Clinical Study to Evaluate the Possible Efficacy and Safety of Antibodies Combination (Casirivimab and Imdevimab) Versus Standard Antiviral Therapy (Remdesivir and Favipravir) as Antiviral Agent Against Corona Virus 2 Infection in Hospitalized COVID-19 Patients
Phase: PHASE4
Conditions: COVID-19
Sponsor: Mansoura University Hospital

                   
         
          
                               
Tanta University
y, 
Pharmac
  
Faculty of
   
 
A Research proposal submitted for partial fulfillment of Master's 
Degree in Pharmacy
 
(Clinical Pharmacy)
 
title
 
Study Protocol
  
 
Clinical Study to Evaluate the Possible Efficacy and Safety of 
Antibodies Combination (Casirivimab and Imdevimab) Versus 
Standard Antiviral Therapy (Remdesivir and Favipravir) as 
Antiviral Agent against Corona Virus 2 Infection in Hospitalized 
COVID-19 Patients
 
 
 
 
Date: 24/01/2023
 
 
Protocol ID: MS.21.11.1737 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
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:
Introduction
 
2 (sever 
-
SARS CoV
caused by 
 
19 is an infectious viral disease
-
COVID
          
that has affected large number of 
corona virus 2) 
-
acute respiratory syndrome
people all over the world with high mortality rate (1). COVID-19 infection has 
been classified(2) as
 
1- Mild Illness: Individuals who have any of the various signs and symptoms 
of COVID-19 (e.g., fever, cough, sore throat, malaise, headache, muscle pain, 
nausea, vomiting, diarrhea, loss of taste and smell) but who do not have 
shortness of breath, dyspnea, or abnormal chest imaging.
 
2-Moderate Illness: Individuals who show evidence of lower respiratory 
disease during clinical assessment or imaging and who have an oxygen 
saturation (SpO2) ≥94% on room air at sea level.
 
3-Severe Illness: Individuals who have SpO2 <94% on room air at sea level, 
 
a ratio of arterial partial pressure of oxygen to fraction of inspired oxygen 
(PaO2/FiO2) <300 mm Hg, respiratory frequency >30 breaths/min, or lung 
infiltrates >50%.
 
4-Critical Illness: Individuals who have respiratory failure, septic shock, 
and/or multiple organ dysfunctions.
 
          Covid-19 pandemic stimulates research works to find a solution to this 
crisis from starting 2020 year up to now. With ending of 2021 year, various 
advances in pharmacotherapy against COVID-19 have emerged (3).
 
 
           Regarding antiviral drugs used in treatment of COVID-19, remdesivir 
has approved by Food and drug administration (FDA)(4). Other drugs have 
shown controversial antiviral activity include: favipravir, ivermectin, 
nitazoxanide, hydroxychloroquine, ribavirin (5). 
 
          Recently, with the end of 2020, immunotherapy to target virus antigen 
has developed (6).Figure 1 shows two types of immunotherapy include active 
and passive immunotherapy. Active immunotherapy is to enhance body to 
produce antibodies against virus as by vaccination. Passive immunotherapy 
involves direct administration of prepared antibodies acting specifically 
against virus or administration of product containing antibodies like plasma 
(6). 
 
          In this study, the point of research is antibodies cocktail including 
targets for 
. There are three 
casirivimab and imdevimab)
3051(
-
REGN3048
these antibodies to work as antiviral including:
 
 
prevent the virus attachment and entry
1) antibodies that 
 
2) antibodies that inhibit the virus replication and transcription
 
3) antibodies that hinder various steps of the immune system response
 
Table 1 includes various types of antibodies under investigation for  treatment 
of COVID-19 and their targets(6).
 
 

 
 
 
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REGN3048 and REGN3051 are human monoclonal antibodies (mAb) 
          
on surface of viral particles thereby 
 
spike glycoprotein
the 
targeting 
preventing viral entry into human cells through the angiotensin-converting 
2(ACE2) enzyme receptor (7, 8), and have shown promising antiviral activity 
and need for further investigation to prove their benefit in COVID patients(9).
 
