ABSTRACT
BackgroundThe COVID-19 pandemic has led to over 600,000 deaths in the United States and continues to disrupt lives even as effective vaccines are available. We aimed to estimate the impact and health system cost of implementing post-exposure prophylaxis against household exposure to COVID-19 with monoclonal antibodies. MethodsWe developed a decision-analytical model analysis of results from a recent randomized controlled trial with complementary data on household demographic structure, vaccine coverage, and COVID-19 confirmed case counts for the representative month of May, 2021. The model population includes individuals of all ages in the United States by sex and race/ethnicity. ResultsIn a month of similar intensity to May, 2021, in the USA, a monoclonal antibody post-exposure prophylaxis program reaching 50% of exposed unvaccinated household members aged 50+, would avert 1,813 (1,171 - 2,456) symptomatic infections, 526 (343 - 716) hospitalizations, and 83 (56 - 116) deaths. Assuming the unit cost of administering the intervention was US$ 1,264, this program would save the health system US$ 3,055,202 (-14,034,632 - 18,787,692). ConclusionsCurrently in the United States, health system and public health actors have an opportunity to improve health and reduce costs through COVID-19 post-exposure prophylaxis with monoclonal antibodies.
Subject(s)
COVID-19ABSTRACT
ImportanceSARS-CoV-2 viral trajectory has not been well-characterized in documented incident infections. These data will inform SARS-CoV-2 natural history, transmission dynamics, prevention practices, and therapeutic development. ObjectiveTo prospectively characterize early SARS-CoV-2 viral shedding in persons with incident infection. DesignProspective cohort study. SettingSecondary data analysis from a multicenter study in the U.S. ParticipantsThe samples derived from a randomized controlled trial of 829 community-based asymptomatic participants recently exposed (<96 hours) to persons with SARS-CoV-2. Participants collected daily mid-turbinate swabs for SARS-CoV-2 detection by polymerase-chain-reaction and symptom diaries for 14-days. Persons with negative swab for SARS-CoV-2 at baseline who developed infection during the study were included in the analysis. ExposureLaboratory-confirmed SARS-CoV-2 infection. Main outcomes and measuresThe observed SARS-CoV-2 viral shedding characteristics were summarized and shedding trajectories were examined using a piece-wise linear mixed-effects modeling. Whole viral genome sequencing was performed on samples with cycle threshold (Ct)<34. ResultsNinety-seven persons (57% women, median age 37-years) developed incident infections during 14-days of follow-up. Two-hundred fifteen sequenced samples were assigned to 15 lineages that belonged to the G614 variant. Forty-two (43%), 18(19%), and 31(32%) participants had viral shedding for 1 day, 2-6 days, and [≥]7 days, with median peak viral load Ct of 38.5, 36.7, and 18.3, respectively. Six (6%) participants had 1-6 days of observed viral shedding with censored duration. The peak average viral load was observed on day 3 of viral shedding. The average Ct value was lower, indicating higher viral load, in persons reporting COVID-19 symptoms than asymptomatic. Using the statistical model, the median time from shedding onset to peak viral load was 1.4 days followed by a median of 9.7 days before clearance. Conclusions and RelevanceIncident SARS-CoV-2 G614 infection resulted in a rapid viral load peak followed by slower decay and positive correlation between peak viral load and shedding duration; duration of shedding was heterogeneous. This longitudinal evaluation of the SARS-CoV-2 G614 variant with frequent molecular testing may serve as a reference for comparing emergent viral lineages to inform clinical trial designs and public health strategies to contain the spread of the virus. KEY POINTSO_ST_ABSQuestionC_ST_ABSWhat are the early SARS-CoV-2 G614 viral shedding characteristics in persons with incident infection? FindingsIn this prospective cohort of 97 community-based participants who collected daily mid-turbinate swabs for SARS-CoV-2 detection after recent exposure to SARS-CoV-2, viral trajectory was characterized by a rapid peak followed by slower decay. Peak viral load correlated positively with symptoms. The duration of shedding was heterogeneous. MeaningA detailed description of the SARS-CoV-2 G614 viral shedding trajectory serves as baseline for comparison to new viral variants of concern and inform models for the planning of clinical trials and transmission dynamics to end this pandemic.
