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Background: The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has posed a threat to society worldwide. The aim of the study was to analyze changes in the physical fitness of 11- to 15-year-olds during the COVID-19 pandemic. Methods: Cross-sectional research was conducted in randomly selected schools in Kraków (Poland) during the years 2020 and 2022. The study group included 1635 adolescents aged 11–15 years. The results of fitness tests such as flexibility, standing broad jump, handgrip strength, overhead medicine ball throw, shuttle run (10 × 5 m), and 30-second sit-ups were analyzed. Body height and weight measurements were also taken. The standing broad jump and handgrip strength were normalized. A statistical analysis was performed to compare the differences between groups using 2-way analysis of variance with the Tukey HSD post hoc test or Kruskal–Wallis test. Results: The test results revealed a deterioration decrease in sit-ups, standing broad jump, shuttle run, and normalized standing broad jump in both sexes. Furthermore, the test results among girls showed a decrease in overhead medicine ball throw and flexibility. An increase in test results of both sexes was noticed in handgrip strength of the right and left hand. Among boys in 2022, the results were better in the flexibility test and overhead medicine ball throw compared with their peers from 2020. Conclusion: This study indicates a decrease in overall physical fitness in adolescents. The observed results may be associated with a decrease in physical activity, changes in nutrition, and restrictions imposed during the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

Objectives: Autoimmune activation by COVID-19 infection/vaccination has been postulated to be responsible for initiating or reactivating multiple types of oral mucosal immune disorders. These include: oral lichen planus; oral pemphigoid; either bullous pemphigoid or mucous membrane pemphigoid with oral involvement; pemphigus vulgaris with oral involvement; and Sjögren disease. In addition, chronic conditions such as oral burning, xerostomia, or changes in taste and/or smell have also been linked to COVID-19 infection/vaccination. Data sources: Part 1 (mucosal conditions): an English-language literature review of Pubmed, Web of Science, Scopus, and Embase was performed searching cases of oral lichen planus, oral bullous pemphigoid, mucous membrane pemphigoid, pemphigus vulgaris, and COVID-19 infection/vaccination, with additional cases from the authors’ clinical practice presented. Part 2 (nonmucosal conditions): Cases of initiated or flared Sjögren disease, chronic oral burning, or xerostomia after COVID-19 infection/vaccination from the authors’ clinical practice were aggregated. Results: The literature review discovered 29 cases of oral lichen planus following COVID-19 infection/vaccination. For bullous pemphigoid, 10 cases were identified after infection/vaccination. The number of pemphigus vulgaris cases following infection/vaccination was 28. The majority of mucosal cases were reported after vaccination. Most reported initial disease, but a substantial amount included recurrences of existing diseases. Nonmucosal disease: Sjögren disease, chronic oral burning, or xerostomia after COVID-19 infection/vaccination cases totaled 12 cases identified from the authors’ clinical practice, with the majority occurring after infection. Conclusions: Chronic conditions after infection with COVID-19 or vaccination remain relatively rare and self-limited, yet reinforce the importance of comprehensive history taking involving COVID-19 to differentiate potential etiologic factors for these conditions. [ABSTRACT FROM AUTHOR]

The binding of the receptor binding domain (RBD) of the SARS-CoV-2 spike protein to the host cell receptor angiotensin-converting enzyme 2 (ACE2) is the first step in human viral infection. Therefore, understanding the mechanism of interaction between RBD and ACE2 at the molecular level is critical for the prevention of COVID-19, as more variants of concern, such as Omicron, appear. Recently, atomic force microscopy has been applied to characterize the free energy landscape of the RBD–ACE2 complex, including estimation of the distance between the transition state and the bound state, xu. Here, using a coarse-grained model and replica-exchange umbrella sampling, we studied the free energy landscape of both the wild type and Omicron subvariants BA.1 and XBB.1.5 interacting with ACE2. In agreement with experiment, we find that the wild type and Omicron subvariants have similar xu values, but Omicron binds ACE2 more strongly than the wild type, having a lower dissociation constant KD. [ABSTRACT FROM AUTHOR]

Since the beginning of COVID-19, more than 13,036,550 people have been infected, and 571,574 died because of the disease by July 13, 2020. Developing new methodologies to predict the COVID-19 pandemic will help policymakers plan to contain the spread of the virus. In this research, we develop a Stochastic Fractal Search algorithm combined with a mathematical model to forecast the pandemic. To enhance the algorithm, we employed a design of the experiments approach for tuning.We applied our algorithm to public datasets to model the COVID-19 pandemic in Canada in the upcoming months. Our algorithm predicts the number of symptomatic, asymptomatic, life-threatening, recovered, and death cases. The outcomes reveal that asymptomatic cases play the main role in the transmission of the virus.Wealso show that increasing the testing capacity would enhance the detection of asymptomatic cases and limit community transmission. Moreover, we performed sensitivity analyses to discover the effects of changes in transmission rates on pandemic growth. The sensitivity analyses provide a realistic overview of the future number of cases if the transmission rates change due to the emergence of new variants or change in social measures. Considering the outcomes, we provide several managerial insights to minimize community transmission. [ABSTRACT FROM AUTHOR]

This paper is aimed at comprehensively reviewing olfactory and gustatory disorders caused by SARS-CoV-2 in children and adults. An electronic and manual search was done on three data bases: MEDLINE, Embase, and Web of Science. Inclusion criteria included publications written in English, involving humans in the age range of 0 to 99 years that were captured by a controlled vocabulary of thesaurus terms. Olfactory and gustatory disorders rates in COVID-19 ranged from 22% to 71.9% in adults and 16.6% to 25.8% in children. Olfactory and gustatory disorders might appear as the first symptom, and in adults might even be the only symptom (4.8% to 10%). Anosmia is the most common olfactory disorder and hypogeusia is the most common gustatory disorder. In 33% to 89% of cases, olfactory and gustatory disorders resolve spontaneously within a few weeks, coinciding with the resolution of other COVID-19 symptoms, both in adults and children. However, in some patients, olfactory and gustatory disorders persist beyond the resolution of other symptoms. Notably, children generally experience a swifter and more favorable recovery compared to adults. The precise pathogenesis underlying olfactory and gustatory disorders in the context of COVID-19 remains unclear and is likely multifactorial. Presently, no established treatment protocol exists for olfactory and gustatory disorders and current treatments reviewed lack robust evidence and are not readily available for clinical use. Olfactory training represents the only therapy currently recommended by international authorities. Pediatric practitioners and general dental practitioners should be aware of olfactory and gustatory disorders in both pediatric and adult populations, including their biologic mechanisms, treatment options, and recovery rates. [ABSTRACT FROM AUTHOR]

Aim: To investigate the association between physical activity and immunogenicity among SARS-CoV-2 seropositive patients with autoimmune rheumatic diseases prior to and following a 2-dose schedule of CoronaVac (Sinovac inactivated vaccine). Methods: This was a prospective cohort study within an open-label, single-arm, phase 4 vaccination trial conducted in Sao Paulo, Brazil. In this substudy, only SARS-CoV-2 seropositive patients were included. Immunogenicity was assessed by seroconversion rates of total anti-SARS-CoV-2 S1/S2 immunoglobulin G (IgG), geometric mean titers of anti-S1/S2 IgG, frequency of positive neutralizing antibodies, and neutralizing activity before and after vaccination. Physical activity was assessed through a questionnaire. Model-based analyses were performed controlling for age (<60 or ≥60 y), sex, body mass index (<25, 25–30, and >30 kg/m2), and use of prednisone, immunosuppressants, and biologics. Results: A total of 180 seropositive autoimmune rheumatic disease patients were included. There was no association between physical activity and immunogenicity before and after vaccination. Conclusions: This study suggests that the positive association between physical activity and greater antibody responses seen in immunocompromised individuals following vaccination is overridden by previous SARS-CoV-2 infection, and does not extend to natural immunity. [ABSTRACT FROM AUTHOR]

