China believes a mysterious pneumonia outbreak that struck 59 people is caused by a new strain of virus from the same family as SARS, which killed hundreds of people more than a decade ago.
Lead scientist Xu Jianguo told the official Xinhua news agency that experts had “preliminarily determined” a new type of coronavirus was behind the outbreak, first confirmed on December 31 in Wuhan, a central Chinese city with a population of over 11 million.
It initially sparked fears of a resurgence of highly contagious Sudden Acute Respiratory Syndrome, and prompted authorities in Hong Kong – badly hit by SARS in 2002-2003 – to take precautions, including stepping up the disinfection of trains and airplanes, and checks of passengers.
China has since ruled out a fresh outbreak of SARS, which killed 349 people in mainland China and another 299 in Hong Kong.
“A total of 15 positive results of the new type of coronavirus had been detected” in the lab, through tests on infected blood samples and throat swabs, Xu said.
The World Health Organization (WHO) confirmed the preliminary discovery of a new coronavirus in a statement.
“Further investigations are also required to determine the source, modes of transmission, extent of infection and countermeasures implemented,” said Gauden Galea, the WHO Representative to China.
Wuhan’s health commission said on Sunday seven of the 59 patients were seriously ill, but none had died. All received treatment in quarantine.
Eight patients have recovered and were discharged from hospital on Wednesday, according to Xinhua.
The commission said the infection broke out between December 12 and 29, with some of the patients employed at a city seafood market since closed for disinfection.
No obvious evidence of human-to-human transmission has been reported so far.
Footage from January 1 by state broadcaster CCTV showed an official notice at the market saying it had been closed in light of the “current pneumonia situation in our city”, without providing a date for reopening.
The outbreak comes just a few weeks before China’s busiest annual travel period, when millions of people take buses, trains and planes for Lunar New Year.
A Chinese transport ministry official said at a briefing that arrangements were made for “disinfection, monitoring and prevention” focusing on areas with large numbers of passengers, including stations and cargo hubs.
Civil aviation and national railway authorities said they had not received any reports of affected patients taking flights or trains, and that they were closely watching the situation.
Wan Xiangdong, chief flight officer of China’s Civil Aviation Administration, said all planes were equipped with emergency medical kits.
WHO representative Galea said “people with symptoms of pneumonia and reported travel history to Wuhan have been identified at international airports”.
The organisation has not recommended any travel restrictions on China.
Hong Kong, Taiwan fears
In Hong Kong, hospitals have raised their alert level to “serious” and stepped up detection measures – including temperature checkpoints for inbound travellers.
Authorities in the financial hub say 38 people have been hospitalised in recent days after returning from Wuhan and displaying flu-like illnesses, but none were confirmed to have contracted the mystery virus.
Some 21 of the 38 patients had been discharged by Wednesday.
City residents worried about the outbreak have rushed to buy face masks from local pharmacies, with many selling out earlier this week.
Inbound trains and flights from the mainland are undergoing extra cleaning and disinfection, authorities said.
Additional thermal imaging systems have been set up at the city’s airport, while inbound high-speed rail passengers from the mainland face checks by hand-held infrared thermometers.
The coming holiday has prompted concerns in Taiwan, where top officials urged the island’s health and welfare ministry to strengthen quarantine controls at airports.
On Monday, the country’s centre for disease control also advised residents planning to travel to or near Wuhan to wear masks and avoid contact with wild animals.
The US embassy in China warned on Tuesday that Americans travelling in the country should avoid animals and contact with sick people.
Fifteen years after the first highly pathogenic human coronavirus caused the severe acute respiratory syndrome coronavirus (SARS-CoV) outbreak, another severe acute diarrhea syndrome coronavirus (SADS-CoV) devastated livestock production by causing fatal diseases in pigs. Both outbreaks began in China and were caused by coronaviruses of bat origin [1,2]. This increased the urgency to study bat coronaviruses in China to understand their potential of causing another virus outbreak.
In this review, we collected information from past epidemiology studies on bat coronaviruses in China, including the virus species identified, their host species, and their geographical distributions. We also discuss the future prospects of bat coronaviruses cross-species transmission and spread in China.
Why Study Bat Coronaviruses in China?
Coronaviruses (CoVs) belong to the subfamily Orthocoronavirinae in the family Coronaviridae and the order Nidovirales. CoVs have an enveloped, crown-like viral particle from which they were named after.
The CoV genome is a positive-sense, single-strand RNA (+ssRNA), 27–32 kb in size, which is the second largest of all RNA virus genomes. Typically, two thirds of the genomic RNA encodes for two large overlapping polyproteins, ORF1a and ORF1b, that are processed into the viral polymerase (RdRp) and other nonstructural proteins involved in RNA synthesis or host response modulation.
The other third of the genome encodes for four structural proteins (spike (S), envelope (E), membrane (M), and nucleocapsid (N)) and other accessory proteins. While the ORF1a/ORF1b and the four structural proteins are relatively consistent, the length of the CoV genome is largely dependent on the number and size of accessory proteins .
