Let Me Sum Up: Time to Take Account of where we are with COVID-19

“I do not feel obliged to believe that the same God who has endowed us with sense, reason, and intellect has intended us to forgo their use.” ― Galileo Galilei, Letter to the Grand Duchess Christina.”

Thought it might be time to consider our status with COVID-19, what we have learned and how we might use it to defeat or control or at least live with it. Knowledge is power and can be used, abused or ignored to our benefit or peril, respectively. Let me recap the US status, in summary, in 6 short months, COVID-19 has killed and incapacitated a large number of the population, damaged the economy, increased unemployment and impoverished working Americans, restricted industrial production, handicapped military operations, divided the public politically, caused panic and social unrest, disrupted education, overwhelmed the medical system and enhanced all these vulnerabilities associated with disparities in wealth, jobs, and access to adequate health care. These same disparities have been recognized as potential impediments to the equitable and timely and effective distribution of a vaccine(s). This became abundantly apparent at a Zoom open forum and comment period (5 hours) with the ad hoc committee of the National Academies of Sciences, Engineering, and Medicine, yesterday, September 2, 2020, for public review of the Discussion Draft of the Preliminary Framework for Equitable Allocation of COVID-19 Vaccine. I would say COVID-19 has done grave damage to the National Security of the United States. What Army could have mobilized and marched across the world so quickly? Can there be any question that this is a defense, National Security and public health issue simultaneously? But what properties of the virus and the disease it causes, COVID-19, make it so insidious and take such advantage of the US political, declining public health system, and socioeconomic state?

Coronaviruses were considered only causes of “colds” in humans until the first SARS (Severe Acute Respiratory Syndrome) came on the scene February 10, 2003 (China, first traced back to palm civets), followed by Middle Eastern Respiratory Syndrome (MERS) in 2012 (Saudi Arabia, first traced back to camels). These were the “warning shots across our bow” and we chose to ignore them.

These increasingly insidious and dangerous coronaviruses originated in bats for evolutionary and ecologically disruptive reasons. However, coronaviruses have been in many species (even marine mammals) and some very closely associated with humans (dogs, cats, cattle) for a very long time without transmission to humans in spite of the latters’ close associations. Yet, before the three very bad ones, the mild ones could only be traced back to rodents. This indicated that although coronaviruses (CoVs) are ubiquitous, it takes special circumstances to cross species lines. CoVs are classified into four genera: alpha-CoV, beta-CoV, gamma-CoV and delta-CoV, among which the beta-CoV genera contains most Human CoVs (HCoVs) and is subdivided into four lineages: A, B, C and D. Bats and rodents are the sources of most alpha-CoVs and beta-CoVs, while birds are the main source of gamma-CoVs and birds and pigs, delta-CoVs. To date, seven human CoVs (HCoVs) are known: HCoV-229E and HCoV-NL63 are alpha-CoVs, the other five beta-CoVs: HCoV-OC43, HCoV-HKU1, severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV) and SARS-CoV-2. HCoV-229E, HCoV-OC43, HCoV-HKU1 and HCoV-NL63 usually cause mild symptoms, of the common cold and/or diarrhea types.

What is apparent is that CoVs can infect the respiratory or gastrointestinal tracts or both. Both facilitate transmission of the viruses, the respiratory tract favoring asymptomatic and acute transmission and the GI tract favoring long term chronic and carrier state transmission. The latter probably most important for maintaining animal reservoirs. Thus, CoVs of all types seem to follow this successful formula. Regardless of crossing over to humans, they maintain these “animal virus” traits and that is important in explaining the mess we are in. Although there was optimism SARS2 would self-attenuate, disappear as SARS1 did or limit its spread as MERS virus has because of limited human to human spread while maintaining the animal reservoir, camels, to re-new infections, SARS2 did not. This is also due to CoV unique resistance to mutations unless a strong selection influence were present to accelerate the mutants’ transmission beyond the original variety. This has not happened, except for D614G which infects even more efficiently but with no substantial change in pathogenicity, because of the continuous availability of naive individuals in the populations exposed and human behaviors insuring rapid, efficient transmission of the original virus. The largely sparing of the young of severe COVID but devastatingly increasing severity with age and mostly cardiovascular underlying conditions (although no underlying conditions necessarily be present for enhanced severity) is also a typical CoV maintenance strategy with a twist. CoVs in cats and dogs are largely inapparent and self-limiting and widespread in their populations, with occasional morbidity and mortality in the young, the reverse of SARS2, but for similar maintenance reasons, such that vaccination for these infections, in the US, are no longer routinely pursued. However, in cats Feline Infectious Peritonitis CoV occasionally erupts into a mutant form that is universally fatal especially in young cats, probably because of high replication rate leading to appearance of the lethal mutant, killing off these individuals as a source of the virus. Although SARS2 prefers to be more pathogenic for the older rather than young, this may be based on which group maintains the virus in the populations. Also, in spite of the rapid spread of the virus, even with mostly mild and asymptomatic infections, most studies have shown relatively low overall infection rates. How can this be? CoVs have developed a common very effective survival strategy: very efficient infectivity but limited transmission efficacy, always leaving a vulnerable large section of a well-spaced population but rapidly and efficiently infecting closely physically associated populations. Why it was so surprising that such a rapidly spreading and killing virus could be stopped by masks, hand and environmental sanitation and social distancing. Also, contributing to this, is the innate limited immunity clearance of the virus in the young and asymptomatic patients without sustained adaptive immunity and killing off those who efficiently kill the virus with an overt immune response, resembling a severe allergic reaction, that increases acute and chronic morbidity and mortality. This is why herd immunity is very unlikely to naturally occur (only can happen with wide, inclusive and intensive effective vaccination). Also, why we have to be very careful that any vaccine deployed does not cause this enhanced lethal immunity. The medical community needs to learn these traits of animal CoVs to avoid tragedy and to treat and vaccinate people appropriately. This lesson needs to be learned now, because we are highly likely to see more spillover of infectious diseases from wild places being invaded and destroyed at an accelerated rate facilitated by global climate change. Before I end, I want to give one last example of this with an agent that is not even a virus, but an obligate tick- borne bacteria, Brazilian Spotted Fever. The Brazilian government decided to kill off a large portion of the giant rodent Capybara population, a reservoir for spotted fever. When they did this, ticks in the area carrying spotted fever bacteria actually increased. They found out, like all rodent populations, killing off adults increases reproduction of those that remain decreasing immunity to spotted fever because of more young naive individuals, in turn, infecting more ticks with higher doses of bacteria. Lesson: Don’t mess with Mother Nature!