Table 2 Published clinical trials of drugs against SARS-CoV-2

Attachment and entry

Viral envelope

Arbidol/umifenovir

N/A

Umifenovir did not improve the prognosis or accelerate SARS-CoV-2 clearance in non-ICU patients

81 moderates to severe COVID-19 patients (umifenovir vs control = 45: 36)

Single-centre, retrospective

N/A

[29]

The ability of arbidol to reduce SARS-CoV-2 RNA load is better than lopinavir–ritonavir

N/A

50 COVID-19 patients (lopinavir/ritonavir vs arbidol = 34:16)

N/A

N/A

[27]

Endosomal acidification

Hydroxychloroquine

N/A

Hydroxychloroquine did not induce SARS-CoV-2 negative conversion. It has cardiotoxicity

150 patients with mainly persistent mild to moderate COVID-19 (hydroxychloroquine + standard of care vs standard of care alone = 75:75)

Multicenter, open label, randomized controlled

ChiCTR2000029868

[33]

Chloroquine diphosphate

N/A

Chloroquine diphosphate did not reduce mortality and may extend QT intervals

81 patients (high-dosage vs low-dosage group = 41:40)

Parallel, double-masked, randomized, phase IIb

N/A

[34]

Replicase protein expression

Mpro (3C-like protease) (nsp5)

Lopinavir/ritonavir

N/A

Lopinavir–ritonavir did not reduce mortality or the time to clinical improvement

199 COVID-19 adults (lopinavir–ritonavir:standard-care = 99:100)

Randomized, controlled, open-label

ChiCTR2000029308

[49]

N/A

Lopinavir–ritonavir did not reduce mortality or prevent progression

5040 (lopinavir/ritonavir:usual care = 1616:3424)

Randomised, controlled, open-label, platform

NCT04381936

[48]

Replication, transcription and translation

Nsp12

Remdesivir

By day 28, 10-day remdesivir group had a better clinical status distribution than standard care group

Remdesivir did not reduce the length of hospitalization or oxygen therapy

584 moderate COVID-19 patients (10-day remdesivir:5-day remdesivir:standard care = 197:199:200)

Randomized, controlled, open-label

NCT04292730

[53]

Remdesivir reduces the duration of hospitalization and infection

N/A

1059 COVID-19 adults with lower respiratory tract infection (remdesivir:placebo = 538:521)

Double-blind, randomized, placebo-controlled

NCT04280705

[54]

N/A

There is no significant clinical difference between a 5-day course and a 10-day course of remdesivir

397 severe COVID-19 patients (5-day remdesivir:10-day remdesivir = 200:197)

Randomized, open-label

NCT04292899

[52]

N/A

Remdesivir did not reduce time to clinical improvement

237 COVID-19 adults (10- day remdesivir vs placebo = 158:79)

Randomised, double-blind, placebo-controlled, multicentre

NCT04257656

[51]

Favipiravir

Favipiravir leads to faster viral clearance and better chest CT changes than patients treated with lopinavir/ritonavir

N/A

80 COVID-19 patients (favipiravir vs lopinavir/ritonavir = 35:45)

Open-label comparative controlled

ChiCTR2000029600

[59]

Immunology

IFN supplement

IFN-α2b

Among severe to critical COVID-19 patients, early treatment with IFN-α2b reduced in-hospital mortality

IFN-α2b did not benefit significantly in moderately ill patients

242 (IFN + LPV/r, IFN + UFV, IFN alone) of 446 COVID-19 patients received IFN-α2b

Retrospective, multicenter

[100]

Protective antibody supplement

Convalescent plasma

Convalescent plasma is most effective in early application and reduces mortality

N/A

39 patients with severe to life-threatening COVID-19 (convalescent plasma vs controls = 1:4 and 1:2 ratios)

Retrospective, propensity score–matched case–control

N/A

[119]

Convalescent plasma was associated with antiviral activity

Convalescent plasma did not significantly reduce time to the clinical improvement

103 patients with severe to life-threatening COVID-19 (Convalescent plasma in addition to standard treatment vs standard treatment alone = 52:51)

Open-label, multicenter, randomized, prospective

ChiCTR2000029757

[120]

Cytokine storm

Corticosteroids

Early, low-dose and short-term application of methylprednisolone helped reach better clinical outcomes in severe patients with COVID-19 pneumonia

N/A

46 severe patients with COVID-19 pneumonia (26 of them received extra low-dose and short-term methylprednisolone treatment)

Retrospective

N/A

[122]

For severe COVID-19 patients, methylprednisolone pulse promoted clinical improvements and reduced mortality

N/A

68 severe COVID-19 patients (methylprednisolone vs standard care alone = 34:34)

Single-blind, randomized, controlled

N/A

[123]

IL-6R

Tocilizumab

N/A

Tocilizumab showed no benefit on disease progression compared with standard care. (early shutdown)

126 adults with COVID-19 pneumonia and PaO₂/FIO₂ ratio between 200 and 300 mmHg (tocilizumab vs supportive care = 60:66)

Prospective, open-label, randomized

NCT04346355

[127]

N/A

Tocilizumab did not promote clinical improvements or reduced mortality

131 COVID-19 patients with moderate or severe pneumonia requiring oxygen but without ventilation or admission to the ICU (tocilizumab vs usual care alone = 64:67)

Multicenter, open-label, Bayesian randomized

NCT04331808

[126]

Tocilizumab reduced serious infections

Tocilizumab did not prevent intubation or death in moderately ill hospitalized patients with COVID-19

243 hospitalized COVID-19 patients (standard care + tocilizumabvs vs standard care + placebo = 162:81)

Randomized, double-blind, placebo-controlled

NCT04356937

[125]