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The zoonotic emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the ensuing coronavirus disease 2019 (COVID-19) pandemic have profoundly affected our society. The rapid spread and continuous evolution of new SARS-CoV-2 variants continue to threaten global public health. Recent scientific advances have dissected many of the molecular and cellular mechanisms involved in coronavirus infections, and large-scale screens have uncovered novel host-cell factors that are vitally important for the virus life cycle. In this Review, we provide an updated summary of the SARS-CoV-2 life cycle, gene function and virus-host interactions, including recent landmark findings on general aspects of coronavirus biology and newly discovered host factors necessary for virus replication., (© 2024. Springer Nature Limited.)

The Nucleocapsid Protein (NP) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is not only the core structural protein required for viral packaging, but also participates in the regulation of viral replication, and its post-translational modifications such as phosphorylation have been shown to be an important strategy for regulating virus proliferation. Our previous work identified NP could be ubiquitinated, as confirmed by two independent studies. But the function of NP ubiquitination is currently unknown. In this study, we first pinpointed TRIM6 as the E3 ubiquitin ligase responsible for NP ubiquitination, binding to NP's CTD via its RING and B-box-CCD domains. TRIM6 promotes the K29-typed polyubiquitination of NP at K102, K347, and K361 residues, increasing its binding to viral genomic RNA. Consistently, functional experiments such as the use of the reverse genetic tool trVLP model and gene knockout of TRIM6 further confirmed that blocking the ubiquitination of NP by TRIM6 significantly inhibited the proliferation of SARS-CoV-2. Notably, the NP of coronavirus is relatively conserved, and the NP of SARS-CoV can also be ubiquitinated by TRIM6, indicating that NP could be a broad-spectrum anti-coronavirus target. These findings shed light on the intricate interaction between SARS-CoV-2 and the host, potentially opening new opportunities for COVID-19 therapeutic development., (© 2024 Wiley Periodicals LLC.)

Background: COVID-19 has placed a disproportionate burden on underserved racial and ethnic groups, community members working in essential industries, those living in areas of high population density, and those reliant on in-person services such as transportation. The goal of this study was to estimate the cross-sectional prevalence of SARS-CoV-2 (active SARS-CoV-2 or prior SARS-CoV-2 infection) in children and adults attending public venues in 15 sociodemographically diverse communities in the United States and to develop a statistical design that could be rigorously implemented amidst unpredictable stay-at-home COVID-19 guidelines., Methods: We used time-location sampling with complex sampling involving stratification, clustering of units, and unequal probabilities of selection to recruit individuals from selected communities. We safely conducted informed consent, specimen collection, and face-to-face interviews outside of public venues immediately following recruitment., Results: We developed an innovative sampling design that adapted to constraints such as closure of venues, changing infection hotspots, and uncertain policies. We updated both the sampling frame and the selection probabilities over time using information acquired from prior weeks. We created site-specific survey weights that adjusted sampling probabilities for nonresponse and calibrated to county-level margins on age and sex at birth., Conclusions: Although the study itself was specific to COVID-19, the strategies presented in this article could serve as a case study that can be adapted for performing population-level inferences in similar settings and could help inform rapid and effective responses to future global public health challenges., Competing Interests: Disclosure: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Bibliometric analysis of highly cited papers facilitates researchers in formulating strategic research possibilities and addressing gaps in specific domains. In this context, a bibliometric analysis was conducted to identify published papers on "oral mucosal lesions in COVID-19" within medical literature. A comprehensive search was performed in the Scopus database in July 2023. Relevant articles were retrieved, reviewed, and data for the bibliometric analysis was recorded. Network visualization of authors, countries, and keywords was generated using VOSviewer software. The analyzed articles were published over the last three years, from 2020 to 2023, with the highest output observed in 2021. The citation count for individual papers ranged from 1 to 340, with a mean of 22.325 ± 58.93 citations. A total of 37 journals were involved in publishing papers on this topic, and five authors each contributed three papers. Notably, Brazil made the highest number of contributions with eight papers. Among the 40 papers, 19 were review papers and 16 were articles discussing various aspects of oral mucosal lesions in COVID-19 patients. Additionally, six papers were identified as systematic reviews, designated with a high level of evidence. This study presents a comprehensive bibliometric analysis of papers published on "oral mucosal lesions in COVID-19." The findings will assist researchers in identifying impactful papers, understanding the prevailing research trends, and guiding future research directions in this domain. The insights gained from this analysis can contribute significantly to advancing knowledge and improving patient care in this critical area of study. • First comprehensive bibliometric analysis on "oral mucosal lesions in COVID-19" in medical literature. • Offers valuable insights to researchers for strategic planning and further exploration in this domain. • Thoroughly examined articles from 2020 to 2023, with a peak in output observed in 2021. • Six systematic reviews among 40 papers, indicating high-quality evidence-based studies. • Brazil emerged as the top contributor with eight papers on the subject. [ABSTRACT FROM AUTHOR]

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SARS-CoV-2 (COVID-19) pandemic has been an unpredicted burden on global healthcare system by infecting over 700 million individuals, with approximately 6 million deaths worldwide. COVID-19 significantly impacted all sectors, but it very adversely affected the healthcare system. These effects were much more evident in the resource limited part of the world. Individuals with acute conditions were also severely impacted. Although classical COVID-19 diagnostics such as RT-PCR and rapid antibody testing have played a crucial role in reducing the spread of infection, these diagnostic techniques are associated with certain limitations. For instance, drawback of RT-PCR diagnostics is that due to degradation of viral RNA during shipping, it can give false negative results. Also, rapid antibody testing majorly depends on the phase of infection and cannot be performed on immune compromised individuals. These limitations in current diagnostic tools require the development of nanodiagnostic tools for early detection of COVID-19 infection. Therefore, the SARS-CoV-2 outbreak has necessitated the development of specific, responsive, accurate, rapid, low-cost, and simple-to-use diagnostic tools at point of care. In recent years, early detection has been a challenge for several health diseases that require prompt attention and treatment. Disease identification at an early stage, increased imaging of inner health issues, and ease of diagnostic processes have all been established using a new discipline of laboratory medicine called nanodiagnostics, even before symptoms have appeared. Nanodiagnostics refers to the application of nanoparticles (material with size equal to or less than 100 nm) for medical diagnostic purposes. The special property of nanomaterials compared to their macroscopic counterparts is a lesser signal loss and an enhanced electromagnetic field. Nanosize of the detection material also enhances its sensitivity and increases the signal to noise ratio. Microchips, nanorobots, biosensors, nanoidentification of single-celled structures, and microelectromechanical systems are some of the most modern nanodiagnostics technologies now in development. Here, we have highlighted the important roles of nanotechnology in healthcare sector, with a detailed focus on the management of the COVID-19 pandemic. We outline the different types of nanotechnology-based diagnostic devices for SARS-CoV-2 and the possible applications of nanomaterials in COVID-19 treatment. We also discuss the utility of nanomaterials in formulating preventive strategies against SARS-CoV-2 including their use in manufacture of protective equipment, formulation of vaccines, and strategies for directly hindering viral infection. We further discuss the factors hindering the large-scale accessibility of nanotechnology-based healthcare applications and suggestions for overcoming them., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

COVID-19, caused by SARS-CoV-2, remains a global health crisis. The emergence of multiple variants with enhanced characteristics necessitates their detection and monitoring. Genome sequencing, the gold standard, faces implementation challenges due to complexity, cost, and limited throughput. The CRISPR-Cas system offers promising potential for rapid variant detection, with advantages such as speed, sensitivity, specificity, and programmability. This review provides an in-depth examination of the applications of CRISPR-Cas in mutation detection specifically for SARS-CoV-2. It begins by introducing SARS-CoV-2 and existing variant detection platforms. The principles of the CRISPR-Cas system are then clarified, followed by an exploration of three CRISPR-Cas-based mutation detection platforms, which are evaluated from different perspectives. The review discusses strategies for mutation site selection and the utilization of CRISPR-Cas, offering valuable insights for the development of mutation detection methods. Furthermore, a critical analysis of the clinical applications, advantages, disadvantages, challenges, and prospects of the CRISPR-Cas system is provided., (© 2024 Wiley Periodicals LLC.)

