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Introduction: This study evaluated the immune response to a multiepitope recombinant chimeric protein (CHIVAX) containing B- and T-cell epitopes of the SARS-CoV-2 spike's receptor binding domain (RBD) in a translational porcine model for pre-clinical studies., Methods: We generated a multiepitope recombinant protein engineered to include six coding conserved epitopes from the RBD domain of the SARS-CoV-2 S protein. Pigs were divided into groups and immunized with different doses of the protein, with serum samples collected over time to determine antibody responses by indirect ELISA and antibody titration. Peptide recognition was also analyzed by Western blotting. A surrogate neutralization assay with recombinant ACE2 and RBDs was performed. Intranasal doses of the immunogen were also prepared and tested on Vietnamese minipigs., Results: When the immunogen was administered subcutaneously, it induced specific IgG antibodies in pigs, and higher doses correlated with higher antibody levels. Antibodies from immunized pigs recognized individual peptides in the multiepitope vaccine and inhibited RBD-ACE2 binding for five variants of concern (VOC). Comparative antigen delivery methods showed that both, subcutaneous and combined subcutaneous/intranasal approaches, induced specific IgG and IgA antibodies, with the subcutaneous approach having superior neutralizing activity. CHIVAX elicited systemic immunity, evidenced by specific IgG antibodies in the serum, and local mucosal immunity, indicated by IgA antibodies in saliva, nasal, and bronchoalveolar lavage secretions. Importantly, these antibodies demonstrated neutralizing activity against SARS-CoV-2 in vitro ., Discussion: The elicited antibodies recognized individual epitopes on the chimeric protein and demonstrated the capacity to block RBD-ACE2 binding of the ancestral SARS-CoV-2 strain and four VOCs. The findings provide proof of concept for using multiepitope recombinant antigens and a combined immunization protocol to induce a neutralizing immune response against SARS-CoV-2 in the pig translational model for preclinical studies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Mosqueda, Hernández-Silva, Vega-López, Vega-Rojas, Beltrán, Velasco-Elizondo, Ramírez-Estudillo, Fragoso-Saavedra, Pérez-Almeida, Hernández, Melgoza-González, Hinojosa-Trujillo, Mercado-Uriostegui, Mejía-López, Rivera-Ballesteros and García-Gasca.)

Background: COVID-19 inequities are abundant in low-income communities of color. Addressing COVID-19 vaccine hesitancy to promote equitable and sustained vaccination for underserved communities requires a multi-level, scalable, and sustainable approach. It is also essential that efforts acknowledge the broader healthcare needs of these communities including engagement in preventive services., Methods: This is a hybrid type 3 effectiveness-implementation study that will include a multi-level, longitudinal, mixed-methods data collection approach designed to assess the sustained impact of a co-created multicomponent strategy relying on bidirectional learning, shared decision-making, and expertise by all team members. The study capitalizes on a combination of implementation strategies including mHealth outreach with culturally appropriate messaging, care coordination to increase engagement in high priority preventive services, and the co-design of these strategies using community advisory boards led by Community Weavers. Community Weavers are individuals with lived experience as members of an underserved community serving as cultural brokers between communities, public health systems, and researchers to co-create community-driven, culturally sensitive public health solutions. The study will use an adaptive implementation approach operationalized in a sequential multiple assignment randomized trial design of 300 participants from three sites in a Federally Qualified Health Center in Southern California. This design will allow examining the impact of various implementation strategy components and deliver more intensive support to those who benefit from it most. The primary effectiveness outcomes are COVID-19 vaccine completion, engagement in preventive services, and vaccine confidence. The primary implementation outcomes are reach, adoption, implementation, and maintenance of the multicomponent strategy over a 12-month follow-up period. Mixed-effects logistic regression models will be used to examine program impacts and will be triangulated with qualitative data from participants and implementers., Discussion: This study capitalizes on community engagement, implementation science, health equity and communication, infectious disease, and public health perspectives to co-create a multicomponent strategy to promote the uptake of COVID-19 vaccination and preventive services for underserved communities in San Diego. The study design emphasizes broad engagement of our community and clinic partners leading to culturally sensitive and acceptable strategies to produce lasting and sustainable increases in vaccine equity and preventive services engagement., Trial Registration: ClinicalTrials.gov Identifier: NCT05841810 May 3, 2023., (© 2023. The Author(s).)

SARS-CoV and SARS-CoV-2 cell entry begins when spike glycoprotein (S) docks with the human ACE2 (hACE2) receptor. While the two coronaviruses share a common receptor and architecture of S, they exhibit differences in interactions with hACE2 as well as differences in proteolytic processing of S that trigger the fusion machine. Understanding how those differences impact S activation is key to understand its function and viral pathogenesis. Here, we investigate hACE2-induced activation in SARS-CoV and SARS-CoV-2 S using hydrogen/deuterium-exchange mass spectrometry (HDX-MS). HDX-MS revealed differences in dynamics in unbound S, including open/closed conformational switching and D614G-induced S stability. Upon hACE2 binding, notable differences in transduction of allosteric changes were observed extending from the receptor binding domain to regions proximal to proteolytic cleavage sites and the fusion peptide. Furthermore, we report that dimeric hACE2, the native oligomeric form of the receptor, does not lead to any more pronounced structural effect in S compared to saturated monomeric hACE2 binding. These experiments provide mechanistic insights into receptor-induced activation of Sarbecovirus spike proteins.

