COVID-19 case tally: 1.72 million cases, 106,469 deaths and U.S. has highest number of fatalities MarketWatch
On any digital dashboard tracking the spread of Covid-19, on any graphic comparing country-by-country case curves or death tolls, they were the champs. Singapore, Hong Kong, Taiwan, South Korealeaders there saw what was headed their way from China in the early days of the new coronavirus, before it became a pandemic. They remembered what happened two decades ago with SARS: People died, economies suffered. So they locked down their immigration hardest and soonest, deployed public health workers to follow up contacts of cases, got their hospitals shored up, and started publishing clear and consistent information and data. They flattened their curves before the rest of the world understood there would be curves to flatten. But in recent weeks, those curves have taken another chilling turn. The numbers of new cases in these places are creeping upward.
Hong Kongs slow and steady case count started going up on March 18, and took an 84-case jump on March 28. After months of new cases barely brushing double digits, Singapores count jumped by 47 on March 16, and since then the city-state has had three days with more than 70 new cases each. Taiwans new-cases-in-a-day peaked at 5 in late January and then jumped into the high 20s per day in, again, mid-March. South Korea had 86 new cases on April 3.
Plus: What it means to flatten the curve, and everything else you need to know about the coronavirus.
These new case numbers are still low, especially compared with the United States, which had 983 new cases on March 16 and 29,874 new cases on April 2 or Italy, which (hopefully) peaked on March 21 with 6,557 new cases. Whats alarming about the numbers of new cases in the would-be success-story locations is that theyre happening at allthat the numbers were going down, and now theyre creeping up. From the outside, that looks like a worst-case scenario: the return of the disease after a country eases off the measures to combat it. But that appearance is deceiving. The bad new numbers come from somewhere elseliterally. And that might have lessons for the next phase of the pandemic in the US.
The real problem is that viruses dont know what a border is. These countries are experiencing reimportation of the disease, infections that are the result of inbound travelers from places that arent winning their fight against Covid-19.
All these countries are, after all, on the same planet. In Singapore, Hong Kong, South Korea, and Taiwan, a few earlier cases from China made it through the barrier and got into the community. That resulted, throughout February, in community infections, or unlinked local cases. Those were worrying, but the overall spread was still slowuntil the pandemic went transnational, and boomeranged back around. There were just a small number, and then they kind of disappeared, says Ben Cowling, an epidemiologist at the University of Hong Kong. But at the end of February and early March we started to get more imported cases from Europe. Hong Kong got a lot from Europe, the US, and other parts of the world, and Taiwan got a lot from the US.
Those all led to a bunch of new unlinked local cases, and the numbers started going up again. In Taiwan, for example, they prolonged the winter break for kids by 10 days so they could prepare kids to go back to school with masks. A lot of people went to Europe for vacation, and they came back with it, says Jason Wang, director of the Center for Policy Outcomes and Prevention at Stanford University School of Medicine and an author of a paper on Taiwans early successes. We did stop all the flights from China before the WHO said we should. But then after we did that, we didnt do too much. So it was brewing in the community, and now we have community spread. And then people started to come back from Europe, and we didnt even think about that.
Until then, Singapore, Hong Kong, and Taiwan had all been able to maintain diligent containment within their own borders, following every infectionor nearly every infection, as it turned outback through its chain of contacts and isolating all those people from the general population. Taiwan had linked its immigration database to its national health system. Singapore had instituted harsh fines for anyone breaking social distancing and published detailed data on every case and cluster. The problem is, you dont pick up every single person, especially when the people with mild symptoms know if they get tested theyre going to be isolated, and their friends and family are going to be isolated, says Cowling. Theres a disincentive. Thats especially bad with Covid-19, which seems to spread in part because of a few days of pre-symptomatic infectiousness before the onset of heavy illness.
Other nations couldnt hold containment, or didnt try. In Europe and the United States, governments dithered about whether and when to institute draconian but necessary measures like social distancing, school closures, and shelter-in-place orders. Now those same governments and public health researchers have to figure out how long to maintain them. Theyre destructive to peoples psyches and the economy, but letting people swirl back into close contact with one another allows the disease to spread again.
