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The novel coronavirus epidemic: How worried should we be?

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The first cases of the coronavirus were reported The first cases of the coronavirus were reported in Wuhan, a city of 11 million people in the Hubei province of China

Medical staff in Wuhan, a city in central China, detected the first cases of pneumonia caused by a mystery pathogen on 8 December 2019. On 31 December, researchers recognised that the growing number of cases clustered around a wholesale market selling seafood and live animals. Chinese authorities closed the market a day later and used ‘genetic fingerprinting’ to find the cause. They reported isolating a new type of coronavirus (2019-nCoV) on 7 January this year.1-4 To try to limit the spread, Chinese authorities restricted travel, limited public gatherings and prolonged the public holiday marking the start of the year of the Rat.

An editorial in Nature Microbiology notes that ‘the speed with which the Chinese authorities reported the outbreak to the international community was commendable and suggests that lessons have been learned from past outbreaks’.1 Without the prompt action of the authorities in China and worldwide, the outbreak could have been much worse. Nevertheless, 2019-nCoV has spread across the globe.

At the time of writing (3 February), the World Health Organisation (WHO) estimates that there have been 14,557 confirmed cases of 2019-nCoV in 24 countries. Of these, 146 were outside China, including two confirmed cases in the UK.5,6 As of the 2nd of February, another 264 people have been tested for 2019-nCoV in the UK, but were negative.6 So, what is 2019-nCoV? How dangerous is this new coronavirus? And how can you and your patients protect yourself?

Introducing coronaviruses

Under an electron microscope, a ‘corona’ or halo made up of protein spikes seems to surround each coronavirus particle (virion).7 These protein spikes bind to receptors on the host cell, which helps the virus infect tissue.4 Coronaviruses carry their genetic code as RNA and cause neurological, respiratory, gastrointestinal and hepatic diseases in numerous species of birds and mammals.2,8,9 Four members of the coronavirus family cause the common cold in humans, for example.2 Other family members cause severe acute respiratory syndrome (SARS) and Middle-East respiratory syndrome (MERS).10

The new coronavirus (2019-nCoV) is the seventh member of the family known to infect humans.2 Genetic analysis of 2019-nCoV obtained from nine patients very early in the outbreak were ‘extremely similar’, sharing more than 99.98% of the sequence. This suggests that the 2019-nCoV came from the same source, over a short time and was detected rapidly:3 essentially the virus didn’t have time to evolve before it was picked up.

The genetic analysis also showed that the new coronavirus was distinct from SARS-CoV and MERS-CoV, which share about 79% and 50% of their genomes respectively with 2019-nCoV.3 Based on the first 425 people with laboratory-confirmed 2019-nCoV, the mean incubation period was 5.2 days. Each person with 2019-nCoV infected, on average two others.11

Patients infected with 2019-nCoV typically present with non-specific symptoms, such as fever, dry cough and malaise.12 A study of 41 people admitted to hospital with laboratory-confirmed 2019-nCoV infection by 2 January 2020 reported that 73% were men, with a median age of 49.0 years, and that 32% had underlying conditions, including diabetes, hypertension or cardiovascular disease. All patients had pneumonia with abnormal findings on computed tomography of their chests. Symptoms at the onset of illness included fever (98% of patients), cough (76%), myalgia or fatigue (44%), sputum production (28%) and headache (8%).13

Fifty-five per cent of these patients experienced dyspnoea, which emerged in a median of eight days from the onset of illness, and 29% developed acute respiratory distress syndrome. A third (32%) were admitted to an ICU for oxygen support to correct hypoxaemia and 15% died.13 Nevertheless, as mentioned later, nurses can reassure worried people that the disease caused by 2019-nCoV seems, based on currently available information, to be ‘relatively mild’ compared with SARS and MERS.14

The epicentre

The first cases of pneumonia clustered around the Huanan wholesale market, which sold seafood and live animals including snakes, marmots, bats, birds, frogs, hedgehogs and rabbits.1,2,4,13 In the study of 41 patients early in the epidemic, 66% had been directly exposed to the Huanan market. As human-to-human transmission became established, fewer infected people had been in direct contact with the market. Of the first 47 cases, 64% had been exposed to the Huanan or another wet market. This declined to 16% of the next 248 cases and 6% of the subsequent 130 cases.11

Genetic analysis found that 2019-nCoV shared 88% of its genome with two bat-derived coronaviruses collected in 2018 in Eastern China.3 The new coronaviruses probably emerged from a recombination of genetic material from a bat coronavirus and another, currently unknown, source: like influenza, coronavirus can swop genetic material.2,4,9 An analysis of the protein spikes suggests that 2019-nCoV probably infected snakes and before infecting humans.4 Ongoing studies will help clarify the infection’s origins.

