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Nearly six million people worldwide have died from the coronavirus disease (COVID-19) outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Although COVID-19 vaccines are largely successful in reducing the severity of the disease and deaths, the decline in vaccine-induced immunity over time and the continuing emergence of new viral variants or mutations underscore the need for an alternative strategy for developing broad-spectrum host-mediated therapeutics against SARS-CoV-2. A key feature of severe COVID-19 is dysregulated innate immune signaling, culminating in a high expression of numerous pro-inflammatory cytokines and chemokines and a lack of antiviral interferons (IFNs), particularly type I (alpha and beta) and type III (lambda). As a natural host defense, the myeloid differentiation primary response protein, MyD88, plays pivotal roles in innate and acquired immune responses via the signal transduction pathways of Toll-like receptors (TLRs), a type of pathogen recognition receptors (PRRs). However, recent studies have highlighted that infection with viruses upregulates MyD88 expression and impairs the host antiviral response by negatively regulating type I IFN. Galectin-3 (Gal3), another key player in viral infections, has been shown to modulate the host immune response by regulating viral entry and activating TLRs, the NLRP3 inflammasome, and NF-κB, resulting in the release of pro-inflammatory cytokines and contributing to the overall inflammatory response, the so-called "cytokine storm". These studies suggest that the specific inhibition of MyD88 and Gal3 could be a promising therapy for COVID-19. This review presents future directions for MyD88- and Gal3-targeted antiviral drug discovery, highlighting the potential to restore host immunity in SARS-CoV-2 infections. [ABSTRACT FROM AUTHOR]

The novel coronavirus disease 2019 (COVID-19) pandemic outbreak caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has garnered unprecedented global attention. It caused over 2.47 million deaths through various syndromes such as acute respiratory distress, hypercoagulability, and multiple organ failure. The viral invasion proceeds through the ACE2 receptor, expressed in multiple cell types, and in some patients caused serious damage to tissues, organs, immune cells, and the microbes that colonize the gastrointestinal tract (GIT). Some patients who survived the SARS-CoV-2 infection have developed months of persistent long-COVID-19 symptoms or post-acute sequelae of COVID-19 (PASC). Diagnosis of these patients has revealed multiple biological effects, none of which are mutually exclusive. However, the severity of COVID-19 also depends on numerous comorbidities such as obesity, age, diabetes, and hypertension and care must be taken with respect to other multiple morbidities, such as host immunity. Gut microbiota in relation to SARS-CoV-2 immunopathology is considered to evolve COVID-19 progression via mechanisms of biochemical metabolism, exacerbation of inflammation, intestinal mucosal secretion, cytokine storm, and immunity regulation. Therefore, modulation of gut microbiome equilibrium through food supplements and probiotics remains a hot topic of current research and debate. In this review, we discuss the biological complications of the physio-pathological effects of COVID-19 infection, GIT immune response, and therapeutic pharmacological strategies. We also summarize the therapeutic targets of probiotics, their limitations, and the efficacy of preclinical and clinical drugs to effectively inhibit the spread of SARS-CoV-2. [ABSTRACT FROM AUTHOR]

Background: Dynamical mathematical models defined by a system of differential equations are typically not easily accessible to non-experts. However, forecasts based on these types of models can help gain insights into the mechanisms driving the process and may outcompete simpler phenomenological growth models. Here we introduce a friendly toolbox, SpatialWavePredict, to characterize and forecast the spatial wave sub-epidemic model, which captures diverse wave dynamics by aggregating multiple asynchronous growth processes and has outperformed simpler phenomenological growth models in short-term forecasts of various infectious diseases outbreaks including SARS, Ebola, and the early waves of the COVID-19 pandemic in the US. Results: This tutorial-based primer introduces and illustrates a user-friendly MATLAB toolbox for fitting and forecasting time-series trajectories using an ensemble spatial wave sub-epidemic model based on ordinary differential equations. Scientists, policymakers, and students can use the toolbox to conduct real-time short-term forecasts. The five-parameter epidemic wave model in the toolbox aggregates linked overlapping sub-epidemics and captures a rich spectrum of epidemic wave dynamics, including oscillatory wave behavior and plateaus. An ensemble strategy aims to improve forecasting performance by combining the resulting top-ranked models. The toolbox provides a tutorial for forecasting time-series trajectories, including the full uncertainty distribution derived through parametric bootstrapping, which is needed to construct prediction intervals and evaluate their accuracy. Functions are available to assess forecasting performance, estimation methods, error structures in the data, and forecasting horizons. The toolbox also includes functions to quantify forecasting performance using metrics that evaluate point and distributional forecasts, including the weighted interval score. Conclusions: We have developed the first comprehensive toolbox to characterize and forecast time-series data using an ensemble spatial wave sub-epidemic wave model. As an epidemic situation or contagion occurs, the tools presented in this tutorial can facilitate policymakers to guide the implementation of containment strategies and assess the impact of control interventions. We demonstrate the functionality of the toolbox with examples, including a tutorial video, and is illustrated using daily data on the COVID-19 pandemic in the USA. [ABSTRACT FROM AUTHOR]

An outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), epi-centred in Hubei Province of the People's Republic of China, quickly spread worldwide and caused COVID-19 pandemic. It infected hundreds of millions of people and caused millions of deaths. In this paper, we develop a compartmental ODE model of COVID-19 transmission. We consider a possibility of breakthrough infections after the vaccination and account for both symptomatic and asymptomatic infections and transmissions. We also incorporate game theory to study the optimal vaccination decisions from the individuals' perspective. We show that vaccination alone is unlikely to eliminate COVID-19. To achieve herd immunity, the individuals would have to receive a dose of a vaccine more frequently than once every 3 months. It is therefore crucial to adhere to various guidelines, such as quarantine, isolate and wear a mask if tested positive for COVID-19. [ABSTRACT FROM AUTHOR]

Human coronavirus (hCoV) OC43 is endemic to global populations and usually causes asymptomatic or mild upper respiratory tract illness. Here, we demonstrate the neutralization efficacy of isolated nanobodies from alpacas immunized with the S1B and S1C domain of the hCoV-OC43 spike glycoprotein. A total of 40 nanobodies bound to recombinant OC43 protein with affinities ranging from 1 to 149 nM. Two nanobodies WNb 293 and WNb 294 neutralized virus at 0.21 and 1.79 nM, respectively. Intranasal and intraperitoneal delivery of WNb 293 fused to an Fc domain significantly reduced nasal viral load in a mouse model of hCoV-OC43 infection. Using X-ray crystallography, we observed that WNb 293 bound to an epitope on the OC43 S1B domain, distal from the sialoglycan-binding site involved in host cell entry. This result suggests that neutralization mechanism of this nanobody does not involve disruption of glycan binding. Our work provides characterization of nanobodies against hCoV-OC43 that blocks virus entry and reduces viral loads in vivo and may contribute to future nanobody-based therapies for hCoV-OC43 infections. IMPORTANCE The pandemic potential presented by coronaviruses has been demonstrated by the ongoing COVID-19 pandemic and previous epidemics caused by severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome coronavirus. Outside of these major pathogenic coronaviruses, there are four endemic coronaviruses that infect humans: hCoV-OC43, hCoV-229E, hCoV-HKU1, and hCoV-NL63. We identified a collection of nanobodies against human coronavirus OC43 (hCoV-OC43) and found that two high-affinity nanobodies potently neutralized hCoV-OC43 at low nanomolar concentrations. Prophylactic administration of one neutralizing nanobody reduced viral loads in mice infected with hCoV-OC43, showing the potential for nanobody-based therapies for hCoV-OC43 infections. [ABSTRACT FROM AUTHOR]

