Comparing the efficacy of regen-cov, remdesivir, and favipiravir in reducing invasive mechanical ventilation need in hospitalized COVID-19 patients

Table 1 Antibodies candidate against severe acute respiratory syndrome coronavirus 2 under investigation by pharmaceutical companies

Antibody	Mechanism	Company	Stage of study/identification method
Canakinumab (ilaris®)	IL-1β inhibitor	Novartis	In clinical stage for several inflammatory diseases including arthritis, periodic fever and lung cancer; repurposed by novartis for COVID-19
Secukinumab (cosentyx®)	IL-17 inhibitor	Novartis	In clinical stage for several autoimmune diseases including psoriasis; repurpose by novartis for COVID-19
TZLS-501	Fully human monoclonal antibody targeting the receptor of IL-6, it binds to both membrane-bound and soluble forms of IL-6R, and rapidly depletes the circulating levels of IL-6 in blood	Tiziana Life Sciences and Novimmune	Preclinical stage
Pritumumab	Fully human IgG antibody targeting vimentin	Nascent Biotech Inc.	Received FDA approve for several carcinoma; Research began for COVID-19
COVID-HIG and COVID-EIG	Hyperimmune polyclonal antibody derived from human plasma or immunized horse	Emergent BioSolutions	Enter clinical trial within 4-5mo
Rcig	Recombinant anti SARS-CoV-2 hyperimmune gamma globulin, 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 completed last year; clinical trial for SARS-CoV-2 starts by early summer

IL: Interleukin; COVID-19: Coronavirus disease 2019; SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2; IgG: Immunoglobulin G; FDA: Food and Drug Administration.

Table 2 The Significance of differences in baseline characteristics between the three groups

