The COVID-19 epidemic, which has claimed 6.4 million lives
since it started almost three years ago, was most likely caused by live animals
sold at the Huanan Seafood Wholesale Market, according to a global team of
academics.
International teams of researchers, under the direction of
University of Arizona virus evolution expert Michael Worobey, have pinpointed
the origin of the pandemic to a market in Wuhan, China, where foxes, raccoon
dogs, and other live mammals susceptible to the virus were sold live just
before the pandemic started. After first being made public in pre-print forms
in February, their results were later published in two publications in the
journal Science.
The articles essentially rule out other hypotheses that have
been put up as possible causes of the pandemic. They have subsequently
undergone peer review and incorporate additional analysis and findings. The
authors also come to the conclusion that two distinct transmission occurrences
at the Huanan market in late November 2019 are most likely what caused the
initial animal-to-human transfer.
One investigation examined the sites of the first confirmed
COVID-19 infections as well as swab samples collected from surfaces at
different market locations. The second focused on SARS-CoV-2 genomic sequences
from samples taken from COVID-19 patients in China during the early stages of
the epidemic.
The first study looked at the geographic distribution of
COVID-19 patients in the first month of the epidemic, December 2019, and was
headed by Worobey and Kristian Andersen from Scripps Research Institute in San
Diego, California. Nearly all of the 174 COVID-19 cases reported by the World
Health Organization in that month—155 of which were in Wuhan—were located by
the researchers.
In contrast to subsequent instances, which were widely
spread around Wuhan, a metropolis of 11 million people, analysis revealed that
these patients were concentrated closely around the Huanan market. Notably, the
researchers discovered that a startling proportion of early COVID patients who
had no known relationship to the market—meaning they did not work there nor do
their shopping there—actually resided close to the market. This reinforces the
theory put out by Worobey that the market served as the epidemic's focal point,
with sellers being sick first and starting a chain reaction of illnesses among
local residents.
According to Worobey, the head of the UA Arizona Department
of Ecology and Evolutionary Biology, "in a city covering more than 3,000
square miles, the area with the highest probability of containing the home of
someone who had one of the earliest COVID-19 cases in the world was an area of
a few city blocks, with the Huanan market smack dab inside it."
A second discovery helped to confirm this conclusion:
According to Worobey, the authors discovered a "polar opposite" trend
when they examined the geographic distribution of subsequent COVID instances,
from January and February 2020. The latter occurrences occurred in regions of
Wuhan with the largest population densities, in contrast to the cases from
December 2019 that "mapped like a bullseye" on the market.
This indicates that the infection was not transmitting
covertly, according to Worobey. The market was where it really started, and it
expanded from there.
Worobey and his colleagues addressed the issue of whether
health officials discovered instances surrounding the market merely because
that's where they searched, which was a significant addition to their previous
results.
It's crucial to understand that each of these situations
included individuals who were located because they were being treated in a
hospital, according to Worobey. "None of them were minor illnesses that
might have been discovered by knocking on the doors of neighbours who lived
close to the market and asking whether they were feeling sick. In other words,
these patients were not registered based on their residence but rather because
they were hospitalised."
Worobey's team went one step farther to eliminate any
remaining chance of bias: They ran the stats again after starting at the market
and gradually moved away from it as they started deleting cases from their
analysis. The results were true even after excluding two-thirds of the
instances.
The remaining instances resided closer to the market than
what would be anticipated if there were no spatial association between these
first COVID cases and the market, Worobey said. "Even in that situation,
with the bulk of cases eliminated," he said.
After Huanan market was shut down, swab samples were
gathered from market surfaces including flooring and cages. SARS-CoV-2 positive
samples were substantially more frequent in areas with live animal markets.
Red foxes, hog badgers, and raccoon dogs were among the
species sold alive at the Huanan market in the days before the first instances
of COVID-19 were discovered, according to the researchers. These creatures are
now known to be vulnerable to SARS-CoV-2. The researchers created a thorough
market map and demonstrated a significant relationship between
SARS-CoV-2-positive samples reported by Chinese researchers in early 2020 and
the western section of the market, where live or recently slaughtered animals
were traded in late 2019.
According to Andersen, a co-senior author of both studies and
professor in the Department of Immunology and Microbiology at Scripps Research,
"Upstream events are still obscure, but our analyses of available evidence
clearly suggest that the pandemic arose from initial human infections from
animals for sale at the Huanan Seafood Wholesale Market in late November
2019."
Most likely, the virus spread from animals to people more
than once.
Jonathan Pekar, Joel Wertheim, and Marc Suchard from the
University of California, San Diego, together with Andersen and Worobey, co-led
the second research, which examined SARS-CoV-2 genomic data from early
patients.
Based on the oldest collected genomes, the researchers
integrated epidemic modelling with early evolution investigations of the virus.
They came to the conclusion that the pandemic, which at first featured two
barely different SARS-CoV-2 lineages, most likely originated from at least two
different infections of people by animals at the Huanan market in November and
maybe December 2019. The studies also revealed that there were several other
animal-to-human viral transmissions at the market during this time that did not
emerge as registered COVID-19 cases.
The scientists developed a framework for the development of
the SARS-CoV-2 viral lineages using a method known as molecular clock analysis,
which relies on the regularity with which genetic changes take place across
time. They discovered that the molecular clock data would be incompatible with
a scenario in which the virus was just once introduced into people as opposed to
many times. Previous research had shown that the virus's A lineage, which is
closely linked to viral cousins in bats, gave birth to the B lineage. The two
lineages most likely transitioned from animals to humans separately, both in
the Huanan market, in accordance with the new evidence, according to Worobey.
If not, Worobey said, "lineage A would have had to have
evolved more slowly than the lineage B virus, which simply doesn't make
biological sense."
The two investigations show that COVID-19 spread from animals
to people at the Huanan market, most likely after the animals had been exposed
to coronavirus-carrying bats in the wild or on Chinese farms. According to the
researchers, in order to reduce the danger of pandemics in the future,
scientists and public authorities should work to get a better knowledge of the
wildlife trade in China and other countries. They should also support more
thorough testing of live animals sold in marketplaces.
The National Science Foundation and the National Institutes
of Health both contributed funding to the study.
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