Over the past decade, the global outbreaks of SARS, influenza A (H1N1), COVID-19, and other major infectious diseases have exposed the insufficient capacity for emergency disposal of medical waste in numerous countries and regions. Particularly during epidemics of major infectious diseases, medical waste exhibits new characteristics such as accelerated growth rate, heightened risk level, and more stringent disposal requirements. Consequently, there is an urgent need for advanced theoretical approaches that can perceive, predict, evaluate, and control risks associated with safe disposal throughout the entire process in a timely, accurate, efficient, and comprehensive manner. This article provides a systematic review of relevant research on collection, storage, transportation, and disposal of medical waste throughout its entirety to illustrate the current state of safe disposal practices. Building upon this foundation and leveraging emerging information technologies like Internet of Things (IoT), cloud computing, big data analytics, and artificial intelligence (AI), we deeply contemplate future research directions with an aim to minimize risks across all stages of medical waste disposal while offering valuable references and decision support to further advance safe disposal practices. [ABSTRACT FROM AUTHOR]

The highly pathogenic coronaviruses SARS-CoV-2 and SARS-CoV have led to the COVID-19 pandemic and SARS outbreak, respectively. The receptor-binding domain (RBD) of the spike (S) protein of SARS-CoV-2, particularly the Omicron variant, has frequent mutations, resulting in the reduced efficiency of current COVID-19 vaccines against new variants. Here, we designed two lipid nanoparticle-encapsulated mRNA vaccines by deleting the mutant RBD of the SARS-CoV-2 Omicron variant (SARS2-S (RBD-del)) or by replacing this mutant RBD with the conserved and potent RBD of SARS-CoV (SARS2-S (SARS-RBD)). Both mRNA vaccines were stable at various temperatures for different time periods. Unlike SARS2-S (RBD-del) mRNA, SARS2-S (SARS-RBD) mRNA elicited effective T-cell responses and potent antibodies specific to both SARS-CoV-2 S and SARS-CoV RBD proteins. It induced strong neutralizing antibodies against pseudotyped SARS-CoV-2 and SARS-CoV infections and protected immunized mice from the challenge of the SARS-CoV-2 Omicron variant and SARS-CoV by significantly reducing the viral titers in the lungs after Omicron challenge and by completely preventing SARS-CoV-induced weight loss and death. SARS2-S (SARS-RBD)-immunized serum antibodies protected naïve mice from the SARS-CoV challenge, with its protective efficacy positively correlating with the neutralizing antibody titers. These findings indicate that this mRNA vaccine has the potential for development as an effective vaccine against current and future SARS-CoV-2 variants and SARS-CoV. [ABSTRACT FROM AUTHOR]

Background: Taiwan, deeply impacted by the 2003 SARS outbreak, promptly implemented rigorous infection control and prevention (ICP) measures in January 2020 to combat the global COVID-19 pandemic. This cross-sectional serologic study was conducted among healthcare workers (HCWs) in a tertiary care hospital in Taiwan from August 1, 2022, to February 28, 2023. The study aimed to assess HCWs' antibody responses to COVID-19 vaccination against Omicron subvariants BA.1, BA.4, and BA.5, considering variations in prior infection. Additionally, it evaluated the effectiveness of ICP and vaccination policies within the hospital setting in Taiwan. Methods: A cross-sectional serology study was conducted in Taiwan to investigate the seroprevalence rates of Omicron subvariants BA.1, BA.4, and BA.5 among HCWs. A total of 777 HCWs participated in this study. A structured questionnaire was collected to obtain the epidemiological characteristics and risk factors for potential exposure. Enzyme-linked immunosorbent assay was used to detect antibody responses. Serum samples were selected for protection against Omicron subvariants BA.1, BA.4, and BA.5 by using a pseudotyped-based neutralization assay. Results: More than 99% of the participants had received SARS-CoV-2 vaccination. Overall, 57.7% had been infected with SARS-CoV-2, with some being asymptomatic. The SARS-CoV-2 Anti-Spike S1 protein IgG (Anti-S) distribution was 40,000 AU/mL for 20.2% (157/777) of participants, with a mean ± standard deviation of 23,442 ± 22,086. The decay curve for Anti-S was less than 20,000 AU/ml after 120 days. The probability curve of 50% neutralization showed an Anti-S of 55,000 AU/ml. The optimum Anti-S was 41,328 AU/mL (equal to 5,869 WHO's standard BAU/mL), with 86.1% sensitivity and 63.5% specificity. Conclusions: In this significant study, 20.2% of HCWs achieved seroprotection against Omicron subvariants BA.1, BA.4, and BA.5. Their immunity against Omicron subvariants was further reinforced through recommended vaccinations and the development of natural immunity from SARS-CoV-2 exposure, collectively enhancing their protection against Omicron. [ABSTRACT FROM AUTHOR]

The coronavirus-2 has led to a global pandemic of COVID-19 with an outbreak of severe acute respiratory syndrome leading to worldwide quarantine measures and a rise in death rates. The objective of this study is to propose a green, sensitive, and selective densitometric method to simultaneously quantify remdesivir (REM) in the presence of the co-administered drug linezolid (LNZ) and rivaroxaban (RIV) in spiked human plasma. TLC silica gel aluminum plates 60 F254 were used as the stationary phase, and the mobile phase was composed of dichloromethane (DCM): acetone (8.5:1.5, v/v) with densitometric detection at 254 nm. Well-resolved peaks have been observed with retardation factors (Rf) of 0.23, 0.53, and 0.72 for REM, LNZ, and RIV, respectively. A validation study was conducted according to ICH Q2 (R1) Guidelines. The method was rectilinear over the concentration ranges of 0.2–5.5 μg/band, 0.2–4.5 μg/band and 0.1–3.0 μg/band for REM, LNZ and RIV, respectively. The sensitivities of REM, LIN, and RIV were outstanding, with quantitation limits of 128.8, 50.5, and 55.8 ng/band, respectively. The approach has shown outstanding recoveries ranging from 98.3 to 101.2% when applied to pharmaceutical formulations and spiked human plasma. The method's greenness was assessed using Analytical Eco-scale, GAPI, and AGREE metrics. [ABSTRACT FROM AUTHOR]

This article examines the historical and current mistreatment of Asian Americans and Pacific Islanders (AAPI) in relation to disease, particularly during the COVID-19 pandemic. It discusses how discriminatory beliefs and policies towards AAPI individuals have been influenced by eugenic ideologies. The article highlights the stigmatization and blame placed on the AAPI community for the spread of COVID-19, perpetuated by media and political figures. It emphasizes the importance of challenging racial stereotypes and labels that undermine the diverse identities within the AAPI community. The text also addresses the fear and stigmatization experienced by AAPI individuals during the pandemic, leading to mental health challenges and a reluctance to seek help. It calls for education, cultural competence, and racial justice to address these issues, and mentions the Hollaback project as a resource for bystander intervention training to combat anti-AAPI harassment. [Extracted from the article]

Coronavirus disease 2019, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), remains an ongoing global public health challenge. This disease causes damage not only to the respiratory system, affecting the normal physiological function of the lungs, but also to other vital organs, such as the heart and testicles. Existing studies have shown that co-expression of angiotensin-converting enzyme 2 and transmembrane serine protease 2 is the main mechanism by which SARS-CoV-2 invades host cells. Angiotensin-converting enzyme 2-expressing cells are widespread in the corpus cavernosum, reproductive tract and testis of men, which has raised concerns. Furthermore, abnormal sex hormone levels and decreased semen parameters were observed in coronavirus disease 2019 patients. This study comprehensively assessed the effects of SARS-CoV-2 infection on the testis, semen parameters, sex hormone levels and erectile function, and discussed possible transmission routes during sexual intercourse and the effect of vaccination on male fertility. Since the outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic in December 2019, coronavirus disease 2019 (COVID-19) has already had a widespread impact on fertility. This study comprehensively assessed the effects of SARS-CoV-2 infection on the testis, semen parameters, sex hormone levels and erectile function, and discussed possible transmission routes during sexual intercourse and the effect of vaccination on male fertility. It provides a reference for maintaining male reproductive health under the background of normalised prevention and control of COVID-19. [ABSTRACT FROM AUTHOR]

