In the year since the novel Corona virus, SARS-CoV-2 or COVID-19, began its worldwide spread, there have been many manifestations of its powerful effect on humanity. Previously bustling cities have been rendered near-ghost towns, entire businesses have been shuttered, and children have been sent home from their schools. As people have experienced major disruptions of their daily lives, many marvel at the power of a simple virus to wreak such havoc in a world in which they thought advanced medical science had relegated such plagues to ancient history. Although virologists have now succeeded in developing effective vaccines and governments have latterly figured out how to deploy them, it is important to reflect on why and how the COVID-19 Pandemic of 2019-21 happened in the first place. What did we learn, and what can we do to prevent future pandemics? A broad, high-level review of the pandemic from the perspective of evolutionary medicine yields important insights.
Viruses are simple and parasitic life forms that are likely holdovers of the RNA World, a hazy netherworld dating back a couple of billion years ago, before even the advent of DNA as the universal genetic material of life on Earth. Viruses have no way to move around by themselves but depend on physical forces of water and air, mediated by the proximity and actions of their hosts, to invade their cells and propagate. Water and air are constants in this scenario. It is the proximity and actions of hosts, ourselves and our fellow cellular organisms included, that explain the how and why of the COVID-19 Pandemic.
In an article entitled “Spreading of COVID-19: Density Matters,” published in PLOS at the end of 2020 Wong and Li (2020) concluded that “research presented here identifies the strong positive association between population density and the number of cases.” As their time sequence of cases shows, this pattern became very apparent as the pandemic progressed (Fig. 1).
Fig. 1. Counties in the continental U.S. with confirmed cases in weeks 7, 11, 15, and 18 (Wong and Li 2020, Fig. 2). https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0242398
If we compare Fig. 1 with a map of population densities in the U.S. (Fig. 2), a swath of sparse population stretches southward discontinuously from Montana through the Great Plains down to southwest Texas that closely matches a mass distribution of low COVID-19 infection rates. The state of Montana has a population density of 2.7 individuals per square km (7 individuals per square mile) which matches a very low incidence of Corona virus infection in 2020. For comparison, New York City, which showed an early and very high incidence of COVID-19 infection, has the highest population density in the U.S. of 10,892 individuals per square km. As of the first quarter of 2021 the virus has spread almost over the entire U.S., which has an overall population density of 36 individuals per square km. Large cities with the population densities generally over 2,600 individuals per square km (1,000 individuals per square mile) (http://www.worldometers.info) are predictably hotspots for the virus. From these data we can reasonably conclude that any population with a density greater than about 3 people per square kilometer (or about 8 people per square mile) will eventually be infected by a viral pandemic like COVID-19. That’s a rather scary prognosis for the world. What else do we know about the Corona virus that can help us prevent or at least minimize future pandemics?
Fig. 2. U.S. population density map closely parallels rates and densities of COVID infections. From https://www.vividmaps.com/wp-content/uploads/2018/08/US-density.jpg
The Corona virus’s evolutionary strategy seems to be to infect via the respiratory tract of forcefully breathing animals who live close together in groups. The SARS-CoV virus, the virus that caused the SARS outbreak in 2003, is a close relative of SARS-CoV-2 (COVID-19). Both viruses share a common animal reservoir of horseshoe bats of the genus Rhinolophus. These microbats live throughout the Old World, in dense colonies, and they echolocate by forcefully expelling air from their lungs. When the virus is expelled from an infected individual in a droplet or aerosol it must soon find a place to land in another host that is wet and appointed with a receptor molecule for Angiotensin Converting Enzyme 2 (ACE-2). All air-breathing vertebrates have this receptor on cells in their nasal cavities and lungs for docking with the endogenously produced protein Angiotensin-2, which stimulates a rise in blood pressure. The Corona virus has evolved the ability to dock with the ACE-2 receptor and by this bit of molecular trickery it gains access to the host’s cell and infects it.
We human beings have discovered over the last year two major ways that the Corona virus can be thwarted in its attempts to infect our cells. We can don masks, which block the transmission of respiratory droplets and aerosols, and we can stay away from others, increasing the distance from potential sources of the live virus floating in the air. In fact, if inter-personal distances are far enough apart, as for example in Montana with its low population density, that alone can impede the spread of the virus. However, we know that eventually even open places on the epidemiological map will become colored in as colonizing viruses come in on planes, roads, and trains from elsewhere, and so-called “herd immunity” of the human population results. Vaccinations will also hasten society’s response to the pandemic but not before much avoidable loss of life.
