In comparison to mature platelets, reticulated platelets (RPs) are newly released from the bone marrow and exhibit a larger size, higher reactivity, and a greater quantity of RNA, and can be an agile indicator of platelet turnover. The transcriptome associated with platelet function is significantly upregulated in RPs, which is a possible explanation for RPs intrinsic hyper-reactivity. We presented a comprehensive overview of the detection techniques for RPs. Current methods to quantify RPs in clinical routine are flow cytometry and fully automated hematology analyzers (Sysmex-XE/XN, Abbott, ADVIA, Mindray), which make the detection of RPs simpler, faster and more affordable. The proportion of RPs increased in the circulation has potential diagnostic and prognostic values in multiple clinical settings (risk stratification in cardiovascular diseases, the effect on antiplatelet drugs, differential diagnosis of thrombocytopenia, monitor platelet recovery after bone marrow or stem cell transplantation, and other diseases). There have been several studies focusing on RPs in recent years, particularly in cardiovascular disease and thrombocytopenia. In this review we summarizes the current study with regard to RPs and discuss their likely contribution in clinical routine.

To determine how much of the current biomedical literature would be flagged or require modification in relation to the presence of terms from leaked lists prepared by the Centers for Disease Control (CDC), the National Science Foundation (NSF), and the National Security Administration (NSA) in early 2025.

We searched PubMed (from 1996 to 2024) for all records that match at least one of the given terms, combined the terms and analyzed yearly and total frequency.

At least 36.3% of all biomedical literature analyzed, representing more than 10 million records, would be flagged for review or modification with the given term lists. It is conservatively estimated that such term lists could impact more than 2.7 million biomedical publications over the next four years.

Censorship of scientific findings and the use of term lists to judge the content of scientific materials could significantly impede scientific progress.

Future research should investigate the long-term implications of, and interim strategies used to navigate, the imposition of censorship on the production and dissemination of scientific knowledge.

In 2021, Jesse Bloom published a study addressing why the earliest SARS-CoV-2 sequences in Wuhan from late December 2019 were not those most similar to viruses sampled in bats. The study concluded that recovered partial sequences from Wuhan and annotation of Wuhan links for other sequences increased support for one genotype as the progenitor of the SARS-CoV-2 pandemic. However, we show that the collection date for the recovered sequences was January 30, 2020, later than that of hundreds of other SARS-CoV-2 sequences. Mutations in these sequences also exhibit diversity consistent with SARS-CoV-2 sequences collected in late January 2020. Furthermore, we found that Wuhan exposure history was common for early samples, so Bloom's annotation for a single familial cluster does not support that an early genotype was undersampled in Wuhan. Both the recovered partial sequences and additional annotation align with contemporaneous data rather than increase support for a progenitor. Our findings clarify the significance of the recovered sequences and are supported by additional data and analysis published since mid-2021.

Human body constitutes unique biological system containing specific fluid mechanics and biomechanics. Traditional cell culture techniques of 2D and 3D do not recapitulate these specific natures of the human system. In addition, they lack the spatiotemporal conditions of representing the cells. Moreover, they do not enable the study of cell-cell interactions in multiple cell culture platforms. Therefore, establishing biological system of dynamic cell culture was of great interest. Organs on chips systems were fabricated proving their concept to mimic specific organs functions. Therefore, it paves the way for validating new drugs and establishes mechanisms of emerging diseases. It has played a key role in validating suitable vaccines for Coronavirus disease (COVID-19). Herein, the concept of organs on chips, fabrication methodology and their applications are discussed.

Two Cox-based multistate modeling approaches are compared for modeling a complex multicohort event history process. The first approach incorporates cohort information as a fixed covariate, thereby providing a direct estimation of the cohort-specific effects. The second approach includes the cohort as a stratum variable, which offers an extra flexibility in estimating the transition probabilities. Additionally, both approaches may include possible interaction terms between the cohort and a given prognostic predictor. Furthermore, the Markov property conditional on observed prognostic covariates is assessed using a global score test. Whenever departures from the Markovian assumption are revealed for a given transition, the time of entry into the current state is incorporated as a fixed covariate, yielding a semi-Markov process. The two proposed methods are applied to a three-wave dataset of COVID-19-hospitalized adults in the southern Barcelona metropolitan area (Spain), and the corresponding performance is discussed. While both semi-Markovian approaches are shown to be useful, the preferred one will depend on the focus of the inference. To summarize, the cohort-covariate approach enables an insightful discussion on the behavior of the cohort effects, whereas the stratum-cohort approach provides flexibility to estimate transition-specific underlying risks according to the different cohorts.

To assess the frequency of and motivations for acute respiratory illness (ARI) presenteeism in healthcare personnel (HCP) during two waves of COVID-19.

Survey.

Large academic medical center, both ambulatory and acute care settings.

All HCPs (n = 11,429) at the University of North Carolina Medical Center were eligible for two voluntary, electronic surveys: pre-Omicron (n = 591, recall period March 2020 - December 2021) and Omicron BA.1 (n = 385, recall period January - April 2022).