In epidemiological terms, this tension is about taking control of whats called the reproductive number, the number of people a contagious person goes on to infect. At the top of the curve in Wuhan, where Covid-19 started to spread, that number was something like 2 or 2.5as it might now be in parts of the US and Europe. After the Chinese government quarantined Wuhan and forced everyone to stay home, it went down to perhaps as low as 0.3. In China, those rules went into effect in January; the government may lift them this week.
The viruss apparent return will spur different kinds of containment measures in different places. Hong Kongs were already strict, though theyd relaxed somewhat in the first weeks of March. Now, Singapore, Hong Kong, South Korea, and Taiwan have all instituted even stricter social distancing rules and immigration controls. Nationals who are allowed in can expect 14-day quarantines, in Hong Kong and Singapore monitored by smartphone app, though those apps efficacy may be doubtful. (Singapores numbers do seem to look better since officials started quarantining everyone coming in, rather than people from specific countries.) Singapore is also closing all schools and most workplaces.
One of Britain's top scientists is "80 percent" confident that a vaccine for COVID-19, which has killed over 108,000 people globally, could be ready by September.
Oxford Universityvaccinology professor Sarah Gilbert told the Times of London Saturday thatif everything goes perfectly" her team's vaccine could be ready by the fall, The Washington Post reported.
I know quite a lot about the Oxford project, and it is really great to see some hope, especially on the front page of the newspapers,Matt Hancock, the U.K.'s health secretary,told the Post.
There are dozens of teamsin various countries globallytrying to come up with a working vaccine for the pandemic that hasplagued the world the past several months.
Anthony FauciAnthony FauciWaPo: Trump allegedly asked Fauci if officials could let coronavirus 'wash over' US Top UK scientist: '80 percent' confident a COVID-19 vaccine could be ready by September Sunday shows preview: Lawmakers, health officials address fallout from coronavirus pandemic MORE, member of the White House coronavirus task force and director of the National Institute of Allergy and Infectious Diseases, and other top U.S. health experts have previously stated thatit could take researchers 18 months to create aworking vaccine.
Gilbert told the London newspaper that human trials of the vaccine are starting in the next two weeks.
I think theres a high chance that it will work, based on other things that we have done with this type of vaccine, Gilbert said. Its not just a hunch, and as every week goes by, we have more data to look at."
The newspaper noted however, that even if an effective vaccine is created by September, it will be difficult to produce it en masse.
Graphics by Donald Pearsall
A vaccine for COVID-19 has entered Phase 1 of clinical trials in Seattle. How was it made? And how likely is it that this vaccine, or any others, will work against the new coronavirus? Science journalist and video producer Anna Rothschild spoke with Dr. John Mascola, the director of the Vaccine Research Center at the National Institutes of Health, which co-created the vaccine being tested, along with Moderna Inc.
When will we have a Covid-19 vaccine? Public-facing scientists such as the UKs chief scientific adviser, Sir Patrick Vallance, and his US counterpart, Anthony Fauci, keep repeating that it wont be before 12 to 18 months. But other voices including some of those in the race to create a vaccine themselves have suggested that it could be as early as June. Who is right?
The former, probably, but its complicated because this pandemic is forcing change at almost every step in the process by which a new vaccine arrives at a needle near us.
It really depends on what you mean by having a vaccine, says Marian Wentworth, president and CEO of Management Sciences for Health, a Massachusetts-based global not-for-profit organisation that seeks to build resilient health systems, and a long-time observer of vaccine development. If you mean one that can be used in a mass vaccination campaign, allowing us all to get on with our lives, then 12 to 18 months is probably right.
But in terms of an experimental vaccine that is deemed safe and effective enough to be rolled out in a more limited way to high-risk groups such as health workers, say that could be ready within weeks or months, under emergency rules developed by drug regulatory agencies and the World Health Organization in the context of the recent Ebola epidemics in Africa.
When the University of Oxfords Adrian Hill told the Guardian that his groups Covid-19 vaccine candidate could be ready by the summer, it was this kind of readiness to which he was probably referring. The group, led by Sarah Gilbert, has since stated that a vaccine shown to be effective in phase-3 clinical trials that could be manufactured in large quantities wont be ready before the autumn even in a best-case scenario. And that scenario is highly ambitious and subject to change.