Compared with other RNA viruses, the expanded genome size of CoVs is believed to be associated with increased replication fidelity, after acquiring genes encoding RNA-processing enzymes .
Genome expansion further facilitates the acquisition of genes encoding accessory proteins that are beneficial for CoVs to adapt to a specific host . As a result, genome changes caused by recombination, gene interchange, and gene insertion or deletion are common among CoVs.
The CoV subfamily is expanding rapidly, due to the application of next generation sequencing which has increased the detection and identification of new CoV species. As a result, CoV taxonomy is constantly changing. According to the latest International Committee of Taxonomy of Viruses (ICTV) classification, there are four genera (α-, β-, δ-, and γ-) consisting of thirty-eight unique species in the subfamily .
The number of species will continue to increase, as there are still many unclassified CoVs [7,8].CoVs cause disease in a variety of domestic and wild animals as well as in humans, where α- and β-CoVs mainly infect mammals and γ- and δ-CoVs mainly infect birds (Table 1). Two highly pathogenic β-CoVs, SARS-CoV, and MERS-CoV have caused pandemics in humans since 2002 [1,9].
Originating in China and then spreading to other parts of the world, SARS-CoV infected around 8000 individuals with an overall mortality of 10% during the 2002–2003 pandemic . Since its emergence in 2012 in the Middle East, MERS-CoV spread to 27 countries, resulting in 2249 laboratory-confirmed cases of infection with an average mortality of 35.5% (until September 2018) .
Besides these two viruses, α-CoVs 229E and NL63 and β-CoVs OC43 and HKU1 can also cause respiratory diseases in humans . Moreover, CoVs cause pandemic disease in domestic and wild animals (Table 1). SADS-CoV was recently identified as the etiological agent responsible for a large-scale outbreak of fatal disease in pigs in China that caused the death of more than 20,000 piglets . Porcine epidemic diarrhea virus (PEDV) and transmissible gastroenteritis virus (TGEV) that belong to α-CoV and porcine δ-CoV (PDCoV) are also important emerging and re-emerging viruses in pigs that pose significant economic threat to the swine industry . In addition, avian infectious bronchitis virus (IBV, γ-CoV) causes a highly contagious disease that affects poultry production worldwide . Coronaviruses have also been associated with catarrhal gastroenteritis in mink (MCoV) and whale deaths (BWCoV-SW1) [13,14].
Table 1. International Committee of Taxonomy of Viruses (ICTV) classification of coronaviruses species, reservoir hosts, and presence reported in China.
|Coronavirus Species||Abbreviations||Human||Bats||Other Animals||Reported in China|
|Bat coronavirus HKU10||BtCoV-HKU10||Yes||Yes [7,8,26,27]||α-CoV|
|Bat coronavirus CDPHE15||BtCoV-CDPHE15||Yes||No|
|Rhinolophus ferrumequinum alphacoronavirus HuB-2013||BtRfCoV-HuB13||Yes||Yes |
|* Human coronavirus 229E||HCoV-229E||Yes||Yes [28,29]|
|Lucheng Rn rat coronavirus||LRNV||Yes (rat)||Yes |
|Ferret coronavirus||FRCoV||Yes (ferret)||No |
|* Mink coronavirus 1||MCoV||Yes (mink)||No |
|Miniopterus bat coronavirus 1||BtMiCoV-1||Yes||Yes [7,8,32,33,34,35,36,37]|
|Miniopterus bat coronavirus HKU8||BtMiCoV-HKU8||Yes||Yes [7,8,33,34,35,37,38,39,40,41]|
|Myotis ricketti alphacoronavirus Sax-2011||BtMy-Sax11||Yes||Yes [8,37]|
|Nyctalus velutinus alphacoronavirus SC-2013||BtNy-Sc13||Yes||Yes |
|* Porcine epidemic diarrhea virus||PEDV||Yes (pig)||Yes |
|Scotophilus bat coronavirus 512||BtScCoV-512||Yes||Yes |
|* Rhinolophus bat coronavirus HKU2 (SADS)||BtRhCoV-HKU2||Yes||Yes||Yes [2,7,8,38,43,44,45]|
|* Human coronavirus NL63||HCoV-NL63||Yes||Yes [28,29]|
|NL63-related bat coronavirus strain BtKYNL63-9b||BtKYNL63||Yes||No |
|* Alphacoronavirus 1 (Transmissible gastroenteritis virus)||TGEV||Yes (pig)||Yes |
|China Rattus coronavirus HKU24||RtCoV-HKU24||Yes (rat)||Yes ||β-CoV|
|* Human coronavirus HKU1||HCoV-HKU1||Yes||Yes [28,29]|
|* Murine coronavirus (Murine hepatitis coronavirus)||MHV||Yes (mouse)||No |
|Bat Hp-betacoronavirus Zhejiang2013||BtHpCoV-ZJ13||Yes||Yes |
|Hedgehog coronavirus 1||EriCoV-1||Yes (hedgehog)||No |
|* Middle East respiratory syndrome-related coronavirus||MERSr-CoV||Yes||Yes||Yes [49,50]|
|Pipistrellus bat coronavirus HKU5||BtPiCoV-HKU5||Yes||Yes [38,39,49,51,52]|
|Tylonycteris bat coronavirus HKU4||BtTyCoV-HKU4||Yes||Yes [36,38,39,49,50,51]|
|Rousettus bat coronavirus GCCDC1||# BtEoCoV-GCCDC1||Yes||Yes [53,54,55]|
