2019-nCov Outbreak: Key questions for impact assessment remain

2020-02-02 Sunney 2019-nCov 0

Scientists and health authorities around the world are racing to halt the spread of a deadly virus — 2019-nCov (2019 novel coronavirus) that emerged in the Chinese city of Wuhan in December, 2019. The virus is a novel coronavirus, and belongs to the same family as the virus that causes SARS (severe acute respiratory syndrome). It causes a respiratory illness, can spread from person to person. Thousands of people have already contracted the new coronavirus, which causes respiratory illness. The death toll is rising daily. On 30 January, the World Health Organization (WHO) declared the outbreak a “public-health emergency of international concern” — an alarm it reserves for events that pose a risk to multiple countries and which requires a coordinated international response.

Crucial details about the virus and how it spreads are still unknown, but experts are considering best- and worst-case scenarios on the basis of previous epidemics and what scientists already know. Here, most pressing questions about 2019-nCov still remain off-limits, but only for now:

What is 2019-nCoV?

People around the world commonly get infected with human coronaviruses 229E, NL63, OC43, and HKU1. Sometimes coronaviruses that infect animals can evolve and make people sick and become a new human coronavirus. Three recent examples of this are SARS-CoV, MERS-CoV and 2019-nCov.

Coronaviruses, one of a variety of viruses that typically cause colds, are named for the crown-like spikes on their surface. There are four main sub-groupings of coronaviruses, known as alpha, beta, gamma, and delta. Human coronaviruses were first identified in the mid-1960s.

There are 7 human coronaviruses known to infect humans. Of those, human coronaviruses 229E (alpha coronavirus), NL63 (alpha coronavirus), OC43 (beta coronavirus), and HKU1 (beta coronavirus) are routinely responsible for mild respiratory illnesses like the common cold but can cause severe infections in immunocompromised individuals.

Bats harbour a wide range of coronaviruses, including severe acute respiratory syndrome coronavirus (SARS-CoV)-like and Middle East respiratory syndrome coronavirus (MERS-CoV)-like viruses. SARS-CoV crossed the species barrier into masked palm civets and other animals in live-animal markets in China; genetic analysis suggests that this occurred in late 2002. Several people in close proximity to palm civets became infected with SARS-CoV. A MERS-CoV ancestral virus crossed the species barrier into dromedary camels; serological evidence suggests that this happened more than 30 years ago. Abundant circulation of MERS-CoV in dromedary camels results in frequent zoonotic transmission of this virus. SARS-CoV and MERS-CoV spread between humans mainly through nosocomial transmission, which results in the infection of health care workers and patients at a higher frequency than infection of their relatives.
A previously unknown coronavirus is behind an outbreak of respiratory illness in China. So far, The clinical severity of the 2019-nCoV is unknown at this time, although fatal cases have occurred (stained yellow in this scanning electron micrograph).

But three members of the viral family have caused deadly outbreaks. SARS-Cov (Severe acute respiratory syndrome), MERS-Cov (Middle East respiratory syndrome), and now 2019-nCov cause more severe disease, including pneumonia. This new coronavirus first emerged in Wuhan, China. (SN: 01/12/20)

2019-nCov_WHO

 

When did the outbreak start?

Chinese officials notified the World Health Organization of a pneumonia-like disease with an unknown cause in 44 patients on December 31, 2019. Initial reports tied the disease — now known to be 2019-nCov — to a seafood market in Wuhan, a city in Hubei Province.

But the earliest cases may not be related to exposure at the market, researchers report January 24 in the Lancet. The earliest known patient with the illness, the “index case” who got sick December 1, was not exposed at the market, according to the study.

“The market was not the [source of the] index case. It was an amplifier. People crowded in the market infected each other,” Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases in Bethesda, Md., said January 29 at the 2020 ASM Biothreats meeting in Arlington, Va.

So far, versions of the new virus isolated from patients in China and other countries aren’t very different from one another. “This lack of diversity fits with an origin in the human population in mid-November,” says Trevor Bedford, an evolutionary biologist at the Fred Hutchinson Cancer Research Center and the University of Washington in Seattle.

Where did the virus come from?

Coronaviruses are zoonotic, meaning they originate in animals and sometimes leap to humans.

Bats are often thought of as a source of coronaviruses, but in most cases they don’t pass the virus directly on to humans. SARS probably first jumped from bats into raccoon dogs or palm civets before making the leap to humans. All the pieces necessary to re-create SARS are circulating among bats, though that virus has not been seen since 2004 (SN: 11/30/17).

