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COVID-19: From bats to another mammal to humans, now deadly pandemic
Published in SUNS #9104 dated 21 April 2020

Geneva, 20 Apr (Chakravarthi Raghavan*) – The deadly novel coronavirus, 2019-nCoV, originated in bats, was transmitted to another mammal between 20-70 years ago and from that yet to be identified mammal, found a human host in Wuhan, China in late November or early December 2019, and has now spread across the globe, according to Indian virus expert and epidemiologist, P. K. Rajagopalan.

[P. K. Rajagopalan is a former Director, Vector Control Research Center (VCRC) under the Indian Council of Medical Research (ICMR); a former WHO Consultant and member of the WHO Expert Committee on Malaria, Filariasis and Vector Control, he is a recipient of the Indian Padma awards.]

On 22 January, two days after China publicised the public health threat from the newly discovered virus, in the first of daily briefings since then, WHO Director-General Dr. Tedros Adhanom Ghebreyesus sounded a note of alarm, initially describing it as “febrile respiratory illness of unknown etiology from Wuhan in China,” and asked all countries to take the threat seriously and take precautions, declining though on 23 January to call it a public health emergency.

Perhaps after more consultations and confirmed information from the Chinese, the WHO reversed course and declared a public health emergency on 29 January, “acting more decisively and firmly than in previous epidemics,” (according to the New York Times, 30 January).

[With COVID-19 spreading rapidly across the United States and the US emerging as the epicentre for the virus and its disease, the Trump administration has tried to divert attention from its own failures to take action early on, by blaming the WHO and its DG for not acting earlier, and is cutting funding to the organization.

[However, according to a report (19/20 April) in the Washington Post, citing US and international officials, more than a dozen US researchers, physicians and public health experts, many of them from the Centers for Disease Control and Prevention, were working full time at the Geneva headquarters of the World Health Organization as the novel coronavirus emerged late last year and transmitted real-time information about its discovery and spread in China to the Trump administration.]

This new coronavirus, 2019-nCoV, causing the highly infectious upper respiratory disease, has now spread across the globe, hitting over 90 countries by March and is still spreading.

The virus has since been named “SARS-CoV-2” by the WHO, and the disease it causes in humans, as COVID-19.

In a Review Article** in the Journal of Communicable Diseases (Submission: 2020-03-11; Acceptance, after peer review: 2020-04-16), Rajagopalan says that there is no evidence so far that SARS-CoV-2 was genetically engineered, but (enough evidence) that it is a natural mutation.

The virus itself, he adds, probably originated, but is yet to be proved, in the Horseshoe bat (Rhinolophus sinicus), then transmitted to another mammal (still to be identified) between 20-70 years ago, and to a human host in Wuhan, in late November or early December 2019.

[** Rajagopalan P. K. The Deadly Corona Virus (Covid-19). J Commun Dis 2020;52(1): 1-4. Journal of Communicable Diseases, Volume 52, Issue 1 – 2020, Pg. No. 1-4.]

For the Review Article, Rajagopalan has cited several published and un-published research papers from a wide range of research institutions and their journals – Chinese, British (The Lancet), John Hopkins and US virus experts and their journals. These can be found in the Review Article in the Journal of Communicable Diseases, cited above.

Just like the SARS epidemic that created panic 18 years ago, a great number of Severe Acute Respiratory Syndrome-related corona viruses (SARSr-CoV) have been discovered in their natural reservoir host, bats. Earlier research have shown that certain bat SARSr-CoVs can infect humans.

Full-length genome sequences of this novel coronavirus in five COVID-19 patients, at the early stage of the outbreak, were found to share 79.5% sequence resembling SARS-CoV. The research proved that SARS-CoV and 2019-nCoV have the same cell entry receptor, ACE2.

A bat coronavirus has been found to be 96% identical at the whole-genome level to this virus. The entry receptor of novel CoV is the same as that of ACE2.

The pair-wise protein sequence analysis of seven conserved non-structural proteins show that this virus belongs to the species of SARSr-CoV.

HOW HAS THE DISEASE ORIGINATED AND HOW HAS IT SPREAD?

The origin of the pandemic, Rajagopalan notes, has been associated with the Huanan seafood market in Wuhan, China where animals such as birds and rabbits were also being sold. What is the host of the virus and how did it enter humans is the puzzle. As it is being resolved by Chinese research teams by means of genomic analysis on viruses isolated from patients, the puzzle pieces are coming together.

The novel coronavirus, 2019-nCoV, Rajagopalan says, has been linked to bats. Bats carry and transmit some of the world’s deadliest zoonotic viruses: Ebola, Marburg, Nipah, and the pathogen behind the severe acute respiratory syndrome, SARS corona virus, to name a few.

And of course KFD.

KFD (Kyasanur forest disease, caused by a virus) was discovered and identified by Rajagopalan, in the Kyasanur forests on the Western Ghats of India (stretching from Kerala to Gujarat), in extensive field work — climbing trees, finding bats at various heights, drawing blood samples, and studying and analysing them in labs. Recognized in 1957, the virus was isolated in 1969 by him from four insectivorous bats, Rhinolophus rouxii, and from Ornithodoros ticks collected from the roosting habitat of these bats, (Ind. J. Med. Res, 1969, 905-8).

