Weekly Respiratory Research Analysis
This week’s respiratory literature prioritized translational models and sensitive diagnostics that can immediately shift preclinical-to-clinic decision making. A robust human ACE2 transgenic pig model for SARS‑CoV‑2 enables large‑animal evaluation of vaccines and therapeutics; an ultrasensitive tumor‑informed ctDNA assay improves preoperative risk stratification in early lung adenocarcinoma; and a validated macaque model of bovine H5N1 defines pathogenesis for pandemic risk and countermeasure te
Summary
This week’s respiratory literature prioritized translational models and sensitive diagnostics that can immediately shift preclinical-to-clinic decision making. A robust human ACE2 transgenic pig model for SARS‑CoV‑2 enables large‑animal evaluation of vaccines and therapeutics; an ultrasensitive tumor‑informed ctDNA assay improves preoperative risk stratification in early lung adenocarcinoma; and a validated macaque model of bovine H5N1 defines pathogenesis for pandemic risk and countermeasure testing. Together the papers push forward platforms for rapid countermeasure testing, earlier detection/stratification, and refined risk assessment for emerging zoonotic threats.
Selected Articles
1. Human ACE2 transgenic pigs are susceptible to SARS-CoV-2 and develop COVID-19-like disease.
Researchers generated human ACE2 transgenic pigs that support productive SARS‑CoV‑2 replication in upper and lower airways and display clinical and lung immunopathology mirroring severe human COVID‑19, establishing a robust large‑animal model for translational testing.
Impact: Provides the first robust, anatomically and immunologically relevant large‑animal COVID‑19 model in swine, enabling mechanistic studies and preclinical evaluation of vaccines, antivirals, and immunomodulators at scales not possible in rodents.
Clinical Implications: Accelerates translational testing of respiratory countermeasures (route/dose/safety) and refines preclinical evidence used to design human trials for vaccines and therapeutics against SARS‑CoV‑2 and related respiratory viruses.
Key Findings
- Transgenic pigs expressing human ACE2 supported SARS‑CoV‑2 replication in nasal turbinates, trachea, and lungs up to 7 days post‑infection.
- Animals developed fever, cough, respiratory distress and lung immunopathology comparable to severe human COVID‑19.
2. Ultrasensitive ctDNA detection for preoperative disease stratification in early-stage lung adenocarcinoma.
An analytically validated, tumor‑informed whole‑genome ctDNA platform detected preoperative ctDNA in 81% of lung adenocarcinomas (53% in pathological stage I) and stratified survival; the assay detects ctDNA at parts‑per‑million sensitivity with 99.9% specificity, improving risk stratification beyond less sensitive methods.
Impact: Demonstrates that ultrasensitive, tumor‑informed liquid biopsy can meaningfully stratify early‑stage lung cancer patients preoperatively, with immediate implications for tailoring adjuvant therapy and surveillance strategies.
Clinical Implications: Supports incorporation of preoperative ctDNA into surgical oncology workflows to identify high‑risk early‑stage patients who may benefit from intensified adjuvant therapy or closer surveillance; requires prospective interventional trials for practice change.
Key Findings
- Preoperative ctDNA detected in 81% of lung adenocarcinomas and 53% of pathologic stage I cases.
- Assay sensitivity at 1–3 ppm with 99.9% specificity; preoperative ctDNA burden associated with worse overall survival.
3. Pathogenesis of bovine H5N1 clade 2.3.4.4b infection in macaques.
A non‑human primate pathogenesis study characterizes respiratory infection and pathology of bovine‑origin H5N1 clade 2.3.4.4b in macaques, providing a translational platform to assess spillover risk and to test vaccines and antivirals against this evolving zoonotic threat.
Impact: Defines a high‑relevance NHP model for a rapidly evolving zoonotic influenza clade, directly enabling high‑confidence countermeasure evaluation and pandemic preparedness assessments.
Clinical Implications: Indirect clinical impact but accelerates preclinical testing of vaccines/antivirals and informs public health risk assessments for potential mammalian adaptation and human spillover.
Key Findings
- Established macaque disease model for bovine‑origin H5N1 clade 2.3.4.4b with defined respiratory tract pathology.
- Provides a platform to evaluate vaccines and antivirals and to quantify spillover risk.