3051 has mentioned that both efficacy 
-
on REGN3048
 
(9)
Previous study
          
19 outpatients 
-
and safety of this antibodies cocktail are proved in COVID
-
COV2), or high (8.0 g of REGN
-
treatment in both low (2.4 g of REGN
as 
COV2) dose when compared to placebo, Efficacy is measured 
 
Virologic Efficacy 
-
1
 
Time-weighted average change from baseline in viral load through day 7 
patient. 
(log10 scale) in 
 
 
2-Clinical Efficacy
 
Percentage of patients with one or more medically attended visits
 
Symptoms offset at day 7
 - 
as
 
Safety is measured
 
Percentage of treated patients who experience infusion related and 
and incidence of any serious and unexpected 
 
hypersensitivity reactions
adverse effect.
 
concluded that efficacy is greater and more 
 
(9)
study
previous 
 
This
          
ped 
obvious in seronegative outpatients (whose immune response is not develo
yet to produce antibodies against virus) and with high baseline viral load 
outpatients. 
 
The U.S. 
 
is available for these new antibodies cocktails.
 
(10)
Now, data
          
Food and Drug Administration (FDA) has allowed an Emergency Use 
Authorization (EUA) for casirivimab and imdevimab combination in the 
treatment and  post-exposure prophylaxis of mild to moderate COVID-19 in 
adults and pediatric outpatients (more than12 years of age and not less than 40 
kg) with positive Polymerase Chain Reaction ( PCR) results of direct SARS-
CoV-2 viral testing, and who are at high risk for progression to severe 
COVID-19 requiring hospitalization or causing death.
 
are still not authorized for use 
 
REGN3048 and REGN3051
In contrast, 
          
in patients(10):
 
-who are hospitalized due to COVID-19, OR
 
-who require oxygen therapy due to COVID-19, OR
 
-who require an increase in baseline oxygen flow rate due to COVID-19 in those 
on chronic oxygen therapy due to underlying non-COVID-19 related 
comorbidity(10).
 
  Now, casirivimab and imdevimab are approved investigational antibodies, 
Serious and unexpected adverse effects can occur that not previously reported 
with their use(10).
 

 
 
 
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          Confirmed adverse effects include hypersensitivity and infusion related 
reactions and the study have showed that there is no difference in safety profile 
between intravenous (I.V) infusion and subcutaneous (S.C) injection. Data about 
use during pregnancy and breastfeeding mother is insufficient yet. Also, Data not 
support any dosage adjustment in hepatic and renal patients (10).
 
 
          This antibody combination follows linear pharmacokinetics after its single 
intravenous doses with half-life of about 25 to 37 days for both antibodies. 
Regarding elimination, this combination is not metabolized by liver cytochrome 
enzymes ,and not excreted by kidneys (10).
 
Limitations of previous study include 
 
of follow up
short duration 
-
1
 
not used much clinical relevant outcomes like mortality rate
-
2
 
Not studied the long term effect of antiviral efficacy in lowering viral load 
 -
3
.
on inflammatory markers
 
4- Study performed on non-hospitalized patients and not included hospitalized 
patients (trial is done only on outpatients and not inpatients)
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
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Fig.1: Immunization approaches against COVID-19(6)
 
 
 
 
 
 
 

 
 
 
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Table 1 shows antibodies candidate against SARS-CoV-2 under 
investigation by pharmaceutical companies(6). 
 
 
Antibody
 
Mechanism
 
Company
 
Stage of 
study/identification 
method
 
VIR-
7831/VIR-
7832
 
-Neutralize highly 
conserved epitope in s 
protein
 
-Induce NK-mediated 
antibody-dependent cell 
cytotoxicity
 
VIR 
biotechnology 
and GSK
 
Designed based on S309 
(isolated from SARS-Cov 
patients)
 
SAB
 
Anti SARS-CoV-2 fully 
human poly clonal 
antibodies
 
SAB 
Biotherapeutics
 
-Antibodies produced in 
genetically engineered cattle 
will enter clinical trial by 
early summer
 
-SAB-301 against MERS 
passes phase 1 of clinical 
trial and entered phase II/III
–
 
Target multiple viral S 
epitope
 
ImmunoPrecise
 
Using B cell Select® and 
Deep Display® technology
 
COVID-HIG 
and COVID-
Hyperimmune polyclonal 
antibody derived from 
Emergent 
BioSolutions
 
Enter clinical trial within 4–
5 months
 

 
 