Variables	Intervention
	Casirivimab/Imdevimab (A)	Remdesivir (B)	Favipiravir (C)	P valuea
Age	58.34 ± 16.096	59.30 ± 15.985	65.02 ± 14.261	0.006
B and C				0.07
A and C				0.07
A and B				0.63
Gender				0.03
Male	24/53	42/106	61/106
Female	29/53	64/106	45/106
B and C				0.09
A and C				0.145
A and B				0.501
Number of co-morbidities				0.022
0	10/53	32/106	22/106
1	16/53	27/106	19/106
2	14/53	28/106	33/106
3	11/53	16/106	18/106
4	2/53	2/106	10/106
5	0/53	1/106	3/106
6	0/53	0/106	1/106
B and C				0.06
A and C				0.32
A and B				0.207
Method of diagnosis				1
Symptoms only	0/53	0/106	0/106
Labs and radiology	0/53	0/106	0/106
PCR confirmed	53/53	106/106	106/106
B and C				NA
A and C				NA
A and B				NA
Severity of COVID				0.024
Moderate	18/53	20/106	20/106
Sever	27/53	60/106	53/106
Critical	8/53	26/106	33/106
B and C				0.475
A and C				0.07
A and B				0.035
Number of symptoms				0.001
2	4/53	2/106	2/106
3	13/53	6/106	4/106
4	32/53	97/106	97/106
5	4/53	1/106	3/106
B and C				0.482
A and C				0
A and B				0.003
Antibiotics use				1
Yes	53/53	106/106	106/106
No	0/53	0/106	0/106
B and C				0.102
A and C				0.002
A and B				0.075
Macrolide use				0.007
Yes	8/53	8/106	2/106
No	45/53	98/106	104/106
B and C				0.102
A and C				0.002
A and B				0.075
Fluroquinolones use				0.106
Yes	41/53	92/106	95/106
No	12/53	14/106	11/106
B and C				NA
A and C				NA
A and B				NA
3rd and 4th generation cephalosporin use				0.551
Yes	39/53	86/106	83/106
No	14/53	20/106	23/106
B and C				NA
A and C				NA
A and B				NA
Carbapenems use				0.168
Yes	10/53	32/106	22/106
No	43/53	74/106	84/106
B and C				NA
A and C				NA
A and B				NA
Piperacillin/tazobactam use				1
Yes	0/53	0/106	0/106
No	53/53	106/106	106/106
B and C				NA
A and C				NA
A and B				NA
Amoxicillin/clavulanate use				0.472
Yes	0/53	0/106	0/106
No	53/53	106/106	106/106
B and C				NA
A and C				NA
A and B				NA
Cotrimoxazole use				1
Yes	0/53	0/106	0/106
No	53/53	106/106	106/106
B and C				NA
A and C				NA
A and B				NA
Linezolid use				0.115
Yes	5/53	12/106	4/106
No	48/53	94/106	102/106
B and C				NA
A and C				NA
A and B				NA
Teicoplanin use				0.365
Yes	1/53	0/106	2/106
No	52/53	106/106	104/106
B and C				NA
A and C				NA
A and B				NA
Anticoagulant use				0.411
Yes	49/53	101/106	96/106
No	4/53	5/106	10/106
B and C				NA
A and C				NA
A and B				NA
Dose of anticoagulant				0.088
Prophylactic	39/53	80/106	81/106
Therapeutic	14/53	26/106	25/106
B and C				NA
A and C				NA
A and B				NA
Antiplatelet use				0.012
Yes	5/53	6/106	0
No	48/53	100/106	106/106
B and C				0.039
A and C				0.005
A and B				0.262
Steroids use				0.002
Yes	45/53	105/106	98/106
No	8/53	1/106	8/106
B and C				0.5
A and C				0.068
A and B				0.001
Additive-therapy use				0.104
Yes	51/53	106/106	105/106
No	2/53	0/106	1/106
B and C				NA
A and C				NA
A and B				NA
Paracetamol use				0.019
Yes	50/53	105/106	106/106
No	3/53	1/106	0/106
B and C				0.574
A and C				0.006
A and B				0.022
Zinc use				0.003
Yes	4/53	0/106	1/106
No	49/53	106/106	105/106
B and C				0.614
A and C				0.004
A and B				0.001
Acetyl cysteine use				0.135
Yes	52/53	106/106	106/106
No	1/53	0/106	0/106
B and C				NA
A and C				NA
A and B				NA
Lactoferrin use				0.135
Yes	1/53	0/106	0/106
No	52/53	106/106	106/106
B and C				NA
A and C				NA
A and B				NA
Vitamin C use				0.07
Yes	4/53	7/106	1/106
No	49/53	99/106	105/106
B and C				NA
A and C				NA
A and B				NA
O2 therapy use				0
Yes	37/53	99/106	102/106
No	16/53	7/106	4/106
B and C				0.497
A and C				0
A and B				0
NP use				0.84
Yes	18/53	35/106	39/106
No	35/53	71/106	67/106
B and C				NA
A and C				NA
A and B				NA
SFM use				0.002
Yes	30/53	82/106	87/106
No	23/53	24/106	19/106
B and C				0.428
A and C				0
A and B				0.004
MR use				0.003
Yes	8/53	33/106	14/106
No	45/53	73/106	92/106
B and C				0.001
A and C				0.783
A and B				0.019
HFNC use				0.202
Yes	5/53	22/106	18/106
No	48/53	84/106	88/106
B and C				NA
A and C				NA
A and B				NA
CPAP use				0
Yes	4/53	39/106	36/106
No	49/53	67/106	70/106
B and C				0.635
A and C				0.001
A and B				0
IMV use				0
Yes	1/53	29/106	29/106
No	52/53	77/106	77/106
B and C				1
A and C				0
A and B				0
Vasopressor use				0.002
Yes	0/53	23/106	18/106
No	53/53	83/106	88/106
B and C				1
A and C				0.016
A and B				0.001
Prone positioning				0.75
Yes	0/53	5/106	9/106
No	53/53	101/106	97/106
B and C				NA
A and C				NA
A and B				NA
O2 saturation on O2 therapy	96.26 ± 2.391	95.86 ± 3.795	96.01 ± 3.130	0.942
B and C				NA
A and C				NA
A and B				NA
O2 saturation on RA	92.36 ± 4.816	87.62 ± 7.171	88.35 ± 7.006	0
B and C				0.448
A and C				0
A and B				0
PaO2	77.868 ± 41.79	56.432 ± 35.30	63.294 ± 39.45	0.005
B and C				0.252
A and C				0.2
A and B				0.001
PaCO2	36.689 ± 12.59	37.325 ± 14.60	37.603 ± 12.08	0.891
B and C				NA
A and C				NA
A and B				NA
PaO2/FiO2	233.5057 ± 207	156.7358 ± 171	164.142 ± 138	0.01
B and C				0.136
A and C				0.69
A and B				0.002

^aP < 0.05 is considered a statistically significant difference between the compared groups. (1) Comparing between the three groups (A, B, C); (2) A pairwise comparison between every 2 groups (A-B, B-C, A-C), if there is a statistically significant difference between the three groups as presented by the comparing between the three groups (A, B, C). NA: Not available; NP: Nasal prongs; SPM: Simple face mask; MR: Mask reservoir; RA: Room air; PCR: Polymerase chain reaction; HFNC: High-flow nasal cannula; COVID: Coronavirus disease; CPAP: Continuous airway positive pressure; IMV: Invasive mechanical ventilation.

