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The devastating damage that the novel coronavirus inflicts on the human body can set off inflammatory havoc. As we learn more, doctors are gaining clues to hopefully prevent deaths and improve treatment.
Last December, COVID-19 entered the world stage as a flu-like illness causing fever, dry cough and a sore throat.
Since then, the list of how the illness can present has expanded, and expanded again, to include gastrointestinal symptoms like diarrhea, general aches, loss of taste and smell and serious blood-clotting problems, among others.
Of the more than five million infections globally so far, 2.4 million have recovered.
Most infected people have so few symptoms they are better off at home. The minority of serious infections in patients — mainly those over 65, though no age group is left unscathed — can confound health professionals caring for them.
The illness can worsen to a severe stage called Acute Respiratory Distress Syndrome, which includes severe lung inflammation and damage. These are often the patients who are admitted to intensive care units and need life support such as ventilation.
Dr. Lynora Saxinger, an infectious disease physician at the University of Alberta, co-chairs a provincial scientific advisory board reviewing how COVID-19 manifests and what it means for reducing transmission and extending treatment beyond current care measures.
“The landscape shifts really quickly,” Saxinger said. “We just want to make sure that we’re not missing [what] could be spreading, because that’s where we’re going to run into trouble.”
Not typical clots
As initial anecdotes about inflammatory-like effects such as blood-clotting complications mounted into a clearer signal for caution, clinicians adapted their care while scientists worked to understand why it happens.
Now, Saxinger said there’s more evidence of clotting damage in both large and small blood vessels. “This virus is doing different things in the body.”
Experts say some of these inflammatory effects look to be unique to this particular coronavirus, which is known as SARS CoV-2.
Dr. Zain Chagla, an associate professor of infectious disease at McMaster University in Hamilton, Ont., said the wide extent of clotting with this virus differs from other infections, including from the deadly SARS and MERS coronaviruses. With COVID-19, the clots occur in veins in the legs and lungs, as well as in arterial ones that cause strokes and can lead surgeons to resort to amputating a patient’s limbs.
Medical researchers have also found tiny clots that damaged tissue throughout the body in hospitalized patients and in autopsies.
Chagla said this means that “from a therapeutic standpoint,” it might be better to give patients a low dose of heparin, an anticoagulant or blood thinner. It’s often used before surgery and in a variety of medical conditions to prevent and treat clots.
Clinical trial researchers are also exploring the use of high-dose anti-coagulants in carefully selected patients, Chagla said.
This week, Health Minister Patty Hajdu announced an accelerated path for clinical trials to help find answers to urgent COVID-19 diagnosis, treatment, mitigation or prevention questions while keeping patients safe.
On Friday, Montserrat Puig of the U.S. Food and Drug Administration and her team published what they called a road map for effective treatment of COVID-19, based on both repurposing existing approved drugs as well as those still under development.
The review, published in Frontiers in Immunology, unravels factors leading to the “cytokine storm” that can rampage in people with severe COVID-19. Cytokines are small molecules released by the body’s immune system to co-ordinate response against an infection or injury, ranging from a mild fever to suspected deaths in the 1918 flu pandemic.
Scientists are still working to understand the key events in cells, tissues and the body’s immune system that tips the balance from a normal, protective, “hey, come help” call for reinforcements to an unnecessary, four-alarm call that leads to a life-threatening overreaction.
Puig wrote that potential drugs include those that could block the virus from entering our cells in the first place, antivirals to stop the virus from making copies of itself and therapies called monoclonal antibodies that dampen the haywire response from cytokines.
Inflammatory storm unleashed
People who develop symptoms of COVID-19 do so within 14 days, and it mostly occurs about five days after exposure.
Saxinger said when patients struggle with congested lungs and poor blood pressure control, it’s often a manifestation of lung inflammation in response to the infection.
She said there’s also an arc to the story of how the disease marches through the body from initial infection to damage to recovery or death.
“The initial infection triggers this body-wide response that is devastating,” Saxinger said. “Then, when the infection itself might be coming under control, it’s almost like you unleash this storm of immune reactivity and inflammation.”
Once the storm is set off, doctors say treating the infection itself is unlikely to help much.
So, what could help? As physicians report more symptoms, scientists working in parallel are exploring why and how the virus replicates in some tissues and organs so well.
Matthew Miller, an associate professor of infectious disease and immunology at McMaster, is following the scientific advances.
The virus seems to use a receptor called ACE2 to enter human cells. Miller said many groups of researchers are working to understand what cells in our body have active proteins where the virus might be able to replicate and cause disease.
“Knowing what cells a virus is capable of infecting is really important, because it can help us anticipate what types of diseases or what types of symptoms it might cause,” Miller said.
It’s thought that the infectious dose a person is exposed to, as well as minute, genetic differences in the individual and whether they have underlying health conditions (like heart disease or diabetes) all play a role in how COVID-19 manifests.
Understand virus to guide reopening
For now, medical researchers are exploring how ramping up a beneficial aspect of the immune response that cells normally use to kill off a virus could be complemented with “immune modulators” to tamp down overreactions. It’s a delicate balance and timing is key.
Miller said as we learn more about the unique features of SARS-CoV-2, governments and public health officials have been forced to “learn on the fly” and adapt pandemic plans built for a different respiratory infection: influenza, commonly called flu.
“One of the areas that this pandemic has really brought to light is that there’s not enough focus on prevention control measures,” he said.
Countries imposed and eased lockdowns without a firm grasp on what measures work best for this particular virus, leading to differences across the globe and shifting recommendations on wearing masks or physical distancing.
“I think we’re all learning that we don’t understand nearly as well as we should,” Miller said.
WATCH | Why we should expect waves of COVID-19:
Public health basics like staying home when sick, handwashing and cough etiquette apply to all respiratory pathogens. It’s the specifics that are still a work in progress.
For Saxinger, these knowledge gaps mean that understanding COVID-19 will be a long-term effort.
“It’s not just going to be a one, we’re done,” Saxinger said. “We are all going to have to figure out the best way to manage people and try to give them the best outcomes possible.”
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