Introduction
The world of viruses is unimaginably vast and scientists suspect there to be millions if not trillions of viruses still waiting to be discovered (Zimmer 2020). But without doubt, this year we have all been introduced to the destructive virus, SARS-CoV-2. Unfortunately, tracing viruses back to their animal origins involves a lot of guesswork. Genomes tell a story of where the virus has been and for how long; however, scientists are still decoding this language. Following genetic clues, we can try to piece together each virus’ story to trace it back to its original zoonotic reservoir (Greger 2007). When humans come into contact with animals through live animal markets, environmental change, or hunting, we expose ourselves to novel pathogens. As long as we continue to disturb ecosystems, future pandemics will be unavoidable.
History of SARS & MERS
Figure 1: The mode by which hCoVs cause multiple organ dysfunction syndrome
Figure 2: The potential animal hosts, biodistribution, and host cell receptors of SARS-CoV, MERS-CoV and SARS-CoV-2
The Coronaviridae family consists of spherical viruses. Their genetic code is cloaked in three different kinds of proteins, one of which decorates the virus’s surface with sprouting spikes, giving the viruses their unique morphology of a crown (Kormann 2020). Within just two decades, three highly pathogenic and deadly human coronaviruses, namely SARS-CoV (2002), MERS-CoV (2015) and SARS-CoV-2 (2019) (Zhu et al., 2020) have forced us to consider how our world is profoundly impacted by organisms we cannot see. Scientists first discovered the coronavirus family in the 1950s while peering through early electron microscopes at samples taken from chickens suffering from infectious bronchitis. These viruses target the lower respiratory tract and produce similar symptoms such as fevers, coughs, sore throat, and headaches. All originated in bats, but often mutate in intermediary mammalian hosts before jumping to humans (WHO 2020). Looking at the genomes of MERS and SARS, we find more distantly related “ancestor viruses” in bats, with more closely related “parent viruses” found in the mammal reservoir hosts. MERS, first detected in 2012 in Saudi Arabia, is suspected to have spread to humans through consumption of unpasteurized camel milk or undercooked camel meat. An even closer cousin to COVID-19, SARS also most likely originated in a Chinese “wet market,” or live animal market, in Guangdong. The SARS virus most likely originated in horseshoe bats, then mutated in civets for a length of time before finally crossing over into human populations. Both SARS and MERS share comparable emergence stories with COVID-19; close human contact with wildlife, specifically for consumption, and subsequent airborne spread (Zhu et al. 2020).
How & When SARS-CoV-2 Made the jump
In order for the virus to have infiltrated into the human population, an animal host needed to come into contact with a human somewhere. That “somewhere” is currently controversial, but a potential host has been identified. Early reports suggest that the spillover event from intermediate host to humans began at the Huanan Seafood Wholesale Market. However, according to scientists at the Wuhan Institute of Virology (WIV), experts believe that the first case of SARS-CoV-2 did not emerge at this Wuhan wet market (Letzter 2020). Instead, this may have actually been the location of the superspreader event where “patient zero” infected countless others sometime late November in 2019. Exactly where and when “patient zero” was infected is still being pieced together. Genomic analysis by a team of scientists from Duke University, Los Alamos National Laboratory, the University of Texas at El Paso and New York University suggests that the intermediate host of SARS-CoV-2 is a scaly animal known as a pangolin. The genome of SARS-CoV-2 is closely related to coronaviruses isolated in horseshoe bats in China, but the virus’s ability to infect humans was likely obtained by exchanging a gene fragment from another coronavirus found in pangolins since they contain a receptor-binding site – a part of the spike protein necessary to bind to the cell membrane – that facilitates human infection and spread (Duke University Medical Center 2020).
Addressing Wuhan Lab Conspiracy Theory
There are many speculations and theories that SARS-CoV-2 was leaked from the Wuhan Institute of Virology in Wuhan, China. The laboratory has researched bat coronaviruses, including the virus RaTG13, whose genome is approximately 96% identical to SARS-CoV-2 (Liu et al. 2020 & Burki 2020). Rumors claim that RaTG13 is the source of SARS-CoV-2, and further speculations claim that the human coronavirus was made intentionally in the lab. Such theories have been perpetuated even by top officials, including President Trump. However, there is no credible evidence for these claims (Liu et al. 2020 & Burki 2020). The 4% dissimilarity between RaTG13 and SARS-CoV-2 results from more than 1,100 nucleotide differences between the two viruses' genomes. These differences are distributed throughout the genome in a pattern which is consistent with the natural evolutionary characteristics of coronaviruses. Viruses constructed in a lab would typically use a known backbone and introduce logical or targeted changes. In contrast, natural viruses evolve by accumulating random mutations gradually over time. The absence of a logical targeted pattern in the viral sequence and a close relative in wildlife species are strong indications that SARS-CoV-2 evolved naturally (Liu et al. 2020 & Burki 2020).
