Middle East Respiratory Syndrome-

Coronavirus

MERS-COV

BY Dr. SHAIMAA

MAGDY

ASS. LectureBenha faculty of

MedicineChest Department

What are Corona viruses?

- CORONA derived from latin word ( means crown or halo) due to short spike like projections.

•single-stranded RNA novel species of the genus Betacoronavirus

•Corona viruses cause colds in humans primarily in the winter and early spring season.

• Corona viruses primarily infect the upper respiratory and gastrointestinal tract of mammals and birds.

What are Corona viruses?

• Virus classification:

•Group: group IV ssRNA viruses.

•Order: nidovirales.

•Family: coronaviridae.

•Subfamily: coronavirinae.

•Genus: betacoronavirus.

•Species: MERS-COV

Ist , known as Novel Coronavirus2012.

NOVEL CORONA VIRUS

• NOVEL CORONA VIRUSREPORTED ON 24/9/2012BY DR. ALI MOHAMMADZAKI

• ISOLATED & IDENTIFIEDFROM PATIENT 60 YEARSOLD WITH ACUTEPNEUMONEA & ARF

MERS CoV

• NAMED AS NOVEL CORONA VIRUS OR SAUDI’S SARS LIKE CORONA VIRUS

• - INTERNATIONAL COMMITTEE ON TOXONOMY OF VIRUS NAME IT AS MERS CoV

Natural Reservoir

• In septemper 2012 was speculated that thevirus might have originated in bats.

• Recent work links camels to the virus,

• The possibility exists that African orAustralian bats harbor the virus and transmitit to camels.

• Imported camels from these regions mighthave carried the virus to middle east.

SPECULATION

BAT VIRUSES

INTERMEDIATE HOST

CAMELS & OTHERS

MULTIPLE GEOGRAPHIC SITES (MULTIPLE ZOOTIC EVENTS)

How is Novel Coronavirus transmitted?

• on 13 february 2013, WHO stated that “ the risk of sustained person to person transmission appears to be very low”.

•On 29 May 2013, WHO warned that “MERS-COV” is a threat to the entire world, and stated that there is a potential danger in that it is possible for the virus to mutate into a strain that does transmit from person to person.

•The Center for Disease Control and Prevention (CDC) lists MERS as transmissible from human to human.

Transmission

• All the clusters of cases seen so farhave been transmitted betweenfamily members or in a health caresetting, the WHO said in an update ,

Human-to-human transmissionoccurred in at least some of theseclusters, however, the exact mode oftransmission is unknown.

•That means it's not yet known howhumans transmit the virus. But,experts say, there has been noevidence of cases beyond the clustersinto communities.

In human , the virus has a strongtropism for non ciliated bronchialepithelial cells, it has been shownto effectively evade the innateimmune response and antagonizeinterferon production in thesecells.

This tropism is unique in thatmost respiratory viruses targetciliated cells.

Tropism

Because of the clinical similaritybetween MERS-COV and SARS-COV,it was proposed that they may usethe same cellular receptors , theexopeptidase, angiotensinconverting enzyme 2 (ACE2)

However, it was discovered thatneutralization of ACE-2 receptors byrecombinant antibodies doesn’tprevent MERS-COV infection.

Further research identified Dipeptylpeptidase 4 (DPP4) as a functionalcellular receptor for MERS-COV

Tropism

MERS-CoV incubation period

• Symptoms:• Fever

• Cough

• Chills

• Sore throat

• Myalgia

• Arthralgia followed by dyspnea

• May present with fever and diarrhea

• Followed by ARDS, septic shock, multiorgan failure

The available datasuggest that symptomshave occurred up to 14days after lastexposure.

First Reported MERS-CoV Case 60 year old Saudi man

•Presented on June 13th with 7d h/o fever andcough; recent shortness of breath

•Increasing blood urea nitrogen (BUN) andcreatinine, starting day 3 of admission

•White cell count normal on admission (but92.5% neutrophils) and increased to a peak of23,800 cells per cubic millimeter on day 10with neutrophilia, lymphopenia, andprogressive thrombocytopenia

First Case: Chest Radiographs

Bilateral enhanced pulmonary hilar vascular shadows (more prominent on the left) and accentuated bronchovascular lung markings. Multiple patchy opacities in middle and lower lung fields Opacities more confluent and dense

A: On admission

B: 2 days later

First Case Outcome

•Patient developed acute respiratory distress syndrome (ARDS) and multiorgan dysfunction syndrome

•Died June 24th

•No close contacts with severe illnesses reported

CDC Case Definitions

Patients to be investigated (referred to as “Patient Under Investigation”):

A person with an acute respiratory infection, which may include fever (≥ 38°C , 100.4°F) and cough;

AND

suspicion of pulmonary parenchymal disease (e.g. pneumonia or Acute Respiratory Distress Syndrome (ARDS)) based on clinical or radiological evidence of consolidation;

AND

Travel (within 14 days) to or residence in an area where infection with novel coronavirus has recently been reported or where transmission could have occurred;*

AND

not already explained by any other infection or etiology, including all clinically indicated tests for community-acquired pneumonia according to local management guidelines.

