CENTRAL PHILIPPINE UNIVERSITY

COLLEGE OF MEDICINE
Lopez Jaena St., Jaro, Iloilo City

Middle East Respiratory Syndrome

Coronavirus (MERS-CoV)
A Case Report

In Partial Fulfilment of the

Requirements for the
Department of Preventive Community and Family Medicine 2

By:
Casuncad, Merry Joy
Serafino, Cherry Lou

March 26, 2019

INTRODUCTION

 Middle East respiratory syndrome (MERS) is an acute viral respiratory tract infection caused by the
novel beta coronavirus Middle East respiratory syndrome coronavirus (MERS-CoV). It was first
identified in Saudi Arabia in 2012. Cases have been limited to the Arabian Peninsula and its
surrounding countries, and to travelers from the Middle East or their contacts.

 The virus is a positive-sense, ssRNA of genus betacoronavirus. It was also termed as novel
coronavirus 2012 or simply novel coronavirus, first reported 2012 after genome sequencing of virus
isolated from sputum samples from patients who fell ill during flu outbreak in 2012
PREVALENCE

 The global prevalence of MERS-CoV infection from June 2012 to April 2018 is 2206 people. The
number of cases reported from Saudi Arabia is 1831 (83%) with mortality rate of 787 (35.67%). The
main clinical manifestations are fever, chills, generalized myalgia, cough, shortness of breath,
nausea, vomiting and diarrhea. The age-allied prevalence of MERS-CoV was highest amongst
elderly people with chronic debilitating diseases such as pulmonary diseases, end-stage renal
illness, diabetes mellitus and malignancy.

SOURCE OF THE VIRUS/ AGENT/ ETIOLOGY

 The virus that causes Middle East Respiratory Syndrome (MERS) has been found in bats in Saudi
Arabia, suggesting a potential origin for the disease. Researchers tested samples from bats living
about 7 miles away from the home of the first person known to be infected with MERS in Saudi
Arabia. A virus found in one of the bats was 100 percent identical to the MERS virus seen in people,
the researchers said.

 The researchers noted that bats are known to be reservoirs of other viruses that can infect people,
including rabies and SARS, the severe respiratory illness that sickened more than 8,000 and killed
nearly 800 in Southeast Asia in 2002 and 2003.

PORTAL OF ENTRY

 ANIMALS TO PEOPLE
 Scientific evidence suggests that people are infected through direct or indirect contact with
infected dromedary camels.
 BETWEEN PEOPLE
 MERS-CoV does not pass easily between people unless there is close contact, such as the
provision of clinical care to an infected patient without strict hygiene measures.
Transmission has been identified among family members, patients, and health care
workers.
 Ample evidence that dromedary camels play an important role in transmission in the region
 Virus has been detected in dromedary camels in: Qatar, Saudi Arabia, UAE, Oman and
Egypt
 Antibodies have been found in Human and camel viruses closely related camels in:
  Jordan, Tunisia, Ethiopia, Nigeria, Egypt, Oman, Kenya, Saudi Arabia, Canary
Islands, UAE…
 Occupationally exposed = higher risk of infection
 Risk factors for infection are unclear
 Several studies are being planned/ are ongoing

INCUBATION PERIOD

 The median incubation period for secondary cases associated with limited human-to-human
transmission is approximately 5 days (range 2-14 days).

CONTAGIOUS PERIOD

 The contagious period (the time that a sick animal or human is infectious) for MERS-CoV is not
known but may last as long as virus is being shed.

CASE SCENARIO

A 50 year old diabetic female OFW who worked in Saudi Arabia as a caregiver came home to the
Philippines for a vacation. 5 days after arrival, she developed flulike symptoms, associated with low –
moderate grade fever & chills & accompanied by rhinorrhea, fatigue, and myalgias. Anorexia, nausea,
diarrhea, and abdominal pain were also noted. She subsequently developed shortness of breath and
dyspnea which increased in severity, thus she was immediately rushed to the emergency room.
APPROACH TO DIAGNOSIS
 Signs and Symptoms
 flulike symptoms, associated  Nausea
with low – moderate grade fever  Diarrhea
 Rhinorrhea  Abdominal pain
 fatigue  Shortness of breath
 Myalgias  Dyspnea
 Anorexia

