The latest research on how COVID-19 kills, and why it’s so effective at it.
Cautious optimism has been spreading across the world in recent weeks, as economies begin to move, people shift towards normal routines, and and communities begin to take stock of the damage left in the wake of the storm.
While 1,536 research teams work feverishly to produce vaccines or other treatments, others have been feverishly painting a picture of what makes the virus tick; the more I learn, the more convinced I become that 1,536 projects is not overkill.
First, it should be clarified that COVID-19 is a truly ‘novel’ virus – although the widespread use of face masks subconsciously reinforced the connection with the flu, scientists are learning that it is tricky to even label it as a ‘respiratory virus.’ A growing proportion of doctors and researchers now favor the argument that our current pandemic is the result of a perfect storm of infectivity characteristics and an unprecedented ability for the SARS-nCoV-2 virus to latch onto certain types of cells. The most persuasive evidence in favor of this theory is the fact that it helps explain one of the biggest mysteries of the pandemic – symptomology.
In early January, Chinese scientists sequenced the genome of a new coronavirus, having correctly identified COVID-19 as the underlying cause of a pneumonia outbreak in Wuhan. For more than a decade, epidemiologists and policymakers had been aware of the threat of a novel corona/flu virus pandemic, but the most likely scenario involved the flu, because SARS and MERS had been so deadly that they couldn’t spread fast enough to compensate, once quarantines were put in place.
COVID-19, by contrast, appears to have hit the trifecta, by being highly infectious, broad in its symptoms, able to spread in asymptomatic individuals for 2-10 days, and also a near-perfect fit with the receptors of three types of cells: epithelial, endothelial and enterocytic. The loophole is the ACE2 receptor, one of a variety of types of cell proteins that performs tasks like reducing blood pressure. So, why is the ACE2 so special?
The answer is that it isn’t – it’s found all over the body, because those cells can be found in major organs like the nasopharynx, oropharynx, lungs, stomach, small intestine, spleen, liver, kidney and brain.
One of the most puzzling elements of the pandemic has been the emerging awareness of odd symptoms appearing all over the body; most pathogens operate within relatively narrow niches, but this coronavirus appears to be more flexible. Rather than being driven by respiratory symptoms specifically, the infection seems to produce symptoms as a function of its point of entry. The first two targets are the lungs and blood vessels, and the longer the infection lasts, the more diverse one’s symptoms become. That makes COVID-19 a kind of Pandora’s Box – once opened, it will spark internal chaos until its symptoms reach the tipping point.
The ACE2 receptor theory would also explain why COVID-19 infection is so much deadlier in adults 50+ than every other age group combined. The ACE2 receptor is common among cells that line the blood vessels, pancreas, kidney & lungs – weak points for those with cardiovascular problems, diabetes and COPD. Other research indicates that ACE2 affinity makes it harder for immune systems to differentiate between SARS-nCoV-2 and the human cells around it, which can further intensify the immune response and precipitate a “cytokine storm,” an often-fatal, overwhelming immune response that ultimately delivers the final blow through organ failure and death.
Perhaps the most important takeaway from these findings is that the pandemic is still largely misunderstood, and politicians remain determined to cast blame on the opposition for the spread of the virus. The truth is that America leads the world because of demographics, not assumptions. The United States enjoys a high standard of living and relatively good healthcare. The former fuels obesity and the latter fuels longevity. It’s no coincidence then, that our number of confirmed cases leads the world; it’s a symptom of our society at large. It’s a demographic reality, not a political statement.
At the moment, it feels like we are in the eye of the storm, unable to forecast what the trailing edge of the hurricane will bring. The good news is that vaccines and treatments are in development, and many existing drugs have shown promise. ACE inhibitors (medicines that lower blood pressure) are being used in many cases, because blood pressure rises when ACE2 levels fall, thus upsetting the balance between the two.
In sum, COVID-19 is a perfect storm of chaos; infectious enough to cover the world, deadly enough to kill large numbers, with an extended incubation period and the ability to spread during that asymptomatic phase. It targets the organs where most pre-existing conditions emerge, while spreading through the ACE2-receptors in cells that help mediate blood pressure. Finally, in immunocompromised individuals, it hastens the process of the immune over-reaction.
The prospect of a vaccine in the near term is exciting, but until proven therapies emerge we should remember the lessons of the 1918 flu pandemic: as time passes, mutations appear, and that can be a blessing or a curse. In 1918, it was a summer mutation that led to devastation across the globe that winter; our best course of action is to plan for the curse and hope for a treatment blessing.
-Rixey
