Table 4.

Summary of COVID-19 therapy studies: Novel specific treatment agents

No	Drug/treatment	Author	Year	Study aim	Study type	Study design	Status	Main findings	Limitations
1.	Monoclonal and polyclonal antibodies	Salma et al [75]	2021	TO investigate the safety and efficacy of tocilizumab in hospitalized patients with COVID-19 pneumonia who were not receiving mechanical ventilation.	Randomised, double-blind, placebo-controlled, phase 3 trial	389 patients were randomised at a 2:1 ratio to the treatment group (n = 249) and the placebo group(n = 128).	Complete	patients who had received mechanical ventilation or who had died by day 28 was 12.0% (95% CI, 8.5 to 16.9) in the tocilizumab group and 19.3% (95% CI = 13.3 to 27.4) in the placebo group (hazard ratio for mechanical ventilation or death, 0.56; 95% CI = 0.33 to 0.97; P = 0.04 by the log-rank test). Clinical	Treatment in control group was not standardised. Based on preliminary data.
		Hermine et al [76]	2021	To determine whether tocilizumab (TCZ) improves outcomes of patients hospitalized with moderate-to-severe COVID-19 pneumonia	Cohort-embedded, multicentre, open-label, Bayesian randomized clinical trial investigating	130 patients from 9 French hospitals were randomly assigned to the TCZ group (n = 63) or the control (n = 67). Followed up after 28 d.	Complete	At day 14, 12% (95% CI = -28% to 4%) fewer patients needed non-invasive ventilation (NIV) or mechanical ventilation (MV) or died in the TCZ group than in the UC group (24%vs 36%, median posterior hazard ratio HR 0.58; 90% credible interval CrI = 0.33-1.00). No difference in 28 d mortality was found.	Not blinded, lack of standardisation of control group treatment, small sample size, results not generalizable. Preliminary results.
		Veiga et al [77]	2021	To determine whether tocilizumab improves clinical outcomes for patients with severe or critical coronavirus disease 2019	Open label RCT	129 hospitalised patients from 9 sites in Brazil were randomised in a 1:1 ratio to treatment group (n = 65) or standard care group (n = 64).	Complete	Treatment was associated with worse outcomes. 18 of 65 (28%) patients in the tocilizumab group and 13 of 64 (20%) in the standard care group were receiving mechanical ventilation or died at day 15 (OR = 1.54, 95% CI = 0.66 to 3.66; P = 0.32). Death at 15 d occurred in 11 (17%) patients in the tocilizumab group compared with 2 (3%) in the standard care group	Open label trial may be subject to bias. Reduction in statistical power due to small sample size and incompatible seven level ordinal scale with proportional odds assumptions. Trial prematurely interrupted due to high death rate.
		Weinreich et al [78]	2021	To describe the initial results involving 275 symptomatic patients from the ongoing phase 1-3 trial involving outpatients with confirmed SARS-CoV-2 infection	Double-blind, phase 1-3 trial, placebo-controlled, RCT	275 un-hospitalised patients with COVID-19 randomly assigned in a 1:1:1 ratio to receive placebo (n = 93), high dose REGN-COV2 (n = 90) or low dose REGN-COV2 (n = 92).	Ongoing	The REGN-COV2 antibody cocktail reduced viral load, with a greater effect in patients whose immune response had not yet been initiated or who had a high viral load at baseline. 6% of the patients in the placebo group and 3% of the patients in the combined REGN-COV2 dose groups reported at least one medically attended visit.	No formal hypothesis testing was performed to control type 1 error. Analyses according to baseline viral load were post hoc.