Severe Acute Respiratory Syndrome Coronavirus Research Articles

Diagnostic accuracy of rapid antigen tests for detection of Delta and Omicron variants of severe acute respiratory syndrome coronavirus 2: Direct evidence from prospective clinical settings.

Despite widespread application during the coronavirus disease-19 pandemic, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection using patient-performed rapid antigen tests (RATs) is limited, especially regarding the Delta and Omicron variants. Therefore, in this study, we evaluated the performance of RATs in identifying Delta and Omicron infections in self-test settings. In this multicenter clinical performance study conducted in Korea between November 2021 and February 2022, we included participants without prior diagnostic device experience. Using 2 RAT types, we compared the results with real-time reverse transcriptase-polymerase chain reaction testing, focusing on clinical sensitivity and specificity. Reverse transcriptase-polymerase chain reaction helped confirm 77 SARS-CoV-2 infections among 280 participants. RATs exhibited high positive agreement for Omicron detection but lower rates for Delta, especially among partially vaccinated individuals. This study provides direct evidence that RATs, originally developed for ancestral strains of SARS-CoV-2, effectively detect major variants such as Delta and Omicron in real patient/clinical settings. By confirming variant presence through sequencing, our research offers significant and novel insights into the performance of RATs, particularly in the context of breakthrough infections postvaccination, with precise data on vaccination status and timing obtained from government records.

A realistic approach for evaluating antimicrobial surfaces for dry surface exposure scenarios.

The severe acute respiratory syndrome coronavirus 2 pandemic has raised public awareness about the importance of hygiene, leading to an increased demand for antimicrobial surfaces to minimize microbial contamination on high-touch surfaces. This is particularly relevant in public and private transportation settings, where surfaces frequently touched by individuals pose a significant, yet preventable, risk of infection transmission. Typically, the antimicrobial activity of surfaces is tested using test methods of the International Standards Organization, American Society for Testing and Materials, or Japanese Industrial Standards, which involve complete submersion in liquid, elevated temperature (37°C), and prolonged (24 h) contact periods. However, these conditions do not accurately represent real-world scenarios where surfaces are exposed to air. In this study, we propose a modified test method designed to better reflect real-life conditions in the intended end-use setting. The modifications included using deionized water instead of nutrient broth while preparing bacterial inoculum, applying a small test inoculum to the surface and allowing it to dry, maintaining ambient temperature and relative humidity throughout the contact period, and reducing the contact period to 4 h. With this modified approach, the antimicrobial activity of 20 samples was reassessed. This screening revealed that out of 20 samples, only 2 samples were effective against all species, while 8 samples demonstrated partial effectiveness against selected species, and 10 samples showed no significant effect. These findings highlight the inadequacy of the current test standard and emphasize the urgent necessity for revised and adapted testing method to ensure a reliable and accurate evaluation.IMPORTANCEThe recent severe acute respiratory syndrome coronavirus 2 pandemic has sparked increased demand for antimicrobial surfaces to mitigate the risk of fomites-transmitted infection in both indoors and confined spaces. Commonly, the antimicrobial activity of these surfaces is assessed using test standards established by national standards bodies, which do not distinguish between different application scenarios. While these test standards are suitable for surfaces intended for submerged application, they are inappropriate for antimicrobial surfaces designed for dry surface exposure. The usage of these standards can lead to an overestimation of antimicrobial efficacy. Thus, this study introduces a modified dry exposure test method aimed at better reflecting real-life conditions in the intended end-use setting. Our results revealed the subpar antimicrobial performance of numerous samples, highlighting the necessity to revise and tailor the universal test standard to real-world scenarios in order to ensure a reliable and accurate evaluation.

Expanding the tool box for native structural biology: 19F dynamic nuclear polarization with fast magic angle spinning.

Obtaining atomic-level information on components in the cell is a major focus in structural biology. Elucidating specific structural and dynamic features of proteins and their interactions in the cellular context is crucial for understanding cellular processes. We introduce 19F dynamic nuclear polarization (DNP) combined with fast magic-angle-spinning (MAS) nuclear magnetic resonance (NMR) spectroscopy as a powerful technique to study proteins in mammalian cells. We demonstrate our approach on the severe acute respiratory syndrome coronavirus 2 5F-Trp-NNTD protein, electroporated into human cells. DNP signal enhancements of 30- to 40-fold were observed, translating into over 1000-fold experimental time savings. High signal-to-noise ratio spectra were acquired on nanomole quantities of a protein in cells in minutes. 2D 19F-19F dipolar correlation spectra with remarkable sensitivity and resolution were obtained, exhibiting 19F-19F cross peaks associated with fluorine atoms as far as ~10 angstroms apart. This work paves the way for 19F DNP-enhanced MAS NMR applications in cells for probing protein structure, dynamics, and ligand interactions.