Normally, a vaccine is developed in the lab before being tested on animals. If it proves safe and generates a promising immune response in this pre-clinical phase, it enters human or clinical trials. These are divided into three phases, each of which takes longer and involves more people than the previous one. Phase 1 establishes the vaccines safety in a small group of healthy individuals, with the goal of ruling out debilitating side effects. Phases 2 and 3 test efficacy, and in an outbreak like the present one they are conducted in places where the disease is prevalent. In parallel with these later phases, production capacity for the candidate vaccine is gradually built up, so that factories are capable of producing it on a large scale if and when regulatory agencies judge that it should be licensed.
In an article published in The New England Journal of Medicine on 30 March, representatives of the Oslo-based not-for-profit Coalition for Epidemic Preparedness Innovations (Cepi), which is helping to finance and coordinate Covid-19 vaccine development, laid out an accelerated version of this process that they believe is more suited to a pandemic. This pandemic paradigm implements certain steps in parallel, such as animal and phase-1 clinical testing. It also involves scaling up production capacity before sufficient safety and efficacy data are available a financially risky step, given that that may never materialise, and one that requires governments and not-for-profit organisations such as Cepi to share that extra financial risk with pharmaceutical companies if they want them to engage. Mass production is critical in a pandemic, when hundreds of millions if not billions of doses are needed and many countries are now scrambling to build new vaccine production facilities.
People now appreciate that the lengthy process of conventional licensing of vaccines is not going to be helpful in the context of an epidemic, says Beate Kampmann, who heads the vaccine centre at the London School of Hygiene and Tropical Medicine.
Bringing a new vaccine to the clinic has taken 10 to 20 years in the past
Prudently, Cepi did not attach a timeline to its accelerated paradigm, but the 12- to 18-month estimate already takes it into account. Bringing a new vaccine to the clinic has taken 10 to 20 years in the past. Nevertheless, the accelerated paradigm is being implemented now. A Boston-based biotech firm, Moderna, saw its experimental Covid-19 vaccine enter human trials on 16 March, just 10 weeks after the first genetic sequences of Sars-CoV-2 the virus that causes the disease were released. Others will follow soon.
Were getting to candidates much more quickly, says Kampmann, who puts this progress down to advances made in the fight against Ebola. The step-up in technology that we have seen in the last five years has really made a difference.
There are many hurdles ahead, though. Most of the 50-odd Covid-19 vaccine candidates being developed and tested will not make it to the licensing stage, and those that have been fastest out of the blocks may still encounter problems later on. Modernas innovative technology allowed it to generate a candidate quickly, but no vaccine using this platform has been licensed to date.
At the Pasteur Institute in Paris, on the other hand, a Covid-19 vaccine candidate is still in pre-clinical development, but because it piggybacks on established technology a licensed measles vaccine the testing and licensing processes will go faster. And this kind of vaccine can already be produced in large quantities.
While there can be no shortcuts to establishing safety and efficacy, proposals have been put forward for how these experimental vaccines might be tested more rapidly without sacrificing scientific rigour. In February, for example, the WHO published a draft protocol for phase 2 and 3 trials that would test a number of candidates simultaneously, in multi-country trials according to standardised criteria.
Another proposal is to conduct controlled human challenge trials, in which healthy volunteers are given a candidate vaccine and then infected with Sars-CoV-2. These are ethically questionable, especially before scientists understand why young and otherwise healthy people are ending up on ventilators. A similar approach, being implemented by the London-based clinical research group Hvivo, invites volunteers to be infected with a milder coronavirus but how applicable its findings will be to Sars-CoV-2 is not clear.
If our own body cant prevent us from getting it again, that would be one pretty damning signal
There are still many unknowns with respect to Covid-19, including for how long any vaccine will provide protection. A strong indication of this will be whether people who have recovered from the disease can catch it again. There have been anecdotal reports of re-infection, but the phenomenon is not well understood. If our own body cant prevent us from getting it again, that would be one pretty damning signal, says Wentworth.