We compared self-reported ARI presenteeism (working despite feeling feverish plus cough and/or sore throat) and motivators across time and demographics. We also estimated effects of workplace perceptions and culture on ARI presenteeism with log-binomial regression, adjusting for age, gender, HCP role, and patient interaction.

In the pre-Omicron and Omicron BA.1 eras, 24% and 34% of respondents respectively reported at least one instance of ARI presenteeism. In both eras, clinical frontline HCP were more likely to report ARI presenteeism than other roles, as were HCP primarily providing direct patient care vs not. Pre-Omicron motivators included disciplinary action and sick leave concerns, whereas workplace culture predominated during Omicron. Feeling professional obligation to attend work and observing colleague presenteeism increased ARI presenteeism in both eras. During Omicron, COVID-19 burnout, fatigue, and unclear call-out procedures increased ARI presenteeism.

ARI presenteeism was common and had diverse motivations, including workplace culture, disciplinary action, and sick leave. Efforts to reduce presenteeism should address these factors and prioritize frontline clinical personnel with direct patient interaction.

COVID- 19, caused by the coronavirus SARS-CoV- 2, has arisen as a global health epidemic, claiming the lives of millions of people throughout the world. Combating the pandemic has involved developing and approving vaccines and antiviral products. Camostat Mesylate (Camo) is a TMPRSS2 inhibitor that inhibits virus-cell membrane fusion and, thereby, viral multiplication. Significant limitations of using oral Camo include the limited amount of Camo reaching the site of action, lungs, side effects due to distribution to all tissues, and enzymatic breakdown in the gut. This investigation aims to develop self-administrable and patient-compliant extended-release Camo-loaded pegylated nanoliposomes (Camo-pegNLs) for delivering Camo directly to the lungs, thereby enabling faster onset of action and overcoming limitations of oral Camo delivery. We developed the Camo-pegNLs were composed of 1,2-dipalmitoyl-sn-glycerol- 3-phosphocholine (DPPC), 1,2-dioleoyl-sn-glycerol- 3-phosphoethanolamine (DOPE-PEG, MW2000) and cholesterol using the ethanol injection technique and syringe pump. The NLs were characterized for their particle size, polydispersity index (PDI), and zeta potential using Malvern Zetasizer. The assay, unentrapped Camo using Vivaspin 500 ultrafilter (10 kDa) and in-vitro release were determined. The Camo content was analyzed using a validated HPLC method. The aerodynamic properties of Camo-pegNLs were determined using a Westech Andersen Cascade Impactor (ACI) at 28.3L/min and a pneumatic jet nebulizer. The antiviral effect of Camo-pegNLs was assessed in Vero cells expressing TMPRSS2 and infected with SARS-CoV- 2. Camo-pegNLs suspension showed size of 167.50 ± 0.90 nm, zeta potential of 0.48 ± 0.04 mV, and PDI of 0.07 ± 0.01. The quantity of entrapped Camo was found to be 44.86 ± 1.35%w/v, and the drug loading was 27.41 ± 0.04%w/w. The Camo-pegNL- 2 had an extended release of up to 24 h, MMAD of 4.295 ± 0.1 µm, GSD of 1.915 ± 0.064, and FPF of 42.01% ± 6.90. Camo-pegNLs showed a significant antiviral effect on Vero cells compared to no treatment group (p < 0.01). An efficacious nebulized Camo-pegNLs suspension product was successfully developed for direct lung delivery to Camo-pegNLs to treat the SARS-CoV- 2 infection.

Scientific evidence is lacking for the respiratory etiquette maneuver of coughing into the elbow. This pilot study introduces and evaluates a novel maneuver " coughing into the shirt" comparing effectiveness of containing respiratory plumes to existing respiratory etiquette strategies.

In this open-bench, observational respiratory etiquette pilot study, five healthcare workers performed four respiratory etiquette maneuvers including: unobstructed, into the elbow, into a mask, and into the shirt. Observational data for the cough maximal plume area, an area calculation, were collected using slow-motion video recording. The various respiratory plume areas of the participants were compared to the unobstructed maneuver, assessing the percent reduction of the maximal plume area.

All respiratory etiquette maneuvers significantly reduced the maximal plume area as compared to the unobstructed condition (F(3,12) = 18.56, P < 0.005). Comparing the maximal plume area of the unobstructed maneuver to the "into the shirt" maneuver, we found a 95.4% decrease for the "into the shirt" respiratory etiquette maneuver (P < 0.005). There was no statistically significant difference when comparing the obstructive maneuvers to each other. Additionally, the maximal plume area from the "into the shirt" maneuver was 35.75% less than the "into the elbow" maneuver (P = 0.15). Comparing the maximal plume area of the "into the shirt" maneuver to the "into the mask" maneuver, results were inconclusive, with an average difference of 2.24% (P = 0.66).

Coughing into the shirt may offer superior containment of the respiratory plume than coughing into the elbow. Larger studies are warranted to validate these findings and guide future public health recommendations.

Open bench, observational, cough etiquette pilot study comparing the into the shirt respiratory etiquette maneuver to other respiratory etiquette maneuvers.

