RESUMO
BACKGROUND: SYN023 is an anti-rabies monoclonal antibody mixture administered as part of post-exposure prophylaxis regimens. The rabies virus neutralizing antibody (RVNA) concentration generally accepted as an adequate immune response to vaccination is ≥ 0.5 IU/mL. METHODS: Within 54 h of potential rabies exposure, 448 patients in two risk substrata of WHO Category III exposure were randomized to receive either 0.3 mg/kg SYN023 or 0.133 mL/kg human rabies immunoglobulin (HRIG) injected in and around the wound site(s) plus a course of rabies vaccination. Patients were followed for safety and absence of rabies for ≥ 365 days. RESULTS: GMT RVNA was higher with SYN023 throughout the 2-week post-treatment period. In the primary analysis group (n = 368), 99.4 % of SYN023 recipients versus 4.5 % of HRIG recipients had protective RVNA levels on Day 4. On Day 8, 98.1 % SYN023 versus 12.2 % HRIG recipients were protected. The SYN023:HRIG ratio of geometric mean titer of RVNA (RVNA GMTs) on Day 8 (19.42) exceeded the 10 % superiority margin (P < 0.0001) indicating higher Day 8 RVNA with SYN023. On Day 99, the SYN023:HRIG RVNA GMT ratio (0.66) was below the non-inferiority margin of 20 % (P = 0.9485) suggesting some moderation of vaccine immune response by SYN023 relative to HRIG. The ratio of percent SYN023:HRIG recipients achieving RVNA ≥ 0.5 IU/mL on Day 99 (0.98) met the non-inferiority margin of 20 % (P = 0.013) indicating anti-rabies immune response with SYN023 was non-inferior to HRIG despite this effect. There were no probable/confirmed rabies cases in any patient. Study regimens were well tolerated. CONCLUSIONS: SYN023 provided higher RVNA than HRIG soon after rabies exposure. By Day 99 post-treatment, GM RVNA with SYN023 was lower than HRIG, however, the percent of SYN023 recipients with a protective response was not inferior at this time point. No rabies cases were reported in the study. The SYN023 safety profile was acceptable. CLINICALTRIALS: gov ID: NCT03961555.
RESUMO
OBJECTIVE: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), primarily targets the respiratory system. This study describes the characteristics associated with mortality among patients infected with SARS-CoV-2 at a single hospital in Baguio City, Philippines. METHODS: We reviewed medical records (including history, laboratory results and treatment regimen) of 280 confirmed COVID-19 patients admitted to a single hospital during March-October 2020. Clinical characteristics and outcomes (frequency and type of complication, recovery rate and mortality) were evaluated. Multiple logistic regression was used to analyse factors associated with mortality. RESULTS: The mean age of COVID-19 patients was 48.4 years and the female-to-male ratio was 1.8:1. Hypertension, cardiovascular disease (CVD) and diabetes were the most frequent comorbidities reported. Common presenting symptoms were respiratory and constitutional, with 41% of patients not reporting symptoms on admission. Patients with moderate, severe and critical disease comprised 45%, 8% and 4%, respectively. A total of 15% had complications, health care-associated pneumonia being the most frequent complication. The recovery rate was 95%; 5% of patients died, with multiorgan failure being the most common cause. The presence of CVD, chronic kidney disease, prolonged prothrombin time and elevated lactate dehydrogenase (LDH) were associated with mortality. DISCUSSION: Most COVID-19 patients in our population had asymptomatic to moderate disease on admission. Mortality from COVID-19 was associated with having CVD, chronic kidney disease, elevated LDH and prolonged prothrombin time. Based on these results, we emphasize that people should take all necessary precautions to avoid infection with SARS-CoV-2.