 
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EIG
 
human plasma or 
immunized horse
 
Rcig
 
Recombinant anti SARS-
CoV-2 hyperimmune 
gammaglobulin, polyclonal 
antibodies
 
GigaGen
 
Preclinical stage
-
 
-Aimed for COVID19 
hospitalized patients and 
prophylaxis in high risk 
individuals
 
 
 
 
Antibody 
cocktail 
including 
REGN3048-
3051
 
Fully human multivalent 
antibodies against the 
spike protein isolated from 
genetically modified mice 
or recovered COVID-19 
patients
 
Regeneron
 
-Phase 1 clinical trial for 
Middle East Respiratory 
Syndrome (MERS) 
completed last year
 
-Clinical trial for SARS-CoV-2 
starts by early summer
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
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:
Aim of the study
 
 
1-To evaluate the efficacy of antibodies cocktail (casirivimab and imdevimab) 
compared to standard antiviral therapy in reducing 28-day mortality in hospitalized 
patients with moderate, severe or critical COVID19 
2-To evaluate safety of antibodies cocktail (casirivimab and imdevimab) compared to 
standard antiviral therapy by monitoring of hypersensitivity and infusion related 
reactions or other significant adverse effects  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
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:
Population
 
 
19 PCR confirmed patients with indication for 
-
COVID
 
265
          
          
and will be randomized (2:1:1) into 3 
 
therapy is included in this study
antiviral 
groups
 
cocktail (casirivimab and 
 
Antibodies
(
3051
-
REGN3048
 
Group A:
 -
1
) 
imdevimab) 
 
group B: Remdesivir
-
2
 
group C: Favipravir
-
3
 
-
zed in isolation hospital
Population in this study are patients hospitali
         
Mansoura university.
 
A computer file containing a written informed consent from included 
          
patients will be provided. Paper will not be a tool for providing agreement by 
infection.
 
patients or their relatives to avoid transmission of
 
 
Inclusion criteria
 
:
all this characteristics to be included
 
fulfill
Patient should 
 
.
years old
 2
age more than 1
-
1
 
weight not less than 40 kg.
-
2
 
 .
19 disease as defined by WHO
-
Moderate, sever or critical COVID
-
3
 
.
before inclusion
 
Positive
confirmed patients to be 
 -
CR
P
-
4
 
Exclusion criteria
 
 
 
Patient should not have any of the following to be included:
 
history of hypersensitivity or infusion related reactions after administration 
-
1
.
of monoclonal antibodies
 
.
y (remedsvir or favipravir)
prior use of standard antiviral therap
-
2
 
antiviral therapy (hydroxychloroquine, 
 
controversial
Current use of 
-
3
ivermectin, nitazoxanide, oseltemavir, acyclovir, ribavirine, lopinvir/rotinvir, 
.
sofosfbuvir, decltasevir, semipirvir, azithromycin)
 
.
die within 48 hours
patients expected to 
-
4
 
 
 
 
 
 
 

 
 
 
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:s
Intervention
 
 
with 1:2:2 
groups 
 3
into 
 
assigned
Population included in this study will be 
          
to receive either antibodies cocktail or standard antiviral therapy (remdesvir, 
 
ratios
.3 
&
 2 s
figure
favipravir) as shown in table2 and 
 
 
cocktail 
 
Antibodies
(
3051
-
REGN3048
Group A patients will receive 
         
dose regimen 1.2 gm (1200 mg of combined 
-
) in low
(casirivimab and imdevimab) 
antibodies) diluted in 250 ml 0.9% sodium chloride solution  as single I.V infusion 
.
minutes
 
60
-
over 30
 
 
        Group B patients will receive Remdesivir :
 
0.9% sodium 
Day1 (loading dose): 200 mg (two 100mg vials) diluted in 500ml 
infused I.V over 60 minutes
 
chloride solution
 
0.9% 
l 
dose): 100 mg (one 100mg vial) in 250 m
maintenance 
10 (
-
5 or Day 2
-
Day 2
 
infused I.V over 30 minutes 
 
sodium chloride solution
 
 
        Group C patients will receive Favipravir :
 
Day 1 (loading dose): 1600 mg (8 tablets) or 1800 mg (9 tablets) orally or in Ryle 
tube / 12 hours 
 
Day 2-5 or day 2-10 (maintenance dose): 600 mg (3 tablets) or 800 mg (4 tablets) 
orally or in Ryle tube / 12 hours
 
 
         Patients will be received standard of care by Physicians, Clinical pharmacist , 
Nurses and as guided by Egyptian COVID-19 treatment protocol.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
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Table 2 : The three intervention groups of the study
 
 
 
 Figure 2: Assignment of the included COVID cases at their groups.
 
