Nipocalimab is a neonatal Fc receptor (FcRn)-blocking monoclonal antibody approved for the treatment of generalized myasthenia gravis (gMG) and is being evaluated for other immunoglobulin G (IgG) autoantibody- or alloantibody-mediated diseases. Nipocalimab binds to FcRn with high specificity and affinity, eliciting increased clearance of IgG antibodies without affecting IgG production or other immune functions. However, nipocalimab's impact on vaccine responses in patients has not been previously reported. The effect of nipocalimab on pre-existing antibodies against tetanus toxoid (TT) and herpes zoster virus (HZV) vaccines as well as humoral responses to TT vaccines, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines, and SARS-CoV-2 infections was examined in post hoc analyses of data from three randomized, placebo-controlled trials in participants with gMG, rheumatoid arthritis, and Sjögren's disease. The levels of pre-existing anti-TT and anti-HZV IgG followed the kinetics of total IgG during nipocalimab treatment (60%-65% and 53%-68% IgG reduction, respectively) and returned to baseline after discontinuation. Nevertheless, the majority of nipocalimab-treated participants maintained pre-existing anti-HZV (66/90, 73.3% above ≥100 IU/L reference threshold) and anti-TT IgG levels (62/81, 76.5% ≥0.16 IU/mL protective threshold) throughout the study period. Participants treated with nipocalimab elicited positive IgG responses to TT and SARS-CoV-2 vaccination, similar to placebo-treated participants. SARS-CoV-2 infections during the studies were mild to moderate in severity with no complications. These results suggest that nipocalimab does not impair the development of humoral responses to vaccines or viral infections in patients with IgG autoantibody-mediated diseases.Trial registration number: NCT04951622, NCT04991753, NCT04968912.

During the COVID-19 pandemic, international border restrictions, along with traveler screening and quarantine, were implemented to limit virus spread. This study analyzes the epidemiological and genomic profiles of SARS-CoV-2 infections imported into Kinshasa (DRC) during the restrictions period in 2021.

As part of the national response to the pandemic, self-reported demographic and clinical data were collected from travelers entering the DRC via N'djili-Kinshasa International Airport. SARS-CoV-2 infection was diagnosed using RT-PCR, and positive samples were subjected to whole genome sequencing (WGS) to determine variant types and viral lineages. The impact of the virus's genomic profile on the clinical presentation of travelers and on the COVID-19 epidemiology in the DRC was then assessed.

Of 102,810 included travelers, 1037 (1.0%) tested positive for SARS-CoV-2 and reported significantly more nausea, diarrhea, and weight loss than uninfected travelers (p < 0.001). SARS-Cov-2-infected travelers were predominantly under 43 years old (p < 0.001) and primarily from France (24.8%) and Belgium (19.5%). Of the 105 WGS analyzed, 86 (81.9%) were variants of concern (VOCs), 14 (13.3%) were variants under monitoring (VUM), and the main genomic lineages identified were Delta-B.1.617.2 (24.8%), Alpha-B.1.1.7 (10.5%), Delta-AY.122 (7.6%), and B.1.620 (5.7%). The Delta-VOC was the most prevalent among positive travelers (61/86) and appeared to cause more symptomatic infections than non-Delta variants, although one-third of positive travelers reported no symptoms.

SARS-CoV-2 importation into Kinshasa (DRC) mirrored global variant circulation patterns at the study's time. This genomic landscape was consistent with in-country clinical observations, emphasizing the importance of robust border surveillance and adaptive public health strategies during pandemics.

This study investigated α-phellandrene (PE)'s therapeutic effects on hypoxia-induced pulmonary hypertension (HPH), with emphasis on pulmonary vasoconstriction and vascular remodeling.

A rat model of HPH was successfully established and then the hemodynamic indexes were assessed. HE and Masson's staining were performed to observe tissue morphological changes and fibrosis. Immunohistochemistry and immunofluorescence were used to quantify Collagen I/III, and alpha-smooth muscle actin (α-SMA). malondialdehyde, glutathione, superoxide dismutase, and glutathione peroxidase assays for antioxidant status. Western blotting to analyse the protein expression levels in lung tissue of HPH rats.

Our results indicate that PE significantly mitigated HPH, as evidenced by reductions in right ventricular (RV) systolic pressure, RV hypertrophy (evaluated via the RV/BW ratio and Fulton index), and key structural changes. PE effectively diminished pulmonary vascular remodeling, demonstrated by decreased vascular wall thickness and area, along with downregulation of Collagen I/III and α-SMA expression. Mechanistically, the protective effects of PE were associated with modulation of the AKT/eNOS/sGC/PKG pathway, a critical regulator of vascular tone and remodeling, as well as a reduction in oxidative stress and apoptosis.

These findings highlight that PE alleviates HPH through a multifaceted approach targeting vasoconstriction and vascular remodeling, underscoring its potential as a novel therapeutic agent.

Massive hemoptysis and postpneumonectomy acute respiratory distress syndrome (ARDS) are rare but life-threatening conditions with limited therapeutic options. This case highlights the feasibility of combining venovenous extracorporeal membrane oxygenation (VV-ECMO) with esophageal pressure-guided ventilation to support both surgical and respiratory management in a critically ill patient.