What has puzzled researchers for a long time is why bats don’t appear to get sick from their unusually high microbial loads. The question has been nagging Peng Zhou, a virologist at China’s Wuhan Institute of Virology, for more than a decade, ever since he took part in a survey of bat populations in southern China.

Zhou and his colleagues were looking for the strain of the SARS coronavirus responsible for the 2003 outbreak that sickened more than 8,000 people worldwide and killed nearly 800. And now we have the deadly novel coronavirus.

Are bats involved? “We started to think, why bats?” he says. An earlier report, published on 23 January, came from a team at the Wuhan Institute of Virology, Chinese Academy of Sciences in Wuhan, China.

Another report, published in The Lancet on 30 January, “Genomic characterization and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding,” came from a group in the Chinese Center for Disease Control and Prevention, Beijing, China.

The Lancet paper analyzed 10 genome sequences from nine patients, eight of whom had visited the Huanan seafood market in Wuhan. The sequences had more than 99.98% sequence identity. In addition, they found that the 2019-nCoV genome had 88% identity to two bat-derived SARS-like corona viruses, 79% identity to SARS-CoV, and only about 50% identity to another coronavirus that is a human pathogen – Middle Eastern respiratory syndrome (MERS-CoV).

The team also found that 2019-nCoV had a similar receptor-binding domain structure to that of SARS-CoV.

They write that “although our phylogenetic analysis suggests that bats might be the original host of this virus, an animal sold at the seafood market in Wuhan might represent an intermediate host facilitating the emergence of the virus in humans.”

During the SARS-CoV outbreak in 2003, scientists and epidemiologists tested various animals to find out the natural reservoir of the virus… horseshoe bats have now been proved to be the natural hosts of coronavirus. This discovery made further research easier.

Since bats were shown to be the carrier of SARS in 2003, not only have many severe acute respiratory syndrome related corona viruses (SARSr-CoV) been isolated from bats, the mammals have also been recognized as the natural reservoir for over 100 other viruses including MERS, Ebola virus, Marburg virus, Hendra virus, and Nipah virus, to name a few.

Why and how are the bats able to carry and spread so many viruses? The reasons may be many.

As reviewed in the article, “Going batty: Studying natural reservoirs to inform drug development”, Chinese researcher Wudan Yan noted:

* Bats’ high-density lifestyle sets up a perfect storm of viral transmission;

* The tremendous diversity in and among the bat species, which accounts for roughly 20% of all mammals;

* Bats fly far and wide carrying the viruses to more areas than most mammals;

* Immunity and body temperature created by high flight.

The immune system of the bat is yet an unexplored area. Indeed, the first bat genome was published in 2013, by an international group that included BGI-Shenzhen, Novo Nordisk Foundation Center for Basic Metabolic Research, and the University of Copenhagen, Denmark.

In 2016, the research group of Michelle Baker, PhD, a bat immunologist at Commonwealth Scientific and Industrial Research Organization (CSIRO), published findings in PNAS (Proceedings of the National Academy of Sciences of the United States of America) that bats’ immune systems are always turned on and have only three interferons – a fraction of the number of interferons found in people.

At that time, Baker noted, “If we can redirect other species’ immune responses to behave in a similar manner to that of bats, then the high death rate associated with diseases, such as Ebola, could be a thing of the past.”

According to Rajagopalan’s Review Article, while COVID-19 and its spread (and deaths) makes it a severe public health hazard, “it’s possible that as we learn more, 2019-nCoV will seem more like the flu than like SARS. Already, the new virus appears to be less deadly than both SARS and MERS.”

The genome of the virus has been found to have no DNA (and thus incapable of multiplying itself outside a biological host), but only the RNA that without a biological host is inert. There is a lot of data on how MERS, SARS, and other respiratory viruses move from person to person — and that’s mainly through exposure to droplets from coughing or sneezing, and if these droplets reach the nose, eyes, or mouth of another person, they can pass on the virus.

According to Jennifer Nuzzo, an infectious disease expert and senior scholar at the Johns Hopkins Center for Health Security, in rare cases, a person might catch a respiratory disease indirectly, “via touching droplets on surfaces – and then touching mucosal membranes” in the mouth, eyes, and nose. That’s why hand-washing is an important public health measure – all the time, and especially in an outbreak.

According to the Review Article, as of 10 March 2020, the situation regarding COVID-19 is still fluid and fast changing day by day. It is very difficult to predict anything.

Writing in the context of India, Rajagopalan adds, while the Government of India and the State governments, appear to be doing a tremendous job in tackling the epidemic, there appears to be a lack of enthusiasm and initiative on the part of Indian researchers to go deep into the reservoir status, and the how and why of its epidemiology.

[* Chakravarthi Raghavan is the Editor-Emeritus of the SUNS. Excerpts from the Review Article are reproduced with permission.]

 


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