Pertussis in early life: underdiagnosed, severe, and risky disease. A seven-year experience in a pediatric tertiary-care hospital

Aim Pertussis continues to be a common worldwide infection in pediatric and adult populations. We aimed to study epidemiological and clinical characteristics of infants and children admitted for pertussis to a tertiary-care hospital and to investigate the risk factors for pediatric intensive care unit (PICU) admission. Materials and Methods With a retrospective study, we analyzed all medical reports of patients admitted to Bambino Gesu Children's Hospital in Rome from January 2011 to December 2018 with a diagnosis of pertussis. Results We examined 195 patients. The majority of hospitalized children (66.15%) were <3 months of age. No mother had received pertussis containing vaccine during pregnancy. Ten cases required admission in PICU. The age at admission was lower in PICU patients with respect to ward patients (42.8 vs 240 days;p< .0007), length of hospital stay was longer in PICU group (24.7 vs 7.52 days;p< .003). Patients who needed PICU admission had greater white blood cell count at hospital admission compared with those hospitalized in the pediatric ward. One infant died and one had encephalitis. Conclusions Pertussis is a remerging disease. In infants, it is associated with significant morbidity and mortality. In recent years, many countries have implemented different vaccination strategies and public health measures to prevent the increase in pertussis cases. Maternal vaccination has been shown to be highly protective for infants <3 months of age before they can develop their own immunity via vaccination

Cytokine expression patterns in hospitalized children with Bordetella pertussis, Rhinovirus or co-infection

Mechanisms of interaction between Bordetella pertussis and other viral agents are yet to be fully explored. We studied the inflammatory cytokine expression patterns among children with both viral-bacterial infections. Nasopharyngeal aspirate (NPA) samples were taken from children, aged < 1 year, positive for Rhinovirus, Bordetella pertussis and for Rhinovirus and Bordetella pertussis. Forty cytokines were evaluated in NPA by using human cytokine protein arrays and a quantitative analysis was performed on significantly altered cytokines. Forty cytokines were evaluated in NPA by using human cytokine protein arrays and a quantitative analysis was performed on significantly altered cytokines. Our results show that co-infections display a different inflammatory pattern compared to single infections, suggesting that a chronic inflammation caused by one of the two pathogens could be the trigger for exacerbation in co-infections

The impact of pertussis in infants: insights from a hospital-based enhanced surveillance system, Lazio region, Italy, 2016 to 2019

Background: Routine surveillance systems for pertussis often suffer from under-recognition and under-reporting. Aim: Our aim was to describe the epidemiology and the clinical features of pertussis in children younger than 1 year in an Italian region, detected through an enhanced hospital surveillance system. Methods: From 2016 to 2019, we monitored the incidence and the clinical characteristics of hospitalised pertussis cases younger than 1 year in two paediatric hospitals involved in the PERTINENT project. Results: We detected 141 pertussis cases, corresponding to an estimated incidence of 105.8 per 100.000 in 2016, 91.7 per 100.000 in 2017, 64.5 per 100.000 in 2018 and 40.9 per 100.000 in 2019, based on the hospitals' catchment area, roughly corresponding to the Lazio region. A total of 101 cases (77.1%) had a household member with cough or other respiratory symptoms. The most frequent combination of symptoms was paroxysmal cough with apnoea in the absence of fever. Almost 40% had been prescribed an antibiotic treatment before hospitalisation, and the median time from symptom onset to contact with the hospital was 8 days. Thirty-one (22.0%) had complications. Conclusion: An enhanced surveillance system showed a high incidence of pertussis among infants in the Lazio region, where the impact of this disease may still be underestimated. Increasing the coverage of pertussis immunisation among pregnant women and improving the capacity for early detection in primary care may contribute to reducing the impact of pertussis among infants

Highly specific memory b cells generation after the 2nd dose of bnt162b2 vaccine compensate for the decline of serum antibodies and absence of mucosal iga