Healthcare-associated infections due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has increased since the discovery of the Omicron variant. We describe a SARS-CoV-2 outbreak in the medicine–surgery unit of a rural community hospital at the time of high community transmission of Omicron variant in our county. The outbreak occurred in the medicine–surgery unit of an 89-bed rural community hospital in northern Maine. The characteristics of the patients and healthcare workers (HCWs) affected by the outbreak are described. Patient and HCW data collected as part of the outbreak investigation were used in this report. The outbreak control measures implemented are also described. A total of 24 people tested positive for SARS-CoV-2 including 11 patients and 13 HCWs. A total of 12 of the 24 (50%) persons were symptomatic, and rhinorrhea was the most common symptom noted (8/12, 67%). None of the symptomatic persons had gastrointestinal symptoms or symptoms of a loss of sense of smell or taste. All HCWs were vaccinated and 8 of the 11 patients were vaccinated. Outbreak control measures in the affected unit included implementation of full PPE (N95 respirators, eye protection, gowns and gloves) during all patient care, serial testing of employees and patients in the affected unit, cohorting positive patients, closing visitation and thorough environmental cleaning including use of ultraviolet (UV) light disinfection. This outbreak exemplifies the high transmissibility of the Omicron variant of SARS-CoV-2. The outbreak occurred despite a well-established infection control program. We noted that serial testing, use of N95 respirators during all patient care and UV disinfection were some of the measures that could be successful in outbreak control. [ABSTRACT FROM AUTHOR]

In the past, scholars of academic dependency have tended to focus their discussions on social sciences while treating other fields as separate. They suggest that in order to escape dependency, alternative discourse and autonomy should be developed. In this paper, we examine the Public Health Liberation (PHL) movement in Taiwan and theorize on the marketization and medicalization of the healthcare system since the 1980s as a dependency syndrome. The PHL was initiated by a group of public health scholars—with the second author of this paper being one of its key protagonists—and frontline public health practitioners after the severe acute respiratory syndrome outbreak in 2003. Inspired by the mass mobilization model in public health in Asian and Latin American countries, particularly China, the Philippines, and Nicaragua, PHL trains grassroots public health educators, nurtures critical research, and has built a network of activists for radical public health reform in Taiwan. Based on participatory action research, this paper analyzes the emergence of this influential public health movement and situates it within the global context of neoliberal health reforms. [ABSTRACT FROM AUTHOR]

COVID-19 and SARS are epidemics which have influenced the largest global economic crisis in recent years. This research reveals that both SARS and COVID-19 have led to fluctuations in the prices of gold and the US dollar index; however, there is no direct causal relationship be-tween COVID-19 and the price of bitcoin. The USD index saw a significant increase during the SARS outbreak, while gold prices surged during the COVID-19 pandemic. The notion that cryptocurrency will surpass the value of gold or traditional currencies seems improbable, given the lack of evidence linking bitcoin prices to COVID-19. Gold is expected to maintain its value in the long term, offering lower risk compared to other currencies. [ABSTRACT FROM AUTHOR]

A large‐scale outbreak of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS‐CoV‐2) occurred in Shanghai, China, in early December 2022. To study the incidence and characteristics of otitis media with effusion (OME) complicating SARS‐CoV‐2, we collected 267 middle ear effusion (MEE) samples and 172 nasopharyngeal (NP) swabs from patients. The SARS‐CoV‐2 virus was detected by RT‐PCR targeting. The SARS‐CoV‐2 virus, angiotensin‐converting enzyme 2 (ACE2), and transmembrane serine protease 2 (TMPRSS2) expression in human samples was examined via immunofluorescence. During the COVID‐19 epidemic in 2022, the incidence of OME (3%) significantly increased compared to the same period from 2020 to 2022. Ear symptoms in patients with SARS‐CoV‐2 complicated by OME generally appeared late, even after a negative NP swab, an average of 9.33 ± 6.272 days after COVID‐19 infection. The SARS‐CoV‐2 virus was detected in MEE, which had a higher viral load than NP swabs. The insertion rate of tympanostomy tubes was not significantly higher than in OME patients in 2019–2022. Virus migration led to high viral loads in MEE despite negative NP swabs, indicating that OME lagged behind respiratory infections but had a favorable prognosis. Furthermore, middle ear tissue from adult humans coexpressed the ACE2 receptor for the SARS‐CoV‐2 virus and the TMPRSS2 cofactors required for virus entry. [ABSTRACT FROM AUTHOR]

The 2002 SARS outbreak, the 2019 emergence of COVID-19, and the continuing evolution of immune-evading SARS-CoV-2 variants together highlight the need for a broadly protective vaccine against ACE2-utilizing sarbecoviruses. While updated variant-matched formulations are a step in the right direction, protection needs to extend beyond SARS-CoV-2 and its variants to include SARS-like viruses. Here, we introduce bivalent and trivalent vaccine formulations using our spike protein nanoparticle platform that completely protect female hamsters against BA.5 and XBB.1 challenges with no detectable virus in the lungs. The trivalent cocktails elicit highly neutralizing responses against all tested Omicron variants and the bat sarbecoviruses SHC014 and WIV1. Finally, our 614D/SHC014/XBB trivalent spike formulation completely protects human ACE2-transgenic female hamsters against challenges with WIV1 and SHC014 with no detectable virus in the lungs. Collectively, these results illustrate that our trivalent protein-nanoparticle cocktail can provide broad protection against SARS-CoV-2-like and SARS-CoV-1-like sarbecoviruses. Evolution of SARS-CoV-2 and emergence of other sarbecoviruses are of potential concern. Here, the authors designed a trivalent spike-protein-nanoparticle vaccine that elicits neutralizing antibodies and protects female hamsters against challenges with SARS-CoV-2-like and SARS-CoV-1-like coronaviruses. [ABSTRACT FROM AUTHOR]

A model of epidemic dynamics is developed that incorporates continuous variables for infection age and vaccination age. The model analyzes pre-symptomatic and symptomatic periods of an infected individual in terms of infection age. This property is shown to be of major importance in the severity of the epidemic, when the infectious period of an infected individual precedes the symptomatic period. The model also analyzes the efficacy of vaccination in terms of vaccination age. The immunity to infection of vaccinated individuals varies with vaccination age and is also of major significance in the severity of the epidemic. Application of the model to the 2003 SARS epidemic in Taiwan and the COVID-19 epidemic in New York provides insights into the dynamics of these diseases. It is shown that the SARS outbreak was effectively contained due to the complete overlap of infectious and symptomatic periods, allowing for the timely isolation of affected individuals. In contrast, the pre-symptomatic spread of COVID-19 in New York led to a rapid, uncontrolled epidemic. These findings underscore the critical importance of the pre-symptomatic infectious period and the vaccination strategies in influencing the dynamics of an epidemic. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) caused a severe epidemic due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Recent studies have found that patients do not completely recover from acute infections, but instead, suffer from a variety of post-acute sequelae of SARS-CoV-2 infection, known as long COVID. The effects of long COVID can be far-reaching, with a duration of up to six months and a range of symptoms such as cognitive dysfunction, immune dysregulation, microbiota dysbiosis, myalgic encephalomyelitis/chronic fatigue syndrome, myocarditis, pulmonary fibrosis, cough, diabetes, pain, reproductive dysfunction, and thrombus formation. However, recent studies have shown that naringenin and naringin have palliative effects on various COVID-19 sequelae. Flavonoids such as naringin and naringenin, commonly found in fruits and vegetables, have various positive effects, including reducing inflammation, preventing viral infections, and providing antioxidants. This article discusses the molecular mechanisms and clinical effects of naringin and naringenin on treating the above diseases. It proposes them as potential drugs for the treatment of long COVID, and it can be inferred that naringin and naringenin exhibit potential as extended long COVID medications, in the future likely serving as nutraceuticals or clinical supplements for the comprehensive alleviation of the various manifestations of COVID-19 complications. [ABSTRACT FROM AUTHOR]

Under probability weighting, entrepreneurs with skewness preference tend to seek rightskewed and avoid left-skewed risks. We show that Chinese firms managed by CEOs with professional epidemic experience, i.e., who previously experienced the outbreak of SARS during their tenure as high level executives, have a lower stock price crash risk measured by the negative skewness of stock prices in subsequent periods. In particular, those firms intentionally avoid stock price crashes by adopting more conservative strategies in decisionmaking. Overall, we provide the first evidence on the unintended effect of entrepreneurs' subjective judgments of the probabilities of disease outbreaks on financial market stability. These have long-term implications for the financial system. [ABSTRACT FROM AUTHOR]

