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February 5, 2020

2019 Novel Coronavirus—Important Information for Clinicians

Author Affiliations
  • 1Division of Infectious Diseases, Department of Internal Medicine, Emory University School of Medicine, Atlanta, Georgia
  • 2Division of Infectious Diseases, Department of Internal Medicine, University of Michigan, Ann Arbor
  • 3Associate Editor, JAMA
JAMA. 2020;323(11):1039-1040. doi:10.1001/jama.2020.1490

In early December 2019 a patient was diagnosed with an unusual pneumonia in the city of Wuhan, China. By December 31 the World Health Organization (WHO) regional office in Beijing had received notification of a cluster of patients with pneumonia of unknown cause from the same city.1 Wuhan, the capital city of Hubei Province in central China, is the nation’s seventh largest city, with a population of 11 million people. Over the next few days, researchers at the Wuhan Institute of Virology performed metagenomics analysis using next-generation sequencing from a sample collected from a bronchoalveolar lavage and identified a novel coronavirus as the potential etiology. They called it novel coronavirus 2019 (nCoV-2019).2 The US Centers for Disease Control and Prevention (CDC) refers to it as 2019 novel coronavirus (2019-nCoV).3

As of February 4, 2020, more than 20 000 cases of 2019-nCoV have been reported, 98.9% of them in China, and the outbreak is linked to more than 400 deaths. As the epidemic is evolving and the situation is rapidly changing, up-to-date reliable information on the number of cases and recommendations on management of cases and preventive interventions can be found at various sites, including the webpage developed by the CDC.3 Currently the number of infections outside of China remains small (approximately 180), but cases have been detected in 26 countries, including 11 cases in the United States.

While it is unclear how many people are truly infected, a modeling study suggests that as of January 25, 2020, 75 815 individuals have been infected in Wuhan alone.4 The authors calculated the basic reproductive number (the number of cases one infected individual generates), R0, of this outbreak to be 2.68 (95% CI, 2.47-2.86) and that the epidemic is doubling every 6.4 days. Because of extensive travel between China and cities like Bangkok, Hong Kong, Singapore, Tokyo, and Taipei, these locations have identified the majority of cases outside of mainland China. As testing becomes more frequent, the true number of cases and the full spectrum of disease will become more clear. However, for now, it appears that compared with the other 2 zoonotic coronaviruses that occurred in the last 20 years (severe acute respiratory syndrome [SARS] in 2002 and Middle East respiratory syndrome [MERS] in 2012), 2019-nCoV seems to have greater infectivity (eg, a higher R0) and a lower case fatality rate.1

From genetic sequencing data, it appears that there was a single introduction into humans followed by human-to-human spread. This novel virus shares 79.5% of genetic sequence with SARS-CoV and has 96.2% homology to a bat coronavirus.2 In addition, 2019-nCoV shares the same cell entry receptor, ACE2, with SARS-CoV. What is yet unclear is which animal is the intermediate species between bats and humans. For SARS it was civet cats, for MERS it is camels. While the source of 2019-CoV is yet unknown, early on the Huanan Seafood Wholesale Market was linked epidemiologically.1,5

The incubation period of this virus has been reported to be 5.2 days (95% CI, 4.1-7.0),6 although there is suggestion that it may be as long as 14 days. It is unclear when transmission begins and, although cases have been reported that suggest transmission during the asymptomatic phase, it is likely that the majority of secondary cases come from symptomatic individuals.

The clinical syndrome is nonspecific and characterized by fever and dry cough in the majority of patients, with about a third experiencing shortness of breath. Some patients have other symptoms such as myalgias, headache, sore throat, and diarrhea7. The median age of patients is between 49 and 56 years.7,8 Cases in children have been rare. Although most cases appear to be mild, all patients admitted to the hospital have pneumonia with infiltrates on chest x-ray and ground glass opacities on chest computed tomography.8,9 About a third of patients subsequently developed acute respiratory distress syndrome and required care in the intensive care unit. This is particularly true for patients with comorbid conditions such as diabetes or hypertension.8

When a patient presents with fever and respiratory symptoms (in particular a dry cough), clinicians should obtain a detailed travel history. If the patient has a history of travel to Hubei Province in the last 14 days, they should be considered a person under investigation (PUI) (Figure).

Figure.  Criteria to Guide Evaluation of Patients Under Investigation for 2019 Novel Coronavirus (2019-nCoV)
Criteria to Guide Evaluation of Patients Under Investigation for 2019 Novel Coronavirus (2019-nCoV)

Adapted from the CDC.3

In the event of a PUI, clinicians should immediately notify their health care facility’s infection prevention team as well as their local or state health department. State health departments then notify the CDC’s Emergency Operations Center. At this time diagnostic testing for 2019-nCoV is conducted only at the CDC, but this is expected to change soon to include state health departments. Clinicians should test for other respiratory pathogens; given that this is influenza season, clinicians should consider prescribing oseltamivir pending results of influenza testing. There is little value to wearing a regular face mask absent a high probability of being exposed to coronavirus, but when there is a high degree of suspicion that a patient might have 2019-nCoV, they should have a face mask placed immediately and health care practitioners should wear N95 respirators.

