Local and global changes in cell density induce reorganisation of 3D packing in a proliferating epithelium.

Tissue morphogenesis is intimately linked to the changes in shape and organisation of individual cells. In curved epithelia, cells can intercalate along their own apicobasal axes, adopting a shape named 'scutoid' that allows energy minimization in the tissue. Although several geometric and biophysical factors have been associated with this 3D reorganisation, the dynamic changes underlying scutoid formation in 3D epithelial packing remain poorly understood. Here, we use live imaging of the sea star embryo coupled with deep learning-based segmentation to dissect the relative contributions of cell density, tissue compaction and cell proliferation on epithelial architecture. We find that tissue compaction, which naturally occurs in the embryo, is necessary for the appearance of scutoids. Physical compression experiments identify cell density as the factor promoting scutoid formation at a global level. Finally, the comparison of the developing embryo with computational models indicates that the increase in the proportion of scutoids is directly associated with cell divisions. Our results suggest that apico-basal intercalations appearing immediately after mitosis may help accommodate the new cells within the tissue. We propose that proliferation in a compact epithelium induces 3D cell rearrangements during development.

Factors Associated with SARS-CoV-2 Infection in Fully Vaccinated Nursing Home Residents and Workers.

Persons living or working in nursing homes faced a higher risk of SARS-CoV-2 infections during the pandemic, resulting in heightened morbidity and mortality among older adults despite robust vaccination efforts. This prospective study evaluated the humoral and cellular immunity in fully vaccinated residents and workers from two nursing homes in Madrid, Spain, from 2020 to 2021. Measurements of IgG levels were conducted in August 2020 (pre-vaccination) and June and September 2021 (post-vaccination), alongside assessments of neutralizing antibodies and cellular responses in September 2021 among the most vulnerable individuals. Follow-up extended until February 2022 to identify risk factors for SARS-CoV-2 infection or mortality, involving 267 residents (mean age 87.6 years, 81.3% women) and 302 workers (mean age 50.7 years, 82.1% women). Residents exhibited a significantly higher likelihood of experiencing COVID-19 before June 2021 compared with nursing staff (OR [95% CI], 7.2 [3.0 to 17.2], p < 0.01). Participants with a history of previous COVID-19 infection showed more significant increases in IgG levels in August 2020, June 2021 and September 2021, alongside an increased proportion of neutralizing antibodies in the most vulnerable individuals. However, IgG decay remained the same between June and September 2021 based on the previous COVID-19 status. During the Omicron variant wave, residents and staff showed a similar rate of SARS-CoV-2 infection. Notably, preceding clinical or immunological factors before receiving three vaccination doses did not demonstrate associations with COVID-19 infection or overall mortality in our participant cohort.

Local and global changes in cell density induce reorganisation of 3D packing in a proliferating epithelium.

Tissue morphogenesis is intimately linked to the changes in shape and organisation of individual cells. In curved epithelia, cells can intercalate along their own apicobasal axes adopting a shape named "scutoid" that allows energy minimization in the tissue. Although several geometric and biophysical factors have been associated with this 3D reorganisation, the dynamic changes underlying scutoid formation in 3D epithelial packing remain poorly understood. Here we use live-imaging of the sea star embryo coupled with deep learning-based segmentation, to dissect the relative contributions of cell density, tissue compaction, and cell proliferation on epithelial architecture. We find that tissue compaction, which naturally occurs in the embryo, is necessary for the appearance of scutoids. Physical compression experiments identify cell density as the factor promoting scutoid formation at a global level. Finally, the comparison of the developing embryo with computational models indicates that the increase in the proportion of scutoids is directly associated with cell divisions. Our results suggest that apico-basal intercalations appearing just after mitosis may help accommodate the new cells within the tissue. We propose that proliferation in a compact epithelium induces 3D cell rearrangements during development.

In vivo behavior in rabbit radius bone defect of scaffolds based on nanocarbonate hydroxyapatite.