Background In autumn 2022, the epidemics due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), respiratory syncytial virus (RSV), and influenza overlapped, and these diseases can present with the same symptomatology. The use of a triple antigen test (SARS-CoV-2 + influenza A/B + RSV) seems crucial for accurate viral diagnosis in the context of implementing long-acting monoclonal antibody vaccination against RSV in the upcoming RSV season. Methods We assessed the usefulness of the triple test in real life in this prospective study performed from October 2022 to May 2023 and involving 116 pediatricians (2 emergency department pediatricians and 114 ambulatory pediatricians). Children <15 years old with flu-like illness (with fever), bronchiolitis (dyspnea ± wheezing), otitis, and croup were enrolled and sampled with a nasal triple test. Results For 8329 children with flu-like illness (65.3%), bronchiolitis (17.9%), otitis (8.8%), and croup (6.3%), the use of the triple test led to a viral diagnosis in 47.9% of cases. The highest RSV positivity occurred in children with bronchiolitis (32.9%). The highest influenza A and B positivity (24.6% and 19.6%) occurred in children with flu-like illness. A succession of 3 epidemics (RSV and influenza A and B) occurred over time with several overlap periods. Conclusions The triple test allowed for a viral diagnosis in half of our cases. The upcoming introduction of RSV prevention will emphasize the need for active surveillance with viral results both in ambulatory settings and hospitals. Clinical Trials Registration. NCT0441231. [ABSTRACT FROM AUTHOR]

The pneumonia outbreak caused by Severe Acute Respiratory Syndrome 2 (SARS‐CoV‐2) infection poses a serious threat to people worldwide. Although vaccines have been developed, antiviral drugs are still needed to combat SARS‐CoV‐2 infection due to the high mutability of the virus. SARS‐CoV‐2 main protein (Mpro) is a special cysteine protease that is a key enzyme for SARS‐CoV‐2 replication. It is encoded by peptides and is responsible for processing peptides into functional proteins, making it an important drug target. The paper reviews the structure and peptide‐like inhibitors of SARS‐CoV‐2 Mpro, also the binding mode and structure–activity relationship between the inhibitors and Mpro are introduced in detail. It is hoped that this review can provide ideas and help for the development of anti‐coronavirus drugs such as COVID‐19, and help to develop broad‐spectrum antiviral drug for the treatment of coronavirus diseases as soon as possible. [ABSTRACT FROM AUTHOR]

COVID-19 has exposed major weaknesses in the healthcare settings. The surge in COVID-19 cases increases the demands of health care, endangers vulnerable patients, and threats occupational safety. In contrast to a hospital outbreak of SARS leading to a whole hospital quarantined, at least 54 hospital outbreaks following a COVID-19 surge in the community were controlled by strengthened infection prevention and control measures for preventing transmission from community to hospitals as well as within hospitals. Access control measures include establishing triage, epidemic clinics, and outdoor quarantine stations. Visitor access restriction is applied to inpatients to limit the number of visitors. Health monitoring and surveillance is applied to healthcare personnel, including self-reporting travel declaration, temperature, predefined symptoms, and test results. Isolation of the confirmed cases during the contagious period and quarantine of the close contacts during the incubation period are critical for containment. The target populations and frequency of SARS-CoV-2 PCR and rapid antigen testing depend on the level of transmission. Case investigation and contact tracing should be comprehensive to identify the close contacts to prevent further transmission. These facility-based infection prevention and control strategies help reduce hospital transmission of SARS-CoV-2 to a minimum in Taiwan. [ABSTRACT FROM AUTHOR]

Over the past two decades, China has become a distinctive and increasingly important donor of development assistance for health (DAH). However, little is known about what factors influence China's priority-setting for DAH. In this study, we provide an updated analysis of trends in the priorities of Chinese DAH and compare them to comparable trends among OECD Development Assistance Committee (DAC) donors using data from the AidData's Global Chinese Development Finance Dataset (2000–2017, version 2.0) and the Creditor Reporting System (CRS) database (2000–2017). We also analyse Chinese medical aid exports before and after the start of the COVID-19 pandemic using a Chinese Aid Exports Database. We further explore the potential factors influencing China's shifting priority-setting processes by reviewing Chinese official documents following Walt and Gilson's policy analysis framework (context–actors–process–content) and by testing our conjectures empirically. We find that China has become an important DAH donor to most regions if measured using project value, including but not limited to Africa. China has prioritized aid to African and Asian countries as well as to CRS subsectors that are not prioritized by DAC donors, such as medical services and basic health infrastructure. Chinese quarterly medical aid exports almost quintupled after the start of the COVID-19 pandemic. Noticeably, China has allocated more attention to Asia, eye diseases and infectious disease outbreaks over time. In contrast, the priority given to malaria has declined over the same period. Regarding factors affecting priority shifts, the outbreaks of SARS and Ebola, the launch of the Belt and Road Initiative and the COVID-19 pandemic appear to be important milestones in the timeline of Chinese DAH. Unlike stereotypes of China as a 'lone wolf' donor, our analysis suggests multilateral processes are influential in informing and setting Chinese DAH priorities. [ABSTRACT FROM AUTHOR]

The novel 2019 coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a highly transmissible and pathogenic coronavirus. Because of the novelty of the COVID-19 pandemic, few data are available on the impact of the SARS-CoV-2 on the different endocrine glands. Previous studies of severe acute respiratory syndrome (SARS) have shown a harmful effect on endocrine function. Notably, the angiotensin-converting enzyme-2 receptor, which is the entry route of coronaviruses to the host cell, is widely expressed in the endocrine organs including testis, endocrine pancreas, thyroid, and adrenal, and pituitary glands. Clinical and biochemical manifestations have been recorded in COVID-19 patients resulting in changes in endocrine activities, which were also recorded during the SARS outbreak in 2003. This review aims to explore the impact of SARS-CoV-2 infection on the function of endocrine glands, based on the latest research in the field. [ABSTRACT FROM AUTHOR]

Introduction: The waning antibody levels several months after prime vaccination and the persistent epidemics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) around the world have generated great interest in the evaluation of a booster dose. We aimed to assess the safety and immunogenicity of a homologous booster dose of the recombinant adenovirus type 5-vectored coronavirus disease 2019 (COVID-19) vaccine (Ad5-nCoV). Methods: In this trial, we recruited healthy adults aged 18–60 years who had received one dose of Ad5-nCoV vaccine (low, middle, or high dose) in the previous phase 1 trial approximately 6 months earlier, and then all participants received a booster dose of 5 × 1010 viral particles (low dose) intramuscularly. The primary outcome was the incidence of adverse reactions within 14 days after booster vaccination. The specific binding antibodies were measured by enzyme-linked immunosorbent assay and the neutralizing antibody responses were assessed with live SARS-CoV-2 and pseudovirus neutralization assay. The cellular immune responses were analyzed by enzyme-linked immunospot assay and intracellular cytokine staining. Results: From September 26 to 28, 2020, 108 volunteers were recruited and 89 eligible participants (52% male) were enrolled and received a booster dose of Ad5-nCoV vaccine: 28 (31%) had received a low prime dose, 30 (34%) a middle prime dose, and 31 (35%) a high prime dose in the previous phase 1 trial. All participants were included in the safety analysis and immunogenicity was assessed in 88 (99%) participants. Twenty-three (82%) participants in the low prime dose group, 23 (77%) participants in the middle prime dose group, and 26 (84%) participants in the high prime dose group reported at least one adverse reaction within the first 14 days post booster. Pain at the injection site and fatigue were the most common adverse reactions. Most adverse reactions were mild or moderate in all groups and no vaccine-related severe adverse event was noted within 12 months after booster vaccination. Neutralizing antibodies increased moderately at day 14 and peaked at 28 days post booster. T cell responses were also boosted at 14 days after vaccination. Conclusions: A homologous booster of Ad5-nCoV vaccine is well tolerated and immunogenic in healthy adults aged 18–60 years who had received a priming dose of Ad5-nCoV 6 months previously. The neutralizing antibodies against SARS-CoV-2 peaked at day 28 and specific T cell responses were noted at day 14 after booster. Ad5-nCoV vaccine can be considered as a homologous booster 6 months after a priming dose. Trial registration: ClinicalTrials.gov, NCT04568811. [ABSTRACT FROM AUTHOR]