ObjectivesDuring the COVID-19 pandemic, a large number of research papers were published, and some of them were retracted. The present study aims to reveal the characteristics of retracted papers before and during the pandemic.MethodsThe study investigated 24,542,394 publications from 1999 to 2022 and analyzed the profiles of retracted papers from the perspectives of year, disease category, country, and journal.ResultsRetraction rates were generally increasing at least until 2019, and were the highest for “Neoplasms.” The number of publications for “Infections” and “Respiratory Tract Diseases” dramatically rose during the COVID-19 pandemic; however, the retraction rates in the two categories or of COVID-19-related papers were not especially high compared to other diseases. The association with retraction was strongest for China in most disease categories, whereas for COVID-19 papers, other countries showed higher retraction rates than China. In recent years, retracted papers have become less likely to be published in high-impact journals.ConclusionThe COVID-19 pandemic does not seem to affect the retractions of research papers much. We should keep monitoring retractions and analyze the effects of pandemics for better science.

Background Since the outbreak of COVID-19, how to reduce the risk of spreading viruses and other microorganisms while performing aerosol generating procedures (AGPs) has become a challenging question within the dental and dental hygiene communities. The purpose of this position paper is to summarize the existing evidence about the effectiveness of various mitigation methods used to reduce the risk of infection transmission during AGPs in dentistry. Methods The authors searched six databases, MEDLINE, EMBASE, Scopus, Web of Science, Cochrane Library, and Google Scholar, for relevant scientific evidence published in the last ten years (January 2012 to December 2022) to answer six research questions about the the aspects of risk of transmission, methods, devices, and personal protective equipment (PPE) used to reduce contact with microbial pathogens and limit the spread of aerosols. Results A total of 78 studies fulfilled the eligibility criteria. There was limited literature to indicate the risk of infection transmission of SARS-CoV-2 between dental hygienists and their patients. A number of mouthrinses are effective in reducing bacterial contaminations in aerosols; however, their effectiveness against SARS-CoV-2 was limited. The combined use of eyewear, masks, and face shields are effective for the prevention of contamination of the facial and nasal region, while performing AGPs. High volume evacuation with or without an intraoral suction, low volume evacuation, saliva ejector, and rubber dam (when appropriate) have shown effectiveness in reducing aerosol transmission beyond the generation site. Finally, the appropriate combination of ventilation and filtration in dental operatories are effective in limiting the spread of aerosols. Conclusion Aerosols produced during clinical procedures can potentially pose a risk of infection transmission between dental hygienists and their patients. The implementation of practices supported by available evidence are best practices to ensure patient and provider safety in oral health settings. More studies in dental clinical environment would shape future practices and protocols, ultimately to ensure safe clinical care delivery. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 as a severe respiratory disease has been prevalent around the world since its first discovery in 2019.As a single-stranded RNA virus, its high mutation rate makes its variants manifold and enables some of them to have high pathogenicity, such as Omicron variant, the most prevalent virus now. Research on the relationship of these SARS-CoV-2 variants, especially exploring their difference is a hot issue. In this study, we constructed a geometric space to represent all SARS-CoV-2 sequences of different variants. An alignment-free method: natural vector method was utilized to establish genome space. The genome space of SARS-CoV-2 was constructed based on the 24-dimensional natural vector and the appropriate metric was determined through performing phylogenetic analysises. Phylogenetic trees of different lineages constructed under the selected natural vector and metric coincided with the lineage naming standards, which means lineages with same alphabetical prefix cluster in phylogenetic trees. Furthermore, the relationships between the various GISAID clades as depicted by the natural graph primarily matched the description provided in the GISAID clade naming.The validity of our geometric space was demonstrated by these phylogenetic analysis results. So in this research, we constructed a geometry space for the genomes of the novel coronavirus SARS-CoV-2, which allows us to compare the different variants. Our geometric space is valuable for resolving the issues insides the virus., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

This article presents a causal inference analysis of vaccine hesitancy for Coronavirus disease 2019 (COVID-19) vaccines based on socio-demographic data obtained via questionnaires applied to a sample of the Brazilian population. This data includes the respondents' political preferences, age group, education, salary range, country region, sex, believing fake news, vaccine confidence, and intention to get the COVID-19 vaccine. The research created a causal graph using these variables, seeking to answer questions about the probability of people getting vaccinated. The results of this research corroborate findings observed in the literature, also presenting unique findings: (i) The perception that the vaccine is safe is positively affected by age group and negatively by religion; (ii) The older the person, the greater the probability of considering the vaccine safe and, consequently, of getting vaccinated; (iii) The religion variable showed great importance in the model since it has a simultaneous causal effect on political preferences and the perception of vaccine safety; (iv) The data reveal that the probability of a person accepting the vaccination against COVID-19 is reduced given the fact that they believe fake news related to the vaccine. The methodology applied in this research can be replicated for populations from other countries so that it is possible to generate customized models. General causal models can be helpful for agencies dealing with vaccine hesitancy to decide which variables should be addressed to reduce this phenomenon., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Adjuvants enhance the body's immune response to a vaccine, often leading to better protection against diseases. Monophosphoryl lipid A analogues (MPLA, TLR4 agonists), α-galactosylceramide analogues (NKT cell agonists), and imidazoquinoline compounds (TLR7/8 agonists) are emerging novel adjuvants on market or under clinical trials. Despite significant interest in these adjuvants, a direct comparison of their adjuvant activities remains unexplored. We initially assessed the activities of various adjuvants from three distinct categories using the SARS-CoV-2 RBD trimer antigen. TLR4 and TLR7/8 agonists are discovered to elicit robust IgG2a/2b antibodies, which is crucial for eliciting antibody dependent cytotoxicity. While α-galactosylceramide analogs induced mainly IgG1 antibody. Then, because of the flexibility of the TLR7/8 agonist, we designed and synthesized a tri-component self-adjuvanting SARS-CoV-2 RBD vaccine, featuring a covalent TLR7 agonist and targeting mannoside. Animal studies indicated that this vaccine generated antigen-specific humoral immunity. Yet, its immunogenicity seems compromised, indicating the complexity of the vaccine., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Long COVID was reported as a multi-systemic condition after the infection of SARS-CoV-2, and more than 65 million people are suffering from this disease. It has been noted that around 10% of severe SARS-CoV-2 infected individuals are suffering from the enduring effects of long COVID. The symptoms of long COVID have also been noted in several mild or asymptomatic SARS-CoV-2 infected individuals. While limited reports on clinical trials investigating new therapeutics for long COVID exist, there is an abundance of scattered information available regarding these trials. This review explores the extensive literature search, and complete clinical trial database search to map the current status of long COVID clinical trials worldwide. The study listed about 110 long COVID clinical trials. In addition to conducting extensive long COVID clinical trials, we have comprehensively presented an overview of the condition, its symptoms, notable manifestations, associated clinical trials, the unique challenges it poses, and our recommendations for addressing long COVID., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

