Real-World Effectiveness of Nirsevimab Against Respiratory Syncytial Virus: A Test-Negative Case-Control Study.

IMPORTANCE: Nirsevimab, a long-acting monoclonal antibody, has demonstrated efficacy against RSV-related lower respiratory tract infections (LRTIs) in clinical trials. Post-licensure monitoring is essential to confirm these benefits in real-world settings. OBJECTIVE: To evaluate the real-world effectiveness of nirsevimab against medically attended RSV infections in infants and to assess how effectiveness varies by disease severity, dosage, and time since immunization. DESIGN SETTING AND PARTICIPANTS: This test-negative case-control study used inpatient, outpatient, and emergency room data from the Yale New Haven Health System. Nirsevimab-eligible infants who were tested for RSV using polymerase chain reaction between October 1, 2023 and May 9, 2024 were included. Cases were infants with confirmed RSV infections; controls were those who tested negative. EXPOSURE: Nirsevimab immunization, verified through state immunization registries. MAIN OUTCOMES AND MEASURES: Effectiveness was estimated using multivariable logistic regression, adjusting for age, calendar month, and individual risk factors. Separate models examined effectiveness by clinical setting, disease severity, dose, and time since immunization. Broader outcomes, including all-cause LRTI and LRTI-related hospitalization, were also analyzed, with stratification by early and late respiratory seasons. RESULTS: The analytic sample included 3,090 infants (median age 6.7 months, IQR 3.6-9.7), with 680 (22.0%) RSV-positive and 2,410 (78.0%) RSV-negative. 21 (3.1%) RSV-positive and 309 (12.8%) RSV-negative infants received nirsevimab. Effectiveness against RSV infection was 68.4% (95% CI, 50.3%-80.8%). Effectiveness was 61.6% (95% CI, 35.6%-78.6%) for outpatient visits and 80.5% (95% CI, 52.0%-93.5%) for hospitalizations. The highest effectiveness, 84.6% (95% CI, 58.7%-95.6%), was observed against severe RSV outcomes requiring ICU admission or high-flow oxygen. Although effectiveness against RSV infections declined over time, it remained significant at 55% (95% credible interval, 16%-75%) at 14 weeks post-immunization. Protective effectiveness was also observed against all-cause LRTI and LRTI-related hospitalizations during peak RSV season (49.4% [95% CI, 10.7%-72.9%] and 79.1% [95% CI, 27.6%-94.9%], respectively). However, from February to May, when RSV positivity was low, effectiveness against these broader outcomes was negligible. CONCLUSIONS AND RELEVANCE: Nirsevimab provided substantial protection against RSV-related outcomes for at least three months. These findings support the continued use of nirsevimab and provide evidence that may help build public confidence in the immunization program.

Therapeutic inefficacy of protocol driven intravenous unfractionated heparin infusion in the current era.

Unfractionated heparin (UFH) is commonly used for several life-threatening conditions requiring anticoagulant therapy but failure to reach therapeutic levels in 24 h can be associated with adverse outcomes. Use of low molecular weight heparin (LMWH) may provide an alternative while providing superior outcomes as compared to UFH. We studied 100 patients who underwent UFH therapy for >24 h and found that theoretically 80 % were eligible for LMWH therapy. Only 29 % and 40 % of the total aPTT draws were in the therapeutic window within the first 24 h and at 25-48 h respectively. This study reports that a vast majority of patients remain outside of therapeutic aPTT within first 24-48 h when anticoagulated with UFH. With high eligibility for LMWH therapy, its substitution can potentially lead to better patient outcomes, higher levels of therapeutic efficacy, and decrease in hospital resources.

Persistence of SARS-CoV-2 in saliva: Implications for late-stage diagnosis and infectious duration.

Saliva has been a COVID-19 diagnostic specimen of interest due to its simple collection, scalability, and yield. Yet COVID-19 testing and estimates of the infectious period remain largely based on nasopharyngeal and nasal swabs. We sought to evaluate whether saliva testing captured prolonged presence of SARS-CoV-2 and potential infectiousness later in the disease course. We conducted an observational study of symptomatic COVID-19 patients at University Hospital in Newark, NJ. Paired saliva and nasal specimens from 96 patients were analyzed, including longitudinal analysis of paired observations from 28 of these patients who had multiple time-points. Saliva detected significantly more cases of COVID-19 beyond 5 days (86.1% [99/115] saliva vs 48.7% [56/115] nasal, p-value < 0.001), 9 days (79.4% [50/63] saliva vs 36.5% [23/63] nasal, p-value < 0.001) and 14 days (71.4% [20/28] saliva vs 32.1% [9/28] nasal, p-value = 0.010) of symptoms. Additionally, saliva yielded lower cycle thresholds across all time periods, indicative of higher viral loads in saliva. In the longitudinal analysis, a log-rank analysis indicated that the survival curve for saliva was significantly different from the curve for nasal swabs (p<0.001) with a median survival time for saliva of 18 days compared to 13 days for nasal swabs. We additionally performed saliva viral cultures among a similar COVID-19 patient cohort and noted patients with positive saliva viral cultures between 7 to 28 days of symptoms. Findings from this study suggest that SARS-CoV-2 RNA persists longer and in higher abundance in saliva compared to nasal swabs, with potential of prolonged propagating virus. Testing saliva may thus increase yield for detecting potentially infectious virus even beyond the first five days of symptomatic COVID-19.

