RESUMO
Background: Incidence data of respiratory syncytial virus-associated lower respiratory tract illness (RSV-LRTI) are sparse in low- and middle-income countries (LMICs). We estimated RSV-LRTI incidence rates (IRs) in infants in LMICs using World Health Organization case definitions. Methods: This prospective cohort study, conducted in 10 LMICs from May 2019 to October 2021 (largely overlapping with the coronavirus disease 2019 [COVID-19] pandemic), followed infants born to women with low-risk pregnancies for 1 year from birth using active and passive surveillance to detect potential LRTIs, and quantitative reverse-transcription polymerase chain reaction on nasal swabs to detect RSV. Results: Among 2094 infants, 32 (1.5%) experienced an RSV-LRTI (8 during their first 6 months of life, 24 thereafter). Seventeen (0.8%) infants had severe RSV-LRTI and 168 (8.0%) had all-cause LRTI. IRs (95% confidence intervals [CIs]) of first RSV-LRTI episode were 1.0 (.3-2.3), 0.8 (.3-1.5), and 1.6 (1.1-2.2) per 100 person-years for infants aged 0-2, 0-5, and 0-11 months, respectively. IRs (95% CIs) of the first all-cause LRTI episode were 10.7 (8.1-14.0), 11.7 (9.6-14.0), and 8.7 (7.5-10.2) per 100 person-years, respectively. IRs varied by country (RSV-LRTI: 0.0-8.3, all-cause LRTI: 0.0-49.6 per 100 person-years for 0- to 11-month-olds). Conclusions: RSV-LRTI IRs in infants in this study were relatively low, likely due to reduced viral circulation caused by COVID-19-related nonpharmaceutical interventions. Clinical Trials Registration: NCT03614676.
RESUMO
BACKGROUND: Development of safe and effective SARS-CoV-2 therapeutics is a high priority. Amubarvimab and romlusevimab are noncompeting anti-SARS-CoV-2 monoclonal antibodies with an extended half-life. OBJECTIVE: To assess the safety and efficacy of amubarvimab plus romlusevimab. DESIGN: Randomized, placebo-controlled, phase 2 and 3 platform trial. (ClinicalTrials.gov: NCT04518410). SETTING: Nonhospitalized patients with COVID-19 in the United States, Brazil, South Africa, Mexico, Argentina, and the Philippines. PATIENTS: Adults within 10 days onset of symptomatic SARS-CoV-2 infection who are at high risk for clinical progression. INTERVENTION: Combination of monoclonal antibodies amubarvimab plus romlusevimab or placebo. MEASUREMENTS: Nasopharyngeal and anterior nasal swabs for SARS-CoV-2, COVID-19 symptoms, safety, and progression to hospitalization or death. RESULTS: Eight-hundred and seven participants who initiated the study intervention were included in the phase 3 analysis. Median age was 49 years (quartiles, 39 to 58); 51% were female, 18% were Black, and 50% were Hispanic or Latino. Median time from symptom onset at study entry was 6 days (quartiles, 4 to 7). Hospitalizations and/or death occurred in 9 (2.3%) participants in the amubarvimab plus romlusevimab group compared with 44 (10.7%) in the placebo group, with an estimated 79% reduction in events (P < 0.001). This reduction was similar between participants with 5 or less and more than 5 days of symptoms at study entry. Grade 3 or higher treatment-emergent adverse events through day 28 were seen less frequently among participants randomly assigned to amubarvimab plus romlusevimab (7.3%) than placebo (16.1%) (P < 0.001), with no severe infusion reactions or drug-related serious adverse events. LIMITATION: The study population was mostly unvaccinated against COVID-19 and enrolled before the spread of Omicron variants and subvariants. CONCLUSION: Amubarvimab plus romlusevimab was safe and significantly reduced the risk for hospitalization and/or death among nonhospitalized adults with mild to moderate SARS-CoV-2 infection at high risk for progression to severe disease. PRIMARY FUNDING SOURCE: National Institute of Allergy and Infectious Diseases of the National Institutes of Health.