SARS-CoV-2 is an enveloped RNA virus that causes severe respiratory illness in humans and animals. It infects cells by binding the Spike protein to the host's angiotensin-converting enzyme 2 (ACE2). The bat is considered the natural host of the virus, and zoonotic transmission is a significant risk and can happen when humans come into close contact with infected animals. Therefore, understanding the interconnection between human, animal, and environmental health is important to prevent and control future coronavirus outbreaks. This work aimed to systematically review the literature to identify characteristics that make mammals suitable virus transmitters and raise the main computational methods used to evaluate SARS-CoV-2 in mammals. Based on this review, it was possible to identify the main factors related to transmissions mentioned in the literature, such as the expression of ACE2 and proximity to humans, in addition to identifying the computational methods used for its study, such as Machine Learning, Molecular Modeling, Computational Simulation, between others. The findings of the work contribute to the prevention and control of future outbreaks, provide information on transmission factors, and highlight the importance of advanced computational methods in the study of infectious diseases that allow a deeper understanding of transmission patterns and can help in the development of more effective control and intervention strategies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The main protease (M Pro ) of SARS-CoV-2, the causative agent of COVID-19, is a pivotal nonstructural protein critical for viral replication and pathogenesis. Its protease function relies on three active site pockets for substrate recognition and a catalytic cysteine for enzymatic activity. To develop potential SARS-CoV-2 antivirals, we successfully synthesized a diverse range of azapeptide inhibitors with various covalent warheads to target M Pro 's catalytic cysteine. Our characterization identified potent M Pro inhibitors, including MPI89 that features an aza-2,2-dichloroacetyl warhead with a remarkable EC 50 value of 10 nM against SARS-CoV-2 infection in ACE2 + A549 cells and a selective index of 875. MPI89 is also remarkably selective and shows no potency against SARS-CoV-2 papain-like protease and several human proteases. Crystallography analyses demonstrated that these inhibitors covalently engaged the catalytic cysteine and used the aza-amide carbonyl oxygen to bind to the oxyanion hole. MPI89 stands as one of the most potent M Pro inhibitors, suggesting the potential for further exploration of azapeptides and the aza-2,2-dichloroacetyl warhead for developing effective therapeutics against COVID-19., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The surveillance of COVID-19 pandemic has led to the determination of millions of genome sequences of the SARS-CoV-2 virus, with the accumulation of a wealth of information never collected before for an infectious disease. Exploring the information retrieved from the GISAID database reporting at that time >13 million genome sequences, we classified the 141,639 unique missense mutations detected in the first two-and-a-half years (up to October 2022) of the pandemic. Notably, our analysis indicates that 98.2 % of all possible conservative amino acid replacements occurred. Even non-conservative mutations were highly represented (73.9 %). For a significant number of residues (3 %), all possible replacements with the other nineteen amino acids have been observed. These observations strongly indicate that, in this time interval, the virus explored all possible alternatives in terms of missense mutations for all sites of its polypeptide chain and that those that are not observed severely affect SARS-CoV-2 integrity. The implications of the present findings go well beyond the structural biology of SARS-CoV-2 as the huge amount of information here collected and classified may be valuable for the elucidation of the sequence-structure-function relationships in proteins., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Antiviral therapeutics are highly effective countermeasures for the treatment of coronavirus disease 2019 (COVID-19). However, development of resistance to antivirals undermines their effectiveness. Combining multiple antivirals during patient treatment has the potential to overcome the evolutionary selective pressure towards antiviral resistance, as well as provide a more robust and efficacious treatment option. The current evidence for effective antiviral combinations to inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication is limited. Here, we demonstrate a combination of nirmatrelvir with ombitasvir, to jointly bring about potent inhibition of SARS-CoV-2 replication. We developed an in vitro 384- well plate cytopathic effect assay for the evaluation of antiviral combinations against Calu-3 cells infected with SARS-CoV-2 and found, that a combination of ombitasvir and nirmatrelvir was synergistic; thereby decreasing the nirmatrelvir IC 50 by approx. 16-fold. The increased potency of the nirmatrelvir-ombitasvir combination, over nirmatrelvir alone afforded a greater than 3 log 10 reduction in viral titre, which is sufficient to fully prevent the detection of progeny SARS-CoV-2 viral particles at 48 h post infection. The mechanism of this potentiated effect was shown to be, in-part, due to joint inhibition of the 3-chymotrypsin-like protease via a positive allosteric modulation mechanism., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Crown Copyright © 2024. Published by Elsevier B.V. All rights reserved.)

