Covid-19 Was a Ticking Time-Bomb, Scientists Warned Since 2007
SARS-related coronaviruses have always been around, so spillover is just a matter of time.
The Covid-19 virus, SARS-CoV-2, came from bats. How it got spread to humans, however, is still up to debate. The two prior coronaviruses epidemics — SARS in 2003 and MERS in 2012 — also originated from bats. Given that SARS and MERS happened, was Covid-19 foreseeable?
A time-bomb, scientists said in 2007
Scientists knew SARS was not going to be the last bat coronavirus infecting humans, let alone MERS or Covid-19. Since the SARS epidemic in 2003, over 4000 papers on coronavirus were soon published, according to a 2007 review led by Prof. Kwok Yung Yuen, Chair of Infectious Diseases of the Department of Microbiology of the University of Hong Kong, who is also a Fellow of the Royal College of Physicians, Surgeons, and Pathologists.
Owing to the thousands of academic papers, scientists have learned many things about coronaviruses. In fact, it is only after the SARS epidemic that science discovered the NL63 and HKU1 coronaviruses that have been causing mild-to-moderate diseases in humans all the while.
Since 2003, animal surveillance studies have also increased and identified at least 36 SARS-related coronaviruses as of 2007. “The presence of a large reservoir of SARS-CoV-like viruses in horseshoe bats, together with the culture of eating exotic mammals in southern China, is a time bomb,” Prof. Kwok and colleagues asserted. “The possibility of the re-emergence of SARS and other novel viruses… should not be ignored,” especially in farms or wildlife markets.
SARS-related coronaviruses (SARSr-CoVs) have always been around
In a 2016 PNAS study, researchers at the University of North Carolina isolated and cloned a bat coronavirus named WIV1-CoV that displayed the ability to infect human lung cells and mice via the ACE2 receptor. The mice then rapidly lost weight and had lung and brain damage. The study authors then warned for the possibility of a W1V1-CoV outbreak in mammals.
“The presence of a large reservoir of SARS-CoV-like viruses in horseshoe bats, together with the culture of eating exotic mammals in southern China, is a time bomb.”
Published in 2017 in PLOS Pathogens, a 5-year surveillance study uncovered another 11 new SARS-related coronaviruses (SARSr-CoVs) in a bat cave in Yunnan, China. Reconstructing these SARSr-CoVs in the lab, researchers at the Center for Emerging Infectious Diseases of Wuhan Institute of Virology noted that three managed to infect mammalian cells via the ACE2 receptor. “Our findings…conclusively demonstrate that all building blocks of the pandemic SARS-CoV genome are present in bat SARSr-CoVs from a single location in Yunnan,” the authors cautioned. “The risk of spillover into people and the emergence of a disease similar to SARS is possible.”
Direct spillover of SARSr-CoVs to humans
Later, virologists at Wuhan Institute of Virology realized that people living near bat caves could contract SARSr-CoVs directly without an intermediate host. Their study, printed in 2018 in Virologica Sinica, reported that 2.7% of 218 villagers in Yunnan produced antibodies to some forms of SARSr-CoVs. Considering that antibodies to coronaviruses could wane, the actual number may be higher, the study also noted. The good news is that the exposed villagers recalled only minor or no symptoms.
“And we found that 3 percent of the population had been exposed — which tells me that these things are spilling over at an incredible rate, as part of everyday business in rural China,” said one of the study’s senior co-author, Dr. Peter Dazak, president of EcoHealth Alliance, a nonprofit non-governmental organization that funds global health programs. “There may have been some little outbreaks that never got noticed, or cases where people even die, and it gets put down to influenza or something,” he added. “It’s not difficult to imagine one of those infections mutating a bit and becoming Covid-19.”
All of these data show that SARSr-CoVs (or SARS-CoV-like viruses) have been circulating in bats all the while. And that spillover to humans had happened upon close contacts with bats.
’12 years of unheeded warnings’
As mentioned above in the 2007 review of Prof. Kwok et al., SARSr-CoVs circulating in bat populations are a ticking ‘time-bomb.’ And that spillover to humans could happen at any time.
But, “unfortunately, outside of some members of the scientific community, there has been little interest and no sense of urgency,” said a 2020 review led by David M. Morens, MD, at the National Institute of Allergy and Infectious Diseases in National Institutes of Health (NIH). “In 2020, we learned, tragically, what 12 years of unheeded warnings have led to: A bat-derived sarbecovirus — from the very same SARS-like bat virus group that had been warned about by multiple voices for over a decade — emerged and proceeded to cause the Covid-19 pandemic that now sweeps the globe.”
Bats are reservoirs for many disease-causing viruses in humans, such as rabies, SARS, MERS, Covid-19, Ebola, Nipah, Hendra, Sosuga, and Marburg viruses, according to a 2020 paper in Nature Reviews Microbiology by researchers at the NIH. Do these viruses not kill the bats? In fact, bats possess unique features that make their immune system highly antiviral.
- Bats are the only mammal capable of prolonged flight, and flying increases bats’ core body temperature to ~40°C and metabolism by 15-fold.
- Bats have an unusually strong interferon antiviral response, which is, in part, driven by fever and increased metabolism during flight. (Interferons are pro-inflammatory cytokines that interfere with virus replication.)
- Bats rarely get cancer due to their highly active DNA repair mechanisms, which could quickly fix the DNA damage caused by viruses or cytokines.
As viruses adapt to the bats’ antiviral immunity, they become overly virulent to humans with a weaker immune system and metabolism. “Such rapidly-reproducing viruses would likely generate extreme virulence upon spillover to hosts lacking similar immune capacities to bats,” explained Dr. Cara Brook, a postdoctoral microbiologist at the Unversity of California.
What should be done
“Future coronavirus transmissions into humans are not only possible, but likely,” Dr. Morens and colleagues also stated. So, we ought to prepare for future spillover events.
Using genetic sequencing and computational techniques, scientists have mapped ‘hotspot’ areas at risk for spillovers. These areas include parts of China, Laos, Myanmar, and Vietnam with diverse populations of bat species harboring different SARSr-CoVs. Gene sequences of such viral discovery efforts are then shared in public databases. Scientists can then construct artificial viruses or use bioinformatics approaches to study antibody responses, vaccines development, diagnostic assays, therapeutics, or disease pathology in animals or cultured cells.
“In 2020, we learned, tragically, what 12 years of unheeded warnings have led to: A bat-derived sarbecovirus — from the very same SARS-like bat virus group that had been warned about by multiple voices for over a decade — emerged and proceeded to cause the Covid-19 pandemic that now sweeps the globe.”
Essentially, preventing possible outbreaks boil down to accurate predictions and early interventions. For example, preventive vaccines can be given to humans or animals inhabiting ‘hotspot’ regions. Antiviral therapeutics can be tested on animals or cell cultures for viruses with high potential for spillover. The habitat of ‘hotspot’ areas must not be disturbed as well. Lastly, wildlife wet markets or farms must be monitored and tested regularly for any appearance of new microbes or diseases.
Since the SARS epidemic in 2003, coronavirus research has gained traction. Academics then realized the rich diversity of SARSr-CoVs circulating in bats, of which some can infect human cells and cause severe diseases in mice. Even direct bat-to-human spillovers of SARSr-CoVs had happened. So these SARSr-CoVs are a ticking time-bomb, scientists warned since 2007. Yet public health measures were not conducted rigorously. Covid-19 was a result of “12 years of unheeded warnings,” researchers say. From hereon, greater efforts must be made to predict future spillover events and intervene early.