The jump from another species follows the pattern established by other serious coronaviruses outbreaks. The SARS and MERS coronaviruses (SARS-CoV and MERS-CoV) probably originated in bats.10,13 SARS-CoV seems to have jumped the species barrier at markets selling exotic live animals. Several species in the crowded market at the epicentre of the SARS outbreak were infected, including Himalayan palm civet cat and raccoon dogs.8,10,15 Camels in Africa and the Arabian Peninnsula are the main reservoir for MERS-CoV.10,15,16

The emerging mortality picture

The mortality picture is still emerging. At the time of writing (3 February), the WHO estimated that 2110 people in China developed severe infections and worldwide 305 died, a mortality rate of 2%.5 One death was outside China. Most people who died from 2019-nCoV had a serious underlying disease.14

So, initial indications suggest that 2019-nCoV is less deadly than SARS and MERS. SARS emerged in 2002 in Foshan, China. MERS followed in Saudi Arabia in 2012.10 SARS spread from China to between 25 and 28 other countries, infecting more than 8,000 people and killing almost 800.1,10 MERS-CoV has infected almost 2500 humans in 27 countries. Of these, at least 851 infections proved fatal.16 So, the mortality rate for SARS and MERS is about 10% and 34-37% respectively.13,14

However, more people have already contracted 2019-nCoV than SARS and MARS combined and the total expected number of deaths is not clear. After all, the 1918 influenza pandemic probably had a case-fatality ratio of about 2.5%. But because the strain passed readily between people, Spanish flu still killed between 40 million and 50 million people worldwide.10 In addition, coronaviruses mutate relatively easily, raising the prospect that 2019-nCoV may evolve to pass more easily between people.12 As with much about this emerging epidemic, only time will tell.

There are currently no specific treatments or vaccines for the coronaviruses responsible for SARS and MERS.10,16 However, a recent study identified a small protein called S-phase kinase-associated protein 2 (SKP2) that seems to be critical for the MERS-CoV lifecycle. Experimental drugs inhibiting SKP2 seem to reduce replication of MERS-CoV.16 A study assessing an antiviral combination (lopinavir plus ritonavir) usually used to treat HIV is underway.13 In the meantime, isolation of infected people and quarantining those they come into contact with are the foundations of control.10

Preventing infection

At the time of writing, the WHO believes that symptomatic cases are the ‘main driver of transmission’.17 Currently available data suggests that infected people occasionally transmit 2019-nCoV before they develop symptoms, during the incubation period.17,18 The WHO says, however, that asymptomatic transmission ‘may be rare’. It note that ‘transmission from an asymptomatic person is very rare with other coronaviruses,’ such as MERS.17

Symptomatic people will spread 2019-nCoV more readily by coughing and sneezing. The WHO added that the coronaviruses responsible for MERS and SARS spread from droplets, contact and fomites (inanimate objects than can transmit an infectious agent). As the presenting symptoms suggest, routes of transmission for 2019-nCoV may be similar to MERS and SARS. So, to reduce the risk of 2019-nCoV and acute respiratory infections, nurses should advise patients to:17

  • Avoid close contact with people suffering from acute respiratory infections.
  • Wash hands frequently, especially following direct contact with ill people or their environment.
  • Avoid unprotected contact with farm or wild animals.
  • People with symptoms of acute respiratory infection should practice ‘cough etiquette’; in other words, maintain distance from other people, cover coughs and sneezes with disposable tissues or clothing, and wash hands.

In addition, during the SARS and MERS outbreaks, 58% and 70% of cases respectively followed nosocomial transmission.14 So, healthcare facilities should enhance standard infection prevention and control practices. Travellers who develop symptoms that may suggest respiratory illness, either during or after travel, should seek medical attention and share their travel history with the healthcare professional.17 NHS England is putting people repatriated from Wuhan in quarantine for two weeks.

Unless something unexpected occurs, the outbreak will eventually die down. But further coronaviruses are likely to leap the species barrier. Coronaviruses are common and widely distributed.2 Virologists have isolated coronavirus from animals as diverse as camels, bats, white beluga whales, bottlenose dolphins, pigs and several bird species.9,15 Coronaviruses are also genetically diverse and undergo frequent mutation and recombination.2,9 So, coronaviruses can jump from animals to humans, from humans to animals and between animals.8

We still have much to learn about 2019-nCoV. But 2019-nCoV is the third member of the coronaviruses family to cause a global health emergency in less than 20 years.14 One thing is almost certain: 2019-nCoV won’t be the last of its kind.

