Respiratory Trials·org

Topic

COVID-19

What the pandemic trials established about steroids, antivirals, and respiratory support.

Dexamethasone is the pandemic's most consequential result. It reduced 28-day mortality in patients receiving oxygen or invasive ventilation, and not in those needing neither (RECOVERY dexamethasone). The subgroup structure is the finding rather than a caveat: benefit tracks the severity of respiratory failure. IL-6 receptor blockade added further benefit in critically ill patients (REMAP-CAP IL-6).

Antivirals performed better on paper than in the populations that followed. Remdesivir shortened recovery by five days without a clear mortality benefit (ACTT-1). Nirmatrelvir-ritonavir cut hospitalisation or death by 89% (EPIC-HR) — in unvaccinated, previously uninfected, high-risk adults facing an earlier variant, which is the context anyone quoting that number needs.

Escalated anticoagulation did not help the critically ill (REMAP-CAP anticoagulation), despite the thrombosis rates that prompted it empirically. The trial was stopped for futility.

The methodological legacy may outlast the therapeutic one: adaptive platform trials answered these questions in months, and have since been turned on other diseases.

Corticosteroids in COVID-19

Trial Year Therapy Effect Finding
COVID STEROID 2 2021 Higher-dose dexamethasone Doubling the dexamethasone dose added nothing over the standard 6 mg
RECOVERY dexamethasone 2021 Dexamethasone Dexamethasone reduced mortality in COVID-19 patients needing oxygen, and not in those who did not
CoDEX 2020 Dexamethasone Dexamethasone gave 2.6 more ventilator-free days in COVID-19 ARDS

Anticoagulation in COVID-19

Trial Year Therapy Effect Finding
INSPIRATION 2021 Intermediate-dose prophylactic anticoagulation Intermediate-dose prophylaxis was no better than standard dose in critically ill COVID-19
REMAP-CAP anticoagulation 2021 Therapeutic-dose heparin Full-dose anticoagulation did not help critically ill COVID-19 patients

Antivirals in outpatients

Trial Year Therapy Effect Finding
EPIC-SR 2024 Nirmatrelvir-ritonavir Nirmatrelvir did nothing for symptoms in a largely vaccinated, standard-risk population
EPIC-HR 2022 Nirmatrelvir-ritonavir Nirmatrelvir-ritonavir cut hospitalisation or death by 89% in unvaccinated high-risk outpatients

Non-invasive support in COVID-19

Trial Year Therapy Effect Finding
RECOVERY-RS 2022 CPAP or high-flow nasal oxygen CPAP reduced intubation or death in COVID-19; high-flow nasal oxygen did not
SOHO-COVID 2022 High-flow nasal oxygen High-flow nasal oxygen did not reduce mortality in COVID-19 respiratory failure

Antivirals in hospitalised patients

Trial Year Therapy Effect Finding
ACTT-1 2020 Remdesivir Remdesivir shortened time to recovery by five days without a clear mortality benefit

Immunomodulation in COVID-19

Trial Year Therapy Effect Finding
ACTT-2 2021 Baricitinib Adding baricitinib to remdesivir shortened recovery by a day, most in those on high-flow oxygen

Immunomodulation in critical COVID-19

Trial Year Therapy Effect Finding
REMAP-CAP IL-6 2021 Tocilizumab or sarilumab IL-6 receptor blockade improved organ support-free days and survival in critical COVID-19

Key references

Guidelines, standards and reviews for this topic.