Bone defects treatment may require the use of biomaterials that behave as a support and promote bone regeneration. Limitations associated with the use of autografts and allografts make it necessary to design new synthetic bone substitutes. Some of the most promising biomaterials currently under investigation are based on nanocarbonate hydroxyapatite (nCHA). In this study, we studied the bone-inducing capacity of nCHA-based scaffolds alone (SAG) and enriched with osteostatin (SAGO) or with bone marrow aspirate(SAGB) after implantation for 12 weeks in a 15-mm long critical defect performed in the radius of New Zealand rabbits. Bone formation obtained was compared with a group with the unfilled defect (CE), as control group, and other with the defect filed with iliac crest autograft (GS), as gold standard. X-ray follow-up was performed at 2, 4, 6 and 12 weeks and µCT and histological studies at 12 weeks. The radiological results showed a greater increment in bone formation in the GS group (75%-100%), followed by the SAG and SAGB groups (50%-75%). µCT results showed an increase of bone volume/tissue volume values in GS group followed by SAG and SAGB groups (0.53, 0.40, and 0.31 respectively) compared with CE group (0.26). Histological results showed limited resorption of the nCHA scaffolds and partial osseointegration in the SAG and SAGB groups. However, in the SAGO group, the presence of connective tissue encapsulating the scaffold was detected. In SAG, SAGB, and increase of bone formation were observed compared with CE group, but less than the GS group. Thus, the investigated materials represent a significant advance in the design of synthetic materials for bone grafting, but further studies are needed to bring their in vivo behavior closer to autograft, the gold standard.

Diagnosis and Management of a Massive Eight-Centimeter Acquired Tracheoesophageal Fistula.

Here, we present the case of a 61-year-old veteran Hispanic male with recurrent aspiration pneumonitis, aerophagia, tympanic abdominal bloating, and a positive Ono's sign; symptoms present were secondary to diagnosed tracheoesophageal fistulas (TEFs). TEFs are abnormal connections between the esophagus and the trachea. In adult cases, several risk factors have been identified for acquired cases, which include infection, trauma, and cancer. Diagnosis of TEF can be challenging and, in most cases, requires high suspicion. Currently, there are no established guidelines for diagnosing and managing TEF. Clinical assessment and various imaging techniques are essential in the diagnostic process. This article will discuss the etiology, clinical presentation, diagnostic approaches, and management options for acquired TEFs.

CartoCell, a high-content pipeline for 3D image analysis, unveils cell morphology patterns in epithelia.

Decades of research have not yet fully explained the mechanisms of epithelial self-organization and 3D packing. Single-cell analysis of large 3D epithelial libraries is crucial for understanding the assembly and function of whole tissues. Combining 3D epithelial imaging with advanced deep-learning segmentation methods is essential for enabling this high-content analysis. We introduce CartoCell, a deep-learning-based pipeline that uses small datasets to generate accurate labels for hundreds of whole 3D epithelial cysts. Our method detects the realistic morphology of epithelial cells and their contacts in the 3D structure of the tissue. CartoCell enables the quantification of geometric and packing features at the cellular level. Our single-cell cartography approach then maps the distribution of these features on 2D plots and 3D surface maps, revealing cell morphology patterns in epithelial cysts. Additionally, we show that CartoCell can be adapted to other types of epithelial tissues.

Expert Consensus: Main Risk Factors for Poor Prognosis in COVID-19 and the Implications for Targeted Measures against SARS-CoV-2.

The clinical evolution of patients infected with the Severe Acute Respiratory Coronavirus type 2 (SARS-CoV-2) depends on the complex interplay between viral and host factors. The evolution to less aggressive but better-transmitted viral variants, and the presence of immune memory responses in a growing number of vaccinated and/or virus-exposed individuals, has caused the pandemic to slowly wane in virulence. However, there are still patients with risk factors or comorbidities that put them at risk of poor outcomes in the event of having the coronavirus infectious disease 2019 (COVID-19). Among the different treatment options for patients with COVID-19, virus-targeted measures include antiviral drugs or monoclonal antibodies that may be provided in the early days of infection. The present expert consensus is based on a review of all the literature published between 1 July 2021 and 15 February 2022 that was carried out to establish the characteristics of patients, in terms of presence of risk factors or comorbidities, that may make them candidates for receiving any of the virus-targeted measures available in order to prevent a fatal outcome, such as severe disease or death. A total of 119 studies were included from the review of the literature and 159 were from the additional independent review carried out by the panelists a posteriori. Conditions found related to strong recommendation of the use of virus-targeted measures in the first days of COVID-19 were age above 80 years, or above 65 years with another risk factor; antineoplastic chemotherapy or active malignancy; HIV infection with CD4+ cell counts < 200/mm3; and treatment with anti-CD20 immunosuppressive drugs. There is also a strong recommendation against using the studied interventions in HIV-infected patients with a CD4+ nadir <200/mm3 or treatment with other immunosuppressants. Indications of therapies against SARS-CoV-2, regardless of vaccination status or history of infection, may still exist for some populations, even after COVID-19 has been declared to no longer be a global health emergency by the WHO.

