Avidity maturation of humoral response following primary and booster doses of BNT162b2 mRNA vaccine among nursing home residents and healthcare workers.

Infections, despite vaccination, can be clinically consequential for frail nursing home residents (NHR). Poor vaccine-induced antibody quality may add risk for such subsequent infections and more severe disease. We assessed antibody binding avidity, as a surrogate for antibody quality, among NHR and healthcare workers (HCW). We longitudinally sampled 112 NHR and 52 HCWs who received the BNT162b2 mRNA vaccine after each dose up to the Wuhan-BA.4/5-based Omicron bivalent boosters. We quantified anti-spike, anti-receptor binding domain (RBD), and avidity levels to the ancestral Wuhan, Delta, and Omicron BA.1 & 4/5 strains. The primary vaccination series produced substantial anti-spike and RBD levels which were low in avidity against all strains tested. Antibody avidity progressively increased in the 6-8 months that followed. Avidity significantly increased after the 1st booster but not for subsequent boosters. This study underscores the importance of booster vaccination among NHR and HCWs. The 1st booster dose increases avidity, increasing vaccine-induced functional antibody. The higher cross-reactivity of higher avidity antibodies to other SARS-CoV-2 strains should translate to better protection from ever-evolving strains. Higher avidities may help explain how the vaccine's protective effects persist despite waning antibody titers after each vaccine dose.

Broad immunogenicity to prior SARS-CoV-2 strains and JN.1 variant elicited by XBB.1.5 vaccination in nursing home residents.

Background: SARS-CoV-2 vaccination has reduced hospitalization and mortality for nursing home residents (NHRs). However, emerging variants coupled with waning immunity, immunosenescence, and variability of vaccine efficacy undermine vaccine effectiveness. We therefore need to update our understanding of the immunogenicity of the most recent XBB.1.5 monovalent vaccine to variant strains among NHRs. Methods: The current study focuses on a subset of participants from a longitudinal study of consented NHRs and HCWs who have received serial blood draws to assess immunogenicity with each SARS-CoV-2 mRNA vaccine dose. We report data on participants who received the XBB.1.5 monovalent vaccine after FDA approval in Fall 2023. NHRs were classified based on whether they had an interval SARS-CoV-2 infection between their first bivalent vaccine dose and their XBB.1.5 monovalent vaccination. Results: The sample included 61 NHRs [median age 76 (IQR 68-86), 51% female] and 28 HCWs [median age 45 (IQR 31-58), 46% female). Following XBB.1.5 monovalent vaccination, there was a robust geometric mean fold rise (GMFR) in XBB.1.5-specific neutralizing antibody titers of 17.3 (95% confidence interval [CI] 9.3, 32.4) and 11.3 (95% CI 5, 25.4) in NHRs with and without interval infection, respectively. The GMFR in HCWs was 13.6 (95% CI 8.4,22). Similarly, we noted a robust GMFR in JN.1-specific neutralizing antibody titers of 14.9 (95% CI 7.9, 28) and 6.5 (95% CI 3.3, 13.1) among NHRs with and without interval infection, and a GMFR of 11.4 (95% CI 6.2, 20.9) in HCWs. NHRs with interval SARS-CoV-2 infection had higher neutralizing antibody titers across all analyzed strains following XBB.1.5 monovalent vaccination, compared to NHRs without interval infection. Conclusion: The XBB.1.5 monovalent vaccine significantly elevates Omicron-specific neutralizing antibody titers to XBB.1.5 and JN.1 strains in both NHRs and HCWs. This response was more pronounced in individuals known to be infected with SARS-CoV-2 since bivalent vaccination. Impact Statement: All authors certify that this work entitled " Broad immunogenicity to prior strains and JN.1 variant elicited by XBB.1.5 vaccination in nursing home residents " is novel. It shows that the XBB.1.5 monovalent vaccine significantly elevates Omicron-specific neutralizing antibody titers in both nursing home residents and healthcare workers to XBB and BA.28.6/JN.1 strains. This work is important since JN.1 increased from less than 0.1% to 94% of COVID-19 cases from October 2023 to February 2024 in the US. This information is timely given the CDC's latest recommendation that adults age 65 and older receive a Spring 2024 XBB booster. Since the XBB.1.5 monovalent vaccine produces compelling immunogenicity to the most prevalent circulating JN.1 strain in nursing home residents, our findings add important support and rationale to encourage vaccine uptake. Key Points: Emerging SARS-CoV-2 variants together with waning immunity, immunosenescence, and variable vaccine efficacy reduce SARS-CoV-2 vaccine effectiveness in nursing home residents.XBB.1.5 monovalent vaccination elicited robust response in both XBB.1.5 and JN.1 neutralizing antibodies in nursing home residents and healthcare workers, although the absolute titers to JN.1 were less than titers to XBB.1.5Why does this paper matter? Among nursing home residents, the XBB.1.5 monovalent SARS-CoV-2 vaccine produces compelling immunogenicity to the JN.1 strain, which represents 94% of all COVID-19 cases in the U.S. as of February 2024.