MERS, meanwhile, went from bats to camels before leaping to humans (SN: 2/25/14). A paper published January 22 in the Journal of Medical Virology suggests that the new coronavirus has components from bat coronaviruses, but that snakes may have passed the virus to humans. But many virologists are skeptical that snakes are behind the outbreak (SN: 1/24/20).

Severe acute respiratory syndrome coronavirus (SARS-CoV) is a new coronavirus that emerged through recombination of bat SARS-related coronaviruses (SARSr-CoVs). The recombined virus infected civets and humans and adapted to these hosts before causing the SARS epidemic. Middle East respiratory syndrome coronavirus (MERS-CoV) likely spilled over from bats to dromedary camels at least 30 years ago and since then has been prevalent in dromedary camels. HCoV-229E and HCoV-NL63 usually cause mild infections in immunocompetent humans. Progenitors of these viruses have recently been found in African bats, and the camelids are likely intermediate hosts of HCoV-229E. HCoV-OC43 and HKU1, both of which are also mostly harmless in humans, likely originated in rodents. Recently, swine acute diarrhoea syndrome (SADS) emerged in piglets. This disease is caused by a novel strain of Rhinolophus bat coronavirus HKU2, named SADS coronavirus (SADS-CoV); there is no evidence of infection in humans. Solid arrows indicate confirmed data. Broken arrows indicate potential interspecies transmission. Black arrows indicate infection in the intermediate animals, yellow arrows indicate a mild infection in humans, and red arrows indicate a severe infection in humans or animals.

Current data suggest that the virus made the leap from animals to humans just once and has been passing from person to person ever since. Based on how closely related the patient viruses are, animals from the seafood market probably didn’t give people the virus multiple times as researchers originally thought, Bedford says. If the virus leaped from animals to humans more than once, the researchers would expect a greater number of mutations. Bedford and colleagues updated their conclusions and supporting data January 29 at nextstrain.org.

Can it infect pets?

There are currently no reports of pets getting sick with 2019-nCov.

Several types of coronaviruses can infect animals and in some cases make them ill. So the U.S. Centers for Disease Control and Prevention advises avoiding contact with pets and wearing a face mask if you are sick. Researchers reported in 2003 in Nature that cats could be infected with the SARS virus and transmit it to other cats in the same cage, but they didn’t show any symptoms. The same was true for ferrets, although the ferrets became sick.

While the CDC recommends that people traveling to China avoid animals, the agency says there is no reason to believe that animals or pets in the United States can transmit the virus.

What are the symptoms of a 2019-nCoV infection?

An infection can cause fever, cough and difficulty breathing, according to the CDC. These symptoms are similar to SARS, researchers report January 24 in the Lancet (SN: 1/24/20). Though many people with 2019-nCov might experience mild symptoms, others can develop pneumonia.

Based on how MERS works, the CDC reports that symptoms of 2019-nCoV may appear from two to 14 days after exposure. On average, it may take a person who was exposed to the virus five days to become visibly sick, researchers report January 29 in the New England Journal of Medicine. That number, however, is based on only 10 patients and needs further study, the researchers wrote.

How infectious is the virus?

Researchers don’t yet know for sure. But since 2019-nCov has never infected humans before last year, it’s likely that everyone is vulnerable to infection with this virus.

A virus’s potential infectivity is described by its reproduction number called R0, or R naught (SN: 1/24/20). It’s a theoretical limit that researchers would expect to see when a disease-causing organism hits a population where no one is immune, says Maimuna Majumder, a computational epidemiologist at Boston Children’s Hospital and Harvard Medical School. “In general, we don’t see transmission rates as high as the reproduction number would suggest,” she says.

The number describes how many other people are likely to catch a virus from an infected person. SARS, for instance, has an R0 of 2.0 to 4.0 — each person who catches that virus has the potential to pass it on to two to four others. Generally, viruses with reproduction numbers greater than 1.0 may keep spreading if nothing is done to stop them. Outbreaks of viruses with an R0 that falls at or below 1.0 may eventually peter out.

Several research groups have been working to pin down an estimate based on outbreak information available to them and by harnessing different methods, such as simulating outbreaks or making assumptions about virus susceptibility, exposure and infection rates. Others have used an approach that pulls data from current cases and allows the researchers to describe what is happening in real time.