Prevalence of hypertensive phase and outcomes in patients with Ahmed valve implantation at one year of follow-up and evaluation of associated risk factors.

Purpose: To evaluate the prevalence of hypertensive phase (HP) and failure in patients who underwent Ahmed Glaucoma Valve (AGV) implantation and identify the possible risk factors for both HP and failure. Methods: A cross-sectional, observational study was conducted. Medical records of patients who underwent AGV implantation and had at least 1 year of follow-up were reviewed. HP was defined as an intraocular pressure (IOP) greater than 21 mmHg between the first week and the third postoperative month not attributable to other causes. Success was defined as an IOP between 6 and 21 mmHg, with preservation of light perception and no additional glaucoma surgeries. Statistical analysis was conducted to identify possible risk factors. Results: A total of 193 eyes of 177 patients were included. HP was present in 58%; a higher preoperative IOP and younger age were associated with HP. Pseudophakic or aphakic eyes had a lower HP rate. Failure was present in 29%; neovascular glaucoma, worse basal best corrected visual acuity (BCVA), higher baseline IOP, and postoperative complications were linked to a higher likelihood of failure. No difference in the HP rate between the failure and success groups was found. Conclusion: A higher baseline IOP and younger age are associated with HP development; pseudophakia and aphakia might be protective factors. Factors for AGV failure are a worse BCVA, neovascular glaucoma, postoperative complications, and a higher baseline IOP. At 1 year, a higher number of medications were needed to achieve IOP control in the HP group.

Hospitalization Burden of Patients with Kidney Stones and Metabolic Comorbidities in Spain during the Period 2017-2020.

Nephrolithiasis has become an increasing worldwide problem during the last decades. Metabolic syndrome, its components, and related dietary factors have been pointed out as responsible for the increasing incidence. The objective of this study was to evaluate the trends in the hospitalization rates of patients with nephrolithiasis, hospitalization features, costs, and how metabolic syndrome traits influence both the prevalence and complications of lithiasic patients. An observational retrospective study was conducted by analyzing hospitalization records from the minimum basic data set, including all patient hospitalizations in Spain in which nephrolithiasis has been coded as a main diagnosis or as a comorbidity during the period 2017-2020. A total of 106,407 patients were hospitalized and coded for kidney or ureteral lithiasis in this period. The mean age of the patients was 58.28 years (CI95%: 58.18-58.38); 56.8% were male, and the median length of stay was 5.23 days (CI95%: 5.06-5.39). In 56,884 (53.5%) patients, kidney or ureteral lithiasis were coded as the main diagnosis; the rest of the patients were coded mostly as direct complications of kidney or ureteral stones, such as "non-pecified renal colic", "acute pyelonephritis", or "tract urinary infection". The hospitalization rate was 56.7 (CI95%: 56.3-57.01) patients per 100,000 inhabitants, showing neither a significant increasing nor decreasing trend, although it was influenced by the COVID-19 pandemic. The mortality rate was 1.6% (CI95%: 1.5-1.7), which was higher, if lithiasis was coded as a comorbidity (3.4% CI95%: 3.2-3.6). Metabolic syndrome diagnosis component codes increased the association with kidney lithiasis when age was higher, reaching the highest in the eighth decade of life. Age, diabetes, and hypertension or lithiasis coded as a comorbidity were the most common causes associated with the mortality of lithiasic patients. In Spain, the hospitalization rate of kidney lithiasis has remained stable during the period of study. The mortality rate in lithiasic patients is higher in elderly patients, being associated with urinary tract infections. Comorbidity conditions such as diabetes mellitus and hypertension are mortality predictors.

