Daily Respiratory Research Analysis

BACKGROUND: Despite several randomised controlled trials (RCTs) on the use of adjuvant treatment with corticosteroids in patients with community-acquired pneumonia (CAP), the effect of this intervention on mortality remains controversial. We aimed to evaluate heterogeneity of treatment effect (HTE) of adjuvant treatment with corticosteroids on 30-day mortality in patients with CAP. METHODS: In this individual patient data meta-analysis, we included RCTs published before July 1, 2024, comparing adjuvant treatment with corticosteroids versus placebo in patients hospitalised with CAP. The primary endpoint was 30-day all-cause mortality, collected across all trials, and analyses followed the intention-to-treat principle. We analysed HTE using risk and effect modelling. For risk modelling, patients were classified as having less severe or severe CAP based on the pneumonia severity index (PSI), comparing PSI class I-III versus class IV-V. For effect modelling, we trained a corticosteroid-effect model on six trials and externally validated it using data from two trials, received after model preregistration. This model classified patients into two groups: no predicted benefit and predicted benefit from adjuvant treatment with corticosteroids. The literature search was registered on PROSPERO, CRD42022380746. FINDINGS: We included eight RCTs with 3224 patients. Across all eight trials, 246 (7·6%) patients died within 30 days (106 [6·6%] of 1618 in the corticosteroid group vs 140 [8·7%] of 1606 in the placebo group; odds ratio [OR] 0·72 [95% CI 0·56-0·94], p=0·017). The corticosteroid-effect model, which selected C-reactive protein (CRP), showed significant HTE during external validation in the two most recent trials. In these trials, 154 (11·4%) of 1355 patients died within 30 days (88 [13·1%] of 671 in the placebo group vs 66 [9·6%] of 684 in the corticosteroid group; OR 0·71 [95% CI 0·50-0·99], p=0·044). Among patients predicted to have no benefit (CRP ≤204 mg/L, n=725), no significant effect was observed (OR 0·98 [95% CI 0·63-1·50]), whereas for those with predicted benefit (CRP >204 mg/L, n=630), 39 (13·0%) of 301 patients died in the placebo group compared with 20 (6·1%) of 329 in the corticosteroid group (0·43 [0·25-0·76], p INTERPRETATION: Overall, adjuvant therapy with corticosteroids significantly reduces 30-day mortality in patients hospitalised with CAP. The treatment effect varied significantly among subgroups based on CRP concentrations, with a substantial mortality reduction observed only in patients with high baseline CRP. FUNDING: None.

The role of viral interaction-where one virus enhances or inhibits infection with another virus-in respiratory virus transmission is not well characterized. This study used data from 4029 total participants from 957 households who participated in a prospective household cohort study in Southeast Michigan, U.S.A to examine how viral coinfection and cocirculation may impact transmission of symptomatic influenza and respiratory syncytial virus infections. We utilized multivariable mixed effects regression to estimate transmission risk when index cases were coinfected with multiple viruses and when viruses cocirculated within households. This analysis included 201 coinfections involving influenza A virus, 67 involving influenza B virus, and 181 involving respiratory syncytial virus. We show that exposure to symptomatic coinfected index cases was associated with reduced risk of influenza A virus and respiratory syncytial virus transmission compared to exposure to singly infected cases, while infection with another virus was associated with increased risk of acquisition of these viruses. Exposure to coinfected cases among contacts infected with other viruses was associated with increased risk of influenza B virus acquisition. These results suggest that viral interaction may impact symptomatic transmission of these viruses.

UNLABELLED: Bronchiolitis is one of the leading reasons for paediatric emergency department (PED) visits. France was one of the few countries in the world to implement nirsevimab during winter 2023-2024 in order to reduce the burden of bronchiolitis each year. We conducted a test-negative design study, including all infants younger than 1, diagnosed with a first episode of bronchiolitis. We included all cases presenting to the PED of five university hospitals across France, between October 1, 2023, and February 29, 2024, and undergoing a nasopharyngeal sample for RSV testing. Case patients were the RSV-positive bronchiolitis and control patients the RSV-negative. As a follow-up, all parents were contacted by e-mail 15 days after inclusion. We included 383 bronchiolitis patients, of which 274 tested positive for RSV (75.2%). Among case patients, 27/274 (9.8%) received nirsevimab, compared to 50/109 (46.2%) among control patients. Nirsevimab had an adjusted estimated effectiveness of 82.5% (95% CI [68.0-90.8]) at PEDs. Sensitivity analyses found similar results. At 15-day follow-up, characteristics were similar between children immunized by nirsevimab or not. CONCLUSION: Our findings advocate for nirsevimab widespread adoption to alleviate the burden of RSV bronchiolitis in paediatric emergency departments. TRIAL REGISTRATION: NCT04743609 (date of registration: February 4, 2021). WHAT IS KNOWN: • Each year, RSV-bronchiolitis places significant pressure on pediatric emergency services. • France is one of the first countries in the world to have implemented nirsevimab in septembre 2023. WHAT IS NEW: • Nirsevimab effectiveness on pediatric emergency visits for RSV-bronchiolitis has been estimated to 82.5% (95% CI [68.0-90.8]) in our study. • The effectiveness was as strong to prevent hospitalizations and sever illnesses.