Abdullatif Sami Al Rashed

OVERVIEW ON MIDDLE EAST Medical Intern (King Faisal

University)
RESPIRATORY SYNDROME- Microbiology Rotation
King Fahd Hospital of The
CORONAVIRUS (MERS-COV) University
Al-Khobar, Saudi Arabia
LEARNING OBJECTIVES
Definition.

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 a
novel coronavirus discovered in 2012 and is responsible for acute
respiratory syndrome in humans.
 This novel coronavirus has been identified in several countries
across the Middle East and Europe and Asia, with primary infections
found 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 distinctive
arrangement of spikes (Peplomers) projecting from their
surface.
These projections have the appearance of a solar corona,
which gives the virus its name.
CoVs cause a variety of diseases in mammals, including
respiratory, hepatic, enteric, and neurologic pathologies of
differing severity in species ranging from humans to
domesticated 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 is
divided into four genera based on phylogenetic clustering:
•HCoV-229E
Alphacoronavirus genus •HCoV- NL63

•lineages A, B, C, and D
Betacoronavirus genus

•predominantly comprise avian CoV species, with some CoVs

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

•Pedominantly comprise avian CoV species, with some CoVs

Deltacoronavirus genus found in mammalian species, but none thus far in human
WHAT IS MERS-COV?
Both MERS and SARS are caused by β-CoVs,
But MERS-CoV belongs to lineage C whereas SARS-CoV belongs to
lineage 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 of
the virus.
 2014

Main differences between SARS-CoV and MERS-CoV

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 to
the hospital with severe pneumonia and acute kidney injury and he
was getting worse and no one knew why. The sample showed no
positive results of any of the virus assays routinely used.
 The hospital contacted Dr. Ron Fouchier, at Erasmus Medical
College in Rotterdam, Netherlands. At his lab, A novel coronavirus
(CoV) related to the severe acute respiratory syndrome (SARS) CoV
was 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 adults
with severe pneumonia and acute respiratory distress syndrome,
and some have had acute kidney injury.
2. Many patients have required mechanical ventilation, and some
have required extracorporeal membrane oxygenation. Other
clinical manifestations that have been reported are gastrointestinal
symptoms (anorexia, nausea, vomiting, abdominal pain, diarrhea),
pericarditis, and disseminated intravascular coagulation.
SIGNS AND SYMPTOMS
3. Among 12 critically ill patients, 11 had extrapulmonary
manifestations 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.
 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:

Fever Fever with Cough Shortness Myalgias Hemoptysis

(>38°C) chills or of breath
(83% of (32% of (17% of
rigors
(98 % of patients) (72% of patients) patients)
patients) (87% of patients)
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:

Sore throat Diarrhea Vomiting Abdominal Abnormal

(21 % of (26 % of pain (17% chest
(21 % of
patients) patients) of patients) radiograph
patients)
(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
airspace
bronchovascular
opacities
markings

patchy airspace
infiltrates consolidations
INVESTIGATIONS

Imaging findings at presentation in Saudi patients

with Middle East respiratory syndrome cororavirus
infection
Assiri A, Al-Tawfiq JA, Al-Rabeeah AA, et al. Lancet Infect Dis 2013; 13:752.
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:

Sputum

Endotracheal Aspirate

Bronchoalveolar Lavage (BAL) fluid

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

The CDC recommends the collection of multiple specimens from

different sites, including upper respiratory tract, lower respiratory
tract and serum, at different times after symptom onset.
If initial testing of respiratory specimens is negative in a patient who
is strongly suspected of having MERS-CoV infection, additional
respiratory specimens should be obtained from multiple respiratory
sites.
Possible reasons for false-negative results include that the specimen
was of poor quality, was collected late or very early in the illness, was
not handled and shipped appropriately, or there were technical
problems 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:
An enzyme-linked immunosorbent assay (ELISA) for screening

followed by an indirect immunofluorescence test or microneutralization test for

confirmation.

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

neutralization assay.
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
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