Temporal Series Analysis of Population Cycle Threshold Counts as a Predictor of Surge in Cases and Hospitalizations during the SARS-CoV-2 Pandemic.

Tools to predict surges in cases and hospitalizations during the COVID-19 pandemic may help guide public health decisions. Low cycle threshold (CT) counts may indicate greater SARS-CoV-2 concentrations in the respiratory tract, and thereby may be used as a surrogate marker of enhanced viral transmission. Several population studies have found an association between the oscillations in the mean CT over time and the evolution of the pandemic. For the first time, we applied temporal series analysis (Granger-type causality) to validate the CT counts as an epidemiological marker of forthcoming pandemic waves using samples and analyzing cases and hospital admissions during the third pandemic wave (October 2020 to May 2021) in Madrid. A total of 22,906 SARS-CoV-2 RT-PCR-positive nasopharyngeal swabs were evaluated; the mean CT value was 27.4 (SD: 2.1) (22.2% below 20 cycles). During this period, 422,110 cases and 36,727 hospital admissions were also recorded. A temporal association was found between the CT counts and the cases of COVID-19 with a lag of 9-10 days (p ≤ 0.01) and hospital admissions by COVID-19 (p < 0.04) with a lag of 2-6 days. According to a validated method to prove associations between variables that change over time, the short-term evolution of average CT counts in the population may forecast the evolution of the COVID-19 pandemic.

Cross-Sectional Analysis of Risk Factors for Outbreak of COVID-19 in Nursing Homes for Older Adults in the Community of Madrid.

INTRODUCTION: Nursing homes for older adults have been hot spots for SARS-CoV-2 infections and mortality. Factors that facilitate COVID-19 outbreaks in these settings need to be assessed. METHODS: A retrospective cross-sectional study of a cohort of residents and workers in nursing homes taking occasion of a point seroprevalence survey was done in the Community of Madrid. Factors related to outbreaks in these facilities were analyzed. RESULTS: A total of 369 nursing homes for older adults, making a population of 23,756 residents and 20,795 staff members, were followed from July to December 2020. There were 54.2% SARS-CoV-2 IgG+ results in residents and in 32.2% of workers. Sixty-two nursing homes (16.8%) had an outbreak during the follow-up. Nursing homes with outbreaks had more residents than those without (median number of 81 [IQR, 74] vs. 50 [IQR, 56], p < 0.001). Seropositivity for SARS-CoV-2 was lower in facilities with versus without outbreaks, for residents (42.2% [IQR, 55.7] vs. 58.7% [IQR, 43.4], p = 0.002) and for workers (23.9% [IQR, 26.4] vs. 32.8% [IQR, 26.3], p = 0.01). For both residents and staff, the number of infections in outbreaks was larger in centers with lower, as compared with intermediate or high seroprevalence. The size of the facility did not correlate with the number of cases in the outbreak. Taking the incidence of cases in the community as a time-dependent variable (p = 0.03), a Cox analysis (HR [95% CI], p) showed that intermediate or high seroprevalence among residents in the facility was related to a reduction of 55% (0.45 [0.25-0.80], p = 0.007) and 78% (0.22 [0.10-0.48], p < 0.001) in the risk of outbreaks, respectively, as compared with low sero-prevalence. Also, as compared with smaller, medium (1.91 [1.00-3.65], p = 0.05) or large centers (4.57 [2.38-8.75], p < 0.001) had more respective risk of outbreaks. CONCLUSIONS: The size of the facility and the seroprevalence among residents in nursing homes, and the incidence of infections in the community, are associated with the risk of outbreaks of COVID-19. Facilities with greater proportion of seropositives had smaller number of cases. Monitoring of immunity in nursing homes may help detect those at a greater risk of future cases.

Surgical outcomes of excisional goniotomy using the kahook dual blade in severe and refractory glaucoma: 12-month results.

