Knowing the origin of COVID-19 won’t change much

More than two years since the first cases started cropping up in Wuhan, China, there is much we don’t know about the origin of SARS-CoV-2, the virus that causes COVID-19. But a quick solution to that question is possible: Scientists could find bats in a cave somewhere in China or Southeast Asia and trace a chain leading from those bats to the COVID-19 outbreak in Wuhan. Realistically, however, recent history offers little promise that this will happen anytime soon. For example, about 14 years passed between the identification of HIV as the virus that caused AIDS and a demonstration of the modern transition to humans from a specific group of chimpanzees, although this had been suspected several years earlier. About a decade passed from the time of the SARS epidemic of 2003-2004 and the final delineation of the origin of the causative coronavirus, and seven years passed before the flu pandemic of 2009-2010 was shown to originate in Mexican pigs. . The alternative possibility for a natural origin – a laboratory leak – will be difficult to definitively prove or disprove.
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More importantly, the focus on origins begs the question: Were there really big changes in health policies or research directions for past pandemics when the origins were determined? Take HIV, for example: we learned that chimpanzee-to-human transmission took place in rainforests, but we didn’t interrupt visits or human lives in rainforests. We learned that HIV probably came to cities because of population movements and increased prostitution, then became global through changes such as frequent travel in large numbers, increased sexual contacts, medical use of blood and plasma, and IV drug addiction. Needless to say, public order changed little. The origin of SARS was learned, but we now have SARS-CoV-2. The great flu pandemic may have originated in WW1 barracks, but we moved on to WWII and didn’t stop with soldiers in barracks. In short, knowing its origin made little difference in how we treated and coped with the disease — in most if not all cases.

Still, the World Health Organization (and much of the scientific community) initially agreed with the Trump administration’s claim that understanding the origins of SARS-CoV-2 was of immediate importance. The government’s concern was, probably, less a matter of sober interest in science, but more of an attempt to open a new front in the US’s response to a nascent China, or an attempt to divert attention. of a delayed and chaotic US response to the pandemic. Those who advocate an intensive effort to determine the origin of SARS-CoV-2 argue that it would be valuable to establish public health policy based on that understanding. What else needs to be done to counter Delta or, now, Omicron by better understanding the origins of SARS-CoV-2? Knowing its origins could put an end to the ongoing politically charged debate and make an important contribution to scientific understanding. However, we doubt whether knowledge of its origins would change how we should respond to the challenges of SARS-CoV-2, or how we would prepare for a future pandemic. We can now act on the assumption that both hypotheses (nature or laboratory leak) can be correct.

This is where the origin discussion now stands: one idea is that there was a natural origin; bat directly or via an intermediate animal on humans. The other is that the cause was a research error. Scientists studying bats in the field may have become infected themselves or returned infected bats to the lab. Then the virus accidentally spreads. It is also possible that gain-of-function research caused SARS-CoV-2 followed by its accidental release. Early expression of support for the gain-of-function hypothesis involved CGG, one of the codons that specifies the amino acid arginine for its insertion into the virus’s newly formed spike protein, allowing a human protease (furin) to spike the spike protein. protein from the coronavirus more efficiently, which can facilitate infection. Nobel laureate David Baltimore has expressed the opinion that CGG encoding for arginine was so exceptional that it would suggest it was man-made, but this proves inconclusive. Other coronaviruses, such as those that cause the common cold, do have the CGG codon for arginine, albeit only a limited number in the so-called beta subgroup to which SARS-CoV-2 belongs.

President Biden gave US Intelligence (IC) agencies 90 days to assess the likelihood of natural causes versus research errors, and they reported their findings in late August. While one bureau concluded that research errors were more likely, four other bureaus concluded that the probability had natural causes, and the National Intelligence Council (NIC) summary conclusion also favored the natural origin hypothesis, although both the individual agencies and the NIC only placed little to moderate confidence in their conclusions. The released version of the IC report also pointed to the “…frustration” of the Chinese government [that] the international community is using the issue to exert political pressure on China…” as one reason why further Chinese cooperation in establishing origins remains unlikely. While research errors remain a possibility, we doubt there will be a definitive answer anytime soon. That said, the evidence is mounting in favor of the natural origin hypothesis, and previous reviews pointing to a lab leak, such as the furin hypothesis discussed above, have been softened on close scrutiny.

We’ll come back to the question of how much it really matters. For origin, we know how to respond to every scenario. There is a very limited number of directions to follow, and caution dictates that each should be followed.

Disease surveillance. More investment in disease surveillance at the human-nature interface and in disrupting potential pathways of animal-to-human viral infection spread are clear priorities. Even if SARS-Cov-2 was created by research error, this remains true. Research safety. Safety expectations for laboratory research into dangerous pathogens must be increased. We have ample evidence of accidental discharges from labs in all parts of the world over the decades. Field investigation safety protocols and specimen management also need to be reviewed and strengthened. Better standards of training must be defined to work with a particular type of pathogenic virus, accompanied by some form of accreditation. Research funding should weigh the (often important) knowledge more carefully against the residual risk of studying dangerous microbes. Gain-of-function research. For most virologists, this phrase, as it is currently used, denotes research that seeks to determine whether certain genetic changes deliberately made in the lab with a virus can lead to an increased ability of the virus to infect cells. In the case of human coronaviruses, this means a greater ability to infect human cells. The goal is to learn how to be better prepared to develop protection against viruses that can develop these changes in nature and potentially cause a serious human epidemic or pandemic. This goal is undoubtedly worthy, as it would give the medical community insider knowledge for diagnostics, vaccines and therapy if such a virus were to emerge. Again, we have to weigh risk versus benefit. Virologists are well aware that viruses can escape from research labs. In each of these experiments, the risk-to-reward has to be estimated. Functional gain research is now being reviewed by established virologists with these points in mind, but we must admit that the scientists involved are generally tempted to proceed with confidence in their ability and confidence that they have adequate control over the laboratory situation. Most scientists will want to move forward. If reviews are positive, such research is more than likely funded by the NIH, and their reviews aren’t very transparent. We could take a page from the molecular biologists and their meetings in Asilomar, Ca. where detailed discussions took place about the ethics and potential dangers of some types of gene cloning experiments. These discussions led to guidelines of the acceptable and the unacceptable. One idea we believe has merit is to include non-specialists, even non-scientists, as part of the review process to provide additional independent oversight of research funding.

There is a lot of scientific interest in understanding the origin of SARS-CoV-2. And let’s face it, it would be nice to know. At the same time, knowing its origins may add little to what we already know in terms of tackling Delta, Omicron, and whatever might come next. Perhaps the best way forward is to minimize the distraction of a politicized effort to assess the origins, and instead invest in long-term international collaboration efforts on SARS-CoV-2 and in preparation to future epidemics and pandemics.

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