Daily Respiratory Research Analysis
Three studies stand out today: a large national test-negative case-control analysis in England shows strong COVID-19 vaccine effectiveness in pregnancy with substantial passive protection for infants; a double-blind RCT of IL-7 in critically ill COVID-19 patients reduces hospital-acquired infections without safety concerns; and a nationwide Japanese cohort finds adult RSV admissions require more ventilation and have worse 1-year outcomes than influenza. Together, these findings directly inform v
Summary
Three studies stand out today: a large national test-negative case-control analysis in England shows strong COVID-19 vaccine effectiveness in pregnancy with substantial passive protection for infants; a double-blind RCT of IL-7 in critically ill COVID-19 patients reduces hospital-acquired infections without safety concerns; and a nationwide Japanese cohort finds adult RSV admissions require more ventilation and have worse 1-year outcomes than influenza. Together, these findings directly inform vaccination policy, ICU therapeutics, and adult RSV preparedness.
Research Themes
- Maternal vaccination and infant protection against respiratory viruses
- Immunomodulatory therapy in critical COVID-19
- Adult RSV burden versus influenza and health system planning
Selected Articles
1. Vaccine effectiveness against mild and severe covid-19 in pregnant individuals and their infants in England: test negative case-control study.
A national test-negative case-control study in England found high COVID-19 vaccine effectiveness in pregnant individuals, with boosters sustaining protection up to 15 weeks. Maternal vaccination, especially in the third trimester, conferred substantial protection to infants up to 6 months against symptomatic infection and hospitalisation for both delta and omicron variants.
Impact: The study provides definitive, policy-relevant evidence that maternal vaccination protects both mothers and infants, informing timing of boosters during pregnancy.
Clinical Implications: Prioritise primary and booster COVID-19 vaccination during pregnancy—particularly in the third trimester—to protect both the mother and the infant up to 6 months of age.
Key Findings
- Booster vaccination yielded peak vaccine effectiveness against symptomatic disease of 98.4% (delta) and 80.1% (omicron) in pregnant individuals.
- Two-dose primary series achieved 92.7% effectiveness against hospital admission for delta in pregnancy.
- Maternal vaccination in the third trimester protected infants up to 6 months: effectiveness against symptomatic disease 86.5% (delta) and 56.6% (omicron), and against hospital admission 94.7% (delta) and 78.7% (omicron).
- Protection did not wane up to 15 weeks post-booster in pregnant individuals.
Methodological Strengths
- Large-scale, linked national datasets with rigorous test-negative case-control design
- Stratified analyses by variant and timing of maternal vaccination with infant outcomes up to 6 months
Limitations
- Test-negative design may be affected by healthcare-seeking behavior and residual confounding
- Effectiveness beyond 15 weeks post-booster and for later omicron sublineages was not assessed
Future Directions: Assess durability of maternal and infant protection across emerging variants and evaluate optimal timing of boosters in different trimesters.
OBJECTIVE: To estimate real world vaccine effectiveness against symptomatic disease and hospital admission with the delta and omicron variants of the SARS-CoV-2 virus in pregnant individuals, and to estimate the protection conferred by previous infection and maternal vaccination in their infants. DESIGN: Test negative case-control study. SETTING: Community and hospital testing for covid-19, in England, 26 April 2021 to 9 January 2022 (delta variant period) and 29 November 2021 to 31 March 2022 (omicron variant period). Testing data were linked to Hospital Episode Statistics and Maternal Services Data Set (for data on pregnant individuals and infants), National Immunisation Management System (for covid-19 vaccinations), and Secondary Uses Service (for hospital admissions). PARTICIPANTS: 35 206 negative and 16 693 positive eligible test results in the delta variant period from pregnant individuals with symptoms of infection, aged 16-55 years, whose pregnancy ended in 2021, and 5974 negative and 4715 positive eligible test results in the omicron