The novel coronavirus disease 2019 (COVID-19) outbreak has caused tremendous turmoil worldwide and is yet to be contained. Therefore, mitigating the number of people infected by COVID-19 remains a fundamental policy goal for several countries. This study aims to analyse the dynamic relationship between mobility and the rate of change in the number of new infections (NNIs) in Japan. Another goal is to evaluate the effects of various policies, such as mobility control and vaccination, as well as the impact of climate factors on the NNIs. The analysis reveals a strong positive relationship between the growth rate of the NNIs and mobility. Our results also indicate that the government-imposed measure of regulating mobility shows a weaker effect on preventing the spread of infection, as the emergency declaration is repeatedly invoked. By contrast, the recent increase in the infection rate seems to reduce the spread of infection by inducing voluntary restraint, and this phenomenon has become even stronger in the recent period. Regarding the effect of vaccination, the results demonstrate little effect on attenuating the spread of infection. However, it has significantly weakened the mobility – spread relationship, suggesting that it may help in the implementation of economic revitalization policies. [ABSTRACT FROM AUTHOR]

A significant Omicron wave emerged in China in December 2022. To explore the duration of humoral and cellular response postinfection and the efficacy of hybrid immunity in preventing Omicron reinfection in patients with lung cancer, a total of 447 patients were included in the longitudinal study after the Omicron wave from March 2023 to August 2023. Humoral responses were measured at pre‐Omicron wave, 3 months and 7 months postinfection. The detected severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) specific antibodies including total antibodies, anti‐receptor binding domain (RBD) specific IgG, and neutralizing antibodies against SARS‐CoV‐2 wild type (WT) and BA.4/5 variant. T cell responses against SARS‐CoV‐2 WT and Omicron variant were evaluated in 101 patients by ELISpot at 3 months postinfection. The results showed that Omicron‐infected symptoms were mild, while fatigue (30.2%), shortness of breath (34.0%) and persistent cough (23.6%) were long‐lasting, and vaccines showed efficacy against fever in lung cancer patients. Humoral responses were higher in full or booster vaccinated patients than those unvaccinated (p <.05 for all four antibodies), and the enhanced response persisted for at least 7 months. T cell response to Omicron was higher than WT peptides (21.3 vs. 16.0 SFUs/106 PBMCs, p =.0093). Moreover, 38 (9.74%) patients were reinfected, which had lower antibody responses than non‐reinfected patients (all p <.05), and those patients of unvaccinated at late stage receiving anti‐cancer immunotherapy alone were at high risk of reinfection. Collectively, these data demonstrate the Omicron infection induces a high and durable immune response in vaccinated patients with lung cancer, which protects vaccinated patients from reinfection. [ABSTRACT FROM AUTHOR]

PurposeMethodsResultsConclusionTo present a presumed case of non-paraneoplastic autoimmune retinopathy (nPAIR) following COVID-19 in a healthy woman.A single case was evaluated and followed for 32 months.A healthy 32-year-old woman presented with photopsia and paracentral scotoma (OU) after a recent COVID-19 infection. Past medical history and family history were unremarkable. Her visual acuity was normal (OU). Retinal atrophy, mild disc pallor, and foveal reflex attenuation were observed (OU). Optical coherence tomography (OCT) scans showed outer nuclear layer thinning and ellipsoid zone disruption (OU). The visual field test showed blind spot enlargement and arcuate scotomas (OU). Uveitis workup and underlying malignancy investigations were negative. A diagnosis of nPAIR was presumed. At the time, she refused therapy, and 20 months later, her visual acuity was stable, but there were progressive retinal atrophic changes and visual field constriction. After initiation of glucocorticoids and immunosuppressive therapy, flashing lights completely disappeared, her visual field was stabilized without progression, and OCT scans showed partial recovery of ellipsoid zone.SARS-CoV-2 infection may be a trigger for nPAIR in susceptible individuals, but further research is needed to determine this association. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

RNA is a central molecule in RNA virus biology; however, the interactions that it establishes with the host cell are only starting to be elucidated. In recent years, a methodology revolution has dramatically expanded the scope of host-virus interactions involving the viral RNA (vRNA). A second wave of method development has enabled the precise study of these protein-vRNA interactions in a life cycle stage-dependent manner, as well as providing insights into the interactome of specific vRNA species. This review discusses these technical advances and describes the new regulatory mechanisms that have been identified through their use. Among these, we discuss the importance of vRNA in regulating protein function through a process known as riboregulation. We envision that the elucidation of vRNA interactomes will open new avenues of research, including pathways to the discovery of host factors with therapeutic potential against viruses. [Display omitted] Viral RNA (vRNA) is a central molecule in viral infection; however, its interactions with the host cell remain largely unknown. The emergence of new methods now enables the comprehensive identification of host-virus interactions involving the vRNA. This review describes these technical advances and the biological insights derived from their application. [ABSTRACT FROM AUTHOR]

Background: Long term respiratory complications of Corona Virus Disease-2019 (COVID-19) are of great concern. Many studies have reported altered respiratory patterns in COVID-19 recovered individuals and most of them were from severe to critically ill patients. The association of viral load at the time of infection with symptoms of long COVID-19 specifically on pulmonary functions after months of recovery is still not known. This study was aimed to assess the impact of SARS-CoV-2 viral load during mild-moderate COVID-19 disease on pulmonary functions in middle-aged population after 6–8 months of acute infection. Methods: This study included 300 (102 healthy controls and 198 COVID-19 recovered) individuals between age 30–60 of either gender. Mild-moderate COVID-19 recovered individuals were recruited between a period of 6–8 months post-acute infection. Spirometry was performed with MIR-Spirolab-III. The association of spirometry pattern was compared with SARS-CoV-2 viral loads during acute infection. Results: We observed up to 70% of the participants presented with either shortness of breath (11.5%), body aches (23.5%), recurrent cough (4.4%), recurrent respiratory infections (9.5%) and/or fatigue (33.3%) at follow up. In our study, 35.5% of COVID-19 recovered individuals had abnormal respiratory patterns (33.5% had restrictive and 2% had obstructive patterns). Viral load ≤ 20 CT value was associated with restrictive respiratory patterns (p = 0.004). No association was found between viral load and disease severity (p = 0.23). Conclusion: In this study, we found one third of mild-moderate COVID-19 recovered individuals have restrictive respiratory patterns after 6–8 months of recovery. These findings had a strong association with SARS-CoV-2 viral loads during acute infection which has been reported for the first time in our study. Studying the relationship between viral load and pulmonary functions can contribute to identifying potential risk factors for long COVID and developing preventive measures to mitigate the long-term impact on lung health. Clinical trial number: Not applicable. [ABSTRACT FROM AUTHOR]

Background Coronavirus disease 2019 (COVID-19) caused a high burden of sick leave worldwide. Long-term sick leave for COVID-19 may be longer than for other influenza-like syndromes. The real impact of long COVID on absenteeism remains uncertain. Aims To investigate the burden of sick leave, especially >12 weeks, in Belgian workers with a positive polymerase chain reaction (PCR) test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from July 2020 to September 2021 and to compare these figures with sick leave for other infectious diseases. Methods We coupled a database of SARS-CoV-2-positive workers and workers who were absent for other infections with objective absence data. Predictors of prolonged sickness were evaluated by negative binomial regression, Cox proportional hazards regression and ordinal logistic regression. Results The study population involved 2569 workers who tested positive for SARS-CoV-2 and 392 workers who were absent for other infectious diseases. In total, 16% (95% CI 14–17%) of workers with a positive SARS-CoV-2 test had no sick leave registered. Fourteen out of 1000 (95% CI 9–20‰) workers with absenteeism for COVID-19 experienced sick leave >12 weeks as compared to 43 out of 1000 workers (95% CI 3–69‰) with absenteeism due to other infections. When including PCR-positive workers without sick leave, the prevalence of long-term sick leave decreased to 12 per 1000 (95% CI8–17‰). Long-term sick leave was associated with older age, high previous sick leave and low educational level. Conclusions The prevalence of long-term sick leave was lower than estimated in earlier investigations regardless of worrying reports about post-COVID-19 syndrome. [ABSTRACT FROM AUTHOR]

Background An outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with an attack rate of 55% (22/40 workers) occurred at a public-facing office in England from August to September 2021. Published evidence regarding outbreaks in office workplaces remains limited. Aims To describe an investigation of workplace- and worker-related risk factors following an outbreak of SARS-CoV-2 in a public-facing office. Methods The COVID-19 (coronavirus disease 2019) Outbreak Investigation to Understand Transmission (COVID-OUT) study undertook an investigation of the outbreak. This included surface sampling, occupational environmental assessment, molecular and serological testing of workers, and detailed questionnaires. Results Despite existing COVID-19 control measures, surface sampling conducted during a self-imposed 2-week temporary office closure identified viral contamination (10/60 samples, 17% positive), particularly in a small, shared security office (6/9, 67% positive) and on a window handle in one open-plan office. Targeted enhanced cleaning was, therefore, undertaken before the office reopened. Repeat surface sampling after this identified only one positive (2%) sample. Ventilation was deemed adequate using carbon dioxide monitoring (typically ≤1000 ppm). Twelve workers (30%) responded to the COVID-OUT questionnaire, and all had been vaccinated with two doses. One-third of respondents (4/12) reported direct physical or close contact with members of the public; of these, 75% (3/4) reported a divider/screen between themselves and members of the public. Conclusions The results highlight the potential utility of surface sampling to identify SARS-CoV-2 control deficiencies and the importance of evolving, site-specific risk assessments with layered COVID-19 mitigation strategies. [ABSTRACT FROM AUTHOR]