Specific memory B cells and antibodies are a reliable read-out of vaccine efficacy. We analysed these biomarkers after one and two doses of BNT162b2 vaccine. The second dose significantly increases the level of highly specific memory B cells and antibodies. Two months after the second dose, specific antibody levels decline, but highly specific memory B cells continue to increase, thus predicting a sustained protection from COVID-19. We show that although mucosal IgA is not induced by the vaccination, memory B cells migrate in response to inflammation and secrete IgA at mucosal sites. We show that the first vaccine dose may lead to an insufficient number of highly specific memory B cells and low concentration of serum antibodies, thus leaving vaccinees without the immune robustness needed to ensure viral elimination and herd immunity. We also clarify that the reduction of serum antibodies does not diminish the force and duration of the immune protection induced by vaccination. The vaccine does not induce sterilizing immunity. Infection after vaccination may be caused by the lack of local preventive immunity because of the absence of mucosal IgA

Persistent B cell memory after SARS-CoV-2 vaccination is functional during breakthrough infections

Breakthrough SARS-CoV-2 infections in fully vaccinated individuals are considered a consequence of waning immunity. Serum antibodies represent the most measurable outcome of vaccine-induced B cell memory. When antibodies decline, memory B cells are expected to persist and perform their function, preventing clinical disease. We investigated whether BNT162b2 mRNA vaccine induces durable and functional B cell memory in vivo against SARS-CoV-2 3, 6, and 9 months after the second dose in a cohort of health care workers (HCWs). While we observed physiological decline of SARS-CoV-2-specific antibodies, memory B cells persist and increase until 9 months after immunization. HCWs with breakthrough infections had no signs of waning immunity. In 3–4 days, memory B cells responded to SARS-CoV-2 infection by producing high levels of specific antibodies in the serum and anti-Spike IgA in the saliva. Antibodies to the viral nucleoprotein were produced with the slow kinetics typical of the response to a novel antigen

Hybrid Lipid/Polymer Nanoparticles to Tackle the Cystic Fibrosis Mucus Barrier in siRNA Delivery to the Lungs: Does PEGylation Make the Difference?

Inhaled siRNA therapy has a unique potential for treatment of severe lung diseases, such as cystic fibrosis (CF). Nevertheless, a drug delivery system tackling lung barriers is mandatory to enhance gene silencing efficacy in the airway epithelium. We recently demonstrated that lipid-polymer hybrid nanoparticles (hNPs), comprising a poly(lactic-co-glycolic) acid (PLGA) core and a lipid shell of dipalmitoyl phosphatidylcholine (DPPC), may assist the transport of the nucleic acid cargo through mucus-covered human airway epithelium. To study in depth the potential of hNPs for siRNA delivery to the lungs and to investigate the hypothesized benefit of PEGylation, here, an siRNA pool against the nuclear factor-κB (siNFκB) was encapsulated inside hNPs, endowed with a non-PEGylated (DPPC) or a PEGylated (1,2-distearoyl-sn-glycero-3-phosphoethanolamine-poly(ethylene glycol) or DSPE-PEG) lipid shell. Resulting hNPs were tested for their stability profiles and transport properties in artificial CF mucus, mucus collected from CF cells, and sputum samples from a heterogeneous and representative set of CF patients. Initial information on hNP properties governing their interaction with airway mucus was acquired by small-angle X-ray scattering (SAXS) studies in artificial and cellular CF mucus. The diffusion profiles of hNPs through CF sputa suggested a crucial role of lung colonization of the corresponding donor patient, affecting the mucin type and content of the sample. Noteworthy, PEGylation did not boost mucus penetration in complex and sticky samples, such as CF sputa from patients with polymicrobial colonization. In parallel, in vitro cell uptake studies performed on mucus-lined Calu-3 cells grown at the air-liquid interface (ALI) confirmed the improved ability of non-PEGylated hNPs to overcome mucus and cellular lung barriers. Furthermore, effective in vitro NFκB gene silencing was achieved in LPS-stimulated 16HBE14o- cells. Overall, the results highlight the potential of non-PEGylated hNPs as carriers for pulmonary delivery of siRNA for local treatment of CF lung disease. Furthermore, this study provides a detailed understanding of how distinct models may provide different information on nanoparticle interaction with the mucus barrier