Coronaviruses contain one of the largest genomes among the RNA viruses, coding for 14-16 non-structural proteins (nsp) that are involved in proteolytic processing, genome replication and transcription, and four structural proteins that build the core of the mature virion. Due to conservation across coronaviruses, nsps form a group of promising drug targets as their inhibition directly affects viral replication and, therefore, progression of infection. A minimal but fully functional replication and transcription complex was shown to be formed by one RNA-dependent RNA polymerase (nsp12), one nsp7, two nsp8 accessory subunits, and two helicase (nsp13) enzymes. Our approach involved, targeting nsp12 and nsp13 to allow multiple starting point to interfere with virus infection progression. Here we report a combined in-vitro repurposing screening approach, identifying new and confirming reported SARS-CoV-2 nsp12 and nsp13 inhibitors., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic led to global shortages in laboratory consumables, in particular for automated PCR. The Technical University of Denmark supported Danish hospitals from 2020 to 2022, conducting SARS-CoV-2 RT-qPCR on around 10,000 patient samples daily. We encountered shortages of disposable pipette tips used with automated liquid handlers that transferred oropharyngeal swab samples to 96-well microplates before RNA extraction. To enable tip reuse, we developed an automated protocol for washing tips with a 0.5 % sodium hypochlorite solution. This effectively eliminated carry-over of genomic material and the wash solution remained effective when stored in an open reservoir at ambient temperatures for 24 h. A three-day validation setup demonstrated the robustness of the tip wash protocol. Reducing the number of tips used for transferring samples to 96-well microplates from 96 to 8 enabled us to mitigate pipette tip shortages, lower costs, and minimize plastic waste generation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Four years after its outbreak, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains a global challenge for human health. At its surface, SARS-CoV-2 features numerous extensively glycosylated spike proteins. This glycan coat supports virion docking and entry into host cells and at the same time renders the virus less susceptible to neutralizing antibodies. Given the high genetic plasticity of SARS-CoV-2 and the rapid emergence of immune escape variants, targeting the glycan shield by carbohydrate-binding agents emerges as a promising strategy. However, the potential of carbohydrate-targeting reagents as viral inhibitors remains underexplored. Here, we tested seven plant-derived carbohydrate-binding proteins, called lectins, and one crude plant extract for their antiviral activity against SARS-CoV-2 in two types of human lung cells: A549 cells ectopically expressing the ACE2 receptor and Calu-3 cells. We identified three lectins and an Allium porrum (leek) extract inhibiting SARS-CoV-2 infection in both cell systems with selectivity indices (SI) ranging between >2 and >299. Amongst these, the lectin Concanavalin A (Con A) exerted the most potent and broad activity against a panel of SARS-CoV-2 variants. We used multiplex super-resolution microscopy to address lectin interactions with SARS-CoV-2 and its host cells. Notably, we discovered that Con A not only binds to SARS-CoV-2 virions and their host cells, but also causes SARS-CoV-2 aggregation. Thus, Con A exerts a dual mode-of-action comprising both, antiviral and virucidal, mechanisms. These results establish Con A and other plant lectins as candidates for COVID-19 prevention and basis for further drug development., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Optimal sampling, preservation, and culturing of SARS-CoV-2 from COVID-19 patients are critical for successful recovery of virus isolates and to accurately estimate contagiousness of the patient. In this study, we investigated the influence of the type of sampling media, storage time, freezing conditions, sterile filtration, and combinations of these to determine the optimal pre-analytic conditions for virus recovery and estimation of infectious viral load in COVID-19 patients. Further, we investigated the viral shedding kinetics and mucosal antibody response in 38 COVID-19 hospitalized patients. We found Universal Transport Medium (Copan) to be the most optimal medium for preservation of SARS-CoV-2 infectivity. Our data showed that the probability of a positive viral culture was strongly correlated to Ct values, however some samples did not follow the general trend. We found a significant correlation between plaque forming units and levels of mucosal antibodies and found that high levels of mucosal antibodies correlated with reduced chance of isolating the virus. Our data reveals essential parameters to consider from specimen collection over storage to culturing technique for optimal chance of isolating SARS-CoV-2 and accurately estimating patient contagiousness., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The symptomatology of COVID-19 is dependent on the immune status and the cytokine response of the host. The cytokine level of the host is influenced by the presence of chronic persistent or latent infections with co-pathogens. Parasitic diseases are known to induce host immune-modulation which may impact the response to co-infection. Toxoplasmosis is a widespread protozoal infection that remains quiescent in its latent form to be re-activated during states of immune depression. Clinical data on the relation between toxoplasmosis and COVID-19 cytokine profile and symptomatology are still insufficient. Seventy-nine subjects were included in this study. Patients were diagnosed with COVID-19 by PCR. Serological testing for toxoplasmosis was performed by the detection of anti-Toxoplasma IgG antibodies, in addition to IgG avidity testing. IFN-γ and TNF-α levels were determined by RT-PCR. Among patients diagnosed with COVID-19, 67.1% were seronegative for anti-Toxoplasma IgG, while 32.9% were seropositive. High avidity was found in 10 cases (40% of seropositive cases), 4 of whom required ICU administration, while low avidity was found in 15 cases (60%), 7 of which were administered to the ICU. TNF-α and INF-γ levels were significantly higher in COVID-19 patients than in healthy control subjects. No significant association was found between the seroprevalence of toxoplasmosis and the presence of COVID-19 and its severity. Cytokines were significantly higher in both seropositive and seronegative COVID-19 patients than in their control counterparts. The high prevalence of toxoplasmosis merits further exploration of its relation to COVID-19 by mass studies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Incarcerated populations experienced high rates of SARS-CoV-2 infection and death during early phases of the COVID-19 pandemic. To evaluate vaccine effectiveness in the carceral context, we investigated the first outbreak of COVID-19 in a California state prison following widespread rollout of vaccines to residents in early 2021. We identified a cohort of 733 state prison residents presumed to be exposed between May 14 and June 22, 2021. 46.9 % (n = 344) were vaccinated, primarily with two doses of mRNA-1273 (n = 332, 93.6 %). In total, 92 PCR-positive cases were identified, of which 14 (14.5 %) occurred among mRNA-1273 vaccinated residents. No cases required hospitalization. All nine isolates collected belonged to the Alpha (B.1.1.7) variant. We used Cox proportional hazard regression to estimate vaccine effectiveness for at least one dose of any vaccine at the start of the outbreak. Vaccine effectiveness was 86 % (95 % CI: 75 %-97 %) against PCR-confirmed infection, with similar results for symptomatic infection. Higher rates of building-level vaccine uptake were associated with a lower overall rate of PCR-confirmed infection and symptomatic infection among unvaccinated residents. Among unvaccinated residents who lived in shared cells at the time of presumed exposure, exposure to a vaccinated cellmate was associated with a 38% (95% CI: 0.37, 1.04) lower hazard rate of PCR-confirmed infection over the study period. In this outbreak involving the Alpha SARS-CoV-2 variant, vaccination conferred direct and possibly indirect protection against SARS-CoV-2 infection and symptomatic COVID-19. Our results support the importance of vaccine uptake in mitigating outbreaks and severe disease in the prison setting and the consideration of community vaccination levels in policy and infection response., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier India Pvt Ltd. All rights reserved.)

Angiotensin-converting enzyme 2 (ACE2) is responsible for cell fusion with SARS-CoV viruses. ACE2 is contained in different areas of the human body, including the nasal cavity, which is considered the main entrance for different types of airborne viruses. We took advantage of the roles of ACE2 and the nasal cavity in SARS-CoV-2 replication and transmission to develop a nasal dry powder. Recombinant ACE2 (rhACE2), after a proper encapsulation achieved via spray freeze drying, shows a binding efficiency with spike proteins of SARS-CoV-2 higher than 77 % at quantities lower than 5 µg/ml. Once delivered to the nose, encapsulated rhACE2 led to viability and permeability of RPMI 2650 cells of at least 90.20 ± 0.67 % and 47.96 ± 4.46 %, respectively, for concentrations lower than 1 mg/ml. These results were validated using nasal dry powder containing rhACE2 to prevent or treat infections derived from SARS-CoV-2., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

This paper presents quasiexperimental evidence of Covid-19 transmission through casual contact between customers in retail stores. For a large sample of individuals in Denmark, we match card payment data, indicating exactly where and when each individual made purchases, with Covid-19 test data, indicating when each individual was tested and whether the test was positive. The resulting dataset identifies more than 100,000 instances where an infected individual made a purchase in a store and, in each instance, allows us to track the infection dynamics of other individuals who made purchases in the same store around the same time. We estimate transmissions by comparing the infection rate of exposed customers, who made a purchase within 5 min of an infected individual, and nonexposed customers, who made a purchase in the same store 16 to 30 min before. We find that exposure to an infected individual in a store increases the infection rate by around 0.12 percentage points ( P < 0.001) between day 3 and day 7 after exposure. The estimates imply that transmissions in stores contributed around 0.04 to the reproduction number for the average infected individual and significantly more in the period where Omicron was the dominant variant., Competing Interests: Competing interests statement:The authors declare no competing interest.

This paper presents an enhanced version of our previously developed bio-optical transceiver, presenting a significant advancement in nanosensor technology. Using self-assembled polymers, this nanodevice is capable of electron detection while maintaining biocompatibility, an essential feature for in vivo medical biosensors. This enhancement finds significance in the field of infectious disease control, particularly in the early detection of respiratory viruses, including high-threat pathogens such as SARS-CoV-2. The proposed system harnesses bioluminescence by converting electric signaling to visible blue light, effectively opening the path of linking nano-sized mechanisms to larger-scale systems, thereby pushing the boundaries of in vivo biomedical sensing. The performance evaluation of our technology is analytical and is based on the use of Markov chains, through which we assess the bit error probability. The calculated improvements indicate that this technology qualifies as a forerunner in terms of supporting the communication needs of smaller, safer, and more efficient manufactured sensor technologies for in vivo medical applications.