Background: The COVID-19 pandemic has caused significant morbidity and mortality globally. The role of plasma-derived extracellular vesicles (EVs) in pediatric COVID-19 patients remains unclear. Methods: We isolated EVs from healthy controls (n = 13) and pediatric COVID-19 patients (n = 104) with varying severity during acute and convalescent phases using serial ultracentrifugation. EV effects on healthy PBMCs, naïve CD4+ T cells, and monocytes were assessed through in vitro assays, flow cytometry, and ELISA. Results: Our findings indicate that COVID-19 severity correlates with diverse immune responses. Severe acute cases exhibited increased cytokine levels, decreased IFNγ levels, and lower CD4+ T cell and monocyte counts, suggesting immunosuppression. EVs from severe acute patients stimulated healthy cells to express higher PDL1, increased Th2 and Treg cells, reduced IFNγ secretion, and altered Th1/Th17 ratios. Patient-derived EVs significantly reduced proinflammatory cytokine production by monocytes (p <.001 for mild, p =.0025 for severe cases) and decreased CD4+ T cell (p =.043) and monocyte (p =.033) populations in stimulated healthy PBMCs. Conclusion: This study reveals the complex relationship between immunological responses and EV-mediated effects, emphasizing the impact of COVID-19 severity. We highlight the potential role of plasma-derived EVs in early-stage immunosuppression in severe COVID-19 patients. [ABSTRACT FROM AUTHOR]

Background: SARS-CoV-2, which causes COVID-19, has killed more than 7 million people worldwide. Understanding the development of postinfectious and postvaccination immune responses is necessary for effective treatment and the introduction of appropriate antipandemic measures. Objectives: We analysed humoral and cell-mediated anti-SARS-CoV-2 immune responses to spike (S), nucleocapsid (N), membrane (M), and open reading frame (O) proteins in individuals collected up to 1.5 years after COVID-19 onset and evaluated immune memory. Methods: Peripheral blood mononuclear cells and serum were collected from patients after COVID-19. Sampling was performed in two rounds: 3-6 months after infection and after another year. Most of the patients were vaccinated between samplings. SARS-CoV-2-seronegative donors served as controls. ELISpot assays were used to detect SARS-CoV-2-specific T and B cells using peptide pools (S, NMO) or recombinant proteins (rS, rN), respectively. A CEF peptide pool consisting of selected viral epitopes was applied to assess the antiviral T-cell response. SARS-CoV-2-specific antibodies were detected via ELISA and a surrogate virus neutralisation assay. Results: We confirmed that SARS-CoV-2 infection induces the establishment of long-term memory IgG+ B cells and memory T cells. We also found that vaccination enhanced the levels of anti-S memory B and T cells. Multivariate comparison also revealed the benefit of repeated vaccination. Interestingly, the T-cell response to CEF was lower in patients than in controls. Conclusion: This study supports the importance of repeated vaccination for enhancing immunity and suggests a possible long-term perturbation of the overall antiviral immune response caused by SARS-CoV-2 infection. [ABSTRACT FROM AUTHOR]

This paper presents a critical analysis of the literature and perspective research ideas for modeling the epidemics caused by the SARS-CoV-2 virus. It goes beyond deterministic population dynamics to consider several key complexity features of the system under consideration. In particular, the multiscale features of the dynamics from contagion to the subsequent dynamics of competition between the immune system and the proliferating virus. Other topics addressed in this work include the propagation of epidemics in a territory, taking into account local transportation networks, the heterogeneity of the population and the study of social and economic problems in populations involved in the spread of epidemics. The overall content aims to show how new mathematical tools can be developed to address the above topics and how mathematical models and simulations can contribute to the decision making of crisis managers. [ABSTRACT FROM AUTHOR]

Background The coronavirus disease 2019 (COVID-19) pandemic impacted cancer services worldwide. We examined the effect of the first three pandemic waves on the number of electronic (e)-referrals to rapid access clinics (RACs) for breast, lung and prostate cancer in Ireland. Methods This study used a retrospective, repeated cross-sectional design. The predicted weekly number of e-referrals by suspected cancer types from March 2020 to May 2021 was calculated using the Holt-Winters seasonal smoothing method, based on the observed numbers from a representative pre-pandemic period (01 January 2019 to 01 March 2020) and compared this with the observed number across the first three pandemic waves (02 March 2020 to 09 May 2021). Percentage differences were calculated between observed and predicted numbers of e-referrals for the three RACs and patterns were examined in each wave. Results Observed e-referrals were lower than predicted for all three RACs in the first wave of the pandemic (15.7% lower for breast, 39.5% lower for lung and 28.1% lower for prostate) with varying levels of recovery in the second and third waves for the three e-referral types. Conclusions The COVID-19 pandemic impacted patterns of e-referrals to RACs in the first three pandemic waves in Ireland. Early identification of changes in engagement with health services, such as a decrease in primary care presentations with a resultant decrease in e-referrals to RACs can allow for a rapid response from cancer control programmes. Continued surveillance of the impact of service disruption on cancer services allows policy makers and strategic leaders in cancer control programmes to respond rapidly to mitigate the impact on cancer outcomes. [ABSTRACT FROM AUTHOR]

This article explores the challenges of determining the viability of infectious agents in tissue samples. It discusses various methods used in histopathology, such as staining techniques and immunohistochemistry, to assess viability. The article also mentions the potential use of mRNA analysis to indicate active replication of infectious agents. The author acknowledges the limitations of current techniques and suggests that nucleic acid amplification from formalin-fixed, paraffin-embedded samples could provide a more accurate assessment of viability. The article emphasizes the need for improved methods to determine the viability of infectious agents in tissue samples and calls for further research in this area. [Extracted from the article]

Objectives: To describe the uptake of anti-SARS-CoV2 vaccination in 2021 and investigate vaccine effectiveness in systemic lupus erythematosus (SLE) patients in Sweden. Methods: The cumulative incidence of first anti-SARS-CoV2 vaccination was estimated among SLE patients from the Swedish National Patient Register and matched comparators living in Sweden on January 1, 2021. To assess vaccine effectiveness, we included the individuals who received two doses of anti-SARS-CoV2 mRNA vaccines before year 2022, with no COVID-19 diagnosis code before the 2nd vaccine dose. Hospitalization rates with COVID-19 as main diagnosis during the year after second dose were compared between SLE patients and comparators in multivariable-adjusted marginal Cox models, overall and stratified by immunosuppressive treatment received during the year before second vaccine dose. Results: Vaccination uptake was similar between SLE patients and comparators. By December 2021, 9% of both SLE and comparators had not received any vaccine doses. Among 5585 SLE patients and 37,102 comparators, 11 COVID-19 hospitalizations in the SLE group and 20 in the comparators occurred. SLE was associated with a higher risk of COVID-19 hospitalization (HR = 3.47, 95%CI 1.63-7.39). The HR was higher for immunosuppressive-treated SLE (7.03 95%CI 3.00-16.46) than for immunosuppressive-untreated (1.50 95%CI 0.34-6.60). Vaccination of immunosuppressive-untreated SLE patients had similar effectiveness as comparators. Conclusion: Anti-SARS-CoV2 vaccination coverage was similar between SLE patients and the general population in Sweden. Even though the incidence of post-vaccination COVID-19 hospitalization was very low, vaccine effectiveness was diminished in SLE patients compared to the general population and lowest in those treated with immunosuppressants. [ABSTRACT FROM AUTHOR]