Mark Greener is a freelance medical journalist

Further information

The WHO regularly publishes Situation Reports at www.who.int/emergencies/diseases/novel-coronavirus...

The NHS offers advice for travellers returning from high-risk areas: www.nhs.uk/conditions/wuhan-novel-coronavirus

Updates on the UK situation: www.gov.uk/guidance/wuhan-novel-coronavirus-inform...

References

1. Anonymous. (2020) Rapid outbreak response requires trust. Nature Microbiology. 5(2):227-8. https://doi.org.10.1038/s41564-020-0670-8

2. Zhu N, Zhang D, Wang W, et al. (2020) A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med.10.1056/NEJMoa2001017. https://doi.org.10.1056/NEJMoa2001017

3. Lu R, Zhao X, Li J, et al. Genomic characterisation and epidemiology of 2019 novel coronavirus: Implications for virus origins and receptor binding. The Lancet. https://doi.org.10.1016/S0140-6736(20)30251-8

4. Ji W, Wang W, Zhao X, Zai J, Li X. Homologous recombination within the spike glycoprotein of the newly identified coronavirus may boost cross-species transmission from snake to human. Journal of Medical Virology. n/a(n/a). https://doi.org.10.1002/jmv.25682

5. World Health Organisation. Novel Coronavirus(2019-nCoV) Situation Report - 13 Available at https://www.who.int/docs/default-source/coronaviru... Accessed 3 February 2020.

6. Department of Health and Social Care and Public Health England. Coronavirus: latest information and advice Available at www.gov.uk/guidance/wuhan-novel-coronavirus-inform... Accessed 3 February 2020.

7. Centers for Disease Control and Prevention. MERS-CoV Photos Available at https://www.cdc.gov/coronavirus/mers/photos.html Accessed February 2020.

8. Graham RL, Baric RS. (2010) Recombination, reservoirs, and the modular spike: Mechanisms of coronavirus cross-species transmission. J Virol. 84(7):3134-46. https://doi.org.10.1128/jvi.01394-09

9. Woo PCY, Lau SKP, Lam CSF, et al. (2012) Discovery of seven novel Mammalian and avian coronaviruses in the genus deltacoronavirus supports bat coronaviruses as the gene source of alphacoronavirus and betacoronavirus and avian coronaviruses as the gene source of gammacoronavirus and deltacoronavirus. J Virol. 86(7):3995-4008. https://doi.org.10.1128/JVI.06540-11

10. Crawford D. Viruses: A Very Short Introduction. 2nd ed. Oxford: Oxford University Press; 2018.

11. Li Q, Guan X, Wu P, et al. (2020) Early transmission dynamics in Wuhan, China, of novel coronavirus-infected pneumonia. N Engl J Med.doi: 10.1056/NEJMoa2001316. https://doi.org.10.1056/NEJMoa2001316

12. Wang C, Horby PW, Hayden FG, Gao GF. A novel coronavirus outbreak of global health concern. The Lancet.doi: 10.1016/S0140-6736(20)30185-9. https://doi.org.10.1016/S0140-6736(20)30185-9

13. Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. The Lancet.doi: 10.1016/S0140-6736(20)30183-5. https://doi.org.10.1016/S0140-6736(20)30183-5

14. Munster VJ, Koopmans M, van Doremalen N, van Riel D, de Wit E. (2020) A Novel Coronavirus Emerging in China - Key Questions for Impact Assessment. N Engl J Med.doi: 10.1056/NEJMp2000929. https://doi.org.10.1056/NEJMp2000929

15. Woo PCY, Lau SKP, Lam CSF, et al. (2014) Discovery of a novel bottlenose dolphin coronavirus reveals a distinct species of marine mammal coronavirus in Gammacoronavirus. J Virol. 88(2):1318-31. https://doi.org.10.1128/JVI.02351-13

16. Gassen NC, Niemeyer D, Muth D, et al. (2019) SKP2 attenuates autophagy through Beclin1-ubiquitination and its inhibition reduces MERS-Coronavirus infection. Nature Communications. 10(1):doi: 10.1038/s41467-019-13659-4. https://doi.org.10.1038/s41467-019-13659-4

17. World Health Organisation. Novel Coronavirus(2019-nCoV) Situation Report - 12 Available at www.who.int/docs/default-source/coronaviruse/situa... Accessed 2 February 2020.

18. Rothe C, Schunk M, Sothmann P, et al. (2020) Transmission of 2019-nCoV infection from an asymptomatic contact in Germany. New England Journal of Medicine.

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