As the COVID-19 pandemic reached its peak, many countries implemented genomic surveillance systems to track the evolution and transmission of SARS-CoV-2. Transition from the pandemic to the endemic phase prioritized alternative testing strategies to maintain effective epidemic surveillance at the population level, with less intensive sequencing efforts. One such promising approach was Wastewater-Based Surveillance (WBS), which offers non-invasive, cost-effective means for analysing virus trends at the sewershed level. From 2020 onwards, wastewater has been recognized as an instrumental source of information for public health, with national and international authorities exploring options to implement national wastewater surveillance systems and increasingly relying on WBS as early warning of potential pathogen outbreaks. In Portugal, several pioneer projects joined the academia, water utilities and Public Administration around WBS. To validate WBS as an effective genomic surveillance strategy, it is crucial to collect long term performance data. In this work, we present one year of systematic SARS-CoV-2 wastewater surveillance in Portugal, representing 35 % of the mainland population. We employed two complementary methods for lineage determination - allelic discrimination by RT-PCR and S-gene sequencing. This combination allowed us to monitor variant evolution in near-real-time and identify low-frequency mutations. Over the course of this year-long study, spanning from May 2022 to April 2023, we successfully tracked the dominant Omicron sub-lineages, their progression and evolution, which aligned with concurrent clinical surveillance data. Our results underscore the effectiveness of WBS as a tracking system for virus variants, with the ability to unveil mutations undetected via massive sequencing of clinical samples from Portugal, demonstrating the ability of WBS to uncover new mutations and detect rare genetic variants. Our findings emphasize that knowledge of the genetic diversity of SARS-CoV-2 at the population level can be extended far beyond via the combination of routine clinical genomic surveillance with wastewater sequencing and genotyping., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: To determine the effect of SARS-CoV-2 variants on non-respiratory features of COVID-19 in vaccinated and not fully vaccinated patients using a University of California database., Methods: A longitudinal retrospective review of medical records (n = 63,454) from 1/1/2020-4/26/2022 using the UCCORDS database was performed to compare non-respiratory features, vaccination status, and mortality between variants. Chi-square tests were used to study the relationship between categorical variables using a contingency matrix., Results: Fever was the most common feature across all variants. Fever was significantly higher in not fully vaccinated during the Delta and Omicron waves (p = 0.001; p = 0.001). Cardiac features were statistically higher in not fully vaccinated during Omicron; tachycardia was only a feature of not fully vaccinated during Delta and Omicron; diabetes and GI reflux were features of all variants regardless of vaccine status. Odds of death were significantly increased among those not fully vaccinated in the Delta and Omicron variants (Delta OR: 1.64, p = 0.052; Omicron OR: 1.96, p < 0.01). Vaccination was associated with a decrease in the frequency of non-respiratory features., Conclusions: Risk of non-respiratory features of COVID-19 is statistically higher in those not fully vaccinated across all variants. Risk of death and correlation with vaccination status varied., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Post vaccine immunity following COVID-19 mRNA vaccination may be driven by extrinsic, or controllable and intrinsic, or inherent health factors. Thus, we investigated the effects of extrinsic and intrinsic on the peak antibody response following COVID-19 primary vaccination and on the trajectory of peak antibody magnitude and durability over time. Participants in a longitudinal cohort attended visits every 3 months for up to 2 years following enrollment. At baseline, participants provided information on their demographics, recreational behaviors, and comorbid health conditions which guided our model selection process. Blood samples were collected for serum processing and spike antibody testing at each visit. Cross-sectional and longitudinal models (linear-mixed effects models) were generated to assess the relationship between selected intrinsic and extrinsic health factors on peak antibody following vaccination and to determine the influence of these predictors on antibody over time. Following cross-sectional analysis, we observed higher peak antibody titers after primary vaccination in females, those who reported recreational drug use, younger age, and prior COVID-19 history. Following booster vaccination, females and Hispanics had higher peak titers after the 3rd and 4th doses, respectively. Longitudinal models demonstrated that Moderna mRNA-1273 recipients, females, and those previously vaccinated had increased peak titers over time. Moreover, drug users and half-dose Moderna mRNA-1273 recipients had higher peak antibody titers over time following the first booster, while no predictive factors significantly affected post-second booster antibody responses. Overall, both intrinsic and extrinsic health factors play a significant role in shaping humoral immunogenicity after initial vaccination and the first booster. The absence of predictive factors for second booster immunogenicity suggests a more robust and consistent immune response after the second booster vaccine administration., Competing Interests: Florian Krammer has been consulting for Curevac, Seqirus and Merck and is currently consulting for Pfizer, Third Rock Ventures, Avimex and GSK. He is named on several patent regarding influenza virus and SARS-CoV-2 virus vaccines, influenza virus therapeutics and SARS-CoV-2 serological tests. Some of these technologies have been licensed to commercial entities and Dr. Krammer is receiving royalties from these entities. Dr. Krammer is also an advisory board member of Castlevax, a spin-off company formed by the Icahn School of Medicine at Mount Sinai to develop SARS-CoV-2 vaccines. The Krammer laboratory has received funding for research projects from Pfizer, GSK and Dynavax and three of Dr. Krammer’s mentees have recently joined Moderna. All other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. This does not alter our adherence to PLOS ONE policies on sharing data and/or materials., (Copyright: © 2024 Tribin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

SARS-CoV-2 spreads pandemically since 2020; in 2021, effective vaccinations became available and vaccination campaigns commenced. Still, it is hard to track the spread of the infection or to assess vaccination success in the broader population. Measuring specific anti-SARS-CoV-2 antibodies is the most effective tool to track the spread of the infection or successful vaccinations. The need for venous-blood sampling however poses a significant barrier for large studies. Dried-blood-spots on filter-cards (DBS) have been used for SARS-CoV-2 serology in our laboratory, but so far not to follow quantitative SARS-CoV-2 anti-spike reactivity in a longitudinal cohort. We developed a semi-automated protocol or quantitative SARS-CoV-2 anti-spike serology from self-sampled DBS, validating it in a cohort of matched DBS and venous-blood samples ( n = 825). We investigated chromatographic effects, reproducibility, and carry-over effects and calculated a positivity threshold as well as a conversion formula to determine the quantitative binding units in the DBS with confidence intervals. Sensitivity and specificity reached 96.63% and 97.81%, respectively, compared to the same test performed in paired venous samples. Between a signal of 0.018 and 250 U/mL, we calculated a correction formula. Measuring longitudinal samples during vaccinations, we demonstrated relative changes in titers over time in several individuals and in a longitudinal cohort over four follow-ups. DBS sampling has proven itself for anti-nucleocapsid serosurveys in our laboratory. Similarly, anti-spike high-throughput DBS serology is feasible as a complementary assay. Quantitative measurements are accurate enough to follow titer dynamics in populations also after vaccination campaigns. This work was supported by the Bavarian State Ministry of Science and the Arts; LMU University Hospital, LMU Munich; Helmholtz Center Munich; University of Bonn; University of Bielefeld; German Ministry for Education and Research (proj. nr.: 01KI20271 and others) and the Medical Biodefense Research Program of the Bundeswehr Medical Service. Roche Diagnostics provided kits and machines for analyses at discounted rates. The project is funded also by the European-wide Consortium ORCHESTRA. The ORCHESTRA project has received funding from the European Union's Horizon 2020 research and innovation program under grant agreement No 101016167. The views expressed in this publication are the sole responsibility of the author, and the Commission is not responsible for any use that may be made of the information it contains.IMPORTANCESARS-CoV-2 has been spreading globally as a pandemic since 2020. To determine the prevalence of SARS-CoV-2 antibodies among populations, the most effective public health tool is measuring specific anti-SARS-CoV-2 antibodies induced by infection or vaccination. However, conducting large-scale studies that involve venous-blood sampling is challenging due to the associated feasibility and cost issues. A more cost-efficient and less invasive method for SARS-CoV-2 serological testing is using Dried-Blood-Spots on filter cards (DBS). In this paper, we have developed a semi-automated protocol for quantifying SARS-CoV-2 anti-spike antibodies from self-collected DBS. Our laboratory has previously successfully used DBS sampling for anti-nucleocapsid antibody surveys. Likewise, conducting high-throughput DBS serology for anti-spike antibodies is feasible as an additional test that can be performed using the same sample preparation as the anti-nucleocapsid analysis. The quantitative measurements obtained are accurate enough to track the dynamics of antibody levels in populations, even after vaccination campaigns., Competing Interests: The study was supported by multiple funders which includes Roche Diagnostics, providing machinery and kits for discounted rates. A.W. and M.H. have received personal (advisory) and material support from Roche, which was not related to the conduct of DBS serology presented within this study. The authors have no other relevant conflicts of interest to declare regarding the conduct of the study.

