As coronavirus cases continue to spread, doctors are learning more about COVID-19 and its symptoms.
So far, the Centers for Disease Control and Prevention has officially listed nine symptoms of the illness caused by the new coronavirus: cough, shortness of breath or difficulty breathing, fever, chills, repeated shaking with chills, muscle pain, sore throat and new loss of taste or smell.
The CDC says these symptoms may appear two to 14 days after exposure to the virus.
However, the unofficial list of symptoms continues to grow. They vary from patient to patient and can range from an acute skin rash to a severe inflammatory reaction. Some doctors have reported gastrointestinal issues such as nausea, vomiting and diarrhea.
How a respiratory virus can trigger all these symptoms?
How does the immune system work?
When a virus is introduced to the body, its immune system kicks into high gear. Each body reacts differently to the virus, which leads to a range of symptoms.
“A response from the body of any form is a sign that our body is trying to fight something,” said Dr. Humberto Choi, pulmonary and critical care specialist at the Cleveland Clinic. “Not everyone has the same symptoms because everyone will respond different ways even to the same infection.”
Antibodies attach to the virus to prevent them from attaching to a protein on the host cell and infecting it. Meanwhile, specialized white blood cells, called macrophages, gobble up free-floating virus as the body’s first line of defense, according to Dr. Raphael Viscidi, an infectious disease specialist at Johns Hopkins Medicine.
“But they don’t have anything to do with antibodies,” he said. “Antibodies are produced by another class of white blood cells as part of the adaptive immune system.”
Macrophages also are responsible for releasing signals, called cytokines, that activate other immune cells to combat the virus and initiate inflammation.
“Cytokines are chemicals in our body that are responsible for our inflammatory and immune response,” said Choi. “They transmit signals to different places of the body for different parts to be activated.”
Interleukin-6 (IL-6) is an inflammatory cytokine, one of the many known to create muscle aches and pains. Dr. Mitchell Grayson, professor and chief of Division of Allergy and Immunology at Nationwide Children Hospital, said these aches and pains act as an alarm bell to signal the body is going through this process.
‘COVID toes,’ rashes and other skin manifestations
Inflammation caused by the cytokines and immune cells can cause different reactions in the body.
This can range from morbilliform rashes or hives. Dr. Lindy Fox, professor of dermatology at the University of California-San Francisco, says morbilliform are pink bumps that can be about 2 to 5 millimeters. They can last from one week to 14 days.
On the other hand, it’s unclear how long hives last, as lesions tend to come and go and show up in different places of the body. According to Fox, hives are raised pink welts that can be round or oddly shaped. They can be big or small and are usually very itchy.
Another perplexing reaction associated with the coronavirus is known as “COVID toes.” The American Academy of Dermatology (AAD) has compiled a registry of skin manifestations associated with COVID-19. About half of the more than 600 total cases on the dermatological registry are COVID toes.
Dr. Esther Freeman, director of Massachusetts General Hospital Global Health Dermatology and member of the AAD task force on COVID-19, said COVID toes are pinkish-reddish “pernio-like lesions” that can turn blueish-purple over time.
She said the reaction shouldn’t be confused with a different medical condition that occurs in critically sick patients called purpura fulminans.
COVID toes occur when immune cells called lymphocytes appear in the second layer of the skin, called the dermis, inflaming the area and causing discoloration. Sometimes the inflammation can damage the small blood vessels in the dermis, which is why some doctors confuse the condition with blood clotting, Fox said.
Freeman says it’s not clear why these immune cells target that area of the body.
As the AAD collected more examples of COVID toes, experts realized they’re more likely to appear after the infection process. While some patients with COVID toes test positive in their polymerase chain reaction (PCR) test and still shed the virus, most are testing negative and instead test positive for antibodies.
“It’s important not to induce panic if you were to develop these lesions on your toes,” Freeman said. “Most of our patients seem to be doing well.”