Noninvasive Cardiac Output Monitoring Using Electrical Cardiometry and Outcomes in Critically Ill Children.

Cardiac output (CO) measurement is an important element of hemodynamic assessment in critically ill children and existing methods are difficult and/or inaccurate. There is insufficient literature regarding CO as measured by noninvasive electrical cardiometry (EC) as a predictor of outcomes in critically ill children. We conducted a retrospective chart review in children <21 years, admitted to our pediatric intensive care unit (PICU) between July 2018 and November 2018 with acute respiratory failure and/or shock and who were monitored with EC (ICON monitor). We collected demographic information, data on CO measurements with EC and with transthoracic echocardiography (TTE), and data on ventilator days, PICU and hospital days, inotrope score, and mortality. We analyzed the data using Chi-square and multiple linear regression analysis. Among 327 recordings of CO as measured by EC in 61 critically ill children, the initial, nadir, and median CO (L/min; median [interquartile range (IQR)]) were 3.4 (1.15, 5.6), 2.39 (0.63, 4.4), and 2.74 (1.03, 5.2), respectively. Low CO as measured with EC did not correlate well with TTE ( p = 0.9). Both nadir and mean CO predicted ventilator days ( p = 0.05 and 0.01, respectively), and nadir CO was correlated with peak inotrope score (correlation coefficient of -0.3). In our cohort of critically ill children with respiratory failure and/or shock, CO measured with EC did not correlate with TTE. Both nadir and median CO measured with EC predicted outcomes in critically ill children.

Thoracic Fluid Content (TFC) Measurement Using Impedance Cardiography Predicts Outcomes in Critically Ill Children.

Objective: Conventional methods of fluid assessment in critically ill children are difficult and/or inaccurate. Impedance cardiography has capability of measuring thoracic fluid content (TFC). There is an insufficient literature reporting correlation between TFC and conventional methods of fluid balance and whether TFC predicts outcomes in critically ill children. We hypothesized that TFC correlates with indices of fluid balance [FIMO (Fluid Intake Minus Output) and AFIMO (Adjusted Fluid Intake Minus Output)] and is a predictor of outcomes in critically ill children. Design: Retrospective chart review. Setting: Pediatric intensive care unit of a tertiary care teaching hospital. Patients: Children <21 years, admitted to our Pediatric Intensive Care Unit (PICU) between July- November 2018 with acute respiratory failure and/or shock and who were monitored for fluid status using ICON® monitor. Interventions: None. Measurements and Main Results: We collected demographic information, data on daily and cumulative fluid balance (CFB), ventilator, PICU and hospital days, occurrence of multi-organ dysfunction syndrome (MODS), and mortality. We calculated AFIMO using insensible fluid loss. We analyzed data using correlation coefficient, chi-square test and multiple linear regression analysis. We analyzed a total 327 recordings of TFC, FIMO and AFIMO as daily records of fluid balance in 61 critically ill children during the study period. The initial TFC, FIMO, and AFIMO in ml [median (IQR)] were 30(23, 44), 300(268, 325), and 21.05(-171.3, 240.2), respectively. The peak TFC, FIMO, and AFIMO in ml were 36(26, 24), 322(286, 334), and 108.8(-143.6, 324.4) respectively. The initial CFB was 1134.2(325.6, 2774.4). TFC did not correlate well with FIMO or AFIMO (correlation coefficient of 0.02 and -0.03, respectively), but a significant proportion of patients with high TFC exhibited pulmonary plethora on x-ray chest (as defined by increased bronchovascular markings and/or presence of pleural effusion) (p = 0.015). The multiple linear regression analysis revealed that initial and peak TFC and peak and mean FIMO and AFIMO predicted outcomes (ventilator days, length of PICU, and hospital days) in critically ill children (p < 0.05). Conclusions: In our cohort of critically ill children with respiratory failure and/or shock, TFC did not correlate with conventional measures of fluid balance (FIMO/AFIMO), but a significant proportion of patients with high TFC had pulmonary plethora on chest x-ray. Both initial and peak TFC predicted outcomes in critically ill children.