Immune triggers preceding neuralgic amyotrophy.

Infections and vaccinations have been identified as potential immunological triggers of neuralgic amyotrophy (NA), but the exact type and frequency of the preceding agents is unknown. This was a multicentre, prospective, observational, matched case-control study. NA was diagnosed by neuromuscular experts according to validated clinical criteria and electrodiagnostic studies. Clinical data and biological samples of NA patients were collected within 90 days from disease onset between June 2018 and December 2023. All NA patients were asked about prior infection and vaccination in the month before disease onset. Serological tests for hepatitis E virus, human immunodeficiency virus, severe acute respiratory syndrome coronavirus 2, Epstein-Barr virus, cytomegalovirus, parvovirus B19, varicella-zoster virus, Borrelia burgdorferi, Mycoplasma pneumoniae and Bartonella henselae were performed in a central laboratory. Each case was matched with a healthy control for age, sex, place of residence and time of blood collection. Fifty-seven patients and corresponding controls were included. The mean age was 45 years for both groups. NA onset was preceded by a symptomatic infectious trigger confirmed by microbiological tests in 15/57 (26.3%) patients. Coronavirus disease 2019 vaccination was considered a potential trigger in 7/57 (12.3%) subjects. An acute viral infection was associated with a bilateral involvement of the brachial plexus (p = 0.003, Cramèr's V = 0.43). Confirmed immune triggers (infection or vaccination) preceded disease onset in 22/57 (38.6%) NA cases. We suggest to test NA patients in the acute phase for intracellular antigens, especially in the case of concomitant bilateral involvement and hepatitis.

HACE2 upregulation and participation of macrophages and clear cells in the immune response of epididymis to SARS-CoV-2 in K18-hACE2 mice.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus caused the coronavirus disease 2019 pandemic, and the prevalence of deaths among men is higher than among women. The epididymis, divided into caput, corpus, and cauda, shows a region-specific immunity. The K18-hACE2 mouse expresses human angiotensin-converting enzyme 2 (hACE2), the receptor that allows SARS-CoV-2 infection. However, studies using this transgenic mouse to evaluate the impact of this viral infection in epididymis have not yet been performed. We evaluated the expression of hACE2 in the epididymis of SARS-CoV-2-infected K18-hACE2 mice, and assessed the epididymal immune response, focusing on F4/80+ mononuclear phagocytes and tumor necrosis factor-alpha expression. The following analyses were performed in the epididymal sections of infected mice: epithelial height and duct diameter, birefringent collagen, Terminal deoxynucleotidyl Transferase-mediated dUTP Nick End Labelling, immunoreactions for detection of hACE2, spike, FGF, V-ATPase, F4/80, tumor necrosis factor-alpha, and iNOS. Viral particles were identified under electron microscopy. hACE2, Rigi, Tgfb1 and Tnfa expression were also evaluated by real-time quantitative polymerase chain reaction. All epididymal regions expressed hACE2, which increased in all epididymal regions in the infected mice. However, the caput appeared to be the most infected region. Despite this, the caput region showed minimal changes while the cauda showed significant epithelial changes associated with increased iNOS immunoexpression. The F4/80+ mononuclear phagocyte area increased significantly in both stroma and epithelium. In addition to the epithelial and stromal mononuclear phagocytes, tumor necrosis factor-alpha was also detected in clear cells, whose cytoplasm showed a significant increase of this cytokine in the infected animals. The K18-hACE2 mouse is a useful model for evaluating the impact of SARS-CoV-2 infection in the epididymis. The infection induced hACE2 upregulation, favoring the virulence in the epididymis. The epididymal regions responded differentially to infection, and the activation of F4/80+ mononuclear phagocytes associated with the increased tumor necrosis factor-alpha immunolabeling in clear cells indicates a role of clear cells/mononuclear phagocytes immunoregulatory mechanisms in the epididymal immune response to SARS-CoV-2 infection.

Outcomes of kidney transplantation in recipients with SARS-cov-2 infection: a 282-case single-center experience in Japan.

