middle east respiratory virus syndrome

1. Middle East
Respiratory Syndrome
(MERS)
Nashaat S. Hamza, M.D
Hospital Gran-Round
April 22nd2014

2. Objectives
• Where did the virus come from?
• How were patients exposed?
• Are certain people at risk?
• How is it transmitted?
• what is the incubation period?
• For how long will patients be infectious?
• Is there a risk from certain animals or other reservoir?
• HCWs one of the commonest fears is will they become infected
and if so will they infect their loved ones at home
JournalofInfectionandPublicHealth(2013)6,317—318

3. Introduction
• Coronaviruses are a large family of viruses that cause illness in humans & animals.
• It causes illnesses ranging from common cold to SARS
• This novel coronavirus, first detected in April 2012
• It is a new virus that has not been seen in humans before.
• In most cases, it has caused severe disease.
• Death has occurred in 35-50% of cases
• Globally: WHO: a total of 211 laboratory-confirmed cases, of which 88 deaths

4. Coronaviruses are medium-sized, enveloped, positive-stranded RNA viruses
whose name derives from their characteristic crown-like appearance in
electron micrographs

5. Life
Cycle
L. Lu et al. / Microbes and Infection 15 (2013) 625e629

6. Epidemiology

7. Morbidity and Mortality Weekly Report

9. The index case was a patient in Jeddah, who was
hospitalized with pneumonia in June 2012. The
patient developed (ARDS) and AKI and died

10. First case
Initial X-ray and 2
days later

11. Transmission
Reservoir: Remains unclear
Proven person-person transmission

12. Hospital Epidemic
• In April 2013, a cluster of 23 confirmed cases and 11 probable cases of
MERS-CoV was detected in Al-Hasa.
• Almost all cases were directly linked to person-to-person exposure, most
of them in the hemodialysis (9 cases) or ICU (4 cases) in a single
hospital.
• There were only 2 proven cases in healthcare workers, and only 3
family members (all of whom had visited the hospital) were proven
infected despite a survey of over 200 household contacts
• Possible modes of transmission may include droplet and contact
transmission.
• Studies of transmissibility and epidemic potential suggests that MERS-
CoV does not yet have pandemic potential.
Assiri A, N Engl J Med. 2013;369(5):407

13. Assiri A, N Engl J Med. 2013;369(5):407

14. Family Cluster
• A cluster occurred in October and November 2012 in 4 men in one family in
Riyadh, Saudi Arabia, 2 of whom died
• None of the 24 other family members who lived with the infected patients or
124 healthcare workers who had contact with them became ill
Memish ZA, N Engl J Med. 2013;368(26):2487

15. Z.A. Memish et al International Journal of Infectious Diseases xxx (2014) e1–e6

16. International Journal of Infectious Diseases xxx (2014) e1–e6
During a 3 month period, June to August 2013, there were 12 positive MERS-CoV cases
reported from the Hafr Al-Batin KSA (host an annual camel festival).
Detailed epidemiological, clinical and genomic study
The genetic data indicated that at least two of the infected contacts could not have
been directly infected from the index patient and alternate source should be
considered. Camels appear as the likely.

17. Hospital Transmission
Nil with percussions
Emerging Infectious Diseases • www.cdc.gov • Vol. 20, No. 4, April 2014

18. None of HCW got infected

19. No Hajj associated Coronavirus infections in 2013
In KSA or Abroad
Clinical Microbiology and Infection, Volume 20 Number 4, April 2014

20. Reservoir
• MERS-CoV is thought to be of animal origin &
related to several bat coronaviruses.
• It is likely that some infections occur via
intermittent zoonotic transmission or possibly via
an environmental source

21. Case definitions
• A confirmed case: laboratory testing now requires a
positive PCR of two, specific genomic targets or a single
positive target with sequencing of a second.
• CDC’s definition of a probable
Morbidity and Mortality Weekly Report

