OVERVIEW ON MIDDLE EAST RESPIRATORY SYNDROME-CORONAVIRUS (MERS-COV)

Abdullatif Sami Al RashedMedical Intern (King Faisal University)Microbiology RotationKing Fahd Hospital of The UniversityAl-Khobar, Saudi Arabia

LEARNING OBJECTIVESDefinition.

Epidemiology.

Clinical Manifestations.

Investigations.

Case Definition (MOH & WHO Guidelines).

Management.

Infection Control and Prevention Precaution.

References.

WHAT IS MERS-COV?

Middle East Respiratory Syndrome-Coronavirus (MERS-CoV) is anovel coronavirus discovered in 2012 and is responsible for acuterespiratory syndrome in humans.

This novel coronavirus has been identified in several countriesacross the Middle East and Europe and Asia, with primary infectionsfound in Saudi Arabia, Qatar, Jordan, and The United Arab Emirates(UAE).

WHAT IS MERS-COV?

The members of Coronaviridae are large, enveloped, positive-sense, single-stranded RNA viruses with distinctivearrangement of spikes (Peplomers) projecting from theirsurface.

These projections have the appearance of a solar corona,which gives the virus its name.

CoVs cause a variety of diseases in mammals, includingrespiratory, hepatic, enteric, and neurologic pathologies ofdiffering severity in species ranging from humans todomesticated and companion animals.

MERS-CoV particles as seen by negative stain electron microscopy. Virions contain characteristic club-like

projections emanating from the viral membrane.Image source: Cynthia Goldsmith/Maureen Metcalfe/Azaibi Tamin

https://www.cdc.gov/coronavirus/mers/photos.html

WHAT IS MERS-COV? MERS-CoV is a member of the family Coronaviridae, which isdivided into four genera based on phylogenetic clustering:

•HCoV-229E

•HCoV- NL63 Alphacoronavirus genus

•lineages A, B, C, and D

Betacoronavirus genus

•predominantly comprise avian CoV species, with some CoVs

found in mammalian species, but none thus far in human Gammacoronavirus genus

•Pedominantly comprise avian CoV species, with some CoVs

found in mammalian species, but none thus far in human Deltacoronavirus genus

WHAT IS MERS-COV?

Both MERS and SARS are caused by β-CoVs,

But MERS-CoV belongs to lineage C whereas SARS-CoV belongs tolineage B.

The origin of MERS-CoV is still obscure but is likely to be zoonotic.It is believed that camels and bats are the probable zoonotic origin ofthe virus.

Main differences between SARS-CoV and MERS-CoV

2014

EPIDEMIOLOGY

The First case discovered was In June of 2012 in a man at the Dr.Soliman Fakeeh Hospital in Jeddah, Saudi Arabia. He was admitted tothe hospital with severe pneumonia and acute kidney injury and hewas getting worse and no one knew why. The sample showed nopositive results of any of the virus assays routinely used.

The hospital contacted Dr. Ron Fouchier, at Erasmus MedicalCollege in Rotterdam, Netherlands. At his lab, A novel coronavirus(CoV) related to the severe acute respiratory syndrome (SARS) CoVwas isolated from this patient and shown to be the etiological agent.

Dr.Soliman Fakeeh Hospital (DSFH), Jeddah

EPIDEMIOLOGY

Shortly thereafter, a report appeared of an almost identical virus detected in a patient in Qatar with acute respiratory syndrome and acute kidney injury; the patient had traveled recently to Saudi Arabia.

After that, subsequent cases and clusters of infections have been reported.

Since April 2012, more than 2060 cases of Middle East respiratory syndrome coronavirus (MERS-CoV) infection have been reported.

Confirmed cases of Middle East respiratory syndrome coronavirus 2012 to 2017, as of

10 February 2017

KSA (2017 GIDEON INFORMATICS, INC.)

1,537 cases (640 fatal) of infection by Middle East

Respiratory Syndrome Coronavirus (MERS-CoV) were

reported by Saudi Arabia during 2012 to January 14, 2017.