Once a vaccine is licensed, there will still be political obstacles to getting it to where its needed, because each country or public health jurisdiction has to make its own decision to roll it out. There will also be issues of prioritisation who should get it first, if supplies are limited which authorities are discussing now.
A vaccine that is approved a year from now may arrive after the end of the current pandemic, but if so it wont be wasted first because Covid-19 may recur seasonally, and second because the vaccine could itself be repurposed in the event of an outbreak of a different coronavirus. That will be no consolation to victims of this pandemic, or their relatives, but it does mean that humanity will be better protected in future. As Wentworth says: That learning, we wont unlearn.
Shares in Novavax jumped 15% on Wednesday, after the biotech firm announced it has identified a coronavirus
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How long will a coronavirus vaccine take? A Q&A with Jerome Kim, head of the International Vaccine Institute South China Morning Post
A 29-year-old haredi (ultra-Orthodox) coronavirus patient who is being treated at Samson Assuta Ashdod University Hospital has improved from serious to serious but stable condition, after receiving multiple doses of plasma over the weekend from a donor who recovered from coronavirus, a spokesperson for the hospital told The Jerusalem Post.On Friday, with the assistance of Health Minister Yaacov Litzman and his assistant, a suitable donor, a resident of Jerusalem, was found, explained MDA director-general Eli Bin. MDA brought her in an ambulance to its blood service center before Shabbat. A special team was waiting for her and transferred the plasma units to the laboratories to perform all required tests and prepare them for transfusion.Then, with the approval of the Health Ministry, the blood units were delivered to Assuta and given to the patient.The man is among the countrys youngest severe patients. He has several underlying medical conditions, and has been hospitalized at Assuta for around a week-and-a-half.The first patient who recovered from coronavirus donated plasma on April 1, according to MDA deputy director-general of blood services Prof. Eilat Shinar. Since then, some six other patients have made donations and, in the last two days, plasma units were provided to three different hospitals. A 60-year-old being treated at Yitzhak Shamir Medical Center in Beer Yaacov also recently received plasma and his situation has likewise slightly improved. A spokesperson for MDA did not have information on the third recipient.Shinar explained that the plasma is being used to create a passive vaccine, based on the assumption that those who have recovered from COVID-19 have developed special antivirus proteins or antibodies in their plasma, which could therefore help sick patients cope with the disease.Passive immunization is when you are given those preformed antibodies. An active vaccine, in contrast, is when you are injected with a dead or weakened version of a virus that tricks your immune system into thinking that youve had the disease, and your immune system creates antibodies to protect you.Currently, MDA is in the first phase of creating this vaccine, whereby the plasma is frozen and then delivered to hospitals across the country for patients to be treated by transfusion, Shinar said. In the second phase, the goal is to collect enough plasma to prepare antibody (immunoglobulin) concentrate with which patients will be treated later.MDA has been collecting plasma for more than 30 years; thousands of volunteers donate every day. Plasma with antibodies was used to treat patients with SARS during the outbreak in 2002. In addition, Israel offered a similar treatment to patients with West Nile fever.Before being able to donate plasma, a patient must wait 14 days from the time he or she was confirmed negative for coronavirus via two separate swab tests.Last month, Shinar said, the FDA approved a similar protocol in the US.
Pfizer Inc. (New York, NY, USA) and Biopharmaceutical New Technologies {(BioNTech) Mainz, Germany} have entered into a collaboration to advance candidates from BioNTechs mRNA vaccine program, previously announced in March. The collaboration aims to rapidly advance multiple COVID-19 vaccine candidates into human clinical testing based on BioNTechs proprietary mRNA vaccine platforms, with the objective of ensuring rapid worldwide access to the vaccine, if approved. The collaboration will leverage Pfizers broad expertise in vaccine research and development, regulatory capabilities, and global manufacturing and distribution network.
The two companies plan to jointly conduct clinical trials for the COVID-19 vaccine candidates initially in the United States and Europe across multiple sites. BioNTech and Pfizer intend to initiate the first clinical trials as early as the end of April 2020, assuming regulatory clearance. During the clinical development stage, BioNTech and its partners will provide clinical supply of the vaccine from its GMP-certified mRNA manufacturing facilities in Europe. BioNTech and Pfizer will work together to scale-up manufacturing capacity at risk to provide worldwide supply in response to the pandemic. BioNTech and Pfizer will also work jointly to commercialize the vaccine worldwide (excluding China, which is already covered by BioNTechs collaboration with Fosun Pharma) upon regulatory approval.