Durability of immunity and clinical protection in nursing home residents following bivalent SARS-CoV-2 vaccination.

Background: Vaccines have substantially mitigated the disproportional impact of SARS-CoV-2 on the high morbidity and mortality experienced by nursing home residents. However, variation in vaccine efficacy, immune senescence and waning immunity all undermine vaccine effectiveness over time. The introduction of the bivalent vaccine in September 2022 aimed to counter this increasing susceptibility and consequences of breakthrough infection, however data on the durability and protection of the vaccine are limited. We evaluated the durability of immunity and protection after the first bivalent vaccination to SARS-CoV-2 in nursing home residents. Methods: For the immunologic evaluation, community nursing home volunteers agreed to serial blood sampling before, at two weeks, three and six months after each vaccination for antibodies to spike protein and pseudovirus neutralization activity over time. Concurrent clinical outcomes were evaluated by reviewing electronic health record data from residents living in Veterans Administration managed nursing home units. Residents without recent infection but prior vaccination to SARS-CoV-2 were followed over time beginning with administration of the newly available bivalent vaccine using a target trial emulation (TTE) approach; TTE compared time to breakthrough infection, hospitalization and death between those who did and did not receive the bivalent vaccine. Results: We evaluated antibodies in 650 nursing home residents; 452 had data available following a first monovalent booster, 257 following a second monovalent booster and 321 following a bivalent vaccine. We found a rise in BA.5 neutralization activity from the first and second monovalent boosters through the bivalent vaccination regardless of prior SARS-CoV-2 history. Titers declined at three and six months after the bivalent vaccination but generally exceeded those at three months compared to either prior boost. BA.5 neutralization titers six months after the bivalent vaccination were diminished but had detectable levels in 80% of infection-naive and 100% of prior infected individuals. TTE evaluated 5903 unique subjects, of whom 2235 received the bivalent boost. TTE demonstrated 39% or greater reduction in risk of infection, hospitalization or death at four months following the bivalent boost. Conclusion: Immunologic results mirrored those of the TTE and suggest bivalent vaccination added substantial protection for up to six months after bivalent vaccination with notable exceptions. However, the level of protection declined over this period, and by six months may open a window of added vulnerability to infection before the next updated vaccine becomes available. We strongly agree with the CDC recommendation that those who have not received a bivalent vaccination receive that now and these results support a second bivalent booster for those at greatest risk which includes many nursing home residents.

Second monovalent SARS-CoV-2 mRNA booster restores Omicron-specific neutralizing activity in both nursing home residents and health care workers.

We examined whether the second monovalent SARS-CoV-2 mRNA booster increased antibody levels and their neutralizing activity to Omicron variants in nursing home residents (NH) residents and healthcare workers (HCW). We sampled 376 NH residents and 63 HCW after primary mRNA vaccination, first and second boosters, for antibody response and pseudovirus neutralization assay against SARS-CoV-2 wild-type (WT) (Wuhan-Hu-1) strain, Omicron BA.1 and BA.5 variants. Antibody levels and neutralizing activity progressively increased with each booster but subsequently waned over 3-6 months. NH residents, both those without and with prior infection, had a robust geometric mean fold rise (GMFR) of 8.1 (95% CI 4.4, 14.8) and 7.8 (95% CI 4.8, 12.9) respectively in Omicron-BA.1 subvariant specific neutralizing antibody levels following the second booster vaccination (p < 0.001). These results support the ongoing efforts to ensure that both NH residents and HCW are up-to-date on recommended SARS-CoV-2 vaccine booster doses.