The male/female ratio among cases was 1.6/1, and both

incidence and case-fatality rates are highest in patients

above age 44 years (2014).

KSA (2017 GIDEON INFORMATICS, INC.)Year Number of Cases Reported (# Fatal)

2012 Five cases (2 fatal).

2013 139 cases (58 fatal) were reported, including foreign travelers who were infected while in Saudi Arabia

2014 683 cases (296 fatal) were reported during January to December 30.

2015 461 cases (195 fatal) were reported to December 31.

2016 141 cases (83 fatal) were reported during January to December 31.

2017 15 cases (8 fatal) were reported during January 1 to 10.

CLINICAL MANIFESTATIONS

INCUBATION PERIOD

Studies of human-to-human MERS-CoV transmission from clusters of MERS patients revealed a median incubation period of 5–7 days, with a range of 2–14 days.

SIGNS AND SYMPTOMS

The clinical presentation of the disease is wide:

1. Most reported cases with MERS-CoV infection have been adultswith severe pneumonia and acute respiratory distress syndrome,and some have had acute kidney injury.

2. Many patients have required mechanical ventilation, and somehave required extracorporeal membrane oxygenation. Otherclinical manifestations that have been reported are gastrointestinalsymptoms (anorexia, nausea, vomiting, abdominal pain, diarrhea),pericarditis, and disseminated intravascular coagulation.

SIGNS AND SYMPTOMS

3. Among 12 critically ill patients, 11 had extrapulmonarymanifestations including shock (in 11) and acute kidney injury (in 7).

4. One immunocompromised patient presented with fever, diarrhea, and abdominal pain but without early respiratory symptoms; pneumonia was identified incidentally on a chest radiograph.

5. Three adults with pneumonia and MERS-CoV infection also developed neurologic symptoms and showed widespread intracranial white matter lesions by magnetic resonance imaging.

SIGNS AND SYMPTOMS

The following clinical findings were observed among 47 patients with MERS-CoV infection in Saudi Arabia:

Fever

(>38°C)

(98 % of

patients)

Fever with

chills or

rigors

(87% of

patients)

Cough

(83% of

patients)

Shortness

of breath

(72% of

patients)

Myalgias

(32% of

patients)

Hemoptysis

(17% of

patients)

Assiri A, Al-Tawfiq JA, Al-Rabeeah AA, et al. 2013. Epidemiological, demographic, and clinical characteristics of 47 cases of Middle East respiratory syndrome coronavirus disease from Saudi Arabia: a descriptive study. Lancet Infect. Dis. 13:752–61

SIGNS AND SYMPTOMS

The following clinical findings were observed among 47 patients with MERS-CoV infection in Saudi Arabia:

Assiri A, Al-Tawfiq JA, Al-Rabeeah AA, et al. 2013. Epidemiological, demographic, and clinical characteristics of 47 cases of Middle East respiratory syndrome coronavirus disease from Saudi Arabia: a descriptive study. Lancet Infect. Dis. 13:752–61

Sore throat

(21 % of

patients)

Diarrhea

(26 % of

patients)

Vomiting

(21 % of

patients)

Abdominal

pain (17%

of patients)

Abnormal

chest

radiograph

(100% of

patients)

INVESTIGATIONS (LABORATORY TESTS)1. CBC: Leukopenia (lymphopenia).

Thrombocytopenia.

Anemia.

2. LFT: Elevated AST.

Elevated ALT.

3. Lactate Dehydrogenase. (elevated)

4. Blood Urea Nitrogen and Creatinine. (Elevated in some reported cases)

INVESTIGATIONS (IMAGING)

Chest Xray and CT Chest findings demonstrated minor to extensive unilateral and bilateral abnormalities including:

Enhanced

bronchovascular

markings

airspace

opacities

patchy

infiltrates

airspace

consolidations

INVESTIGATIONS

Imaging findings at presentation in Saudi patients with Middle East respiratory syndrome cororavirus

infectionAssiri A, Al-Tawfiq JA, Al-Rabeeah AA, et al. Lancet Infect Dis 2013; 13:752.