The K18-hACE2 transgenic mice, a model animal having human ACE receptors, is employed in studies against the SARS-CoV-2 virus all over the world. Aged Balb/C mice utilized during the SARS-CoV outbreak were compared to non-T-cell, immunosuppressive Nude mice often employed in cancer research and K18-hACE2 transgenic mice used as a model animal against the SARS-CoV-2 virus challenge assay. At the same time, the role of the model animal K18-hACE2 transgenic mice in organs other than the lung was studied. The BSL3 facility was used for the challenge experiment in this study. In three groups, 105 TCID50 SARS-CoV-2 virus B.1.1.7 (the alpha variant was gavaged and intranasally administered to mice under anesthesia. The experiment was ended on the tenth day, and gross pathology was done. The viral load of SARS-CoV-2 was determined by RT-PCR after collecting the target organ lungs from all mice as well as the spleen, liver, heart, and kidneys from the K18-hACE2 transgenic mouse group. In comparison to Balb/C and Nude mice, the K18-hACE2 transgenic mouse model animal has been shown to be a suitable model against the SARS-CoV-2 virus in our study. At the same time, when the organs of K18-hACE2 transgenic mice were compared, viral load retention occurred in the target organ, the lung, with no significant retention in other organs. [ABSTRACT FROM AUTHOR]

With the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), global researchers were confronted with major challenges. The German National Pandemic Cohort Network (NAPKON) was launched in fall 2020 to effectively leverage resources and bundle research activities in the fight against the coronavirus disease 2019 (COVID-19) pandemic. We analyzed the setup phase of NAPKON as an example for multicenter studies in Germany, highlighting challenges and optimization potential in connecting 59 university and nonuniversity study sites. We examined the ethics application process of 121 ethics submissions considering durations, annotations, and outcomes. Study site activation and recruitment processes were investigated and related to the incidence of SARS-CoV-2 infections. For all initial ethics applications, the median time to a positive ethics vote was less than two weeks and 30 of these study sites (65%) joined NAPKON within less than three weeks each. Electronic instead of postal ethics submission (9.5 days (Q1: 5.75, Q3: 17) vs. 14 days (Q1: 11, Q3: 26), p value = 0.01) and adoption of the primary ethics vote significantly accelerated the ethics application process. Each study center enrolled a median of 37 patients during the 14-month observation period, with large differences depending on the health sector. We found a positive correlation between recruitment performance and COVID-19 incidence as well as hospitalization incidence. Our analysis highlighted the challenges and opportunities of the federated system in Germany. Digital ethics application tools, adoption of a primary ethics vote and standardized formal requirements lead to harmonized and thus faster study initiation processes during a pandemic. [ABSTRACT FROM AUTHOR]

This study performs empirical tests to show several behavioral patterns in managerial decision-making using Chinese data. Based on the outbreak of Severe Acute Respiratory Syndrome (SARS) in 2003, caused by the same family of viruses as COVID-19, we show that firms with board chairs that experienced SARS during their tenure as senior executives invested less in subsequent periods. This effect is evident for board chairs that personally experienced the pandemic and those who prominently perceived their neighbor's operating distress during the SARS outbreak. The impact persists and is amplified by other negative shocks, such as infectious diseases and economic uncertainty, which supports the validity of stimulus generalization theory in corporate finance. Firms with board chairs that experienced SARS invested even less during the COVID-19 pandemic but performed relatively better during this same period than during normal business operations. However, the benefit was somewhat smaller than the overall loss. This study supports the finding that the long-lasting impact of pandemic-induced operating distress can distort the real economy. Our findings have meaningful implications for assessing the long-term economic effects of COVID-19. [ABSTRACT FROM AUTHOR]

Background: The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has triggered a global health crisis, with genetic mutations and evolution further creating uncertainty about epidemic risk. It is imperative to rapidly determine the nucleic acid sequence of SARS-CoV-2 and its variants to combat the coronavirus pandemic. Our goal was to develop a rapid, room-temperature, point-ofcare (POC) detection system to determine the nucleic acid sequences of SARS-CoV-2 isolates, especially omicron variants. Methods: Based on the conserved nucleotide sequence of SARS-CoV-2, bioinformatics software was used to analyze, design, and screen optimal enzymatic isothermal amplification primers and efficient CRISPR RNAs (crRNAs) of CRISPR/Cas13a to the target sequences. Reverse transcription-recombinase polymerase amplification (RT-RPA) was used to amplify the virus, and CRISPR/Cas13a-crRNA was used to cleave the SARS-CoV-2 target sequence. The sensitivity of nucleic acid detection was assessed by serial dilution of plasmid templates. All reactions were performed at room temperature. Results: RT-RPA, combined with CRISPR/Cas13a, can detect the SARS-CoV-2 with a minimum content of 10² copies/μL, and can effectively distinguish between the original strain and the Omicron variant with a minimum limit of detection (LOD) of 10³ copies/μL. Conclusion: The method developed in this study has potential application in clinical detection of SARSCoV-2 and its omicron variants. [ABSTRACT FROM AUTHOR]

In recent years, especially since the outbreak of the severe acute respiratory syndrome coronavirus 2 pandemic, the cell-permeable itaconate derivative 4-octyl itaconate (4-OI) has gained traction as a potential antiviral agent. Here, we demonstrate that 4-OI inhibits replication of multiple influenza A viruses (IAV) by restricting nuclear export of viral ribonucleoproteins, a key step in the IAV replication cycle. This nuclear retention is achieved by deactivation and subsequent degradation of chromosomal maintenance 1 protein (CRM1), also known as exportin 1 (XPO1), a host cell protein exploited by IAV during replication. 4-OI-mediated deactivation of CRM1 resulted in the accumulation of the IAV nucleoprotein, the Rev protein of feline immunodeficiency virus, as well as the natural CRM1 cargos p53 and p65, in the nucleus of treated cells. Further mechanism of action studies revealed that, similar to known CRM1 inhibitors, 4-OI modifies a key cysteine in the cargo binding pocket of CRM1 at position 528 through an alkylation reaction called 2,3-dicarboxypropylation. Subsequent studies in a cell line in which the cysteine at position 528 in CRM1 protein was substituted by a serine confirmed that modification of this residue was indeed the cause for the observed inhibitory effect induced by 4-OI on CRM1 function. Overall, this study demonstrated a mechanism through which 4-OI directly interferes with the replication cycle of CRM1- dependent viruses, which contributes to the understanding of the antiviral and antiinflammatory properties of this multifaceted immuno-metabolite. IMPORTANCE Itaconate derivates, as well as the naturally produced metabolite, have been proposed as antivirals against influenza virus. Here, the mechanism behind the antiviral effects of exogenous 4-octyl itaconate (4-OI), a derivative of itaconate, against the influenza A virus replication is demonstrated. The data indicate that 4-OI targets the cysteine at position 528 of the CRM1 protein, resulting in inhibition of the nuclear export of viral ribonucleoprotein complexes in a similar manner as previously described for other selective inhibitors of nuclear export. These results postulate a mechanism not observed before for this immuno-metabolite derivative. This knowledge is helpful for the development of derivatives of 4-OI as potential antiviral and anti-inflammatory therapeutics. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has had a distinctive impact on Hong Kong, especially given the city's prior experience with the SARS outbreak. The resulting psychological distress has been exacerbated by Hong Kong's extreme density and compactness, which places residents in proximity on the streets searching for outdoor activities. Streets are a precious source of space for social interactions, but, unfortunately, the pandemic has forced them to empty, leading to increased distress and challenging the psychological well-being of the urban population. In this study, we explore street vibrancy patterns in terms of outdoor activities, here addressed through a decision-making psychological perspective as volitional behaviors determined by psychological factors and essential for well-being, in one of the densest neighborhoods in Hong Kong. We statistically analyzed behavioral monitoring data in relation to spatial and morphological characteristics of their environments under COVID-19 psychological distress. The results highlighted the relevance of specific parcels of the streets acting as clusters and vibrancy initiators, stressing their significance in terms of affective and cognitive inputs determining context-based outdoor activities. The decision-making psychological perspective adopted here to address outdoor activities has relevant implications for design and planning strategies for post-pandemic scenarios, for psychological well-being, and for the future of urban density. [ABSTRACT FROM AUTHOR]