A 67-year-old woman developed massive hemoptysis after bronchoscopic biopsy of a left hilar lung mass. Despite bronchial artery embolization and selective right lung ventilation, severe ARDS ensued. A salvage left pneumonectomy was performed under VV-ECMO due to refractory bleeding. Postoperatively, the patient developed right-lung ARDS with total airway closure and high elastance. Esophageal pressure monitoring enabled safe adjustment of ventilator settings. She was weaned from ECMO on postoperative day 16 and later discharged from ICU. Final pathology confirmed an atypical carcinoid tumor with negative margins.

VV-ECMO can enable life-saving pneumonectomy in select patients. Esophageal pressure monitoring may optimize ventilation in postpneumonectomy ARDS with severe mechanical impairment.

Post-COVID-19 condition is associated with persistent respiratory symptoms and impaired functional capacity. This study evaluated the effects of adding an incentive spirometer to standard rehabilitation in adults with post-COVID-19 condition, with peak expiratory flow, dyspnoea, and quality of life as the prespecified primary outcomes.

Randomized controlled trial.

Eighty-two previously hospitalized adults diagnosed with post-COVID-19 condition, were randomly assigned to an experimental group (rehabilitation plus incentive spirometer, n = 41) or a control group (rehabilitation alone, n = 41).

Eight outcomes were assessed at baseline and 1 month, including peak expiratory flow, Medical Research Council dyspnoea scale, EQ-5D-5L, and functional performance tests.

Both groups improve at 1-month follow-up. The experimental group showed greater improvements in peak expiratory flow (between-group difference = 65.85 L/min; 95% CI: 4.35 to 127.35; p = 0.007), and dyspnoea (MRC difference = -1.08; 95% CI: -1.54 to -0.62; p < 0.001) compared with the control group. No significant between-group differences were observed for quality of life or functional performance measures.

Adding incentive spirometry to standard rehabilitation improved peak expiratory flow and reduced dyspnoea in adults with post-COVID-19 condition, supporting its use as a low-cost adjunct for respiratory symptom management.

Chalcones, a naturally occurring class of molecules found in various plants, serve as both precursors and final products in the biosynthesis of flavonoids. Renowned for their diverse therapeutic actions, chalcones demonstrate anti-inflammatory, antitumoral, antimalarial and antiviral activities. The structure of chalcones allows chemical manipulation, making them attractive for metal coordination, such as with copper, an essential metal for living organisms. Here, we characterize the activity of CuL₂phen and CuL₁phen against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in which L1 and L2 are two forms of the chalcones 3-(4-(benzyloxy)phenyl)-1-(4-fluoro-2-hydroxyphenyl)prop-2-en-1-one and 3-(4-(benzyloxy)phenyl)-1-(2-hydroxyphenyl)prop-2-en-1-one, respectively, and phen is phenanthroline. CuL₁phen and CuL₂phen anti-SARS-CoV-2 activity were studied in the viral replication cycle employing both the SARS-CoV-2-NeonGreen infectious clone and wild-type isolates. The SI of CuL₁phen and CuL₂phen was found to be 1.7 and 5.5, respectively, demonstrating that CuL₂phen is a more promising compound. CuL₂phen impaired SARS-CoV-2 entry, predicted by molecular docking calculations to disrupt the glycoprotein S and angiotensin-converting enzyme 2 (ACE2) binding, emphasized by the low EC₅₀ in pseudotyped virus entry assay. Further, CuL₂phen was identified as SARS-CoV-2 post-entry inhibitor, probably due to its strong interaction with SARS-CoV-2 double stranded RNA. Altogether, the data suggest that CuL₂phen acts by impairing SARS-CoV-2 entry by disrupting the viral envelope as well as interrupting RNA replication through specifically intercalating into the dsRNA. The obtained results give us mechanistic insights into the activity of this promising Cu(II) metallodrug candidate in SARS-CoV-2 infection.

Randomized clinical trials comparing the breadth and long-term persistence of immunity between different COVID-19 vaccine types and between ancestral and Omicron-targeted vaccines are limited. The PRIBIVAC study (Phase D) is a randomized clinical trial comparing the immunogenicity of monovalent mRNA vs bivalent mRNA vs protein-based NVX-CoV2373 administered as second booster in 176 triple mRNA-vaccinated adults. Primary objective was neutralizing antibody levels against Omicron subvariants at day 28. A 4th vaccine dose significantly boosted 50% neutralization titers against emerging strain XBB.1.16 by 3.2-, 4.1- and 1.6-fold in monovalent mRNA, bivalent mRNA and NVX-CoV2373 group respectively at day 28. The largest absolute increase in inhibition level at day 28 post-booster was observed against the KP.2 subvariant, with bivalent mRNA vaccines exhibiting the highest neutralization level (91.7%) compared with monovalent mRNA (84.4%; p = .027) and NVX-CoV2373 (81.4%; p < .0001). While bivalent mRNA vaccines elicited the highest early immunogenicity, neutralization levels against all Omicron variants tested waned to similar levels between groups by 12 months post-vaccination. Although NVX-CoV2373 induced a lower peak anti-S antibody response, anti-S decay rate was slower in NVX-CoV2373 compared with mRNA vaccines. The geometric mean anti-S fold change (D360/D28) in NVX-CoV2373 group was higher (0.51) relative to both mRNA vaccines (monovalent: 0.31, p = .010 and bivalent: 0.35, p = .017). Improved neutralizing antibody responses against diverse SARS-CoV-2 variants by the ancestral or variant vaccine highlight the immunological benefits of COVID-19 vaccine boosters regardless of the latest variant-based vaccine. Further studies to determine if different vaccine combinations translate to differing protection against infection remain necessary.

