This document provides an overview of the 2019 novel coronavirus (2019-nCoV) outbreak that began in Wuhan, China in December 2019. It describes the clinical presentation and management of 2019-nCoV, compares it to other coronaviruses like SARS and MERS, and outlines current WHO guidance on case definitions, investigations and infection control.

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EMERGENCIES
SARI CRITICAL CARE TRAINING
2019-NCOV
CLINICAL UPDATE
V1. 30 January 2020

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EMERGENCIES
Learning objectives
At the end of this lecture, you will be able to:
• Describe clinical presentation of COVID-2019
infection.
• Compare COVID-2019 infection to MERS and SARS,
other coronavirus.
• Provide links to WHO case definition and other
guidance

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EMERGENCIES
Coronaviruses (1/3)
• Large, enveloped, positive-strand RNA viruses
• 4 human (H)CoVs cause 10-30% of URTIs in adults
• SARS-CoV, MERS-CoV & SARS-CO2 can cause
severe human infections

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EMERGENCIES
2019-novel Coronavirus
Electron microscopy:
A nCoV virus particles
B nCoV particles within
human airway epithelial
cells
Na Zhu et al. A Novel Coronavirus from Patients with Pneumonia in
China, 2019. DOI: 10.1056/NEJMoa2001017

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Coronaviruses (2/3)
Key feature of coronaviruses which cause SARI:
• Limited human-human transmission, predominantly
nosocomial (SARS-CoV-2>MERS > SARS).
• Viral replication in the upper and lower respiratory tract.
• Aberrant host immune response (upregulation of pro-
inflammatory cytokines)

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EMERGENCIES
Coronaviruses (3/3)
NAME
ANIMAL
RESERVOIR
BINDING
RECEPTOR
(predominant)
RECEPTOR
LOCATION
(predominant)
NUMBER OF
CASES TO
DATE*
CASE
FATALITY
RATE
SARS-CoV Bats ACE2 Lower resp tract 8098 10%
MERS-CoV Dromedaries DPP4
Lower resp tract
GI tract, kidneys
2494 34%
SARS-CoV-2 ? ACE2 Lower resp tract 79,336 ?
CFR remains unknown as large numbers
of patients remain still in hospital

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EMERGENCIES
Coronavirus comparison
https://www.thelancet.com/action/showPdf?pii=S0140-
6736%2820%2930185-9

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EMERGENCIES
CASE DEFINITION
A. Patients with severe acute respiratory infection (fever, cough, and requiring admission to hospital), AND
with no other aetiology that fully explains the clinical presentation AND at least one of the following:
• a history of travel to or residence in the city of Wuhan, Hubei Province, China in the 14 days prior to
symptom onset,
or
• patient is a health care worker who has been working in an environment where severe acute respiratory
infections of unknown aetiology are being cared for.
B. Patients with any acute respiratory illness AND at least one of the following:
• close contact with a confirmed or probable case of 2019-nCoV in the 14 days prior to illness onset, or
• visiting or working in a live animal market in Wuhan, Hubei Province, China in the 14 days prior to
symptom onset,
or
• worked or attended a health care facility in the 14 days prior to onset of symptoms where patients with
hospital associated 2019-nCov infections have been reported.
https://www.who.int/publications-detail/global-surveillance-
for-human-infection-with-novel-coronavirus-(2019-ncov)

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COVID-2019 - TRANSMISSION
• Cluster of cases of pneumonia reported in Wuhan on 31 Dec
2019, with 1st case symptomatic on 8 Dec
• Initial cases associated with a market in Wuhan, animal
source remains to be identified
• Rapid spread within Wuhan and to many other Chinese
provinces and other countries
• Human-human transmission, but full extent not yet
known
• Nosocomial transmission to HCWs have occurred
• Spread is through droplets and contact

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EMERGENCIES
China CDC Epidemiologic study
• N = 72,314 total
• N = 44, 672 confirmed
• 3,019 HCW infections
The Novel Coronavirus Pneumonia Emergency Response Epidemiology Team.
The Epidemiological Characteristics of an Outbreak of 2019 Novel Coronavirus
Diseases (COVID-19) – China, 2020. China CDC Weekly.