In puzzling out the “Why?” and “Why now?” questions of the COVID-19 Pandemic, density of populations seems to lie at the heart of the answer. The Corona virus’s basic adaptation of respiratory attack at close range makes sense to have evolved in bats, who live in colonies of thousands, roosting together in caves, setting out en masse on their nightly hunting excursions, breathing heavily as they flap away, and emitting blasts of air along with virus-infected aerosols as they echolocate (Fig. 3). From the virus’s perspective, a human scenario of maskless New Yorkers rushing breathlessly into a crowded subway, emitting blasts of air along with potentially virus-infected aerosols as they elocute, is not too different (Fig. 4). In the parlance of Evolutionary Medicine, we humans find ourselves in an evolutionary mismatch – faced with a a new and challenging health situation as a colonial species, thrust into a demographic for which we are not adapted.
Fig. 3. A colony of horseshoe bats. (Adobe Stock photo).
Fig. 4. New York City subway scene at rush hour. (Adobe Stock photo).
The global population is now at the highest level that it has ever been in human history. Reconstructing population densities of early hominins from large controlled excavations in Africa dating 2.3 million years ago, I estimated that our ancestors were quite rare members of the fauna at that time (Boaz 1979). Their population densities were calculated to have been between less than 1 to 2.5 individuals per km2, or only slightly lower than that of rural Montana today. This range of population densities is equivalent to modern hunting and gathering peoples as well as to extant free-ranging chimp populations, so it is likely that early hominin population densities remained in this same range for millennia. Significant population increase did not occur until the Neolithic Revolution, only some 10,000 years ago, when the advent of agriculture allowed the establishment of permanent towns and villages as preserved in the archaeological record. The inescapable deduction is that our ancestors over a vast period of time lived in small groups spread out over large home ranges, under ecological conditions very unlike that of colony-living bats, and in which a viral pandemic such as COVID-19 could not have occurred. Humans thus find themselves unprepared evolutionarily to deal with the formidable health challenges of the moment, as well as the future, which seems to promise an ever-expanding global population boom.
Medical science is not likely to discover a way any time soon to solve humanity’s rising population numbers, but the fruits of epidemiological research can point the way to avoiding future pandemics. By understanding how COVID-19 arose and spread, it is possible to propose ways to intervene and break the train of viral transmission from animal reservoirs to humans. Comparing viral DNA sequences across species can establish relationships, patterns of contact, and mechanisms of spread, culminating in more comprehensive knowledge of the evolution and ecology of the virus.
Genomic studies show conclusively that colony-living horseshoe bats are the reservoir population of Corona viruses that then zoonotically become transmitted to humans. Humans, however, being large, terrestrial, and diurnal only rarely interact directly with small, flying, and nocturnal bats. So, it is most likely that humans have been infected from intermediate animal hosts. In the case of the SAR-CoV virus DNA comparisons indicated that this intermediate host was a viverrid, the masked palm civet cat, Paguma larvata, a predator of bats in the wild and also sold in live-animal wet markets throughout eastern Asia (https://pubmed.ncbi.nlm.nih.gov/17848070/).
Fig. 5. The pangolin, the only scaled mammal and one whose high population densities in Asian wet live-animal markets and lowered immune response likely conspired to make it an intermediate host of the COVID-19 virus, infecting humans. (Adobe Stock photo.)
COVID-19 also has its reservoir in horseshoe bats, making it likely that it would have required an intermediate animal reservoir to be transmitted to humans. In this case genomic evidence points to the pangolin, an unusual mammal composed of several species in the Order Pholidota native to southeastern Asia and sub-Saharan Africa (Fig. 5). Known by their colloquial name, the Spiny Anteater, pangolins are said to be the most trafficked animal in the world and are sold as a delicacy in live-animal wet markets in China and Vietnam. Pangolins are toothless insectivores with solitary and nocturnal habits, so they would not appear on first blush to be good candidates for having contacts with bats in the wild. However, their high population densities in live-animal wet markets, coupled with their lowered interferon-mediated immune systems and consequent heightened susceptibility to disease (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5052048/), make them prime candidates for contracting the virus from nearby bats also sold in wet markets. Understanding this connection as a way to counteract future spread of the virus has led Chinese authorities to close down the Wuhan market where the COVID-19 outbreak first occurred. Although this may be an effective strategy in the short term it is unlikely to change the cultural predilections of millions of Chinese and Vietnamese who will continue to constitute a substantial market for “bush meat.”
Regularly testing animal populations in large aggregations and regulating their population numbers may be the best way to avoid viral outbreaks and spread to humans in the future. Better and more effective wildlife conservation and anti-poaching efforts to cut off supply to wet live-animal markets are another obvious and beneficial approach to pandemic prevention. Importantly, regardless of the species concerned, population density matters when it comes to understanding viral spread.
Boaz, N.T. 1979 Early hominid population densities: New estimates. Science 206:592-595.
Wong, D.W.S. and Li, Y. 2020 Spreading of COVID-19: Density matters. PLOS Published: December 23, 2020. https://doi.org/10.1371/journal.pone.0242398