Recent events have raised concerns about the outbreak of a pandemic by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). An infection caused by a virus can provoke an inflammatory reaction, which can result in severe lung damage, failure of several organs, and death. The unique genetic makeup of each individual may be a component in the development of each of these responses. In this context, genetic variants of the genes linked to the invasion of the virus into the host's body can be analyzed. Various elements have a function in viral entry. ACE2 is used by SARS-CoV-2 as a receptor to enter the cell. TMPRSS2 is then responsible for cutting the virus into its components. In addition, lung damage occurs when there is an imbalance between ACE1 and ACE2. Another component that plays a significant role in virus penetration is called IFITM3, which is created as a reaction to interferon. This protein prevents viruses in the Coronaviridae family from entering cells. This study aimed to analyze DNA polymorphisms in the ACE2 , ACE1 , TMPRSS2 , and IFITM3 genes. Findings showed certain polymorphisms appear to be associated with the severity of the disease, including respiratory, coronary, and neurological disorders. The results also indicated that certain polymorphisms were protective against this virus. Varying populations have a different frequency of high-risk polymorphisms, so different treatment and preventative techniques must be implemented. Additional population studies should be conducted in this region to reduce the incidence of COVID-19-related morbidity and mortality. [ABSTRACT FROM AUTHOR]

The article recounts the life and work of Carlo Urbani, a communicable disease expert for the World Health Organization (WHO) in Hanoi, Vietnam. It highlights the career of Urbani with WHO and his accomplishments including identification of severe acute respiratory syndrome (SARS) in Vietnam which later became an outbreak and led to the global surveillance of SARS cases. It commends Urbani for his dedication to helping protect and save the lives of people.

In China, the emergence of a nationally widespread epidemic infection of severe acute respiratory syndrome coronavirus 2 (SARS‐COV‐2) has appeared within a month since December 7, 2022. To evaluate the risk factors for suffering from coronavirus disease 2019 (COVID‐19) pneumonia due to infection with SARS‐CoV‐2 in different kinds of interstitial lung disease (ILD) patients with diverse immunizations, we conducted this retrospective study on 525 patients with ILDs who underwent regular follow‐up in our ILD clinic. Among them, 128 ILD patients (24.4%) suffered from COVID‐19 pneumonia after SARS‐CoV‐2 infection. Patients were older with a male predominance in the pneumonia group than in the nonpneumonia group (65.0 ± 10.0 years vs. 56.4 ± 11.7 years, p < 0.001, 55.5% vs. 39.5%, p = 0.002, respectively). Connective tissue disease‐associated ILD (CTD‐ILD) (25%), idiopathic pulmonary fibrosis (23.4%), and interstitial pneumonia with autoimmune features (21.1%) were the main pre‐existing ILDs in the pneumonia group. In Cox multivariable analysis, only male sex and corticosteroid use were risk factors for COVID‐19 pneumonia after infection. Two or three doses of vaccination were a protective factor for pre‐existing ILD patients suffering from COVID‐19 pneumonia. More than two doses of vaccination were strongly recommended for pre‐existing ILD patients, particularly for males who were administered corticosteroids. [ABSTRACT FROM AUTHOR]

Since the outbreak of severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) and its resultant pneumonia in December 2019, the cumulative number of infected people worldwide has exceeded 670 million, with over 6.8 million deaths. Despite the marketing of multiple series of vaccines and the implementation of strict prevention and control measures in many countries, the spread and prevalence of SARS-CoV-2 have not been completely and effectively controlled. The latest research shows that in addition to angiotensin converting enzyme II (ACE2), dozens of protein molecules, including AXL, can act as host receptors for SARS-CoV-2 infecting human cells, and virus mutation and immune evasion never seem to stop. To sum up, this review summarizes and organizes the latest relevant literature, comprehensively reviews the genome characteristics of SARS-CoV-2 as well as receptor-based pathogenesis (including ACE2 and other new receptors), mutation and immune evasion, vaccine development and other aspects, and proposes a series of prevention and treatment opinions. It is expected to provide a theoretical basis for an in-depth understanding of the pathogenic mechanism of SARS-CoV-2 along with a research basis and new ideas for the diagnosis and classification, of COVID-19-related disease and for drug and vaccine research and development. [ABSTRACT FROM AUTHOR]

Background: Severe acute respiratory syndrome (SARS) is a form of atypical pneumonia which took hundreds of lives when it swept the world two decades ago. The pathogen of SARS was identified as SARS-coronavirus (SARS-CoV) and it was mainly transmitted in China during the SARS epidemic in 2002-2003. SARS-CoV and SARS-CoV-2 have emerged from the SARS metapopulation of viruses. However, they gave rise to two different disease dynamics, a limited epidemic, and an uncontrolled pandemic, respectively. The characteristics of its spread in China are particularly noteworthy. In this paper, the unique characteristics of time, space, population distribution and transmissibility of SARS for the epidemic were discussed in detail. Methods: We adopted sliding average method to process the number of reported cases per day. An SEIAR transmission dynamics model, which was the first to take asymptomatic group into consideration and applied indicators of R0, Reff, Rt to evaluate the transmissibility of SARS, and further illustrated the control effectiveness of interventions for SARS in 8 Chinese cities. Results: The R0 for SARS in descending order was: Tianjin city (R0 = 8.249), Inner Mongolia Autonomous Region, Shanxi Province, Hebei Province, Beijing City, Guangdong Province, Taiwan Province, and Hong Kong. R0 of the SARS epidemic was generally higher in Mainland China than in Hong Kong and Taiwan Province (Mainland China: R0 = 6.058 ± 1.703, Hong Kong: R0 = 2.159, Taiwan: R0 = 3.223). All cities included in this study controlled the epidemic successfully (Reff<1) with differences in duration. Rt in all regions showed a downward trend, but there were significant fluctuations in Guangdong Province, Hong Kong and Taiwan Province compared to other areas. Conclusion: The SARS epidemic in China showed a trend of spreading from south to north, i.e., Guangdong Province and Beijing City being the central regions, respectively, and from there to the surrounding areas. In contrast, the SARS epidemic in the central region did not stir a large-scale transmission. There were also significant differences in transmissibility among eight regions, with R0 significantly higher in the northern region than that in the southern region. Different regions were able to control the outbreak successfully in differences time. [ABSTRACT FROM AUTHOR]

The wild meat trade poses a significant threat to public health as it facilitates the spillover of zoonotic pathogens through high-risk activities such as the hunting, butchering, trade, and consumption of wild animals. Despite the health risks and association with marking epidemics including SARS, Ebola, and COVID-19, the global wild meat trade continues to thrive. To summarize the evidence available, primary literature published between 2000 and 2022 was systematically and critically assessed for evidence of zoonotic pathogens or other infectious organisms detected in samples directly from wild meat, from animals hunted for wild meat, or from humans exposed through high-risk activities. Within the 97 articles analyzed, a total of 114 pathogen genera (15 viruses, 40 bacteria, 54 parasites, and 5 fungi) were detected in wild meat animals belonging to 168 vertebrate species including mammals, reptiles and birds sampled in 32 countries. In the context of wild meat specifically, infectious organisms were differentiated between those with zoonotic potential (32% of reported genera), ectoparasitic vectors (1%), and possible opportunistic or environmental contaminants. Thirteen viral, four bacterial, and one parasitic genera were also documented in humans participating in wild meat trade activities, supporting pathogen spillover potential. Most studies employed a targeted approach to evaluate the presence of (i.e., polymerase chain reaction (PCR); n = 65) or exposure to (i.e., ELISA; n = 19) a specific pathogen, while only one study employed broad-spectrum metabarcoding techniques. The diversity of infectious organisms associated with wild meat are highlighted through this review and could be used to guide policy development. However, the common use of a selected set of targeted detection assays likely biases the exploration of pathogen diversity, therefore potentially preventing the discovery of "disease x". The global health risk demonstrated should make the illegal wild meat trade a priority for law-enforcement agencies and future research. [ABSTRACT FROM AUTHOR]