Long COVID, a type of post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (PASC) defined by medically unexplained symptoms following infection with SARS-CoV-2, is a newly recognized infection-associated chronic condition that causes disability in some people. Substantial progress has been made in defining its epidemiology, biology, and pathophysiology. However, there is no cure for the tens of millions of people believed to be experiencing long COVID, and industry engagement in developing therapeutics has been limited. Here, we review the current state of knowledge regarding the biology and pathophysiology of long COVID, focusing on how the proposed mechanisms explain the physiology of the syndrome and how they provide a rationale for the implementation of a broad experimental medicine and clinical trials agenda. Progress toward preventing and curing long COVID and other infection-associated chronic conditions will require deep and sustained investment by funders and industry. Known under competing terms and definitions such as post-COVID-19 condition, post-COVID-19 conditions, post-acute sequelae of SARS-CoV-2 (PASC), post-COVID-19 syndrome, post-COVID-19, or long COVID, this review provides a framework for interpreting the literature and discusses how mechanistic studies are influencing the development of biomarkers, functional tests, and, ultimately, clinical interventions. [ABSTRACT FROM AUTHOR]

Introduction: Due to the increase in infections of the Omicron variant of Coronavirus Disease 2019, the Mexican health authority authorized the oral antiviral Paxlovid® for the outpatient treatment of patients with mild to mod- erate infection. Having a limited safety profile, the objective was to describe the adverse reactions and other safety problems related to the use, treated in a tertiary hospital in Mexico and compare them with those reported in other countries. Method: Semilongitudinal and prospective clinical series developed out at the Regional High Specialty Hospital of the Yucatan Peninsula between October 17, 2022, and July 10, 2023. Patients treated with Paxlovid® were inter- viewed by telephone calls and were asked about any adverse reactions presented. Results: A total of 65 patients were included. The average age was 46,8±15,3 years. 89,2 % (n=58) presented one or more adverse reactions and 13,8 % (n=9) discontinued treatment due to them. In general, 132 adverse reactions were identified, 2±1 per patient, the most frequent being mild (78 %) such as bitter taste, nausea and fatigue. Other adverse reactions not reported in the Paxlovid® package insert was identified. Conclusions: Paxlovid® has an acceptable safety profile comparable to that of other studies, this being consistent with previous clinical experience and supporting the safety of the use of nirmatrelvir y ritonavir combination drug as a therapeutic option against Coronavirus Disease 2019. [ABSTRACT FROM AUTHOR]

We tested 130 rats captured in Berlin for coronaviruses. SARS-CoV-2 antibodies were detected in 1 rat, but all animals were negative by reverse transcription PCR, suggesting SARS-CoV-2 was not circulating in the rat population. However, alphacoronaviruses were found. Monitoring rodent populations helps to determine coronavirus occurrence, transmission, and zoonotic potential. [ABSTRACT FROM AUTHOR]

The southern United States (U.S.) produces approximately 60% of the Nation's timber products, almost entirely from private forests. This work explores the perspectives of stakeholders with regards to the interrelated impacts of the COVID-19 pandemic (SARS-CoV-2) on the timber supply chain in the U.S. South. Four focus groups were held with key stakeholders to explore the effects of the pandemic on forest landowners, loggers, and wood mill workers. We compared focus group participant insights to published research and other summary information from reputable sources. We found that supply, demand, and government factors were interdependent and affected the timber supply chain heterogeneously during the pandemic. Focus group participant discussions generated many new hypotheses, which can be empirically or qualitatively tested in future analyses. [ABSTRACT FROM AUTHOR]

Individuals with chronic lung disease (CLD) are more susceptible to respiratory viral infections; however, significant heterogeneity exists in the literature on CLD and COVID-19 outcomes. Data are lacking on outcomes with newer variants (eg, Omicron) and in vaccinated and boosted populations. What are the outcomes of SARS-CoV-2 infection in individuals with CLD during Delta and Omicron transmission in a highly vaccinated and boosted population-based cohort? Outcomes of Delta and Omicron SARS-CoV-2 infection in a highly vaccinated and boosted cohort of adult Singaporeans with CLD (including asthma, COPD, bronchiectasis, and pulmonary fibrosis) were contrasted against matched population control participants. Calendar time-scale Cox regressions were used to compare risk of infection, COVID-19-related hospitalizations, and severe COVID-19 disease, adjusting for sociodemographic factors and comorbidities. Overall, 68,782 individual patients with CLD and 534,364 matched population control participants were included. By the end of the Omicron wave, 92.7% of patients with CLD were boosted. Compared with control participants, patients with CLD showed higher risk of SARS-CoV-2 infection, COVID-19-related hospitalization, and severe COVID-19 during both the Delta wave (infection: adjusted hazards ratio [aHR], 1.22 [95% CI, 1.17-1.28]; hospitalization: aHR, 1.76 [95% CI, 1.61-1.92]; severe COVID-19: aHR, 1.75 [95% CI, 1.50-2.05]) and Omicron wave (infection: aHR, 1.15 [95% CI, 1.14-1.17]; hospitalization: aHR, 1.82 [95% CI, 1.74-1.91]; severe COVID-19: aHR, 2.39 [95% CI, 2.18-2.63]). During Omicron, significantly higher risk of infection, hospitalization, and severe COVID-19 was observed among patients with asthma (severe COVID-19: aHR, 1.31 [95% CI, 1.10-1.55]) and COPD (severe COVID-19: aHR, 1.36 [95% CI, 1.12-1.66]) compared with control participants. Severe exacerbation (requiring hospitalization) in the preceding year was associated with higher risk of poorer outcomes (Delta, severe COVID-19: aHR, 9.84 [95% CI, 6.33-15.28]; Omicron, severe COVID-19: aHR, 19.22 [95% CI, 15.35-24.06]). Risk was attenuated in the boosted group, with numerically lower HRs against hospitalization and severe COVID-19 in the four-dose group compared with the three-dose group. Increased risk of COVID-19-related hospitalization and severe COVID-19 was observed among patients with CLD compared with matched population control participants during Delta and Omicron predominance. Boosting attenuated serious COVID-19 outcomes. [ABSTRACT FROM AUTHOR]

In this work, theoretical and experimental studies of a new Indazole derivative named 2-(5-nitro-1-H-indazol-1-yl) acetic acid (3), including the synthesis and characterization by 1H and 13C-NMR, FT-IR, UV spectroscopies are reported together with its X-ray crystal structure. The compound crystallizes in the monoclinic crystal system of P21/c space group and unit cell constants: a = 7.8541(10) Å, b = 7.9274(11) Å, c = 15.877(2) Å, β = 101.149(5)°. In the crystal, O–H···N and C–H···O hydrogen bonds form a 3-D network structure containing small channels running parallel to the b-axis. B3LYP/6-311++G** calculations in the gas phase and ethanol solution suggest the existence of C1 and C2 conformers where the structure of C1 in both media is in agreement with that observed by X-ray diffraction. Probably, the high values observed in the dipole moments of C1 justify its presence in gas and solution phases. The stabilities of both forms were justified by NBO and AIM calculations where C1 is more stable than C2. C1 shows a higher solvation energy, dipole moment, and higher hydration than C2 while the frontier orbitals suggest a higher reactivity of C1 over C2. Force fields and complete vibrational assignments were performed for the C1 conformer because it was detected in the solid phase. Scaled force constants for both forms are also reported. Calculated chemical shifts for (3) are consistent with the experimental 1H and 13C-NMR spectra in the DMSO-d6 solution. The anti-COVID activity of 3 is investigated by its molecular docking into the binding site of SARS CoV-2 3CLpro (3 C-like protease). It shows a moderate binding affinity into the binding site of 3 C-like protease with a maximum binding energy of −5.57 kcal mol−1. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has significantly changed the understanding of the safety profile of therapies for immunoinflammatory rheumatic diseases (IRDs). This is primarily due to the negative impact of a number of basic disease-modifying antirheumatic drugs (DMARDs) and genetically engineered biological drugs (biological DMARDs, or biologics) on the course and outcomes of a new coronavirus infection. A number of studies have shown that anti-B-cell therapy (rituximab) gave a statistically significant increase in the risk of severe COVID-19 and an increase in mortality. At the same time, the analysis of real clinical practice data dictated the need to establish a number of restrictions on the use of certain classes of biologics and to search for alternative therapy programs to maintain control over disease activity. Purpose of the study. The purpose of the study was to evaluate the efficacy and safety of the drug Artlegia® (olokizumab), solution for subcutaneous injection, 160 mg/ml-0.4 ml, manufactured by R-Pharm JSC, Russia) for the treatment of patients with rheumatoid arthritis in real clinical practice after switching with rituximab during the COVID-19 pandemic. Materials and methods. The study included 14 patients with a confirmed diagnosis of rheumatoid arthritis (RA), who were previously on rituximab therapy at a dose of 1000–500 mg twice with an interval of 2 weeks, who received at least one course of therapy with this drug. As RA worsened, patients were switched to olokizumab against the background of standard DMARDs. On weeks 0, 4, 8, and 12 after the switch, the severity of pain was assessed on the VAS scale, the number of tender and swollen joints (TJC28 and SJC28), the level of acute-phase inflammation markers, the DAS28 (disease activity score), ESR, CRP, CDAI (clinical activity index), and the functional state index HAQ (Health Assessment Questionnaire) were determined, as well as the safety profile of therapy was assessed. Results. Data analysis was performed using median values (Me) were used for data analysis. A significant decrease in TJC28 was detected after 8 and 12 weeks of treatment with olokizumab (Artlegia®) (Me baseline = 10, Me 8 weeks = 4, Me 12 weeks = 4, p < 0.05) and a decrease in TSC28 was detected after 4, 8, and 12 weeks of treatment (Me baseline = 9, Me 4 weeks = 3.5, Me 8 weeks = 2.5, Me 12 weeks = 2.0, p < 0.05). Laboratory markers of inflammation showed a decrease in CRP and ESR levels after 4 weeks of treatment (CRP: Me4 weeks = 21, Me4 weeks = 1, p < 0.05, ESR: Mesno = 31, Me4 weeks = 7, p < 0.05). Positive dynamics persisted on 8 and 12 weeks (CRP: Me 8 weeks = 1, Me 12 weeks = 0; ESR: Me 8 weeks = 4, Me 12 weeks = 5). The level of CRP by week 4 became within the normal range, regardless of the initial values. All activity indices improved from week 4 in each evaluation period compared to baseline: DAS28-ESR: Me baseline = 5.52, Me 4 weeks = 3.59, Me 8 weeks = 3.33, Me 12 weeks = 3.22, p < 0.05; DAS28CRP: Me baseline = 5.39, Me 4 weeks = 3.71, Me 8 weeks = 3.35, Me 12 weeks = 3.45, p < 0.05; CDAI: Me baseline = 28.5, Me 4 weeks = 18.0, Me 8 weeks = 16.5, Me 12 weeks = 16.0, p < 0.05. All patients showed a reduction in pain (VAS scale) by week 8. The functional status of patients, according to the HAQ index, showed a significant decrease only by week 12 of the study: Me baseline = 1.62, Me 12 weeks = 1.31, p < 0.05. Conclusions. The study found that switching from rituximab to olokizumab was effective and safe during the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