Another post-viral reaction from the coronavirus is the Kawasaki-like inflammatory disease that has affected children across the country.
Dr. Sunil Sood, a pediatric infectious disease physician at Northwell Health’s Southside Hospital and Cohen Children’s Medical Center, estimates his patients may have had the coronavirus, even unknowingly, four weeks before developing the mystery inflammatory condition.
“The immune system can overreact in a delayed timeline many weeks later,” Sood said. “We know this from other infectious diseases.”
Symptoms of the Kawasaki-like disease including abdominal pain, confusion, diarrhea, red eyes, rash, swollen hands and feet, difficulty breathing and fainting. Sometimes the abdominal pain can be so severe it mimics appendicitis.
New loss of taste or smell
One of the newer coronavirus symptoms added to the CDC’s list is a loss of taste or smell. Anosmia is the loss of smell; dysgeusia is an altered sense of taste.
Experts say damage to nerves in the nasal cavity is believed to cause the loss of smell.
“The same way we have nerve endings that stimulate someone to cough, we have those nerve endings in our nose that are responsible for our sense of smell,” Viscidi said. “It could be a sign that the nerve endings are inflamed.”
When air and scent molecules enter the nose, they move past the olfactory (smell) receptors that relay a signal to the olfactory bulb located in the forebrain. The olfactory bulb then processes these smells.
Smell receptors are located in two narrow passageways called the olfactory clefts, according to a study published in the journal Chemical Senses. If the olfactory clefts are inflamed from immune cells attacking the virus, smell receptors are unable to detect scent molecules.
Experts say this odd symptom usually appears in patients under the age of 40. Since a loss of taste or smell indicates the virus is in the upper respiratory tract, it’s most commonly a marker for mild COVID-19 and isn’t associated with a severe development.
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Why does COVID-19 cause strokes?
New York City doctors say the coronavirus is triggering a surge in strokes in younger patients, causing alarm among medical experts.
Over a two-week period, Mount Sinai doctors reported five patients who suffered large vessel strokes in patients under the age of 50, according to a letter they published in the New England Journal of Medicine (NEJM).
All five patients tested positive for COVID-19 but had mild to no symptoms.
“That creates a big alarm,” said Dr. J Mocco, director of the Cerebrovascular Center at Mount Sinai and one of the letter’s authors. “Our spider sense goes up to say that there’s something not right here.”
Mocco said he’s heard from colleagues in heart, lungs and kidney medicine who have also seen complications in coronavirus patients caused by blood clots.
So how can the coronavirus sometimes cause these blood clots?
Virus that leaks into the blood binds to endothelial cells located in the inside lining of the blood vessel. Both endothelial cells in the blood vessel and epithelial cells in the respiratory tract have the same protein receptor that binds with the virus.
Once the virus attaches to the protein receptor located on the outside of the endothelial cell, the virus penetrates it and multiplies inside. Damage to these cells triggers a response that promotes blood clotting.
If clots form in larger blood vessels and increase in size over time, they can be dislodged and travel to other places in the body, said Viscidi. Clots in the veins go to the lung and can cause a pulmonary embolism, while clots in arteries can go to the brain and cause a stroke.
Fever: Is headache a sign of the coronavirus?
A headache is not a common symptom of the coronavirus but it is possible for headaches to occur with a fever.
Fevers occur when cytokines released by macrophages, specifically a cytokine called Interleukin-1 (IL1), travel through the body to the hypothalamus in the brain. The cytokines tell the hypothalamus to increase the body’s temperature creating a fever, according to Viscidi, which helps slow down the virus.
Experts say the increase in temperature can sometimes dilate the blood vessels in the brain causing a headache. However, this is uncommon.
When the fever starts to subside, the body feels cooler and can create a chill. The body’s natural response to this chill is shaking.
“Chills and shaking are less common and generally occur in an extreme form of fever,” Viscidi said. “Temperatures going up to 103 or 104… you can have a fever without chills but you can’t have chills without a fever.”
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