This cross-sectional study presents socioecological, epidemiological aspects, and the seroprevalence of immunoglobulin G (IgG) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a group of quilombola (afro-derived) communities in the states of Pará and Tocantins, in the Brazilian Amazon, to evaluate the impact of SARS-CoV-2 prevalence among them.

A total of 551 individuals participated. The detection of anti-SARS-CoV-2 antibodies was performed using an enzyme immunoassay. Socioeconomic and ecological data was collected from all participants 7 years of age or older who were not previously vaccinated.

The seroprevalence of antibodies in both states was 40.7% and was associated with factors such as age group, contact with infected individuals, and being in lockdown inside the quilombos. In Pará, a statistically significant association was observed between seroprevalence and females, and the age group of 12-18 years. In addition, seroprevalence in Pará was higher than in Tocantins, and the reported use of masks was a protective factor, while in Tocantins, the reported use of masks was associated with the presence of antibodies. There was no association between the prevalence of antibodies and the presence of COVID-19 symptoms in Pará. However, in Tocantins, diarrhea and loss of taste were associated with infection.

Quilombola are highly vulnerable groups due to the long history of enslavement in Brazil. This is the first investigation of SARS-CoV-2 seroprevalence and its impact in these groups in the Amazon. The study helps us to understand the relationship of socioecological differences, behavioral characteristics, and the dynamics of viral transmission associated with the risk of infection by SARS-CoV-2 among traditional populations, and can be useful to the planning of more culturally adequate public health policies for future epidemics.

The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has had a devastating impact worldwide. Currently, several vaccines are approved for emergency use in humans, and these vaccines have played a large role in controlling COVID-19. Pregnant women and newborns constitute a special population for vaccine policy. Here, we established a maternal vaccination model by injecting pregnant mice with a SARS-CoV-2 receptor-binding domain (RBD) homodimer. Maternal immunization with the RBD dimer did not cause obvious adverse effects on pregnancy or fetal development. Moreover, two-shot immunization fully protected dams and fetuses from SARS-CoV-2 infection during pregnancy. Neutralizing antibodies can be transferred from immunized dams to pups, providing protection for both lactating and weaned pups against SARS-CoV-2 infection. Our results indicate that, in addition to being used to vaccinate nonpregnant individuals, the RBD dimer can also be considered for maternal vaccination.

The World Health Organization (WHO) has determined a series of guidelines to contain the advance and spread of COVID-19 and other influenza viruses. Among them, frequent hand hygiene has been widely recommended, resulting in an increased consumption of alcohol-based antiseptic products or synthetic molecules. However, when used in excess, these products might cause adverse consequences for human health, such as dermatitis, and for the environment, i.e., the selection of resistant bacterial genotypes. One of the alternatives to overcome this problem is the replacement of common antiseptics by formulations based on natural bioactive compounds with antimicrobial/antiviral activity. In addition, by nanostructuring formulations, it is possible to increase the bioavailability, stability, solubility, and absorption of bioactives in biological systems. In this sense, this study aimed to develop an antiseptic nanoemulsion based on natural bioactive compounds with virucidal activity against SARS-CoV-2. For that, oil-in-water (O/W) nanoemulsions were prepared, being the oil phase composed by Melaleuca alternifolia essential oil, quercetin, PEG400, and surfactants, while the aqueous phase presented carrageenan and purified water. Physicochemical characterization and stability studies were developed to evaluate the viability of the formulations over time. In addition, bactericidal activities against Staphylococcus aureus and antiviral activity against SARS-CoV-2 were determined by in vitro assays. As a result, the average size of the nanoparticles was recorded at 150 nm, with a Polydispersity Index (PdI) of 0.2 and a zeta potential around -10.0 mV. The stability of nanoformulations indicated the occurrence of quercetin-dependent creaming and sedimentation. In addition, the products presented a minimum shelf-life of 3 months. Regarding the bactericidal activity, a minimum inhibition concentration of 1.25 % for S. aureus was found. The cytotoxicity and antiviral assays revealed that the nano-based products showed 100 % of viral replication inhibition and proved to be safe for epithelial cells. In conclusion, two antiseptic nanoformulations with high anti-SARS-CoV-2 activity and great industrial and pharmacological potential were developed.

Infectious diseases can sometimes lead to pandemics, often transmitted through public and social gatherings, including in-person hospital visits. Consequently, there is an urgent need for innovative approaches to prevent their spread. Taking COVID-19 as an example, we have explored a remote, contactless hospital online model that offers the public online medical consultations, professional psychological counseling, and chronic disease management consultations, thereby mitigating the risk of new transmissions resulting from hospital visits. This model was implemented, validated, and practiced at West China Hospital in China from 29 January 2020, to 12 March 2020. It was also applicable to other infectious diseases, such as influenza A. In this research, we utilized the hospital's internet platform, supplemented by telephone services, to offer the following to the public: 1) General medical education and consultation related to epidemics and psychological anxiety; 2) Online screening for at-risk populations; 3) Online prescription and medication delivery services for patients with chronic diseases. Consequently, over a period of more than 1 month, the online epidemic platform completed a total of 32,755 cases, including 8,783 internet consultations and 1,082 telephone consultations for the public, as well as 22,890 internet consultations for chronic disease patients. Among these, 289 high-risk individuals were identified, with 3 cases confirmed as COVID-19 during follow-up diagnoses, while no infections were detected in the remaining individuals. In conclusion, this innovative medical model serves as a significant supplement to existing healthcare systems and has the potential to be expanded to other hospitals and other infectious diseases. It is particularly beneficial in scenarios where medical resources are limited, populations are under quarantine, and there is a large demand for medical services and anxiety management during infectious disease pandemics.