Cultural Practices
Illegal animal trade is under intense scrutiny, especially because pangolins, which are highly trafficked, are the suspected reservoirs of SARS-CoV-2. Pangolins are endangered and supposedly protected by international treaties. Nonetheless, pangolin meat is a famed delicacy across Asia, so trafficked pangolins are one of many exotic animals likely to be found alive in wet markets like the Wuhan Seafood Market (Quammen 2020). Wildlife trade is a high risk activity that facilitates novel virus spillover from animal to human populations. Unfortunately, the illicit nature of international wildlife trade makes it hard to regulate or monitor.
Similarly, the hunting and consumption of wildlife facilitates spillover of novel viruses from animals. Wild meat, or “bushmeat” hunting and consumption entails contact with a diverse array of tissues and fluids. Primates are genetically similar to humans, so their pathogens are more susceptible to spillover into human populations (Wolfe et. al. 2007). HIV and the Ebolavirus are both suspected to have spilled over through contact with primate blood or excretions. Rodents and bats also carry a host of diseases which have caused past epidemics such as Monkeypox (Greger 2007).
Calls to ban bushmeat consumption and wet-market practices have sparked debate. Wet markets and bushmeat trade allow families to access cheap, fresh protein. Some argue that scapegoating these traditional markets is a form of exoticism and racism (Seay 2019). Nonetheless, China has enacted measures banning the sale or consumption of wild animals in light of the recent pandemic (Westcott 2020).
Figure 3: Main trafficking flows and reported origins/destinations of seized pangolin scales (2007-2018)
Environmental Change
The emergence of many novel zoonotic diseases can be linked to environmental change. Land use change, such as deforestation, agricultural expansion, and urbanization, has been exacerbated by growing human populations and increasing demand for animal protein. These activities disrupt ecosystems and stress wildlife. Land use change puts humans into contact with animals and increases our exposure to novel viruses (Greger 2007). For example, in 1998, there was an outbreak of Nipah virus in Malaysia. The virus first appeared in pig farmers, who had been exposed to sick pigs. The pigs were infected by fruit bats which came into contact with the pigs after being displaced from their natural habitat by slash-and-burn deforestation (Greger 2007). Land use change has increased over the last 100-200 years and there has been a corresponding increase in spillover events (Welsh & Allmann-Updyke 2020). Since land use change has important implications for our health, further research should be done to identify and assess the costs and benefits of land use change scenarios to health and the environment. Policy decisions on land use should balance the needs of people, wildlife, and the ecosystem (Patz et al. 2004).
Surveillance
Surveillance of animal viruses which could potentially spillover to humans is a crucial aspect of pandemic preparedness. Surveillance begins with the identification of hotspots, which are places where people interact with wildlife. These places tend to be stressed environments where population growth, biodiversity, and land use change are high (Welsh & Allmann-Updyke 2020). Once hotspots are identified, samples can be collected, and virus genomes can be sequenced. National governments and local communities should be involved in the surveillance, and viruses with spillover potential should be reported to them (Welsh & Allmann-Updyke 2020). The USAID launched a surveillance project called Predict in 2009, which collected over 140,000 biological samples from animals and discovered over 1,000 new viruses. The project also trained about 5,000 people in 30 African and Asian countries, and has built or strengthened 60 medical research laboratories, primarily in poor countries (McNeil 2019). Unfortunately, Predict’s funding cycle ended in 2019 and was not renewed. Experts fear that the loss of this program will leave the world vulnerable to new pathogens. Knowledge of potential threats can help prevent spillovers, for example, by shutting down markets where wildlife is butchered for food. Surveillance efforts like Predict, which has cost $207 million, are far less expensive than trying to fight viruses after they emerge (McNeil 2019).
Conclusion
Disease emergence is an increasingly urgent public health phenomenon. To mitigate future pathogenic burden, we must take steps to limit our interactions with wildlife whether through environmental change, animal trade, hunting, or wet markets. Furthermore, we must act now to form a Global Early Warning System to catch viruses and bacteria as they spillover, contain the spread, and document new types of microbes. Thanks to past research into SARS and MERS, we were able to develop COVID-19 vaccines in record time. With a pathogen archive, we can hope to combat the onslaught of emerging infectious diseases and save more lives when future outbreaks occur.
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