To date, the management of infection has been largely supportive. Lopinavir/ritonavir is being investigated (Chinese clinical trial registry identifier: ChiCTR2000029308) based on previous studies suggesting possible clinical benefit in SARS and MERS.1 In addition, remdesivir, available through compassionate use, has also been tried and this latter antiviral was used in the first US patient identified.9

In response to the outbreak, on January 23, 2020, Chinese authorities suspended travel in and out of Wuhan.10 Similar travel bans followed in other cities in Hubei Province, and in total close to 50 million people have been quarantined, an unprecedented effort to control any infectious disease. Similarly, other countries have responded by suspending travel to and from China and establishing screening at airports that have flights from China. The WHO on January 30 declared the outbreak a Public Health Emergency of International Concern (and the US State Department has increased the alert level to 4, recommending that citizens not travel to China). On January 31 the Trump administration took the unprecedented action to suspend entry into the United States of all immigrants and nonimmigrants who have physically been in China, Hong Kong, or Macau in the previous 14 days. All US citizens and permanent residents who have been in Hubei Province in the last 14 days will also be subject to quarantine. The effectiveness of these quarantines in curtailing the outbreak is doubtful because these measures have not worked in prior outbreaks, such as the 2009 influenza A(H1N1) or the 2014 Ebola pandemics, and quarantines are contrary to previously proven public health measures and the International Health Regulations.10

What interventions will ultimately control this outbreak is unclear because there is currently no vaccine, and the effectiveness of antivirals is unproven. However, basic public health measures such as staying home when ill, handwashing, and respiratory etiquette including covering the mouth and nose during sneezing and coughing were effective in controlling SARS. As a new outbreak confronts frontline clinicians and public health authorities, these groups must work together to educate the public by providing accurate and up-to-date information and by taking care of patients with respiratory illness in a timely and effective way.

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Article Information

Corresponding Author: Carlos del Rio, MD, Emory University School of Medicine, 69 Jesse Hill Jr Dr, FOB Room 201, Atlanta, GA 30303 (cdelrio@emory.edu).

Published Online: February 5, 2020. doi:10.1001/jama.2020.1490

Conflict of Interest Disclosures: Dr Del Rio reports receiving grants from the National Institute of Allergy and Infectious Diseases, National Institutes of Health. Dr Malani reported no disclosures.