Innate lymphoid cells (ILCs) have emerged as pivotal players in the field of immunology, expanding our understanding of innate immunity beyond conventional paradigms. This comprehensive review delves into the multifaceted world of ILCs, beginning with their serendipitous discovery and traversing their ontogeny and heterogeneity. We explore the distinct subsets of ILCs unraveling their intriguing plasticity, which adds a layer of complexity to their functional repertoire. As we journey through the functional activities of ILCs, we address their role in immune responses against various infections, categorizing their interactions with helminthic parasites, bacterial pathogens, fungal infections, and viral invaders. Notably, this review offers a detailed examination of ILCs in the context of specific infections, such as Mycobacterium tuberculosis, Citrobacter rodentium, Clostridium difficile, Salmonella typhimurium, Helicobacter pylori, Listeria monocytogenes, Staphylococcus aureus, Pseudomonas aeruginosa, Influenza virus, Cytomegalovirus, Herpes simplex virus, and severe acute respiratory syndrome coronavirus 2. This selection aimed for a comprehensive exploration of ILCs in various infectious contexts, opting for microorganisms based on extensive research findings rather than considerations of virulence or emergence. Furthermore, we raise intriguing questions about the potential immune functional resemblances between ILCs and epithelial cells, shedding light on their interconnectedness within the mucosal microenvironment. The review culminates in a critical assessment of the therapeutic prospects of targeting ILCs during infection, emphasizing their promise as novel immunotherapeutic targets. Nevertheless, due to their recent discovery and evolving understanding, effectively manipulating ILCs is challenging. Ensuring specificity and safety while evaluating long-term effects in clinical settings will be crucial.

Polyphenol-rich extracts derived from agricultural by-products exhibit promising antiviral properties. This study evaluated the antiviral potential of extracts from red onion peels, vineyard prunings, olive prunings and chicory leaves against human coronavirus HuCoV-229E. Subcritical water extraction and resin adsorption techniques were applied to produce the extracts. The extracts were further characterised for their bioactive content, and three out of four extracts showed a high polyphenol content (>200 mg/g). The antiviral activity was assessed through viral infectivity and replication inhibition assays in human MRC-5 host cells. The results indicate that chicory leaf and red onion peel extracts demonstrated significant antiviral effects, with effective concentrations (EC50) of 61.43 µg/mL and 10.1 µg/mL, respectively. Olive pruning extract exhibited moderate activity, while vineyard pruning extract showed limited efficacy. These findings suggest that polyphenol-rich agricultural by-products could serve as sustainable sources for antiviral agents, warranting further investigation into their mechanisms of action and potential applications against other coronaviruses, including SARS-CoV-2.

To address the occurrence of an outbreak of vancomycin-resistant Enterococcus in inpatient units intended for COVID-19 patients in a hospital in Salvador, Brazil, specialized in infectious diseases, which underwent several adaptations with effect from March 2020.

This is a descriptive study of patients with positive culture results for vancomycin-resistant Enterococcus between January 2021 and December 2023. The vanA/vanB genotype was defined by real-time polymerase chain reaction, and the clonal profile, by pulsed-field gel electrophoresis. Descriptive analyses were performed and presented as proportions.

Fifteen Enterococcus spp. infected/colonized patients were identified, of which 7 were E. faecalis, 7 were E. faecium and 1 was E. gallinarum. Two clonal profiles were identified: E. faecalis profile A and E. faecium profile C. The vanA genotype was predominant. Possible cross-contamination of disinfected materials and other dirty materials used for bathing and waste disposal was detected in utility/sluice room sinks.

The vancomycin-resistant Enterococcus outbreak in the inpatient units was controlled after implementing a unidirectional flow of disinfection of materials in utility/sluice rooms.

The COVID-19 pandemic highlighted the significance of mathematical modelling in decision-making and the limited capacity in many low-income and middle-income countries (LMICs). Thus, we studied how modelling supported policy decision-making processes in LMICs during the pandemic (details in a separate paper).We found that strong researcher-policymaker relationships and co-creation facilitated knowledge translation, while scepticism, political pressures and demand for quick outputs were barriers. We also noted that routine use of modelled evidence for decision-making requires sustained funding, capacity building for policy-facing modelling, robust data infrastructure and dedicated knowledge translation mechanisms.These lessons helped us co-create a framework and policy roadmap for improving the routine use of modelling evidence in public health decision-making. This communication paper describes the framework components and provides an implementation approach and evidence for the recommendations. The components include (1) funding, (2) capacity building, (3) data infrastructure, (4) knowledge translation platforms and (5) a culture of evidence use.

