Role of antiviral in COVID 19 IDSA GUIDELINE CDC GUIDELINE SAUDI MOH GUIDELINE NEW ORAL ANTIVIRAL FOR COVID 19 INVESTIGTIONAL ANTIVIRAL FOR COVID19 LAST UPDATE OF ANTIVIRAL COVID 19

1. Role and efficacy of antiviral
in
COVID-19
BY : DR . Abdulaziz AL Jumman
KKH ( Najran)

2. Objectives
 Clinical trial process.
 Antiviral agents for COVID19 .
 IDSA recommendation for COVID 19
treatment .
 CDC recommendation for COVID 19
treatment .
 SAUDI guidelines for COVID 19 treatment
.

4. Antiviral in
COVID-19
 Favipiravir
 Remdesivir
 Molnupiravir

5. * Is an oral broad-spectrum antiviral that
selectively inhibits RNA-dependent RNA
polymerase (RdRp), which ultimately prevents viral
transcription and replication
* Licensed in Japan and China for treatment of
influenza.
Favipiravir

6. Approved dose :
 1800 mg BID for first day followed by 800
mg BID for7-10 days
CONTRAINDICATIONS:
 pregnancy

7. Global clinical studies of
favipiravir usage in covid 19
• multicenter, open label, randomized, phase 2/3
clinical trial of favipiravir compared with
standard of care in hospitalized patients with
moderate COVID-19 was conducted in Russia.
• Both dosing regimens of favipiravir
demonstrated similar virologic response.

8. Global clinical studies of
favipiravir usage in covid 19
 Viral clearance on Day 5 was achieved in 25/40
(62.5%) patients on in the favipiravir group
compared with 6/20 (30%) patients in the standard
care group.
 Viral clearance on Day 10 was achieved in 37/40
(92.5%) patients taking favipiravir compared with
16/20 (80%) in the standard care group .

9.  The phase 3 PRESECO (PREventing SEvere
COVID-19) study evaluated early treatment in
patients with mild-to-moderate symptoms to
prevent disease progression and hospitalization.
Entrollment was completed in September 2021.[
 The phase 3 PEPCO (Post Exposure Prophylaxis
for COVID-19) study in asymptomatic individuals
with direct exposure (within 72 hours) to an
infected individual is ongoing.

10. ADVERSE EFFECTS
o Hyperuricemia
o Hematopoietic tissues such as
decreased RBC production
o increases in liver function parameters
o Testis toxicity was also noted
o Teratogenic

11. Drug interactions

12. Remdesivir
• was the first drug approved by the FDA for
treating the SARS-CoV-2 virus.
• It is indicated for treatment of COVID-19
disease in hospitalized adults and children
aged 12 years and older who weigh at least
40 kg.

13.  The broad-spectrum antiviral is a
nucleotide analog prodrug.
 Full approval was preceded by the US
FDA issued an EUA (emergency use
authorization) on May 1, 2020 to allow
prescribing of remdesivir for severe
COVID-19 (confirmed or suspected) in
hospitalized adults and children prior to
approval.

14.  Upon approval of remdesivir in adults and
adolescents, the EUA was updated to
maintain the ability for prescribers to treat
pediatric patients weighing 3.5 kg to less
than 40 kg or children younger than 12
years who weigh at least 3.5 kg.

15. Approved dose :
o 200 mg loading dose (IV, within 30 min) followed by 100
mg once daily for 5 to 10 days
CONTRAINDICATIONS
There are no known contraindications at this time, but most
studies have excluded use of remdesivir in the following
situations:
 Allergy to remdesivir.
 Alanine aminotransferase (ALT) and/or aspartate
aminotransferase (AST) greater than 5 times the upper limit of
normal.
 Estimated glomerular filtration rate (eGFR) less than 30 mL/min
or requiring dialysis.
 Pregnancy or breast feeding.

16. Global clinical studies
 Three retrospective real-world studies presented
at the 2021 World Microbe Forum showed
remdesivir-treated hospitalized patients had
significantly lower risk for mortality compared with
matched controls.
 The studies included 98,654 patients and results
are summarized below.

17. Global clinical studies
 Aetion and HealthVerity:
Remdesivir-treated patients (n = 24,856) had a
23% lower mortality risk compared with controls (n
= 24,856), regardless of baseline oxygen
requirement from May 1, 2020 to May 3, 2021.
Patients who received a 5-day regimen also had a
significantly greater likelihood of discharge by day
28.