Aim: The effectiveness of the coronavirus disease (COVID‐19) vaccine in Japanese patients undergoing haemodialysis has previously not been evaluated on a large scale. We analyzed data from the Japanese Society for Dialysis Therapy Renal Data Registry (JRDR), covering nearly all Japanese patients undergoing dialysis (~95% coverage), to examine the association between COVID‐19 vaccination and infection or mortality. Methods: We used data from the JRDR end‐of‐year surveys conducted in 2020 and 2021, including information on the COVID‐19 vaccination and infection months. COVID‐19 infection incidence and its associated mortality rates based on vaccination status (time updated) and odds ratio (OR) (vaccinated vs. unvaccinated) were estimated monthly from April 2021, when vaccination commenced in Japan. Results: COVID‐19 infection analysis included 228 865 patients (215 941 vaccinated and 12 924 unvaccinated patients at the end of 2021). The age‐ and sex‐adjusted ORs (aORs) were significantly lower in August, September, October and November 2021, especially in September (aOR [95% confidence interval (CI)]: 0.25 [0.18–0.36]). Additional adjustments for past medical history and laboratory results rarely affected these results. Similarly, in the COVID‐19‐related mortality analysis with 228 731 patients, including 216 781 vaccinated and 11 950 unvaccinated at the end of 2021, COVID‐19‐related mortality risk was significantly lower in the vaccinated group in August, September, October and November (aOR [95% CI]: August, 0.32 [0.12–0.84], September, 0.04 [0.01–0.11]; October, 0.10 [0.01–0.81]; November, 0.05 [0.00–0.79]). Conclusion: In Japanese patients undergoing haemodialysis, the first or second COVID‐19 vaccine dose was significantly associated with decreased COVID‐19 infection and mortality rates, suggesting its effectiveness in this population. [ABSTRACT FROM AUTHOR]

Purpose: To study the positivity rate of conjunctival realtime polymerase chain reaction (RT-PCR) testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Design: Systematic review and diagnostic accuracy meta-analysis. Methods: MEDLINE and EMBASE were queried using medical subject headings terms. Diagnostic accuracy meta-analyses and forest plots were obtained using the RevMan software. Results: After deduplication, appraisal of abstract titles and full-text analysis of 1441 articles, 42 articles with 3351 COVID-19 patients were included in this review. Of these, 412 conjunctival swabs/Schirmer paper strips tested positive for SARS-CoV-2 by RT-PCR. The pooled sensitivity of the RT-PCR tests across the 24 studies with laboratory-confirmed COVID-19 patients was 10.3%. Conclusions: Only 1 in 10 RT-PCR tests performed on conjunctival swabs were positive for SARS-CoV-2. Although this suggests that SARS-CoV-2 is likely present and detectable in the conjunctiva, this detection method has low diagnostic potential. [ABSTRACT FROM AUTHOR]

The TMPRSS2 protease plays a key role in the entry of the SARS-CoV-2 into cells. The TMPRSS2 gene is highly polymorphic in humans, and some polymorphisms may affect the susceptibility to COVID-19 or disease severity. rs75603675 (c.23G > T) is a missense variant that causes the replacement of glycine with valine at position 8 (p.G8V) in the TMPRSS2 isoform 1. According to GnomAD v4.0.0 database, the allele frequency of the rs75603675 on a global scale is 38.10 %, and range from 0.92 % in East Asian to 40.77 % in non-Finnish European (NFE) population. We analyzed the occurrence of the rs75603675 in two cohorts of patients, the first with severe/critical COVID-19 enrolled in a French hospital (42 patients), and the second with predominantly asymptomatic/pauci-symptomatic/mild COVID-19 enrolled in an Italian hospital (69 patients). We found that the TMPRSS2 -c.23T minor allele frequency was similar in the two cohorts, 46.43 % and 46.38 %, respectively, and higher than the frequency in the NFE population (40.77 %). Chi-square test provided significant results (p < 0.05) when the genotype data (TMPRSS2 -c.23T/c.23T homozygotes + TMPRSS2 -c.23G/c.23T heterozygotes vs. TMPRSS2 -c.23G/c.23G homozygotes) of the two patient groups were pooled and compared to the expected data for the NFE population, suggesting a possible pathogenetic mechanism of the p.G8V substitution. We explored the possible effects of the p.G8V substitution and found that the N-terminal region of the TMPRSS2 isoform 1 contains a signal for clathrin/AP-2-dependent endocytosis. In silico analysis predicted that the p.G8V substitution may increase the accessibility to the endocytic signal, which could help SARS-CoV-2 enter cells. • Polymorphism rs75603675 is a missense variant that causes the replacement of glycine with valine at position 8 in TMPRSS2 • Minor allele of rs75603675 is associated with increased susceptibility to COVID-19 in a retrospective cohort analysis. • G8V substitution affects the stability of the N-terminal region of the TMPRSS2 as revealed by molecular dynamic simulation. • In silico analysis shows that an endocytic signal may be more exposed in TMPRSS2-p.8V variant, helping the virus enter cells. [ABSTRACT FROM AUTHOR]

