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Q: How do scientists trace the origin or "ground zero" of a pandemic?

Krishna: Scientists read the virus ( or microbes') genome, tracing its origins and looking for dangerous mutations to understand how it spreads.
It really is difficult to find ground zero of a pandemic, especially if the country of origin doesn't co-operate. If the world doesn't cooperate.
However, genetic technologies: a deep-dive into the genome of the virus ( or other microorganisms), can give us some clues.  Analyses of the viral genomes are already providing clues to the origins of the outbreaks happened till now and even possible ways to treat the infections. Reading the genome  also allows researchers to monitor how   pandemic is changing and provides a roadmap for developing  diagnostic tests and  vaccines.
According to experts ( like virologists, epidemiologists, microbiologists, molecular biologists, and zoologists ), it can also tell us how the outbreak started — from a single event of a virus jumping from an infected animal to a person or from a lot of animals being infected. And the genetics can tell us what’s sustaining the outbreak — new introductions from animals or human-to-human transmission.
In case of pandemics like covid-19, scientists first sequence the virus’s genome at the place they think the virus has originated - usually disease outbreaks  will be reported by the governments and make it available to others in the field through publishing papers or sending the reports to WHO. Other experts too join the war and sequence all the available variants. 

Viruses are compact nucleic acid packages of either DNA or  RNA associated with proteins, and in some cases with lipids. Viruses are not living organisms and can only reproduce inside living cells susceptible to viral entry and with the capacity to replicate viral nucleic acids and translate nucleic acid signals into amino acids to build viral proteins. Viruses are therefore nonliving self-contained genetic programs capable of redirecting a cell’s machinery to produce more of themselves.

It follows that when a virus enters a human cell for the first time, it has very recently been transmitted from cells of some other host, that is, from another animal or, for example, an insect vector. Emergence of a pathogen between a vertebrate or an insect has been referred to as host-switching, sometimes described as a spillover event. Most of the human viral and nonviral infectious diseases that have existed for centuries—measles, influenza, cholera, smallpox , falciparum malaria, dengue, HIV, and many others—originated by animal-to-human host-switching. The complex genetic events that underlie host-switching differ greatly from pathogen to pathogen, but general mechanisms have been recognized for many(3).

Host-switching determinants prominently include social, environmental, and biological factors providing the opportunity for host–species interaction; shared host cell receptors; genetic distance between transmitting and receiving hosts; and characteristics and complexity of the viral quasi-species or viral swarm. RNA viruses in particular are not transmitted to multiple cells as identical virions, but as collections of thousands of different genetically related virions. The ever-changing complexity of the viral swarm varies among species, genetically distinct but related individuals of the same species, and in single hosts over time.

Studying animal viruses that have previously spilled over into humans provides clues about host-switching determinants.

 Human pandemic and seasonal influenza viruses arise from enzootic viruses of wild waterfowl and shore birds. From within this natural reservoir, the 1918 pandemic “founder” virus somehow host-switched into humans. We know this from genetic studies comparing avian viruses, the 1918 virus, and its descendants, which have caused three subsequent pandemics, as well as annual seasonal influenza in each of the 102 years since 1918. Similarly, other avian influenza viruses have host-switched into horses, dogs, pigs, seals, and other vertebrates, with as yet unknown pandemic potential. Although some molecular host-switching events remain unobserved, phylogenetic analyses of influenza viruses allow us to readily characterize evolution and host-switching as it occurs in nature.(3)

The genome of the Wuhan virus, for instance is 29,903 bases long, one of many clues that have led scientists to believe it is very similar to SARS.

By comparing the several genomes, scientists can address the “when did this start” question. All the available samples first tested in this case show “very limited genetic variation”: Scientists concluded on an online discussion forum where virologists have been sharing data and analyses. “This is indicative of a relatively recent common ancestor for all these viruses.”

Given what’s known about the pace at which viral genomes mutate, if nCoV had been circulating in humans since significantly before the first case was reported on Dec. 8, the 24 genomes would differ more. Applying ballpark rates of viral evolution, scientists estimate that the "parents of the virus" from which all others are descended first appeared no earlier than Oct. 30, 2019, and no later than Nov. 29.

The progenitor virus itself was almost certainly one that circulates harmlessly in bats (as SARS does) but has an “intermediate reservoir” in one or more animals that come into contact with people.  Presumably, that reservoir is one of the species of animals at the Wuhan market thought to be ground zero for the outbreak. The ancestor of 2019-nCoV existed in that species for some unknown time, never infecting people, until by chance a single virus acquired a mutation that made it capable of jumping into and infecting humans.