The R0 for 2019-nCov New England Journal of Medicine. This number is close to Majumder’s and her Harvard colleague Kenneth Mandl’s estimate, which falls between 2.0 and 3.1. Other groups have also posted various estimates online, ranging from 1.4 to 4.13.

R0 is a tricky number to pin down, as the varying estimates reflect. It can also change as control measures are put in place, suggesting that as more cases emerge, these estimates will probably continue to shift. But currently the groups are coming up with similar numbers, suggesting 2019-nCov’s R0 is in the same ballpark as SARS.

How long does it stay on surfaces?

Researchers aren’t sure, but not very long, based on what they know about other coronaviruses. These viruses typically only survive on a surface for a few hours, Nancy Messonnier, director of the CDC’s National Center for Immunization and Respiratory Disease in Atlanta, said in a news conference January 27.

While it’s still unclear how 2019-nCov spreads, coronaviruses in general are thought to be spread primarily by respiratory droplets — such as when patients cough. There is no evidence suggesting 2019-nCov can be transmitted from things such as imported goods, according to the CDC.

How does it spread?

Human-to-human transmission is driving the spread in China, and has been reported in a few other countries, including the United States (see below, What is the situation in the United States?). But the exact mechanism is still unknown.

Coronaviruses like SARS and MERS — and now 2019-nCov — probably spread between people similar to other respiratory diseases, the CDC says. Respiratory droplets from an infected person’s cough or sneeze can carry virus to another person, something that generally happens between close contacts.

Because severe coronaviruses infect deeper parts of the respiratory tract, compared with the kinds of coronaviruses that cause colds, people tend not to be contagious until they start to show symptoms, says Stanley Perlman, a virologist at the University of Iowa in Iowa City.

In previous outbreaks, “if somebody was going to get infected from [an] infected person, the virus had to get up into the upper airway so it could spread,” Perlman says, which wouldn’t happen until the patient was sick enough to start coughing.

Unlike SARS and MERS, however, there is now evidence that the new coronavirus can be spread by people without symptoms. A cluster of 2019-nCov cases in Germany were caused by asymptomatic transmission of the virus, doctors report January 30 in the New England Journal of Medicine (SN 1/31/20). A woman from Shanghai passed the virus to business colleagues in Germany before she showed signs of the illness. One of the infected passed the virus to two other coworkers before he became ill and still showed high levels of the coronavirus in his nasal passages and phlegm after his symptoms subsided.

Asymptomatic transmission is common for contagious viruses such as influenza or measles, but would be a new feature for the types of coronaviruses that cause epidemics, Perlman says.

It could make the outbreak harder to control because such patients can spread disease without signs that they’re sick themselves, making efforts such as airport screenings less useful. But asymptomatic people have never been the major driver of epidemics, NIAID’s Fauci said in a news conference January 28.

How far has it spread?

So far, it’s unclear exactly how many cases there are, although epidemiologists are attempting to calculate this number. By January 31, the number of officially diagnosed cases of 2019-nCov infections hit 9,836, according to a situation update by the European Center for Disease Control and Prevention. That exceeds the total number of SARS cases over that coronavirus’s eight-month run between November 1, 2002 and July 31, 2003.

Most of the thousands of people with confirmed diagnoses of the new virus are in China. Several other countries — 22 as of January 31 — have also confirmed isolated cases of the disease, many of whom had just returned from a trip to China.

Given that symptoms don’t appear right away and many exposed people may experience no or mild symptoms, those numbers are likely too low, researchers say.

Epidemiologist and biostatistician Joseph T. Wu of the University of Hong Kong and colleagues report January 31 in the Lancet that an estimated 75,815 people in Wuhan had been infected as of January 25, with numbers of cases doubling, on average, every 6.4 days.

Quarantine measures that locked down Wuhan probably came too late to do much to contain the spread (SN: 1/28/20). Wu and colleagues calculated that Wuhan had already exported 461 cases to Chongqing, 113 to Beijing, 98 to Shanghai and 111 to Guangzhou. Those cities now may become hubs for further spread.

Wu’s group used exported case counts and travel data to forecast the epidemic’s future spread. If the virus continues spreading at the current rate, the epidemic could peak in Wuhan in April with other cities lagging by a week or two. Reducing transmission rates by 25 percent would slow the epidemic’s growth, delaying the peak by about a month and also cutting the total number of cases in half, the researchers estimate.

How many people will the virus infect?