The SARS-CoV-2 virus was detected for the first time in December 2019 in Wuhan, China. Currently, this virus has spread around the world, and new variants have emerged. This new pandemic virus provoked the rapid development of diagnostic tools, therapies and vaccines to control this new disease called COVID-19. Antibody detection by ELISA has been broadly used to recognize the number of persons infected with this virus or to evaluate the response of vaccinated individuals. As the pandemic spread, new questions arose, such as the prevalence of antibodies after natural infection and the response induced by the different vaccines. In Mexico, as in other countries, mRNA and viral-vectored vaccines have been widely used among the population. In this work, we developed an indirect ELISA test to evaluate S1 antibodies in convalescent and vaccinated individuals. By using this test, we showed that IgG antibodies against the S1 protein of SARS-CoV-2 were detected up to 42 weeks after the onset of the symptoms, in contrast to IgA and IgM, which decreased 14 weeks after the onset of symptoms. The evaluation of the antibody response in individuals vaccinated with Pfizer-BioNTech and CanSinoBio vaccines showed no differences 2 weeks after vaccination. However, after completing the two doses of Pfizer-BioNTech and the one dose of CanSinoBio, a significantly higher response of IgG antibodies was observed in persons vaccinated with Pfizer-BioNTech than in those vaccinated with CanSinoBio. In conclusion, these results confirm that after natural infection with SARS-CoV-2, it is possible to detect antibodies for up to 10 months. Additionally, our results showed that one dose of the CanSinoBio vaccine induces a lower response of IgG antibodies than that induced by the complete scheme of the Pfizer-BioNTech vaccine., (© 2021 Wiley-VCH GmbH.)

Introduction: Primary immune thrombocytopenia (ITP) is an acquired bleeding disorder. Conventionally, first-line ITP therapy aims to obtain a rapid response and stop or decrease the risk of bleeding by increasing the platelet count. At this point, the duration of the response, the tolerability, and the long-term safety of pharmacologic interventions are considered less of a priority. Combination treatments that simultaneously address multiple disease mechanisms are an attractive strategy to increase efficacy in acute ITP therapy. In this review, we discuss the treatment of newly diagnosed ITP patients, emphasizing the use of new combinations to benefit from their synergy., Areas Covered: This article summarizes conventional treatment, recent and novel combinations, and COVID-19 management recommendations of newly diagnosed ITP patients., Expert Opinion: The key areas for improvement consider the long-term effects of conventional first-line therapy, reducing relapse rates, and extending responses to achieve long-term remission. Although corticosteroids remain a first-line therapy, restricting their use to avoid toxicity and the increasing use of rituximab and TPO-RAs in the first three months after diagnosis open the landscape for future interventions in frontline therapy for ITP. First-line therapy intensification or synergistic drug combination offers a potential and realistic shift in future treatment guidelines.

Coronavirus desease 2019 (COVID-19) is responsible for more than 1.80 M deaths worldwide. A Quantitative Structure-Activity Relationships (QSAR) model is developed based on experimental pIC 50 values reported for a structurally diverse dataset. A robust model with only five descriptors is found, with values of R 2 = 0.897, Q 2 LOO = 0.876 and complying with all the parameters established in the validation Tropsha's test. The analysis of the applicability domain (AD) reveals coverage of about 90% for the external test set. Docking and molecular dynamic analysis are performed on the three most relevant biological targets for SARS-CoV-2: main protease, papain-like protease, and RNA-dependent RNA polymerase. A screening of the DrugBank database is executed, predicting the pIC 2 value of 6664 drugs, which are IN the AD of the model (coverage = 79%). Fifty-seven possible potent anti-COVID-19 candidates with pIC ext values > 6.6 are identified, and based on a pharmacophore modelling analysis, four compounds of this set can be suggested as potent candidates to be potential inhibitors of SARS-CoV-2. Finally, the biological activity of the compounds was related to the frontier molecular orbitals shapes.50 value of 6664 drugs, which are IN the AD of the model (coverage = 79%). Fifty-seven possible potent anti-COVID-19 candidates with pIC 50 values > 6.6 are identified, and based on a pharmacophore modelling analysis, four compounds of this set can be suggested as potent candidates to be potential inhibitors of SARS-CoV-2. Finally, the biological activity of the compounds was related to the frontier molecular orbitals shapes.

COVID-19 morbidity and mortality are increased via unknown mechanisms in patients with diabetes and kidney disease. SARS-CoV-2 uses angiotensin-converting enzyme 2 (ACE2) for entry into host cells. Because ACE2 is a susceptibility factor for infection, we investigated how diabetic kidney disease and medications alter ACE2 receptor expression in kidneys. Single cell RNA profiling of kidney biopsies from healthy living donors and patients with diabetic kidney disease revealed ACE2 expression primarily in proximal tubular epithelial cells. This cell-specific localization was confirmed by in situ hybridization. ACE2 expression levels were unaltered by exposures to renin-angiotensin-aldosterone system inhibitors in diabetic kidney disease. Bayesian integrative analysis of a large compendium of public -omics datasets identified molecular network modules induced in ACE2-expressing proximal tubular epithelial cells in diabetic kidney disease (searchable at hb.flatironinstitute.org/covid-kidney) that were linked to viral entry, immune activation, endomembrane reorganization, and RNA processing. The diabetic kidney disease ACE2-positive proximal tubular epithelial cell module overlapped with expression patterns seen in SARS-CoV-2-infected cells. Similar cellular programs were seen in ACE2-positive proximal tubular epithelial cells obtained from urine samples of 13 hospitalized patients with COVID-19, suggesting a consistent ACE2-coregulated proximal tubular epithelial cell expression program that may interact with the SARS-CoV-2 infection processes. Thus SARS-CoV-2 receptor networks can seed further research into risk stratification and therapeutic strategies for COVID-19-related kidney damage., (Copyright © 2020 International Society of Nephrology. All rights reserved.)

