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WUHAN CORONAVIRUS (2019-nCoV)

As the world steps into the 3rd decade of the new millennium, we are now faced with the 3rd instance of an outbreak due to a zoonotic coronavirus jumping across species to infect humans. While it is still early days, the new 2019-nCoV strain outbreak in Wuhan seems to be following in the footsteps of the earlier SARS-CoV and MER-CoV outbreaks.
The severe acute respiratory syndrome (SARS) outbreak of 2002-2003 lasted about six months, resulting in more than 8,000 cases and killing 774 people.

The Middle-East respiratory syndrome (MERS) was first identified in Saudi Arabia in Sep. 2012. By June 2013, there were 55 laboratory-confirmed cases reported to WHO. Cases were reported in Saudi Arabia, Qatar, Jordan and the United Arab Emirates and some infected travelers were reported in the United Kingdom, Italy, France and Tunisia. In 2015, there was a separate outbreak of MERS-CoV in South Korea. The first patient of the outbreak developed symptoms on May 11, 2015. WHO and the South Korean government estimated that the outbreak ended in July 2015, after about two months by which time, there were 186 confirmed cases and 38 deaths.

The illness caused by a new coronavirus in Wuhan, currently being called 2019-nCoV, was first reported to WHO on Dec. 31, 2019 as a “cluster of cases” in Wuhan. The earliest cases were estimated to have started on Dec. 8. As per the WHO status report of 28th January, 2020, a total of 4593 confirmed 2019-nCoV cases have been reported globally. Of the 4593 cases reported, 4537 cases were reported from China with a 106 deaths. 56 confirmed cases have been reported outside of China in 14 countries.

WHAT IS THE CORONAVIRUS?

Coronaviruses are enveloped non-segmented positive sense RNA viruses. They belong to the subfamily Coronavirinae in the family of Coronaviridae of the order Nidovirales, and this subfamily includes four genera:

  • Alphacoronavirus
  • Betacoronavirus
  • Gammacoronavirus
  • Deltacoronavirus

They can infect respiratory, gastrointestinal, hepatic and central nervous system of human, livestock, avian, bat, mouse and many other wild animals. Since the outbreaks of SARS in 2002 and MERS in 2012, the possibility of CoVs transmission from animals to human has been proved.

Before 2019, there were only six CoVs that can infect humans and cause respiratory diseases:

  • HCoV-229E, HCoV-OC43, HCoV-NL63 and HKU1 induce only mild upper respiratory disease, and in rare cases some of them can cause severe infection in infants, young and the elderly.
  • SARS-CoV and MERS-CoV can infect lower respiratory tract and cause severe respiratory syndrome in human.

WHAT ABOUT THE NEW STRAIN?

Since the end of December 2019, an outbreak of mystery pneumonia in Wuhan has been drawing tremendous attention around the world. Chinese government and researchers have taken swift measures to control the outbreak and conduct the etiological studies. The causative agent of the mystery pneumonia has been identified as a novel coronavirus by deep sequencing and etiological investigations by at least 5 independent laboratories of China. On 12 January 2020, the World Health Organization temporarily named the new virus as 2019 novel coronavirus (2019-nCoV). The formal name of the virus will be given by the International Committee of Taxonomy of Viruses (ICTV) according to the guidelines of viral nomenclature.

The new coronavirus 2019-nCoV, which belongs to betacoronaviruses according to the genome analysis, can also infect lower respiratory tract and cause pneumonia, but in general, the symptoms are milder than SARS and MERS.

Figure 1

SOURCE & TRANSMISSION

The initial source of 2019-nCoV still remains unknown.

Given its close similarity to bat coronaviruses, it may be likely that bats are the primary reservoir for the virus. SARS-CoV was transmitted to humans from exotic animals in wet markets, whereas MERS-CoV is transmitted from camels to humans. In both cases, the ancestral hosts were probably bats.

There is now evidence that 2019-nCoV spreads from human- to- human and also across generations of cases.

WHAT ARE THE SYMPTOMS?

The most common symptoms at onset of illness are:

  • Fever (which may be absent in persons at extremes of age or with immunocompromise)
  • Cough
  • Myalgia
  • Fatigue

Less common symptoms which have been observed include:

  • Sputum production
  • Headache
  • Hemoptysis
  • Diarrhoea

Chest radio-graphs may show bilateral infiltrates. Clinical illness varies from mild to severe; about 25% of confirmed cases have been classified as severe, and there are increasing numbers of deaths. In early cases, mortality was associated with advanced age or comorbidities.

Figure 2 - Timeline of coronavirus onset
Figure 2 – Timeline of coronavirus onset (adapted from Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. The Lancet. 2020 Jan;S0140673620301835)

One of the earliest studies on 41 admitted patients found that 51% had dyspnea after 8 days. 27% had ARDS after 11 days and 39% required ICU admission after a median of 10.5 days.

WHO SHOULD BE TESTED?