Combating the COVID-19 pandemic will require unprecedented collaboration across the innovation ecosystem, with companies coming together to unite capabilities like never before, said Mikael Dolsten, Chief Scientific Officer and President, Worldwide Research, Development & Medical, Pfizer. I am proud of Pfizers collaboration with BioNTech and have every confidence in our ability to harness the power of science together to bring forth a potential vaccine that the world needs as quickly as possible.
We have already started working with Pfizer on our COVID-19 vaccine and are pleased to announce these further details of our ongoing collaboration, which reflects both companies strong commitment to move quickly to bring a safe and efficacious vaccine to patients worldwide, said Co-Founder and CEO of BioNTech, Ugur Sahin, M.D.
Related Links:Pfizer Inc. Biopharmaceutical New Technologies (BioNTech)
Subfamily of viruses in the family Coronaviridae
Coronaviruses are a group of related viruses that cause diseases in mammals and birds. In humans, coronaviruses cause respiratory tract infections that can range from mild to lethal. Mild illnesses include some cases of the common cold (which has other possible causes, predominantly rhinoviruses), while more lethal varieties can cause SARS, MERS, and COVID-19. Symptoms in other species vary: in chickens, they cause an upper respiratory tract disease, while in cows and pigs they cause diarrhea. There are yet to be vaccines or antiviral drugs to prevent or treat human coronavirus infections.
Coronaviruses constitute the subfamily Orthocoronavirinae, in the family Coronaviridae, order Nidovirales, and realm Riboviria.[5][6] They are enveloped viruses with a positive-sense single-stranded RNA genome and a nucleocapsid of helical symmetry. The genome size of coronaviruses ranges from approximately 26 to 32 kilobases, one of the largest among RNA viruses.[7] They have characteristic club-shaped spikes that project from their surface, which in electron micrographs create an image reminiscent of the solar corona from which their name derives.[8]
Coronaviruses were first discovered in the 1930s when an acute respiratory infection of domesticated chickens was shown to be caused by infectious bronchitis virus (IBV). In the 1940s, two more animal coronaviruses, mouse hepatitis virus (MHV) and transmissible gastroenteritis virus (TGEV), were isolated.[9]
Human coronaviruses were discovered in the 1960s.[10] The earliest ones studied were from human patients with the common cold, which were later named human coronavirus 229E and human coronavirus OC43.[11] Other human coronaviruses have since been identified, including SARS-CoV in 2003, HCoV NL63 in 2004, HKU1 in 2005, MERS-CoV in 2012, and SARS-CoV-2 in 2019. Most of these have involved serious respiratory tract infections.
The name "coronavirus" is derived from Latin corona, meaning "crown" or "wreath", itself a borrowing from Greek korn, "garland, wreath". The name refers to the characteristic appearance of virions (the infective form of the virus) by electron microscopy, which have a fringe of large, bulbous surface projections creating an image reminiscent of a crown or of a solar corona. This morphology is created by the viral spike peplomers, which are proteins on the surface of the virus.[8][12]
Coronaviruses are large pleomorphic spherical particles with bulbous surface projections.[13] The average diameter of the virus particles is around 120nm (.12 m). The diameter of the envelope is ~80 nm (.08 m) and the spikes are ~20 nm (.02 m) long. The envelope of the virus in electron micrographs appears as a distinct pair of electron dense shells.[14][15]
The viral envelope consists of a lipid bilayer where the membrane (M), envelope (E) and spike (S) structural proteins are anchored.[16] A subset of coronaviruses (specifically the members of betacoronavirus subgroup A) also have a shorter spike-like surface protein called hemagglutinin esterase (HE).[5]
Inside the envelope, there is the nucleocapsid, which is formed from multiple copies of the nucleocapsid (N) protein, which are bound to the positive-sense single-stranded RNA genome in a continuous beads-on-a-string type conformation.[15][17] The lipid bilayer envelope, membrane proteins, and nucleocapsid protect the virus when it is outside the host cell.[18]
Coronaviruses contain a positive-sense, single-stranded RNA genome. The genome size for coronaviruses ranges from 26.4 to 31.7 kilobases.[7] The genome size is one of the largest among RNA viruses. The genome has a 5 methylated cap and a 3 polyadenylated tail.[15]
