infection." Immune-mediated chemicals (including the above-mentioned cytokines) trigger widespread inflammation, which leads to blood clots and leaky blood vessels. As a result, blood flow is impaired, which deprives organs of nutrients and oxygen and leads to organ damage.
Sepsis is common in COVID-19 patients. A looked at 191 patients, of which 137 were discharged and 54 died in hospital. Those in the non-survival group had a "statistically significant prevalence of sepsis (100% [n=54] vs 42% [n=58], P<0.0001) and septic shock (70% [n=38] vs 0%, P<0.0001) compared to the survival group."
Patients with COVID-19 and sepsis can have a wide range of signs and symptoms of multiorgan involvement. The signs and symptoms of pulmonary failure has been described above.
Kidney failure may result in reduced urine output, high levels of protein in the urine, and abnormal blood work. According to , of Johns Hopkins Medicine, "Early reports say that up to 30% of patients hospitalized with COVID-19 in China and New York developed moderate or severe kidney injury. Reports from doctors in New York are saying the percentage could be higher." Causes of kidney damage are unclear at the present time but may include targeting of kidney cells by coronavirus, low oxygen levels in the kidneys, cytokine storm, or blood clots. In some patients, the damage is significant enough to require dialysis. It is uncertain at present how many patients with COVID-19 induced kidney failure can regain normal or partial kidney function.
Some patients hospitalized for COVID-19 show signs of liver involvement. They have increased levels of liver enzymes -- like alanine aminotransferase (ALT) and aspartate aminotransferase (AST) -- that indicate their livers are at least temporarily damaged. Also, liver damage is more common in patients who have severe COVID-19 disease. However, we do not know if this increase in liver enzyme levels is related directly to SARS-CoV-2 being in the liver or if liver damage results from other factors. Some researchers postulated that "liver injury may be due to a direct effect of SARS-CoV-2, or an indirect effect following septic shock, multiorgan dysfunction, drug-related toxicity, immune-related hepatitis, or a systemic inflammatory response (cytokine release or storm) of the COVID-19 syndrome."
Cardiovascular Complications
Cardiovascular complications of COVID-19 include myocardial injury and myocarditis, acute myocardial infarction, acute heart failure and cardiomyopathy, dysrhythmias, and venous thrombotic events.
Patients with myocardial injury and myocarditis have elevated levels of troponin (a heart muscle protein) which may be due to increased cardiac physiologic stress, hypoxia, or direct myocardial injury. that myocardial injury with an elevated troponin level may occur in 7%-17% of patients hospitalized with COVID-19 and 22%-31% of those admitted to the ICU.
In the Wuhan study cited above, acute heart failure was present in 23% of patients in their initial presentation, with cardiomyopathy occurring in 33% of patients.
Palpitations is a presenting symptom in about 7% of patients with COVID-19. found that dysrhythmias were present in 17% of hospitalized and 44% of ICU patients with COVID-19. The most common arrhythmia is sinus tachycardia which may be caused by a variety of factors including hypoperfusion, fever, hypoxia, and even anxiety.
Patients with COVID-19 are at increased risk of venous thrombotic events. A number of studies suggest significant coagulation pathway abnormalities. Manifestations include pulmonary emboli, lower limb venous thrombosis, systemic deep venous thrombosis, as well as microemboli that can affect the liver, kidney, brain (strokes), and other organs.
Neurologic Complications
The mechanism of damage to the brain of COVID-19 is likely due to hypoxic brain injury as well as immune-mediated brain damage. CNS manifestations include dizziness, headache impaired consciousness, encephalopathy and encephalitis, seizures, and stroke. Strokes caused by COVID have been found to be both of the hemorrhagic and ischemic types.
Peripheral nervous system manifestations include hypogeusia (decreased taste), hyposmia (decreased smell), neuralgia, Guillain-Barré syndrome, and skeletal muscle injury.
A Surprising Theory About "COVID Toe"
Because our son, , is a podiatrist, we would be remiss in not mentioning the phenomenon of "COVID Toe" that is thought to be a cutaneous manifestation of SARS-CoV-2 infection. However, two recently in JAMA Dermatology question a causative association because many patients presenting with the phenomenon test negative for the virus. Instead, both groups of authors suggest that environmental (lifestyle) changes imposed by quarantines could explain the association.
Michele R. Berman, MD, and Mark S. Boguski, MD, PhD, are a wife and husband team of physicians who have trained and taught at some of the top medical schools in the country, including Harvard, Johns Hopkins, and Washington University in St. Louis. Their mission is both a journalistic and educational one: to report on common diseases affecting uncommon people and summarize the evidence-based medicine behind the headlines.