Chinese authorities have locked down cities at the centre of the epidemic, and researchers were quick to share data on the virus with the World Health Organization and researchers. But the case numbers have been rising, and surged past 9,000 in the past day, mostly in China. This has led to one prediction that the virus could infect about 39,000 of the 30 million people living in the region of Wuhan. “It seems like the virus has got out of hand in China, spread too far, too quickly to really be contained,” says Ian Mackay, a virologist at the University of Queensland in Brisbane, Australia.

In the best case, fewer people will be infected because the effects of the control measures will start kicking in, says Ben Cowling, an epidemiologist at the University of Hong Kong. But it’s too early to tell whether efforts to quarantine people, and the widespread use of face masks, are working. The incubation period for the virus — up to 14 days — is longer than most control measures have been in place, he says.

In a worst-case scenario, some 190,000 people could be infected in Wuhan, according to another prediction model. Scientists are particularly concerned about fresh outbreaks emerging outside China. The virus has already spread in small, localized clusters in Vietnam, Japan, Germany and the United States, but authorities have been quick to isolate the people affected. Fewer than 100 cases have been recorded outside China as of 30 January.

How deadly is the disease?

Coronaviruses usually cause fairly mild illness, affecting just the upper airway. But the new virus, like SARS and MERS, penetrates much deeper into the respiratory tract. 2019-nCov is “a disease that causes more lung disease than sniffles,” NIAID’s Fauci says. And damage to the lungs can make these illnesses deadly.

An analysis of 99 hospitalized patients, including the first cases from Wuhan, shows that 17 developed acute respiratory distress syndrome and 11 subsequently died from multiple organ failure, the Lancet reports January 29.

The 2003 SARS outbreak killed nearly 10 percent of the 8,000 people sickened (SN 3/26/03). MERS, a disease that still circulates in the Middle East, is even more deadly, claiming about 30 percent of the people it infects (SN: 7/8/16). Right now, 2019-nCov appears to be less virulent, with about a 4 percent mortality rate, the World Health Organization reported on January 24. But that number is still a moving target as more cases are diagnosed, Fauci says.

“There almost certainly is asymptomatic infection,” Fauci said January 29 at the 2020 ASM Biothreats meeting. “We don’t know at what level yet.” Knowing that number affects the calculation of how deadly the virus is. “Right now the denominator is people who come to the hospital and are recognized. But with asymptomatic infections, the denominator is going to be bigger and the mortality [rate] will be less,” he said.

The fatality rate for a virus — the proportion of infected people who die — is difficult to calculate in the middle of an outbreak because records on new cases and deaths are constantly being updated. With 213 deaths so far out of nearly 10,000 infections, the new coronavirus has a death rate of 2–3%. This is significantly lower than SARS, which killed around 10% of the people it infected. The known death rate for the new coronavirus is likely to decrease as mild and asymptomatic cases are identified, virologist Mark Harris at the University of Leeds, UK, told the Science Media Centre in London.

There is currently no effective drugs against the virus. Two HIV drugs thought to target a protein that helps coronaviruses to replicate are being tested as a treatment. Scientists have also identified other existing medications that target this function, and several international research groups are working on a vaccine.

The number of deaths will also depend on how China’s health system copes with the high number of cases. Putting people on drips and ventilators can ensure that they get enough fluids and oxygen while their body’s immune system fights the virus. China is building two new hospitals in Wuhan to accommodate the people infected, but if the virus spreads to parts of the world with fewer resources, such as income regions of Africa, their health systems could struggle, says Sanjaya Senanayake, an infectious-disease specialist at the Australian National University in Canberra.

In declaring a global health emergency, the WHO’s director-general, Tedros Adhanom Ghebreyesus, said his main concern was that the outbreak could spread to countries with fragile health systems.

If the virus spreads throughout the world, the number of deaths could be substantial. The current death rate of 2–3% — while not as high as for SARS — is still quite high for an infectious disease, says Adam Kamradt-Scott, a global health-security specialist at the University of Sydney, Australia. The 1918 influenza outbreak, known as the Spanish flu, infected around half a billion people, one-third of the world’s population at the time, and killed more than 2.5% of those infected — an estimated 50 million people.

The China coronavirus probably won’t trigger such an apocalyptic scenario, because it isn’t typically infecting or killing young, healthy people, says Kamradt-Scott.

What is the situation in the United States?