The WHO recommends that patients fitting the following criteria be tested for the 2019-nCoV virus: (10)

1. Severe acute respiratory infection (SARI) in a person, with history of fever and cough requiring admission to hospital, with no other etiology that fully explains the clinical presentation (clinicians should also be alert to the possibility of atypical presentations in patients who are immunocompromised);
AND any of the following:

  • a history of travel to or a person who lived in Wuhan, Hubei Province China in the 14 days prior to symptom onset; or
  • the disease occurs in a health care worker who has been working in an environment where patients with severe acute respiratory infections are being cared for, without regard to place of residence or history of travel.

2. The person develops an unusual or unexpected clinical course, especially sudden deterioration despite appropriate treatment, without regard to place of residence or history of travel, even if another etiology has been identified that fully explains the clinical presentation.

3. A person with acute respiratory illness of any degree of severity who, within 14 days before onset of illness, had any of the following exposures:

  • close physical contact with a confirmed case of nCoV infection; or
  • a healthcare facility in a country where hospital associated nCoV infections have been reported; or
  • visiting or working in a live animal market in Wuhan, China
  • direct contact with animals (if animal source is identified) in countries where the nCoV is known to be circulating in animal populations or where human infections have occurred as a result of presumed zoonotic transmission.

The WHO defines “close contact” as:

  • Health care associated exposure, including providing direct care for nCoV patients, working with health care workers infected with nCoV,
  • Visiting patients or staying in the same close environment of a nCoV patient.
  • Working together in close proximity or sharing the same classroom environment with a with nCoV patient
  • Traveling together with nCoV patient in any kind of conveyance
  • Living in the same household as a nCoV patient

However, the CDC defines “close contact” as:

  • Being within approximately 6 feet (2 meters), or within the room or care area, of a novel coronavirus case for a prolonged period of time while not wearing recommended personal protective equipment or PPE (e.g., gowns, gloves, NIOSH-certified disposable N95 respirator, eye protection); close contact can include caring for, living with, visiting, or sharing a health care waiting area or room with a novel coronavirus case.– or –
  • Having direct contact with infectious secretions of a novel coronavirus case (e.g., being coughed on) while not wearing recommended personal protective equipment.

PRECAUTIONS FOR HEALTHCARE WORKERS

The following is a highly abridged version of the WHO document “Infection prevention and control during health care when novel coronavirus (nCoV) infection is suspected: Interim Guidance” – the complete document is available at:

https://www.who.int/publications-detail/infection-prevention-and-control-during-health-care-when-novel-coronavirus-(ncov)-infection-is-suspected-20200125

  • Ensure that all patients cover their nose and mouth with a tissue or elbow when coughing or sneezing;
  • Offer a medical mask to patients with suspected 2019-nCoV infection while they are in waiting/public areas or in cohorting rooms;
  • Perform hand hygiene after contact with respiratory secretions:
    • Hand hygiene includes either cleansing hands with an alcohol-based hand rub (ABHR) or with soap and water;
      • alcohol-based hand rubs are preferred if hands are not visibly soiled;
      • wash hands with soap and water when they are visibly soiled.
    • When dealing with suspected cases of 2019-nCoV:
      • Wear an N95 rated medical mask, eye protection (googles) or facial protection (face shield) to avoid contamination of mucous membranes; clean, non-sterile, long-sleeved gown and gloves
      • The use of boots, coverall and apron is not required during routine care;
      • After patient care, appropriate doffing and disposal of all personal protective equipment (PPE) and hand hygiene should be carried out.
      • A new set of PPEs is needed, when care is given to a different patient.
      • Equipment should be either single-use and disposable or dedicated equipment (e.g., stethoscopes, blood pressure cuffs and thermometers). If equipment needs to be shared among patients, clean and disinfect it between use for each individual patient (e.g., by using ethyl alcohol 70%) Refrain from touching eyes, nose or mouth with potentially contaminated gloved or bare hands; avoid moving and transporting patients out of their room or area unless medically necessary.
      • Use designated portable X-ray equipment and/or other designated diagnostic equipment. If transport is required, use predetermined transport routes to minimize exposure for staff, other patients and visitors, and have the patient using a medical mask;
      • Routinely clean and disinfect surfaces which the patient is in contact;
      • Limit the number of HCWs, family members and visitors who are in contact with a suspected and confirmed 2019-nCoV patient;
      • Maintain a record of all persons entering the patient’s room, including all staff and visitors.