 Figure 3: Frequency of interventions in included patients 
265 eligible 
patients
 
Antibodies 
cocktail
 
53
 
Remdesvir
 
106
 
Favipravir
 
106
 
Frequency 
Percent 
Valid Percent 
Cumulative Percent 
Valid 
A 
53 
20.0 
20.0 
20.0 
B 
106 
40.0 
40.0 
60.0 
C 
106 
40.0 
40.0 
100.0 
Total 
265 
100.0 
100.0 

 
 
 
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:
Method
 
 
RCT and is considered a Phase IV 
-
non
blind 
 
single
The type of this study is 
          
marketing study) to report efficacy and safety of new medicine.
-
Clinical trial (post
 
 
We use PubMed search tool to find clinical studies that performed to test 
          
19 with 
-
efficacy and safety of developed immunotherapy in treatment of COVID
results with focusing on antibodies developed as antiviral against 
 
4,000
about 
COVID-19 obtaining only 70 results from which REGN-COV2, a Neutralizing 
Antibody Cocktail is selected with its only one clinical study up to now (REGN-
COV2, a Neutralizing Antibody Cocktail, in Outpatients with Covid-19) which is 
published in New England Journal of Medicine on January 21, 2021.
 
 
          Another resource used to obtain data is Fact Sheet for Health Care Providers- 
EUA OF casirivimab and imdevimab which provides clinical data about the use of 
this antibodies cocktail. Endnote citation software is used for citation of references. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
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Outcomes:
 
 
0(baseline), day 
 
Parameters that will be assessed during hospitalization at day
          
include: 
 
3, 7, 14, 28
 
reactive protein (CRP)
-
C
 -
 
ferritin
 -
 
dehydrogenase (LDH) 
 
lactate
 -
 
dimer
-
D
 -
 
CrCl)
(
and estimated creatinine clearance
 
S.Cr)
(
serum creatinine
 -
 
albumin, 
, 
ALT), aspartate aminotransferase (AST)
) (
alanine aminotransferase
 -
  
bilirubin
 
Clinical outcomes measured before & during intervention
 
outcomes
 
Primary
1) 
 
). 
efficacy
rate (
days mortality 
-
28
 -
1
 
). 
efficacy
visit (
PCR test results at end of hospital 
-
2
 
rsensitivity 
precentage of patients who developed infusion related or hype
-
3
and reporting of any 
 
reactions during and after the end of drug infusion
Serious and unexpected adverse events may occur that have not been 
that may cause drug 
 
COV use
-
previously reported with REGEN
.)
Safety
( 
discontinuation
 
mes
2) Secondary outco
 
 .
Need for invasive mechanical ventilation
-
1
 
.
Invasive mechanical ventilation and oxygen support duration (days)
 -
2
 
Time to clinical improvement (defined as 2 points reduction in the WHO 
 -
3
or discharge, whatever happens 
 
(11&12)
disease ordinal progression scale
first)
 
ICU and hospitalization length of stay (days).
 -
4
 
on day 0,3,7,14, and 28.
 
(13)
SOFA score
 -
5
 
.
28
0 to day 
 
day
 
from
 
(11&12)
COVID19 WHO disease progression score
 -
6
 
LDH
ferritin, 
 ,
CRP
Inflammatory markers including 
 -
7
 
liver and kidney functions
 -
8
 
          In addition to clinical outcomes measured before and during intervention, Vital 
signs, glasgow coma score (GCS),complete blood count (CBC), artieral blood gas 
(ABG) and prothrombin time (PT) is recorded at day0.
 
          Patients' charactrestics(age,gender) and relevant medical and medication history 
and current COVID-19 treatment drugs will be recorded on admission 
 
 
Duration of research will be about 6 months from Novmber 2021 to March 2022
 
 
 
 
 
 

 
 
 
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:
Statistical Analysis Plan (SAP)
 
 
        Intention-to-treat strategy will be used in this study. Intention-to-treat strategy 
will be used in this study. Statistical analysis will be achieved with SPSS, version 26.
 
 
          Categorical variables will be presented as proportion and percent. Continuous 
variables will be presented as mean (standard deviation) for parametric data or as a 
median (25th-75th percentile) for non-parametric data.
 