A safe, effective, and scalable vaccine is needed to halt the ongoing SARS-CoV-2 pandemic. We describe the structure-based design of self-assembling protein nanoparticle immunogens that elicit potent and protective antibody responses against SARS-CoV-2 in mice. The nanoparticle vaccines display 60 SARS-CoV-2 spike receptor-binding domains (RBDs) in a highly immunogenic array and induce neutralizing antibody titers 10-fold higher than the prefusion-stabilized spike despite a 5-fold lower dose. Antibodies elicited by the RBD nanoparticles target multiple distinct epitopes, suggesting they may not be easily susceptible to escape mutations, and exhibit a lower binding:neutralizing ratio than convalescent human sera, which may minimize the risk of vaccine-associated enhanced respiratory disease. The high yield and stability of the assembled nanoparticles suggest that manufacture of the nanoparticle vaccines will be highly scalable. These results highlight the utility of robust antigen display platforms and have launched cGMP manufacturing efforts to advance the SARS-CoV-2-RBD nanoparticle vaccine into the clinic., Competing Interests: Declaration of Interests A.C.W, D.V., and N.P.K. are named as inventors on patent applications filed by the University of Washington based on the studies presented in this paper. N.P.K. is a co-founder, shareholder, paid consultant, and chair of the scientific advisory board of Icosavax, Inc. and has received an unrelated sponsored research agreement from Pfizer. D.V. is a consultant for and has received an unrelated sponsored research agreement from Vir Biotechnology Inc. H.Y.C. is a consultant for Merck and Pfizer and has received research funding from Sanofi-Pasteur, Roche-Genentech, Cepheid, and Ellume outside of the submitted work. P.K., A.P., and S.C. are employees and shareholders of Kymab Ltd. The other authors declare no competing interests., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

The COVID-19 pandemic required that people make rapid changes in their lifestyles. Since the beginning of the pandemic, it was necessary for teachers and learners to adapt teaching and learning practices to a remote mode. Following this, our study seeks to contribute to the field of English as a foreign language (EFL) teaching and learning by suggesting tasks. These tasks which intend to assist EFL teachers in the promotion of interactions and particularly negotiation for meaning (NfM) in virtual classes. Seven tasks are included, six of which are adaptations of the tasks that were used in the previous studies that explored NfM. The seven tasks were modified since they were originally designed to be carried out in face-to-face interactions, but our objective is to encourage virtual NfM. To this end, we include a review of the literature that will serve as the rationale behind each task, and we also provide the details regarding their implementation in virtual classes.

The objective of the research was to analyze the levels of computational self-efficacy and information skills in postgraduate students in administration at the time of COVID-19 with the aim of determining their relationship in academic performance. The type of study was a quantitative investigation with a correlational scope. The students were the graduate students in administration. The instruments used were two specific questionnaires with a Likert scale of five points each. The main results indicate that, during confinement, students had a frequency of using the laptop for three or more hours with a fixed connection. The level of their computational self-efficacy had an average of 4.55, which is interpreted as a high level where women were valued to a greater extent; while the level of information skills was 4.00 on average, which implies that, almost always, the participants carry out actions aimed at fulfilling the need for information they need to continue their distance educational process during the confinement, regularly using search, use and organization strategies, as well as the evaluation of information sources.

With all learning institutions pre-maturely closed on 20 March 2020 and all citizens advised to self-isolate in a bid to control the spread of COVID-19, it was hypothesized that COVID-19 would negatively impact on the performance of students in the 2020 Grade 12 national examinations vis-à-vis mathematics, science and design and technology subjects. An observed steady increase in the number of COVID-19 confirmed cases and the low levels of technology use in secondary schools in Zambia due to limited technology resources signifies a very difficult period in a young country which has just rolled out a nation-wide implementation of STEM education, This study collected data from three teachers at a public secondary school in Chipata District of Eastern Province in the Republic of Zambia. The Head of Department for Mathematics, the Head of Natural Sciences Department and one science teacher were interviewed. Semi-structured interviews via mobile phone were used to collect views of what these specialists thought would be the COVID19 effects on the general performance of students in their subject areas. Results of this study revealed that there is likely to be a drop in the pass percentage of secondary school students in this year's national examinations if the COVID-19 epidemic is not contained in the shortest possible time considering that the school academic calendar was abruptly disturbed by the early untimely closure of all schools in the country.

