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. |