Illustration used with the permission of Elsevier Inc. All rights reserved.

INVESTIGATIONS (LABORATORY DIAGNOSIS) Lower respiratory tract specimens should be the first priority for collection and real-time reverse-transcriptase polymerase chain reaction (rRT-PCR) testing.

Studies shows that rRT-PCR testing of lower respiratory specimens appears to be more sensitive for detection of Middle East respiratory syndrome coronavirus (MERS-CoV) than testing of upper respiratory tract specimens.

A serum sample (at least 0.2 mL of serum) should be obtained in the first 10 to 12 days after onset of illness for rRT-PCR, and a second serum sample (also at least 0.2 mL of serum) should be collected at least 14 days after onset of illness for antibody detection

INVESTIGATIONS (LABORATORY DIAGNOSIS)Lower respiratory tract specimens such as:

Should be obtained for rRT-PCR testing from all cases of severe disease and from milder cases

when possible.

Sputum

Endotracheal Aspirate

Bronchoalveolar Lavage (BAL) fluid

INVESTIGATIONS (LABORATORY DIAGNOSIS)●Upper respiratory tract specimens should be obtained for rRT-PCR testing and should be either:

1. A combined nasopharyngeal and oropharyngeal swab specimen (two synthetic fiber swabs with plastic shafts, combined in a single collection container) or

2. A 2 to 3 mL nasopharyngeal aspirate.

Obtaining upper respiratory tract specimens is especially important if the patient does not have

signs or symptoms of lower respiratory tract disease or if the collection of lower respiratory tract

specimens is not possible.

INVESTIGATIONS

The CDC recommends the collection of multiple specimens fromdifferent sites, including upper respiratory tract, lower respiratorytract and serum, at different times after symptom onset.

If initial testing of respiratory specimens is negative in a patient whois strongly suspected of having MERS-CoV infection, additionalrespiratory specimens should be obtained from multiple respiratorysites.

Possible reasons for false-negative results include that the specimenwas of poor quality, was collected late or very early in the illness, wasnot handled and shipped appropriately, or there were technicalproblems with the test.

INVESTIGATIONS (SEROLOGY)Several serology assays have been developed for the detection of MERS-CoV antibodies, including immunofluorescence assays and a protein microarray assay.

The CDC has developed a two-stage approach which uses:

Any positive test by a single serologic assay should be confirmed with a

neutralization assay.

followed by an indirect immunofluorescence test or microneutralization test for

confirmation.

An enzyme-linked immunosorbent assay (ELISA) for screening

INVESTIGATIONS (SEROLOGY)

THERE ARE LIMITED DATA ON THE SENSITIVITY AND SPECIFICITY OF ANTIBODY TESTS FOR MERS-COV.

CASE DEFINITION (MOH GUIDELINES)

CASE DEFINITION (WHO GUIDELINES)

PROBABLE CASE – A PROBABLE CASE IS DEFINED BY THE FOLLOWING CRITERIA:1. A febrile acute respiratory illness with clinical, radiographic, or

histopathologic evidence of pulmonary parenchymal disease (eg, pneumonia or acute respiratory distress syndrome) and

2. A direct epidemiologic link with a confirmed MERS-CoV case and

3. Testing for MERS-CoV is unavailable, negative on a single inadequate specimen, or inconclusive

OR

1. A febrile acute respiratory illness with clinical, radiographic, or histopathologic evidence of pulmonary parenchymal disease (eg, pneumonia or acute respiratory distress syndrome) and

2. The person resides in or traveled to the Middle East or countries where MERS-CoV is known to be circulating in dromedary camels or where human infections have recently occurred and

3. Testing for MERS-CoV is inconclusive

PROBABLE CASE – A PROBABLE CASE IS DEFINED BY THE FOLLOWING CRITERIA:OR

1. An acute febrile respiratory illness of any severity and

2. Direct epidemiologic link with a confirmed MERS-CoV case and

3. Testing for MERS-CoV is inconclusive

CONFIRMED CASE

A person with laboratory confirmation of infection with MERS-CoV irrespective of clinical

signs and symptoms

MANAGEMENT

MANAGEMENT

Currently there is no specific approved therapeutic agent available to treat MERS. Supportive care is the mainstay of treatment.

