Pan American Health Organization · Rapid review, 23 May 2020
Rapid systematic review of COVID-19 therapeutic options for clinicians and public-health professionals (23 May 2020)
- Issuer
- Pan American Health Organization
- Edition
- Rapid review, 23 May 2020
- Audience
- Clinicians and public-health professionals managing COVID-19 patients
- Evidence
- GRADE-rated systematic review of RCTs and observational studies; nearly all evidence rated as very low to low certainty
- Reviewed
- 20 Oct 2026 · GMJ
What this guideline says
GMJ summary
This rapid systematic review assessed the evidence for potential COVID-19 therapeutics as of 23 May 2020, examining nearly 200 therapeutic options across more than 1,700 clinical trials. The central message is stark: no therapeutic option had been conclusively shown to be effective (though remdesivir showed promise), and most investigational drugs should only be used within patient-consented randomized clinical trials.
The review found that hydroxychloroquine/chloroquine (with or without azithromycin) showed no benefit across 28 studies and demonstrated evidence of harm, including QT prolongation and increased mortality in some series. Remdesivir showed significant reductions in mortality, time to clinical improvement, and adverse events in pooled analysis of 2 RCTs, though the certainty of evidence remained low-moderate. Other agents (tocilizumab, convalescent plasma, lopinavir/ritonavir, arbidol, ivermectin, corticosteroids, interferon) had insufficient evidence, with nearly all evidence rated as very low certainty using GRADE methodology.
A critical concern highlighted was that COVID-19 patients—often elderly with comorbidities—were receiving multiple concomitant medications without adequate consideration of drug interactions and adverse events. The review emphasized that patient safety must remain the key priority and that the ethical use of investigational drugs should follow WHO guidance on compassionate use and unauthorized indications.
Key points
For clinicians — doses and thresholds as stated in the guideline
- No therapeutic option conclusively proven effective as of May 2020; remdesivir showed promise but required further study in adequately powered trials
- Hydroxychloroquine/chloroquine (alone or with azithromycin) showed no benefit in the vast majority of 28 studies and demonstrated harm including QT prolongation, with adverse events in 25.4% vs 7.5% in controls (RR 2.86, 95% CI 1.51–5.45)
- Remdesivir reduced mortality (HR 0.70, 95% CI 0.47–1.04), time to clinical improvement, all adverse events, and serious adverse events in pooled analysis of 2 RCTs, though certainty of evidence was low-moderate
- Corticosteroids in ARDS (not COVID-19 specific) reduced all-cause mortality (RR 0.75, 95% CI 0.59–0.95, moderate certainty) and duration of mechanical ventilation (MD −4.93 days, 95% CI −7.81 to −2.06, low certainty)
- Tocilizumab/IL-6 inhibitors: insufficient evidence; observational data showed mixed results with concerns about secondary bacterial infections and superinfection in critically ill patients
- Convalescent plasma showed potential in small case series (5–21 patients) with no serious adverse events in larger series (5,000 patients: <1% serious adverse events in first 4 hours)
- All investigational medications should be used only within randomized clinical trials evaluating safety and efficacy; nearly all evidence rated as very low certainty by GRADE
- Drug interactions and concomitant medication toxicity in elderly patients with comorbidities represent an overlooked area requiring urgent attention
GRADE certainty hydroxychloroquine/chloroquine adverse events (all combined)
Table extracted from the guideline
| Studies | Design | Risk of bias | Inconsistency | Indirectness | Imprecision | HCQ/CQ patients with adverse events | Control patients with adverse events | Relative effect (95% CI) | Absolute effect (95% CI) | Certainty | Importance |
|---|---|---|---|---|---|---|---|---|---|---|---|
| 4 RCTs | Randomised trials | Serious | Not serious | Not serious | Serious | 32/126 (25.4%) | 10/133 (7.5%) | RR 2.86 (1.51 to 5.45) | 140 more per 1,000 (from 38 more to 335 more) | ⨁⨁◯◯ LOW | CRITICAL |
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
“Currently, no therapeutic option has been shown to be effective (though remdesivir is revealing promise as one option) and that conclusively allows for safe and effective use to mitigate or eliminate the causative agent of COVID-19”
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 we reflect on the early pandemic period documented in this May 2020 PAHO rapid review, I recall the intense pressure Georgian clinicians faced to offer treatments when evidence was scarce and mortality high. This systematic review—rating nearly all COVID-19 therapeutic evidence as very low certainty—provided crucial guidance against the widespread off-label use of hydroxychloroquine that occurred globally, including in Georgia. The finding of harm rather than benefit from hydroxychloroquine, combined with the emphasis on drug interactions in elderly patients with comorbidities (a significant proportion of Georgia's COVID-19 hospitalisations), reinforced the need for evidence-based protocols rather than empiric polypharmacy. For Georgian clinicians, I would stress the review's core principle: that investigational drugs should only be used within properly designed randomized trials with ethical oversight and robust pharmacovigilance—a lesson applicable beyond COVID-19 to any emerging infectious disease. The realistic caveat is that conducting high-quality trials during a rapidly evolving pandemic requires infrastructure (research ethics committees, data management, laboratory capacity) that was stretched thin in 2020; strengthening this research capacity remains essential for Georgia's preparedness for future 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 from May 2020 documented the chaotic early therapeutic landscape of COVID-19, when Georgia—like all countries—faced urgent pressure to offer treatments amid profound uncertainty. The finding that hydroxychloroquine showed no benefit but clear harm, while most other agents lacked quality evidence, would have been critical for Georgian clinicians managing the first COVID-19 waves in 2020. The emphasis on using investigational drugs only within clinical trials, on monitoring drug interactions in elderly patients with comorbidities, and on cardiovascular adverse events (QT prolongation with hydroxychloroquine/azithromycin) provided essential safety guidance. For Georgia’s national COVID-19 treatment programme, the review underscored the need for: robust pharmacovigilance systems to detect adverse drug reactions; ethical frameworks for compassionate use aligned with WHO guidance; laboratory capacity for monitoring QT intervals and other toxicities; and resistance to political or commercial pressure to adopt unproven therapies. The subsequent evolution of evidence (dexamethasone, antivirals, monoclonal antibodies) reinforces the review’s core message: that only high-quality randomized trials can establish therapeutic benefit in pandemic settings.