  
         Regarding baseline characteristics, Kruskal-Wallis or ANOVA test (depending 
on type of data and the continous data distrubation (normal or not)) will be used to 
compare these characteristics between the study groups. We will report the P-value 
for our statistical tests with level of statistical significance will be P-value ≤ 0.05.
 
 
        In case of existiing differences in some basline characteristics, logestic 
regression will be performed.  This allows studying the effect of these variables on the 
primary outcomes of the study  to exclude the effect of these confounding vaiables 
and to ensure the effect on the outcomes is due to interventions.
 
 
          Regarding the outcomes, we will compare the 28-day all-cause mortality rate, 
result of PCR test at hospital discharge and incidence of infusion related or 
hypersensitivity reactions during and after the end of drug infusion (primary outcome) 
using the Kruskal-Wallis test with reporting the P-value.
 
 
        While the secondary outcomes (hospital stay duration, icu stay duration and 
others) are compared using Kruskal-Wallis or ANOVA test depending on type of data 
and the distrubation of data (normal or not)
 
          
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
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Sample Size: 
 
          A total sample sizes of 246  patients would achieve at least 80 % power to 
detect a risk difference of 0.2 (20%) in the 28-day all-cause mortality (primary 
outcome) with a significance level (α) of 0.05 and 95% confidence level using the 
 ANOVA or Kruskal-Wallis test of independent proportion in G*Power software. 
To compensate for the estimated loss-to-follow-up and increase the study power, 
we will increase the sample size in both remdesivir and favipravir groups to be 
106 patients compared to 53 patients in Antibodies cocktail Group As Antibodies 
cocktail product is available for only about 50 COVID-19 patients. In addition,the 
ratio (1:2:2) is the clostest to reality according to number of patients who recieve 
each drug. 
 
 
         The mortality data was estimated from the average mortality in Augest, 
Septmper, and Octobar 2021 at the Mansoura University Isolation Hospital among all 
hospitalized patients. Mortality rate is found to be about 360 cases in these 3 months  
 
(120 cases / month). The online system has been used to obtain mortality rate in these 
three monthes.
 
  
         The current admission rate at the Mansoura University – Isolation Hospital is 
250 cases per month on average; our needed sample is about 250 cases.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
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:
Ethical approval
 
 
         Ethical approval will be taken from the Research Ethics Committes of 
Mansoura and Tanta Unversity. Informed consents will be obtained from all 
participants in this research.Privacy of participants and confidentially of data will be 
maintined.Benefits of the intervention to the patients outweigh expected risks .Any 
unexpected risk appered during the course of the research will be cleared to 
participants and the ethical committee on time.All study procedures will obey the 
standard of the Declaration of Helsinki (1964) principles.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
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Data Quality and Safety:
 
 
  
We will collect the data directly into an electronic CRF , no papers are used to collect 
clinical data to avoid transmission of infection from area of isolation.
 
Patient confidentiality will be kept before, during and after the study
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
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: 
and funding
 
Study results
 
ment of 
ublish
P
 
 
          We would register protocol and results in Clinicaltrial.gov  and aim to publishe 
this study in peer-review journals.
 
 
Funding: 
 
The company of intervention drugs  will not support with additional fund or interests. 
The investigators declare no relevant conflict of interest
 
 
Confilct of interest:
 
 none
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
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IRB, Faculty of medicine, Mansoura university
 
Informed Consent Form (ICF) 
 
 
 
Title of Research
 
 
Clinical Study to Evaluate the Possible Efficacy and Safety of 
Antibodies Combination (Casirivimab and Imdevimab) 
Versus Standard Antiviral Therapy (Remdesivir and 
Favipravir) as Antiviral Agent Against Corona Virus 2 
Infection in Hospitalized COVID-19 Patients
 
 
 
 
Steps of Research
 
1. Divide the cases into 3 groups according to 
antiviral therapy
 
2 - Follow up cases before, during and after taking 
doses of medicine while they are in the hospital and 
after their discharge
 
3 - Collect clinical data on cases to compare them 
statistically and obtain results
 
Duration of Research
 
 
 
   6 months after receiving the approval of the scientific 
committee
 
 
Location
 
Isolation Hospital-Mansoura University
 
 
Benefits of Research
 
1 -to benefit COVID-19 patients by determining the mo
appropriate antiviral treatment according to the case
 
2 - Inform the community of the results of this researc
which may change the protocol of treatment of 
COVID-19 patients
 
Possible side effects
 
Some rare allergy symptoms that may have been 
produced from vein injections. 
 