 A person who has both clinical features and an epidemiologic risk should be considered a patient
under investigation (PUI) based on one of the following scenarios:
o Confirmed Case
 A confirmed case is a person with laboratory confirmation of MERS-CoV infection.
o Probable Case
 A probable case is a PUI with absent or inconclusive laboratory results for MERS-
CoV infection who is a close contact of a laboratory-confirmed MERS-CoV case.
 Investigations to order
o FBC
 leukopenia; lymphopenia, thrombocytopenia
o comprehensive metabolic panel
 elevated creatinine; elevated LFTs; elevated lactate dehydrogenase
o pulse oximetry
 low ox ygen saturation (SpO2 <90%)
o Blood cultures
 negative
o real-time reverse transcription polymerase chain reaction (RTPCR)
 positive for MERS-CoV RNA
o chest x-ray
 diffuse bilateral infiltrates; possibly lobar infiltrates or absence of
 infiltrates
SPECIMEN

 The following specimens should be collected in all patients for diagnostic testing:
o Blood cultures: for potential bacterial pathogens that can also cause pneumonia or sepsis
o Lower respiratory tract specimens (e.g., sputum, tracheal aspirates, bronchoalveolar
lavage): for bacterial and viral testing
o Upper respiratory tract specimens (e.g., nasopharyngeal and throat swabs): for molecular
viral testing • Serum: for molecular and serological testing.

SEROLOGY ALGORITHM

DIFFERENTIAL Rule in Rule out Differentiating Signs/Symptoms Differentiating

DIAGNOSIS Tests

Influenza Influenza-like illness Frontal or Lack of travel history to or from RT-PCR:

infection low mod grade retro-orbital the Middle East (or country positive for
fever headache where there is an ongoing influenza A or B
IP. 2 days or 1- Chills Sore throat outbreak) in the preceding 14 viral RNA.
4days length Cough Tachycardia days.
Aerosol Fatigue Red, watery No close contact with a
transmission myalgia eyes symptomatic traveler from the
may occur 1 Nausea sore throat Middle East or a suspected or
day before the abdominal pain vomiting confirmed case of MERS in the
onset of Diarrhea preceding 14 days.
symptoms Severe respiratory Seasonal outbreak during winter.
illness (e.g., Differentiating MERS from
shortness of breath, community-acquired respiratory
difficulty breathing) tract infections is not possible
from signs and symptoms.
Community- Dyspnea Productive Lack of travel history to or from the Blood or sputum
acquired Fatigue cough, often Middle East (or country where there culture, or
is an ongoing outbreak) in the multiplex RT-PCR
pneumonia Fever, sweating with pleuritic testing: positive for
and shaking chills chest pain. preceding 14 days.
causative organism
No close contact with a symptomatic
Nausea (e.g., Streptococcus
traveler from the Middle East or a pneumoniae, Hae
diarrhea Confusion or suspected or confirmed case of mophilus
Shortness of breath changes in MERS in the preceding 14 days. influenzae, Mycopl
mental Differentiating MERS from asma
awareness (in community-acquired respiratory pneumoniae, Chla
adults age 65 tract infections is not possible from mydophila
and older) signs and symptoms. pneumoniae, Mora
xella catarrhalis).
vomitting

Respiratory Fever (typically low- Tachypnea Lack of travel history to or from the RT-PCR:
syncytial virus grade) Cyanosis Middle East (or country where there is an positive for RSV
Retractions ongoing outbreak) in the preceding 14
(RSV) infection Cough days. RNA.
Fever. Wheezing
No close contact with a symptomatic
Rales
Difficulty breathing traveler from the Middle East or a
Sepsis like suspected or confirmed case of MERS in
presentation or the preceding 14 days.
apneic episodes Common cause of lower respiratory tract
(in very young infection in children <1 year of age.
infants) Seasonal outbreak during winter.
Cyanosis Differentiating MERS from community-
acquired respiratory tract infections is
not possible from signs and symptoms.
Avian influenza Influenza-like illness Barking cough Lack of travel history to or from the RT-PCR:
A( low mod grade fever Coryza Middle East (or country where there is an positive for
Chills Stridor ongoing outbreak) in the preceding 14
Avian influenza days. H5N1 viral RNA
A (H5N1) virus Cough Retractions
No close contact with a symptomatic
Fatigue Tachypnea
infection traveler from the Middle East or a
myalgia Irritability suspected or confirmed case of MERS in
Nausea Wheezing the preceding 14 days.
abdominal pain altered mental Close contact with infected birds (e.g.,
Diarrhea status, farmer or visitor to a live market in
Severe respiratory seizures), and endemic areas) or living in an area where
illness (e.g., shortness the involvement avian influenza is endemic.
of breath, difficulty of other organ Differentiating MERS from community-
acquired respiratory tract infections is
breathing) systems.
not possible from signs and symptoms.

