UPDATE MANAGEMENT OF MERS-COV INFECTION - MUNA AL-MASLAMANI, MBBS, CABM, MSC HCM-RCSI - HAMAD MEDICAL CORPORATION
←
→
Page content transcription
If your browser does not render page correctly, please read the page content below
Update Management of
MERS-CoV Infection
Muna Al-Maslamani, MBBS, CABM, MSc HCM-RCSI.
Medical Director-CDC
Senior Consultant Infectious Disease, HGH-HMC.
Director of Infectious Disease Fellowship Training
Program , ACGME-I.
Assistant Professor of WCMC-Q
MEF-23/03/2019
DECLARATION OF CONFLICT OF
INTEREST OR RELATIONSHIP
I have no conflicts of interest to disclose
with regard to the subject matter of this
presentation
Treatment of MERS-CoV Infection • This novel coronavirus, initially termed human coronavirus-EMC (for Erasmus Medical Center), has been named Middle East respiratory syndrome coronavirus (MERS-CoV). ¹ • As with other coronaviruses, no antiviral agents are recommended for the treatment of MERS-CoV infection.² 1. De groot RJ, etal. J.Virol 2013;87.7790 2. Arabi YM, etal. MERS. N Engl J Med 2017;376;584.
Cell Culture & Animal Experiments
When used in combination at lower concentrations, IFN-alpha-2b
and ribavirin resulted in a comparable reduction in viral replication
as high concentrations of either agent alone.
• Combination therapy
with interferon (IFN)-
alpha-2b & ribavirin
appears promising.
• High concentrations of
IFN-alpha-2b or
ribavirin were required
to inhibit viral
Falzarano D, etal. Sci Rep 2013; 3: 1686.
replication.
Cell Culture
Animal & Animal
Experiments
Experiments
• In a study of rhesus macaques, two
groups of three monkeys were
inoculated with MERS-CoV through
a combination of intratracheal,
intranasal, oral, and ocular routes.
• One group was treated with
subcutaneous IFN-alpha-2b plus IM
ribavirin beginning 8 hours after
inoculation, and the other group
was not treated.
Falzarano D, etal. Nat Med 2013; 19:1313.
Animal Experiments
Cell Culture & Animal
Experiments
• Treated animals :
• Did not develop breathing
abnormalities and showed no
or very mild radiographic
evidence of pneumonia.
• Had lower concentrations of
serum &
• lung proinflammatory markers.
• Fewer viral genome copies, &
fewer severe histopathologic
changes in the lungs.
Falzarano D, etal. Nat Med 2013; 19:1313.
Animal Experiments
Cell Culture & Animal
Experiments
The lopinavir/ritonavir-treated and interferon-β1b-treated
animals had better outcome than the untreated animals, with
improved clinical , radiological , pathological, and virological
load.
In contrast MMF all MMF-treated animals developed severe
and/or fatal disease with higher mean viral loads than the
untreated animals.
Chan JF, etal. J Infect Dis 2015;212:1908
• Combination
In patients with severe MERS-CoV infection, therapy
ribavirin and with
interferon
ribavirinimproved
alfa-2a therapy is associated with significantly & IFN-alpha-2a,
survival at
14 days, but not at 28 days. started a median of three
days after
Further assessment in appropriately designed diagnosistrials
randomised (20 is
recommended. patients), was associated with
significantly improved survival
at 14 days, compared with 24
patients who received only
supportive care (70 versus 29
% survival), but not at 28 days
(30 versus 17 % survival, a
nonsignificant difference)
Omrani AS, etal. Lancet Infect Dis 2014; 14:1090.
critically ill patients with multiple comorbidities who are diagnosed late
in the course of their illness may not benefit from combination antiviral
therapy as preclinical data suggest.
Combination therapy with ribavirin plus IFN-alpha-2a, IFN-
alpha-2b, or IFN-beta-1a has not been associated with a
mortality benefit.
There is clearly an urgent need for a novel effective antiviral
therapy for this emerging global threat
Al-Tawfiq JA, etal. Int J Infect Dis 2014; 20:42
Shaloub S, etal. J Antimicrobial chemother 2015; 70:2129.
Other Experimental Therapies
1. Convalescent plasma
2. Neutralizing monoclonal • A placebo-controlled trial of
antibodies oral lopinavir/ritonavir and
3. A polyclonal hyper-immune subcutaneous interferon-beta
is in progress in Saudi Arabia
antibody produced from
trans-chromosomic cattle
4. An inhibitor of the main viral
protease, entry/fusion
inhibitors targeting the MERS-
CoV spike protein &
5. A prodrug of a nucleotide
analogVaccine Development
• No licensed MERS-CoV
vaccine for use in humans,
although several
experimental candidate
MERS-CoV vaccines are being
developed .
• Vaccine based on the major
surface spike protein using
recombinant nanoparticle
technology.
Arabi YM, etal. MERS. N Engl J Med 2017;376;584An alternative approach to vaccinating
humans
• Immunizing camels against
MERS-CoV, since camels
are hosts for MERS-CoV
and are likely to be an
important source of MERS-
CoV.
• Protection correlated with
the presence of serum
neutralizing antibodies
against MERS-CoV.
Haagmans BL, etal. Science 2016;351:77Monoclonal Antibodies
There is currently no treatment recommended
• Investigated for
for both
coronavirus infections except for supportive
prophylaxis care
and treatment
as neededof MERS.
• None are licensed for useThank you for your attention
malmaslamani@hamad.qaYou can also read