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COVID-2019 - COMORBIDITIES
Any co-morbidity: 46% (50% without data)
• Hypertension 13%
• Diabetes 5%
• Cardiovascular disease 5%
• Chronic respiratory disease 2%
• Malignancy 0.5%
The Novel Coronavirus Pneumonia Emergency Response Epidemiology Team.
The Epidemiological Characteristics of an Outbreak of 2019 Novel Coronavirus
Diseases (COVID-19) – China, 2020. China CDC Weekly.
Confirmed Deaths CFR

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COVID-2019 - CLINICAL FEATURES
• Symptoms at onset*:
• fever (83-98%), dry cough (59-82%),
• fatigue & myalgia (11-44%), sputum production (15-
28%), headache (8%), haemoptysis (5%),
• diarrhoea (3-10%)
• dyspnoea (31-55%)
Huang, C. et al Lancet 2020 China CDC 2020
Wang, D. et al JAMA 2020
Chen, D et al. Lancet 2020

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COVID-2019: newborns and pregnant women
• Small cohort of 9 COVID-2019 pregnant women and 10
neonates.
– All neonates tested negative by throat swab,
– Intrauterine fetal distress in 6 of 10 neonates,
– 4 full term, 6 premature, 1 died.
– Conclusion: no evidence of vertical transmission.

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COVID-2019 - INVESTIGATIONS*
INVESTIGATIONS*:
• Blood: leucopenia (25%), lymphopenia (9-70%),
elevated AST (37%)
• Radiology - CT chest abnormalities in all patients
(bilateral in 98%); typically bilateral lobular & sub
segmental consolidation
Huang, C. et al Lancet 2020
Wang, D. et al JAMA 2020
Chen, D et al. Lancet 2020

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EMERGENCIES
COVID-2019- Radiographic findings
Za Nau et al. A Novel Coronavirus from Patients with
Pneumonia in China, 2019. DOI: 10.1056/NEJMoa2001017.
Courtesy Wuhan State Hospital

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2019-nCoV – Natural history (China CDC)
• Pneumonia (100%)
• ARDS (17-29%)
• Viral RNA detected in blood (15%)
• Acute cardiac injury (7-12%)
• Secondary infection (5-10%)
• 5% admitted to ICU, 4-12% required mechanical ventilation
• 31-68% discharged, 4-15% dead, 17% remain in hospital.
Huang, C. et al Lancet 2020 De Chang, JAMA 2020
Wang, D. et al JAMA 2020
Chen, D et al. Lancet 2020

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2019-nCoV – Natural history (China CDC)
• 81% mild illness:
– no complication
• 14% severe:
– SpO2 < 94%, progressive infiltrates
• 5% critically ill:
– Shock, acute respiratory failure, organ failure needing ICU
Huang, C. et al Lancet 2020 De
Chang, JAMA 2020
Wang, D. et al JAMA 2020
Chen, D et al. Lancet 2020

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COVID-2019 Critical illness
• Single-centre, retrospective study: 170 total patients, 52 ICU
patients:
– 40% chronic disease (co-morbid condition before)
– 71% treated with invasive ventilation
– 67% ARDS, 29% AKI, 23% cardiac injury, 29% liver dysfunction,
35% hyperglycemia
– 31 deaths at 28 days (62%)* Could be higher as patients still on
ventilator when published.

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EMERGENCIES
COVID-2019 –histopathology (post mortem)
• Lung: diffuse alveolar damage
• Liver: microvascular steatosis
• Heart: normal

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2019-nCoV – CLINICAL MANAGEMENT
1. Triage and early recognition
2. Implement immediate strict IPC interventions.
3. Early diagnosis and alert of public health authorities.
4. Supportive and intensive care interventions for SARI and sepsis.
5. Antimicrobials therapy for co-infection (sepsis)
6. Prevention of complications .
7. Quality care and Ethics.
8. Clinical Research

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COVID-2019 Research and innovation
• Therapeutics: prioritization of antivirals to be tested in randomized clinical
trials.
• Master clinical trial protocol: available on website and can be adapted and
submitted to ethical review board, choose national sponsor.
• Clinical characterization: Global COVID-2019 Clinical Data Platform, email
EDCARN@who.int to get log-in credentials, observational cohort studies.
• Other priority topics: High flow oxygen (safety and efficacy); steroids
(safety and efficacy); and COVID-2019 ventilator bundle (QI project)

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2019-nCoV – WHO Website
• https://www.who.int/emergencies/diseases/novel-coronavirus-2019
• https://www.who.int/blueprint/priority-diseases/key-action/novel-
coronavirus/en/
• https://www.who.int/emergencies/diseases/novel-coronavirus-
2019/technical-guidance

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Summary
• In December 2019, a novel coronavirus (2019-nCoV) started
an outbreak of pneumonia in Wuhan, China
• 2019-nCoV is related to SARS-CoV and MERS-CoV.
• Initial origin was probably zoonotic but human-human
transmission is highly likely.
• Number of cases is increasing rapidly, most patients have
mild illness, presenting with fever, cough, fatigue & myalgia.
• Management involves early recognition, strict IPC and
supportive case, oxygen for severe cases.