Background: The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been followed by many reports of the development and relapse of autoimmune diseases associated with SARS-CoV-2 vaccination. Some of these reports have involved relapse or onset of immunoglobulin A (IgA) nephropathy following SARS-CoV-2 vaccination. Here, we report on a patient with IgA nephropathy who presented with gross hematuria and rapidly progressive glomerulonephritis following SARS-CoV-2 vaccination. Case presentation: A 63-year-old male patient with a history of habitual tonsillitis underwent bilateral tonsillectomy. He had a history of alcoholic cirrhosis of the liver and microscopic hematuria and proteinuria were indicated during a health checkup 2 years before hospital admission. He developed hematuria after the SARS-CoV-2 vaccination, which led to rapidly progressive glomerulonephritis, for which he was hospitalized. A renal biopsy led to the diagnosis of IgA nephropathy. Although pulse steroid therapy during his condition resulted in hepatic encephalopathy, three courses combined with mizoribine improved his renal function. Conclusion: SARS-CoV-2 mRNA vaccines activate T cells, which are involved in the pathophysiology of IgA nephropathy. Therefore, this case suggests that the exacerbation of IgA nephropathy by the vaccine favors the vasculitis aspect of the disease. [ABSTRACT FROM AUTHOR]

Kawasaki disease (KD) is an acute self‐limiting systemic vasculitis of unknown etiology affecting predominantly the coronary arteries. The role of circulating immune complexes (ICs) in the pathogenesis of KD has been studied using the sera of patients with KD. It has been proposed that ICs are triggered by single or multiple unknown causative agents as well as vasculitis. The outbreak of severe acute respiratory syndrome coronavirus 2 infections caused similar pathophysiology in producing vasculitis, and the RNA virus may have triggered signs and symptoms similar to KD. For clinicians and researchers alike, detecting the causative agents of KD remains a challenge. According to studies in animal models, type III hypersensitivity reactions caused by serum sickness are a prototype for IC vasculitis. The signs and symptoms of coronary artery dilation in swine are similar to those of KD. These models may be used to evaluate new pharmacological agents for KD. The pathogenesis of KD is complex and remains inadequately understood at present. However, circulating ICs may play a key role in the pathophysiology of KD and coronary artery vasculitis. Various therapeutic agents are being explored in the management of KD and these agents act at various stages of the production of pro‐inflammatory cytokines and chemokines. In this review, we discuss recent developments in the pathogenesis of KD and provide insights into the innate immune response and mechanisms behind coronary artery damage in KD. We specifically explore the potential role of ICs in the pathogenesis of KD. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which emerged as a novel pathogen in 2019. The virus is responsible for a severe acute respiratory syndrome outbreak, affecting the respiratory system of infected individuals. COVID-19 is a super amplifier of basic diseases, and the disease with basic diseases is often more serious. Controlling the spread of the COVID-19 pandemic relies heavily on the timely and accurate detection of the virus. To resolve the problem, a polyaniline functionalized NiFeP nanosheet array-based electrochemical immunosensor using Au/Cu2O nanocubes as a signal amplifier is fabricated for the detection of SARS-CoV-2 nucleocapsid protein (SARS-CoV-2 NP). Polyaniline (PANI) functionalized NiFeP nanosheet arrays are synthesized as an ideal sensing platform for the first time. PANI is coated on the surface of NiFeP by electropolymerization to enhance biocompatibility, beneficial for the efficient loading of the capture antibody (Ab1). Significantly, Au/Cu2O nanocubes possess excellent peroxidase-like activity and exhibit outstanding catalytic activity for the reduction of H2O2. Therefore, Au/Cu2O nanocubes combine with a labeled antibody (Ab2) through the Au–N bond to form labeled probes, which can effectively amplify current signals. Under optimal conditions, the immunosensor for the detection of SARS-CoV-2 NP shows a wide linear range of 10 fg mL−1–20 ng mL−1 and a low detection limit of 1.12 fg mL−1 (S/N = 3). It also exhibits desirable selectivity, repeatability, and stability. Meanwhile, the excellent analytical performance in human serum samples confirms the practicality of the PANI functionalized NiFeP nanosheet array-based immunosensor. The electrochemical immunosensor based on the Au/Cu2O nanocubes as a signal amplifier demonstrates great potential for application in the personalized point-of-care (POC) clinical diagnosis. [ABSTRACT FROM AUTHOR]

B Methods b GBD 2019 estimated disease burden due to 369 diseases and injuries, and 86 risk factors and 54 new risk-outcomes [1,2]. B Methods b From the Worldometer, a provider of global COVID-19 statistics for many countries around the world [6], the cumulative number of total registered COVID-19 cases, COVID-19 deaths and conducted COVID-19 tests, all calculated per 1,000,000 for 47 European countries/territories for the period from the beginning of COVID-19 outbreak until July 19th, 2022, were analyzed with the Pearson correlation coefficient using the SPSS v 26. Jalal Arabloo1, Samad Azari2 1Health Management and Economics Research Center, Health Management Research Institute, Iran... Correspondence: Jalal Arabloo (mailto:arabloo j64@yahoo.com) I Archives of Public Health 2023 i , B 81(Suppl 2): b A1 B Background b Mental disorders are increasing in Iran. B Methods b The current study has adopted the European Burden of Disease Network consensus disease model for COVID-19 to estimate DALYs due to COVID-19. [Extracted from the article]

Background: Accessory proteins have diverse roles in coronavirus pathobiology. One of them in SARS-CoV (the causative agent of the severe acute respiratory syndrome outbreak in 2002–2003) is encoded by the open reading frame 8 (ORF8). Among the most dramatic genomic changes observed in SARS-CoV isolated from patients during the peak of the pandemic in 2003 was the acquisition of a characteristic 29-nucleotide deletion in ORF8. This deletion cause splitting of ORF8 into two smaller ORFs, namely ORF8a and ORF8b. Functional consequences of this event are not entirely clear. Results: Here, we performed evolutionary analyses of ORF8a and ORF8b genes and documented that in both cases the frequency of synonymous mutations was greater than that of nonsynonymous ones. These results suggest that ORF8a and ORF8b are under purifying selection, thus proteins translated from these ORFs are likely to be functionally important. Comparisons with several other SARS-CoV genes revealed that another accessory gene, ORF7a, has a similar ratio of nonsynonymous to synonymous mutations suggesting that ORF8a, ORF8b, and ORF7a are under similar selection pressure. Conclusions: Our results for SARS-CoV echo the known excess of deletions in the ORF7a-ORF7b-ORF8 complex of accessory genes in SARS-CoV-2. A high frequency of deletions in this gene complex might reflect recurrent searches in "functional space" of various accessory protein combinations that may eventually produce more advantageous configurations of accessory proteins similar to the fixed deletion in the SARS-CoV ORF8 gene. [ABSTRACT FROM AUTHOR]

Taiwan was one of the places most affected by SARS in 2003—but one of the least affected by COVID-19 in the first year of the pandemic. Taiwan deployed a centralised approach and has been able to effectively eliminate the threat of the spread of COVID-19 through swift decisions and effective action. This paper compares and evaluates the Taiwanese government's emergency responses to two health crises: SARS in 2003 and COVID-19 in 2020. The policy responses to both are mapped out on easily comprehensible timelines. The study also explores how one crisis governance influences another—how the mishandling of the SARS outbreak influenced early governmental responses to COVID-19. These are described in more detail, divided into thematic sections, and accompanied by illustrative images. [ABSTRACT FROM AUTHOR]

