Ongoing Living Update of Potential COVID-19 Therapeutics: Summary of Rapid Systematic Reviews

What this guideline says

GMJ summary

This rapid living systematic review, published 16 June 2020, synthesizes evidence on 24 potential COVID-19 therapeutics from over 1,700 clinical trials. At the time of publication, no therapeutic had conclusive evidence of safe and effective use to eliminate SARS-CoV-2, though two showed promise: remdesivir demonstrated modest mortality reduction and faster clinical improvement in randomized controlled trials, and preliminary unpublished findings from the RECOVERY Trial indicated that dexamethasone 6 mg once daily for 10 days significantly reduced mortality by one-third in ventilated patients and one-fifth in patients receiving oxygen only.

The review found that hydroxychloroquine/chloroquine showed no benefit across 38 studies (8 RCTs, 30 observational), with accumulating evidence of harm including cardiac toxicity. Convalescent plasma showed early promise but lacked definitive evidence from adequately powered trials. Tocilizumab, lopinavir/ritonavir, arbidol, interferons, and other agents had insufficient or conflicting evidence. The review emphasizes that COVID-19 patients—frequently older adults with comorbidities such as diabetes, hypertension, and cardiovascular disease—are receiving multiple concomitant medications without adequate consideration of adverse events and drug interactions.

PAHO strongly recommends that investigational medications be used only within patient-consented randomized clinical trials evaluating safety and efficacy, following WHO guidance on ethical use of drugs in emergencies. Patient safety remains the key priority, and high-quality randomized controlled trials are urgently needed before any therapeutic can be administered with confidence.

Key points

For clinicians — doses and thresholds as stated in the guideline

1. Dexamethasone 6 mg once daily (oral or intravenous) for 10 days reduced mortality by one-third (rate ratio 0.65, 95% CI 0.48–0.88) in ventilated COVID-19 patients and by one-fifth (rate ratio 0.80, 95% CI 0.67–0.96) in patients receiving oxygen only; no benefit in those not requiring respiratory support.
2. Remdesivir (200 mg loading dose on day 1, then 100 mg daily for 4–9 days) showed modest mortality reduction (RR 0.67, 95% CI 0.46–0.97, moderate certainty), 3.95 fewer days to clinical improvement, and fewer serious adverse events (RR 0.77, 95% CI 0.63–0.94) versus placebo in pooled RCT analysis.
3. Hydroxychloroquine with or without azithromycin showed no mortality benefit across 38 studies and was associated with increased adverse events including QTc prolongation, cardiac arrest (adjusted OR 2.13, 95% CI 1.12–4.05 for HCQ+AZ), and higher risk of death when combined with azithromycin.
4. Convalescent plasma in one RCT (103 patients) showed no significant difference in 28-day mortality (15.7% vs 24.0%, OR 0.65, 95% CI 0.29–1.46) but improved viral clearance at 72 hours (87.2% vs 37.5%, OR 11.39, 95% CI 3.91–33.18); trial was underpowered.
5. Tocilizumab observational studies showed conflicting results; no definitive RCT evidence available at time of review; pooled mortality data suggested no benefit with high risk of bias.
6. Use of medications such as ivermectin, antivirals, immunomodulators, and IL-6 inhibitors should occur only within randomized clinical trials due to insufficient evidence of efficacy and potential for harm from drug interactions in patients on multiple concomitant medications.
7. Hydroxychloroquine 400 mg twice on day 1, then 400 mg weekly for postexposure prophylaxis did not prevent COVID-19 illness within 4 days after exposure (incidence 11.8% vs 14.3% placebo, absolute difference −2.4%, 95% CI −7.0 to 2.2).
8. Enoxaparin 1 mg/kg subcutaneously every 24 hours (or unfractionated heparin 5,000–15,000 units daily) in observational studies showed reduced mortality in patients with sepsis-induced coagulopathy score ≥4 or D-dimer >6-fold upper limit of normal (32.8% vs 52.4%, p=0.017).

Remdesivir outcomes: fixed-effect versus random-effects modeling sensitivity analysis

Table extracted from the guideline

Source: Pan American Health Organization, Ongoing Living Update of Potential COVID-19 Therapeutics: Summary of Rapid Systematic Reviews. Reproduced in summary form.

From the guideline

Verbatim

“There is currently sufficient evidence on the benefits of hydroxychloroquine and the vast majority of research thus far on hydroxychloroquine suggests no benefit.”

Editor’s perspective

Why this matters for Georgia and the region

Applicability

Georgia and the South Caucasus

Questions this guideline answers

Quick answers

Related on GMJ

Interconnected resources

GMJ Guidelines Library records are original summaries written by the GMJ editorial team from the issuer’s published document and reviewed by a physician. They do not replace the full guideline. The document is the copyright of its issuer and is linked, not hosted. Spotted an error or a newer edition? Tell the Guidelines Desk.