Daily Respiratory Research Analysis
Three papers stand out today: a national French cohort characterizes severe adult Mycoplasma pneumoniae during the 2023–24 outbreak and links severity to delayed use of active antibiotics; the first perinatal controlled human infection model shows Neisseria lactamica safely colonizes pregnant individuals but does not sustain transmission to infants; and an in vivo cotton rat model demonstrates EV-D68 associates with extracellular vesicles to disseminate systemically and reach the CNS.
Summary
Three papers stand out today: a national French cohort characterizes severe adult Mycoplasma pneumoniae during the 2023–24 outbreak and links severity to delayed use of active antibiotics; the first perinatal controlled human infection model shows Neisseria lactamica safely colonizes pregnant individuals but does not sustain transmission to infants; and an in vivo cotton rat model demonstrates EV-D68 associates with extracellular vesicles to disseminate systemically and reach the CNS.
Research Themes
- Outbreak characterization and antibiotic timing in atypical pneumonia
- Selective transmission in the perinatal respiratory microbiome
- Extracellular vesicle-mediated viral dissemination beyond the respiratory tract
Selected Articles
1. Mycoplasma pneumoniae infection in adult inpatients during the 2023-24 outbreak in France (MYCADO): a national, retrospective, observational study.
In a national cohort of 1,309 hospitalized adults during France’s 2023–24 M. pneumoniae epidemic, 32% met a severe composite outcome (ICU admission or in-hospital death) and 2% died. Severity was associated with comorbidities, atypical CT patterns, inflammatory/hematologic indices, and notably lack of pre-admission use of an antibiotic active against M. pneumoniae, supporting macrolide-active empiric therapy during epidemics.
Impact: This study provides timely, practice-informing evidence that delayed active therapy contributes to severe outcomes during a national M. pneumoniae outbreak and highlights atypical imaging presentations.
Clinical Implications: During M. pneumoniae epidemics, consider macrolides as first-line empiric therapy or reassess β-lactam monotherapy early; triage using risk factors (hypertension, obesity, chronic liver disease, bilateral CT involvement, systemic inflammation) and do not exclude M. pneumoniae based on imaging alone.
Key Findings
- 32.4% had severe outcomes (31.7% ICU admission; 2.1% in-hospital mortality) during the epidemic.
- Severity associated with hypertension, obesity, chronic liver failure, extra-respiratory manifestations, consolidation/bilateral CT involvement, elevated inflammatory markers, lymphopenia or neutrophilia.
- Not receiving an antibiotic active against M. pneumoniae before admission was linked to severe outcomes.
- Atypical radiological presentations were common, indicating imaging alone cannot rule out M. pneumoniae.
Methodological Strengths
- Large, multi-center national cohort with standardized data extraction across 76 hospitals
- Multivariable logistic regression to adjust for confounders
Limitations
- Retrospective design susceptible to residual confounding and selection bias
- Antibiotic exposure timing and diagnostic heterogeneity may influence associations
Future Directions: Prospective interventional studies testing macrolide-first strategies during epidemics; improved rapid diagnostics; surveillance of macrolide resistance and host factors underpinning severe disease.
2. Enterovirus D68 infection in cotton rats results in systemic inflammation with detectable viremia associated with extracellular vesicle and neurologic disease.
In immunocompetent cotton rats, EV-D68 respiratory infection led to viremia and extra-respiratory organ involvement with inflammation, and EV-D68 was physically associated with extracellular vesicles purified from plasma. Intraperitoneal infection and direct EV-associated virus delivery enabled CNS detection and neurologic signs, providing the first in vivo evidence that EVs facilitate EV-D68 dissemination beyond the respiratory tract.
Impact: This work reveals a plausible mechanism linking respiratory EV-D68 infection to systemic and CNS disease via extracellular vesicles and delivers practical animal models to evaluate anti-dissemination strategies.
Clinical Implications: While preclinical, these findings suggest therapeutic avenues targeting extracellular vesicle biogenesis or uptake to limit EV-D68 dissemination and AFM risk; they also refine pathogenesis models for testing antivirals or vaccines.
Key Findings
- EV-D68 was detected in blood and extra-respiratory organs following respiratory infection, indicating systemic dissemination with accompanying inflammation.
- Virus was physically associated with extracellular vesicles purified from plasma.
- Intraperitoneal infection and EV-associated virus delivery led to CNS detection and neurologic signs in young cotton rats.
- Provides first in vivo experimental support that EVs mediate EV-D68 dissemination beyond the respiratory tract.
Methodological Strengths
- Use of immunocompetent animal model with both respiratory and intraperitoneal infection routes
- Biochemical isolation of plasma extracellular vesicles demonstrating virus association
Limitations
- Preclinical animal model limits direct generalizability to humans
- Strain- and species-specific effects not fully explored; lack of interventional blockade experiments
Future Directions: Test pharmacologic or genetic inhibition of EV biogenesis/uptake to curb dissemination; validate across EV-D68 clades and in human biospecimens; integrate with AFM clinical cohorts.
3. Controlled human infection model of Neisseria lactamica in late pregnancy investigating mother-to-infant transmission in the UK: a single-arm pilot trial.
In this first perinatal CHIM, 71% of inoculated pregnant participants became colonized with N. lactamica without sustained transmission to their infants, despite evidence of Moraxella catarrhalis strain sharing in mother-infant pairs. Maternal anti-N. lactamica IgG increased, and no serious adverse reactions occurred, indicating feasibility and safety while challenging assumptions of passive maternal-to-infant respiratory commensal transfer.
Impact: Establishes the feasibility and safety of a perinatal CHIM and provides evidence that respiratory commensal transmission is selective, informing future microbiome-targeted interventions.
Clinical Implications: Immediate clinical change is not indicated; however, peripartum inoculation to shape infant microbiomes may require alternative strategies, timing, or organisms given the lack of sustained infant colonization observed.
Key Findings
- 71% (15/21) of inoculated pregnant participants were colonized by N. lactamica.
- No sustained transmission of the inoculated N. lactamica strain to infants was observed.
- Maternal anti-N. lactamica IgG titres increased in 88% of colonized mothers; infant titres did not rise.
- Strain sharing was observed for Moraxella catarrhalis in 38% of mother-infant pairs; no serious adverse reactions occurred.
Methodological Strengths
- Controlled human infection model with strain-level microbiology and paired serology
- First feasibility and safety data for perinatal CHIM in pregnancy
Limitations
- Single-arm pilot with small sample size and limited demographic diversity
- Follow-up duration and environmental factors may limit detection of transient infant colonization
Future Directions: Randomized designs comparing strains, doses, and timing; exploration of alternative commensals; longer infant follow-up; integration with safety/ethics frameworks for perinatal CHIMs.