Inhibition of autophagy is one of the hallmarks of the SARS-CoV-2 infection. Recently it was reported that SARS-CoV-2 protein ORF3a inhibits fusion of autophagosomes with lysosomes via interaction with VPS39 thus preventing binding of homotypic fusion and protein sorting (HOPS) complex to RAB7 GTPase. Here we report that myelin basic protein (MBP), a major structural component of the myelin sheath, binds ORF3a and is colocalized with it in mammalian cells. Co-expression of MBP with ORF3a restores autophagy in mammalian cells, inhibited by viral protein. Our data suggest that basic charge of MBP drives suppression of ORF3a-induced autophagy inhibition as its deaminated variants lost ability to bind ORF3a and counteract autophagy blockade. These results together with our recent findings, indicating that MBP interacts with structural components of the vesicle transport machinery-synaptosomal-associated protein 23 (SNAP23), vesicle-associated membrane protein 3 (VAMP3) and Sec1/Munc18-1 family members, may suggest protective role of the MBP in terms of the maintaining of protein traffic and autophagosome–lysosome fusion machinery in oligodendrocytes during SARS-CoV-2 infection. Finally, our data may indicate that deimination of MBP observed in the patients with multiple sclerosis (MS) may contribute to the previously reported worser outcomes of COVID-19 and increase of post-COVID-19 neurologic symptoms in patients with MS. [Display omitted] • MBP interacts with SARS-CoV-2 proteins N, E, nsp9 and nsp16 in mammalian cells. • MBP interacts and colocalizes with SARS-CoV-2 protein ORF3a in mammalian cells. • MBP counteracts ORF3a-mediated failure of the autophagy machinery. • Basic charge of MBP drives suppression of ORF3a-induced autophagy inhibition. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic affected daily life significantly and had massive consequences for healthcare systems with tremendous regional differences. This retrospective study aimed to investigate whether the pandemic and resulting societal changes impacted the diagnosis of pediatric malignancies in a distinct region. Pediatric cancer cases in Bavaria (2016–2021) and SARS-CoV-2 proceedings during the peak phase of the pandemic (2020–2021) were retrospectively analyzed. All new diagnoses of pediatric malignancies reported from cancer centers in Bavaria were included. Clinical data from pre-pandemic years was compared to diagnoses made during the pandemic. Official SARS-CoV-2 reports were received from the Bavarian Health and Food Safety Authority and data on regional pandemic measures were obtained from the Healthcare Data Platform. With this design, a comprehensive analysis of the pandemic proceedings was performed. We found significantly decreased incidence-rate ratios for pediatric cancer diagnosis during the early spring peak of SARS-CoV-2 as it was observed in May during the pandemic, followed by non-significantly increased metastatic cancer diagnosis two months later. Additionally, the time-to-diagnosis of pediatric malignancies was significantly prolonged during the pandemic, and outpatient contacts were significantly reduced, although the availability of consultations remained the same. From our findings, we may hypothesize that there have been effects on pediatric cancer diagnosis during the COVID-19 pandemic at vulnerable times. Interpretation of changes remains speculative with potential causes from behavior patterns, such as hesitation, concerns, and potential societal changes during phases of public restrictions, rather than overwhelmed medical capacities. Nevertheless, specific awareness is needed to protect this patient population during potential future pandemics. [ABSTRACT FROM AUTHOR]

Fatigue is a pervasive symptom experienced by many individuals after COVID-19. Despite its widespread occurrence, fatigue remains a poorly understood and complex phenomenon. Our aim is to evaluate the subjective experience of mental fatigue after COVID-19 and to assess its significance for daily life functioning. In this online questionnaire study (N = 220), the Fatigue Severity Scale (FSS), World Health Organization Quality-of-Life assessment (WHOQoL) and a subjective severity rating of the COVID-19 disease progression were used. For our statistical analyses we utilized independent samples t-tests, one-way ANOVA with post-hoc analyses, and a multiple regression. As expected our findings revealed the COVID group reported significantly higher levels of subjective fatigue compared to the control group. Moreover, there was a significant difference between experienced fatigue across the four severity groups. Participants who had a milder course of disease also experienced severe subjective fatigue. Subjective fatigue explained 40% variance in quality-of-life. In conclusion, severe subjective fatigue appears to be associated with increased self-reported COVID-19 symptom severity and lower quality-of-life but is already observable in milder cases. This underscores, firstly, the importance of considering also less severe cases and, secondly, the need to develop rehabilitation and psychological interventions for fatigue. [ABSTRACT FROM AUTHOR]

Background and purpose: In October 2020, the European Academy of Neurology (EAN) consensus statement for management of patients with neurological diseases during the coronavirus disease 2019 (COVID‐19) pandemic was published. Due to important changes and developments that have happened since then, the need has arisen to critically reassess the original recommendations and address new challenges. Methods: In step 1, the original items were critically reviewed by the EAN COVID‐19 Task Force. In addition, new recommendations were defined. In step 2, an online survey with the recommendations forged in step 1 was sent to the Managing Groups of all Scientific and Coordinating Panels of EAN. In step 3, the final set of recommendations was made. Results: In step 1, out of the original 36 recommendations, 18 were judged still relevant. They were edited to reflect the advances in knowledge and practice. In addition, 21 new recommendations were formulated to address the new knowledge and challenges. In step 2, out of the 39 recommendations sent for the survey, nine were approved as they were, whilst suggestions for improvement were given for the rest. In step 3, the recommendations were further edited, and some new items were formed to accommodate the participants' suggestions, resulting in a final set of 41 recommendations. Conclusion: This revision of the 2020 EAN Statement provides updated comprehensive and structured guidance on good clinical practice in people with neurological disease faced with SARS‐CoV‐2 infection. It now covers the issues from the more recent domains of COVID‐19‐related care, vaccine complications and post‐COVID‐19 conditions. [ABSTRACT FROM AUTHOR]

The Coronavirus Disease 2019 (COVID-19) has caused massive losses for the global economy. Scholars have used different methods to study the transmission mode and influencing factors of the virus to find effective methods to provide people with a healthy built environment. However, these studies arrived at different or even contradictory conclusions. This review presents the main research methodologies utilized in this field, summarizes the main investigation methods, and critically discusses their related conclusions. Data statistical analysis, sample collection, simulation models, and replication transmission scenarios are the main research methods. The summarized conclusion for prevention from all reviewed papers are: adequate ventilation and proper location of return air vents, proper use of personal protective equipment, as well as the reasonable and strict enforcement of policies are the main methods for reducing the transmission. Recommendations including standardized databases, causation clarification, rigorous experiment design, improved simulation accuracy and verification are provided. [ABSTRACT FROM AUTHOR]

Introduction: Japan will be transitioning from the free-of-charge COVID-19 vaccination program to annual periodic vaccination under a national immunization program for old adults and high-risk patients from 2024 fall/winter season. The policy transition including out-of-pocket payment requirement may discourage vaccination, leading to a lower vaccination rate. This study aimed to estimate the impact of varying vaccination rates with BNT162b2 COVID-19 mRNA vaccine on economics and public health in an illustrative prefecture which administers and promotes the periodic vaccination program, using budget impact analysis. Methods: A combined cohort Markov decision tree model estimated the public health outcomes of COVID-19-related symptomatic cases, hospitalizations and deaths; and the economic outcomes including vaccine-related cost, non-vaccine-related medical cost, and productivity loss from the societal perspective. The base case examined the impact on the outcomes when vaccination coverage changed from the reference value of 50% to upper and lower values, respectively. Scenario analyses were performed based on multiple scenarios. Results: Increase in the vaccination rate demonstrated improvement in all public health outcomes. At 50% vaccination, the vaccine-related cost for 3 years in a prefecture was estimated at JPY 7.58 billion (USD 57.67 million), the non-vaccine-related medical cost at JPY 79.22 billion (USD 602.48 million), the productivity loss at JPY 253.11 billion (USD 1.92 billion), and the total cost at JPY 339.92 billion (USD 2.59 billion). When the vaccination rate increased to 90%, the total cost decreased by JPY 4.88 billion (USD 37.11 million) (1.4%). When the vaccination rate decreased to 10%, the total cost increased by JPY 5.73 billion (USD 43.58 million) (1.7%). Results were consistent across almost all scenario analyses. Conclusions: Maintaining a high vaccination rate with BNT162b2 is important from both public health and economic perspectives in Japan. The findings highlight to local governments the importance of continued effort to promote vaccination. [ABSTRACT FROM AUTHOR]

