Coronavirus Disease 2019 Treatment: A Review of Early and Emerging Options

McCreary, Erin K; Pogue, Jason M

The first report of a remdesivir-treated patient with COVID-19 in the United States was a 35-year-old male in Snohomish County, Washington who received treatment on hospital day 7 (illness day 11) due to developing pneumonia and persistent fevers [11] . The patient experienced clinical improvement and negativity of oropharyngeal swab on hospital day 8, although nasopharyngeal swab remained positive. No adverse events to remdesivir were reported for the patient, which is consistent with previous case reports of use in other viruses [12, 13] . Among the first 12 patients confirmed by the CDC to have COVID-19 in the United States, 3 were treated with remdesivir via compassionate use protocol [14] . All patients reported transient gastrointestinal symptoms and aminotransferase elevation. All patients are reportedly recovering, but the authors were unable to assess the efficacy or safety of remdesivir based on the lack of comparator and confounding treatments, including concomitant use of corticosteroids in one patient. There are 4 clinical trials currently enrolling patients in the United States (Table 1) . Two additional trials recruiting only in China have been registered on ClinicalTrials.gov NCT04257656 (severe disease) and NCT04252664 (mild/moderate disease). Remdesivir may also be obtained through compassionate use and the emergency Investigational New Drug (eIND) application process. At the time of this review, requests for compassionate use must be submitted online via https://rdvcu.gilead. com/. Compassionate use is only considered for hospitalized patients with polymerase chain reaction (PCR)-confirmed SARS-CoV-2 requiring mechanical ventilation in whom enrollment in a clinical trial is not feasible. Patients are excluded from the compassionate use program if they do not meet the above criteria, have evidence of multiorgan failure, are receiving vasopressors for hypotension, have liver disease defined as alanine aminotransferase (ALT) >5 × upper limit of normal (ULN) or renal impairment defined as creatinine clearance (CrCl) <30 mL/min, or receiving dialysis or continuous venovenous hemofiltration. Inclusion and exclusion criteria for compassionate use may change, so applicants are encouraged to review the most up to date criteria for all potential patients. Clinicians should be cognizant that it typically takes a minimum of 72 hours for institutions to receive emergency institutional review board authorization (if required), protocol, and consent forms from Gilead, US Food and Drug Administration (FDA)-approval for the eIND, and eventual drug shipment. Clinicians should coordinate with their local information technology teams to build a medication order sentence into the electronic health record during this time. Patients may receive other antiviral therapies during the waiting period but must immediately discontinue them if they receive remdesivir for compassionate use.