The coronavirus disease 2019, caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), has become a global epidemic. There are concerns regarding the severity of SARS-CoV-2 infections in kidney transplant (KTx) recipients. However, there is limited data on how the epidemic has affected the treatment and prognosis of these patients. Therefore, we aimed to report the changes in the treatment and outcomes of KTx recipients infected with SARS-CoV-2 during each wave at our institution. A total of 282 KTx recipients who were infected with SARS-CoV-2 during the study period were followed up at Tokyo Women's Medical University between March 2020 and August 2022. We investigated the outcomes and treatments of infected KTx recipients. Nineteen (6.7%) patients showed severe outcomes, including eight SARS-CoV-2 infection-related deaths. Risk factors associated with severe outcomes included underlying conditions, such as diabetes mellitus, heart disease, and liver disease (odds ratios, 2.09, 2.88, and 5.52, respectively). Treatment strategies changed throughout the epidemic in response to changes in the SARS-CoV-2 variants. Antiviral drugs were gradually administered as soon as they were approved for use. Treatment strategies for KTx recipients were gradually established over the course of the epidemic. Although the proportion of infected KTx recipients decreased compared to that of the general population throughout the epidemic, many patients still followed a severe course.

Implementation and validation of MICaFVi: A highly efficient nanotechnology-based method for coronaviruses detection

Coronaviruses have emerged as a significant public health concern due to the global impact of Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which cause COVID-19. The development of sensitive and accurate detection methods is critical for early diagnosis, disease management, and outbreak control. In a previous study, we developed and optimized a nanobased detection methodology called Magnetic Immuno-Capture Followed by Flow Virometry (MICaFVi) using virus-mimicking silica nanoparticles and MERS-CoV/SARS-CoV-2 pseudoviral particles. In the present study, we have extended this methodology to evaluate its specificity and sensitivity for detecting wild-type MERS-CoV and SARS-CoV-2 in human and camel samples. Our results demonstrated that MICaFVi successfully detected MERS-CoV and SARS-CoV-2 viruses with high sensitivity and specificity, although it showed reduced performance for samples with Ct values of 30 or lower compared to qPCR. Despite some limitations in detection speed and sensitivity, MICaFVi represents a significant advancement in diagnostic methodologies by combining nanotechnology with flow cytometry. Additionally, we adapted the MICaFVi methodology to simultaneously detect MERS-CoV and SARS-CoV-2 in a single multiplex assay. The successful implementation of this advanced detection approach has important implications for improving early detection, surveillance, and control of both current and future viral or bacterial pandemics. Our results underscore the potential of MICaFVi as a valuable tool for monitoring the spread of these viruses and highlight its role in advancing diagnostic technologies. This extension of our earlier work offers new insights into the application of nanotechnology and flow cytometry for viral detection.

SARS-CoV-2 ORF 3a-mediated currents are inhibited by antiarrhythmic drugs.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been linked to cardiovascular complications, notably cardiac arrhythmias. The open reading frame (ORF) 3a of the coronavirus genome encodes for a transmembrane protein that can function as an ion channel. The aim of this study was to investigate the role of the SARS-CoV-2 ORF 3a protein in COVID-19-associated arrhythmias and its potential as a pharmacological target. Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) and cultured human fibroblasts were infected with SARS-CoV-2. Subsequent immunoblotting assays revealed the expression of ORF 3a protein in hiPSC-CM but not in fibroblasts. After intracytoplasmic injection of RNA encoding ORF 3a proteins into Xenopus laevis oocytes, macroscopic outward currents could be measured. While class I, II, and IV antiarrhythmic drugs showed minor effects on ORF 3a-mediated currents, a robust inhibition was detected after application of class III antiarrhythmics. The strongest effects were observed with dofetilide and amiodarone. Finally, molecular docking simulations and mutagenesis studies identified key amino acid residues involved in drug binding. Class III antiarrhythmic drugs are potential inhibitors of ORF 3a-mediated currents, offering new options for the treatment of COVID-19-related cardiac complications.