|Rousettus bat coronavirus HKU9||BtRoCoV-HKU9||Yes||Yes [39,55,56,57]|
|* Severe acute respiratory syndrome-related coronavirus||SARSr-CoV||Yes||Yes||Yes [7,8,20,21,22,27,37,40,45,58,59,60,61,62,63,64]|
|* Betacoronavirus 1 (Human coronavirus OC43)||HCoV-OC43||Yes||Yes [28,29]|
|Wigeon coronavirus HKU20||WiCoV-HKU20||Yes (bird)||Yes ||δ-CoV|
|Bulbul coronavirus HKU11||BuCoV-HKU11||Yes (bird)||Yes |
|Coronavirus HKU15||PoCoV-HKU15||Yes (pig)||Yes |
|Munia coronavirus HKU13||MuCoV-HKU13||Yes (bird)||Yes |
|White-eye coronavirus HKU16||WECoV-HKU13||Yes (bird)||Yes |
|Night heron coronavirus HKU19||NHCoV-HKU19||Yes (bird)||Yes |
|Common moorhen coronavirus HKU21||CMCoV-HKU21||Yes (bird)||Yes |
|*? Beluga whale coronavirus SW1||BWCoV-SW1||Yes (whale)||No ||γ-CoV|
|* Avian infectious bronchitis virus||IBV||Yes (bird)||Yes |
* The disease-causing CoVs are indicated and the three zoonotic CoVs are in bold. *? BWCoV-SW1 was found in a sick whale, but whether it was the etiological agent of the infection was not proven. # Carrier of this virus was confirmed as Eonycteris spelaea, but not Rousettus bats. The virus was renamed accordingly.
Linking Bats to Coronaviruses
Bat are the only mammals with the capability of powered flight, which enables them to have a longer range of migration compared to land mammals.
Bats are also the second largest order of mammals, accounting for about a fifth of all mammalian species, and are distributed worldwide. Phylogenetic analysis classified bats into two large suborders – the Yinpterochiroptera, consisting of one Pteropodidae (megabat) and five Rhinolophoidea (microbat) families, and the Yangochiroptera comprising a total of thirteen microbat families .
It is hypothesized that flight provided the selection pressure for coexistence with viruses, while the migratory ability of bats has particular relevance in the context of disease transmission .
Indeed, bats were linked to a few highly pathogenic human diseases, supporting this hypothesis. Some of these well characterized bat viruses, including bat lyssaviruses (Rabies virus), henipaviruses (Nipah virus and Hendra virus), CoVs (SARS-CoV, MERS-CoV, and SADS-CoV), and filoviruses (Marburg virus, Ebola virus, and Mengla virus), pose a great threat to human health [16,17].
A comprehensive analysis of mammalian host–virus relationships demonstrated that bats harbor a significantly higher proportion of zoonotic viruses than other mammalian orders . Viruses from most of the viral families can be found in bats .Bats are now recognized as important reservoir hosts of CoVs (Table 1).
Although civet cats were initially identified as the animal origin of SARS-CoV, bats were soon found to be the most likely natural reservoir hosts of this virus [19,20,21]. Long-term surveillance revealed an average 10% SARS-related CoV nucleotide positivity in bats, including some viruses that can use same human entry receptor ACE2 as SARS-CoV [7,22].
Similarly, bats have been proposed to harbor the progenitor viruses of MERS-CoV, although dromedary camels can transmit this virus to humans directly .
The most recent SADS-CoV spillover was traced back to bats . In addition, bats also carry α-CoVs that are related to pathogenic human 229E- and NL63-CoVs, as well as pandemic swine coronavirus PEDV [23,24]
In summary, bats carry major α- (10 out of 17) and β- (7 out of 12) CoV species that may spillover to humans and cause disease (Table 1). Attributed to the wide distribution of bats, CoVs can be found worldwide, including China .
Two bat CoVs caused outbreaks in China; it is thus urgent to study the reasons to avoid future outbreaks. China is the third largest territory and is also the most populous nation in the world.
A vast homeland plus diverse climates bring about great biodiversity including that of bats and bat-borne viruses—most of the ICTV coronavirus species (22/38) were named by Chinese scientists studying local bats or other mammals. The majority of the CoVs can be found in China (Table 1).
Moreover, most of the bat hosts of these CoVs live near humans, potentially transmitting viruses to humans and livestock. Chinese food culture maintains that live slaughtered animals are more nutritious, and this belief may enhance viral transmission.It is generally believed that bat-borne CoVs will re-emerge to cause the next disease outbreak. In this regard, China is a likely hotspot. The challenge is to predict when and where, so that we can try our best to prevent such outbreaks.