So cases are followed up while taking the meds.
 
I (who signature below) acknowledge that the researcher has informed me 
that:
 
1-Research does not conflict with the values and ethics of society.
 
2- Emphasizing the confidentiality of the research and my right to leave it 
unaccountable and without affecting medical care
 
The name of the participating patient:
 
Signature of the participating patient:
 
Signature of the principal researcher:
 
Date:
 

 
 
 
20 | P a g e  
  
:
References
 
 
 
1-Okonji EF, Okonji OC, Mukumbang FC, Van Wyk B. Understanding varying 
COVID-19 mortality rates reported in Africa compared to Europe, Americas and 
Asia. Trop Med Int Health. 2021;26(7):716-9.
 
 
 
2-COVID-19 Treatment Guidelines Panel. Coronavirus Disease 2019 
(COVID-19) Treatment Guidelines  [updated September 29, 2021. Available from: 
https://www.covid19treatmentguidelines.nih.gov.
/
 
 
3- Basavarajegowda A,Umakanthan S, Chattu VK, Ranade AV, Das D, Bukelo M. A 
rapid review of recent advances in diagnosis, treatment and vaccination for COVID-
19. AIMS Public Health. 2021;8(1):137-53
.
 
 
 
4-Aleem A, Kothadia JP. Remdesivir.  StatPearls. Treasure Island (FL): 
StatPearls Publishing Copyright © 2021, StatPearls Publishing LLC.; 2021
. 
 
 
5-de Almeida SMV, Santos Soares JC, Dos Santos KL, Alves JEF, Ribeiro 
AG, Jacob Í TT, et al. COVID-19 therapy: What weapons do we bring into battle? 
Bioorg Med Chem. 2020;28(23):115757
.
 
 
 
6-Owji H, Negahdaripour M, Hajighahramani N. Immunotherapeutic 
approaches to curtail COVID-19. Int Immunopharmacol. 2020;88:106924
.
 
 
 
7-Baum A, Fulton BO, Wloga E, Copin R, Pascal KE, Russo V, et al. 
Antibody cocktail to SARS-CoV-2 spike protein prevents rapid mutational escape 
seen with individual antibodies. Science. 2020;369(6506):1014-8
.
 
 
 
8-Hansen J, Baum A, Pascal KE, Russo V, Giordano S, Wloga E, et al. 
Studies in humanized mice and convalescent humans yield a SARS-CoV-2 antibody 
cocktail. Science. 2020;369(6506):1010-4
.
 
 
 
9-Weinreich DM, Sivapalasingam S, Norton T, Ali S, Gao H, Bhore R, et al. 
REGN-COV2, a Neutralizing Antibody Cocktail, in Outpatients with Covid-19. New 
England Journal of Medicine. 2020;384(3):238-51
.
 
 
 
10-FDA. EMERGENCY USE AUTHORIZATION (EUA) OF REGEN-COV 
(casirivimab and imdevimab): Food and Drug Adminsteration (FDA); 2021 [updated 
16/9/2021. first:[FACT SHEET FOR HEALTH CARE PROVIDERS,]. Available 
https://www.fda.gov/media/145611/download
from: 
. 
11-WHO COVID19 disease progression ordinal scale. February 18, 2020.  [Available 
-
action/COVID
-
diseases/key
-
https://www.who.int/blueprint/priority
from: 
synopsis_Final_18022020.pdf
19_Treatment_Trial_Design_Master_Protocol_
 
19: a 
-
Immune interventions in COVID
 
et al.
 
Plaçais, L., Richier, Q., Noël, N.
-
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–
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Mucosal Immunol
 
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https://doi.org/10.1038/s41385
 

 
 
 
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Yang, Zheng MM; Hu, Qinming MM; Huang, Fei MM; Xiong, Shouxin 
-
13
-
The prognostic value of the SOFA score in patients with COVID
 .
Sun, Yi MD
 
MM;
p 
 -
Issue 32 
 -
Volume 100 
 -
19, Medicine: August 13, 2021 
e26900doi:10.1097/MD.0000000000026900