Objective: The purpose of this article is to evaluate the COVID-19 Care in the Home (CCITH) program during the first COVID-19 omicron wave across Torres Strait and Cape York region of Far North Queensland in 2022., Methods: A mixed-method study: An online survey and semi-structured interviews of CCITH internal and external stakeholders and participants was utilised to develop a greater understanding of perspectives of the program., Results: Survey participants n=140. Most survey respondents did not attend hospital, emergency, or primary healthcare centre during isolation for medical assistance (82%, 115/140) and most strongly agreed/agreed (87%, 122/140) that the CCITH program cared for their health needs. Interview participants n=14. Thematic analysis of interviews verified survey responses and identified successes of this program including improved community relationships and primary healthcare centres and community members felt supported. Limitations included rapid changes to policies and roles and limited food availability during isolation., Conclusions: The CCITH program highlights the resilience and self-determination of First Nations communities and primary health staff across the Torres Strait and Cape York throughout the first COVID-19 outbreak in the region., Implications for Public Health: This virtual model of care could be employed in similar settings to improve service provision in both primary and public health to increase community safety and achieve good health outcomes., Competing Interests: Conflicts of interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

This paper evaluates the effects of economic shocks to current and expected income reduction on mental wellbeing. We use individual-level data from three East Asian countries; China, Japan, and South Korea, during the early phases of the pandemic when the COVID-induced economic shocks were severe. The findings reveal significant causal effects from current and expected income reduction on different aspects of mental health deterioration, including anxiety, trouble sleeping, boredom, and loneliness. Interestingly, we found that expectations of future income loss have a significantly larger effect on people's mental wellbeing compared to current falls in income. This has significant implications for the design of policies to support income during pandemics., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Neighborhood parks are important venues to support moderate-to-vigorous (MVPA) activity. There has been a noticeable increase promoting physical activity among youth in neighborhood parks. This paper aims to assess the association between park use and MVPA among low-income youth in a large urban area. We recruited a cohort of 434 youth participants during the COVID pandemic years (2020-2022) from low-income households in Washington, D.C. We collected multiple data components: accelerometry, survey, and electronic health record data. We explored the bivariate relationship between the accelerometer-measured daily MVPA time outcome and survey-based park use measures. A mixed-effect model was fitted to adjust the effect estimate for participant-level and time-varying confounders. The overall average daily MVPA time is 16.0 min (SD = 12.7). The unadjusted bivariate relation between daily MVPA time and frequency of park visit is 1.3 min of daily MVPA time per one day with park visits (p < 0.0001). The model-adjusted estimate is 0.7 daily MVPA minutes for 1 day with park visit (p = 0.04). The duration of a typical park visit is not a significant predictor to daily MVPA time with or without adjustments. The initial COVID outbreak in 2020 resulted in a significant decline in daily MVPA time (- 4.7 min for 2020 versus 2022, p < 0.0001). Park visit frequency is a significant predictor to low-income youth's daily MVPA time with considerable absolute effect sizes compared with other barriers and facilitators. Promoting more frequent park use may be a useful means to improve low-income youth's MVPA outcome., (© 2024. The New York Academy of Medicine.)

The SARS-CoV-2 caused COVID-19 pandemic has posed a global health hazard. While some vaccines have been developed, protection against viral infection is not perfect because of the urgent approval process and the emergence of mutant SARS-CoV-2 variants. Here, we employed UDCA as an FXR antagonist to regulate ACE2 expression, which is one of the key pathways activated by SARS-CoV-2 Delta variant infection. UDCA is a well-known reagent of liver health supplements and the only clinically approved bile acid. In this paper, we investigated the protective efficacy of UDCA on Omicron variation, since it has previously been verified for protection against Delta variant. When co-housing with an Omicron variant-infected hamster group resulted in spontaneous airborne transmission, the UDCA pre-supplied group was protected from weight loss relative to the non-treated group at 4 days post-infection by more than 5%-10%. Furthermore, UDCA-treated groups had a 3-fold decrease in ACE2 expression in nasal cavities, as well as reduced viral expressing genes in the respiratory tract. Here, the data show that the UDCA serves an alternative option for preventive drug, providing SARS-CoV-2 protection against not only Delta but also Omicron variant. Our results of this study will help to propose drug-repositioning of UDCA from liver health supplement to preventive drug of SARS-CoV-2 infection., (© 2024 The Authors. Pharmacology Research & Perspectives published by British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics and John Wiley & Sons Ltd.)

