IMPORTANCEThe monoclonal antibody combination of casirivimab and imdevimab reduced viral load, hospitalization, or death when administered as a 1200-mg or greater intravenous (IV) dose in a phase 3 COVID-19 outpatient study. Subcutaneous (SC) and/or lower IV doses should increase accessibility and/or drug supplies for patients. OBJECTIVE To assess the virologic efficacy of casirivimab and imdevimab across different IV and SC doses compared with placebo. DESIGN, SETTING, AND PARTICIPANTS This phase 2, randomized, double-blind, placebocontrolled, parallel-group, dose-ranging study included outpatients with SARS-CoV-2 infection at 47 sites across the United States. Participants could be symptomatic or asymptomatic; symptomatic patients with risk factors for severe COVID-19 were excluded. Data were collected from December 15, 2020, to March 4, 2021. INTERVENTIONS Patients were randomized to a single IV dose (523 patients) of casirivimab and imdevimab at 300, 600, 1200, or 2400 mg or placebo; or a single SC dose (292 patients) of casirivimab and imdevimab at 600 or 1200 mg or placebo. MAIN OUTCOMES AND MEASURES The primary end point was the time-weighted average daily change from baseline (TWACB) in viral load from day 1 (baseline) through day 7 in patients seronegative for SARS-CoV-2 at baseline. RESULTS Among 815 randomized participants, 507 (282 randomized to IV treatment, 148 randomized to SC treatment, and 77 randomized to placebo) were seronegative at baseline and included in the primary efficacy analysis. Participants randomized to IV had a mean (SD) age of 34.6 (9.6) years (160 [44.6%] men; 14 [3.9%] Black; 121 [33.7%] Hispanic or Latino; 309 [86.1%] White); those randomized to SC had a mean age of 34.1 (10.0) years (102 [45.3%] men; 75 [34.7%] Hispanicor Latino; 6 [2.7%] Black; 190 [84.4%] White). All casirivimab and imdevimab treatments showed significant virologic reduction through day 7. Least-squares mean differences in TWACB viral load for casirivimab and imdevimab vs placebo ranged from -0.56 (95% CI; -0.89 to -0.24) log 10 copies/mL for the 1200-mg IV dose to -0.71 (95% CI, -1.05 to -0.38) log 10 copies/mL for the 2400-mg IV dose. There were no adverse safety signals or dose-related safety findings, grade 2 or greater infusionrelated or hypersensitivity reactions, grade 3 or greater injection-site reactions, or fatalities. Two serious adverse events not related to COVID-19 or the study drug were reported.

Lyme carditis (LC), a manifestation of early disseminated Lyme disease, most commonly presents with cardiac conduction abnormalities. It is a transient condition with good prognosis but in extremely rare cases may be life-threatening. We describe a 42-year-old man who presented with progressively worsening generalized weakness, presyncope and dyspnea on exertion for 2 weeks after sustaining a tick bite. He subsequently developed a ‘bull’s eye rash’ on his flank 2 days before his presentation. He was found to have symptomatic third-degree AV conduction blockade with a ventricular escape rhythm resulting in a brief cardiac arrest. Intravenous (IV) ceftriaxone was commenced empirically and a temporary transvenous pacemaker was placed. In a few days he showed dramatic, rapid improvement; the pacemaker was removed, and the patient was discharged on oral doxycycline to complete a 24-day course. This case is unique due to its occurrence in an urban hospital where such cases are uncommon. Cardiac arrest, although brief in this case, is a rare occurrence. Lyme carditis was a surprise diagnosis in our hospital due to the patient’s geographical dislocation during the COVID-19 pandemic.

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