Our framework integrates the supply (modellers) and demand (policymakers) sides and contextual factors that enable change. It is designed to be generic and disease-agnostic for any policy decision-making that modelling could support. It is not a decision-making tool but a guiding framework to help build capacity for evidence-based policy decision-making. The target audience is modellers and policymakers, but it could include other partners and implementers in public health decision-making.

The framework was created through engagements with policymakers and researchers and reflects their real-life experiences during the COVID-19 pandemic. Its purpose is to guide stakeholders, especially in lower-resourced settings, in building modelling capacity, prioritising efforts and creating an enabling environment for using models as part of the evidence base to inform public health decision-making. To validate its robustness and impact, further work is needed to implement and evaluate this framework in diverse settings.

In recent years, the scientific community has worked intensively in the search and development of new drugs to suppress viral infections, such as COVID-19. In fact, a number of active compounds have been tested; however, the absence of significant structure-activity relationships hinders the production of optimized drugs. In this study, molecular modeling techniques were employed to investigate the electronic, structural and chemical reactivity properties of a set α-ketoamides whose antiviral activities have been reported in the literature, aiming to propose new promising derivatives. The local reactivity of the compounds was evaluated via condensed-to-atoms Fukui indexes and molecular electrostatic potential. Multivariate data analysis and random forests machine learning techniques were employed to correlate the antiviral properties and electronic and structural descriptors and identify relevant variables. A series of new derivatives were then proposed and evaluated via density functional theory-based calculations, and docking/molecular dynamics with the target protein of the virus. The results suggest that active derivatives present reduced reactivity towards electrophilic agents on the central core of the molecules and high reactivity on R1 ligands. Derivatives with higher predicted antiviral activities were proposed based on simple electronic descriptors, and their efficacies are reinforced by docking and molecular dynamics simulations.

Coronavirus disease (COVID-19) is still a severe concern, especially in Africa with suboptimal intention rates of vaccination. This flagged the requirement of plant-based remedies as an alternative treatment. In this study we integrated metabolomics and chemometrics approaches with In silico and In vitro approaches to accelerate and unravel compounds from commonly used South African plants that may inhibit SARS-CoV-2 main protease. The selected commonly used plants, Artemisia afra and Artemisia annua, were found to be non-toxic against Vero cells, as determined by the resazurin cell viability assay. Metabolites profiling revealed eighty-one compounds and the top three hit compounds, quercetin 3-O-(6"-acetyl-glucoside), 2"-O-acetylrutin, and quercetin 3-(6"-malonyl-glucoside), had binding affinities of -9.3 kcal/mol, -9.5 kcal/mol, and -9.3 kcal/mol, respectively. The 2"-O-acetyl group of the rutin moiety and quercetin moiety produces a hydrogen bond with the amide nitrogen of His41 and with the side chain carboxylate of Cys145, respectively. Molecular dynamics simulations revealed a stable binding of the docked complexes. In silico observations were validated by In vitro bioassay, which flagged the ability of these compounds to inhibit SARS-CoV-2 3CLpro. The collected analysed data of this study does not only draw special attention to the surfaced 2"-O-acetylrutin as the best suitable inhibitor of SARS-CoV-2 3CLpro, but also indirectly reveals the importance of integrating metabolomics and chemometrics approaches with In silico and In vitro approaches to accelerate and unravel compounds from South African commonly used plants.

The evolution of COVID-19 pandemic has been characterized by the rapid emergence of new SARS-CoV-2 variants, each of which poses unique challenges to public health. This study analyzes the dispersion profiles during the Pre-Omicron and Post-Omicron phases in different epidemiological contexts. The Brazilian state of Espirito Santo, despite its low population density, plays a critical role as a commercial hub due to its intense port activity, which may have contributed to COVID-19 cases and mortality rates being higher than the national average. The state recorded 34,000 confirmed cases and 377 deaths per 100,000 inhabitants. Genomic surveillance revealed that the Pre-Omicron phase was dominated by the B.1.1.33 lineage, characterized by localized intraregional circulation. In contrast, the Post-Omicron phase, dominated by the BQ.1.1 lineage, exhibited greater diversity in circulating lineages, increased international interactions, and rapid viral dissemination, highlighting distinct transmission dynamics between such periods. This study highlights the need for adaptive public health strategies that account for both viral behavior and regional socioeconomic factors, while highlighting the strategic importance of Espirito Santo in monitoring SARS-CoV-2 evolution.

