Daily Respiratory Research Analysis

IMPORTANCE: The impact of awake prone positioning (APP) on clinical outcomes in patients with COVID-19 and acute hypoxemic respiratory failure (AHRF) remains uncertain. OBJECTIVE: To assess the association of APP with improved clinical outcomes among patients with COVID-19 and AHRF, and to identify potential effect modifiers. DATA SOURCES: PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov were searched through August 1, 2024. STUDY SELECTION: Randomized clinical trials (RCTs) examining APP in adults with COVID-19 and AHRF that reported intubation rate or mortality were included. DATA EXTRACTION AND SYNTHESIS: Individual participant data (IPD) were extracted according to PRISMA-IPD guidelines. For binary outcomes, logistic regression was used and odds ratio (OR) and 95% CIs were reported, while for continuous outcomes, linear regression was used and mean difference (MD) and 95% CIs were reported. MAIN OUTCOMES AND MEASURES: The primary outcome was survival without intubation. Secondary outcomes included intubation, mortality, death without intubation, death after intubation, escalation of respiratory support, intensive care unit (ICU) admission, time from enrollment to intubation and death, duration of invasive mechanical ventilation, and hospital and ICU lengths of stay. RESULTS: A total of 14 RCTs involving 3019 patients were included; 1542 patients in the APP group (mean [SD] age, 59.3 [14.1] years; 1048 male [68.0%]) and 1477 in the control group (mean [SD] age, 59.9 [14.1] years; 979 male [66.3%]). APP improved survival without intubation (OR, 1.42; 95% CI, 1.20-1.68), and it reduced the risk of intubation (OR, 0.70; 95% CI, 0.59-0.84) and hospital mortality (OR, 0.77; 95% CI, 0.63-0.95). APP also extended the time from enrollment to intubation (MD, 0.93 days; 95% CI, 0.43 to 1.42 days). In exploratory subgroup analyses, improved survival without intubation was observed in patients younger than age 68 years, as well as in patients with a body mass index of 26 to 30, early implementation of APP (ie, less than 1 day from hospitalization), a pulse saturation to inhaled oxygen fraction ratio of 155 to 232, respiratory rate of 20 to 26 breaths per minute (bpm), and those receiving advanced respiratory support at enrollment. However, none of the subgroups had significant interaction with APP treatment. APP duration 10 or more hours/d within the first 3 days was associated with increased survival without intubation (OR, 1.85; 95% CI, 1.37-2.49). CONCLUSIONS AND RELEVANCE: This IPD meta-analysis found that in adults with COVID-19 and AHRF, APP was associated with increased survival without intubation and with reduced risks of intubation and mortality, including death after intubation. Prolonged APP duration (10 or more hours/d) was associated with better outcomes.

IMPORTANCE: Nirsevimab, a long-acting monoclonal antibody, demonstrated efficacy against respiratory syncytial virus (RSV)-associated lower respiratory tract infections (LRTI) in clinical trials. Postlicensure monitoring is essential to confirm these benefits in clinical settings. OBJECTIVE: To estimate the 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 utilized inpatient, outpatient, and emergency department 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. Infants with RSV-positive results were cases and infants with RSV-negative results were controls. 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 potential confounders. Separate models examined estimated effectiveness by clinical setting, dosage, time since immunization, and severity (defined as needing high-flow oxygen or intensive care unit admission). Broader outcomes were also analyzed, including all-cause LRTI and all-cause LRTI-associated hospitalization. RESULTS: The analytic sample included 3090 infants (1722 male [57.3%]; median [IQR] age at testing, 6.7 [3.6-9.7] months), with 680 (22.0%) RSV-positive cases and 2410 (78.0%) RSV-negative controls. Nirsevimab uptake was 10.7% (330 patients), with 21 RSV-positive cases and 309 RSV-negative controls immunized. Adjusted effectiveness was 68.4% (95% CI, 50.3%-80.8%) against medically attended RSV infection, 61.6% (95% CI, 35.6%-78.6%) against outpatient visits, and 80.5% (95% CI, 52.0%-93.5%) against hospitalizations. The highest estimated effectiveness (84.6%; 95% CI, 58.7%-95.6%) was observed against severe RSV disease. Although estimated effectiveness against RSV infections declined from 79.3% (95% CI, 63.4%-90.6%) at 2 weeks postimmunization to 54.8% (95% CI, 16.3%-74.7%) at 14 weeks postimmunization, it remained significant. Estimated effectiveness did not vary substantially by dosage. During peak RSV season, nirsevimab appeared effective against all-cause LRTI (49.4%; 95% CI, 10.7%-72.9%) and all-cause LRTI-associated hospitalizations (79.1%; 95% CI, 27.6%-94.9%). From February to May 2024, when most LRTIs were caused by other viruses, its estimated effectiveness against these broader outcomes was negligible. CONCLUSIONS AND RELEVANCE: In this case-control study, nirsevimab provided substantial protection against RSV-associated outcomes. These findings support its continued use and provide evidence that may help boost public confidence in the immunization program.

BACKGROUND: More data is required to contextualise respiratory-syncytial-virus (RSV) disease burden, versus other vaccine-preventable respiratory-viral-infections (RVIs) in older adults. We aimed to compare severity of RSV in hospitalized adults versus influenza/boosted COVID-19. METHODS: Retrospective population-based cohort study, including all adult RSV hospitalizations (2021-2023) in Singapore. Disease severity (28-day mortality/intensive-care-unit [ICU] admission) and healthcare utilization in RSV hospitalizations were compared with contemporaneous influenza hospitalizations and COVID-19 hospitalizations in 2023. Outcomes for COVID-19 were stratified by type/receipt of boosters. Comparative severity of RSV versus COVID-19/influenza was evaluated using multivariate logistic regression, adjusted for confounders. Generalized linear models were utilized to estimate excess length-of-stay/costs of RSV hospitalization versus COVID-19/influenza as a rate-ratio. FINDINGS: 12,811 hospitalized adults were included (RSV: N = 1332; influenza: N = 3999; COVID-19: N = 7480). Amongst RSV hospitalizations, 5.4% (72/1332) died within 28 days; 3.8% (51/1332) required ICU. Median length-of-stay (RSV) was 5.0 days (IQR = 3.0-8.0). Older age/diabetes were associated with greater odds of 28-day mortality in RSV hospitalizations. Higher odds of 28-day mortality/ICU admission and higher healthcare utilization was observed in RSV hospitalizations versus influenza. Conversely, RSV was less severe than unboosted COVID-19, with lower odds of 28-day mortality (adjusted-odds-ratio, aOR = 0.56 [95% CI = 0.40-0.79]) and rate-ratio for length-of-stay/costs significantly <1. However, higher odds of ICU (aOR = 1.80 [95% CI = 1.07-3.00]) were observed in RSV hospitalizations, versus COVID-19 hospitalizations boosted <1 year prior with updated vaccines. INTERPRETATION: Hospitalizations attributed to RSV were more severe than influenza. RSV disease was less severe versus COVID-19 in unboosted patients but severity was not significantly different from COVID-19 in boosted individuals. FUNDING: National Medical Research Council, Singapore.