SARS-CoV-2 has brought a global health crisis worldwide. IgM is an early marker in sera after the infections, and the detection of IgM is crucial to assist diagnosis and evaluate the vaccination clinically. Herein, we developed an automated platform to identify IgM against SARS-CoV-2 in sera. Streptavidin-magnetic beads were utilized to bind to a biotinylated anti-IgM antibody, which was employed to capture IgM in sera. RBD fused luciferase hGluc was employed to label the trapped IgM against RBD and the signal of luminescence of hGluc with the substrate of coelenterazine corresponded to the amount of SARS-CoV-2 IgM conjugated to the magnetic beads. An appropriate cut-off value of the designed method was defined by a set of negative samples and positive samples with 100 % sensitivity and 100 % specificity. Through serial dilution of a positive sample, it was found that the method has a better sensitivity than ELISA. The application to determine IgM against SARS-CoV-2 demonstrated a good performance of the method. The developed system can complete the analysis of SARS-CoV-2 IgM within 25 min. Through the substitution of RBD antigen with antigens of other pathogens in this platform, the automated detection of IgM against the corresponding pathogens can be realized., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The main proteinase (M pro ) of SARS-CoV-2 plays a critical role in cleaving viral polyproteins into functional proteins required for viral replication and assembly, making it a prime drug target for COVID-19. It is well known that noncompetitive inhibition offers potential therapeutic options for treating COVID-19, which can effectively reduce the likelihood of cross-reactivity with other proteins and increase the selectivity of the drug. Therefore, the discovery of allosteric sites of M pro has both scientific and practical significance. In this study, we explored the binding characteristics and inhibiting process of M pro activity by two recently reported allosteric inhibitors, pelitinib and AT7519 which were obtained by the X-ray screening experiments, to probe the allosteric mechanism via molecular dynamic (MD) simulations. We found that pelitinib and AT7519 can stably bind to M pro far from the active site. The binding affinity is estimated to be -24.37 ± 4.14 and - 26.96 ± 4.05 kcal/mol for pelitinib and AT7519, respectively, which is considerably stable compared with orthosteric drugs. Furthermore, the strong binding caused clear changes in the catalytic site of M pro , thus decreasing the substrate accessibility. The community network analysis also validated that pelitinib and AT7519 strengthened intra- and inter-domain communication of M pro dimer, resulting in a rigid M pro , which could negatively impact substrate binding. In summary, our findings provide the detailed working mechanism for the two experimentally observed allosteric sites of M pro . These allosteric sites greatly enhance the 'druggability' of M pro and represent attractive targets for the development of new M pro inhibitors., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Competing Interests: Conflicts of interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Until now, the World Health Organization registered over 771 million cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection worldwide, of which 6.97 million resulted in death. Virus-related cardiovascular events and pre-existing heart problems have been identified as major contributing factors to global infection-related morbidity and mortality, emphasizing the necessity for risk assessment and future prevention. In this review, we highlight cardiac manifestations that might arise from an infection with SARS-CoV-2 and provide an overview of known comorbidities that worsen the outcome. Additionally, we aim to summarize the therapeutic strategies proposed to reverse virus-associated myocardial damage, which will be further highlighted in this review, with an outlook to successful recovery and prevention., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The COVID-19 pandemic has shown the need to develop effective therapeutics in preparedness for further epidemics of virus infections that pose a significant threat to human health. As a natural compound antiviral candidate, we focused on α-dystroglycan, a highly glycosylated basement membrane protein that links the extracellular matrix to the intracellular cytoskeleton. Here we show that the N-terminal fragment of α-dystroglycan (α-DGN), as produced in E. coli in the absence of post-translational modifications, blocks infection of SARS-CoV-2 in cell culture, human primary gut organoids and the lungs of transgenic mice expressing the human receptor angiotensin I-converting enzyme 2 (hACE2). Prophylactic and therapeutic administration of α-DGN reduced SARS-CoV-2 lung titres and protected the mice from respiratory symptoms and death. Recombinant α-DGN also blocked infection of a wide range of enveloped viruses including the four Dengue virus serotypes, influenza A virus, respiratory syncytial virus, tick-borne encephalitis virus, but not human adenovirus, a non-enveloped virus in vitro. This study establishes soluble recombinant α-DGN as a broad-band, natural compound candidate therapeutic against enveloped viruses., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. Maria Giulia Bigotti, Katja Klein, Andrea Brancaccio and Yohei Yamauchi have patent #GB 2315095.6. issued to University of Bristol. Eng Eong Ooi has served in various advisory capacities on dengue vaccines for Sanofi Pasteur and MSD and served on the advisory board on dengue vaccines and antiviral drugs for Takeda. All other authors declare that they have no competing interests If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Chimeric antigen receptor (CAR)-immune cell therapy has revolutionized the anti-tumor field, achieving efficient and precise tumor clearance by directly guiding immune cell activity to target tumors. In addition, the use of CAR-immune cells to influence the composition and function of the immune system and ultimately achieve virus clearance and immune system homeostasis has attracted the interest of researchers. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) triggered a global pandemic of coronavirus disease 2019 (COVID-19). To date, the rapidly mutating SARS-CoV-2 continues to challenge existing therapies and has raised public concerns regarding reinfection. In patients with COVID-19, the interaction of SARS-CoV-2 with the immune system influences the course of the disease, and the coexistence of over-activated immune system components, such as macrophages, and severely compromised immune system components, such as natural killer cells, reveals a dysregulated immune system. Dysregulated immune-induced inflammation may impair viral clearance and T-cell responses, causing cytokine storms and ultimately leading to patient death. Here, we summarize the research progress on the use of CAR-immune cells against SARS-CoV-2 infection. Furthermore, we discuss the feasibility, challenges and prospect of CAR-immune cells as a new immune candidate therapy against SARS-CoV-2., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Manila, a highly urbanized city, is listed as one of the top cities with the highest recorded number of coronavirus disease 2019 (COVID-19) cases in the Philippines. This study aimed to detect and quantify the RNA of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the Omicron variant in 51 wastewater samples collected from three locations in Manila, namely Estero de Santa Clara, Estero de Pandacan, which are open drainages, and a sewage treatment plant (STP) at De La Salle University-Manila, between July 2022 and February 2023. Using one-step reverse transcription-quantitative polymerase chain reaction, SARS-CoV-2 and Omicron variant RNA were detected in 78 % (40/51; 4.9 ± 0.5 log 10 copies/L) and 60 % (24/40; 4.4 ± 0.3 log 10 copies/L) of wastewater samples collected from all sampling sites, respectively. SARS-CoV-2 RNA was detected frequently at Estero de Santa Clara (88 %, 15/17); its highest concentration was at the STP (6.3 log 10 copies/L). The Omicron variant RNA was present in the samples collected (4.4 ± 0.3 log 10 copies/L) from all sampling sites, with the highest concentration at the STP (4.9 log 10 copies/L). Regardless of normalization, using concentrations of pepper mild mottle virus RNA, SARS-CoV-2 RNA concentrations exhibited the highest positive correlation with COVID-19 reported cases in Manila 5 days after the clinical report. These findings revealed that wastewater-based epidemiology may aid in identifying and monitoring of the presence of pathogens in open drainages and STPs in the Philippines. This paper provides the first documentation on SARS-CoV-2 and the Omicron variant in wastewater from Manila., Competing Interests: Declaration of competing interest Eiji Haramoto received research funding from Takara Bio Inc. Masaaki Kitajima received research funding from Shionogi & Co., Ltd. and AdvanSentinel, Inc. and patent royalties from Shionogi & Co., Ltd. The other authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Nonpharmaceutical interventions (NPI) are an important tool for countering pandemics such as COVID-19. Some are cheap; others disrupt economic, educational, and social activity. The latter force governments to balance the health benefits of reduced infection and death against broader lockdown-induced societal costs. A literature has developed modeling how to optimally adjust lockdown intensity as an epidemic evolves. This paper extends that literature by augmenting the classic SIR model with additional states and flows capturing decay over time in vaccine-conferred immunity, the possibility that mutations create variants that erode immunity, and that protection against infection erodes faster than protecting against severe illness. As in past models, we find that small changes in parameter values can tip the optimal response between very different solutions, but the extensions considered here create new types of solutions. In some instances, it can be optimal to incur perpetual epidemic waves even if the uncontrolled infection prevalence would settle down to a stable intermediate level., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The large amount of viral RNA produced during infections has the potential to interact with and effectively sequester cellular RNA binding proteins, thereby influencing aspects of post-transcriptional gene regulation in the infected cell. Here we demonstrate that the abundant 5' leader RNA region of SARS-CoV-2 viral RNAs can interact with the cellular polypyrimidine tract binding protein (PTBP1). Interestingly, the effect of a knockdown of PTBP1 protein on cellular gene expression is also mimicked during SARS-CoV-2 infection, suggesting that this protein may be functionally sequestered by viral RNAs. Consistent with this model, the alternative splicing of mRNAs that is normally controlled by PTBP1 is dysregulated during SARS-CoV-2 infection. Collectively, these data suggest that the SARS-CoV-2 leader RNA sequesters the cellular PTBP1 protein during infection, resulting in significant impacts on the RNA biology of the host cell. These alterations in post-transcriptional gene regulation may play a role in SARS-CoV-2 mediated molecular pathogenesis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Owing to the high mortality and strong infection ability of COVID-19, the early rapid diagnosis is essential to reduce the risk of severe symptoms and the loss of lung function. In clinic, the commonly used detection methods, including the computed tomography (CT) and reverse transcription-polymerase chain reaction (RT-PCR), are often time-consuming with bulky instruments, which normally require more than one hour to report the results. To shorten the analytical period for testing the COVID-19 virus (SARS-CoV-2), we proposed an ultrafast and ultrasensitive DNA sensors to achieve an accurate determination of the DNA sequence by the RNA reverse transcription (rtDNA) of the SARS-CoV-2. A nanocubic architecture of the MnFe@Pt crystals was constructed to integrate both electrocatalysis and conductivity to greatly improve the biosensing performance. After the immobilization of a specific capture and report DNA on above nanocomposite, the rtDNA can be rapidly caught to the DNA sensor to form a double-helix structure, thus generating the current signal change. Within only 10 min, the as-prepared DNA sensors exhibited ultralow detection limit (1 × 10 -20 M) and wide linear detection range, together with an outstanding selectivity among various interfering substances., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Introduction: With the reopening of schools during the coronavirus disease 2019 (COVID-19) pandemic, it was imperative to understand the role of students and education professionals in the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this paper, we determined the seroprevalence of the SARS-CoV-2 anti-nucleocapsid antibodies in the school community in Campo Grande, the capital and most populous city of the state of Mato Grosso do Sul (Brazil) and evaluated its association with sex, school level, and school type., Materials and Methods: The survey was carried out in 20 public and private schools in the urban region of Campo Grande using the TR DPP ® COVID-19 immunoglobulin M/immunoglobulin G (IgM/IgG) kit from the Immunobiological Technology Institute (Bio-Manguinhos, Rio de Janeiro, Brazil). Testing was carried out in three periods: from October to December 2021; from March to July 2022; and from August to November 2022. The participants were students aged 6-17 years enrolled in primary or secondary schools and professionals of different ages and roles., Results: During the first testing period, 162 participants were seropositive for the IgM and/or IgG anti-nucleocapsid SARS-CoV-2 antibodies, with an estimated seroprevalence of 19.6% using Bayesian multilevel regression. In the second period, 251 participants were seropositive (estimated seroprevalence, 34.6%), while in the third period, 393 participants were seroconverted (estimated seroprevalence, 56.7%). In 2022, there was an increase in the seroconversion rate compared to that in 2021. The most frequently described acute manifestations in the three periods were fever, headache, sore throat, and runny nose. In terms of the demographic profile, there was no predominance of seropositivity between the sexes, although women represented approximately 70% of the study population. There were also no differences between students and school staff., Discussion: The results made it possible to evaluate the extent of SARS-CoV-2 transmission in the school community through immunity developed against the virus, in addition to providing information about COVID-19 symptoms in children, adolescents, and adults., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Stutz, Alcantara, Santos, Torres, Rodrigues, Marcon, Ferreira, Sarti, Oliveira, Mendes, Lemos, Demarchi, Lichs, Zardin, Gonçalves, Guilhermino, Perdomo and Fernandez.)