The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to the global coronavirus disease 2019 (COVID-19) pandemic, and the search for effective treatments has been limited. Furthermore, the rapid mutations of SARS-CoV-2 have posed challenges to existing vaccines and neutralizing antibodies, as they struggle to keep up with the increased viral transmissibility and immune evasion. However, there is hope in targeting the CD147-spike protein, which serves as an alternative point for the entry of SARS-CoV-2 into host cells. This protein has emerged as a promising therapeutic target for the development of drugs against COVID-19. Here, we demonstrate that the RNA-binding protein Human-antigen R (HuR) plays a crucial role in the post-transcriptional regulation of CD147 by directly binding to its 3′-untranslated region (UTR). We observed a decrease in CD147 levels across multiple cell lines upon HuR depletion. Furthermore, we identified that niclosamide can reduce CD147 by lowering the cytoplasmic translocation of HuR and reducing CD147 glycosylation. Moreover, our investigation revealed that SARS-CoV-2 infection induces an upregulation of CD147 in ACE2-expressing A549 cells, which can be effectively neutralized by niclosamide in a dose-dependent manner. Overall, our study unveils a novel regulatory mechanism of regulating CD147 through HuR and suggests niclosamide as a promising therapeutic option against COVID-19. [ABSTRACT FROM AUTHOR]

In Finland, the first wave of the COVID-19 epidemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) took place from March to June 2020, with the majority of COVID-19 cases diagnosed in the Helsinki-Uusimaa region. The magnitude and trend in the incidence of COVID-19 is one way to monitor the course of the epidemic. The diagnosed COVID-19 cases are a subset of the infections and therefore the COVID-19 incidence underestimates the SARS-CoV-2 incidence. The likelihood that an individual with SARS-CoV-2 infection is diagnosed with COVID-19 depends on the clinical manifestation as well as the infection testing policy and capacity. These factors may fluctuate over time and the underreporting of infections changes accordingly. Quantifying the extent of underreporting allows the assessment of the true incidence of infection. To obtain information on the incidence of SARS-CoV-2 infection in Finland, a series of serological surveys was initiated in April 2020. We develop a Bayesian inference approach and apply it to data from the serological surveys, registered COVID-19 cases, and external data on antibody development, to estimate the time-dependent underreporting of SARS-Cov-2 infections during the first wave of the COVID-19 epidemic in Finland. During the entire first wave, there were 1 to 5 (95% probability) SARS-CoV-2 infections for every COVID-19 case. The underreporting was highest before April when there were 4 to 17 (95% probability) infections for every COVID-19 case. It is likely that between 0.5%–1.0% (50% probability) and no more than 1.5% (95% probability) of the adult population in the Helsinki-Uusimaa region were infected with SARS-CoV-2 by the beginning of July 2020. [ABSTRACT FROM AUTHOR]

Background: Circulation of multidrug-resistant bacteria (MRB) in healthcare facilities is a major public health problem. These settings have been greatly impacted by the Coronavirus Disease 2019 (COVID-19) pandemic, notably due to surges in COVID-19 caseloads and the implementation of infection control measures. We sought to evaluate how such collateral impacts of COVID-19 impacted the nosocomial spread of MRB in an early pandemic context. Methods and findings: We developed a mathematical model in which Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and MRB cocirculate among patients and staff in a theoretical hospital population. Responses to COVID-19 were captured mechanistically via a range of parameters that reflect impacts of SARS-CoV-2 outbreaks on factors relevant for pathogen transmission. COVID-19 responses include both "policy responses" willingly enacted to limit SARS-CoV-2 transmission (e.g., universal masking, patient lockdown, and reinforced hand hygiene) and "caseload responses" unwillingly resulting from surges in COVID-19 caseloads (e.g., abandonment of antibiotic stewardship, disorganization of infection control programmes, and extended length of stay for COVID-19 patients). We conducted 2 main sets of model simulations, in which we quantified impacts of SARS-CoV-2 outbreaks on MRB colonization incidence and antibiotic resistance rates (the share of colonization due to antibiotic-resistant versus antibiotic-sensitive strains). The first set of simulations represents diverse MRB and nosocomial environments, accounting for high levels of heterogeneity across bacterial parameters (e.g., rates of transmission, antibiotic sensitivity, and colonization prevalence among newly admitted patients) and hospital parameters (e.g., rates of interindividual contact, antibiotic exposure, and patient admission/discharge). On average, COVID-19 control policies coincided with MRB prevention, including 28.2% [95% uncertainty interval: 2.5%, 60.2%] fewer incident cases of patient MRB colonization. Conversely, surges in COVID-19 caseloads favoured MRB transmission, resulting in a 13.8% [−3.5%, 77.0%] increase in colonization incidence and a 10.4% [0.2%, 46.9%] increase in antibiotic resistance rates in the absence of concomitant COVID-19 control policies. When COVID-19 policy responses and caseload responses were combined, MRB colonization incidence decreased by 24.2% [−7.8%, 59.3%], while resistance rates increased by 2.9% [−5.4%, 23.2%]. Impacts of COVID-19 responses varied across patients and staff and their respective routes of pathogen acquisition. The second set of simulations was tailored to specific hospital wards and nosocomial bacteria (methicillin-resistant Staphylococcus aureus, extended-spectrum beta-lactamase producing Escherichia coli). Consequences of nosocomial SARS-CoV-2 outbreaks were found to be highly context specific, with impacts depending on the specific ward and bacteria evaluated. In particular, SARS-CoV-2 outbreaks significantly impacted patient MRB colonization only in settings with high underlying risk of bacterial transmission. Yet across settings and species, antibiotic resistance burden was reduced in facilities with timelier implementation of effective COVID-19 control policies. Conclusions: Our model suggests that surges in nosocomial SARS-CoV-2 transmission generate selection for the spread of antibiotic-resistant bacteria. Timely implementation of efficient COVID-19 control measures thus has 2-fold benefits, preventing the transmission of both SARS-CoV-2 and MRB, and highlighting antibiotic resistance control as a collateral benefit of pandemic preparedness. In this modelling study, David Smith and colleagues, demonstrate the potential of COVID-19 to impact the in-hospital epidemiology of antibiotic resistance. Author summary: Why was this study done?: Antibiotic resistance is a major global health problem, and healthcare settings are hotspots for the spread of antibiotic-resistant bacteria. Healthcare settings have been heavily impacted by the Coronavirus Disease 2019 (COVID-19) pandemic, in particular due to sudden surges of COVID-19 cases, the ensuing disorganization of care delivery, and the enactment of infection control measures designed to curb viral transmission. The COVID-19 pandemic has led to shifts in the epidemiological dynamics of diverse infectious diseases, but its impacts on the spread of antibiotic-resistant bacteria remain poorly understood, due in part to the largely unobserved nature of bacterial colonization. What did the researchers do and find?: A mathematical model was developed and used to assess how outbreaks of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in healthcare settings may impact patient colonization with antibiotic-resistant bacteria. Surges in COVID-19 cases fostered conditions favourable for bacterial transmission, on average resulting in a 14% increase in colonization acquisition and a 10% increase in rates of antibiotic resistance. Conversely, the implementation of COVID-19 control measures provided the unintended benefit of limiting bacterial spread, leading to a 28% reduction in patient acquisition of drug-resistant bacteria. Impacts of SARS-CoV-2 outbreaks on antibiotic resistance were found to depend fundamentally on the particular characteristics of different hospital wards and bacterial species, but more timely implementation of effective COVID-19 control policies helped to limit the spread of antibiotic resistance across a wide range of contexts. What do these findings mean?: Outbreaks of respiratory pathogens like SARS-CoV-2 risk aggravating the concomitant spread of antibiotic-resistant bacteria. Healthcare facilities with greater underlying risk of bacterial transmission are likely more vulnerable to surges in antibiotic resistance in the event of a pandemic. Limiting the spread of antibiotic resistance should be considered as a collateral benefit of pandemic preparedness initiatives that enable more efficient public health responses to counter emerging infectious threats. [ABSTRACT FROM AUTHOR]