Vaccines against COVID-19 have high efficacy and low rates of adverse events. However, none of the available vaccines provide sterilizing immunity, and reinfections remain possible. This review aims to summarize the immunological responses elicited by different immunization strategies, examining the roles of homologous and heterologous vaccination and hybrid immunity. Homologous vaccination regimens exhibit considerable variation in immune responses depending on the vaccine platform, particularly concerning antibody titers, B cell activation, and T cell responses. mRNA vaccines, such as mRNA-1273 and BNT162b2, consistently generate higher and more durable levels of neutralizing antibodies and memory B cells compared to adenovirus-based vaccines like Ad26.COV2.S and ChAdOx1. The combination of two distinct vaccine platforms, each targeting different immune pathways, seems to be more effective in promoting long-lasting B cell responses and potent T cell responses. The high heterogeneity of the available studies, the different dosing schemes, the succession of new variants, and the subjects' immunological background do not allow for a definitive conclusion. Overall, heterologous vaccination strategies, combining sequentially viral vector and mRNA may deliver a more balanced and robust humoral and cellular immune response compared to homologous regimens. Hybrid immunity, which arises from SARS-CoV-2 infection preceded or followed by vaccination produces markedly stronger immune responses than either vaccination or infection alone. The immune response to SARS-CoV-2 variants of concern varies depending on both the vaccine platform and prior infection status. Hybrid immunity leads to a broader antibody repertoire, providing enhanced neutralization of variants of concern. Heterologous vaccination and hybrid immunity may provide further opportunities to enhance immune responses, offering broader protection and greater durability of immunity. However, from all-cause mortality, symptomatic or severe COVID, and serious adverse events at present it is not possible to infer different effects between homologous and heterologous schemes. Next-generation vaccines could involve tweaks to these designs or changes to delivery mechanisms that might improve performance.

Background and objective Treatment in ICUs became extremely difficult due to the growing number of coronavirus disease 2019 (COVID-19) patients at the height of the pandemic. Consequently, prompt patient triage depends on the early categorization of severe cases in such scenarios. This study aimed to provide an evidence-based strategy to ensure the best use of resources by triaging patients based on objective risk factors. Methods This retrospective observational study comprised 500 inpatients (>age 18 years) who were hospitalized between March 20 and April 19, 2020, at the Khyber Teaching Hospital (KTH) and Hayatabad Medical Complex (HMC) in Peshawar, Pakistan. The clinical, laboratory, and radiological parameters were assessed. Real-time polymerase chain reaction (RT-PCR) findings were used to confirm the diagnosis of COVID-19. Results A total of 19 potential clinical and laboratory risk factors associated with ICU admissions were identified. At least one comorbidity among chronic lung disease, cardiovascular disease (CVD), and diabetes was the factor with the strongest association with ICU admission with a univariable odds ratio (OR) of over 27, followed by renal disease and other COVID-19 sequelae such as diarrhea, respiratory rate (>24 breaths/minute), and positive RT-PCR (vs. negative) with an univariable OR between 9 and 15. Furthermore, a multivariate logistic regression model was further developed with five risk factors, including comorbidity, presence of chronic lung disease, presence of diabetes, and RT-PCR (positive vs. negative), male sex (vs. female), and older age (65.0-80.5 years), suggesting a good fit of the model to the data shown by the area under the receiver operator characteristic curve (AUC) of 0.943 (95% CI: 0.917, 0.969). Additionally, a chest CT scan showed the typical COVID-19 pneumonia with pulmonary involvement of 30-40%, which was further evaluated by the COVID-19 Reporting and Data System (CO-RADS). The typical COVID-19 pneumonia was on a scale of four (15/25) or five (19/25) lung lesions. Conclusions Based on our findings, this approach could be used to screen the severe cases of COVID-19 patients and help them to be treated in ICUs on time while preventing others from unnecessarily using ICUs in the setting of limited medical resources, such as the outbreak of a pandemic.

Accurate estimation of the effects of mutations on SARS-CoV-2 viral fitness can inform public-health responses such as vaccine development and predicting the impact of a new variant; it can also illuminate biological mechanisms including those underlying the emergence of variants of concern. Recently, Lan et al. reported a model of SARS-CoV-2 secondary structure and its underlying dimethyl sulfate reactivity data (Lan et al., 2022). I investigated whether base reactivities and secondary structure models derived from them can explain some variability in the frequency of observing different nucleotide substitutions across millions of patient sequences in the SARS-CoV-2 phylogenetic tree. Nucleotide basepairing was compared to the estimated 'mutational fitness' of substitutions, a measurement of the difference between a substitution's observed and expected frequency that is correlated with other estimates of viral fitness (Bloom and Neher, 2023). This comparison revealed that secondary structure is often predictive of substitution frequency, with significant decreases in substitution frequencies at basepaired positions. Focusing on the mutational fitness of C→U, the most common type of substitution, I describe C→U substitutions at basepaired positions that characterize major SARS-CoV-2 variants; such mutations may have a greater impact on fitness than appreciated when considering substitution frequency alone.

The SARS-CoV-2 Spike (S) protein plays a central role in viral entry into host cells, making it a key target for therapeutic interventions. Oxidative stress, often triggered during viral infections, can cause oxidation of cysteine in this protein. Here we investigate the impact of cysteine oxidation, specifically the formation of cysteic acid, on the conformational dynamics of the SARS-CoV-2 S protein using atomistic simulations. In particular, we examine how cysteine oxidation influences the transitions of the S protein's receptor-binding domain (RBD) between "down" (inaccessible) and "up" (accessible) states, which are critical for host cell receptor engagement. Using solvent-accessible surface area (SASA) analysis, we identify key cysteine residues susceptible to oxidation. The results of targeted molecular dynamics (TMD) and umbrella sampling (US) simulations reveal that oxidation reduces the energy barrier for RBD transitions by approximately 30 kJ mol-1, facilitating conformational changes and potentially enhancing viral infectivity. Furthermore, we analyze the interactions between oxidized cysteine residues and glycans, as well as alterations in hydrogen bonds and salt bridges. Our results show that oxidation disrupts normal RBD dynamics, influencing the energy landscape of conformational transitions. Our work provides novel insights into the role of cysteine oxidation in modulating the structural dynamics of the SARS-CoV-2 S protein, highlighting potential targets for antiviral strategies aimed at reducing oxidative stress or modifying post-translational changes. These findings contribute to a deeper understanding of viral infectivity and pathogenesis under oxidative conditions.

