Pan American Health Organization · Rapid review, 8 September 2020
Rapid evidence review of COVID-19 treatments for clinicians managing hospitalised and outpatient cases (8 September 2020)
- Issuer
- Pan American Health Organization
- Edition
- Rapid review, 8 September 2020
- Audience
- Clinicians and public-health professionals managing COVID-19 patients in hospital and outpatient settings
- Evidence
- GRADE-rated systematic review of randomised and non-randomised controlled trials; living evidence synthesis updated continuously
- Reviewed
- 20 Oct 2026 · GMJ
What this guideline says
GMJ summary
This living rapid systematic review synthesises randomised and non-randomised controlled trials evaluating more than 40 therapeutic options for COVID-19. The review provides certainty-rated evidence on patient-important outcomes including mortality, mechanical ventilation, symptom resolution, infection prevention, and severe adverse events.
High-certainty evidence demonstrates that low-to-moderate dose corticosteroids (dexamethasone 6 mg daily for 10 days) reduce mortality in patients with severe COVID-19. Remdesivir shows low-certainty evidence of mortality reduction and improved symptom resolution. Hydroxychloroquine/chloroquine and lopinavir-ritonavir show no mortality benefit with moderate certainty. Convalescent plasma and tocilizumab show non-significant trends toward benefit but require further research. Evidence for ivermectin, anticoagulation strategies, and most other interventions remains uncertain.
The review emphasises that most investigational therapies should only be used within ethically approved, randomised controlled trials. Thromboprophylaxis is recommended for all hospitalised COVID-19 patients with severe disease, following existing guidelines for acute medical conditions.
Key points
For clinicians — doses and thresholds as stated in the guideline
- Corticosteroids (dexamethasone 6 mg oral or IV once daily for 10 days, or equivalent methylprednisolone or hydrocortisone doses) significantly reduce mortality in severe COVID-19 (RR 0.90, 95% CI 0.84–0.97; high certainty)
- Remdesivir (200 mg IV loading dose day 1, then 100 mg daily days 2–10) may reduce mortality (RR 0.78, 95% CI 0.56–1.08) and improves symptom resolution time (low certainty)
- Hydroxychloroquine/chloroquine does not reduce mortality (RR 1.08, 95% CI 0.97–1.19; moderate certainty) or mechanical ventilation requirements and should not be used outside trials
- Lopinavir-ritonavir (400/100 mg twice daily) does not reduce mortality (RR 1.00, 95% CI 0.83–1.21; moderate certainty)
- Convalescent plasma (200–300 mL in 1–2 infusions) shows non-significant trend toward mortality reduction (RR 0.77, 95% CI 0.48–1.24; low certainty); further research needed
- Tocilizumab (8 mg/kg IV once, or 400 mg once or twice) may not reduce mortality (RR 1.01, 95% CI 0.68–1.52; low certainty) but may reduce mechanical ventilation needs
- Thromboprophylaxis with heparins is recommended for all hospitalised COVID-19 patients with severe or critical disease, following standard medical thromboprophylaxis protocols
- Ivermectin, interferons, mesenchymal stem cells, vitamin C/D, and most other experimental therapies have very low certainty evidence and should only be used in randomised controlled trials
Interventions effects and certainty in randomised controlled trials (RCT)
Table extracted from the guideline
| Intervention | Mortality effect | Mechanical ventilation effect | Symptom resolution | Certainty of evidence |
|---|---|---|---|---|
| Corticosteroids (9 RCT, 7823 patients) | RR 0.90 (0.84–0.97); RD –3.3% | RR 0.84 (0.67–1.04); RD –1.8% | RR 1.41 (1.08–1.83); RD +22.7% | High ⊕⊕⊕⊕ for mortality |
| Remdesivir (4 RCT, 2277 patients) | RR 0.78 (0.56–1.08); RD –7.3% | Very low certainty | RR 1.17 (1.03–1.33); RD +3.8% | Low ⊕⊕○○ |
| Hydroxychloroquine/chloroquine (16 RCT, 10066 patients) | RR 1.08 (0.97–1.19); RD +2.6% | RR 1.1 (0.89–1.35); RD +1.2% | RR 1.1 (0.92–1.31); RD +5.5% | Moderate ⊕⊕⊕○ |
| Lopinavir-ritonavir (6 RCT, 5391 patients) | RR 1.00 (0.83–1.21); RD 0% | Very low certainty | Very low certainty | Moderate ⊕⊕⊕○ |
| Convalescent plasma (4 RCT, 734 patients) | RR 0.77 (0.48–1.24); RD –7.6% | RR 0.79 (0.44–1.44); RD –2.4% | Very low certainty | Low ⊕⊕○○ |
| Tocilizumab (1 RCT, 438 patients) | RR 1.01 (0.68–1.52); RD +0.5% | RR 0.76 (0.53–1.09); RD –2.8% | HR 1.26 (0.97–1.64); RD +8.4% | Low ⊕⊕○○ |
Source: Pan American Health Organization, Ongoing Living Update of Potential COVID-19 Therapeutics: Summary of Rapid Systematic Reviews. Reproduced in summary form.
What changed in this edition
Versus the previous edition
- This is a living update as of 8 September 2020; the review is continuously updated as new evidence becomes available
- RECOVERY trial results for dexamethasone now included, providing high-certainty evidence for corticosteroid mortality benefit
- RECOVERY trial preliminary results showing no benefit for hydroxychloroquine and lopinavir-ritonavir incorporated
- Four RCT on convalescent plasma now available (previously fewer studies)
- Remdesivir evidence expanded to four RCT including ACTT-1 and SIMPLE trials
From the guideline
Verbatim
“The body of evidence on steroids including nine RCT shows that low/moderate dose treatment schemes (RECOVERY trial dose was 6 mg of oral or intravenous preparation once daily for 10 days) are effective in reducing mortality in patients with severe COVID-19 infection.”