18.  Premier Healthcare: Assessed mortality in
hospitalized patients who were initiated remdesivir
(n=28,855) within the first 2 days of hospitalization
versus matched patients not receiving remdesivir
(n=16,687) between August and November 2020.
 Patients were matched on baseline level of
oxygenation, hospital, within a 2-month hospital
admission period, and all stayed in the hospital for
a minimum of 3 days after initiating treatment.
 Remdesivir-treated patients had a significantly
lower risk of mortality at Day 14 and Day 28
compared with those not given remdesivir.

19.  SIMPLE-Severe: Compared outcomes in
patients receiving 10-days of remdesivir in
the extension phase of the open-label
SIMPLE-Severe trial.
 Regardless of baseline oxygen
requirements, treatment with remdesivir
results in a 54% lower mortality risk at
Day 28 compared with the control group .

20. Remdesivir use in children
 Remdesivir has been available through
compassionate use to children with severe
COVID-19 since February 2020.
 Data were presented on compassionate use
of remdesivir in children at the virtual COVID-
19 Conference held July 10-11, 2020.
 Results showed most of the 77 children with
severe COVID-19 improved with remdesivir.
 Clinical recovery was observed in 80% of
children on ventilators or ECMO and in 87%
of those not on invasive oxygen support.

21. Remdesivir use in pregnant
women
 Outcomes in the first 86 pregnant women
who were treated with remdesivir (March
21 to June 16, 2020) have been
published.
 Recovery rates were high among women
who received remdesivir (67 while
pregnant and 19 on postpartum days 0-3).
 No new safety signals were observed.

22.  At baseline, 40% of pregnant women (median
gestational age 28 weeks) required invasive
ventilation compared with 95% of postpartum
women (median gestational age at delivery 30
weeks)
 Among pregnant women, 93% of those on
mechanical ventilation were extubated, 93%
recovered, and 90% were discharged.
 Among postpartum women, 89% were extubated,
89% recovered, and 84% were discharged.
 There was 1 maternal death attributed to
underlying disease and no neonatal deaths.

23. ADVERSE EFFECTS
* Elevation in hepatic aminotransferase
levels
* Hematochezia
* Nausea and vomiting

24. Drug interactions
 Coadministration of remdesivir is not
recommended with chloroquine or
hydroxychloroquine.
 Based on in vitro data, chloroquine
demonstrated an antagonistic effect on the
intracellular metabolic activation and antiviral
activity of remdesivir.

25. Remdesivir
Favibravir
Intravenous
Oral
Rout of
administration
Needed
Needed
Loading dose
Nedded
Not neede
LFT monitoring
Not studied
Contraindicated
Pregnancy
expensive
$520/100-mg vial,
totaling $3,120 for a
5-day treatment
course.
Less expensive
Cost

26. Molnupiravir
• is an oral antiviral agent that is a prodrug
of the nucleoside derivative
N4hydroxycytidine.
• It elicits antiviral effects by introducing
copying errors during viral RNA replication
of the SARS-CoV-2 virus.

27.  According to a published preprint of the
Phase II trial results, virus isolation from
evaluable nasopharyngeal swabs
decreased from 43.5% at baseline to
1.9% in the 800 mg molnupiravir group
compared with 16.7% in the placebo
group at Day 3 .
 The trial is concluding the Phase 3 portion
as of late 2021.

28.  Molnupiravir is also being evaluated in a
phase 3 trial for postexposure prophylaxis
for individuals residing in the same
household with someone who tests
positive for SARS-CoV-2 in the phase 3
MOVE-AHEAD trial. [37]
 An EUA for molnupiravir was requested in
October 2021. The FDA’s Antimicrobial
Drugs Advisory Committee is scheduled to
discuss the request November 30, 2021.

29. Background
 Easily distributed oral antivirals are
urgently needed to treat coronavirus
disease-2019 (COVID-19), prevent
progression to severe illness, and block
transmission of severe acute respiratory
syndrome coronavirus 2 .
 the results of a Phase 2 trial evaluating
the safety, tolerability, and antiviral
efficacy of molnupiravir in the treatment of
COVID-19 .

