What is nCoV-2019? Update

I spoke to the Imperial College School of Public Health’s Prof Steven Riley (SR) about the coronavirus outbreak that recently began in Wuhan, China.

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So what is nCoV-2019?

It is a viral infection that was first discovered in the Chinese city of Wuhan in 2019 that has been associated with a number of cases of pneumonia – an infection of the tissue in the lungs. You might see it being called ‘2019-nCoV’, which stand for novel (or new) coronavirus. More information has been provided by the World Health Organisation.

·       What is a coronavirus?

John Tregoning (JT): Viruses are infectious organisms that rely upon the cells in our bodies to replicate. A virus needs to enter our cells and hijack them to make copies of itself. They enter our cells by sticking to the outside of the cell, using viral proteins to recognise proteins made by the human cells. Coronavirus are respiratory viruses, which means they are viruses that infect the nose and the lungs. They are a large family of different viruses causing a range of different illnesses from colds to more severe diseases. The coronavirus family is known to be potentially zoonotic, so able to jump between different species. They are from a broader group of viruses called RNA viruses, which means their genetic material is carried on RNA molecules, not DNA molecules, which is important when it comes to thinking about how they can mutate.

·       What are the symptoms?

SR: Since nCoV is a respiratory virus, it will cause symptoms ranging from a cold (blocked nose) and a cough, to chest infection and pneumonia. Fever (a temperature over 38°C or 100.4°F) has been commonly observed with nCoV infections. As the virus was first identified in a cluster of pneumonia patients, we can probably assume that it can cause pneumonia in the more severe cases.

·       Is it anything like SARS, MERS or Ebola?

SR: The novel coronavirus (nCoV) associated with this outbreak, is somewhat similar to SARS (Severe acute respiratory syndrome) which emerged in 2003 and MERS (Middle east respiratory syndrome) which emerged in 2012. Both of these infections, SARS and MERS, are caused by coronaviruses and are respiratory infections.

It is nothing like Ebola, which is caused by a different virus type altogether (Filoviridae). Ebola spreads from person to person by contact with bodily fluids from infected individuals.

·       How does nCoV spread?

SR: We don’t fully know. However, we can compare it to other respiratory viruses. Most of which are spread by respiratory droplets, for example from a sneeze to a hand to a surface, which is then picked up by a new person who then touches their face. Sometimes the virus can be airborne and then inhaled, but it’s more difficult to measure how much transmission happens this way.

·       How was it discovered?

SR: There was a cluster of pneumonia cases in Wuhan, China. Genetic material was isolated from these patients and this coronavirus was found. The team that found it have rapidly shared this information with the global research community, which has enabled research towards new vaccines and diagnostics.

·       How do you test patients for a new virus like this?

SR: Following the identification of the virus causing the infection, we can use pre-existing technology called PCR to test patients. PCR (polymerase chain reaction) is a highly specific test that recognises a genetic sequence and amplifies it so that its presence can be detected.

·       Where did it come from – did it ‘jump’ from reptiles or bats?

SR: The first cases have been closely tied to a specific market in Wuhan. These no reliable evidence for it coming from snakes. The closest known virus is found in bats, but we don’t know for sure if this is where it came from.

·       And how did it jump to humans?

JT: Viruses, and in particular RNA viruses, mutate over time. This is because when they use your cells to make copies of themselves they have poor proofreading, so each copy is not quite the same as the original. Most of these changes will make the virus less infectious, but some might enable them to infect a slightly different type of cell or species.

SR: For other zoonotic viruses (viruses which spread between animals and humans), the viruses normally move from a species with which we are closely physically associated, so for example influenza can move from pigs and chickens to people. The huge number of animals raised for meat and their close physical proximity to people can make these jumps more likely.

·       How is it spreading now?

SR: One of the tools we use as epidemiologists is the R0 value. This is the number of new individuals infected by the first infected person. So for example an R0 of 2 means that each infected person infects 2 more people: in an unbroken transmission chain these 2 people would then infect 2 more each – so 2 becomes 4, which becomes 8 and so on. We then want to apply behavioural and treatment approaches to reduce the R0 to less than 1 so the infection contracts. We do not know the R0 value for nCoV yet and it is too early to be confident about what it is.

·       Is the virus mutating?

SR: It is very hard to tell. Viruses mutate all the time as part of their replication process. It’s very difficult to detect significant mutations that really change the behaviour of a virus.

