IMPORTANCE: Easy-to-administer antiviral treatments may be used to prevent 
progression from asymptomatic infection to COVID-19 and to reduce viral 
carriage.
OBJECTIVE: Evaluate the efficacy and safety of subcutaneous casirivimab and 
imdevimab antibody combination (REGEN-COV) to prevent progression from early 
asymptomatic SARS-CoV-2 infection to COVID-19.
DESIGN: Randomized, double-blind, placebo-controlled, phase 3 study that 
enrolled asymptomatic close contacts living with a SARS-CoV-2-infected household 
member (index case). Participants who were SARS-CoV-2 RT-qPCR-positive at 
baseline were included in the analysis reported here.
SETTING: Multicenter trial conducted at 112 sites in the United States, Romania, 
and Moldova.
PARTICIPANTS: Asymptomatic individuals ≥12 years of age were eligible if 
identified within 96 hours of collection of the index case's positive SARS-CoV-2 
test sample.
INTERVENTIONS: A total of 314 asymptomatic, SARS-CoV-2 RT-qPCR-positive 
individuals living with an infected household contact were randomized 1:1 to 
receive a single dose of subcutaneous REGEN-COV 1200mg (n=158) or placebo 
(n=156).
MAIN OUTCOMES AND MEASURES: The primary endpoint was the proportion of 
participants who developed symptomatic COVID-19 during the 28-day efficacy 
assessment period. The key secondary efficacy endpoints were the number of weeks 
of symptomatic SARS-CoV-2 infection and the number of weeks of high viral load 
(>4 log10 copies/mL). Safety was assessed in all treated participants.
RESULTS: Subcutaneous REGEN-COV 1200mg significantly prevented progression from 
asymptomatic to symptomatic disease compared with placebo (31.5% relative risk 
reduction; 29/100 [29.0%] vs 44/104 [42.3%], respectively; P=.0380). REGEN-COV 
reduced the overall population burden of high-viral load weeks (39.7% reduction 
vs placebo; 48 vs 82 total weeks; P=.0010) and of symptomatic weeks (45.3% 
reduction vs placebo; 89.6 vs 170.3 total weeks; P=.0273), the latter 
corresponding to an approximately 5.6-day reduction in symptom duration per 
symptomatic participant. Six placebo-treated participants had a COVID-19-related 
hospitalization or ER visit versus none for those receiving REGEN-COV. The 
proportion of participants receiving placebo who had ≥1 treatment-emergent 
adverse events was 48.1% compared with 33.5% for those receiving REGEN-COV, 
including events related (39.7% vs 25.8%, respectively) or not related (16.0% vs 
11.0%, respectively) to COVID-19.
CONCLUSIONS AND RELEVANCE: Subcutaneous REGEN-COV 1200mg prevented progression 
from asymptomatic SARS-CoV-2 infection to COVID-19, reduced the duration of high 
viral load and symptoms, and was well tolerated.
TRIAL REGISTRATION: ClinicalTrials.gov Identifier, NCT04452318.