30. Methods
 Eligible participants included outpatients with
confirmed SARS-CoV-2 infection and
symptom onset within 7 days.
 Participants were randomized 1:1 to 200 mg
molnupiravir or placebo, or 3:1 to molnupiravir
(400 or 800 mg) or placebo, twice-daily for 5
days.
 Antiviral activity was assessed as time to
undetectable levels of viral RNA by reverse
transcriptase polymerase chain reaction and
time to elimination of infectious virus isolation
from nasopharyngeal swabs.

31. Results
 Among 202 treated participants, virus isolation was
significantly lower in participants receiving 800 mg
molnupiravir (1.9%) versus placebo (16.7%) at Day 3
.
 At Day 5, virus was not isolated from any participants
receiving 400 or 800 mg molnupiravir, versus 11.1%
of those receiving placebo.
 Time to viral RNA clearance was decreased and a
greater proportion overall achieved clearance in
participants administered 800 mg molnupiravir versus
placebo .
 Molnupiravir was generally well tolerated, with similar
numbers of adverse events across all groups.

32. Conclusions
 Molnupiravir is the first oral, direct-acting
antiviral shown to be highly effective at
reducing nasopharyngeal SARS-CoV-2
infectious virus and viral RNA and has a
favorable safety and tolerability profile.
 https://www.ncbi.nlm.nih.gov/pmc/articles/
PMC8219109/

33. Other Investigational
Antivirals for COVID-19 :
Antiviral Agent Description
Lufotrelvir (PF-
07304814; Pfizer) [48]
IV SARS-CoV2-3CL protease
inhibitor in phase 1 clinical trial
in hospitalized patients as of
March 2021.
Remdesivir inhaled
(Gilead Science) [58]
A phase 1 trial of inhaled
nebulized remdesivir initiated
in late June 2020 to determine
if remdesivir can be used on
an outpatient basis and at
earlier stages of disease.

34.  IDSA recommendation for COVID 19
antiviral treatment .
 CDC recommendation for COVID 19
antiviral treatment .
 SAUDI MOH guidelines for COVID 19
antiviral treatment .

35. Saudi MOH
Recommendation for
favipiravir
 Use with Mild to Moderate cases:
 Symptoms (no O2 requirements/no
evidence of pneumonia but with other
symptoms of covid-19 e.g., fever)

36.  IDSA NO MORE RECOMMENDATION
FOR FAVIPIRAVIR .
 CDC NO MORE RECOMMENDATION
FOR FAVIPIRAVIR .

37. IDSA RECOMMENDATION
TO USE REMDESIVIR
 The guideline panel suggests against
remdesivir for routine treatment of patients
with oxygen saturation >94% and no
supplemental oxygen.
 The guideline panel suggests remdesivir
rather than no remdesivir for treatment of
severe COVID-19 in hospitalized patients with
SpO2 <94% on room air.
 However, the guideline panel suggests
against the routine initiation of remdesivir
among patients on invasive ventilation and/or
ECMO.

38.  Prescribing information in the United
States recommends against use of
remdesivir in patients with estimated
glomerular filtration rate less than 30 mL
per minute.

39.  In Immunocompromised patients who are
unable to control viral replication may still
benefit from remdesivir despite SpO2 that
exceeds 94% on room air or a
requirement for mechanical ventilation.
 Management of immunocompromised
patients with uncontrolled viral replication
is a knowledge gap and additional
research into such populations is needed.

40. CDC RECOMMENDATION
TO USE REMDESIVIR

41. Saudi MOH
Recommendation for
REMDESIVIR
 Use In Severe cases :
 Clinical signs of pneumonia (fever, cough,
dyspnea, fast breathing) and one of the
following:
 - Respiratory rate >30/min (adults);
≥40/min (children < 5 years)
 - Blood oxygen saturation <90% on room
air
 - Severe respiratory distress

42. o Use In Critical cases :
 Symptoms of the following:
 ARDS
 Respiratory failure
 requiring ventilation
 Sepsis
 Septic Shock

43. Conclusions

44. SAUDI MOH
IDSA
CDC
ANTIVIRAL
AGENT
Recommended
for Mild to
Moderate.
Not included
Not included
FAVIPIRAVIR
Recommended
for severe and
critical cases .
Recommended
for Hospitalized
patient with
severe but non-
critical disease
(SpO2 ≤94% on
room air)
Recommended
for hospitalized
patient on
oxygen
requirement .
REMDESIVIR
Not included
Under study
Under study
MOLNUPIRAVIR

45. References
UpToDate
Medscape
CDC
IDSA
INH
SAUDI MOH