Confirmed Case

•A person with laboratory confirmation of infection with MERS-CoV

Positive PCR for confirmation

Confirmed cases of MERS-CoV and history of travel from the Arabian Peninsula

Numbers Reported up-to-date

• Globally, from September 2012 to date, WHO has been informed of a total of 198laboratory-confirmed cases of infection with MERS-CoV, including 84 deaths

MERS-CoV CLOSE CONTACT definition

• A close contact* is defined as a person who:

• Did not use respiratory protection (N95 or higher level respirator); AND

• Shared the same airspace within 10 feet for at least 5 minutes. Examples of close contact include providing care for the case (e.g., a healthcare worker or family member), or having similar close physical contact; or stayed at the same place (e.g., lived with, visited) as the case during their infectious period.

Complications

• Complications have included severe

1- pneumonia,

2- acute respiratory distress syndrome

(ARDS) with multi-organ failure,

3- renal failure requiring dialysis,

4- coagulopathy and pericarditis

Investigations

• Chest x – ray findings:

• Bilateral patchy infiltrate

• Segmental or lobar opacity

• Pleural effusion

Laboratory testing

• Lower respiratory specimens (sputum, bronchoalveolar lavage, endotracheal) for real time reverse transcription polymerase chain reaction (RT-PCR) testing

• •other specimens, stool, throat swab, serum.

• It is not always possible to identify patientswith MERS-CoV early because some have mildor unusual symptoms. For this reason, it isimportant that health-care workers applystandard precautions consistently with allpatients – regardless of their diagnosis – in allwork practices all the time.

precautions• Patient Isolation: in Airborne Infection

Isolation Room (AIIR)

• Droplet precautions should be added to thestandard precautions (hand wash, gloves,gowns)when providing care to all patientswith symptoms of acute respiratory infection.

• Contact precautions and eye protectionshould be added when caring for probable orconfirmed cases of MERS-CoV infection.Airborne precautions should be applied whenperforming aerosol generating procedures.

Personal Protective Equipment (PPE) for Healthcare personnel

(HCP) • Recommended PPE should be worn by HCP

upon entry into patient rooms or care areas.

•Upon exit from the patient room or care area, PPE should be removed and either:

–Discarded, or

–For re-useable PPE, cleaned and disinfected according to the manufacturer’s reprocessing instructions.

Management:• Oxygen support

• Prevention of complications

• Empiric use of:

Broad spectrum antibiotic

Antiviral (oseltamivir)

Plus or minus antifungal

Lung protective ventilator Strategies for ARDS

Treatment of complication (RENAL FAILURE)

Steroids (no benefits)

Treatment of HCAI

Therapeutics • No vaccines developed as of yet

• No antivirals identified as of yet

FUTURE TREATMENT

INTERFERON ALFA 2a + RIBAVERIN

IF YOU HAVE A DYING PATIENT YOU SHOULD TRY IT AS LAST EFFORT

• Selection criteria:

• To be considered eligible for oral ribavirin andsubcutaneous pegylated interferon therapy, thepatient

• must fulfill ALL the following criteria:

1. Laboratory-confirmed MERS-CoV infection

2. Clinical and radiological evidence of pneumonia

3. The patient requires invasive or non-invasiveventilatory support or showing progressivehypoxemia

4. Approval by one consultants in Adult InfectiousDiseases

following investigations are essential before starting

a. Complete blood count

b. Renal function

c. Liver function

Administration Protocol:

• CrCl‡ > 50ml/min Ribavirin 2000mg po loading dose, followed by

1200mg po q8h for 4 days

then 600mg po q8h for 4-6 days

CrCl 20-50 ml/min

2000mg po loading dose, followed by 600mg po q8h for 4 days then 200mg po q6h for 4-6 day

CrCl <20 ml/min or on dialysis

• 2000mg po loading dose, followed by 200mgpo q6h for 4 days then 200mg po q12h for 4-6 days

• Pegelated interferon alfa 2a 180 mcg subcutaneously once per week (up to 2

weeks)

• CDC does not recommend that travelers change their plans because of MERS. However, the Saudi Arabia Ministry of Health has made special recommendations for travelers to Hajj and Umrah. Because of the risk of MERS, Saudi Arabia recommends that the following groups should postpone their plans for Hajj and Umrah this year:

• 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

• How Can Travelers Protect Themselves?

• Taking these everyday actions can help prevent the spread of germs and protect against colds, flu, and other illnesses:

• Wash your hands often with soap and water. If soap and water are not available, use an alcohol-based hand sanitizer.

• Avoid touching your eyes, nose, and mouth. Germs spread this way.

• Avoid close contact with sick people.

• If you are sick:– Cover your mouth with a tissue when you

cough or sneeze, and throw the tissue in the trash.

– Avoid contact with other people to keep from infecting them.

LAST REMINDER,

NO UNNECESSARY PANIC…

•Widespread transmission hasn't been seen

•Always comply with infection control prevention standards

• Underlying health conditions may make you more susceptible

• No travel warnings have been issued

• There are no treatments and no vaccine

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