The COVID-19 pandemic has underscored the importance of in-depth research into the proteins encoded by coronaviruses (CoV), particularly the highly conserved nonstructural CoV proteins (nsp). Among these, the nsp13 helicase of severe pathogenic MERS-CoV, SARS-CoV-2, and SARS-CoV is one of the most preserved CoV nsp. Utilizing single-molecule FRET, we discovered that MERS-CoV nsp13 unwinds DNA in distinct steps of about 9 bp when ATP is employed. If a different nucleotide is introduced, these steps diminish to 3-4 bp. Dwell-time analysis revealed 3-4 concealed steps within each unwinding process, which suggests the hydrolysis of 3-4 dTTP. Combining our observations with previous studies, we propose an unwinding model of CoV nsp13 helicase. This model suggests that the elongated and adaptable 1B-stalk of nsp13 may enable the 1B remnants to engage with the unwound single-stranded DNA, even as the helicase core domain has advanced over 3-4 bp, thereby inducing accumulated strain on the nsp13-DNA complex. Our findings provide a foundational framework for determining the unwinding mechanism of this unique helicase family.

The aim of this study was to analyze clinical strategies supported by validated references during two of the most frequent dental emergencies (i.e. restorative and endodontic treatment) in the COVID-19 pandemic. Coronavirus disease 2019 (COVID-19) was caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of an emergency in the health system worldwide and a potentially fatal disease. Person-to-person transmission of SARS-CoV-2 through aerosol and droplets led to extensive preventive measures to contain COVID-19 outbreak. Dental care providers have been exposed to a high risk of SARS-CoV-2 infection, due to the face-to-face communication and the exposure to saliva, blood, and other body fluids during routine interventions; this can also contribute to a high risk for cross-infection, even though dentist usually cope with those situations in everyday practice. Restorative and endodontic emergencies represented a high proportion of dental emergencies, with prolonged exposure time for dentists/endodontists in contact with suspected or confirmed infected patients. Lack of knowledge and undefined progression controlled the decision-making in clinical dentistry. The dynamicity of the situation determined change of views and recommendations in dental setting. The implementation of strict restorative and endodontics protocols are aimed at preventing circumstances similar to those observed with COVID-19.

The impact of wearing a face mask for an extended duration is unknown. This study aimed to determine if wearing a face mask for 10 h impacts blood pressure (BP) and arterial stiffness. Subjects received an ambulatory blood pressure cuff and were asked to wear it for 10 h while readings were taken every 15 min. During the face mask trial, subjects wore an N95 mask for 10 h. During the control, subjects did not wear a mask. Subjects were randomized to start their trial. An accelerometer was given to ensure no physical activity differences. Linear mixed models were used to determine group differences, and McNemar test was used to assess frequency differences when determining BP load. Twelve college-aged (20.5 ± 1.5 years) male ( n  = 5) and female ( n  = 7) individuals with normal BP participated in this study. There were no differences in time spent in any physical activity domain (all P  > 0.05). There was no difference in brachial SBP ( P  = 0.688), brachial DBP ( P  = 0.063), central SBP ( P  = 0.875), central DBP ( P  = 0.246), heart rate ( P  = 0.125), and augmentation pressure ( P  = 0.158) between conditions. During mask condition, augmentation pressure was reduced by 5.2 ± 3.1% compared to control ( P  < 0.001). There were no frequency differences in the number of BP readings above 140 mmHg for SBP ( P  = 0.479) and >90 mmHg for DBP ( P  = 0.212). The current study found that wearing an N95 mask for 10 h did not affect brachial or central BP but significantly decreased augmentation pressure.

Abnormal coagulation and thrombotic complications prompted many guidelines to recommend thromboprophylaxis for patients hospitalised with COVID-19, but the dose required for prophylaxis remains unclear. This systematic review (SR) analyses the safety and efficacy of therapeutic dose anticoagulation (TDA) versus non-therapeutic dose anticoagulation (NDA) in COVID-19 patients.

According to the Cochrane Handbook of Systematic Review of Interventions, we performed an SR. The protocol is registered in Prospero (CRD42021269197, date 12 August 2021).

In this SR of 18 studies, TDA was shown to reduce all-cause mortality (risk ratio [RR] 0.83; 95% confidence interval [95% CI] 0.70, 0.99) in COVID-19 infection. TDA also reduced thrombosis (RR 0.55; 95% CI 0.48, 0.72) but increased major bleeding (RR 1.87; 95% CI 1.29, 2.69). A stratified analysis according to severity revealed that, in non-critical patients, TDA resulted in mortality benefit (RR 0.79; 95% CI 0.67, 0.94). In critical patients, TDA did not affect all-cause mortality (RR 1.03; 95% CI 0.89, 1.18) but reduced thrombosis (RR 0.65; 95% CI 0.48, 0.86) and increased major bleeding (RR 1.85; 95% CI 1.06, 3.23).