Class II/III Obesity Prevalence in Residents of US Nursing Homes: Cross-sectional Study and Forecasting 2030 with COVID-19 Perspective.

OBJECTIVES: This study aimed to better understand Class II/III obesity prevalence trends among older adults residing in nursing homes (NH) nationwide. METHODS: Our retrospective cross-sectional study evaluated Class II/III obesity (BMI ≥35 kg/m²) prevalence among NH residents in two independent national NH cohorts. We used databases from Veterans Administration NHs called Community Living Centers (CLCs) covering 7 years to 2022, and Rhode Island Medicare data covering 20 years ending in 2020. We also performed forecasting regression analysis of obesity trends. RESULTS: While VA CLC resident obesity prevalence was less overall and dipped during the COVID-19 pandemic, obesity prevalence increased in NH residents in both cohorts over the last decade and is predicted to do so through 2030. CONCLUSION: Obesity prevalence in NHs is on the rise. It will be important to understand clinical, functional, and financial implications for NHs, particularly if predictions on increases materialize.

Second monovalent SARS-CoV-2 mRNA booster restores Omicron-specific neutralizing activity in both nursing home residents and health care workers.

We examined whether the second monovalent SARS-CoV-2 mRNA booster increased antibody levels and their neutralizing activity to Omicron variants in nursing home residents (NH) residents and healthcare workers (HCW). We sampled 367 NH residents and 60 HCW after primary mRNA vaccination, first and second boosters, for antibody response and pseudovirus neutralization assay against SARS-CoV-2 wild-type (WT) (Wuhan-Hu-1) strain and Omicron BA1 variant. Antibody levels and neutralizing activity progressively increased with each booster but subsequently waned over weeks. NH residents, both those without and with prior infection, had a robust geometric mean fold rise (GMFR) of 10.2 (95% CI 5.1, 20.3) and 6.5 (95% CI 4.5, 9.3) respectively in Omicron-BA.1 subvariant specific neutralizing antibody levels following the second booster vaccination (p<0.001). These results support the ongoing efforts to ensure that both NH residents and HCW are up to date on recommended SARS-CoV-2 vaccine booster doses.

Epidemiology and Clinical Presentation of COVID-19 in Older Adults.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection remains asymptomatic in 33% to 90% of older adults depending on their immune status from prior infection, vaccination, and circulating strain. Older adults symptomatic with SARS-CoV-2 often both present atypically, such as with a blunted fever response, and develop more severe disease. Early and late reports showed that older adults have increased severity of coronavirus disease 2019 (COVID-19) with higher case fatality rates and higher intensive care needs compared with younger adults. Infection and vaccine-induced antibody response and long-term effects of COVID-19 also differ in older adults.

SARS-CoV-2 Antibody Responses to the Ancestral SARS-CoV-2 Strain and Omicron BA.1 and BA.4/BA.5 Variants in Nursing Home Residents After Receipt of Bivalent COVID-19 Vaccine - Ohio and Rhode Island, September-November 2022.

Introduction of monovalent COVID-19 mRNA vaccines in late 2020 helped to mitigate disproportionate COVID-19-related morbidity and mortality in U.S. nursing homes (1); however, reduced effectiveness of monovalent vaccines during the period of Omicron variant predominance led to recommendations for booster doses with bivalent COVID-19 mRNA vaccines that include an Omicron BA.4/BA.5 spike protein component to broaden immune response and improve vaccine effectiveness against circulating Omicron variants (2). Recent studies suggest that bivalent booster doses provide substantial additional protection against SARS-CoV-2 infection and severe COVID-19-associated disease among immunocompetent adults who previously received only monovalent vaccines (3).* The immunologic response after receipt of bivalent boosters among nursing home residents, who often mount poor immunologic responses to vaccines, remains unknown. Serial testing of anti-spike protein antibody binding and neutralizing antibody titers in serum collected from 233 long-stay nursing home residents from the time of their primary vaccination series and including any subsequent booster doses, including the bivalent vaccine, was performed. The bivalent COVID-19 mRNA vaccine substantially increased anti-spike and neutralizing antibody titers against Omicron sublineages, including BA.1 and BA.4/BA.5, irrespective of previous SARS-CoV-2 infection or previous receipt of 1 or 2 booster doses. These data, in combination with evidence of low uptake of bivalent booster vaccination among residents and staff members in nursing homes (4), support the recommendation that nursing home residents and staff members receive a bivalent COVID-19 booster dose to reduce associated morbidity and mortality (2).

