To date, there has been very little about the science, specifically biology and disease model, of COVID-19 by the mass media. The lack of these information, coupled with term “novel” coronavirus, creates a heightened fear about COVID-19. Fear and anxiety comes from uncertainty of not knowing. As the general population is fed by the mass media numbers after numbers each day, without understanding the relevance of each set of numbers, the fear and anxiety is bound to increase abundantly.
COVID-19 is a member of the coronavirus family like the common cold, SARS, and MERS. What is atypical about COVID-19 is its high transmissibility (akin to common cold and influenza) and its perceived danger (CFR 3.4% projected by the WHO; CFR = Case Fatality Rate, number of deaths/number of diagnosed) which is now known not to be the case. As reference points, recent viral outbreaks have the following CFR’s—SARS (9.4%), MERS (34.4%), and H1N1 “Swine Flu” (17.4%). The latest figure from CDC puts the CFR of COVID-19 in US around 0.26% (35% “asymptomatic” cases; CFR 0.4% “symptomatic” cases). In general, the more dangerous the virus is, the less spread is the virus transmission because 1) people inevitably will take greater protective measures and 2) the virus kills its host (the person) before it is transmitted to more and more people. The fact that up to half of the cases are “asymptomatic” and up to nine-out-of-ten cases do not need any hospitalization gives factual assurance that COVID-19 is not as dangerous as being portrayed.
A look at the working disease model of COVID-19 and the vulnerable “at-risk” groups gives a clearer understanding of the risk at the biology level. We actually have a good head-start in understanding the biology of COVID-19 virus (known as SARS-CoV-2) based on the discovered biology of SARS virus (known as SARS-CoV) from 2003. Similar to SARS virus, COVID-19 virus binds to angiotensin-converting enzyme 2 (ACE2) for cell entry.[i] The binding to ACE2 by the virus “knocks down” ACE2 production.[ii] ACE2 is a very important regulator in the RAS (Renin-Angiotensin-System) and provides protection that is vital to cardio-pulmonary health. In addition, RAS plays a pivotal role in vascular health (health of blood vessels), relating to diseases such as atherosclerosis, stroke, and diabetes. The “knock-down” of ACE2 could result in severe acute lung failure[iii] and heart failure,[iv] the main causes of acute death observed with COVID-19 patients (see Figure 1).
As documented, 90% of patients who died in New York State—epicenter of COVID-19 outbreak in US—had one or more pre-existing conditions, the majority of which are chronic diseases. These diseases have problems with RAS balance. A list of chronic diseases with RAS dysfunctions are shown in Table 1. Applying this ratio to the national numbers from CDC, the CFR for people with no pre-existing condition is 0.026% (influenza CFR 0.1%).
The inter-connections between COVID-19 severity of outcome and chronic diseases with RAS dysfunctions are shown in Scheme 1. When a healthy person (with no pre-existing condition) is infected with COVID-19, the “knock-down” of ACE2 protection is not so severe that it affects the RAS balance in a deadly manner. For most part, the healthy person walks away from COVID-19 without even noticing any symptoms (“asymptomatic” cases) or with some minor symptoms without need for hospitalization (“mild” cases). The healthy person’s immune system is able to clear out the virus before any severe harm from ACE2 “knock-down” occurs. For a person with pre-existing condition(s) (chronic diseases with RAS dysfunctions), the person’s RAS balance is already tilted down in the “disease” state. When that person is infected with COVID-19, the person’s RAS balance has a double “take-down” putting the person at high risk for severity of outcome including death. The double “take-down” leads to great harm including acute death while the person’s immune system attempts to clear out the virus. From a report of hospitalized patients in New York City, patients with no pre-existing condition accounted for only 6% of that patient population; the median number of pre-existing conditions was 4.[v] From a report of Italian patients who died,[vi] the mean number of pre-existing conditions was 2.7. The higher the number of pre-existing condition a person has, the greater is the risk for severity of outcome and death from COVID-19.
The key take-away’s from this analysis of the biology behind COVID-19 are:
- The young and the healthy (people with no pre-existing condition) have negligible risk.
- The elderly people in general (most have some chronic diseases) and the people with pre-existing conditions (chronic diseases with RAS dysfunctions and immunocompromised diseases) are the “at-risk” population. More refined risk assessment could be made when data are available on “stages” of a pre-existing condition (for example, hypertension and diabetes are not the same for every patient; these are the most prevalent pre-existing conditions in COVID-19 deaths).
- Regular check-up’s and testings are very important for management of chronic diseases. There should be a clear intention to bring these patients back into “normal” care as before, especially since they are the most vulnerable to COVID-19 severity of outcome.
- Any activity that improves a person’s cardio-pulmonary health and immunity (exercise, proper diet and stress management, etc.) are preventive measures against severity of outcome from COVID-19. Fitness and wellness facilities are as essential as other services provided to the general population.
[i] https://doi.org/10.1101/2020.01.22.915660
[ii] Kuba, K. et al. Nature Medicine (2005) 11: 875
[iii] Imai, Y. et al. Nature (2005) 436: 112
[iv] Patel, V. B. et al. Circ Res. (2016) 118: 1313
[v] doi:10.1001/jama.2020.6775
[vi] https://jamanetwork.com/journals/jama/fullarticle/2763667