As of January 30, health officials have confirmed the coronavirus in six patients, including the first known person-to-person transmission in the United States. An Illinois woman who had traveled to Wuhan and was diagnosed with coronavirus illness on January 21 has spread the virus to her husband, the CDC announced in a news conference January 30.

Twenty U.S. airports are actively screening travelers from China for symptoms, according to the CDC. Because of the relatively rapid release of information from China, countries like the United States had time to put proper screening procedures in place, giving them a leg up in keeping the virus from spreading, says Allison McGeer, an infectious disease expert at Mount Sinai Hospital in Toronto who herself contracted SARS in 2003 while taking care of patients.

With news that the virus can spread asymptomatically and the growing number of cases in China, officials have now quarantined a group of 195 U.S. citizens evacuated from Wuhan, the CDC announced January 31. The evacuees, who landed at March Air Reserve Base in Ontario, Calif., on January 29, had remained on base for health assessments. The goal of this legally mandated two-week quarantine, says the CDC’s Messonnier, is “to prevent, as much as possible, community spread with this novel virus in the United States.”

Is the virus here to stay?

When a virus circulates continuously in a community, it is said to be endemic. The viruses that cause chicken pox and influenza are endemic in many countries, but outbreaks can be controlled through vaccination and keeping people at home when they are ill.

One big question is whether the coronavirus is also here to stay. If efforts to contain it fail, there’s a high chance that it will become endemic. As with influenza, this could mean that deaths occur every year as the virus circulates, until a vaccine is developed. If the virus can be spread by people who are infected but don’t have symptoms, it will be more difficult to control its spread, making it more likely that the virus will become endemic.

There have been several cases of infected people displaying no symptoms, but it’s still unclear whether such asymptomatic or mild cases are common, and whether or how infectious they are. “We’re possibly looking at a virus that’s going to be with us for a long time, possibly forever,” says Mackay.

Asymptomatic cases set the new virus apart from the related coronavirus that causes severe acute respiratory syndrome (SARS). There was a global outbreak of this virus in 2002–03, but it usually spread only once people were ill enough to need hospital care. Once outbreaks in hospitals were brought under control, SARS was contained. There is no evidence that the virus is still circulating in humans, says Mackay.

If control measures are effective, and transmission slows so that each infected person infects no more than one other person, the current outbreak could simply peter out, says Cowling.

Is the virus likely to change?

Some researchers are worried that as the China coronavirus spreads, the pathogen could mutate so it can spread more efficiently, or become more likely to cause disease in young people. Currently, the virus has caused severe illness, and death, mainly in older people, particularly those with pre-existing conditions such as diabetes and heart disease. A 36-year-old Wuhan man with no known pre-existing health conditions is the youngest victim reported so far.

Kristian Andersen, an infectious-disease researcher at Scripps Research in La Jolla, California, is not concerned about the virus becoming more virulent. He says that viruses constantly mutate as part of their life cycle, but those mutations don’t typically make the virus more virulent or cause more serious disease. “I can’t think of any examples of this having happened with an outbreak pathogen,” he says.

In situations where a virus jumps from one animal host to another species — which is probably how the new coronavirus began to infect humans — there might be a selection pressure to improve survival in the new host, but that rarely, if ever, has any effect on human disease or the virus’s transmissibility, says Andersen. Most mutations are detrimental to the virus or have no effect, he says. A 2018 study of SARS in primate cells found that a mutation the virus sustained during the 2003 outbreak probably reduced its virulence.

Researchers have shared dozens of genetic sequences from strains of the new coronavirus, and a steady supply of those sequences will reveal genetic changes as the outbreak progresses, says MacKay. “Viruses don’t change behaviour unless they change sequence, and we need to see constant or consistent virus change,” he says.

What are the best ways to protect yourself?

The CDC recommends practices similar to preventing the spread of other respiratory viruses, such as washing hands with soap and water for at least 20 seconds, covering your cough or sneeze, and not touching your eyes, nose and mouth.

Personal actions, such as wearing a mask, could also help contain the spread of the virus, though experts say the evidence is inconclusive. “If you’re infected and you wear a mask, you’ll shed less virus in to the air around you” and potentially reduce the risk that others get infected, McGeer says. For uninfected people, the effects of a mask are less clear, since they usually aren’t sealed tight around the nose and mouth.

References

Share
About Sunney 116 Articles
I am currently a Professor of Zhejiang Gongshang University, Hangzhou, China.

Be the first to comment

Leave a Reply

Your email address will not be published.


*