variant period. For infants born in 2021, 23 053 negative and 2924 positive eligible test results in the delta variant period and 13 908 negative and 5669 positive test results from infants in the omicron period. MAIN OUTCOME MEASURES: Vaccine effectiveness against symptomatic disease and hospital admission with the delta and omicron variants of the SARS-CoV-2 virus in pregnant women. Also, effectiveness of maternal vaccination and the protection conferred by previous infection in mothers in preventing symptomatic disease and hospital admission in their infants in the first six months of life. Symptomatic SARS-CoV-2 infection was confirmed by a positive polymerase chain reaction test result. RESULTS: Vaccine effectiveness against symptomatic disease (delta and omicron infection) and against hospital admission (delta infection only) in pregnant individuals was high, as seen in the general population. A booster dose of vaccine gave sustained protection, with no evidence of waning up to 15 weeks after vaccination. Vaccine effectiveness against symptomatic disease peaked at 98.4% (95% confidence interval (CI) 88.4% to 99.8%) and 80.1% (73.8% to 84.9%) against the delta and omicron variants, respectively, after the booster dose of vaccine. Vaccine effectiveness after a two dose primary schedule against hospital admission with delta infection peaked at 92.7% (95% CI 79.9% to 97.4%) in pregnant individuals. Maternal vaccination during and after pregnancy also provided sustained protection from symptomatic disease and hospital admission after delta and omicron infection in infants aged up to six months, with the highest protection seen when maternal vaccination occurred during later pregnancy. The effectiveness of two maternal doses when the last dose was given in the third trimester was 86.5% (95% CI 81.9% to 90.0%) and 56.6% (46.7% to 64.6%) against symptomatic disease with delta and omicron infection, respectively, in infants, and effectiveness against hospital admission was 94.7% (78.2% to 98.7%) and 78.7% (58.2% to 89.1%), respectively. Previous infection with wild-type, alpha, and delta variants of the SARS-CoV-2 virus in pregnant individuals was more protective against mild and severe delta infection than omicron infection in their infants. CONCLUSIONS: The results of this study indicated that maternal vaccination prevented mild and severe disease in pregnant individuals and their infants for up to six months after birth. The findings support the promotion of both primary and booster vaccination for pregnant individuals to protect themselves and their infants.
2. A randomized, double-blind, placebo-controlled trial of IL-7 in critically ill patients with COVID-19.
In a double-blind RCT (n=109) of critically ill COVID-19 patients with lymphopenia, recombinant IL-7 (CYT107) was safe, reduced treatment-emergent adverse events, and decreased hospital-acquired infections by 44% compared to placebo. Although the primary endpoint of lymphocyte recovery was not significantly different overall, a trend favored IL-7 in patients not receiving concomitant antivirals.
Impact: This pragmatic ICU RCT identifies a safe immunorestorative strategy that reduces nosocomial infections, a major driver of late COVID-19 mortality, with implications for future respiratory pandemics.
Clinical Implications: Consider IL-7 as an adjunct in clinical trials for critically ill viral pneumonia with lymphopenia to reduce secondary infections; monitor concomitant antivirals as potential effect modifiers.
Key Findings
- CYT107 (IL-7) was well tolerated with no cytokine storm or pulmonary function worsening.
- Treatment-emergent adverse events were significantly fewer in IL-7 versus placebo (P < 0.001).
- Hospital-acquired infections were reduced by 44% with IL-7 (P = 0.014).
- Overall lymphocyte recovery did not differ, but trended higher (+43%) without concomitant antivirals (P = 0.067).
Methodological Strengths
- Prospective, randomized, double-blind, placebo-controlled ICU trial
- Clinically meaningful secondary outcomes including nosocomial infections and safety
Limitations
- Primary endpoint (lymphocyte recovery) was not met overall
- Modest sample size limits power for mortality and subgroup analyses
Future Directions: Larger, stratified trials across respiratory viral pathogens to confirm infection reduction, explore mortality effects, and define interaction with antivirals.