Severe acute 100.4°F [>38.0°C]). Lack of travel history to or from the Real-time
respiratory Chills Middle East (or country where there reverse
syndrome SARS headache is an ongoing outbreak) in the transcription
Fatigue preceding 14 days. polymerase
No close contact with a symptomatic
Myalgias chain reaction
traveler from the Middle East or a
After 2 to 7 days, suspected or confirmed case of
(RT-PCR):
SARS patients may MERS in the preceding 14 days. positive for
develop a dry, Patients have lower incidence of SARS
nonproductive comorbidities compared with MERS. coronavirus
cough or feel short Clinical features are similar; (SARS-CoV)
of breath. however, patients are less likely to RNA.
hypoxia present with hemoptysis (1% of
patients with SARS) or dyspnea (42%
of patients with SARS). [8]
Usually less aggressive than MERS as
reflected by the lower mortality rate.
 MERS COV Influenza-like illness Travel history to or from the Real-time
low mod grade fever Middle East (or country where reverse
IP: 5 days Chills there is an ongoing outbreak) in transcription
(range 2-14 Cough the preceding 14 days. polymerase
Fatigue
days) Close contact with a symptomatic chain reaction
myalgia
Nausea
traveler from the Middle East or (RT-PCR):
abdominal pain a suspected or confirmed case of positive for
Diarrhea MERS in the preceding 14 days. MERS COV
Severe respiratory
illness (e.g., shortness
of breath, difficulty
breathing)
DIAGNOSIS: Acute Respiratory Distress Syndrome Probably due to MERS-CoV Infection
PATHOPHYSIOLOGY
 The pathogenesis is not completely understood.
 The virus is transmitted primarily via respiratory droplets from an infected person which enter the
human body via the respiratory tract mucosa.
 The virus binds to the functional receptor dipeptidyl peptidase-4 (DPP4; also called CD26) on the
surface of host cells (e.g., type I and II alveolar cells, ciliated and non-ciliated bronchial epithelium,
endothelium, alveolar macrophages, leukocytes).
 Binding is mediated by a receptor binding domain on the S1 subunit of the virus’ surface spike (S)
proteins.
 Membrane fusion and cell entry is facilitated by the S2 unit through the actions of 2 heptad repeat
domains (HR1 and HR2) and a fusion protein.
 The virus can also bind to DPP4 receptors in several species (e.g., camels, rabbits, sheep, goats,
non-human primates).
 DPP4 is expressed on the epithelial and endothelial cells of most human organs (e.g., kidney, liver,
intestines). T
 This may explain the multisystem clinical spectrum of the infection which includes severe (and
sometimes fatal) pneumonia, acute respiratory distress syndrome, and multi-organ failure.
COMPLICATIONS

 Acute Respiratory Failure

o Reported 25-95% of confirmed cases
o Median time to invasive mechanical ventilation was 7 days in a cohort of 47 patients
o Risk factors include age ≥50 years, diabetes mellitus, end-stage renal disease, and obesity.
 Acute respiratory distress syndrome
o New or worsening respiratory symptoms within one week of presentation. Chest x-ray shows
bilateral opacities.
o High-flow oxygen (up to 50 mL/minute) is recommended in some patients, although mechanical
ventilation and intubation is usually required.
 Acute renal failure
o Initially reported in a few case reports. Has since been reported in 58% of critically ill patients.
o Possibly due to the presence of dipeptidyl peptidase-4 (DPP4) receptors in renal epithelial cells.
o Detection of the virus in urine samples has been previously documented.
 Multi-organ failure
o Occurs in a minority of patients late in the course of illness.
o Underlying mechanism of action is unknown.
o Usually presents with thrombocytopenia, prolonged coagulation profile, and circulatory collapse
o Patients may require vasopressor and inotrope support.
PHARMACOLOGIC TREATMENT

 There is no vaccine available to prevent MERS-CoV infection

 Antimicrobials: empirical antimicrobial therapy (including antibiotics and antivirals) should be
started in inpatients with suspected MERS pneumonia
  Antimicrobial selection should be based on local epidemiology, susceptibility data, and guidelines
until diagnosis is confirmed, and empirical therapy adjusted based on results
 Antipyretics/analgesics: recommended for the control of fever and pain.
 EMERGING
o There is no conclusive evidence at this time to recommend any virus-specific treatments for patients
with suspected or confirmed infection. If investigational agents are used, the World Health
Organization (WHO) recommends that these drugs only be used under standard research treatment
protocols and occur in the context of research trials.
 Interferon alfa
 Interferon beta
 Lopinavir

NON-PHARMACOLOGIC TREATMENT

 Oxygen: patients with signs of severe respiratory distress, shock, or hypoxemia should be started
on oxygen therapy immediately
 Fluids: cautious fluid management is recommended in patients if necessary, provided that there is
no evidence of shock (more aggressive resuscitation may be required in patients with shock)