·       Is this virus any more or less dangerous than seasonal flu?

SR: We don’t know. We are concerned that it is more dangerous than the 2009 strain of influenza, which was milder than other influenza pandemics. One way to think about this is the difference between case fatality rate and infection fatality rate. Very roughly speaking case fatality rate (CFR) is the number of deaths per confirmed cases of the virus (so in this example people who have gone to a doctor or a hospital and had a confirmed diagnosis of the virus). Infection fatality rate (IFR) is the number of deaths of all the people who have been infected.

·       Why is the difference between IFR and CFR important?

JT: If the majority of people who get infected with the virus do not have severe enough illness to need to go to hospital or the Doctor, then the case fatality rate will be higher than the infection fatality rate and the disease will be less serious than it appears. Essentially clinical cases, those that require medical assistance is the tip of an iceberg and the question is how big is the underlying iceberg? If most people infected don’t develop any symptoms, then it is a mild disease, if most people infected need hospitalisation, it is a cause for concern.

·       Why don’t our existing vaccines or antiviral drugs work?

JT: Vaccines work by training your immune system to recognise specific features (called antigens) of the virus it is protecting you against. Since this is a new virus, which looks different to other viruses and has different antigens, current vaccines cannot provide protection.

Why don’t we have a new vaccine?

JT speaking to Professor Robin Shattock (Imperial College London): Vaccines take time to manufacture, even with our best new platforms, any new vaccine takes at least 3 months to manufacture enough material to test in people for safety. It is then a big step from there to manufacture enough doses of vaccine to cover the world population.

 In the last week, CEPI (the Coalition for Epidemic Preparedness Innovation, which is a foundation for vaccine research) has announced it will support fast track vaccine research programs for three vaccines against coronavirus. The vaccines use different technologies to make the vaccines: one is based on DNA, one on RNA and one on proteins. They will all make a region of the virus which your body will then recognise as foreign and make an immune response against. Other programs are also ongoing, for example Johnson & Johnson are also developing a vaccine. It is good that there are multiple approaches being developed as this will reduce the risk of any single approach not working, but also might mean there is more capacity to manufacture enough doses of the vaccine if they prove to be safe and effective.

What about antiviral drugs?

JT: Antiviral drugs also target key components of the viral replication. They have been developed for other families of viruses and so are not necessarily specific enough to inhibit the coronaviruses. Interestingly, compared to other virus families coronaviruses have more genetic material (they have a larger RNA genome). It is of note that coronaviruses make a protein which ensures that their genetic material is copied correctly, this has an impact on what classes of drugs can be used against them. Many antiviral drugs work by affecting the ability of the virus to make copies of themselves. In the current outbreak a combination of anti-HIV drugs (lopinavir and ritonavir) is being tested as a possible therapy, based on an earlier study during the SARS-coronavirus outbreak.

What about antibiotics?

JT: Antibiotics are drugs that are used to control bacterial infections. Since 2019-nCoV is a virus, they will have no effect on this infection.

·       Is there anything people can do to reduce their risk: for example wearing facemasks or washing hands?

JT: Masks are important in clinical settings when properly used, however they have little value for the general public. Handwashing and reducing contact from hands to face can be helpful, as this helps stop the spread of the virus through respiratory droplets from coughs and sneezes.

·       Will the quarantine in Wuhan work?

SR: It is an unprecedented step, so we have no evidence either way. But it is a strong statement from the government and this will increase the awareness of the infection and therefore reduce spread.

  • Why are people coming back from Wuhan being quarantined?

SR: This is a control measure to reduce the risk of further spread if those travelling have been infected but were not as yet showing symptoms. The most recently reported data indicates that the average incubation period, the time between infection and symptoms, is 5.2 days.

  •  What is a A Public Health Emergency of International Concern (PHEIC)?

JT: This is a situation declared by the World Health Organisation (WHO), when a public health risk (normally an infection) spreads beyond national borders. There have been 6 PHEIC declarations since 2009, including swine flu and 2014 Ebola outbreak. The aim is to coordinate the international response.


John Tregoning

Reader in Respiratory Infections, Imperial College London

I have studied the immune responses to vaccination and respiratory infection for 15 years and have been an independent PI for 10 years. My group’s research program is focussed on prevention of respiratory infections. This research has focused on vaccines to a range of respiratory pathogens.

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