Conformational dynamics of SARS-CoV-2 Omicron spike trimers during fusion activation at single molecule resolution

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron entry involves spike (S)glycoprotein-mediated fusion of viral and late endosomal membranes. Here, using single-molecule Förster resonance energy transfer (sm-FRET) imaging and biochemical measurements, we directly visualized conformational changes of individual spike trimers on the surface of SARS-CoV-2 Omicron pseudovirions during fusion activation. We observed that the S2 domain of the Omicron spike is a dynamic fusion machine. S2 reversibly interchanges between the pre-fusion conformation and two previously undescribed intermediate conformations. Acidic pH shifts the conformational equilibrium of S2 toward an intermediate conformation and promotes the membrane hemi-fusion reaction. Moreover, we captured conformational reversibility in the S2 domain, which suggests that spike can protect itself from pre-triggering. Furthermore, we determined that Ca2+ directly promotes the S2 conformational change from an intermediate conformation to post-fusion conformation. In the presence of a target membrane, low pH and Ca2+ stimulate the irreversible transition to S2 post-fusion state and promote membrane fusion.

Improved deep learning prediction of antigen–antibody interactions

Identifying antibodies that neutralize specific antigens is crucial for developing effective immunotherapies, but this task remains challenging for many target antigens. The rise of deep learning-based computational approaches presents a promising avenue to address this challenge. Here, we assess the performance of a deep learning approach through two benchmark tests aimed at predicting antibodies for the receptor-binding domain of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein. Three different strategies for constructing input sequence alignments are employed for predicting structural models of antigen-antibody complexes. In our initial testing set, which comprises known experimental structures, these strategies collectively yield a significant top-ranked prediction for 61% of cases and a success rate of 47%. Notably, one strategy that utilizes the sequences of known antigen binders outperforms the other two, achieving a precision of 90% in a subsequent test set of ~1,000 antibodies, balanced between true and control antibodies for the antigen, albeit with a lower recall of 25%. Our results underscore the potential of integrating deep learning methods with single B cell sequencing techniques to enhance the prediction accuracy of antigen-antibody interactions.

Impact of Respiratory Syncytial Virus and Severe Acute Respiratory Syndrome Coronavirus 2 Coinfection on Clinical Severity and Outcomes Among Children Hospitalized With Lower Respiratory Tract Infections in Soweto, South Africa

Background: No data are available regarding the interplay and clinical manifestations of respiratory syncytial virus (RSV) and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) coinfection in African children. We compared clinical characteristics and outcomes between RSV-only, SARS-CoV-2–only and RSV/SARS-CoV-2 coinfection lower respiratory tract infections (LRTI) in hospitalized African children. Methods: Prospective surveillance of children (0–59 months) hospitalized with severe LRTI was undertaken between March 1, 2020, and March 31, 2023, in Johannesburg, South Africa. Nasopharyngeal swabs for respiratory viruses and clinical data were collected, and clinical characteristics and outcomes were described and compared. Respiratory index of severity in children (RISC) scores were calculated for HIV-uninfected children, and covariates associated with high RISC scores (≥5) were evaluated. Results: Seven thousand four hundred fifty-six children [6.1 months (interquartile range, 14.4–18.6); 57.7% male] were enrolled, 1372 (18.4%) testing RSV+/SARS-CoV-2– (RSV only), 223 (3.0%) RSV−/SARS-CoV-2+ (SARS-CoV-2–only) and 28 (0.4%) RSV+/SARS-CoV-2+ (RSV/SARS-CoV-2 coinfection). Children with RSV only and RSV/SARS-CoV-2 coinfection were more likely to present with bronchiolitis than those with SARS-CoV-2–only (673/1372 and 15/28 vs. 46/223; P < 0.001). Children with RSV/SARS-CoV-2 coinfection had more severe disease than those with RSV or SARS-CoV-2–only, as well as a higher RISC score than SARS-CoV-2–only. Weight-for-age Z scores [adjusted risk ratio (aRR): 0.92], room air saturations (aRR: 0.988) and RSV+ status (aRR: 1.40) were independently associated with severe disease. Conclusions: Although both RSV and SARS-CoV-2 LRTI occurred commonly, coinfection did not. Children with RSV/SARS-CoV-2 coinfection had a higher prevalence of severe LRTI than those with RSV or SARS-CoV-2–only. These findings reinforce the urgent need for safe and effective RSV and SARS-CoV-2 vaccines, especially in children in low- and middle-income countries, where the burden of disease is the highest and the access to medical resources the lowest.

Long-term COVID-19 sequelae by Theta and SARS-CoV-2 variants in a Philippine cohort.