CONTROL AND PREVENTION

 Good Hygiene practices

 Avoidance of travel to high risk areas
 In case of contact with camel, wash hands and avoid touching eyes, nose and mouth.
 Avoid consumption of meat and unpasteurized milk
 Proper cooking and pasteurization prevents infection
 Persons who are immunocompromised or with DM or chronic lung dse are at high risk and must
avoid contact with sick animals
 Cover your nose and mouth with a tissue when you cough or sneeze, then throw the tissue in the
trash.
 Avoid personal contact, such as kissing, or sharing cups or eating utensils, with sick people.
 Clean and disinfect frequently touched surfaces and objects, such as doorknobs.
 Wash your hands often with soap and water for 20 seconds, and help young children do the same.
If soap and water are not available, use an alcohol-based hand sanitizer.
 One must remember that infected animals with MERS-COV may shed the virus from nasal, eye
discharge, feces, urine and milk
 It may also be found in organs and meat of infected animal.

CONTACT TRACING : WHY IS IT IMPORTANT?

 Those in close contact with someone who has MERS are at higher risk of infection, and of
potentially infecting others if they begin to show symptoms. Closely watching such persons for 14
days from the last day of exposure to a confirmed case will help that person to get care and
treatment and will prevent further transmission of the virus to others. This monitoring process is
called contact tracing, which can be broken down into three basic steps:

 Contact identification: Once a case is confirmed, contacts are identified by asking about the
activities of the case and the activities and roles of the people around the case since onset
of illness. Contacts can be family members or anyone who has been in contact with the
case, for example, people encountered at work, social events or in health care facilities.

 Contact listing: All persons considered to have contact with the confirmed case should be
listed as contacts. Efforts should be made to identify every listed contact and inform them
of their contact status, what it means, the actions that will follow, and the importance of
receiving early care if they develop symptoms. The contact should also be provided with
 information about prevention of the disease. In some cases, quarantine or isolation is
required for high risk contacts, either at home, or in hospital.

 Contact follow-up: Follow-up all listed contacts daily for 14 days from the last time they
were in contact with the confirmed MERS patient for the development of signs and
symptoms and for testing for MERS-CoV.

CASE RESOLUTION

The patient should be admitted and undergone series of tests to rule out other etiology regarding her
presenting signs and symptoms. If negative for the said tests and with based on the history gathered,
patient had a probable Mers-cov infection. Hence, WHO recommends a screening assay to be performed
first to those suspected patients of MERS-Cov and, if positive, a confirmatory assay should be performed.
If the confirmatory assay is positive, infection is confirmed. If the confirmatory assay is negative, consider
repeating the tests (if epidemiological evidence is suggestive of infection) or perform sequencing assays. If
sequencing indicates the presence of MERS-CoV, infection is confirmed

Further more, patient should be given supportive care and monitoring to prevent further complications of
MERS-Cov infection. Contact tracing is also done and immediate screening for MERS-CoV should be done
not just for the families of the said patients but also to those who are in close contact with the patient to
avoid spread our possibly, outbreak.

SUMMARY OF CARE
Patient-Centered Family - Focused Community-oriented to
community based
History and PE Triage Family history and Place of Origin and work
Mode of acquisition and determinants (abroad)
transmission monitoring Confidentiality and disclosure Possible mode of acquisition
Travel history issues (foreign place/person)
Identify case definition Financial issues
category whether suspected
or probable
SARS contact exposure
Diagnostic evaluation, Voluntary Home isolation Tools for family assessment Availability f testing for
screening and confirmatory Telephone contact if: Impact of illness suspects
diff dx Confirmed + for PCR for SARS Isolation issues Identification of SARS referral
in atleast 2 clinical specimens Family financial stability hospital
Nasopharyngeal or stool on 2
or more days during the
course of illness
Serconversion on ELISA or IFA
Neg AB test on acute serum
then + AB test on
convalescent serum
Virus isolation
Isolation of virus plus PCR
confirmation

Plan of management Education Medical conseling Contact tracing

Biomedical: RITM/ San
Lazaro (DOH) hospital
admission foe medical mngt
Psychosocial: medical
counseling
Family education
Reassurance
Undergo initial screening for
MERS-CoV if exposed to a
patient with the illness
Support group
Preventive isolation
Medical gear for protection
from exposure
Availability of treatment hub
In the nearest area
Community and national
impact

REFERENCES  https://www.who.int/
 https://cdc.gov  http://www.annsaudimed.net/
 https://www.ncbi.nlm.nih.gov