High-dose influenza vaccines for the prevention of hospitalization due to cardiovascular events in older adults in the nursing home: Post-hoc analysis of a cluster-randomized trial.

Older adults are at high risk of major acute cardiovascular events (MACE) linked to influenza illness andpreventable by influenza vaccination. It is unknown whether high-dose vaccine might incrementally reduce the risk of MACE.We conducted a post-hoc analysis of data collected from a pragmatic cluster randomized study of 823 nursing homes (NH) randomized to standard-dose (SD) or high-dose (HD) influenza vaccine in the 2013-14 season. Adults age 65 year or older who are Medicare-enrolled long-stay residents were included in the analysis.There were no statistically significant differences in hospitalization for MACE, acute coronary syndromes (ACS), stroke or heart failure between the HD and SD arms. However, in the fee-for-service group, participants in the HD arm had significantly decreased risk of hospitalization for respiratory problems, which was not observed in the Medicare Advantage group.High-dose influenza vaccine was not shown to be incrementally protective against MACE relative to standard-dose vaccine.

Prognostic value of red cell distribution width and echocardiographic parameters in patients with pulmonary embolism.

INTRODUCTION: Pulmonary embolism (PTE) is a common cardiovascular emergency. We aimed to predict mortality in the acute phase and to assess the development of pulmonary hypertension in the chronic period with the combined use of red cell distribution width (RDW) and echocardiography (ECHO) for the prognosis of PTE. MATERIAL AND METHODS: Cases diagnosed with acute PTE were prospectively monitored in our clinic. The initial data of 56 patients were evaluated. The subjects were separated into two groups basing on RDW; group 1 had RDW ≥ 15.2%, while group 2 had RDW < 15.2%. RESULTS: Ninety-eight patients were enrolled in the study. We established the sensitivity (73.3%) and the specificity (73.2%) of RDW to determine mortality in the cases with PTE. RDW ≥ 15.2% value was significant as an independent risk factor for predicting mortality (OR:7.9 95% CI, 1.5-40.9 p = 0.013) in acute PTE. The mean tricuspid annular plane systolic excursion (TAPSE) value was significantly different between the group-1 (RDW ≥ 15.2%, 2.20 cm (± 0.43)) and group-2 (RDW < 15.2%, 1.85 cm (± 0.53))(p = 0.007). The threshold value for tricuspid jet velocity was > 2.35m/s, the sensitivity and specificity were 76.9% and 61.9%, respectively for predicting mortality (AUC: 0.724, 95% CI: 0.591-0.858, p = 0.033). CONCLUSION: Our results indicate that high RDW levels are an independent predictor of mortality in acute PTE. Lower TAPSE levels show right heart failure in PTE patients; this may also be indicative of right ventricular systolic function. We believe that developing new scoring systems, including parameters such as RDW, TAPSE, and tricuspid jet velocities, may be effective in determining the prognosis of pulmonary embolism.

Safety and Efficacy of Oki Stenting Used to Treat Obstructions in the Right Mainstem Bronchus.

