Table 1: Summary table of trialled therapies for Covid-19.

Drug/treatment Class/Mechanism of action Results of Covid-19 trials
Drugs with antiviral activity
Chloroquine/ Hydroxychloroquine -Quinolone class (antimalarial) -Alkalinisation of endosomes & inhibition of ACE-II glycosylation, preventing virus binding & cell entry RECOVERY trial- no significant difference in mortality or TTR. Confirmed with multiple meta-analyses Aug 2020 [21,22]
Azithromycin -Macrolide bacteriostatic antibiotic -Inhibits mRNA translation on bacterial ribosome; theorised to have similar effect on virus Increased risk of adverse effects and mortality in combination with hydroxychloroquine (meta-analysis of 7 studies) RR1.27, 95% CI 1.04-1.54 [22]
Ivermectin -Antiparasitic macrocyclic lactone -Cellular hyperpolarisation via binding glutamate-gated chloride channel receptor (GluClR) causing cell paralysis/death In Vitro effectiveness against SARS-CoV-2; cohort study meta-analysis suggests mortality and TTR benefits [27,28]. RCTs awaited.
Remdesivir -Prodrug- active metabolite ATP analogue -Inhibits RNA-dependent RNA polymerase, preventing viral replication 31% Improvement in TTR, no effect on mortality in ACTT trial (p < 0.001) [35]. SIMPLE trial showed no additional safety concerns (not placebo controlled) [36]. Approved by US FDA Oct 2020.
Favipiravir -Prodrug- active metabolite inhibits RNA-dependent RNA polymerase -Prevents viral replication WHO SOLIDARITY Study: No significant benefit in mortality, TTR or illness severity [42].
Lopinavir/ Ritonavir -Anti-retroviral drug combination (HIV protease inhibitors) -Bind viral protease, preventing antigen production Largest RCT (n = 199) showed no benefit in TTR, mortality or viral load clearance [40]. WHO SOLIDARITY Study: No significant benefit in mortality, TTR or illness severity [42].
Drugs with immunomodulatory functions
Interferon Beta-1a -Recombinant human interferon (cytokine); licensed for Multiple sclerosis -Reduces inflammation, inhibits production of T helper cells WHO SOLIDARITY Study: No significant benefit in mortality, TTR or illness severity [42]. RCTs ongoing trialling inhaled regimen.
Glucocorticoids -Anti-inflammatory, pleotropic effects and usage -Bind glucocorticoid receptors, stimulating anti-inflammatory protein production RECOVERY trial (n = 2104 vs. 4321 usual care): Decreased 28-day mortality HR0.83, p < 0.001 [49]. Confirmed with Pooled meta-analysis of 7 RCTs [50].
Tocilizumab -Humanised monoclonal antibody (anti-IL6 cytokine receptor); licensed for Rheumatoid arthritis -Suppression of pro-inflammatory interleukin 6 COVACTA trial- no significant difference in mortality, TTR [55]. Cohort studies suggest benefit in combination with steroids [56,57]. RECOVERY trial ongoing.
Sarilumab - Humanised monoclonal antibody (anti-IL6 cytokine receptor); licensed for Rheumatoid arthritis -Suppression of pro-inflammatory interleukin 6 CORIMUNO trial halted in Sep 2020 due to lack of efficacy [55].
Convalescent plasma -Antibodies from the plasma of Covid-19-recovered individuals -Likely to confer passive immunity only Two RCTs (China, India) failed to show mortality or TTR benefit despite significantly quicker viral load clearance [61,62].
Bamlanivimab -Monoclonal antibody identified from convalescent plasma -Likely to confer passive immunity only Interim RCT results show significant viral load reduction with lower dose (2800 mg) not seen with 7000 mg dose [64]. US FDA approval in Nov 2020 for non-hospitalised Covid-19 cases (prior to full publication of trial results) [65].
REGN-COV2 -Combination of two monoclonal antibodies identified from convalescent plasma - Likely to confer passive immunity only   Interim RCT results show significant viral load reduction but no difference in TTR in non- hospitalised Covid-19 patients [67]. RECOVERY trial ongoing for hospitalised patients [68].
Supportive measures
Anticoagulation -Heparin and derivatives -To treat hypercoagulable pro-inflammatory state Evidence base from historical (pre-Covid-19 era) meta-analysis of RCTs in ARDS patients showing 48% 7-day and 37% 28-day reduction in mortality [75]. Retrospective analyses of Covid-19 patients in China show apparent mortality benefit of 7 days anticoagulation with LMWH [73,74].
Non-invasive ventilation, conscious proning -Positive/bi-level pressure mask ventilation to aid oxygenation in hypoxic states -Proning (alternating supine and prone positioning during ventilation to allow aeration of entire lung) RECOVERY-RS trial ongoing to evaluate HFNO vs. CPAP [81]. Case series show conscious proning in moderate cases of Covid-19 shown improves hypoxia and decreases risk of progression to intubation [84,85].
Invasive ventilation -Mechanical ventilation after endotracheal intubation used in cases of severe hypoxia and poor respiratory reserve Mechanical ventilation known to be lifesaving in ARDS. Difficult to ethically design RCT.
The Vaccines
Pfizer/BioNTech -messenger RNA coding for SARS-CoV-2 surface spike glycoprotein -Stimulates production of antibodies to the resulting antigen without viral infection Approved by UK MHRA and US FDA in Dec 2020 on basis of results made available prior to peer-reviewed publication [89].
Moderna -messenger RNA coding for SARS-CoV-2 surface spike glycoprotein -Stimulates production of antibodies to the resulting antigen without viral infection Awaiting publication of full results; interim results announced claiming 95% efficacy
Oxford/AstraZeneca (ChAdOx1 nCOV-19) -Replication deficient adenovirus modified to express SARS-CoV-2 surface spike glycoprotein Interim results of 11,636 trial participants showing up to 90% efficacy at low dose regimen with no significant safety concerns [90]. Full results awaited.