22. Probable case
• 3 combinations of clinical, epidemiological and laboratory criteria can define a
probable case:
• 1-A person with a febrile acute respiratory illness + clinical, radiological,
(pneumonia or ARDS) AND Testing for MERS-CoV is unavailable or negative on a
single inadequate specimen AND
The patient has a direct epidemiologic-link with a confirmed MERS-CoV case.
• 2-A person with a febrile acute respiratory illness with clinical AND
An inconclusive MERS-CoV laboratory test AND A resident of or traveler to Middle
Eastern countries where MERS-CoV virus is believed to be circulating in the 14 days
before onset of illness.
• 3-A person with an acute febrile respiratory illness of any severity AND
An inconclusive MERS-CoV laboratory test (that is, a positive screening test without
confirmation) AND The patient has a direct epidemiologic-link with a confirmed
MERS-CoV case2.
http://www.who.int/csr/disease/coronavirus_infections/case_definition/en/index.html

23. CLINICAL MANIFESTATIONS
• Incubation period: in one study of 23 individuals, the median
incubation period was 5.2 days (95% CI 1.9-14.7 days).
• In one secondary case that occurred in a patient in France who,
the incubation period was estimated at 9 to 12 days.
• WHO and CDC recommend that an evaluation for MERS-CoV be
considered in individuals with a syndrome of MERS who returned
from travel to the Arabian peninsula or neighboring countries
within the past 14 days

24. Underlying medical conditions
• In a study of 47 patients in Saudi Arabia, 45 (96 %) had
underlying comorbidities
• DM(68 %), HTN (34 %), IHD (28 %), and CKD(49 %)
• One patient was on chronic glucocorticoids.
• In a study of 12 critically ill patients with MERS-CoV infection,
each individual had at least one comorbid condition; the median
number of comorbid conditions was 3 (range 1 to 6)
• The high rate of comorbidities reported must be interpreted with
caution, since DM is very common in KSA,
Assiri A, N Engl J Med. 2013;369(5):407

25. Clinical features
• Most patients have been severely ill with pneumonia
and ARDS, and some have had AKI
• Many patients have required MV and & ECMO.
• Other S/S: GI (anorexia, N/V, abdominal pain,
diarrhea), pericarditis, and DIC.

26. 18 March 2014 Annals of Internal Medicine Volume 160 • Number

29. clinical findings were observed among 47
• ●Fever (>38°C) – 46 patients (98 %)
• ●Cough – 39 patients (83 %)
• ●Shortness of breath – 34 patients (72 %)
• ●Hemoptysis – 8 patients (17 %)
• ●Sore throat – 10 patients (21 %)
• ●Myalgias – 15 patients (32 %)
• ●Diarrhea – 12 patients (26 %)
• ●Vomiting – 10 patients (21 %)
• ●Abdominal pain – 8 patients (17 %)
• ●Abnormal chest x-ray – 47 patients (100 %)
Assiri A, N Engl J Med. 2013;369(5):407

30. Many asymptomatic carriers
• As an example, the Saudi MOH screened >3000 close
contacts of case patients using RT-PCR: nasopharyngeal
swabs and identified seven healthcare workers were
positive
• 2 were asymptomatic and five of whom had mild URI

32. Laboratory abnormalities
• leukopenia (14 %), lymphopenia (34 %), lymphocytosis
(11 %),
• Thrombocytopenia (36 %)
• Elevated AST (15 %), ALT (11 %), LDH (49 %)
• Few had anemia,
• Some patients: progressive renal failure
• DIC
Assiri A, N Engl J Med. 2013;369(5):407

33. SPECIMENS COLLECTION:
RESPIRATORY SPECIMENS
• BAL, tracheal aspirate, pleural fluid :
• Sputum:
• B. Upper respiratory tract:

34. Diagnosis: PCR is the Gold standard
• Three rRT-PCR assays for routine detection of MERS-
CoV have been developed. Currently described tests are
an assay targeting a region upstream of the E protein gene
(upE) and assays targeting the open reading frame 1b
(ORF 1b) and the open reading frame 1a (ORF 1a)
• In some cases, sequencing should be performed for
confirmation.