The genome organization for a coronavirus is 5-leader-UTR-replicase/transcriptase-spike (S)-envelope (E)-membrane (M)-nucleocapsid (N)-3UTR-poly (A) tail. The open reading frames 1a and 1b, which occupy the first two-thirds of the genome, encode the replicase/transcriptase polyprotein. The replicase/transcriptase polyprotein self cleaves to form nonstructural proteins.[15]
The later reading frames encode the four major structural proteins: spike, envelope, membrane, and nucleocapsid.[19] Interspersed between these reading frames are the reading frames for the accessory proteins. The number of accessory proteins and their function is unique depending on the specific coronavirus.[15]
Infection begins when the viral spike (S) glycoprotein attaches to its complementary host cell receptor. After attachment, a protease of the host cell cleaves and activates the receptor-attached spike protein. Depending on the host cell protease available, cleavage and activation allows the virus to enter the host cell by endocytosis or direct fusion of the viral envelop with the host membrane.[20]
On entry into the host cell, the virus particle is uncoated, and its genome enters the cell cytoplasm.[15] The coronavirus RNA genome has a 5 methylated cap and a 3 polyadenylated tail, which allows the RNA to attach to the host cell's ribosome for translation.[15] The host ribosome translates the initial overlapping open reading frame of the virus genome and forms a long polyprotein. The polyprotein has its own proteases which cleave the polyprotein into multiple nonstructural proteins.[15]
A number of the nonstructural proteins coalesce to form a multi-protein replicase-transcriptase complex (RTC). The main replicase-transcriptase protein is the RNA-dependent RNA polymerase (RdRp). It is directly involved in the replication and transcription of RNA from an RNA strand. The other nonstructural proteins in the complex assist in the replication and transcription process. The exoribonuclease nonstructural protein, for instance, provides extra fidelity to replication by providing a proofreading function which the RNA-dependent RNA polymerase lacks.[21]
One of the main functions of the complex is to replicate the viral genome. RdRp directly mediates the synthesis of negative-sense genomic RNA from the positive-sense genomic RNA. This is followed by the replication of positive-sense genomic RNA from the negative-sense genomic RNA.[15] The other important function of the complex is to transcribe the viral genome. RdRp directly mediates the synthesis of negative-sense subgenomic RNA molecules from the positive-sense genomic RNA. This is followed by the transcription of these negative-sense subgenomic RNA molecules to their corresponding positive-sense mRNAs.[15]
The replicated positive-sense genomic RNA becomes the genome of the progeny viruses. The mRNAs are gene transcripts of the last third of the virus genome after the initial overlapping reading frame. These mRNAs are translated by the host's ribosomes into the structural proteins and a number of accessory proteins.[15] RNA translation occurs inside the endoplasmic reticulum. The viral structural proteins S, E, and M move along the secretory pathway into the Golgi intermediate compartment. There, the M proteins direct most protein-protein interactions required for assembly of viruses following its binding to the nucleocapsid.[22] Progeny viruses are then released from the host cell by exocytosis through secretory vesicles.[22]
The interaction of the coronavirus spike protein with its complement host cell receptor is central in determining the tissue tropism, infectivity, and species range of the virus.[23][24] The SARS coronavirus, for example, infects human cells by attaching to the angiotensin-converting enzyme 2 (ACE2) receptor.[25]
The scientific name for coronavirus is Orthocoronavirinae or Coronavirinae.[2][3][4] Coronaviruses belong to the family of Coronaviridae, order Nidovirales, and realm Riboviria.[5][6] They are divided into alphacoronaviruses and betacoronaviruses which infect mammals, and gammacoronaviruses and deltacoronaviruses which primarily infect birds.[26]
