Novel Coronavirusspotlight

Dr. Waleed AletrebyICU specialist, King Saud Medical City,

Riyadh, KSA.

The situation is dynamic and subject to new discoveries and changes.

Data are up to 15/May/2013.

Coronaviruses are important human and animal pathogens.

Up to 1/3 of community acquired upper respiratory tract infections in adults.

Play a role in severe respiratory tract infections in both adults and children.

They were first identified in the 1960s, and were named after the crown-like projections on the surface of the virus.

Members of nidovirus family.Replicate using a nested set of mRNAs.Human coronaviruses are classified into 2

genera:oAlpha: HCoV-229E and HCoV-NL63oBeta: HCoV-HKU1, HCoV-OC43, nCoV, and

the SARS coronavirus

Coronaviruses are medium-sized, enveloped, positive-stranded RNA viruses.

Have the largest known viral RNA genomes, with a length of 27 to 32 kb.

The genome encodes four or five structural proteins, S, M, N, HE, and E.

Replication of viral RNA occurs in the host cytoplasm by a unique mechanism in which RNA polymerase binds to a leader sequence and then detaches and reattaches at multiple locations, allowing for the production of a nested set of mRNA molecules

Proteins Function

M (Membrane glycoprotein) Budding, envelope formation

S (Spike glycoprotein) R. binding, cell fusion, as Ag

HE (Hemagglutinin-acetylesterase gp)

Beta, adsorption to host cell

N (Nucleocapsid phosphoprotein) Ribonucleoprotein

E (envelope) Unknown function

The novel coronavirus (nCoV; also abbreviated as HCoV-EMC), has been classified through sequencing as a betacoronavirus.

Closely related to several bat coronaviruses.Dipeptidyl peptidase 4 (DPP4; also known as CD26), which

is present on the surfaces of human non-ciliated bronchial epithelial cells, is a functional receptor for nCoV.

nCoV appears to infect several other human cell lines, including lower (but not upper) respiratory, kidney, intestinal, and liver cells, as well as histiocytes.

nCoV can also infect non-human primate, porcine, bat, and rabbit cell lines

EpidemiologySo far …

On 19 Apr 2012, Jordan: outbreak of pneumonia in the Zarqa Public Hospital’s ICU. 7 nurses, 1 doctor and 1 brother of a nurse were among

the 11 affected. In Nov 2012, testing of stored samples from two died patients of this cluster confirmed novel coronavirus infection

22/Sep/2012: UK: 49 yrs previously healthy Qatari male.Travel history to KSA

23/Nov/2012: 3 cases in KSA, 2 died, 1 survived, 2 are family members1 case in Qatar.

28/Nov/2012: 1 case in KSA, died.

Oct 2012: KSA: A family member of the 2 earlier cases in Nov.

11/Feb/2013: UK: Critically ill male, with travel history to Pakistan and KSA.

Later he died.

13/Feb/2013: UK: Relative of the patient reported 2 days earlier, no travel history, no comorbidities.

Later he died.

16/Feb/2013: UK: Relative of the other 2 UK cases.Mild

21/Feb/2013: KSA: Sporadic case, died.

6/Mar/2013: KSA: Sporadic case, no contact with other reported cases, and no travel history.

Died.

12/Mar/2013: KSA: Sporadic case, no contact with other reported cases, and no travel history.

Died.

23/Mar/2013: KSA: Relative of the patient reported on 12/MarMild, Recovered.

26/Mar/2013: Germany: 73 yrs Male, from Abu-Dhabi hospital.

2/May/2013: KSA: 7 cases, no travel history, no animal contact, not relatives or cluster.

3/May/2013: KSA: 3 cases, same region, 2 are family members, critical condition.

6/May/2013: KSA: 3 cases, 2 died, 1 in critical condition.

8/May/2013: France: immunocompromised, travel history to Dubai.

9/May/2013: KSA: 2 cases, both with comorbidities, both recovered.Same cluster

12/May/2013: France: 1 case, shared a room with the other French case

14/May/2013: KSA: 4 cases, all with comorbidities, 1 died, 1 recovered, 2 in critical condition.

15/May/2013: KSA: 2 cases, a male in critical condition, a female in stable condition.

From September 2012 to 15/May/2013 WHO has been informed of 40 laboratory confirmed cases.

Of whom 20 died.

Summary

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Clinical Features

The incubation period is currently considered to be up to ten days.

Clinical features: Incubation period

The mode of transmission is currently unknown. Coronaviruses typically spread like other respiratory infections such as influenza.

The two clusters in Saudi Arabia and Jordan raise the possibility of limited human-to-human transmission, but could also be explained by exposure to a common source.

It is possible that some infections occur via intermittent zoonotic transmission or an environmental source.

Clinical features: Transmissibility

All patients presented generally as pneumonia with symptoms of fever, cough, shortness of breath and breathing difficulties.

Some cases have had acute kidney injury.Other clinical manifestations that have been

reported (in one patient each) are pericarditis and DIC.

Two cases presented with mild respiratory illness.

Clinical features:Signs and symptoms

Pulmonary parenchymal disease.Evidence of consolidation.Localized infiltrates and increased

interstitial markings.

Clinical features: Radiological

Patient under investigation:

WHO definitions:

Considered for evaluation:

WHO definitions:

Probable case:

WHO definitions:

Confirmed case:

WHO definitions:

Laboratory diagnosis

Testing for the novel coronavirus is undertaken only when there is clinical or epidemiological evidence that nCOV may be the cause in an individual or cluster of patients.

To avoid the inappropriate use of scarce resources, the generation of false positives and the risk of overwhelming the health system by unnecessary activation of hospital-based and public health response teams.

Lab diagnosis

Lab diagnosis: Specimens

Routine confirmation of of nCOV will be based on detection of unique sequences of viral RNA by real-time reverse-transcriptase polymerase chain reaction (RT-PCR) and sequencing.

Laboratories with the appropriate experience and containment facilities, may attempt to isolate the virus in cell culture, not routine.

Lab diagnosis: Test

A number of RT-PCR assays that are specific for nCOV have been developed and published. Currently described tests include:

o Upstream of the E protein gene (upE)

o open reading frame 1b (ORF 1b) geneo open reading frame 1a (ORF 1a) gene. The assay for the upE target is considered highly sensitive, with

the ORF 1a assay considered of equal sensitivity. The ORF 1b assay is considered less sensitive than the ORF 1a

assay but may be more specific. Other target sites on the nCOV genome suitable for sequencing

to aid confirmation: RNA-dependent RNA polymerase (RdRp) and nucleocapsid (N) protein genes.

Lab diagnosis: Assays

Lab diagnosis: Algorithm

Management

As with other CoVs, no antiviral agents are recommended for the treatment of nCoV infection.

The WHO has issued recommendations for the management of severe respiratory infections suspected to be caused by nCoV.

Clinical management

Patient under investigation for nCOV.Severe pneumonia, ARDS.Sepsis, septic shock. Initiate infection prevention and control measures. Collect specimens for laboratory testing.Empiric antimicrobials to treat suspected pathogens including

community acquired pathogens. Conservative fluid management if there is no evidence of shock

Clinical management

Clinical management

Clinical management

Permissive hypercapnia, PEEP, double triggering, deep sedation, prolonged inspiratory time.

Neuromuscular block, prone, recruitment maneuvers.

Clinical management

Clinical management

Thank you…