The genome sequences suggest that was a one-time-only jump. The genomes [from the 24 samples first tested] are very uniform. If there had been multiple introductions, including from many different animals, there would be more genomic diversity. This was a single introduction.

An analysis by a team from the Wuhan Institute of Virology(1), determined that the genome of this coronavirus (the seventh known to infect humans) is 96% identical to that of a bat coronavirus, suggesting that species is the original source.

Another team of scientists in China reported that the new coronavirus is 86.9% identical to the bat SARS-like coronavirus

The first known infections from SARS‑CoV‑2 were reported in Wuhan, China. The original source of viral transmission to humans remains unclear, as does whether the virus became pathogenic before or after the spillover event. Because many of the early infectees were workers at the Huanan Seafood Market, it has been suggested that the virus might have originated from the market. However, other research indicates that visitors may have introduced the virus to the market, which then facilitated rapid expansion of the infections.

 Phylogenetic network analysis on 160 complete SARS-CoV-2 genomes  has revealed 3 central variants (A, B, and C) distinguished by amino acid differences. Variant A is the closest to that discovered in bats, that had 96.2% sequence similarity to the human virus, and was thus considered the original human virus genome. Although present in Wuhan, where the explosion of the pandemic had taken place, in the city it was not the predominant genome. Large number of A genomes were instead found in Americans who had lived in Wuhan and in the USA and Australia. The predominant genome in Wuhan and East Asia was variant B, which is separated from variant A by two mutations: the finding that it did not travel much beyond China and South East Asia without further mutations, implies a founder event in Wuhan and/or East Asia. Variant C differs from its parent variant B by a G-V change: it is the major European type, initially found in patients from France, Italy, England, and Sweden. It is absent from mainland China, but has been found in Singapore, Hong Kong, Taiwan and South Korea: the earliest introductions of the variant in Italy actually occurred from a first documented German case in January 27, 2020, and from the Singapore cluster. The German infection had occurred from an employee of the Webasto Company in Munich, who had contracted the disease from a Chinese colleague in Shanghai, who had in turn received a visit by her Wuhan parents (from Italy the variant had then spread to Brazil and Mexico by people who had visited Italy): during its travel from its origin in Wuhan to Italy, and to Brazil and Mexico the virus had undergone 10 mutations (2).

The Black Death, the biggest pandemic of our history, was caused by the bacterium Yersinia pestis and lasted in Europe between the years 1346 and 1353. Despite the pandemic’s immense demographic and societal impacts, its origins have long been elusive till date. Now, a multidisciplinary team of scientists, including researchers from the Max Planck Institute for Evolutionary Anthropology in Leipzig, the University of Tübingen, in Germany, and the University of Stirling, in the United Kingdom, have obtained and studied ancient Y. pestis genomes that trace the pandemic’s origins to Central Asia.

In this study, an international team of researchers analysed ancient DNA from human remains as well as historical and archaeological data from two sites that were found to contain “pestilence” inscriptions. The team’s first results were very encouraging, as DNA from the plague bacterium, Yersinia pestis, was identified in individuals with the year 1338 inscribed on their tombstones.

But could this have been the origin of the Black Death? Researchers have previously associated the Black Death’s initiation with a massive diversification of plague strains, a so-called Big Bang event of plague diversity. But the exact date of this event could not be precisely estimated, and was thought to have happened sometime between the 10th and 14th centuries. The team now pieced together complete ancient plague genomes from the sites in Kyrgyzstan and investigated how they might relate with this Big Bang event. They found that the ancient strains from Kyrgyzstan are positioned exactly at the node of this massive diversification event. In other words, scientists found the Black Death’s source strain and they even now know its exact date [meaning the year 1338.

But where did this strain come from? Did it evolve locally or did it spread in this region from elsewhere? Plague is not a disease of humans; the bacterium survives within wild rodent populations across the world, in so-called plague reservoirs. Hence, the ancient Central Asian strain that caused the 1338-1339 epidemic around Lake Issyk Kul must have come from one such reservoir. “We found that modern strains most closely related to the ancient strain are today found in plague reservoirs around the Tian Shan mountains, so very close to where the ancient strain was found. This points to an origin of Black Death’s ancestor in Central Asia (4).

So, governments can run away from the world but can't hide from scientists! 

People can speculate things, spread misinformation about 'biological warfare', but can't escape from the surveillance of scientists. 






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