Millions have been infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) since its emergence in 2019, but most patients make a full recovery. The long-term consequences of the infection are anticipated to unravel in the succeeding years with reports of patients experiencing chronic, debilitating sequelae post-infection commonly referred to as Long COVID. Various Variants of Concern (VoCs) have emerged as the SARS-CoV-2 virus evolved displaying increased infectivity and immune evasiveness. We investigate whether the infecting VoCs affect the sequelae of Long COVID in a Philippine cohort. SARS-CoV-2 cases confirmed using RT-PCR followed by Next Generation Sequencing were identified from selected regions of the Philippines and recruited through a retrospective-prospective cohort design. Participants were divided based on the initial infecting VoC or Variant of Interest (VoI) and were subsequently interviewed regarding the presence, intensity, and frequency of key Long COVID symptoms, and followed up on two more separate sessions at least three (3) months apart for a total of three (3) data collection points (S1, S2, S3) to document changes in symptoms throughout the year-long study period. Long COVID symptoms were reported in 88, 82, and 68% of participants in S1, S2, and S3, respectively, showing declining incidence with elapsed time since the first reported infection. General symptoms including headache, fatigue, and post-exertional malaise were the most frequently reported symptoms, while neuropsychiatric symptoms were the second most frequently reported symptoms. In all three (3) sessions, intermittent brain fog, fatigue, and headache were the most frequently reported symptoms in all SARS-CoV-2 variant cohorts. Factors such as age, sex, comorbidities, and disease severity influenced symptom frequency, providing insight into the risk factors that contribute to the prevalence of this disease. A large proportion (>68%) of cases in this Philippine cohort previously infected with different SARS-CoV-2 variants presented with long-term complications of COVID-19 characterized by a highly heterogeneous set of debilitating symptoms. The study highlights the need for long-term monitoring of Long COVID and its impact on human health and the need for our health systems to adopt policy response strategies.

Unraveling the pathogenic interplay between SARS-CoV-2 and polycystic ovary syndrome using bioinformatics and experimental validation

The prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among polycystic ovary syndrome (PCOS) is significantly higher than in the general population. However, the mechanisms underlying this remain obscure. This study aimed to explore the mechanisms by identifying the genetic signature of SARS-CoV-2 infection in PCOS. In the present study, a total of 27 common differentially expressed genes (DEGs) were selected for subsequent analyses. Functional analyses showed that immunity and hormone-related pathways collectively participated in the development and progression of PCOS and SARS-CoV-2 infection. Under these, 7 significant hub genes were identified, including S100A9, MMP9, TLR2, THBD, ITGB2, ICAM1, and CD86 by using the algorithm in Cytoscape. Furthermore, hub gene expression was confirmed in the validation set, PCOS clinical samples, and mouse model. Immune microenvironment analysis with the CIBERSORTx database demonstrated that the hub genes were significantly correlated with T cells, dendritic cells, mast cells, B cells, NK cells, and eosinophils and positively correlated with immune scores. Among the hub genes, S100A9, MMP9, THBD, ITGB2, CD86, and ICAM1 demonstrated potential as possible diagnostic markers for COVID-19 and PCOS. In addition, we established the interaction networks of ovary-specific genes, transcription factors, miRNAs, drugs, and chemical compounds with hub genes with NetworkAnalyst. This work uncovered the common pathogenesis and genetic signature of PCOS and SARS-CoV-2 infection, which might provide a theoretical basis and innovative ideas for further mechanistic research and drug discovery of the comorbidity of the two diseases.

A-279 Performance Evaluation of the Respiratory Viral for BD MAX™ System in Geriatric Population