References
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Paules  CI, Marston  HD, Fauci  AS.  Coronavirus infections—more than just the common cold.  JAMA. Published online January 23, 2020. doi:10.1001/jama.2020.0757PubMedGoogle Scholar
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Zhou  P, Yang  XL, Wang  XG,  et al. Discovery of a novel coronavirus associated with the recent pneumonia outbreak in humans and its potential bat origin. Preprint. https://www.biorxiv.org/content/10.1101/2020.01.22.914952v2.full.pdf. Posted January 23, 2020. Accessed February 3, 2020.
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Centers for Disease Control and Prevention. Coronavirus. https://www.cdc.gov/coronavirus/about/index.html. Accessed February 2, 2020.
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Wu  JT, Leung  K, Leung  GM.  Nowcasting and forecasting the potential domestic and international spread of the 2019-nCoV outbreak originating in Wuhan, China: a modelling study.  Lancet. Published online January 31, 2020. doi:10.1016/S0140-6736(20)30260-9Google Scholar
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Cohen  J.  Mining coronavirus genomes for clues to the outbreak’s origins.  Science. Published online January 31, 2020. doi:10.1126/science.abb1256Google Scholar
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Li  Q, Guan  X, Wu  P,  et al.  Early transmission dynamics in Wuhan, China, of novel coronavirus-infected pneumonia.  N Engl J Med. Published online January 29, 2020. doi:10.1056/NEJMoa2001316PubMedGoogle Scholar
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Chen  N, Zhou  M, Dong  X,  et al.  Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study.  Lancet. Published online January 30, 2020. doi:10.1016/S0140-6736(20)30211-7PubMedGoogle Scholar
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    7 Comments for this article
    EXPAND ALL
    "EPIDEMIOLOGIC RISK" SHOULD BE WIDENED FOR PATIENT INVESTIGATION
    Kilsoo Yie, M.D. | Jeju Soo Cardiovascular Center (JSCVC)
    As of Feb 5, 2020, South Korea has identified 19 patients with 2019-nCoV. Among them, 4 patients did not have a travel history to Wuhan city or even to China mainland. Korea CDC reported that one patient (12th patient) had been infected in Japan and had confirmed 2019-nCoV on returning to Korea. The patient has a contact history with 2019-nCoV patient during their time in Japan. The other three patients have a travel history including Singapore within the last 14 days. It is unclear where and who infected these three patients. However, recent increased number of patients in Asian country (26 patients in Singapore, 10 patients in Malaysia etc.) and the fact that patients occurrence without the history of China requires more widened risk indication for patient investigation.
    CONFLICT OF INTEREST: None Reported
    READ MORE
    Fatality Rate Comparison between SARS, MERS, and 2019-nCoV Adjustments.
    Jairo Campos, M.D. |
    SARS and MERS fatality rates used here are "end epidemic" rates against a 2019-nCoV fatality rate that is an "epidemic outbreak" rate. An adjustment formula is possible using the denominator(total number of deaths) in the fatality rate formula from a previous date found by the subtraction of the average of days between the date of case notification and the date of death notification. This is specially valuable as the curve hasn't reached its peak and has predictive "end epidemic" rate value.
    CONFLICT OF INTEREST: None Reported
    Hong Kong and Macao excluded
    Justin Choi, MB ChB (CUHK) | Hospital Authority
    According to Section 1 of Proclamation on Suspension of Entry as Immigrants and Nonimmigrants of Persons who Pose a Risk of Transmitting 2019 Novel Coronavirus (https://www.whitehouse.gov/presidential-actions/proclamation-suspension-entry-immigrants-nonimmigrants-persons-pose-risk-transmitting-2019-novel-coronavirus/), immigrants and nonimmigrants from Hong Kong and Macao are allowed to enter the US, subject to other immigration requirements.
    CONFLICT OF INTEREST: None Reported
    Pathology Studies Necessary to Determine Cause of Death
    Giuliano Ramadori, Professor of Medicine | University Clinic, Internal Medicine, Göttingen,Germany
    The new coronavirus pandemic originating from Wuhan, China has had a tremendous impact on the Chinese population and all nations around the world. The description of the cases in whom the coronavirus has been isolated and its genome has been sequenced has to be hugely appreciated.The coronavirus is supposed to be the cause of pneumonia in all patients and of the death of > 1100 Chinese patients. However it would be very important to obtain tissue pathology findings of the lung and of the other organs. In fact cofactors such as bacterial coinfection or even or even pollution particles in the patient´s bronchial macrophages may have played a role in inducing respiratory problems which may have led to the death of the patients, and should be investigated. We still do not know whether the new coronavirus is really more dangerous than the
    already known human coronavirus strains HKU1, NL63, 229E and 0C43, or the different influenza viruses.
    CONFLICT OF INTEREST: None Reported
    READ MORE
    Is "Hands Only" CPR Safe in COVID-19 Suspected Cases?
    Ornella Piazza, MD; Giuseppina Moccia; Francesco de Caro | Università di Salerno, Department of Medicine and Surgery
    In January 2020, an elderly man wearing a facemask collapsed and died on a street near a hospital in Wuhan.  He could have had a cardiac arrest but there were only a few passers-by, and they dared not go near him. Is it safe to perform cardiopulmonary resuscitation (CPR) on a cardiac arrest victim affected by COVID-19? A Singapore government website states that: “Members of the public can perform “hands-only CPR” without the need for mouth-to-mouth breathing...members of the public are also reminded to practice good personal hygiene after attending to an incident (1). “Hands-only CPR” has been found to be effective in increasing the chance of survival when performed early, but in our opinion, it is not risk free.

    Reference

    1. https://www.gov.sg/article/is-it-safe-to-perform-cpr-covid-19-situation, accessed 05 Feb 2020
    CONFLICT OF INTEREST: None Reported
    READ MORE
    Air Pollution an Important Cofactor to Consider in Pathogenicity Studies
    Giuliano Ramadori, Professor of Medicine | University Clinic,Göttingen, Germany
    We all know that the Chinese and some inhabitants in northern Italy used to put masks on to avoid inhalation of microparticles before COVID-19 was discovered in Wuhan.The NASA pictures (now published by Spiegel online) of the China region taken by the NASA before and after the beginning of the COVID-epidemic show the impressive changes of the sky color (now blue) (1).Similar pictures of the nothern italian regions and of South Korea or of Iran would also be very informative when thinking about causes of death and antiviral therapies.

    Reference

    1. https://www.axios.com/coronavirus-nasa-images-china-pollution-clears-7dd8961d-0627-4342-ab0d-029c872ced1e.html
    CONFLICT OF INTEREST: None Reported
    Cross-Reactivity Between COVID-19 and Childhood Vaccines?
    Arturo Tozzi, Pediatrician, Physicist (1); Gennaro D'Amato (2) | (1) Center for Nonlinear Science, Department of Physics, University of North Texas, Denton, Texas, USA; (2) University of Naples
    One speculation for why SARS is less infective in children is that cross‐protective antibodies are elicited in children in response to childhood vaccines. A 2007 paper (on mice immunised with various vaccines) states that children's vaccines do not induce cross reactivity against SARS‐CoV (1), but the study has several biases.

    Would it be feasible to look for correlations between the RNA and protein sequences of SARS-CoV-2 and the immunogenic epitopes of the vaccines administered to children?

    If a correlation does exist, it could be possible to vaccinate the whole sensitive population.

    Reference

    1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1860633/
    CONFLICT OF INTEREST: None Reported
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