BACKGROUND: Lymphopenia and failure of lymphocytes to mount an early IFN-γ response correlate with increased mortality in COVID-19. Given the essential role of CD4 helper and CD8 cytotoxic cells in eliminating viral pathogens, this profound loss in lymphocytes may impair patients' ability to eliminate the virus. IL-7 is a pleiotropic cytokine that is obligatory for lymphocyte survival and optimal function. METHODS: We conducted a prospective, double-blind, randomized, placebo-controlled trial of CYT107, recombinant human IL-7, in 109 critically ill, patients with lymphopenia who have COVID-19. The primary endpoint was to assess CYT107's effect on lymphocyte recovery with secondary clinical endpoints including safety, ICU and hospital length-of-stay, incidence of secondary infections, and mortality. RESULTS: CYT107 was well tolerated without precipitating a cytokine storm or worsening pulmonary function. Absolute lymphocyte counts increased in both groups without a significant difference between CYT107 and placebo. Patients with COVID-19 receiving CYT107 but not concomitant antiviral medications, known inducers of lymphopenia, had a final lymphocyte count that was 43% greater than placebo (P = 0.067). There were significantly fewer treatment-emergent adverse events in CYT107 versus placebo-treated patients (P < 0.001), consistent with a beneficial drug effect. Importantly, CYT107-treated patients had 44% fewer hospital-acquired infections versus placebo-treated patients (P = 0.014). CONCLUSION: Given that hospital-acquired infections are responsible for a large percentage of COVID-19 deaths, this effect of CYT107 to decrease nosocomial infections could substantially reduce late morbidity and mortality in this highly lethal disease. The strong safety profile of CYT107 and its excellent tolerability provide support for trials of CYT107 in other potential pandemic respiratory viral infections. TRIAL REGISTRATION: NCT04379076, NCT04426201, NCT04442178, NCT04407689, NCT04927169. FUNDING: Funding for the trial was provided by RevImmune and the Cancer Research Institute.
3. Severity and outcomes of adult respiratory syncytial virus inpatient compared with influenza: observational study from Japan.
In a nationwide Japanese cohort of 56,980 adults, RSV admissions required more mechanical ventilation than influenza and had higher risks of 1-year readmission and all-cause mortality, particularly in those aged ≥60 years. In-hospital mortality was similar between pathogens.
Impact: Quantifies adult RSV severity and long-term burden relative to influenza, informing adult RSV vaccination and resource planning.
Clinical Implications: Prioritise RSV prevention in older adults (≥60 years), anticipate higher ventilation needs, and plan post-discharge follow-up to mitigate 1-year readmission and mortality.
Key Findings
- RSV admissions had higher mechanical ventilation rates than influenza (9.7% vs 7.0%; RR 1.35, 95% CI 1.08–1.67).
- In-hospital mortality was similar (7.5% vs 6.6%; RR 1.05, 95% CI 0.82–1.34).
- RSV was associated with increased 1-year readmission (RR 1.19) and 1-year all-cause mortality (RR 1.17), particularly in adults ≥60 years.
Methodological Strengths
- Very large nationwide sample with inverse probability weighting to balance groups
- Assessment of both short-term (in-hospital) and long-term (1-year) outcomes
Limitations
- Retrospective administrative data subject to coding misclassification and residual confounding
- Virological details and treatment nuances not fully captured
Future Directions: Evaluate RSV vaccine effectiveness and cost-effectiveness in older adults and identify modifiable factors driving 1-year readmission and mortality.
BACKGROUND: Respiratory syncytial virus (RSV) significantly impacts not only children but also adults. However, knowledge of the severity and outcomes among adult RSV inpatients is still limited. OBJECTIVES: To clarify the short- and long-term health threats associated with adult RSV infections. METHODS: This retrospective observational study included 56,980 adult inpatients aged 18 years and older due to RSV or influenza infection between April 2010 and March 2022. After inverse probability weighting adjustment, we used Poisson's regression to estimate the risk of outcomes. RESULTS: The RSV group had a higher risk of requiring mechanical ventilation during hospitalization compared to the influenza group (9.7% vs. 7.0%; risk ratio (RR), 1.35; 95% confidence interval (CI), 1.08-1.67). In-hospital mortality was comparable between RSV and influenza groups (7.5% vs. 6.6%; RR, 1.05; 95% CI, 0.82-1.34). RSV group was associated with increased risk of readmission within 1 year after surviving discharge (34.0% vs. 28.9%; RR, 1.19; 95% CI, 1.07-1.32) and all-cause mortality within 1 year of admission (12.9% vs. 10.3%; RR, 1.17; 95% CI, 1.02-1.36). In the age-stratified analysis, the RSV group aged 60 years and older had a higher risk than the influenza group for in-hospital death, readmission and all-cause mortality within one year. CONCLUSIONS: RSV infections demonstrated comparable or greater health threats than influenza infections not only during hospitalization but also in long-term outcomes. The findings underscore the threat of RSV in adults, the impact on healthcare systems and the need for continued development of public health counter measures against RSV.