OBJECTIVES: To describe the efficacy and safety of goniotomy with trabecular meshwork excision using the Kahook Dual Blade (KDB, New World Medical Inc., Rancho Cucamonga, CA) in patients with severe or refractory glaucoma. METHODS: This retrospective multicentre case series reports on 40 eyes with severe or refractory open-angle glaucoma that underwent standalone or combined KDB goniotomy and were followed for 12 months post-operatively in the United-States, Mexico and Switzerland. Surgical success was defined as an intraocular pressure (IOP) reduction ≥20% from baseline at 12 months, with fewer medications than preoperatively. Mean IOP and antiglaucoma medication reduction, probabilities of achieving an IOP ≤16 or 18 mmHg, and adverse events were also analysed. RESULTS: Mean IOP decreased from 18.1 ± 5.0 mmHg at baseline to 14.8 ± 3.7 mmHg at 12 months (18.2% reduction, P < 0.001). Concomitantly, the mean number of glaucoma medications decreased from 2.5 ± 1.4 to 1.7 ± 1.2 (32% reduction, P = 0.002). The proportion of eyes achieving an IOP reduction of more than 20% from baseline was 37.5% (n = 15) at 12 months. At 12 months, 67.5% and 82.5% achieved a medicated IOP ≤ 16 and ≤18 mmHg, respectively. No severe complications were reported. CONCLUSION: Excisional goniotomy with KDB achieves a statistically significant IOP and antiglaucoma medication reduction in severe or refractory glaucoma over a period of 12 months. While its efficacy decreases with time, its favourable safety profile makes it a potentially useful primary or adjunctive procedure in high-risk eyes.

Endocrine Sequelae in 157 Pediatric Survivors of Hematopoietic Stem Cell Transplantation (HSCT).

Context: Successful rates of hematopoietic stem cell transplantation (HSCT) face paralleled escalation of late endocrine and metabolic effects. Objective: This work aimed to characterize these sequelae distinguishing between the underlying pathologies and treatments received. Methods: A retrospective descriptive study was conducted in 157 children post-HSCT (hematopoietic pathology [N = 106], solid tumors [N = 40], and rare entities [N = 11]) followed at a single endocrine department between 2009 and 2019. Regression analysis was used to ascertain association. Results: Of all patients, 58.7% presented with at least one endocrine abnormality. Endocrinopathies post HSCT were most frequently developed in lymphoblastic leukemia (60.5% of them), whereas myeloid leukemias had the fewest. A total of 64% of patients presented with primary hypogonadism, 52% short stature, and 20% obesity. Endocrinopathy was associated with older age at HSCT (9.78 years [6.25-12.25] vs 6.78 years [4.06-9.75]) (P < .005), pubertal Tanner stage V (P < .001), chronic graft-vs-host disease (GVHD) (P = .022), and direct gonadal therapy (P = .026). The incidence of endocrinopathies was higher in girls (15% more common; P < .02) and in patients who received radiotherapy (18% higher), steroids (17.4% increase), allogenic HSCT (7% higher), thymoglobulin, or cyclophosphamide. Those on busulfan presented with a 27.5% higher rate of primary hypogonadism (P = .003). Conclusion: More than half of children surviving HSCT will develop endocrinopathies. Strikingly, obesity has risen to the third most frequent endocrine disruption, mainly due to steroids, and partly adhering to the general population tendency. Lymphoblastic leukemia was the condition with a higher rate of endocrine abnormalities. Female sex, older age at HSCT, pubertal stage, allogenic transplant, radiotherapy, alkylating drugs, and GVHD pose risk factors for endocrine disturbances.

Vulnerability to SARS-CoV-2 infection and disease: ripping the curl after the storm

SARS-CoV-2 infection now seems to have entered the announced endemic phase. The population’s immunity is increasingly more robust, thanks to successive vaccination and booster campaigns, and the almost inevitable exposure and re-exposure to the virus itself, which has truly served as a natural immunizing mechanism. On the other hand, the genetic drift of the virus is leading it to become another catarrhal agent, as are the other endemic human coronaviruses. However, it should not be lost sight of that there are still segments of the population with susceptibility to severe COVID, who will be candidates to continue receiving vaccine boosters or antiviral drugs in the initial stages of infection. (AU)

Knowledge and awareness of glaucoma in Mexican patients with and without glaucoma diagnosis in an Ophthalmology Referral Center.