This study explored counsellors' experiences with online therapy during the COVID-19 crisis, which presented an opportunity to examine how counsellors evaluated the drawbacks, benefits, and appropriateness of online therapy. Data collected through surveys from 114 professional counsellors, school counsellors, addiction counsellors, clinical social workers, and marriage and family therapists in the United States were analysed. Results indicated the level of preparation for online therapy varied. The process was heavily impacted by technical functionality and perceived as more effective face-to-face. Counsellors found clients disengaged and distracted rather than comfortable and open. The effectiveness of online therapy was more strongly associated with client characteristics and treatment approaches than with diagnoses and treatment goals. Interpretations, clinical implications, and further research recommendations are provided.

Abstract The absence of a long COVID (LC) or post-acute sequelae of COVID-19 (PASC) diagnostic has profound implications for research and potential therapeutics given the lack of specificity with symptom-based identification of LC and the overlap of symptoms with other chronic inflammatory conditions. Here, we report a machine-learning approach to LC/PASC diagnosis on 347 individuals using cytokine hubs that are also capable of differentiating LC from chronic lyme disease (CLD). We derived decision tree, random forest, and gradient-boosting machine (GBM) classifiers and compared their diagnostic capabilities on a dataset partitioned into training (178 individuals) and evaluation (45 individuals) sets. The GBM model generated 89% sensitivity and 96% specificity for LC with no evidence of overfitting. We tested the GBM on an additional random dataset (106 LC/PASC and 18 Lyme), resulting in high sensitivity (97%) and specificity (90%) for LC. We constructed a Lyme Index confirmatory algorithm to discriminate LC and CLD.

BackgroundWhile vaccines have established utility against COVID-19, phase 3 efficacy studies have generally not comprehensively evaluated protection provided by previous infection or hybrid immunity (previous infection plus vaccination). Individual patient data from US government-supported harmonized vaccine trials provide an unprecedented sample population to address this issue. We characterized the protective efficacy of previous SARS-CoV-2 infection and hybrid immunity against COVID-19 early in the pandemic over three-to six-month follow-up and compared with vaccine-associated protection.MethodsIn this post-hoc cross-protocol analysis of the Moderna, AstraZeneca, Janssen, and Novavax COVID-19 vaccine clinical trials, we allocated participants into four groups based on previous-infection status at enrolment and treatment: no previous infection/placebo; previous infection/placebo; no previous infection/vaccine; and previous infection/vaccine. The main outcome was RT-PCR-confirmed COVID-19 >7-15 days (per original protocols) after final study injection. We calculated crude and adjusted efficacy measures.FindingsPrevious infection/placebo participants had a 92% decreased risk of future COVID-19 compared to no previous infection/placebo participants (overall hazard ratio [HR] ratio: 0.08; 95% CI: 0.05-0.13). Among single-dose Janssen participants, hybrid immunity conferred greater protection than vaccine alone (HR: 0.03; 95% CI: 0.01-0.10). Too few infections were observed to draw statistical inferences comparing hybrid immunity to vaccine alone for other trials. Vaccination, previous infection, and hybrid immunity all provided near-complete protection against severe disease.InterpretationPrevious infection, any hybrid immunity, and two-dose vaccination all provided substantial protection against symptomatic and severe COVID-19 through the early Delta period. Thus, as a surrogate for natural infection, vaccination remains the safest approach to protection.FundingNational Institutes of Health.

Abstract Background Following the World Health Organization’s declaration of COVID-19 as a global pandemic, several countries implemented population-wide lockdowns. However, these responses to COVID-19 caused severe healthcare system disruptions to service delivery. The TB case notification rate in Uganda decreased by 22% between January and April 2020, which coincided with a lockdown and an increase in COVID-19 cases. In this study, we tested the effect of screening all patients with both COVID-19-positive and negative symptom screen for TB at a National Referral Hospital. Design/Methods Following our formative assessment, we identified potential barriers to and facilitators of integrating screening for COVID-19 and TB at Kiruddu National Referral Hospital. To address the barriers, in February 2021 we trained healthcare providers on integrated COVID-19-TB screening tools and provided COVID-19/TB screening tools/Standard operating procedures and personal protective equipment. From March 1, 2021, to June 30, 2021, we screened patients presenting to the emergency and outpatient departments for COVID-19 symptoms, and subsequently, we performed TB symptom screening for both patients with COVID-19 positive and negative symptom screen using the intensified tuberculosis case-finding (ICF) guide. We then compared the outcomes of TB symptom screening for patients initially with a positive COVID-19 symptom screen with those who initially had a negative COVID-19 symptom screen. Results From March 2021 to June 2021, we screened 1464 patients (44.3% male and 55.7% female) for COVID-19 symptoms. Out of these participants, 1252 (85.5%) screened positive for COVID-19 symptoms, while 212 (14.5%) screened negative. The majority of patients with a positive COVID-19 symptom screen, 717 (57.3%), also screened positive for TB symptoms compared to 19 (8.9%) among patients with a negative COVID-19 symptom screen. Out of the total 736 presumptive TB cases identified, 717 (97.4%) initially screened positive for COVID-19 symptoms. TB was diagnosed in 110 individuals including 104 who had positive COVID-19-symptom screen and six who had a negative COVID-19 symptom screen. All of the 110 newly diagnosed TB cases were linked to TB treatment. Conclusions Patients who screen positive for COVID-19 symptoms should be routinely screened for TB to mitigate missed opportunities for TB case identification.