Since its emergence in late 2019, SARS-CoV-2 has diversified into a large number of lineages and caused multiple waves of infection globally. Novel lineages have the potential to spread rapidly and internationally if they have higher intrinsic transmissibility and/or can evade host immune responses, as has been seen with the Alpha, Delta, and Omicron variants of concern. They can also cause increased mortality and morbidity if they have increased virulence, as was seen for Alpha and Delta. Phylogenetic methods provide the "gold standard" for representing the global diversity of SARS-CoV-2 and to identify newly emerging lineages. However, these methods are computationally expensive, struggle when datasets get too large, and require manual curation to designate new lineages. These challenges provide a motivation to develop complementary methods that can incorporate all of the genetic data available without down-sampling to extract meaningful information rapidly and with minimal curation. In this paper, we demonstrate the utility of using algorithmic approaches based on word-statistics to represent whole sequences, bringing speed, scalability, and interpretability to the construction of genetic topologies. While not serving as a substitute for current phylogenetic analyses, the proposed methods can be used as a complementary, and fully automatable, approach to identify and confirm new emerging variants., Competing Interests: Competing interests statement:The authors declare no competing interest.

As COVID-19 becomes endemic, public health departments benefit from improved passive indicators, which are independent of voluntary testing data, to estimate the prevalence of COVID-19 in local communities. Quantification of SARS-CoV-2 RNA from wastewater has the potential to be a powerful passive indicator. However, connecting measured SARS-CoV-2 RNA to community prevalence is challenging due to the high noise typical of environmental samples. We have developed a generalized pipeline using in- and out-of-sample model selection to test the ability of different correction models to reduce the variance in wastewater measurements and applied it to data collected from treatment plants in the Chicago area. We built and compared a set of multi-linear regression models, which incorporate pepper mild mottle virus (PMMoV) as a population biomarker, Bovine coronavirus (BCoV) as a recovery control, and wastewater system flow rate into a corrected estimate for SARS-CoV-2 RNA concentration. For our data, models with BCoV performed better than those with PMMoV, but the pipeline should be used to reevaluate any new data set as the sources of variance may change across locations, lab methods, and disease states. Using our best-fit model, we investigated the utility of RNA measurements in wastewater as a leading indicator of COVID-19 trends. We did this in a rolling manner for corrected wastewater data and for other prevalence indicators and statistically compared the temporal relationship between new increases in the wastewater data and those in other prevalence indicators. We found that wastewater trends often lead other COVID-19 indicators in predicting new surges., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The microbiological analysis of wastewater samples is increasingly used for the surveillance of SARS-CoV-2 globally. We described the setup process of the national SARS-CoV-2 wastewater-based surveillance system in Denmark, presented its main results during the first year of activities, from July 2021 to June 2022, and discussed their operational significance. The Danish SARS-CoV-2 wastewater-based surveillance system was designed to cover 85 % of the population in Denmark and it entailed taking three weekly samples from 230 sites. Samples were RT-qPCR tested for SARS-CoV-2 RNA, targeting the genetic markers N1, N2 and RdRp, and for two faecal indicators, Pepper Mild Mottle Virus and crAssphage. We calculated the weekly SARS-CoV-2 RNA concentration in the wastewater from each sampling site and monitored it in view of the results from individual testing, at the national and regional levels. We attempted to use wastewater results to identify potential local outbreaks, and we sequenced positive wastewater samples using Nanopore sequencing to monitor the circulation of viral variants in Denmark. The system reached its full implementation by October 2021 and covered up to 86.4 % of the Danish population. The system allowed for monitoring of the national and regional trends of SARS-CoV-2 infections in Denmark. However, the system contribution to the identification of potential local outbreaks was limited by the extensive information available from clinical testing. The sequencing of wastewater samples identified relevant variants of concern, in line with results from sequencing of human samples. Amidst the COVID-19 pandemic, Denmark implemented a nationwide SARS-CoV-2 wastewater-based surveillance system that integrated routine surveillance from individual testing. Today, while testing for COVID-19 at the community level has been discontinued, the system is on the frontline to monitor the occurrence and spread of SARS-CoV-2 in Denmark., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)