Admission to the intensive care unit represents a profound psychological ordeal for patients' family members. Far beyond the initial shock related to the severity of the illness, the hospital experience exposes families to a cumulative burden of stress, including prolonged uncertainty, confrontation with medical technology, physical exhaustion, loneliness, opaque medical language, and a sense of helplessness. Numerous studies show that during the months following an ICU stay, up to 70% of relatives experience symptoms of anxiety, 35% symptoms of depression, and nearly one third symptoms consistent with post-traumatic stress disorder. To name this specific burden, we propose the concept of HILLY (healthcare-associated family mental injury). HILLY does not pathologize families' experiences nor does it assign individual blame; rather, it highlights the often-unintentional role of certain care-delivery and organizational practices in the emergence of an avoidable trauma, which adds to that of critical illness itself. Restricted visiting policies, fragmented or jargon-laden communication, lack of dedicated spaces for listening, and insufficient recognition of the role of relatives all contribute to exacerbating this injury. The COVID-19 pandemic starkly illustrated the consequences of family exclusion, leading to complicated grief and heightened psychological symptoms among both relatives and healthcare professionals. Preventing HILLY requires a systemic approach: acknowledging this injury, training teams in communication skills, integrating family mental health into quality indicators, valuing relational time, and organizing structured follow-up after ICU discharge. Thinking HILLY means broadening the ethical framework of care to include those who accompany patients, and recognizing that caring for a patient also means caring for their family.

Respiratory infections with influenza, respiratory syncytial virus (RSV), and SARS-CoV-2 are a major cause of global mortality. Vaccination is a cornerstone of disease prevention, though traditional platforms face challenges. Recently, several vaccines utilizing mRNA and adenovirus platforms were brought to the market, with additional vaccines undergoing Phase 3 clinical testing.

This review assesses vaccine literature primarily from 2020 to the present, using National Library of Medicine databases. The rapidity of mRNA technology was tested and implemented successfully during the COVID-19 pandemic. Since then, the mRNA RSV vaccine has been licensed as well. mRNA platforms also offer the ability of combining antigens for multivalent vaccines against multiple pathogens. Several combination products have been used in phase III clinical trials. Adenovirus-vectored vaccines for respiratory viruses have the added advantage of mucosal-based delivery and inducing a potentially stronger local immune response. However, both of these platforms have immunogenicity and safety shortcomings.

Novel respiratory virus vaccine platforms have demonstrated their importance with both endemic and pandemic pathogens, because of decades of concerted efforts and investment in research. Expediting future vaccine development requires a continuation of these efforts with a focus on pre-clinical models and a better understanding of correlates of protection.

Respiratory syncytial virus (RSV) is a leading cause of hospitalization in children. The impact of viral factors like RSV subtype and viral load (VL) on disease severity remains unclear.

We screened 1171 hospitalized children ≤3 years of age with respiratory symptoms in winter seasons (2017-2020) for RSV infection by Reverse Transcription Polymerase Chain reaction. Disease severity was assessed using length of hospital stay and a previously validated disease severity score (RSV-CLASS, range 0-4, higher scores indicating more severe disease). Univariate/multivariate analyses were performed to identify predictors of VL.

In total, n = 351/1171 children were tested RSV positive (RSV A: n = 146/351 [41.6%], RSV B: n = 205/351 [58.4%]) with a median VL of 4.7 × 108 (interquartile range [IQR] 5.6 × 107 to 1.3 × 109). The median age was 3.5 months (IQR 1.5-11.0), and most children were <6 months (n = 223/351 [63.5%]). Bronchiolitis was the leading admission diagnosis, and children were hospitalized for a median duration of 3 days (IQR 2-5), and the median RSV-CLASS disease severity score value was 2 (IQR 1-3). Higher clinical severity scores were observed in children with lower respiratory tract infections (P < 0.01) and were associated with longer hospital stay (ρ = 0.14, 95% confidence interval [CI]: 0.04-0.25). Clinical symptoms did not differ between RSV subtypes. However, younger age, shorter symptom duration, lower weight and reduced blood leukocyte count were associated with higher VL. In multivariate linear regression analysis adjusted for age and sex, weight and leukocyte count remained significant.

This study highlights that RSV subtype and VL are not associated with disease severity in hospitalized children.