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
This PAHO rapid living review arrived at a critical moment when evidence-based COVID-19 treatment protocols were urgently needed across the Americas and globally, including Georgia and neighbouring countries. The high-certainty finding that widely available, inexpensive corticosteroids reduce mortality in severe COVID-19 by approximately 3.3 percentage points was immediately actionable for our national protocols; Georgia's Ministry of Health swiftly incorporated dexamethasone into COVID-19 management guidelines in 2020. Equally important for our context was the moderate-certainty evidence that hydroxychloroquine and lopinavir-ritonavir—both of which had seen widespread off-label use in Georgia and the region during early 2020—confer no benefit and should be reserved for trials only. I would emphasise to Georgian clinicians that thromboprophylaxis must be systematically applied to all hospitalised severe cases, as thromboembolic complications are frequent and standard prophylactic heparin regimens are well-established and safe. The realistic implementation caveat is that this is a living review dated September 2020; subsequent evidence (including the WHO SOLIDARITY trial published October 2020 and later meta-analyses) has further refined recommendations, so clinicians must consult the most current WHO or national guidance and recognise that remdesivir, convalescent plasma, and tocilizumab recommendations have evolved since this document was issued.
ORCID 0000-0001-7609-4515 · Perspective written for the GMJ Guidelines Library, 20 Oct 2026
Applicability
Georgia and the South Caucasus
For Georgia and the South Caucasus, this evidence synthesis is directly applicable to COVID-19 case management in hospital and outpatient settings. Corticosteroids (dexamethasone, methylprednisolone, or hydrocortisone) are widely available, inexpensive, and should be prioritised for all hospitalised patients with severe COVID-19 requiring oxygen. Remdesivir availability may be limited by cost and supply; national protocols should clarify access criteria for severe cases. Hydroxychloroquine and lopinavir-ritonavir, which were widely used early in the pandemic across the region, should be discontinued outside research trials given moderate-certainty evidence of no benefit. Thromboprophylaxis with low-molecular-weight or unfractionated heparin is standard practice and should be systematically applied. National programmes should ensure that experimental therapies (ivermectin, convalescent plasma, tocilizumab) are restricted to approved clinical trials with informed consent, and that therapeutic protocols are updated as new evidence emerges from this living review.
Questions this guideline answers
Quick answers
Which corticosteroid dose should I use for severe COVID-19?
Dexamethasone 6 mg once daily (oral or IV) for 10 days is the best-studied regimen (RECOVERY trial, 2104 patients). Equivalent doses of methylprednisolone (32 mg daily) or hydrocortisone (160–200 mg daily) are acceptable alternatives. Use in patients with severe disease (oxygen requirement); benefit is greatest in those requiring mechanical ventilation or oxygen but was also seen in the broader population with 14% control-group mortality.
Should I use hydroxychloroquine or lopinavir-ritonavir for COVID-19?
No. Moderate-certainty evidence from large RCT (including RECOVERY trial with >4700 patients for hydroxychloroquine, >4900 for lopinavir-ritonavir) shows no mortality benefit, no reduction in mechanical ventilation, and no improvement in symptom resolution. Both should be discontinued outside clinical trials. Hydroxychloroquine may slightly increase severe adverse events (RR 1.22, low certainty).
When should I give remdesivir?
Remdesivir (200 mg IV day 1, then 100 mg daily for up to 10 days or until discharge) may reduce mortality and improve symptom resolution in severe COVID-19, but certainty is low due to imprecision and risk of bias. It is not a substitute for corticosteroids. Use should follow national protocols and consider limited availability. The ACTT-1 trial (1059 patients) showed a mortality RR of 0.78 (95% CI 0.56–1.08) and faster symptom resolution (RR 1.17, 95% CI 1.03–1.33).
Should all hospitalised COVID-19 patients receive thromboprophylaxis?
Yes. Thromboembolic complications are frequent in COVID-19. Current guidelines recommend thromboprophylactic doses of heparin (low-molecular-weight or unfractionated) for all hospitalised patients with severe or critical COVID-19, as for other acute severe medical conditions. Optimal dosing strategy (prophylactic vs. therapeutic anticoagulation) is not yet established by RCT; standard prophylactic doses are recommended until further evidence is available.
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Quality & accreditation
Other guidelines on this topic
- Ongoing Living Update of Potential COVID-19 Therapeutics: Summary of Rapid Systematic Reviews
- Considerations for the Implementation and Management of Contact Tracing for Coronavirus Disease 2019 (COVID-19) in the Region of the Americas
- 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, 8 September 2020
- Status
- Current
- Published
- 2020-01-01
- Languages
- English, Spanish
- Scope
- Adults and children with confirmed or suspected COVID-19 (exposed, mild, moderate, severe, critical); >40 pharmacological interventions evaluated
- Audience
- Clinicians and public-health professionals managing COVID-19 patients in hospital and outpatient settings
- Licence
- CC BY-NC-SA 3.0 IGO
- Evidence
- GRADE-rated systematic review of randomised and non-randomised controlled trials; living evidence synthesis updated continuously
- Next review
- Continuously updated (living review); check L·OVE platform (app.iloveevidence.com/covid-19) for latest version
- 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, 8 September 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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