Table 3 The best regression model for studying effects of confounding variables on need for invasive mechanical ventilation

	Unstandardized coefficients		Standardized coefficients		t-value	P value
	B	Std. Error	Beta	Std. Error
(Constant)	0.806	1.297			0.621	0.535
Age	0.003	0.001	0.098	0.053	1.835	0.068
Gender	0.029	0.044	0.038	0.058	0.652	0.515
No of co-morbidities	-0	0.015	-0.01	0.048	-0.144	0.885
Severity of COVID	-0	0.036	-0.01	0.059	-0.123	0.903
No of symptoms	0.029	0.033	0.049	0.057	0.854	0.394
Macrolide	-0.03	0.083	-0.03	0.074	-0.362	0.718
Fluroquinolones	0.001	0.068	0.001	0.073	0.02	0.984
Cephalosporin	0.046	0.071	0.052	0.081	0.646	0.519
Carbapenems	0.057	0.07	0.065	0.08	0.818	0.415
Amox/calv	-0.19	0.398	-0.02	0.039	-0.479	0.632
Linezolid	-0.01	0.072	-0.01	0.058	-0.097	0.923
Teicoplanin	-0.2	0.316	-0.03	0.044	-0.636	0.526
Other Antibiotics	-0.03	0.105	-0.01	0.043	-0.274	0.784
Anticoagulant	-0.1	0.099	-0.07	0.067	-1.033	0.303
Prophylaxis/therapeutic	-0.01	0.048	-0.02	0.063	-0.298	0.766
Antiplatelet	-0.03	0.083	-0.02	0.06	-0.34	0.734
Steroids	-0.04	0.078	-0.04	0.065	-0.561	0.576
Additive therapy	0.096	0.12	0.041	0.051	0.803	0.423
Paracetamol	-0.05	0.095	-0.02	0.05	-0.475	0.635
Zinc	-0.1	0.084	-0.06	0.049	-1.21	0.228
Acetylcysteine	-0.03	0.176	-0.01	0.052	-0.151	0.88
Lactoferrin	0.312	0.237	0.092	0.07	1.315	0.19
Vitamin C	0.044	0.072	0.031	0.05	0.615	0.539
Nasal prongs use	-0	0.043	-0.01	0.055	-0.083	0.934
FM use	0.04	0.053	0.046	0.06	0.764	0.446
MR use	-0.03	0.05	-0.03	0.054	-0.538	0.591
HFNC use	0.004	0.05	0.003	0.048	0.071	0.944
CPAP	0.003	0.092	0.004	0.101	0.035	0.972
vasopressor	0.054	0.093	0.042	0.072	0.579	0.563
Prone position	-0.18	0.105	-0.08	0.046	-1.74	0.084
PaO2	-0	0.001	-0.19	0.067	-2.841	0.005
PaCO2	-0.01	0.002	-0.15	0.052	-2.852	0.005
PaO2/Fio2	0.001	0	0.175	0.065	2.695	0.008

P < 0.05 mean the baseline characteristic does not affect the study outcomes; P ≥ 0.05 mean the baseline characteristic can affect the study outcomes. COVID: Coronavirus disease; FM: Face mask; MR: Mask reservoirs; HFNC: High-flow nasal cannula; CPAP: Continuous airway positive pressure.

Table 4 The Significance of differences in baseline characteristics between the three groups

Variables	Intervention
	Casirivimab/Imdevimab(A)	Remdesivir (B)	Favipiravir (C)	P valuea
PaO2/FiO2 on day 3	298.57 ± 211.3	154.14 ± 138.9	166.96 ± 130	0
B and C				0.478
A and C				0
A and B				0
PaO2/FiO2 on day 7	320.62 ± 93.64	163.55 ± 172.6	178.59 ± 138	0
B and C				0.413
A and C				0
A and B				0
PaO2/FiO2 on day 14	389.75 ± 51.93	154.67 ± 174	165.2 ± 98.87	0.005
B and C				0.155
A and C				0.022
A and B				0.001
PaO2/FiO2 on day 28		172.75 ± 181	53 ± 0	0.48
B and C				NA
Need for IMV				0.005
Yes	1/53	22/106	22/106
No	52/53	84/106	84/106
B and C				1
A and C				0.003
A and B				0.003
Duration of need for O2 therapy and IMV	3.72 ± 3.527	9.2 ± 7.107	7.46 ± 5.077	0
B and C				0.119
A and C				0
A and B				0

^aP < 0.05 is considered a statistically significant difference between the compared groups. (1) Comparing between the three groups (A, B, C); (2) A pairwise comparison between every 2 groups (A-B, B-C, A-C), if there is a statistically significant difference between the three groups as presented by the comparing between the three groups (A, B, C); NA: Not available. IMV: Invasive mechanical ventilation.