In cell culture and animal experiments, combination therapy with interferon (IFN)-alpha-2b and ribavirin appears promising.

INFECTION CONTROL AND PREVENTION PRECAUTION

INFECTION CONTROL AND PREVENTION PRECAUTION

A. Standard Precautions:

Hand hygiene:

1. HCWs should apply “My 5 moments for hand hygiene”: before touching a patient, before any clean or aseptic procedure, after body fluid exposure, after touching a patient, and after touching a patient’s surroundings, including contaminated items or surfaces.

2. Hand hygiene includes either washing hands with antiseptic soap and water or the use of an alcohol-based waterless hand sanitizer (waterless hands rub).

3. Wash hands with antiseptic soap and water when they are visibly soiled.

4. The use of gloves does not eliminate the need for hand hygiene. Hand hygiene is necessary after taking off gloves and other personal protective equipment (PPE).

INFECTION CONTROL AND PREVENTION PRECAUTION

B. Respiratory precautions:

1. Visual Alerts.

2. Masking and Separation of Persons with Respiratory Symptoms. a) Offer regular (surgical) masks to persons who are coughing. Regular (surgical) masks may be used to contain respiratory secretions (N-95 masks are not necessary for this purpose).

b) When space and chair availability permit, encourage coughing persons to sit at least 1 meter away from others in common waiting areas.

c) Healthcare facilities should ensure the availability of materials for adhering to Respiratory Hygiene/Cough Etiquette in waiting areas for patients and visitors.

d) Provide tissues and no-touch receptacles for used tissue disposal.

e) Provide conveniently located dispensers of alcohol-based hand sanitizer.

f) Where sinks are available, ensure that supplies for hand washing (i.e., antiseptic soap and disposable towels) are consistently available.

INFECTION CONTROL AND PREVENTION PRECAUTION

C. Prevention of overcrowding:

oIn clinical areas is essential to prevent cross infection.

oMany of the outbreaks of MERS has been linked to overcrowding in clinical units especially emergency room and dialysis units

REFERENCES

• Manual of Clinical Microbiology 11th Edition.

• Infectious Diseases of Saudi Arabia - 2017 edition Stephen Berger, MD by GIDEON Informatics.

• Infection Prevention and Control Guidelines for the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Infection 4th Edition January 2017. MOH

• ProMed Mail: Novel coronavirus - Saudi Arabia: human isolate; Archive Number: 20120920.1302733 http://www.promedmail.org/direct.php?id=20120920.1302733 (Accessed on April 22, 2013).

• https://www.uptodate.com

• http://www.who.int

• https://www.cdc.gov/

• Coleman CM, Frieman MB (2013) Emergence of the Middle East Respiratory Syndrome Coronavirus. PLoS Pathog 9(9): e1003595. https://doi.org/10.1371/journal.ppat.1003595

• Fehr, A. R., Channappanavar, R., & Perlman, S. (2017). Middle East respiratory syndrome: emergence of a pathogenic human coronavirus. Annual review of medicine, 68, 387-399.

• Reusken, C. B., Haagmans, B. L., Müller, M. A., Gutierrez, C., Godeke, G. J., Meyer, B., ... & Drexler, J. F. (2013). Middle East respiratory syndrome coronavirus neutralising serum antibodies in dromedary camels: a comparative serological study. The Lancet infectious diseases, 13(10), 859-866.

• Assiri A, Al-Tawfiq JA, Al-Rabeeah AA, et al. (2013). Epidemiological, demographic, and clinical characteristics of 47 cases of Middle East respiratory syndrome coronavirus disease from Saudi Arabia: a descriptive study. Lancet Infect. Dis. 13:752–61

THANK YOU