Abstract Background Respiratory Viral Infection is one of the most common infection in the geriatric population and cause major concern in the Long-Term Care Facilities. Influenza A and B, SARS-CoV-2, and respiratory syncytial virus (RSV) are responsible for most of the hospitalization and deaths among elderly patients. Rapid identification, treatment, and isolation are among the most important steps to fight the spreading of the infection. Methods The BD Respiratory Viral Panel for BD MAX™ System is an automated multiplexed real-time reverse transcriptase polymerase chain reaction (RT- PCR) test intended for the simultaneous, qualitative detection and differentiation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza A, influenza B, and/or respiratory syncytial virus (RSV) nucleic acid in nasopharyngeal swab (NPS) and anterior nasal swab (ANS) specimens from individuals with signs and symptoms of respiratory tract infection. The assay is targeting RNA from the nucleocapsid phosphoprotein gene (N1 and N2 regions) of the SARS-CoV-2, a conserved region of the matrix protein M1 gene for influenza A, conserved regions of the matrix protein M1 gene and HA gene for influenza B, conserved regions of the N and M genes for RSV, and the human RNase P gene. The assay was evaluated for: precision, reproducibility, accuracy, and correlation with BioGx for SARS-CoV-2, Solana (Quidel) for influenza A, influenza B and RSV; the percentage agreement for the evaluation steps was calculated. We ran 86 samples collected from patients residing in Long-Term Care Facilities. Statistical analyses were done using Analyse-it. Results The percentage agreement for precision, reproducibility, and accuracy were 100%. The patients’ correlation was 100% when compared to the existing molecular testing in the laboratory. Female patients accounted for 62.8% (54 female and 32 male); 2 patients were positive for both influenza A and RSV, and one patient was positive for both influenza A and SAR-CoV-2. Conclusions The Respiratory Viral panel for BD MAX™ System gave the benefit of a fully automated, high precision, accuracy and acceptable sensitivity assay; in addition, it offers easier collection (one swabs versus multiple swabs), faster turnaround time for four targets in less than three hours which allow for earlier isolation to prevent the spreading of the infection and initiating treatment when needed. As with every molecular assay avoiding contamination is very important to eliminated false positive results.

Exploring organizational aspects that promote health-related preventive behavior: using the example of work-related SARS-CoV-2 infection control measures in Germany, August 2020 to November 2021.

During the communicable coronavirus disease (COVID-19) pandemic, organizational infection control measures (oICMs) were introduced in the workplace. The employees' positive attitudes and active participation are relevant for full effectiveness regarding disease prevention. Therefore, we explore changes in employees' attitudes toward oICM at work from August-October 2020 (T0) over January 2021 (T1) to October-November 2021 (T2). We further investigate the role an organization can play in supporting health-related preventive behavior. We considered repeated cross-sectional and longitudinal panel survey data from 5,554 employees of a global supplier of technology and services in Germany. A total of 16 items constitute the attitude scores toward oICM (5-point Likert scale). Via mixed-effect model, aspects associated with employees' attitudes toward oICM were explored. Via 'extreme-group' approach, we compared the 20% of participants with the largest changes into less favorable to the 20% with the largest changes into more favorable attitudes toward oICM over time. The overall positive attitudes toward work-related oICM were more favorable at T1 (mean ± SD: 4.2 ± 0.6, median (IQR): 4.3 (0.8), n = 2,515) compared to T0 (4.1 ± 0.6, 4.1 (0.8), n = 2,417) but less favorable at T2 (3.9 ± 0.7, 4.0 (0.9), n = 2,062). Among others, feeling well-informed about possible work-related risks of infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), perceived psychosocial demands through work environment aspects, and perceived management's commitment to safety and health were associated with long-term positive attitudes toward oICM. Individuals developing more favorable attitudes toward oICM reported feeling well-informed about possible work-related SARS-CoV-2 infection risks and improved COVID-19-specific resilience over time. Individuals developing less favorable attitudes toward oICM reported decreased perceptions of COVID-19-associated risks. oICMs in the workplace were perceived appropriate even after COVID-19 vaccines were widely available although the perceived affective risks about SARS-CoV-2 decreased. Taken together, our findings highlight how organizations can support employees in adopting health-related preventive behavior. Among others, we found that feeling well-informed about possible work-related health risks was positively associated with long-term favorable attitudes toward work-related oICM. We expect that the results contribute to the development of interventions to prepare and adapt to future global public health concerns.

Impact and Effectiveness of COVID-19 Vaccines Based on Machine Learning Analysis of a Time Series: A Population-Based Study.

Background: Although confirmed cases of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been declining since late 2020 due to general vaccination, little research has been performed regarding the impact of vaccines against SARS-CoV-2 in Spain in terms of hospitalizations and deaths. Objective: Our aim was to identify the reduction in severity and mortality of coronavirus disease 2019 (COVID-19) at a nationwide level due to vaccination. Methods: We designed a retrospective, population-based study to define waves of infection and to describe the characteristics of the hospitalized population. We also studied the rollout of vaccination and its relationship with the decline in hospitalizations and deaths. Finally, we developed two mathematical models to estimate non-vaccination scenarios using machine learning modeling (with the ElasticNet and RandomForest algorithms). The vaccination and non-vaccination scenarios were eventually compared to estimate the number of averted hospitalizations and deaths. Results: In total, 498,789 patients were included, with a global mortality of 14.3%. We identified six waves or epidemic outbreaks during the observed period. We established a strong relationship between the beginning of vaccination and the decline in both hospitalizations and deaths due to COVID-19 in all age groups. We also estimated that vaccination prevented 170,959 hospitalizations (CI 95% 77,844-264,075) and 24,546 deaths (CI 95% 2548-46,543) in Spain between March 2021 and December 2021. We estimated a global reduction of 9.19% in total deaths during the first year of COVID-19 vaccination. Conclusions: Demographic and clinical profiles changed over the first months of the pandemic. In Spain, patients over 80 years old and other age groups obtained clinical benefit from early vaccination. The severity of COVID-19, in terms of hospitalizations and deaths, decreased due to vaccination. Our use of machine learning models provided a detailed estimation of the averted burden of the pandemic, demonstrating the effectiveness of vaccination at a population-wide level.