The most recent common ancestor (MRCA) of all coronaviruses is estimated to have existed as recently as 8000 BCE, although some models place the common ancestor as far back as 55 million years or more, implying long term coevolution with bat and avian species.[27] The MRCAs of the alphacoronavirus line has been placed at about 2400 BCE, the betacoronavirus line at 3300 BCE, the gammacoronavirus line at 2800 BCE, and the deltacoronavirus line at about 3000 BCE. Bats and birds, as warm-blooded flying vertebrates, are ideal hosts for the coronavirus gene pool (bats the reservoir for alphacoronavirus and betacoronavirus and birds the natural reservoir for gammacoronavirus and deltacoronavirus). The large number of host bat and avian species, and their global range, has enabled extensive coronavirus evolution and dissemination.[28]
Many human coronavirus have their origin in bats.[29] MERS-CoV, although related to several bat coronavirus species, appears to have diverged from these several centuries ago.[30] The human coronavirus NL63 and a bat coronavirus shared an MRCA 563822 years ago.[31] The most closely related bat coronavirus and SARS-CoV diverged in 1986.[32] A path of evolution of the SARS virus and keen relationship with bats have been proposed. The authors suggest that the coronaviruses have been coevolved with bats for a long time and the ancestors of SARS-CoV first infected the species of the genus Hipposideridae, subsequently spread to species of the Rhinolophidae and then to civets, and finally to humans.[33][34]
Bovine coronavirus is thought to have originated in rodents, unlike most other betacoronaviruses which originated in bats.[29] In the 1790s, equine coronavirus diverged from the bovine coronavirus after a cross-species jump.[35] Later in the 1890s, human coronavirus OC43 evolved from bovine coronavirus after another cross-species spillover event.[36][35] It is speculated that the flu pandemic of 1890 may have been caused by this spillover event, and not by the influenza virus, because of the timing, neurological symptoms, and unknown causative agent of the pandemic.[37] In the 1950s, the human coronavirus OC43 began to split into its present genotypes.[38]
Alpaca coronavirus and human coronavirus 229E diverged before 1960.[39]
Coronaviruses vary significantly in risk factor. Some can kill more than 30% of those infected (such as MERS-CoV), and some are relatively harmless, such as the common cold.[15] Coronaviruses cause colds with major symptoms, such as fever, and a sore throat from swollen adenoids, occurring primarily in the winter and early spring seasons.[40] Coronaviruses can cause pneumonia (either direct viral pneumonia or secondary bacterial pneumonia) and bronchitis (either direct viral bronchitis or secondary bacterial bronchitis).[41] The human coronavirus discovered in 2003, SARS-CoV, which causes severe acute respiratory syndrome (SARS), has a unique pathogenesis because it causes both upper and lower respiratory tract infections.[41]
Six species of human coronaviruses are known, with one species subdivided into two different strains, making seven strains of human coronaviruses altogether. Four of these strains produce the generally mild symptoms of the common cold:
Three strains (two species) produce symptoms that are potentially severe; all three of these are -CoV strains:
The coronaviruses HCoV-229E, -NL63, -OC43, and -HKU1 continually circulate in the human population and cause respiratory infections in adults and children worldwide.[43]
In 2003, following the outbreak of severe acute respiratory syndrome (SARS) which had begun the prior year in Asia, and secondary cases elsewhere in the world, the World Health Organization (WHO) issued a press release stating that a novel coronavirus identified by a number of laboratories was the causative agent for SARS. The virus was officially named the SARS coronavirus (SARS-CoV). More than 8,000 people were infected, about ten percent of whom died.[25]
In September 2012, a new type of coronavirus was identified, initially called Novel Coronavirus 2012, and now officially named Middle East respiratory syndrome coronavirus (MERS-CoV).[53][54] The World Health Organization issued a global alert soon after.[55] The WHO update on 28 September 2012 said the virus did not seem to pass easily from person to person.[56] However, on 12 May 2013, a case of human-to-human transmission in France was confirmed by the French Ministry of Social Affairs and Health.[57] In addition, cases of human-to-human transmission were reported by the Ministry of Health in Tunisia. Two confirmed cases involved people who seemed to have caught the disease from their late father, who became ill after a visit to Qatar and Saudi Arabia. Despite this, it appears the virus had trouble spreading from human to human, as most individuals who are infected do not transmit the virus.[58] By 30 October 2013, there were 124 cases and 52 deaths in Saudi Arabia.[59]