BACKGROUND: The COVID 19 pandemic adversely impacted delivery of preventive, routine, urgent, and essential care worldwide. Dialysis access care was particularly affected due to the lack of specific guidelines regarding procedures for its creation and maintenance. Early guidance by Centers for Medicare and Medicaid was inadvertently interpreted as guidance to stop dialysis access procedures. Prompt action by professional societies was needed to furnish detailed guidance to establish essential nature of these procedures. METHODS: The American Society of Diagnostic and Interventional Nephrology (ASDIN) issued a joint statement with Vascular Access Society of the Americas (VASA) - Maintaining Lifelines for ESKD Patients to clearly establish the role of vascular access as a lifeline for ESKD (End Stage Kidney Disease) patients and the importance and urgency of its timely management. ASDIN also conducted a survey in mid-2020, that was administered to the ASDIN database as well as shared with the general public via the organizations social media platforms. The respondents reported their experiences in the care of dialysis access, practice patterns and the utility of the ASDIN-VASA statement during the COVID 19 pandemic. RESULTS: Of the 2030 individual surveys sent, 581 were opened and 53 (9.1%) responses were received from different parts of the country and from different practice settings. ASDIN COVID 19 triage document was frequently utilized and 83% of respondents found the document valuable. The survey also revealed multiple obstacles, including logistical and financial issues that led to significant disruption of services. CONCLUSIONS: The care of dialysis access was significantly affected in the United States during the COVID 19 pandemic due to multiple reasons. ASDIN actions provided valuable specific guidance regarding and explored barriers to dialysis access care. We describe those results and discuss strategies to prevent COVID 19 transmission with innovative strategies of providing access care. Individualized decision making is of essence when considering dialysis access procedures.

KEY POINTS: IgAN and MCD are the most common de novo glomerular diseases reported after COVID-19 vaccination, particularly after mRNA vaccination. Membranous nephropathy, pauci-immune GN, and collapsing GN have also been attributed to COVID-19 vaccination, some with dual histologies. Recovery of kidney function and proteinuria remission is more likely in IgAN and MCD by 4–6 months compared with the other glomerular diseases. BACKGROUND: Patients with de novo glomerular disease (GD) with various renal histologies have been reported after vaccination against SARS-CoV-2. Causality has not been established, and the long-term outcomes are not known. To better characterize the GDs and clinical courses/outcomes, we created the International Registry of COVID-19 vaccination and Glomerulonephritis to study in aggregate patients with de novo GN suspected after COVID-19 vaccine exposure. METHODS: A REDCap survey was used for anonymized data collection. Detailed information on vaccination type and timing and GD histology were recorded in the registry. We collected serial information on laboratory values (before and after vaccination and during follow-up), treatments, and kidney-related outcomes. RESULTS: Ninety-eight patients with GD were entered into the registry over 11 months from 44 centers throughout the world. Median follow-up was 89 days after diagnosis. IgA nephropathy (IgAN) and minimal change disease (MCD) were the most common kidney diseases reported. Recovery of kidney function and remission of proteinuria were more likely in IgAN and MCD at 4–6 months than with pauci-immune GN/vasculitis and membranous nephropathy. CONCLUSIONS: The development of GD after vaccination against SARS-CoV-2 may be a very rare adverse event. Temporal association is present for IgAN and MCD, but causality is not firmly established. Kidney outcomes for IgAN and MCD are favorable. No changes in vaccination risk-benefit assessment are recommended based on these findings.

Introduction: SARS-CoV-2 infection can lead to acute respiratory distress syndrome with a prolonged need for mechanical ventilation and delayed tracheostomy, resulting in an increase in cases of tracheal stenosis and the necessity for less invasive approaches. Methods: A descriptive cross-sectional study was conducted from March 2020 to December 2021 at the Hospital Universitario Nacional de Colombia, focusing on adults with post-intubation tracheal stenosis associated with SARS-CoV-2. Univariate analysis was performed between groups with or without SARS-CoV-2 infection as a control, considering reintervention, degree of stenosis, use of intratracheal steroids, or multiple stenoses as important outcomes. Fisher's exact test, Student's t-test, and Mann-Whitney test were employed based on the nature of variables. A p-value less than 0.05 was considered statistically significant. Results: A total of 26 patients were included, with 20 having COVID-19 and 6 without. Significant differences were found in age (p=0.002), epilepsy (p=0.007), and multiple stenosis (p=0.04). In 85% of cases, laser blue plus balloon pulmonary dilation was used, intratracheal dexamethasone in 35%, and reintervention in 35%, with no significant differences between groups. Conclusions: A threefold increase in subglottic stenosis was observed during the SARS-CoV-2 pandemic, with more instances of multiple stenosis and predominantly the use of laser blue plus balloon pulmonary dilation as a successful recanalization technique. There was a higher use of intratracheal dexamethasone in this group compared to other pathologies causing tracheal stenosis.

BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to cause very high morbidity and mortality throughout Latin American countries. However, few population-based seroprevalence surveys have been conducted to quantify attack rates and characterize drivers of transmission.MethodsWe conducted a population-based cross-sectional study to assess the seroprevalence of antibodies against SARS-CoV-2 in ten cities in Colombia between September and December 2020. The study involved multi-stage cluster sampling at each city. Participants provided a serum sample and answered a demographic and risk factor questionnaire. Prior infection by SARS-CoV-2 was ascertained using the "SARS-CoV-2 Total (COV2T) Advia Centaur - Siemens" chemiluminescence assay.FindingsA total of 17863 participants from 7320 households participated in the study. Seroprevalence varied substantially between cities, ranging from 26% (95%CI 23-29 %) in Medellín to 68% (95%CI 62-74 %) in Guapi. There were no differences in seroprevalence by sex, but seropositivity was higher in certain ethnic groups. There was substantial heterogeneity in seroprevalence within cities, driven to a large extent by a strong association between socioeconomic stratum and seropositivity.InterpretationColombia has been one of the Latin American countries most affected by the COVID-19 pandemic. This study documented very high attack rates in several Colombian cities by the end of 2020 and identified key drivers of heterogeneities including ethnicity and socioeconomic stratum. Few studies of seroprevalence of SARS-CoV-2 have been conducted in Latin America, and therefore this study contributes to the fundamental understanding of the pandemic in the region.FundingThe study was sponsored by, Ministerio de Ciencia y Tecnología e Innovación -CT361/2020, Ministerio de Salud y Protección Social, Fundación Universitaria del Norte, Imperial College of London, Universidad Nacional de Colombia (Sede Medellín), Universidad de Córdoba, California University, Unidad Nacional de Gestión del Riesgo, Centro de Atención y Diagnóstico de Enfermedades Infecciosas -CDI-, Centro Internacional de Entrenamiento e Investigaciones Médicas -CIDEIM-, Departamento Administrativo Nacional de Estadística - DANE, Fondo Nacional de Turismo -FONTUR-, Secretarías de Salud Departamentales, Distritales y Municipales and Instituto Nacional de Salud.

COVID-19 oral treatments require initiation within 5 days of symptom onset. Although antigen tests are less sensitive than RT-PCR, rapid results could facilitate entry to treatment. We collected anterior nasal swabs for BinaxNOW and RT-PCR testing and clinical data at a walk-up, community site in San Francisco, California between January and June 2022. SARS-CoV-2 genomic sequences were generated from positive samples and classified according to subtype and variant. Monte Carlo simulations were conducted to estimate the expected proportion of SARS-CoV-2 infected persons who would have been diagnosed within 5 days of symptom onset using RT-PCR versus BinaxNOW testing. Among 25,309 persons tested with BinaxNOW, 2,799 had concomitant RT-PCR. 1137/2799 (40.6%) were SARS-CoV-2 RT-PCR positive. We identified waves of predominant omicron BA.1, BA.2, BA.2.12, BA.4, and BA.5 among 720 sequenced samples. Among 1,137 RT-PCR positive samples, 788/1137 (69%) were detected by BinaxNOW; 94% (669/711) of those with Ct value

Summary: Human genetic studies of critical COVID-19 pneumonia have revealed the essential role of type I interferon-dependent innate immunity to SARS-CoV-2 infection. Conversely, an association between the HLA-B∗15:01 allele and asymptomatic SARS-CoV-2 infection in unvaccinated individuals was recently reported, suggesting a contribution of pre-existing T cell-dependent adaptive immunity. We report a lack of association of classical HLA alleles, including HLA-B∗15:01, with pre-omicron asymptomatic SARS-CoV-2 infection in unvaccinated participants in a prospective population-based study in the United States (191 asymptomatic vs. 945 symptomatic COVID-19 cases). Moreover, we found no such association in the international COVID Human Genetic Effort cohort (206 asymptomatic vs. 574 mild or moderate COVID-19 cases and 1,625 severe or critical COVID-19 cases). Finally, in the Human Challenge Characterisation study, the three HLA-B∗15:01 individuals infected with SARS-CoV-2 developed symptoms. As with other acute primary infections studied, no classical HLA alleles favoring an asymptomatic course of SARS-CoV-2 infection were identified.

Objectives: To analyze the gene variants of the renin-angiotensin-aldosterone system and determine their association with the severity and outcome of COVID-19. Methods: A total of 104 patients were included in the study: 34 asymptomatic patients with COVID-19 as controls and 70 symptomatic patients as cases. The genetic variants ACE rs4343, ACE2 rs2074192, AGTR1 rs5182, and AGT rs4762 were identified using TaqMan genotyping tests. Results: Patients with the T/T genotype of AGTR1 rs5182 have a higher probability of developing symptomatic COVID-19 (odds ratio [OR] 12.25, 95% confidence interval [CI] 1.34-111.9, P ≤0.001) and a higher risk of hospitalization because of disease (OR 14.00, 95% CI 1.53-128.49, P = 0.012). The haplotype CTG (AGTR1 rs5182, ACE2 rs2074192, ACE rs4343) decreased the odds of death related to COVID-19 in the study population (OR 0.03, 95% CI 0.0-0.06, P = 0.026). Conclusions: The T/T genotype of the AGTR1 rs5182 variant increased the probability of symptomatic COVID-19 and hospitalization, whereas the haplotype CTG (consisting of AGTR1 rs5182, ACE2 rs2074192, and ACE rs4343) decreased the odds of death related to COVID-19 by 97% in the hospitalized patients with COVID-19. These results support the participation of renin-angiotensin-aldosterone system gene variants as modifiers of the severity of symptoms associated with SARS-CoV-2 infection and the outcome of COVID-19.

