Antiviral Combination Clinically Better Than Standard Therapy in Severe but Not in Non-Severe COVID-19

Figures & data

Figure 1 The study flow.

Abbreviations: NS, Non-severe; S, Severe category of intervention arms.

Table 1 Demographic and Clinical Characteristics of the Patients at Baseline

	Non-Severe A	Non-Severe B	Severe A	Severe B	Severe C
Participants analyzed (n)	16	17	24	20	24
Mean Age (in years)	42.56	43.94	56.67	50.05	52.42
Male gender (%)	68.8	88.2	70.8	85	62.5
Coexisting medical conditions at the time enrolment	6	6	16	12	16
1. Diabetes Mellitus	2	3	7	5	11
2. COPD	1	1	4	2	0
3. Hypertension	2	0	10	5	16
4. Chronic Cardiac Disease	1	1	5	4	1
5. Asthma	0	0	0	1	1
6. Malignancy	0	1	0	0	0
Presenting complaints
1. Fever/history of fever	11	15	15	16	20
2. Cough	7	11	18	15	21
3. Shortness of breath	7	6	20	16	22
4. Headache	1	0	1	1	0
5. Loose stools	0	0	0	4	0
6. Pain abdomen	0	0	1	1	0
7. Body ache	0	0	0	0	2
8. O2 supplementation at admission	2	3	18	12	21
Treatments used	Standard Treatment* = Strict Isolation, Standard Precautions (Hand hygiene, Cough Etiquette, Wear surgical mask), Hydration, Proper Nutrition, Supportive Pharmacotherapy (Antipyretic, Antiallergic, Cough Suppressant), Treatment of Comorbid Diseases, Oseltamivir (75 mg BD) for patients who are tested positive for H1N1	Hydroxychloroquine 400 mg twice on first day followed by 400 mg per oral daily for 10 days + Ribavirin (1.2 g orally as a loading dose followed by 600mg orally every 12 hours) for 10 days + Standard Treatment*	Standard Treatment# = Strict Isolation, Standard Precautions (Hand hygiene, Cough Etiquette, Wear surgical mask), Fluid Therapy, Supportive Pharmacotherapy (Antipyretic, Antiallergic, Cough Suppressant), Oxygen supplementation (as required), Invasive ventilation (as required), Antibiotic agents for other associated infections (according to 2019 ATS/IDSA guidelines for non-ICU and ICU patients), Vasopressor support, Renal-replacement therapy, Treatment of Comorbid Diseases, Oseltamivir (75 mg BD) for patients who are tested positive for H1N1	Hydroxychloroquine 400 mg BD on day 1 followed by 400 mg once daily + Ribavirin (1.2 g orally as a loading dose followed by 600 mg orally every 12 hours) for 10 days + Standard Treatment#	Lopinavir (200 mg) + Ritonavir (50 mg) two tablets twice daily + Ribavirin (1.2 g orally as a loading dose followed by 600 mg orally every 12 hours) for 10 days + Standard Treatment#
Severe adverse reactions (Name and severity)		1-Drug induced liver injury (DAIDS grade-2) 1-QT prolongation		1-Drug induced liver injury (DAIDS grade-2)

Notes: Standard Treatment* = for non-severe category; Standard Treatment# = for severe category.

Abbreviation: DAIDS, Division of acquired immune deficiency syndrome table for grading the severity of adverse events.

Figure 2 (A–D) Time trend of clinical recovery of major symptoms among different intervention arms.

Figure 3 (A–D) Time trend of laboratory recovery of major tests among different intervention arms.

Table 2 The Time to a Negative SARS-CoV-2 RT-PCR in Nasopharyngeal and Throat Swab Specimens

	Non-Severe A	Non-Severe B	Severe A	Severe B	Severe C
No of participants having Negative RT-PCR at follow-up intervals until discharge	3	3	2	3	2
Mean duration (in days)	5.66	6.33	12.5	8.5	8
P-value	Intergroup >0.05 (non-significant)

Table 3 Secondary Outcomes Among Participants in the Severe Category

	Severe A		Severe B		Severe C		P-value (Intergroups)
	Number	%	Number	%	Number	%
Number of deaths during the study period
All-cause mortality	6/21	28.57	3/20	15	5/22	22.72	>0.05
Increase in oxygen requirement on 1st follow-up (at 72 hours)	15/21	71.42	17/20	85	18/21	85.71	>0.05
Increase in oxygen requirement on 2nd follow-up (at 144 hours)	6/11	54.54	9/13	69.23	9/12	75	>0.05
Requirement of non-invasive ventilation (NIV)
NIV on 1st follow-up (at 72 hours)	5/21	23.8	2/20	10	5/21	23.8	>0.05
NIV on 2nd follow-up (144 hours)	3/9	33.33	1/11	9.09	1/6	16.66	>0.05
Requirement of mechanical ventilation (MV)
MV on 1st follow-up (at 72 hours)	2/21	9.52	1/20	5	5/21	23.8	>0.05
MV on 2nd follow-up (144 hours)	3/11	27.27	1/13	7.69	1/12	8.33	>0.05
Mean duration of hospital stays	14.08 days (SD=11.35)		14.15 days (SD=6.08)		14.42 days (SD=13.27)		>0.05

Notes: Participants who are already on NIV/MV at the time of allocation were excluded in determining the proportion.

Abbreviation: SD, standard deviation.