Introduction: The monoclonal antibody therapies bamlanivimab (BAM) + etesevimab (ETE) received emergency use authorization (EUA) from the US Food and Drug Administration (February 9, 2021) for treatment of mild-to-moderate COVID-19. The EUA of BAM + ETE was revoked (December 14, 2023) due to the high prevalence of BAM + ETE-resistant variants of SARS-CoV-2. Efficacy and safety of 700/1400 mg and 2800/2800 mg BAM + ETE are well established and published; however, efficacy and safety of 350/700 mg BAM + ETE have not been disclosed to date. Methods: This portion of phase 3, BLAZE-1 trial (J2X-MC-PYAB) enrolled patients (between June 17, 2020 and April 9, 2021) with mild-to-moderate COVID-19 within 3 days of laboratory diagnosis of SARS-CoV-2 infection. In total, 354 patients with at least one risk factor for severe COVID-19 were enrolled, randomized (2:3), and infused with placebo (N = 141) or 350/700 mg BAM + ETE (N = 213), over ~ 8 min. Primary endpoint was to assess proportion of patients with persistently high SARS-CoV-2 viral load (PHVL) (log viral load > 5.27) 7 days after infusion. Results: Patients were aged (mean) 53 years, 49.7% female, and 82.7% White. Seven days after drug infusion, 10.8% (95% confidence interval: 6.6, 15.0; p < 0.001) of BAM + ETE-treated patients and 34.8% (26.9, 42.6) of placebo-treated patients had PHVL, and the viral load change from baseline (least square mean [standard error]) was − 3.50 (0.15; p < 0.001) in BAM + ETE-treated patients versus − 2.51 (0.19) in placebo-treated patients. The majority of treatment-emergent adverse events were considered mild or moderate in severity (BAM + ETE: 6.6%; placebo: 14.2%). No deaths were reported. Conclusions: Consistent with previous studies, patients treated with BAM + ETE (350/700 mg) had a significantly lower proportion of PHVL and greater reduction in viral load compared with placebo. The overall safety profile is consistent with higher doses of BAM + ETE. Infusions of over ~ 8 min did not result in meaningful increase in incidence of TEAEs compared to higher doses of BAM + ETE administered over 30–60 min. Trial Registration: Clinical trial.gov identifier, NCT04427501. [ABSTRACT FROM AUTHOR]

This document is a response to a letter to the editor that raised questions about the methodology used in a systematic literature review and meta-analysis comparing the effectiveness of two COVID-19 vaccines, mRNA-1273 and BNT162b2, among older adults. The authors of the response defend their methodology and conclusions, disagreeing with the claim that their analysis was based on inaccurate and out-of-date data. They also address concerns about the use of crude data in the meta-analysis, the exclusion of eligible studies, and errors in data extraction. The authors maintain the validity of their methods and affirm that they followed the appropriate analysis framework. This document is a response to criticisms made by Volkman and colleagues regarding a meta-analysis conducted by Kavikondala et al. The response addresses specific points raised by Volkman and provides clarification and evidence to support the original study's methodology and findings. The authors disagree with Volkman's opinion that there is no difference in effectiveness between the mRNA COVID-19 vaccines and argue that the literature supports their findings. The response also acknowledges the funding and contributions of Moderna, Inc. and ICON plc in conducting the study and providing medical writing assistance. [Extracted from the article]

This letter to the editor raises concerns about a systematic review and meta-analysis comparing the vaccine effectiveness of mRNA-1273 and BNT162b2 COVID-19 vaccines in adults aged 50 and older. The authors argue that the meta-analysis was flawed because it used crude data instead of adjusted estimates, leading to incorrect conclusions and exaggerated differences in vaccine effectiveness. They also criticize the inclusion of studies that were not head-to-head comparisons and the reliance on outdated data that does not reflect the current state of population immunity against SARS-CoV-2. The authors conclude that recent studies during the Omicron era have shown no difference in effectiveness between the two vaccines. [Extracted from the article]

Since the start of the pandemic, considerable advancements have been made in our understanding of the effects of SARS-CoV-2 infection and the associated COVID-19 on the hepatic system. There is a broad range of clinical symptoms for COVID-19. It affects multiple systems and has a dominant lung illness depending on complications. The progression of COVID-19 in people with pre-existing chronic liver disease (CLD) has also been studied in large multinational groups. Notably, SARS-CoV-2 infection is associated with a higher risk of hepatic decompensation and death in patients with cirrhosis. In this review, the source, composition, mechanisms, transmission characteristics, clinical characteristics, therapy, and prevention of SARS-CoV-2 were clarified and discussed, as well as the evolution and variations of the virus. This review briefly discusses the causes and effects of SARS-CoV-2 infection in patients with CLD. As part of COVID-19, In addition, we assess the potential of liver biochemistry as a diagnostic tool examine the data on direct viral infection of liver cells, and investigate potential pathways driving SARS-CoV-2-related liver damage. Finally, we explore how the pandemic has had a significant impact on patient behaviors and hepatology services, which may increase the prevalence and severity of liver disease in the future. The topics encompassed in this review encompass the intricate relationships between SARS-CoV-2, liver health, and broader health management strategies, providing valuable insights for both current clinical practice and future research directions. [ABSTRACT FROM AUTHOR]

In severe COVID-19 cases, an exacerbated inflammatory response triggers a cytokine storm that can worsen the prognosis. Compounds with both antiviral and anti-inflammatory activities show promise as candidates for COVID-19 therapy, as they potentially act against the SARS-CoV-2 infection regardless of the disease stage. One of the most attractive drug targets among coronaviruses is the main protease (MPro). This enzyme is crucial for cleaving polyproteins into non-structural proteins required for viral replication. The aim of this review was to identify SARS-CoV-2 MPro inhibitors with both antiviral and anti-inflammatory properties. The interactions of the compounds within the SARS-CoV-2 MPro binding site were analyzed through molecular docking when data from crystallographic structures were unavailable. 18 compounds were selected and classified into five different superclasses. Five of them exhibit high potency against MPro: GC-376, baicalein, naringenin, heparin, and carmofur, with IC50 values below 0.2 μM. The MPro inhibitors selected have the potential to alleviate lung edema and decrease cytokine release. These molecules mainly target three critical inflammatory pathways: NF-κB, JAK/STAT, and MAPK, all previously associated with COVID-19 pathogenesis. The structures of the compounds occupy the S1/S2 substrate binding subsite of the MPro. They interact with residues from the catalytic dyad (His41 and Cys145) and/or with the oxyanion hole (Gly143, Ser144, and Cys145), which are pivotal for substrate recognition. The MPro SARS-CoV-2 inhibitors with potential anti-inflammatory activities present here could be optimized for maximum efficacy and safety and be explored as potential treatment of both mild and severe COVID-19. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The coronavirus 2019 (COVID-19) pandemic has evolved over time by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant, disease severity, treatment, and prevention. There is evidence of an elevated risk of incident diabetes after COVID-19; our objective was to evaluate whether this association is consistent across time and with contemporary viral variants. RESEARCH DESIGN AND METHODS: We conducted a retrospective cohort study using National COVID Cohort Collaborative (N3C) data to evaluate incident diabetes risk among COVID-positive adults compared with COVID-negative patients or control patients with acute respiratory illness (ARI). Cohorts were weighted on demographics, data site, and Charlson comorbidity index score. The primary outcome was the cumulative incidence ratio (CIR) of incident diabetes for each viral variant era. RESULTS: Risk of incident diabetes 1 year after COVID-19 was increased for patients with any viral variant compared with COVID-negative control patients (ancestral CIR 1.16 [95% CI 1.12–1.21]; Alpha CIR 1.14 [95% CI 1.11–1.17]; Delta CIR 1.17 [95% CI 1.13–1.21]; Omicron CIR 1.13 [95% CI 1.10–1.17]) and control patients with ARI (ancestral CIR 1.17 [95% CI 1.11–1.22]; Alpha CIR 1.14 [95% CI 1.09–1.19]; Delta CIR 1.18 [95% CI 1.11–1.26]; Omicron CIR 1.20 [95% CI 1.13–1.27]). There was latency in the timing of incident diabetes risk with the Omicron variant; in contrast with other variants, the risk presented after 180 days. CONCLUSIONS: Incident diabetes risk after COVID-19 was similar across different SARS-CoV-2 variants. However, there was greater latency in diabetes onset in the Omicron variant era. [ABSTRACT FROM AUTHOR]

The primary aim of this investigation is to shed light on potential targets within the main protease Mpro, spike protein of SARS-CoV-2, and Angiotensine converting enzyme 2 (ACE2) for the exploration of novel inhibitors derived from therapeutic natural compounds originating from Atriplex halimus (AH). Many constituents were discerned within AH extracts through comprehensive gas chromatography/mass spectrometry (GC/MS). Notably, compounds, such as oleocanthal and methyl stearate, exhibited promising attributes across various biological activities, including inhibition of key proteins associated with SARS-CoV-2. Furthermore, absorption, distribution, metabolism, excretion, and toxicity (ADMET) settings were evaluated to explore the potential safety and viability of these compounds for pharmaceutical application, affirming their non-interference with human physiology and thus suggesting their suitability for pharmaceutical use. Catechin, epigallocatechin, and methyl stearate were discovered to be the compounds with the highest affinity to the studied protein showing a great potential to be inhibitors to COVID-19. Consequently, this discovery highlights Atriplex halimus as a promising candidate for utilization in combating the virus. In our study, several compounds from Atriplex halimus showed a significant inhibition activity against SARS-COV-2 Mpro and Spike protein, which promotes Atriplex halimus as a potential agent that can be used in the treatment of COVID-19. [ABSTRACT FROM AUTHOR]

