Recommendation 1: In ambulatory patients with mild-to-moderate COVID-19 at high risk for progression to severe disease, the IDSA guideline panel suggests nirmatrelvir/ritonavir initiated within five days of symptom onset rather than no nirmatrelvir/ritonavir. (Conditional recommendation†, Low certainty of evidence) Remarks: • Patients’ medications need to be screened for serious drug interactions • Dosing based on renal function: o Estimated glomerular filtration rate (eGFR) > 60 ml/min: 300 mg nirmatrelvir/100 ritonavir every 12 hours for five days o eGFR ≤60 mL/min and ≥30 mL/min: 150 mg nirmatrelvir/100 mg ritonavir every 12 hours for five days o eGFR <30 mL/min: not recommended • Patients with mild-to-moderate COVID-19 who are at high risk of progression to severe disease admitted to the hospital may also receive nirmatrelvir/ritonavir *Options for treatment and management of ambulatory patients include nirmatrelvir/ritonavir, remdesivir for a 3-day course, molnupiravir, and neutralizing monoclonal antibodies. Patient-specific factors (e.g., symptom duration, renal function, drug interactions) as well as product availability should drive decision-making regarding choice of agent. Data for combination treatment do not exist in this setting

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