After the Dutch Erasmus Medical Centre sequenced the virus, the virus was given a new name, Human CoronavirusErasmus Medical Centre (HCoV-EMC). The final name for the virus is Middle East respiratory syndrome coronavirus (MERS-CoV). The only U.S. cases (both survived) were recorded in May 2014.[60]
In May 2015, an outbreak of MERS-CoV occurred in the Republic of Korea, when a man who had traveled to the Middle East, visited four hospitals in the Seoul area to treat his illness. This caused one of the largest outbreaks of MERS-CoV outside the Middle East.[61] As of December 2019, 2,468 cases of MERS-CoV infection had been confirmed by laboratory tests, 851 of which were fatal, a mortality rate of approximately 34.5%.[62]
In December 2019, a pneumonia outbreak was reported in Wuhan, China.[63] On 31 December 2019, the outbreak was traced to a novel strain of coronavirus,[64] which was given the interim name 2019-nCoV by the World Health Organization (WHO),[65][66][67] later renamed SARS-CoV-2 by the International Committee on Taxonomy of Viruses. Some researchers have suggested the Huanan Seafood Wholesale Market may not be the original source of viral transmission to humans.[68][69]
As of 12 April 2020, there have been at least 108,862[49] confirmed deaths and more than 1,777,515[49] confirmed cases in the coronavirus pneumonia pandemic. The Wuhan strain has been identified as a new strain of Betacoronavirus from group 2B with approximately 70% genetic similarity to the SARS-CoV.[70] The virus has a 96% similarity to a bat coronavirus, so it is widely suspected to originate from bats as well.[68][71] The pandemic has resulted in travel restrictions and nationwide lockdowns in several countries.
Coronaviruses have been recognized as causing pathological conditions in veterinary medicine since the 1930s.[9] Except for avian infectious bronchitis, the major related diseases have mainly an intestinal location.[72]
Coronaviruses primarily infect the upper respiratory and gastrointestinal tract of mammals and birds. They also cause a range of diseases in farm animals and domesticated pets, some of which can be serious and are a threat to the farming industry. In chickens, the infectious bronchitis virus (IBV), a coronavirus, targets not only the respiratory tract but also the urogenital tract. The virus can spread to different organs throughout the chicken.[73] Economically significant coronaviruses of farm animals include porcine coronavirus (transmissible gastroenteritis coronavirus, TGE) and bovine coronavirus, which both result in diarrhea in young animals. Feline coronavirus: two forms, feline enteric coronavirus is a pathogen of minor clinical significance, but spontaneous mutation of this virus can result in feline infectious peritonitis (FIP), a disease associated with high mortality. Similarly, there are two types of coronavirus that infect ferrets: Ferret enteric coronavirus causes a gastrointestinal syndrome known as epizootic catarrhal enteritis (ECE), and a more lethal systemic version of the virus (like FIP in cats) known as ferret systemic coronavirus (FSC).[74] There are two types of canine coronavirus (CCoV), one that causes mild gastrointestinal disease and one that has been found to cause respiratory disease. Mouse hepatitis virus (MHV) is a coronavirus that causes an epidemic murine illness with high mortality, especially among colonies of laboratory mice.[75] Sialodacryoadenitis virus (SDAV) is highly infectious coronavirus of laboratory rats, which can be transmitted between individuals by direct contact and indirectly by aerosol. Acute infections have high morbidity and tropism for the salivary, lachrymal and harderian glands.[76]
A HKU2-related bat coronavirus called swine acute diarrhea syndrome coronavirus (SADS-CoV) causes diarrhea in pigs.[77]
Prior to the discovery of SARS-CoV, MHV had been the best-studied coronavirus both in vivo and in vitro as well as at the molecular level. Some strains of MHV cause a progressive demyelinating encephalitis in mice which has been used as a murine model for multiple sclerosis. Significant research efforts have been focused on elucidating the viral pathogenesis of these animal coronaviruses, especially by virologists interested in veterinary and zoonotic diseases.[78]