BACKGROUND: Silicone stenting has been used to palliatively manage respiratory symptoms in patients with airway stenoses. Oki and Saka recently developed stents that can be used to manage stenoses around the carina between the bronchus to the right upper lobe and the bronchus intermedius (termed the primary right carina). The aim of this study was to assess the efficacy and safety of Oki stenting used to treat airway stenosis around the primary right carina. METHODS: We included 5 patients with airway stenoses. All Oki stenting procedures were performed with the patients under general anesthesia using either rigid or flexible bronchoscopy. RESULTS: Oki stents were successfully placed in all 5 patients, and the dyspnea index improved in all. Modified Oki stenting was performed at the anastomotic site of 1 patient who had undergone sleeve resection. Four patients had airway obstructions caused by malignant disease. No serious procedural or early complication was noted. One patient died of liver insufficiency, and another with a malignancy died from cranial metastasis of the primary tumor. CONCLUSION: Oki stenting of the primary right carina is safe, efficient, and acceptable when used for palliative management of airway obstruction, even after sleeve resection; in the latter case, some procedural modifications are required.

Efficacy and safety of electromagnetic navigation bronchoscopy with or without radial endobronchial ultrasound for peripheral lung lesions.

BACKGROUND AND OBJECTIVES: Electromagnetic navigation bronchoscopy (ENB) is a promising new technology to increase the diagnostic yield of peripheral lung and mediastinal lesions. Conventional flexible bronchoscopy has a limited yield in peripheral pulmonary lesions, even in experienced hands. Radial endobronchial ultrasound (r-EBUS) with its real-time imaging capability can help to diagnose peripheral pulmonary lesions. In the present study, we aimed to investigate the diagnostic yield and safety of ENB with or without r-EBUS for peripheral lung lesions. MATERIALS AND METHODS: This study was conducted in a tertiary medical center, and 56 consecutive patients who were thought to be the best candidates for bronchoscopic biopsies at a multidisciplinary meeting were enrolled. ENB was performed under conscious sedation by using an electromagnetic tracking system with multiplanar reconstruction of previously acquired computed tomography (CT) data. Sampling was performed by biopsy forceps, endobronchial brush, and bronchoalveolar lavage. RESULTS: Fifty-six patients (50 men and 6 women; mean age, 60 ± 9 years) were studied. While an electromagnetic navigation system was used in all patients, r-EBUS was used in 26 of 56 patients. The median diameter of the lesions was 30 mm (interquartile range: 23-44 mm). Mean distance of the lesions from the pleura was 14.9 ± 14.6 mm. Mean procedure time was 20 ± 11.5 min. Mean registration error was 5.8 ± 1.5 mm. Mean navigation error was 1.2 ± 0.5 mm. The diagnostic yield of the procedure was 71.4% for peripheral lesions (non-small cell lung cancer = 23, small cell lung cancer = 3, benign diseases = 14). Pneumothorax occurred in only 1 patient (1.7%). CONCLUSION: ENB with or without r-EBUS is a safe, efficient, and easily applied method for sampling of peripheral lung lesions, with high diagnostic yield independent of lesion size and location.

Therapeutic bronchoscopic interventions for malignant airway obstruction: A retrospective study from experience on 547 patients.

There is no definitive consensus about the factors affecting the choice of interventional bronchoscopy in the management of malignant airway obstruction. The present study defines the choice of the interventional bronchoscopic modality and analyzes the factors influencing survival in patients with malignant central airway obstruction. Totally, over 7 years, 802 interventional rigid bronchoscopic procedures were applied in 547 patients having malignant airway obstruction. There was a significant association between the type of stent and the site of the lesion in the present study. Patients with tracheal involvement and/or involvement of the main bronchi had the worst prognosis. The sites of the lesion and endobronchial treatment modality were independent predictors of survival in the present study. The selection of different types of airway stents can be considered on the base of site of the lesion. Survival can be estimated based on the site of the lesion and endobronchial brochoscopic modality used.

Extranodal pulmonary marginal zone B-cell lymphoma.