Omicron XBB.1.5 subvariant causes severe pulmonary disease in K18-hACE-2 mice.

Owing to their continuous evolution, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) display disparate pathogenicity in mouse models. Omicron and its sublineages have been dominant worldwide. Compared to pre-Omicron VOCs, early Omicron subvariants reportedly cause attenuated disease in human ACE-2-expressing mice (K18-hACE-2). In late 2022, the frequency of Omicron subvariant XBB.1.5 rapidly increased and it progressively replaced other circulating strains. The emergence of new strains requires current SARS-CoV-2 clinical animal model re-evaluation. In this study, we aim to characterize XBB.1.5 pathogenesis in K18-hACE-2. Herein, we demonstrated that XBB.1.5 infection is associated with significant weight loss, severe lung pathology, and substantial mortality. Intranasal XBB.1.5 infection resulted in 100% mortality in K18-hACE2 mice. High virus titers were detected in the lungs on days 3 and 5 after infection. Moreover, XBB.1.5 productively infected the cells within the nasal turbinate, olfactory bulb, intestines, and kidneys. In addition, in a subset of infected mice, we detected high virus titers in the brain. Consistently, we detected high viral antigen expression in the lungs. Furthermore, we observed severe lung injury hallmarks (e.g., immune cell infiltration, perivascular cuffing, and alveolar consolidation). Using immunofluorescence labeling and cytometric analysis, we revealed that XBB.1.5 infection leads to CD45+ cell influx into the lung parenchyma. We further demonstrated that most immune infiltrates are CD11b+ CD11c+ dendritic cells. Additionally, we detected significant induction of proinflammatory cytokines and chemokines in infected lungs. Taken together, our data show that Omicron subvariant XBB.1.5 is highly pathogenic in K18-hACE2 mice.

Lateral flow assay sensitivity and signal enhancement via laser µ-machined constrains in nitrocellulose membrane

Lateral flow assay (LFA) is a handful diagnostic technology that can identify severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other common respiratory viruses in one strip, which can be tested at the point-of-care without the need for equipment or skilled personnel outside the laboratory. Although its simplicity and practicality make it an appealing solution, it remains a grand challenge to substantially enhance the colorimetric LFA sensitivity. In this work, we present a straightforward approach to enhance the sensitivity of LFA by imposing the flow constraints in nitrocellulose (NC) membranes via a number of vertical femtosecond laser micromachined microchannels which is important for prolonged specific binding interactions. Porous NC membrane surfaces were structured with different widths and densities µ-channels employing a second harmonic of the Yb:KGW femtosecond laser and sample XYZ translation over a microscope objective-focused laser beam. The influence of the microchannel parameters on the vertical wicking speed was evaluated from the video recordings. The obtained results indicated that µ-channel length, width, and density in NC membranes controllably increased the immunological reaction time between the analyte and the labeled antibody by 950%. Image analysis of the colorimetric indicators confirmed that the flow rate delaying strategy enhanced the signal sensitives by 40% compared with pristine NC LFA.

D-dimer as a Predictor of ICU Admission and Mortality in COVID-19 Patients: Insights From a Two-Year Retrospective Study From a Tertiary Care Center in South India.

