Pan American Health Organization · Rapid Review, 13 July 2020
Rapid evidence review of 26 therapeutic options for COVID-19, including dexamethasone, remdesivir, hydroxychloroquine, and convalescent plasma.
- Issuer
- Pan American Health Organization
- Edition
- Rapid Review, 13 July 2020
- Audience
- Clinicians, public health professionals, and policymakers managing COVID-19 patients
- Evidence
- GRADE-rated rapid systematic review of RCTs and observational studies; most evidence rated very low to moderate certainty
- Reviewed
- 20 Oct 2026 · GMJ
What this guideline says
GMJ summary
This living rapid review, released 13 July 2020, synthesized evidence on 26 therapeutic options for COVID-19 from more than 1,700 ongoing clinical trials. The review found that dexamethasone 6 mg once daily (oral or intravenous) for 10 days significantly reduced mortality by one-third in ventilated patients and by one-fifth in patients receiving oxygen only, based on the RECOVERY trial. Both the RECOVERY and WHO SOLIDARITY trials showed no benefit for hydroxychloroquine or lopinavir/ritonavir in reducing 28-day mortality or improving clinical outcomes.
Remdesivir showed promise based on two randomized controlled trials, with modest reductions in mortality, time to clinical improvement, and serious adverse events, though certainty of evidence was rated as moderate. For ivermectin and favipiravir, only weak observational studies and small trials were available, judged to be of high risk of bias and very low quality of evidence. Convalescent plasma evidence was limited to largely observational studies with one small underpowered RCT.
The review emphasized that all therapeutic options should be used only within ethically approved, randomized clinical trials. A critical concern raised was the potential for drug-drug interactions and toxicity, particularly in older patients with multiple comorbidities receiving concomitant medications. The review applied GRADE methodology to rate certainty of evidence, with most studies judged as very low quality due to poor methodology, small sample sizes, and high risk of bias.
Key points
For clinicians — doses and thresholds as stated in the guideline
- Dexamethasone 6 mg once daily (oral or intravenous) for 10 days reduced deaths 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 those receiving oxygen only.
- Hydroxychloroquine showed no significant difference in 28-day mortality (25.7% vs. 23.5% usual care; HR 1.11, 95% CI 0.98–1.26) and is not recommended outside clinical trials.
- Lopinavir/ritonavir showed no benefit in reducing 28-day mortality (RR 1.06, 95% CI 0.97–1.17) or time to clinical improvement.
- Remdesivir demonstrated modest reductions: mortality (RR 0.67, 95% CI 0.46–0.97), time to clinical improvement (3.95 fewer days), and serious adverse events (RR 0.77, 95% CI 0.63–0.94), all with moderate certainty.
- Ivermectin evidence comprised only one in vitro study and four weak observational studies with high risk of bias and very low quality; no dose recommendations possible.
- Favipiravir data from one small RCT (n=236) and two observational studies were inconclusive; viral clearance median time was 4 days vs. 11 days in controls in one study.
- Tocilizumab pooled mortality data (adjusted and unadjusted) showed no significant benefit; evidence quality very low.
- Convalescent plasma: one RCT (n=103) stopped early showed no significant improvement in time to clinical recovery or 28-day mortality (15.7% vs. 24.0%; OR 0.65, 95% CI 0.29–1.46); a convenience sample of 20,000 patients suggested overall safety with <1% serious adverse events.
Therapeutics Reviewed with Number of Published Studies
Table extracted from the guideline
| Drug name | Number of studies (RCT and observational) |
|---|---|
| Meplazumab | 1 |
| Ivermectin | 5 |
| Siltuximab | 1 |
| Danoprevir | 1 |
| Tocilizumab (IL-6) | 20 |
| Favipiravir (avigan) | 3 (+2 unpublished) |
| Darunavir | 1 |
| Nelfinavir | 1 |
| Remdesivir | 5 |
| Chloroquine or hydroxychloroquine | 41 (2 retracted) |
| Convalescent plasma | 14 |
| Corticosteroids (dexamethasone, methylprednisolone etc.) | 8 (+1 combination) |
| Arbidol/Umifenovir | 9 |
| Lopinavir/ritonavir | 9 |
| Interferon-alpha | 3 |
| Interferon-beta | 4 |
| Heparin (anti-coagulants) | 4 |
| α-Lipoic acid | 1 |
| Ruxolitinib | 1 |
| IVIG | 1 |
| Sarilumab | 1 |
| Famotidine | 1 |
| Lenzilumab | 1 |
| Leflunomide | 1 |
| Statins | 1 |
| Colchicine | 1 |
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
“Dexamethasone reduced deaths by 1/3 in ventilated patients (rate ratio 0.65, 95% CI 0.48 to 0.88, p=0.0003), and by 1/5 in other patients receiving oxygen only (rate ratio 0.80, 95% CI 0.67 to 0.96, p=0.0021).”