Questions this guideline answers
Quick answers
What was the evidence for hydroxychloroquine for COVID-19 in May 2020?
As of May 2020, 28 studies (6 RCTs, 22 observational) found that hydroxychloroquine (with or without azithromycin) showed no benefit for COVID-19 in the vast majority of research, and demonstrated evidence of harm including adverse events in 25.4% vs 7.5% controls (RR 2.86, 95% CI 1.51–5.45), QT prolongation >500ms in 11–15.9% of patients, and increased risk of cardiac arrest with HCQ+azithromycin (adjusted OR 2.13, 95% CI 1.12–4.05). All evidence was rated as very low to low certainty.
Did remdesivir show benefit for COVID-19 in this review?
Pooled analysis of 2 RCTs showed remdesivir significantly reduced mortality (HR 0.70, 95% CI 0.47–1.04), time to clinical improvement, all adverse events, and serious adverse events compared to placebo. However, the certainty of evidence was only low-moderate due to small sample sizes, small event numbers, inconsistency between trials (one Chinese trial showed 22 deaths in remdesivir group vs 10 in placebo), and indirectness (pooling 14-day and 28-day mortality). The review noted remdesivir as an antiviral may not be sufficient alone and might require combination with other treatments.
Should investigational COVID-19 drugs be used outside clinical trials?
No. The review strongly recommended that investigational medications such as chloroquine, hydroxychloroquine (alone or with azithromycin), ivermectin, antivirals, and immunomodulators should only be used within patient-consented randomized clinical trials that evaluate safety and efficacy. Countries should follow WHO guidance on ethical use of drugs in emergencies, including use on unauthorized indications and compassionate use. Patient safety was identified as a key priority to improve quality of care.
What were the concerns about drug interactions in COVID-19 patients?
The review highlighted that COVID-19 patients—frequently older adults with established comorbidities—were receiving multiple concomitant medications without adequate consideration of possible adverse events and interactions. This was identified as an overlooked area of research where the potential toxicity due to concomitant treatments must be urgently addressed. Specific concerns included QT prolongation with hydroxychloroquine plus azithromycin, and the combination of multiple experimental agents with unknown interactions in critically ill patients receiving polypharmacy.
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Quality & accreditation
Other guidelines on this topic
- COVID-19: Chloroquine and hydroxychloroquine research
- Guidelines for Critical Care of Seriously Ill Adult Patients with Coronavirus (COVID-19) in the Americas (Short Version)
- Managing People with Asthma during COVID-19: Considerations for Health Providers
- Technical recommendations for the configuration of a specialized Emergency Medical Team for the treatment of Severe Acute Respiratory Infection (SARI). Version 3.5
- Technical and Regulatory Aspects of the Use of Pulse Oximeters in Monitoring COVID-19 Patients
- Issuer
- Pan American Health Organization
- Type
- Procedures, manuals, guidelines
- Edition
- Rapid review, 23 May 2020
- Status
- Current
- Published
- 2020-01-01
- Languages
- English
- Scope
- Systematic review of therapeutic options for COVID-19 including antivirals, immunomodulators, corticosteroids, convalescent plasma, and other investigational agents
- Audience
- Clinicians and public-health professionals managing COVID-19 patients
- Licence
- CC BY-NC-SA 3.0 IGO
- Evidence
- GRADE-rated systematic review of RCTs and observational studies; nearly all evidence rated as very low to low certainty
- Next review
- Living update (document states updates will be developed according to new available evidence)
- 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, 23 May 2020. Washington, D.C.: PAHO; 2020. Licence: CC BY-NC-SA 3.0 IGO.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.
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