Safety and Efficacy of Antiviral Drugs for the Treatment of COVID-19: A Systematic Review

Figures & data

Table 1 Characteristics of the Included Studies

Reference	Region	Research Type	Age of Patients	Disease Classification	Number of Cases in Trial/Control	Number of Deaths	Treatment	Course
[6]	China	RCT	58±10	Severe	199 (99 vs 100)	44	Test group: lopinavir/ritonavir 400mg/100mg, po, bid; control group: conventional treatment.	14
[7]	China	RCT	28~69 vs 29~68	Moderate	60 (30 vs 30)	0	Test group: α-interferon 5 million IU aerosol inhalation, bid + Lianhua Qingwen capsule 4 tablets, po, tid + lopinavir/ritonavir 2 tablets, po, bid; control group: no use of lopinavir/ritonavir, other with experimental group.	7~10
[8]	China	N-RCT		Mild and Moderate	80 (35 vs 45)	0	Test group: fapiravir 1600 mg, po, bid on day 1, 600 mg, po, bid on day 2–14; control group: lopinavir/ritonavir 400 mg/100 mg, po, bid.	14
[12]	China	N-RCT	8.0±14.1 vs 44.1±15.0	Mild and Moderate	150 (75 vs 75)	0	Test group: hydroxychloroquine 1200 mg/d on 1~3 days, then 800 mg/d, 2–3 weeks of treatment; control group: standard nursing	14~21
[11]	China	N-RCT	50.5±3.8 vs 46.7±3.6	Moderate	30 (15 vs 15)	0	Test group: hydroxychloroquine 400 mg, po, qd; control group: conventional treatment.	5
[14]	France	N-RCT	5.1±22.0	Non classification	42 (26 vs 16)	1	Test group: hydroxychloroquine 200 mg, po, tid (6 patients also received azithromycin: 500 mg, po, qd on day 1; 250 mg, po, qd on day 2–5); control group: no treatment or no use of the above treatment regimen.	10
[13]	USA	Retrospective cohort	68 (59~74) vs 70 (60~75) vs 69 (59~75)	Non classification	368 (113 vs 97 vs 158)	70	Group 1: hydroxychloroquine + azithromycin; group 2: hydroxychloroquine; Group 3: no use of hydroxychloroquine (50 of them used azithromycin).	-
[15]	China	N-RCT	49.4 (19 ~ 79)	Mild and Moderate	86 (34 vs 35 vs 17)	0	Group A: lopinavir/ritonavir 400mg/100mg, po, bid; group B: Abidol 0.2g, po, tid; group C: no antiviral drugs.	7~14
[16]	China	Retrospective cohort	4.56±15.7	Mild	33 (16 vs 17)	0	Test group: abidol 0.2 g, po, q8h + lopinavir/ritonavir 400 mg/100 mg, po, q12h; control group: lopinavir/ritonavir 400 mg/100 mg, po, q12 h; treatment to PCR for 3 consecutive negatives.	5~21
[17]	China	RCT	70.3% < 65 years	Moderate 88.6%, Severe and Critical 11.4%	240 (120 vs 120)	0	Test group: fapiravir 1600 mg, po, bid on day 1, 600 mg, po, bid on day 2–10; control group: Abidol 0.2g, po, tid	10
[18]	China	Retrospective cohort	46.3 (2~18)	Mild 15 cases, Moderate 178 cases, Severe 15 cases, Critica 15 cases	224 (38 vs 137 vs 34 vs 7 vs 3 vs3 vs 1 vs 1)	0	Group 1: INFα+ ribavirin; group 2: INFα+ lopinavir/ritonavir; group 3: INFα+ lopinavir/ritonavir + ribavirin; group 4: INFα; group 5: INFα+ arbidol; group 6: Darunavir cobicistat + arbidol; group 7: INFα+ darunavir cobicistat; group 8: Arbidol + ribavirin	5~21
[19]	China	RCT	45.12±2.15 vs 51.32±5.29	Mild 4 cases, Moderate 26 cases, Severe 7 cases, Critica 6 cases	62 (43 vs 19)	0	Control group: interferon α-2b, 5 million U, atomizing inhalation, twice a day; abidol, 200 mg/time, 3 times/d, orally; ribavirin, 500 mg/time, 1time/d, intravenous infusion; lianhuaqingwen capsule, 4 grains/time, 4 times/d, orally. Treatment group: Patients were treated with lopinavir/ritonavir on the basis of routine treatment in the control group. The specifications were 200 mg/50 mg, 2 tablets/time, twice daily, orally, for 7 days.	-
[20]	China	Retrospective case series	44 (34, 53) vs 47.43±16.26	Non classification	294 (147 vs 147)	0	Treatment group: FPV 1600 mg, twice a day, then 600 mg, twice a day, for 9 days; control group: Chinese medicine, nutritional support, oxygen inhalation, etc.	22~44
[21]	China	Observational studies	44 (18~66)	Moderate	11	0	Danovavir 100 mg, po, bid + ritonavir 100 mg, po, bid (6 patients also received IFN-α, 5 million IU aerosol inhalation, bid)	4~12
[22]	China	RCT	66 (57~73) vs 64 (53~70)	Severe	237 (158 vs 79)	32	Test group: Redsivir 200 mg, ivgtt, qd on day 1, 100 mg, ivgtt, qd on day 2–10; control group: same dose of placebo	10
[23]	Multi-national	Observational studies	64 (48~ 71)	Severe and Critical	61	7	Redsivir 200 mg, ivgtt, qd, day 1, 100 mg, ivgtt, qd, days 2–10	10