Introduction: The COVID-19 pandemic has disproportionately affected individuals residing in Long-Term Care Facilities (LTCFs), necessitating tailored strategies to manage outbreaks. This study examines the outcomes of the ILPI BH project, a collaborative effort between the Municipal Health Department and the Hospital das Clínicas of the Federal University of Minas Gerais, designed to mitigate COVID-19 spread within LTCFs. Methods: Prospective cohort of secondary data: 1,794 old residents in 99 long-term care facilities of Belo Horizonte, Brazil, were followed from May 2020 to January 2021. The study analyzed the prevention strategies, residents’ clinical data, and the characteristics of the long-term care facilities, correlating these variables with the number of infections, hospitalizations, and deaths from COVID-19. It checked absolute numbers and rates of incidence, hospitalization, mortality, and lethality. Results: There have been 58 COVID-19 outbreaks in long-term care facilities. There were 399 cases among residents, 96 hospitalizations for COVID-19 and 48 deaths from COVID-19 (2.7 % of the cohort), with a case fatality rate of 12 %. After multivariate analysis, the intrinsic variables to residents associated with higher mortality risk were higher degree of frailty (OR=1.08; p = 0.004) and the fact of living in a long-term care facility with a considerable proportion of residents’ coverage by health plans (OR = 1.01; p = 0.028). Early geriatric follow-up showed an association with a reduction in the number of hospitalizations due to COVID-19. Conclusion: The correct classification of the degree of frailty of institutionalized older people seems to have been relevant for predicting mortality from COVID-19. The extensive assistance by private health plans, contrary to what is supposed, did not result in better health protection. Early geriatric follow-up was beneficial and may be an attractive strategy in the face of health emergencies that affect long-term care facilities to reduce hospital admissions.

BACKGROUND: The COVID-19 pandemic has adversely affected health care systems and dialysis access care in the US and across the globe. Beyond the initial challenges posed by the pandemic and despite the actions taken by health care leaders/organizations/professional societies such as the Maintaining Lifelines for ESKD Patients joint statement, there continues to be delays in providing timely care and performing elective and emergent dialysis access procedures worldwide. The aim of this study was to assess the global challenges associated with providing dialysis vascular access care across the international vascular access community during the pandemic. METHODS: The American Society of Diagnostic and Interventional Nephrology (ASDIN) conducted an online survey in 2021, that was administered to an expert panel of dialysis vascular access specialists and global leaders spanning across the international community. The respondents who are members of ASDIN, Association of Vascular Access and InTerventionAl Renal physicians (AVATAR), Asia Pacific Society of Dialysis Access (APSDA), Peruvian Vascular Access Society (APDAV), and Australia/New Zealand Society of Interventional Nephrology (ANZSIN) reported their experiences in the care of dialysis vascular access, practice patterns, and challenges faced during the COVID pandemic. RESULTS: Of the 53 individual surveys sent, 16 were opened and 11 (69%) responses were received from across the world and from different practice settings. The survey revealed the continued challenges facing the international community, the stark disparities in care delivery, supply chain disruption and logistical, regulatory, and financial issues that the global community continues to face in the ongoing pandemic. CONCLUSIONS: The COVID19 pandemic is far from over, and the challenges and barriers to providing dialysis access care seen on the initial ASDIN survey in the US seem to extend across the globe. We describe those results and discuss options, opportunities, and innovative tools to provide dialysis and access care during these trying times.

Abstract Background Coronavirus disease (COVID-19) vaccine hesitancy is a global challenge. In low- and middle-income countries (LMICs), the problem has persisted despite vaccine availability and decreasing infections. In Uganda, there is still limited information on the extent and predictors of vaccine hesitancy. This study sought to assess the prevalence and predictors of COVID-19 vaccine hesitancy, and the effectiveness of an intervention that involved community pharmacy counseling in combating COVID-19 vaccine hesitancy. Methods A total of 394 participants were enrolled in a 4-week prospective cohort interventional study. The study was conducted across eight community pharmacies in Mbarara City, between 9:00 AM and 5:00 PM daily. The study personnel ascertained the vaccination status of all clients seeking community pharmacy services. All unvaccinated clients were consecutively assessed for eligibility, and eligible clients were systematically enrolled after receiving the community pharmacy services for which they requested. The study intervention involved structured participant counseling (within the pharmacy premise), follow-up short message service (weekly), and telephone calls (bi-weekly). Only participants who did not accept to receive the COVID-19 vaccine despite counseling were followed up for four weeks, or until they accepted to receive a COVID-19 vaccine. The effectiveness of the community pharmacy counseling intervention was determined as an increase in COVID-19 vaccine acceptance, and desirable attitudinal change towards COVID-19 disease, vaccination exercise, and vaccines. Descriptive analysis was used to summarize data, and multivariate analysis was used to determine the predictors of COVID-19 vaccine hesitancy. A p-value < 0.05 was considered statistically significant. Results Out of 394 participants, 221 (56%) were hesitant to receive a COVID-19 vaccine. Participants expressed several reasons (mean 2±1) for COVID-19 vaccine hesitancy, mostly concerning vaccine safety (N=160, 47.3%). The overall COVID-19 vaccine acceptance rate increased by 25.4 percent points (43.9 – 69.3 percent points) after the study intervention. Age, religion, level of education, distance from the nearest public health facility, having a friend/family diagnosed with COVID-19, and personal suspicion of contracting COVID-19 were significant predictors of COVID-19 vaccine hesitancy. Conclusion COVID-19 vaccine hesitancy is a big challenge in Uganda. A mix of sociodemographic and COVID-19 vaccine perceptions are the key predictors of COVID-19 vaccine hesitancy. Although COVID-19 vaccines were not available at the time of the study, this study found that structured counseling interventions can improve COVID-19 vaccine acceptance rates. Larger prospective studies should evaluate the effectiveness of similar interventions in community pharmacies and other healthcare settings.

