*Bat signal*The hunt for the origins of SARS-CoV-2 will look beyond China

The virus may have been born in South-East Asia
*Science & technology <>*
Jul 22nd 2020

ONE OF THE great questions of the past six months is where SARS-CoV-2, the
virus that causes covid-19, came from. It is thought the answer involves
bats, because they harbour a variety of SARS-like viruses. Yunnan, one of
China’s southernmost provinces, has drawn the attention of virus hunters,
as the closest-known relatives of SARS-CoV-2 are found there. But some
think the origins of the virus are not to be found in China at all, but
rather just across the border in Myanmar, Laos or Vietnam.

This is the hunch of Peter Daszak, head of EcoHealth Alliance, an
organisation which researches animals that harbour diseases that move into
people. Since the outbreak, in 2003, of the original SARS (now known as
SARS-CoV), scientists have paid close attention to coronaviruses. Dr Daszak
says that around 16,000 bats have been sampled and around 100 new SARS-like
viruses discovered. In particular, some bats found in China are now known
to harbour coronaviruses that seem pre-adapted to infect people. The
chiropteran hosts of these viruses have versions of a protein called ACE2
that closely resemble the equivalent in people. This molecule is used by
SARS-like viruses as a point of entry into a cell.

That such virological diversity has so far been found only in China is
because few people have looked at bats in countries on the other side of
the border. Yet these places are likely to be an evolutionary hotspot for
coronaviruses—one that mirrors bat diversity (see map). The horseshoe bats
in Yunnan which harbour close relatives of SARS-CoV-2 are found across the
region. Other countries are thus likely to have bats with similar viral
building blocks. Dr Daszak believes it is “quite likely that bats in
Myanmar, Laos and Vietnam carry similar SARS-related coronaviruses, maybe a
huge diversity of them, and that some of them could be close to SARS-CoV-2”.

None of this, though, explains how a virus whose ancestor may be found in
South-East Asian bats went on to start a pandemic from central China.
China’s government has agreed that a mission led by the World Health
Organisation (WHO) can visit later this year to help answer this question.
There is particular interest in how much sampling has been conducted to
look for the missing link in places like the wildlife market in Wuhan (the
first known centre of the outbreak) and more generally in farmers, traders
and possible intermediate or host species.

Jeremy Farrar, the head of the Wellcome Trust, a large medical-research
charity, and a former professor of tropical medicine, says his guess is
that either SARS-CoV-2 or something similar to it has been circulating in
people in parts of South-East Asia and southern China, probably for many
years, and that intermediate hosts have not yet been identified. Dr Farrar
spent 18 years working in Vietnam as the head of an Oxford University
research unit. He says people go searching for bats for food and sell them
in markets in what is a sophisticated trade that can end up in big cities
like Wuhan. Bats are able to carry a huge diversity of viruses without
getting sick, and are also more mobile than people realise. As he puts it,
bats “congregate in huge colonies, and poo everywhere. And then other
mammals live off that poo and then act as a mixing vessel for these sorts
of viruses.”

Support for the idea that something resembling SARS-CoV-2 might have been
circulating in the region before the pandemic began also comes from another
intriguing observation: the low incidence of covid-19 in South-East Asia,
particularly in Vietnam. John Bell, a professor of medicine at the
University of Oxford, says everyone thought there would be a flood of cases
in Vietnam because the country is right across the border from China. Yet
Vietnam has reported only 300 in a population of 100m, and no deaths. The
country did not have a great lockdown either, he adds. Nobody could work
out what was going on.

One explanation, he suggests, is that Vietnam’s population is not as
immunologically “naive” as has been assumed. The circulation of other
SARS-like viruses could have conferred a generalised immunity to such
pathogens. So, if a new one emerged in the region, it was able to take hold
in the human population only when it travelled all the way to central
China—where people did not have this natural resistance.

This would tie in with the idea that infection with one coronavirus can
provide protection against others, and that even in countries away from the
evolutionary cauldron of South-East Asia part of the population may have
some protection against the current pandemic. In particular, there are
suggestions that protection might be conferred mainly via part of the
immune system called T-cells (which work by killing virus-infected cells)
rather than via antibodies (which work by gumming up pathogens). If that is
the case, then serological studies which look at antibodies may be
underestimating natural immunity.

Sunetra Gupta, an epidemiologist at Oxford, argues that natural immunity to
covid-19 is conferred by infections with seasonal coronaviruses. If
correct, this has implications for the level of vaccination needed to reach
herd immunity. It is widely assumed that over 50% of people need to be
vaccinated to prevent a resurgence of SARS-CoV-2. In a preprint released on
July 15th Dr Gupta says this figure could be much lower if a significant
part of the population is already resistant to infection.

As for the mystery of the origin of covid-19, more answers will come when
the WHO mission takes place, perhaps in August. The critical steps that led
a South-East Asian bat virus to start a pandemic could have happened inside
or outside of China—whether in wild-animal markets or farms, or in traders
or hunters. The virus may have jumped directly from bats into people, or
come via an intermediate species. The story is waiting to be told.