AIM: To assess and compare knowledge and awareness of glaucoma in subjects with and without glaucoma diagnosis attending an Ophthalmology Referral Center. METHODS: This cross-sectional study was conducted at Asociación Para Evitar la Ceguera in Mexico City, using a questionnaire formulated by a group of experts following the Delphi panel rules, and pre-tested in a pilot study. The questionnaire was applied and compared between: glaucoma patients, relatives of glaucoma patients and patients without glaucoma. Socio-demographic data was collected to assess correlation with the level of knowledge using Logistic regression models, estimating the odds ratios (OR), 95% confidence intervals, and P<0.05. RESULTS: Three hundred and ninety-four subjects were enrolled; with a median age of 61y. One hundred and thirty-four (34%) were patients with glaucoma, 152 (38.6%) patients without glaucoma, and 108 (27.4%) relatives of patients with glaucoma. Two hundred and ninety-one (73.9%) participants were aware of the term "glaucoma". Regarding knowledge 46.7% had moderate knowledge, 37.8% had poor knowledge, and 15.5% good knowledge. Overall, relatives of glaucoma patients had the highest scores, and patients without glaucoma got the lowest scores. A positive correlation was found between better knowledge and frequent ophthalmological examinations OR 2.24 (P=0.02), higher education level OR 4.17 (P=0.00) and having a family member with glaucoma OR 3.28 (P=0.00). CONCLUSION: Awareness and knowledge of glaucoma in subjects attending an Ophthalmology Referral Center is predominantly moderate or poor. This has important implications regarding attitudes that can result in lack of follow up in ophthalmological care.

A quantitative biophysical principle to explain the 3D cellular connectivity in curved epithelia.

Epithelial cell organization and the mechanical stability of tissues are closely related. In this context, it has been recently shown that packing optimization in bended or folded epithelia is achieved by an energy minimization mechanism that leads to a complex cellular shape: the "scutoid". Here, we focus on the relationship between this shape and the connectivity between cells. We use a combination of computational, experimental, and biophysical approaches to examine how energy drivers affect the three-dimensional (3D) packing of tubular epithelia. We propose an energy-based stochastic model that explains the 3D cellular connectivity. Then, we challenge it by experimentally reducing the cell adhesion. As a result, we observed an increment in the appearance of scutoids that correlated with a decrease in the energy barrier necessary to connect with new cells. We conclude that tubular epithelia satisfy a quantitative biophysical principle that links tissue geometry and energetics with the average cellular connectivity.

The Role of Walking in the Relationship between Catastrophizing and Fatigue in Women with Fibromyalgia.

Walking is one of the most beneficial treatments for fibromyalgia patients. However, adherence to walking behavior is low due to the initially associated symptoms (including pain and fatigue). Although the association of catastrophism with greater symptoms is known, the results regarding fatigue have not always been consistent. Nevertheless, it is unknown whether the association between catastrophism and fatigue could, in turn, be conditioned by whether the patients walk or not. Therefore, our goal was to explore the moderating effect of walking on the association between catastrophizing and fatigue in patients with fibromyalgia. A cross-sectional study was carried out with 203 women with fibromyalgia. We used the Multidimensional Fatigue Inventory to assess fatigue and the Pain Catastrophizing Scale to assess pain catastrophizing (differentiating between its three dimensions). An ad hoc item was used to evaluate walking (moderator). Lower scores for fatigue and pain catastrophizing were found among patients who walked versus those who did not. Walking moderated the relationship between rumination and fatigue (Beta = 0.16, t = 1.96, p = 0.049) and between magnification and fatigue (Beta = 0.22, t = 21.83, p = 0.047). Helplessness showed no direct or interaction effect for fatigue. Nevertheless, higher rumination and magnification were associated with higher fatigue only in patients who walked. Therefore, to promote adherence to walking and reduce the effects of catastrophizing on fatigue, it seems necessary to manage rumination and magnification among patients who walk.

Humoral and Cellular Response after mRNA Vaccination in Nursing Homes: Influence of Age and of History of COVID-19.

