COVID-19 is the biggest threat facing our world given its pronounced effects on the health of individuals and the socio-economic welfare of nations. With the varied pandemic responses, the one constant scientific theme is—the virus is “new” and we know “so little” about the virus. Eight months into the pandemic with both COVID-19 biology findings and human patient data, this continual theme engenders heightened fear and deep anxiety for people and policy makers because of the “unknown” factor. The truth is the “unknown” narrative is not scientifically accurate.
By now, people have heard the COVID-19 virus binds to a receptor called ACE2 (Angiotensin-Converting-Enzyme-2). The most fundamental aspects in drug discovery and development is knowing: 1) the site-of-action (i.e., receptor) and 2) mechanism-of-action. If one knows the site-of-action with published findings on the mechanism-of-action, then one knows a lot about the disease. If one goes to PubMed (NIH science publication database), we see there are close to 3,000 publications for ACE2 in title or abstract. Yes, 3,000 publications! How can any scientist then say we know very little about COVID-19?
ACE2 plays a very important role in the Renin-Angiotensin-System (RAS) and is vital to cardio-pulmonary as well as vascular health. ACE2 is part of the “protective” axis comprising ACE2-Ang(1-7)-Mas that counterbalances the “disease” axis comprising ACE-AngII-AT1R in RAS; this is the cornerstone therapeutic modality in cardiology. A very common drug for heart disease is ACE inhibitor (ACEi) that fights against the activity of the “disease” axis. With COVID-19, similar to SARS, binding of ACE2 by the virus leads to decreased production (or down-regulation) of ACE2. This down-regulation of ACE2 leads to pathologies such as vasoconstriction, hypoxia, edema, thrombosis, and excess inflammation which have been described among the ACE2 publications already. The uncontrolled development of these pathologies lead to acute death, mainly from respiratory failure; acute death could also be attributed to heart failure and multi organ failure. The “puzzling” diverse manifestations or complications of COVID-19 such as loss of smell, neurovascular deterioration, and renal disorder are all explained by what is known and published about ACE2 biology and RAS human effects.
Putting aside politics, we can parley these scientific knowledge into more effective public health decision-making. Let’s look at two very tangible examples. First, there is much debate on school re-opening in the Fall. Empirically, 166 children died from the flu and 30 children died from COVID-19 as reported by CDC as of July. There is at least five times greater mortality risk for children from exposure to flu vs. COVID-19. In addition, from large studies done in France (covering primary schools)[i] and in Germany (covering high schools),[ii] no transmission of COVID-19 was observed among school children and from school children to school staff. This is a highly sensitive subject given the position children holds in society and sheer numerical arguments might not suffice. To support these observations and data, we know from published studies that ACE2 levels in the nasal passage–place of first contact between the virus and the human body–of children are less than those in adults. So there are less receptors for the virus to bind in children compared with adults. In addition, the RAS imbalance observed in people with the greatest vulnerability (pre-existing chronic conditions such as hypertension, diabetes, heart disease, etc.) is never observed in children, barring genetic abnormalities. Any resultant ACE2 down-regulation by COVID-19 infection is strongly buffered by the healthy RAS balance in children. Furthermore, another key component to the viral entry process is TMPRSS2 and the TMPRSS2 levels in children are found to be less than those in adults.[iii] The lower levels of TMPRSS2 in children temper viral replication and damage. All these scientific findings corroborate with the observations that children have negligible risks to COVID-19. There is no scientific evidence against school re-opening.
The second example comes from the importance of exercise. Numerous studies have shown the benefits of exercise especially in reducing the risks associated with chronic conditions. Exercise reduces the risk of cardiovascular disease by up to 35%, type 2 diabetes by up to 40%, and dementia by up to 30%. These chronic diseases are the same pre-existing conditions that exacerbate COVID-19 and increase likelihood of severe outcome including death. A publication this year found that exercise leads to elevated levels of ACE2.[iv] This leads to an improved RAS balance and a stronger protection/buffering against ACE2 down-regulation caused by COVID-19 infection. The pandemic is a time when we need to make use the feasible forms of protection as much as possible. Yet the opening of gyms and other fitness centers are among the least prioritized of all businesses. In light of the known science, gyms and other fitness centers should be considered as “essential” businesses.
Science is meant to illuminate and guide people and societies to better decisions and results. We know a lot about COVID-19 based on the science published on ACE2 and RAS. The human data collected from the pandemic worldwide are consistent with those facts. We must leverage the science that is present and clear to overcome COVID-19. If we do not, this will be the greatest tragedy of our time!
[i] https://www.pasteur.fr/en/press-area/press-documents/covid-19-primary-schools-no-significant-transmission-among-children-students-teachers
[ii] https://www.theguardian.com/world/2020/jul/13/german-study-covid-19-infection-rate-schools-saxony
[iii] https://doi.org/10.1101/2020.04.12.037580
[iv] https://doi.org/10.1016/j.heliyon.2020.e03208