The SARS-CoV-2 virus under a microscope. Photo credit: National Institute of Allergy and Infectious Diseases
Using molecular dating tools and epidemiological simulations, researchers from the San Diego School of Medicine in California estimate, along with colleagues at the University of Arizona and Illumina, Inc. that the SARS-CoV-2 virus would probably circulate unnoticed for a maximum of two months. before describing the first human cases of COVID-19 in late December 2019 in Wuhan, China.
They write in the online edition of Science of March 18, 2021, and also note that their simulations indicate that the mutation virus naturally dies more than three-quarters of the time without causing an epidemic.
“Our study was designed to answer the question of how long SARS-CoV-2 could spread in China before it was discovered,” said senior author Joel O. Wertheim, PhD, associate professor in the Division of Infectious Diseases and Global Public Health. at the UC San Diego School of Medicine.
To answer this question, we have put together three key pieces of information: a detailed understanding of how SARS-CoV-2 spread in Wuhan before exclusion, the genetic diversity of the virus in China, and reports of the earliest cases of COVID. 19 in China. By combining this diverse evidence, we were able to set an upper limit of mid-October 2019 for the time when SARS-CoV-2 began circulating in Hubei Province. ‘
Cases of COVID-19 were first reported at the end of December 2019 in Wuhan, located in Hubei Province in Central China. The virus spread rapidly beyond Hubei. Chinese authorities have cordoned off the region and applied mitigation measures nationwide. By April 2020, the local transmission of the virus was under control, but then COVID-19 was pandemic with more than 100 countries reporting cases.
SARS-CoV-2 is a zoonotic coronavirus that presumably jumped from an unknown animal gas to humans. Several attempts have been made to determine when the virus first began to spread among humans, based on investigations into early-diagnosed cases of COVID-19. The first group of cases – and the earliest consecutive SARS-CoV-2 genomes – were associated with the Huanan Seafood Wholesale market, but the study’s authors say the market group is unlikely to be the start of the pandemic. earliest documented COVID-19 cases had no connection with the market.
Regional newspaper reports indicate that COVID-19 diagnoses in Hubei date from at least November 17, 2019, indicating that the virus was already actively circulating when Chinese authorities instituted public health measures.
In the new study, researchers used molecular clock evolution analyzes to try in when the first case, or index, of SARS-CoV-2 occurred. ‘Molecular clock’ is a term for a technique that uses the mutation rate of genes to deduce when two or more life forms were different – in this case, when the common ancestor of all variants of SARS-CoV-2 existed , estimated in this study to be as early as mid-November 2019.
Molecular dating of the most recent ancestor is often considered synonymous with the index case of an emerging disease. However, co-author Michael Worobey, PhD, professor of ecology and evolutionary biology at the University of Arizona, said: ‘The index case could be conceivable before the common ancestor – the actual first case of this outbreak may have days, weeks or even many months. occurred before the estimated common ancestor. The core of our investigation was to determine the length of the ‘phylogenetic fuse’. ”
Based on this work, the researchers estimate that the average number of people infected with SARS-CoV-2 in China was less than one until November 4, 2019. Thirteen days later, it was four individuals, and only nine on December 1, 2019. first hospitalizations in Wuhan with a condition later identified as COVID-19 occurred in mid-December.
Study authors used a variety of analytical tools to model how the SARS-CoV-2 virus may have acted during the initial outbreak and early days of the pandemic when it was largely an unknown entity and the extent of the threat to public health is not yet fully realized.
These instruments included epidemic simulations based on the known biology of the virus, such as its transmissibility and other factors. In only 29.7 percent of these simulations, the virus was able to create self-sustaining epidemics. In the other 70.3 percent, the virus infected relatively few people before they died. The average failed epidemic ended just eight days after the index fall.
“Usually, scientists use viral genetic diversity to get the timing of when a virus started spreading,” Wertheim said. “Our study added an important layer in addition to this approach by modeling how long the virus could circulate before it led to the observed genetic diversity.
‘Our approach has yielded some surprising results. We have seen that more than two thirds of the epidemics we are trying to simulate have become extinct. This means that if we could go back in time and repeat 2019 a hundred times, two out of three times, COVID-19 would have flowed on its own without triggering a pandemic. This finding supports the notion that humans are constantly being bombarded with zoonotic pathogens. ”
Wertheim noted that even while SARS-CoV-2 spread in China in the fall of 2019, the researchers’ model suggests that it did so at low levels until at least December of that year.
“Given that it is difficult to reconcile these low virus levels in China with claims of infections in Europe and the US at the same time,” Wertheim said. “I’m quite skeptical about the demands of COVID-19 outside of China at that point.”
The original strain of SARS-CoV-2 became epidemic, the authors write, because it was widespread, favoring persistence, and because it thrived in urban areas where transmission was easier. In simulated epidemics involving less dense rural communities, epidemics became extinct 94.5 to 99.6 percent of the time.
The virus has mutated several times since then, with a number of variants being more transmissible.
“Pandemic surveillance has not been prepared for a virus like SARS-CoV-2,” Wertheim said. “We were looking for the next SARS or MERS, something that killed people at a high rate, but looking back, we see how a highly transmissible virus with a modest mortality rate can also make the world low.”
Co-authors include: Jonathan Pekar and Niema Moshiri, UC San Diego; and Konrad Scheffler, Illumina, Inc.
Funding for this research comes in part from the National Institutes of Health (grants AI135992, AI136056, T15LM011271), the Google Cloud COVID-19 Research Credits Program, the David and Lucile Packard Foundation, the University of Arizona and the National Science Foundation (grant 2028040 ).
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