Background: Most residents and staff in nursing homes have received full vaccination. Factors related to the immune response to vaccination might be related to the risk of future severe COVID-19 and may guide the need for vaccine boosters. Design: Nursing homes that were tested in a point survey in July-October 2020 were again analyzed after a vaccination campaign in June-July 2021. Immune responses according to IgG against nucleocapsid and spike antigens, and CD4 and CD8 interferon-gamma release assay against spike antigens, were evaluated. Results: A total of 1973 subjects were tested (61.7% residents, 48.3% staff), with a mean (SD) follow-up of 46.4 (3.6) weeks between assessments. More than half of residents and more than a third of staff had evidence of COVID-19 before vaccination; 26.9% and 22.7% had seroreversion of IgG-N, and 8.9% and 4.6% had IgG-N seroconversion at second assessment, respectively. Up to 96.8% of residents and 98.1% of workers had positive IgG-S after a mean of 19.9 (2.1) weeks after vaccination. In residents with vs without a history of COVID-19, IgG-S titers were 4.11 (0.54) vs. 2.73 (0.74) logAU/mL (p < 0.001); in workers these titers were 3.89 (0.61) vs. 3.15 (0.64) logAU/mL (p < 0.001). Linear regression analysis showed that younger age (OR: −0.03 per 10 years-older [95% CI, −0.04 to −0.02], p < 0.001) and evidence of COVID-19 (OR: 1.14 [95% CI, 1.08 to 1.20], p < 0.001) are associated with greater IgG-S titers after vaccination. A direct association was found between IgG-S titers and the intensity of IFN-gamma response against spike antigens. Conclusions: Waning of humoral response and reinfection seems to be more frequent in older as compared to younger adults, although cellular responses shortly after vaccination are comparable between these groups. Younger age and prior COVID-19 are related to greater humoral response after vaccination against SARS-CoV-2.

A Pilot Study for the Evaluation of an Interferon Gamma Release Assay (IGRA) To Measure T-Cell Immune Responses after SARS-CoV-2 Infection or Vaccination in a Unique Cloistered Cohort.

Assessment of T-cell responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigens may be of value to determine long-lasting protection to breakthrough infections or reinfections. Interferon gamma release assay is a validated method to test cellular immunity in mycobacterial infections and has been proposed for patients with SARS-CoV-2 infection or vaccination. Quantitative IgG to spike and qualitative IgG to nucleocapsid antigens were determined by chemiluminescence microparticle immunoassay using the Architect platform (Abbott), and interferon gamma release assays against two Qiagen proprietary mixes of SARS-CoV-2 spike protein (antigen 1 and antigen 2) were performed for a selected group of subjects. A total of 121 subjects in a cloistered institution after a COVID-19 outbreak was studied. IgG spike levels and interferon gamma concentrations were highest among subjects after two doses of vaccine, followed by patients with a longer history of past COVID-19 and no vaccination. The best cutoff for the interferon gamma assay was 25 IU/L for all subgroups of individuals and the two sets of SARS-CoV-2 antigens studied. Testing T-cell response may be of clinical utility to determine immunity after exposure to SARS-CoV-2 antigens, with the interferon gamma concentration of 25 IU/L as the best cutoff either after infection or vaccination.

Hospitalizations related to meningococcal infection in Spain from 1997 to 2018.

BACKGROUND: Baseline hospitalization, mortality, and in-hospital fatality rates for meningococcal infection are required to evaluate preventive interventions, such as the inclusion of the conjugated quadrivalent meningococcal vaccine and serogroup B based protein vaccines. METHODS: All meningococcal infection-related hospitalizations in any diagnostic position in Spain from 1st January 1997 through 31st December 2018 were analysed. The annual hospitalization rate, mortality rate and case-fatality rate were calculated. RESULTS: The average hospitalization rate for meningococcal infection was 1.64 (95% CI 1.61 to 1.66) hospitalizations per 100,000 inhabitants during the study period and significantly decreased from 1997 to 2018. Hospitalizations for meningococcal infection decreased significantly with age and were concentrated in children under 5 years of age (46%). The hospitalization rates reached 29 per 100,000 and 24 per 100,000 children under 1 and 2 years of age, respectively. The in-hospital case-fatality rate was 7.45% (95% CI 7.03 to 7.86). Thirty percent of the deaths occurred in children under 5 years of age, and more than half occurred in adults. The case fatality rate increased significantly with age (p < 0.001). CONCLUSION: It is necessary to maintain epidemiological surveillance of meningococcal infection to determine the main circulating serogroups involved, track their evolution, and evaluate preventive measures whose effectiveness must be assessed in all age groups.