The impact of the COVID‐19 pandemic on xenophobia in South Africa is little understood. The Behavioural Immune System (BIS) theory would predict that hostility towards immigrants increases during periods of heightened pathogen stress. This BIS‐hypothesis is tested against the relative strength of three other possible drivers of anti‐immigrant sentiment. These included anger at the national lockdown system, intertemporal relative deprivation, and racial transformation ideology. For these tests nationally representative data (N = 2996), gathered during the height of the 'Omicron' wave, were used. Multivariate analysis showed that COVID‐19 exposure was not associated with more negative sentiments towards immigrants. Fear‐based reactions to the Coronavirus were, in fact, correlated with pro‐immigrant attitudes. Intertemporal relative deprivation and transformation orientations were much better predictors of anti‐immigrant sentiment than pathogen stress. These findings raised questions about the applicability of the BIS‐hypothesis in the context of the Coronavirus and suggest new avenues of academic inquiry. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19), a kind of respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), primarily spreads through the respiratory tract from human to human. Its extensive and rapid spread has led to a global pandemic, causing great harm to human health and economic development all over the world. Current known evidence indicates that SARS-CoV-2 has evolved accumulating multiple mutations, with altered infectivity and viral replication capacity. A better understanding of the complications of COVID-19 and its relationship with underlying diseases is crucial for the prevention and treatment of SARS-CoV-2. This case series reviewed case data of our 4 recent patients with severe or critical COVID-19, including treatment plan, status of pulmonary infection and their microbiology workup with metagenomic next-generation sequencing with bronchoalveolar lavage fluid. This report shed light on the significance of rapid and accurate clinical diagnosis and treatment on COVID-19. [ABSTRACT FROM AUTHOR]

Using a stratified sample of German residents (N = 1,508), we examined intentions to avoid information about vaccination against COVID-19. The study was guided by the planned risk information seeking model (PRISM), also taking into consideration benefit perceptions, positive affective responses, and discrete emotions. Our findings generally supported the utility of the extended PRISM to predict information avoidance intentions; most of the hypothesized relationships were supported and the model accounted for 58.8% of the variance in intentions to avoid information about COVID-19 vaccination. Furthermore, perceived benefits of vaccination, and positive affect felt toward vaccination played significant roles in explaining intentions to avoid information about vaccination. A more nuanced view on affective predictors showed that hope and interest were weakly associated with less pronounced avoidance intent, whereas we found no link between avoidance intent and fear, anxiety, and anger. [ABSTRACT FROM AUTHOR]

Background: Immunocompromised individuals are at high risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and subsequent severe or fatal coronavirus disease 2019 (COVID-19), yet they have suboptimal responses to mRNA and inactivated COVID-19 vaccines. The efficacy of tixagevimab–cilgavimab in reducing symptomatic SARS-CoV-2 infection was demonstrated in phase III clinical trials. Nevertheless, real-world data on the effectiveness and safety of tixagevimab–cilgavimab remain limited. Objective: The aim was to evaluate the effectiveness and safety of tixagevimab–cilgavimab among immunocompromised individuals. Methods: Adults who were immunocompromised or receiving immunosuppressive therapies were included in this target trial emulation using territory-wide electronic health records in Hong Kong. A sequential trial emulation approach was adopted to compare effectiveness and safety outcomes between individuals who received tixagevimab–cilgavimab and individuals who did not. Results: A total of 746 tixagevimab–cilgavimab recipients and 2980 controls were included from 1 May 2022 to 30 November 2022. Tixagevimab–cilgavimab significantly reduced the risk of COVID-19 infection (hazard ratio [HR] 0.708, 95% confidence interval [CI] 0.527–0.951) during a median follow-up of 60 days. No significant difference was observed in the risk of COVID-19-related hospitalisation. Zero versus eight COVID-19 mortality cases and zero versus two severe COVID-19 cases were observed in tixagevimab–cilgavimab recipients and controls, respectively. Notably, significant risk reduction in COVID-19 infection was also observed among immunocompromised individuals who had been previously vaccinated with three or more doses of COVID-19 vaccine, or had no prior COVID-19 infection history. Conclusions: Tixagevimab–cilgavimab was effective in reducing COVID-19 infection among immunocompromised patients during the Omicron wave. Findings were consistent among individuals who previously received three or more doses of COVID-19 vaccine, or had no previous history of COVID-19 infection. [ABSTRACT FROM AUTHOR]

In 2016, we initiated a quality improvement endeavor to increase pediatric heart offer acceptance. This study assessed the effect of these interventions at our center. We evaluted pre- and postimplementation cohorts (January 1, 2008-December 31, 2016 vs January 1, 2017-July 1, 2023) comparing donor heart utilization. Six interventions were iterated over time to increase offer acceptance ("extended criteria"): ABO-incompatible transplant, ex vivo perfusion for distanced donors, 3-dimensional total cardiac volume (TCV) assessment, acceptance of hepatitis-C or Severe Acute Respiratory Syndrome Coronavirus 2 infected donors, and institutional culture change favoring consideration of donors previously considered unacceptable. Outcomes studied included annual HT volume, median waitlist duration, sequence number at acceptance, and post-transplant clinical outcomes. During the study period, annual transplant volume increased from 16/year to 25/year pre- and postimplementation. Three hundred thirteen of 389 (80%) listed patients were transplanted. Waitlist duration shortened postimplementation (p = 0.01), as did the percentage of accepted heart offers utilizing at least 1 extended criterion (p < 0.001). Institutional culture change and TCV assessment had the largest impact on donor heart utilization (p = 0.04 and p < 0.001). There was no difference in post-HT intubation or intensive care unit days (p = 0.05-0.9), though post-transplant hospitalization duration (p < 0.001) increased. Post-transplant survival was unaffected by the use of extended criteria hearts (p = 0.3). We report a successful longitudinal, multifaceted effort to increase organ offer utilization, with institutional culture change and TCV assessments most impactful. The use of extended criteria hearts was not associated with inferior survival. [ABSTRACT FROM AUTHOR]

• The accurate identification of phosphorylation sites in SARS-CoV-2-infected host cells would contribute to the investigation of SARS-CoV-2 pathogenic mechanism and the mining of candidate therapy targets. • This work constructed a phosphorylation site computational approach (named PhosBERT) based on a pre-trained protein language model through self-supervised learning from the BERT architecture. • Prediction accuracy and AUC for SARS-CoV-2-infected serine and threonine phosphorylation sites are 81.9% and 0.896. • Prediction accuracy and AUC for SARS-CoV-2-infected tyrosine phosphorylation sites are 87.1% and 0.902. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a single-stranded RNA virus, which mainly causes respiratory and enteric diseases and is responsible for the outbreak of coronavirus disease 19 (COVID-19). Numerous studies have demonstrated that SARS-CoV-2 infection will lead to a significant dysregulation of protein post-translational modification profile in human cells. The accurate recognition of phosphorylation sites in host cells will contribute to a deep understanding of the pathogenic mechanisms of SARS-CoV-2 and also help to screen drugs and compounds with antiviral potential. Therefore, there is a need to develop cost-effective and high-precision computational strategies for specifically identifying SARS-CoV-2-infected phosphorylation sites. In this work, we first implemented a custom neural network model (named PhosBERT) on the basis of a pre-trained protein language model of ProtBert, which was a self-supervised learning approach developed on the Bidirectional Encoder Representation from Transformers (BERT) architecture. PhosBERT was then trained and validated on serine (S) and threonine (T) phosphorylation dataset and tyrosine (Y) phosphorylation dataset with 5-fold cross-validation, respectively. Independent validation results showed that PhosBERT could identify S/T phosphorylation sites with high accuracy and AUC (area under the receiver operating characteristic) value of 81.9% and 0.896. The prediction accuracy and AUC value of Y phosphorylation sites reached up to 87.1% and 0.902. It indicated that the proposed model was of good prediction ability and stability and would provide a new approach for studying SARS-CoV-2 phosphorylation sites. [ABSTRACT FROM AUTHOR]