Editor’s perspective
Why this matters for Georgia and the region
Prof. Giorgi Pkhakadze, MD, MPH, PhD
Editor-in-Chief, Georgian Medical Journal · Chair, Public Health Institute of Georgia · WHO consultant, health and migration
As Editor-in-Chief of the Georgian Medical Journal and Chair of the Public Health Institute, I recognize this PAHO rapid review as critically important for Georgian clinicians navigating the COVID-19 pandemic. The clear evidence for dexamethasone—a medication readily available in Georgia—provides an immediately actionable, low-cost intervention that our hospitals can implement for patients requiring oxygen or mechanical ventilation. I would particularly stress to Georgian colleagues the finding that hydroxychloroquine offers no mortality benefit and may cause harm, especially when combined with azithromycin, given the drug's early widespread use in our region. The realistic implementation caveat for Georgia is that the review's call for restricting experimental therapies to ethically approved randomized trials must be balanced against the urgent clinical need and limited research infrastructure; our priority should be ensuring access to dexamethasone and remdesivir while strengthening pharmacovigilance systems to monitor the safety of any off-label treatments, particularly given the high prevalence of elderly patients with cardiovascular comorbidities in Georgia. This living review model—continuously updated as evidence emerges—should serve as a template for how Georgia approaches evidence synthesis during health emergencies.
ORCID 0000-0001-7609-4515 · Perspective written for the GMJ Guidelines Library, 20 Oct 2026
Applicability
Georgia and the South Caucasus
This rapid review is highly relevant for Georgia and the South Caucasus region as it provides evidence-based guidance during the COVID-19 pandemic when many therapeutic options were being used empirically. Georgian clinicians should note that dexamethasone, a widely available and affordable corticosteroid, showed clear benefit in hospitalized patients requiring respiratory support—a finding that can be immediately implemented in Georgian hospitals. The review’s caution regarding hydroxychloroquine and lopinavir/ritonavir is important, as these drugs were being used in the region early in the pandemic. For resource-limited settings in the South Caucasus, the emphasis on avoiding polypharmacy and monitoring drug-drug interactions is particularly relevant given the prevalence of elderly patients with multiple comorbidities (hypertension, diabetes, cardiovascular disease). National programmes should prioritize access to dexamethasone and remdesivir while ensuring robust pharmacovigilance systems to monitor adverse events, and should restrict other experimental therapies to the context of properly designed clinical trials with ethical approval and patient consent.
Questions this guideline answers
Quick answers
Which COVID-19 treatment showed the clearest mortality benefit as of July 2020?
Dexamethasone 6 mg once daily (oral or IV) for 10 days showed the clearest benefit, reducing deaths by one-third in ventilated patients and one-fifth in those receiving oxygen only. No benefit was seen in patients not requiring respiratory support.
Should hydroxychloroquine be used for COVID-19 treatment?
No. The RECOVERY trial found no significant difference in 28-day mortality (25.7% vs. 23.5% usual care) and no beneficial effects on hospital stay or other outcomes. The data convincingly rule out meaningful mortality benefit in hospitalized COVID-19 patients.
What is the evidence quality for ivermectin in COVID-19?
Evidence is very low quality: only one in vitro study and four weak observational studies that were largely non-randomized, confounded, and lacked methodological rigor. Pre-print, non-peer-reviewed studies were judged high risk of bias. Large RCTs are needed before any clinical recommendation.
What are the main safety concerns with experimental COVID-19 therapies?
The review highlights that COVID-19 patients, often elderly with multiple comorbidities (diabetes, hypertension, cardiovascular disease), receive multiple concomitant medications without considering adverse events and interactions. Hydroxychloroquine with azithromycin showed significant QTc prolongation and increased cardiovascular mortality (HR 2.19, 95% CI 1.22–3.94). Drug-drug toxicity is being overlooked and must be urgently addressed.
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Quality & accreditation
Other guidelines on this topic
- Considerations for the Implementation and Management of Contact Tracing for Coronavirus Disease 2019 (COVID-19) in the Region of the Americas
- Reliance for Emergency Use Authorization of Medicines and Other Health Technologies in a Pandemic (e.g. COVID-19)
- Ethics guidance for the use of scarce resources in the delivery of critical health care during the COVID-19 pandemic
- Ongoing Living Update of Potential COVID-19 Therapeutics: Summary of Rapid Systematic Reviews
- An Overview of Current Social Distancing Measures and Required Evidence for Determining Optimal Time for Relaxing Such Measures
- Issuer
- Pan American Health Organization
- Type
- Procedures, manuals, guidelines
- Edition
- Rapid Review, 13 July 2020
- Status
- Current
- Published
- 2020-01-01
- Languages
- English
- Scope
- 26 therapeutic options for COVID-19 including antivirals, immunomodulators, corticosteroids, and convalescent plasma
- Audience
- Clinicians, public health professionals, and policymakers managing COVID-19 patients
- Licence
- CC BY-NC-SA 3.0 IGO
- Evidence
- GRADE-rated rapid systematic review of RCTs and observational studies; most evidence rated very low to moderate certainty
- Next review
- Living update (continuously updated as new evidence emerges)
- Record history
- Created 20 Oct 2026 · updated 20 Oct 2026 · next check Apr 2027
Pan American Health Organization. Ongoing Living Update of Potential COVID-19 Therapeutics: Summary of Rapid Systematic Reviews. Rapid Review, 13 July 2020. Washington, D.C.: PAHO; 2020. Available from: https://iris.paho.org/handle/10665.2/52481GMJ 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.
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