35. G Lu et al. Nature 000, 1-5 (2013)
The overall structure of MERS-CoV RBD.

37. Presence of other organisms should not
exclude MERS-CoV
• CDC has changed its guidance to indicate that testing for MERS-CoV and
other respiratory pathogens* can be conducted simultaneously and that
positive results for another respiratory pathogen should not necessarily
preclude testing for MERS-CoV.
MMWR / September 27, 2013 / Vol. 62 / No. 38

38. Serology
• The CDC has developed a two-stage approach, 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. There are limited data on the sensitivity and specificity
of antibody tests for MERS-CoV.
• According to the WHO, cases with a positive serologic test in the absence of
PCR testing or sequencing are considered probable cases

39. TREATMENT
• In cell culture and animal experiments, (nterferon (IFN)-alpha-2b and
ribavirin) appears promising
• In a study of rhesus macaques, two groups of three monkeys were inoculated
with the virus; one group was treated with subcutaneous IFN-alpha-2b plus
intramuscular ribavirin beginning eight hours after inoculation and the other
group was not treated
• The treated animals did not develop breathing abnormalities and showed no
or very mild radiographic evidence of pneumonia & lower concentrations of
serum and lung pro-inflammatory markers, fewer viral genome copies, and
fewer severe histopathologic changes in the lungs.
• Combination therapy with IFN-alpha-2b and ribavirin was started a median
of 19 days following admission in five critically ill patients in KSA:None of the
patients responded to therapy and all died of their illness.

40. EXPERIENCE FROM SARS
H. Al-Momattin et al. / International Journal of Infectious Diseases 17 (2013)

41. Ribavirin Didn't improve outcome in SARS

42. Vaccine development
• There is no licensed vaccine for MERS-CoV
• An experimental candidate MERS-CoV vaccine based on the major surface
spike protein using recombinant nanoparticle technology.
• Other candidate vaccines that are being studied include a full-length
infectious cDNA clone of the MERS-CoV

43. Late therapy in
International Journal of Infectious Diseases 20 (2014) 42–46

44. OUTCOME
• As of March 27, 2014, 86 of 206 patients with laboratory-
confirmed MERS-CoV infection (42 percent) have died.
• Because individuals with mild symptoms are less likely to be
evaluated than patients with severe disease, those with MERS-
CoV and mild disease might be underrepresented in published
reports
• The reported case-fatality rate might therefore be an overestimate.
• In a study of 47 patients with MERS-CoV in Saudi Arabia, case-
fatality rates rose with increasing age, from 39 % in < 50 years of
age, to 48 % in those < 60 years of age, to 75 % >60 years or older

45. Travelers evaluation
• Health-care providers in the United States should continue to evaluate
patients for MERSCoV infection if they develop fever and pneumonia or
acute respiratory distress syndrome (ARDS) within 14 days after traveling
from countries in or near the Arabian peninsula. Providers also should
evaluate patients for MERS-CoV infection if they have ARDS or fever and
pneumonia, and have had close contact with a recent traveler from this area
who has fever and acute respiratory illness.
MMWR / September 27, 2013 / Vol. 62 / No. 38

46. Saudi Arabia Ministry of Health has made
special recommendations
• Following groups should postpone their Hajj and Umrah this year 2013:
• People over 65 years old
• Children under 12 years old
• Pregnant women
• People with chronic diseases (such as heart disease, kidney disease, diabetes,
or respiratory disease)
• People with weakened immune systems
• People with cancer or terminal illnesses

47. Duration of isolation precautions for novel
coronavirus (nCoV) infection
• The duration of infectivity for nCoV infection is unknown.
• Also little information is currently available on viral shedding and the
potential for transmission of nCoV.
• While Standard Precautions should continue to be applied always, additional
isolation precautions should be used during the duration of symptomatic
illness and continued for 24 hours after the resolution of symptoms.

48. Thank You