Abstract Aims/Introduction Coronavirus disease 2019 (COVID‐19) vaccinations have been proven to be generally safe in healthy populations. However, the data on vaccine safety in patients with type 1 diabetes are scarce. This study aimed to evaluate the frequency and severity of short‐term (

Abstract Background Acute Respiratory Distress Syndrome (ARDS) due tocoronavirus disease (COVID-19) infection has a unique phenotype generating a growing need to determine the existing differences that can alter existing evidence-based management strategies for ARDS. Research Question: What differences does the clinical profile of patients with ARDS due to COVID 19 and Non-COVID 19 have? Study Design and methods We conducted a comparative, observational, retrospective study in the Intensive Care Unit (ICU)of a third-level hospital in Mexico City, from March 2020 through March 2022. Clinical, echocardiographic, and laboratory variables were compared between patients with ARDS due to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and those due to other etiologies. Results We enrolled 140 patients with a diagnosis of ARDS. The study group of COVID-19 etiology were younger males, higher body mass index, progressed to organ dysfunction, required more frequently renal replacement therapy, and higher SOFA score. There was no difference in rates of right ventricular dysfunction. Interpretation COVID-19 ARDS exhibit much greater severity that led to higher admission and mortality rates, whilst being younger and less comorbid.

Wastewater-based surveillance has emerged as an important method for monitoring the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). This study investigated the presence of SARS-CoV-2 in wastewater in Zambia. We conducted a longitudinal study in the Copperbelt and Eastern provinces of Zambia from October 2023 to December 2023 during which 155 wastewater samples were collected. The samples were subjected to three different concentration methods, namely bag-mediated filtration, skimmed milk flocculation, and polythene glycol-based concentration assays. Molecular detection of SARS-CoV-2 nucleic acid was conducted using real-time Polymerase Chain Reaction (PCR). Whole genome sequencing was conducted using Illumina COVIDSEQ assay. Of the 155 wastewater samples, 62 (40%) tested positive for SARS-CoV-2. Of these, 13 sequences of sufficient length to determine SARS-CoV-2 lineages were obtained and 2 sequences were phylogenetically analyzed. Various Omicron subvariants were detected in wastewater including BA.5, XBB.1.45, BA.2.86, and JN.1. Some of these subvariants have been detected in clinical cases in Zambia. Interestingly, phylogenetic analysis positioned a sequence from the Copperbelt Province in the B.1.1.529 clade, suggesting that earlier Omicron variants detected in late 2021 could still be circulating and may not have been wholly replaced by newer subvariants. This study stresses the need for integrating wastewater surveillance of SARS-CoV-2 into mainstream strategies for monitoring SARS-CoV-2 circulation in Zambia.

Introduction: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of Coronavirus Disease 2019 (COVID-19). The disease has a wide range of clinical manifestations, from asymptomatic to severe. Ancestral contribution, sex, immune response, and genetic factors influence the presentation of the disease. The objective of the present study was to validate these genetic variants in patients with severe COVID-19 who died and in survivor patients. Methods: Single nucleotide variants (SNVs) in six genes: ATPase plasma membrane Ca2+ transporting 2 (ATP2B2), transmembrane serine protease 2 (TMPRSS2), dedicator of cytokinesis 2 (DOCK2), (interferon alpha and beta receptor subunit 2) IFNAR2, tumor necrosis factor receptor superfamily, member 1A (TNFRSF1A), and tumor necrosis factor receptor superfamily, member 1B (TNFRSF1B), were explored in two groups: the first consisted of severe COVID-19-related patients (familial cases from 58 families, n = 130), and the second group of unrelated severe COVID-19 patients (n = 1045). In each study group, death was evaluated as the outcome. Results: In non-related patients with severe COVID-19, carriers of GG genotype (rs2289274) in the ATP2B2 gene showed a high-risk probability of non-surviving (OR = 1.43). Survival analysis to 75 days indicates that carriers of GG have a higher risk than GA or AA genotypes (p = 0.0059). The haplotype GG (rs2289273-rs2289274) in ATP2B2 was found to be associated with a high risk of death in severe non-related COVID-19 patients. No significant associations were found between severe COVID-19-related patients and SNVs in ATP2B2, TMPRSS2, DOCK2, IFNAR2, TNFRSF1A, or TNFRSF1B. Conclusions: Unrelated patients with severe COVID-19 that carry the GG genotype (rs2289274) in ATP2B2 showed a high death risk. Survival analysis to 75 days indicates that carriers of GG have a higher risk of non-survival compared to GA or AA genotypes.