In Canada, about 1.1 percent of infected patients (about 46,000 people) have died. This is the story of how a team gathered during the pandemic identified the mechanism by which these viruses were reducing oxygen levels in patients by injuring the lungs: it’s a return to the primitive war between viruses and bacteria – Specifically, between our mitochondria, the evolutionary progeny of novel viruses and bacteria. SARS-CoV-2 is the third novel coronavirus to cause a human outbreak in the 21st century, after SARS-CoV in 2003, and MERS-CoV in 2012. To prepare for the next pandemic, we need to better understand how coronaviruses cause lung damage.
How does COVID-19 affect the lungs?
People with severe COVID-19 pneumonia often arrive at the hospital with abnormally low oxygen levels. They differ from patients with other types of pneumonia in two ways: First, they have extensive damage to the lower airways (alveoli, where oxygen is taken in). Second, they move blood to non-ventilated areas of the lungs. This means that the blood is going to parts of the lungs where it will not get enough oxygen. Together, these abnormalities reduce blood oxygenation. However, the cause of these abnormalities was unknown. In 2020, our team of 20 researchers from three Canadian universities set out to uncover this mystery.
We proposed that SARS-CoV-2 made COVID-19 pneumonia worse by targeting mitochondria in cells that line the airways and in pulmonary muscle cells of the pulmonary artery. We already knew that the mitochondria is not only the powerhouse of the cell, but also its main consumer and sensor of oxygen. Mitochondria control the process of programmed cell death (called apoptosis), and they control the distribution of blood flow to the lungs by a mechanism called hypoxic pulmonary vasoconstriction. This system has an important function. This directs blood away from areas of pneumonia into the superior ventilated lobes of the lungs, which optimize oxygen-receptivity.
Oxygen absorption is hindered
By damaging the mitochondria in the smooth muscle cells of the pulmonary artery, the virus allows blood flow to areas of pneumonia, which also reduces oxygen levels. It seems possible that Sas-Cov-2 damages mitochondria, the consequences of which – increased apoptosis in airway epithelial cells, and loss of hypoxic pulmonary vasoconstriction – damage to the lungs and worsen hypoxemia (low blood oxygen). Our discovery, published in Redox Biology, describes how SARS-CoV-2, the coronavirus that causes COVID-19 pneumonia, lowers blood oxygen levels.
We showed that SARS-Cov-2 kills airway epithelial cells by damaging their mitochondria. This results in accumulation of fluid in the lower airways, which hinders the absorption of oxygen. We also showed that SARS-Cov-2 damages mitochondria in pulmonary artery smooth muscle cells, which inhibits hypoxic pulmonary vasoconstriction and reduces oxygen levels. Our discovery is expected to be used in new drugs to combat future pandemics.
(Stephen L. Archer, Head of the Department of Medicine, Queen’s University, Ontario)