Introduction Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced pneumonitis results in a prothrombotic and hypercoagulable state. Prognostic indicators are crucial for identifying patients at risk of complications. D-dimer, a degradation product of cross-linked fibrin, is a specific marker for thrombosis. Elevated D-dimer levels have been strongly correlated with poor prognosis and increased severity of illness in COVID-19 patients. Given D-dimer's eight-hour half-life, periodic measurement is necessary to track disease progression. This study aimed to analyze and derive threshold and peak D-dimer values to predict outcomes in COVID-19 patients, comparing those treated in isolation wards to those requiring intensive care. Methods This two-year retrospective observational study included patients above 18 years with confirmed COVID-19. Patients were categorized into those treated in isolation wards and those admitted to the intensive care unit (ICU). Based on the outcome, they were further divided into survivors and non-survivors. Demographic and outcome-related data were collected from the hospital's laboratory information system. Serial D-dimer measurements were taken at eight time points. Statistical analysis was performed using the Mann-Whitney test for laboratory values and the chi-square test for demographic data. Receiver operating characteristic (ROC) curve analysis was utilized to derive critical D-dimer values. The area under the curve (AUC) was calculated for initial and peak D-dimer values. Results Of 2.149 patients with confirmed COVID-19, 811 (38%) presented with elevated D-dimer levels. ICU admission was required for 239 patients, either due to direct admission or worsening conditions. An initial D-dimer value of ≥0.93 mg/L FEU indicated the need for ICU admission, while a peak D-dimer value of 5.65 mg/L FEU predicted mortality. The AUC for the initial D-dimer was 0.60 (95% CI: 0.55-0.64), indicating moderate discriminatory power. The AUC for the peak D-dimer was 0.58 (95% CI: 0.54-0.62), suggesting lower predictive accuracy for peak values. Sensitivity was high for both initial (0.925) and peak (0.960) D-dimer values, although specificity was lower, especially for the peak D-dimer (0.486), resulting in a higher rate of false positives. Among the ICU patients, the age range was 27-97 years, with a mean of 53.5 years. Males were more affected than females (71% vs. 29%), with a male-to-female ratio of 1.4:1. Of the ICU patients, 64.8% recovered, while 35.2% succumbed to the disease. Younger patients (mean age: 50.5 ± 12 years) recovered faster than older patients (mean age: 64 ± 16 years), with a significant difference in recovery time (p < 0.001). Gender did not significantly impact outcomes (p = 0.743). Survivors spent less time in the ICU (3-7 days) compared to non-survivors (4-14 days) (p = 0.041). Conclusion Serial D-dimer monitoring is essential for predicting outcomes and guiding treatment in COVID-19 patients. Initial and peak D-dimer values can help identify patients requiring intensive care and those at risk of mortality, allowing for timely interventions. D-dimer levels should be integrated into routine clinical assessments for managing COVID-19 patients.

The Effect of COVID-19 on the Efferent Auditory System in Adults.

This study evaluated the effects of coronavirus disease 2019 (COVID-19) on the cochlea and auditory efferent system with transient evoked otoacoustic emissions (TEOAE) and contralateral suppression (CS). We aimed to evaluate the pre- and post-COVID-19 TEOAE and CS results in the same participants to reveal the effect of COVID-19 on the efferent auditory system. The CS measurement was performed twice for each participant before a diagnosis of COVID-19 and after treatment for COVID-19 as a within-subjects study design. All participants exhibited hearing thresholds below 25 dB HL at all frequencies and all participants demonstrated bilateral Type A tympanograms. The tests were performed in the linear mode using a double probe on the Otodynamics ILO292-II device. The CS of the otoacoustic emissions was measured at 65 dB peSPL TEOAE stimulus and 65 dB SPL broadband noise. All parameters including reproducibility, noise, and stability were considered during the measurements. The study included 11 patients (eight females and three males) aged between 20 and 35 years (mean age, 26 ± 3.66). Wilcoxon signed rank test and Spearman's correlation test were used for statistical analysis using the Statistical Package for the Social Sciences version 23.0. The Wilcoxon signed rank test showed that there was no significant difference between the pre-and post-COVID-19 TEOAE CS results in all tested frequencies and measurement parameters, 1000 to 4000 Hz, Z = -0.356, -0.089, -0.533, -0.533, -1.156, and p < 0.05. Although not statistically significant, the CS results obtained post-COVID-19 at all frequencies, except 4000 Hz, were lower than those before COVID-19. According to the overall TEOAE results after COVID-19, a statistically significant decrease was observed at 3000 Hz (Z = -2.847, p < 0.01) and 4000 Hz (Z = -2.401, p < 0.05) compared with the premeasurement. The study findings show that severe acute respiratory syndrome coronavirus 2 can affect the cochlea and the auditory efferent system in adults. Post-COVID-19 audiological evaluation can also be considered part of a general medical examination.