Subject(s)
COVID-19 , Severe Acute Respiratory SyndromeABSTRACT
BackgroundCasirivimab and imdevimab (REGEN-COV) markedly reduces risk of hospitalization or death in high-risk individuals with Covid-19. Here we explore the possibility that subcutaneous REGEN-COV prevents SARS-CoV-2 infection and subsequent Covid-19 in individuals at high risk of contracting SARS-CoV-2 by close exposure in a household with a documented SARS-CoV-2-infected individual. MethodsIndividuals [≥]12 years were enrolled within 96 hours of a household contact being diagnosed with SARS-CoV-2 and randomized 1:1 to receive 1200 mg REGEN-COV or placebo via subcutaneous injection. The primary efficacy endpoint was the proportion of participants without evidence of infection (SARS-CoV-2 RT-qPCR- negative) or prior immunity (seronegative) who subsequently developed symptomatic SARS-CoV-2 infection during a 28-day efficacy assessment period. ResultsSubcutaneous REGEN-COV significantly prevented symptomatic SARS-CoV-2 infection compared with placebo (81.4% risk reduction; 11/753 [1.5%] vs. 59/752 [7.8%], respectively; P<0.0001), with 92.6% risk reduction after the first week (2/753 [0.3%] vs. 27/752 [3.6%], respectively). REGEN-COV also prevented overall infections, either symptomatic or asymptomatic (66.4% risk reduction). Among infected participants, the median time to resolution of symptoms was 2 weeks shorter with REGEN-COV vs. placebo (1.2 vs. 3.2 weeks, respectively), and the duration of time with high viral load (>104 copies/mL) was lower (0.4 vs. 1.3 weeks, respectively). REGEN-COV was generally well tolerated. ConclusionsAdministration of subcutaneous REGEN-COV prevented symptomatic Covid-19 and asymptomatic SARS-CoV-2 infection in uninfected household contacts of infected individuals. Among individuals who became infected, REGEN-COV reduced the duration of symptomatic disease, decreased maximal viral load, and reduced the duration of detectable virus. (ClinicalTrials.gov number, NCT04452318.)
Subject(s)
COVID-19ABSTRACT
Background: Casirivimab and imdevimab administered together (REGEN-COV) markedly reduces the risk of hospitalization or death in high-risk, symptomatic individuals with COVID-19. Here, we report phase 3 results of early treatment of asymptomatic, SARS-CoV-2-positive adults and adolescents with subcutaneous REGEN-COV. Methods: Individuals [≥]12 years of age were eligible if identified within 96 hours of a household contact being diagnosed as SARS-CoV-2-positive; 314 were randomized 1:1 to receive subcutaneous REGEN-COV 1200mg or placebo. The primary endpoint was the proportion of infected participants without evidence of prior immunity (i.e., SARS-CoV-2-RT-qPCR-positive/seronegative) who subsequently developed symptomatic Covid-19 during a 28-day efficacy assessment period. 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=0.0380). REGEN-COV also reduced the overall population burden of high viral load weeks (39.7% reduction vs. placebo; 48 vs. 82 total weeks; P=0.0010) and of symptomatic weeks (45.3% reduction vs. placebo; 89.6 vs. 170.3 total weeks; P=0.0273), the latter corresponding to an approximately 5.6-day reduction 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 to 33.5% for those receiving REGEN-COV, including Covid-19-related (39.7% vs. 25.8%, respectively) or non-Covid-19-related (16.0% vs. 11.0%, respectively) events. Conclusions: Subcutaneous REGEN-COV 1200mg prevented progression from asymptomatic to symptomatic infection, reduced the duration of high viral load and symptoms, and was well tolerated.