AIM: Extranodal mucosa-associated lymphoid tissue (MALT) arises a number of epithelial tissues, including the stomach, salivary gland, lung, small bowel, and elsewhere. Here we present a male patient with an uncommon site of extranodal MALT such as a pelvic mass diagnosed after a long period of evaluation, which initially presented with an incidental pulmonary nodule. METHOD: We report a 60 years old man presenting with pulmonary nodules and consolidation. He refused invasive procedures and 3 years later was administered to our clinic with disseminated pulmonary nodules on chest X-ray. Subsequently a thin needle aspiration biopsy was performed and candida geotrichum was suspected in the specimen of the lung biopsy by light microscopic examination. After this time the patient was referred to our clinic, bronchoscopy, mediastinoscopy and abdominal computerized tomography (CT) scans were performed. RESULTS: Lymphoid hyperplasia was seen in the mediastinal lymph nodes biopsy specimens and the pelvic mass (52 × 18 mm) on the superior iliac muscles not related to any organs. Thin needle biopsy revealed MALT lymphoma and pathological examination of pulmonary nodule was similar to pelvic mass (MALT lymphoma). After the diagnosis, the thin needle biopsy of lung was repeated. The specimen appeared to be similar to the pelvic mass (MALT lymphoma) in the pathologic examination. The patient survived 5 years after initial diagnosis. CONCLUSION: MALT has an affinity for the different tissues however has not been located in the pelvis. Our case represent an unusual presentation in a 60 years old man with lung and a pelvic mass.

Bronchoscopic Treatment in the Management of Benign Tracheal Stenosis: Choices for Simple and Complex Tracheal Stenosis.

BACKGROUND: Bronchoscopic treatment is 1 of the treatment choices for both palliative and definitive treatment of benign tracheal stenosis. There is no consensus on the management of these patients, however, especially patients having complex stenoses. The aim of the present study was to assess, in the largest group of patients with complex stenoses yet reported, which types of tracheal stenosis are amenable to optimal management by bronchoscopic treatment. METHODS: The present study was a retrospective cohort study including 132 consecutive patients with benign tracheal stenoses diagnosed between August 2005 and January 2013. The mean age of the study population was 52 ± 18 years; 62 (47%) were women and 70 (53%) were men. Their lesions were classified as simple and complex stenoses. RESULTS: Simple stenoses (n = 6) were treated with 12 rigid and flexible bronchoscopic procedures (mean of 2 per patient); 5 stents were placed. The total success rate was 100%. Among the 124 complex stenoses, 4 were treated directly with surgical intervention. In total, 481 rigid and 487 flexible bronchoscopic procedures were performed in these patients. In this group, the success rate was 69.8%. CONCLUSIONS: From the present study, we propose that after accurate classification, interventional bronchoscopic management may have an important role in the treatment of benign tracheal stenosis. Bronchoscopic treatment should be considered as first-line therapy for simple stenoses, whereas complex stenoses need a multidisciplinary approach and often require surgical intervention. However, bronchoscopic treatment may be a valid conservative approach in the management of patients with complex tracheal stenosis who are not eligible for operative treatment.

Diagnostic value of suPAR in differentiating noncardiac pleural effusions from cardiac pleural effusions.

INTRODUCTION: Soluble urokinase plasminogen activator receptor (suPAR) is a newly discovered inflammatory biomarker. suPAR has not been previously studied in differentiating noncardiac pleural effusion (PF) from cardiac PF. The aim of our study was to assess the diagnostic value of suPAR in PF. METHODS: The concentration of PF-suPAR was measured by a commercialized enzyme-linked immunosorbent assay in a prospective cohort of 74 patients with PF, 18 patients with PF due to cardiac failure (CF) and 56 patients with noncardiac PF. The area under the curve quantified the overall diagnostic accuracy of the tests. RESULTS: The median pleural fluid suPAR level was found as 23 (5.4-102.8) ng/mL. The median PF-suPAR level in CF was significantly lower than that of noncardiac effusions [11.8 (5.4-28.9) ng/mL vs 26.7 (8.2-102.8) ng/mL, respectively, P < 0.001]. The area under the receiver operating characteristic curve was 0.878 (95% confidence interval: 0795-0.962, P < 0.001) for noncardiac pleural fluid suPAR. The sensitivity, specificity and positive predictive value of PF-suPAR for noncardiac effusions at the cutoff level of ≥17.6 n/mL was 88%, 83% and 94%, respectively. The suPAR level in PF was found to correlate with all of the biochemical parameters of PF. CONCLUSIONS: suPAR is a potential new marker for the discrimination between cardiac and noncardiac PF.