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Antiviral Therapies for Adults with Mild to Moderate COVID-19 Infection

Author/s: 
Kristen M. Marks, Andrew M. Davis

With increasing population immunity through vaccination and prior infection, the risk of severe COVID-19, hospitalization, and death has substantially decreased in all age groups in the US since 2021.1 However, certain populations, especially those aged 65 years or older, remain at increased risk for progression to severe disease. This updated guideline provides a risk-stratified approach to antiviral therapies for patients with mild to moderate COVID-19 (defined as symptoms of respiratory infection with oxygen saturation >94% while breathing room air). Antiviral therapies are most effective when initiated within 5 to 7 days of COVID-19 symptom onset.

Keywords 
COVID-19 Antiviral

Olgotrelvir as a Single-Agent Treatment of Nonhospitalized Patients with Covid-19

Author/s: 
Rongmeng Jiang, Bing Han, Wanhong Xu, Xiaoying Zhang, Chunxian Peng, Qiang Dang, Wei Sun, Ling Lin

Background: Olgotrelvir is an oral antiviral with dual mechanisms of action targeting severe acute respiratory syndrome coronavirus 2 main protease (i.e., Mpro) and human cathepsin L. It has potential to serve as a single-agent treatment of coronavirus disease 2019 (Covid-19).

Methods: We conducted a phase 3, double-blind, randomized, placebo-controlled trial to evaluate the efficacy and safety of olgotrelvir in 1212 nonhospitalized adult participants with mild to moderate Covid-19, irrespective of risk factors, who were randomly assigned to receive orally either 600 mg of olgotrelvir or placebo twice daily for 5 days. The primary and key secondary end points were time to sustained recovery of a panel of 11 Covid-19-related symptoms and the viral ribonucleic acid (RNA) load. The safety end point was incidence of treatment-emergent adverse events.

Results: The baseline characteristics of 1212 participants were similar in the two groups. In the modified intention-to-treat population (567 patients in the placebo group and 558 in the olgotrelvir group), the median time to symptom recovery was 205 hours in the olgotrelvir group versus 264 hours in the placebo group (hazard ratio, 1.29; 95% confidence interval [CI], 1.13 to 1.46; P<0.001). The least squares mean (95% CI) changes of viral RNA load from baseline were -2.20 (-2.59 to -1.81) log10 copies/ml in olgotrelvir-treated participants and -1.40 (-1.79 to -1.01) in participants receiving placebo at day 4. Skin rash (3.3%) and nausea (1.5%) were more frequent in the olgotrelvir group than in the placebo group; there were no treatment-related serious adverse events, and no deaths were reported.

Conclusions: Olgotrelvir as a single-agent treatment significantly improved symptom recovery. Adverse effects were not dose limiting. (Funded by Sorrento Therapeutics, a parent company of ACEA Therapeutics; ClinicalTrials.gov number, NCT05716425.).

Keywords 
COVID-19 Antiviral oral

Oral Antiviral Medications for COVID-19

Author/s: 
Petty, L. A., Malani, P. N.

Twonewantiviralmedications, ritonavir-boostednirmatrelvir (Paxlovid,
ie, nirmatrelvir-ritonavir) and molnupiravir (Lagevrio), are currently
available in theUS underemergency useauthorization. These 2 drugs
areauthorized for treatmentofpatientswithmild tomoderateCOVID19 who are not currently hospitalized but are at high risk of developingseveredisease.Nirmatrelvir-ritonavirandmolnupiravirareapproved
for use only within 5 days of onset of COVID-19 symptoms.
Nirmatrelvir-ritonavir andmolnupiravir should be considered for
patients with symptoms of COVID-19 who test positive for SARSCoV-2 and either are an older adult (aged 65 years or older) or are
aged 12 years or older with an underlying condition that increases
risk of severe outcomes of COVID-19 (such as cancer, heart disease,
diabetes, and obesity).

Keywords 
medication Antiviral COVID-19 treatment
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