Brown AJ, Won JJ, Graham RL, et al. Broad spectrum antiviral remdesivir inhibits human endemic and zoonotic deltacoronaviruses with a highly divergent RNA dependent RNA polymerase. Antiviral Res. 2019;169:104541. doi:10.1016/j.antiviral.2019.104541

 PubMed Web of Science ®Google Scholar

Cao B, Wang Y, Wen D, et al. A trial of lopinavir-ritonavir in adults hospitalized with severe Covid-19. N Engl J Med. 2020;382(19):1787–1799. doi:10.1056/NEJMoa2001282

 PubMed Web of Science ®Google Scholar

Wang SZ, Wang HJ, Chen HM, et al. Lianhua Qingwen capsule and interferon-α combined with lopinavir/ritonavir for the treatment of 30 COVID-19 patients. J Bengbu Med Coll. 2020;45:154–155.

 Google Scholar

Chen Y, Li XP, Jiang YH, Wang YP, Yu WJ. Clinical features and treatment of 11 cases of COVID-19. Mod Pract Med. 2020;32(2):5.

 Google Scholar

Liu F, Xu A, Zhang Y, et al. Patients of COVID-19 may benefit from sustained Lopinavir-combined regimen and the increase of Eosinophil may predict the outcome of COVID-19 progression. Int J Infect Dis. 2020;95:183–191. doi:10.1016/j.ijid.2020.03.013

 PubMed Web of Science ®Google Scholar

Gautret P, Lagier JC, Parola P, et al. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int J Antimicrob Agents. 2020;56(1):105949. doi:10.1016/j.ijantimicag.2020.105949

 PubMed Web of Science ®Google Scholar

Tang W, Cao Z, Han M, et al. Hydroxychloroquine in patients with mainly mild to moderate coronavirus disease 2019: open label, randomised controlled trial. BMJ. 2020;14(369):m1849. doi:10.1136/bmj.m1849

 Web of Science ®Google Scholar

Magagnoli J, Narendran S, Pereira F, et al. Outcomes of hydroxychloroquine usage in United States veterans hospitalized with Covid-19. medRxiv. 2020;1:114–127.

 Google Scholar

Li Y, Xie Z, Lin W, et al. Efficacy and safety of lopinavir/ritonavir or arbidol in adult patients with mild/moderate COVID-19: an exploratory randomized controlled trial. Med. 2020;1(1):105–113.e4. doi:10.1016/j.medj.2020.04.001

 PubMed Web of Science ®Google Scholar

Deng L, Li C, Zeng Q, et al. Arbidol combined with LPV/r versus LPV/r alone against Corona Virus Disease 2019: a retrospective cohort study. J Infect. 2020;81(1):e1–e5. doi:10.1016/j.jinf.2020.03.002

 PubMed Web of Science ®Google Scholar

Chen C, Zhang Y, Huang J, et al. Favipiravir versus arbidol for clinical recovery rate in moderate and severe adult COVID-19 patients: a prospective, multicenter, open-label, randomized controlled clinical trial. Front Pharmacol. 2021;12:683296. doi:10.3389/fphar.2021.683296

 PubMed Web of Science ®Google Scholar

Yuan J, Yan XF, Zhang W, et al. Retrospective analysis of antiviral efficacy of 224 cases of novel coronavirus pneumonia. Chin J Infect Chemother. 2021;21(04):406–410.

 Google Scholar

Zhao L, Zhao P, Zhang DW, et al. The efficacy of lopinavir/ritonavir combined with interferon in the treatment of new coronavirus pneumonia. Infect Dis Info. 2021;34(01):15–19.

 Google Scholar

Tiandi GZ, Qian F, Zhang TY, et al. Clinical observation on the incidence of severe cases of new coronavirus pneumonia treated with favelavir. Chin J Pharmacov. 2021;18(10):901–904 + 909.

 Google Scholar

Chen H, Zhang Z, Wang L, et al. First clinical study using HCV protease inhibitor danoprevir to treat COVID-19 patients. Medicine. 2020;99(48):e23357. doi:10.1097/MD.0000000000023357

 PubMed Web of Science ®Google Scholar

Wang Y, Zhang D, Du G, et al. Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial. Lancet. 2020;395(10236):1569–1578. doi:10.1016/S0140-6736(20)31022-9

 PubMed Web of Science ®Google Scholar