COLLECTING AND HANDLING LABORATORY SPECIMENS FROM PATIENTS WITH SUSPECTED 2019-NCOV INFECTION

All specimens collected for laboratory investigations should be regarded as potentially infectious. Health care workers who collect, handle or transport any clinical specimens should adhere rigorously to the following standard precaution measures and biosafety practices to minimize the possibility of exposure to pathogens. The WHO has put forward the following general guidelines for healthcare workers who may collect or handle patient samples. The following is an abridged version – the document is available at:

https://www.who.int/publications-detail/infection-prevention-and-control-during-health-care-when-novel-coronavirus-(ncov)-infection-is-suspected-20200125

  • Use appropriate PPE (i.e., eye protection, a medical mask, a long-sleeved gown, gloves).
  • If the specimen is collected with an aerosol-generating procedure, personnel should wear a particulate respirator at least as protective as a NIOSH-certified N95, an EU standard FFP2, or the equivalent;
  • All personnel who transport specimens should be trained in safe handling practices and spill decontamination procedures;
  • Place specimens for transport in leak-proof specimen bags (i.e., secondary containers) that have a separate sealable pocket for the specimen (i.e., a plastic biohazard specimen bag), with the patient’s label on the specimen container (i.e., the primary container), and a clearly written laboratory request form;
  • Deliver all specimens by hand whenever possible. DO NOT use pneumatic-tube systems to transport specimens;
  • Document clearly each patient’s full name, date of birth and suspected nCoV of potential concern on the laboratory request form. Notify the laboratory as soon as possible that the specimen is being transported.

GUIDANCE ON SAMPLE COLLECTION

The WHO has also released an interim guidance on sample collection for testing: The WHO has also mentioned that serum and whole blood samples may be used for testing once serological assays become available.

Given below is a table with the relevant details. The full WHO document is available

Specimen type Collection materials Transportation Storage till testing Comment
Nasopharyngeal and oropharyngeal swab Dacron or polyester flocked swabs in viral transport medium 4 °C ≤5 days: 4 °C >5 days: -70 °C The nasopharyngeal and oropharyngeal swabs should be placed in the same tube to increase the viral load.
Bronchoalveolar lavage sterile container 4 °C ≤48 hours: 4 °C >48 hours: –70 °C There may be some dilution of pathogen, but still a worthwhile specimen
(Endo)tracheal aspirate, nasopharyngeal aspirate or nasal wash sterile container 4 °C ≤48 hours: 4 °C >48 hours: –70 °C
Sputum sterile container 4 °C ≤48 hours: 4 °C >48 hours: –70 °C Ensure the material is from the lower respiratory tract
Tissue from biopsy or autopsy including from lung sterile container with saline 4 °C ≤24 hours: 4 °C >24 hours: –70 °C

TESTING AND DIAGNOSIS

Laboratory confirmation of a 2019-nCoV infection is at present possible at a few reference laboratories and higher-level institutions worldwide (eg: ICMR-NIV, Pune in India).

The only testing methodologies available at present are RT-PCR and viral culture (viral culture requires a biosafety level of BSL3). No commercial RT-PCR kits are available at the time of writing this article. No immunoassays have been developed as of yet.

TREATMENT GUIDELINES

There is no specific treatment or vaccines for the nCoV, however R&D efforts are ongoing. In the meantime, the WHO has released a 10-page interim guidance document on how to manage severe acute respiratory infection when novel coronavirus (2019-nCoV) infection is suspected. This document is available at:

https://www.who.int/publications-detail/clinical-management-of-severe-acute-respiratory-infection-when-novel-coronavirus-(ncov)-infection-is-suspected

References:

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  2. Update: Severe Respiratory Illness Associated with Middle East Respiratory Syndrome Coronavirus (MERS-CoV) — Worldwide, 2012–2013 [Internet]. [cited 2020 Jan 28]. Available from: https://www.cdc.gov/mmwr/preview/mmwrhtml/mm6223a6.htm
  3. 2015 MERS outbreak in Republic of Korea [Internet]. [cited 2020 Jan 28]. Available from: https://www.who.int/westernpacific/emergencies/2015-mers-outbreak
  4. Novel Coronavirus [Internet]. [cited 2020 Jan 28]. Available from: https://www.who.int/westernpacific/emergencies/novel-coronavirus
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  6. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. The Lancet. 2020 Jan;S0140673620301835.
  7. Chen Y, Liu Q, Guo D. Coronaviruses: genome structure, replication, and pathogenesis. J Med Virol. 2020 Jan 22;jmv.25681.
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  11. Clinical Criteria: Evaluating 2019-nCoV PUIs | CDC [Internet]. 2020 [cited 2020 Jan 28]. Available from: https://www.cdc.gov/coronavirus/2019-ncov/clinical-criteria.html
  12. Infection prevention and control during health care when novel coronavirus (nCoV) infection is suspected [Internet]. [cited 2020 Jan 28]. Available from: https://www.who.int/publications-detail/infection-prevention-and-control-during-health-care-when-novel-coronavirus-(ncov)-infection-is-suspected-20200125
  13. Laboratory testing for 2019 novel coronavirus (2019-nCoV) in suspected human cases [Internet]. [cited 2020 Jan 28]. Available from: https://www.who.int/publications-detail/laboratory-testing-for-2019-novel-coronavirus-in-suspected-human-cases-20200117
  14. Disease commodity package – Novel Coronavirus (nCoV) [Internet]. [cited 2020 Jan 29]. Available from: https://www.who.int/publications-detail/disease-commodity-package—novel-coronavirus-(ncov)
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