TDA significantly reduced all-cause mortality and thrombosis in non-critical COVID-19 patients at the expense of increased major bleeding. In critical COVID-19, this mortality benefit was not observed.

In March 2020, the World Health Organization (WHO) declared SARS-CoV-2 a pandemic after identifying it as the causative agent of COVID-19. Hydroxychloroquine (HCQ) was widely used as a prophylactic measure among healthcare workers (HCWs). However, its use as a preventive medication in asymptomatic individuals, particularly given its known adverse effect profile, remains relatively unexplored. This study aimed to evaluate the safety of HCQ prophylaxis among HCWs in Mumbai, India.

A survey-based, cross-sectional study was conducted using a self-designed questionnaire distributed to HCWs in Mumbai who had direct or indirect patient contact and were taking HCQ for COVID-19 prevention.

A total of 125 responses were collected, with males accounting for 80 (64%) of the participants. The majority of HCWs had a medical doctor background, and the mean age was 41.8 years. Thirty-eight HCWs (30.4%) reported frequent exposure to COVID-19, while 106 (84.8%) had direct patient contact. A minority (34 participants, 27.2%) received HCQ prophylaxis for seven weeks, and 123 (98.4%) adhered to the standard prophylactic regimen. Comorbidities were present in 27 (21.6%) HCWs, with hypertension (19, 15.2%) being the most common. Among the participants, 64 (51.2%) underwent an electrocardiogram (ECG) before prophylaxis, while 56 (44.8%) had follow-up ECGs. Adverse effects were reported by 44 (35.2%) HCWs, with a statistically significant higher incidence among females. The most common adverse effects were gastrointestinal symptoms (48, 38.4%). While HCWs with hypertension and diabetes mellitus experienced more adverse effects, this association was not statistically significant. Cardiac adverse effects were reported in 13 cases (10.5%); however, no significant cardiovascular complications were observed.

This study found a higher occurrence of adverse effects among female participants, though previous research does not provide conclusive evidence for this finding. The incidence of gastrointestinal side effects was consistent with other studies on HCQ prophylaxis among HCWs. Although HCWs with hypertension and diabetes mellitus experienced more adverse effects, these were not statistically significant. No serious cardiovascular effects were observed. Given the evolving landscape of COVID-19 treatment and prevention, further large-scale trials are necessary to establish the safety and efficacy of HCQ prophylaxis among HCWs.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19) is a public health problem and may result in co-infection with other pathogens such as influenza virus. This review investigates the co-infection of SARS-CoV-2 and influenza A/B among patients with COVID-19.

This meta- analysis included 38 primary studies investigating co-infection of SARS-CoV-2 with influenza in confirmed cases of COVID-19. The global online databases were used to identify relevant studies published between December 2019 and July 2024. Data analysis was performed using STATA Ver. 17 software, and standard errors of prevalence were calculated using the binomial distribution formula. Heterogeneity of study results was evaluated using the I-square and Q index, and publication bias was examined using the Begg's and Egger's tests, as well as funnel plot. A random effects model was used to determine prevalence rates, and a forest plot diagram was used to present results with 95% confidence intervals. In addition, sensitivity analyses were performed to check the impact of each primary study on the overall estimate.

The analysis found that the prevalence of influenza in co-infected patients at 95% confidence interval using a random effect model was 14% (95% CI: 8-20%). Significant heterogeneity was observed in the random-effects model for influenza A, 11% (95% CI: 5-18%) and B, 4% (95% CI: 2-7%) in co-infected patients. The highest prevalence of influenza A/B (21%), influenza A (17%) and influenza B (20%) was shown in Asia and Europe respectively. Subgroup analysis by study year showed that the co-prevalence of COVID-19 and influenza A/B was similar in the pre-2021 and post-2021 time periods, at 14% (95% CI: 5-23%) for pre-2021 and 6-22% for 2021 and post-2021. Also, the overall prevalence of influenza A and B in COVID-19 patients is 11% and 4%, and there was no significant difference between the time periods before and after 2021. Meta-regression with a random-effects model showed that the variables location, year group, and total patients showed only 2.71% of very high heterogeneity (I² = 99.92%), and none of these variables had a significant effect on the co-prevalence of COVID-19 and influenza A/B (p > 0.05). Also, meta-regression results showed that these variables had no significant effect on influenza A and B prevalence (p > 0.05) and showed only a small proportion of the very high heterogeneity (I² = 99.72%), (I² = 68.78%). In our study, Egger's test indicated that there was publication bias or small study effects in this meta-analysis (p = 0.0000).

The combination of SARS-CoV-2 with influenza and other respiratory viruses requires the best treatment protocols to reduce the severity of the disease. In this approach, high vaccination coverage against seasonal influenza and SARS-CoV-2 could reduce the risk of co-infection in the recent pandemic.

Pathogen mutations present an inevitable and challenging problem for therapeutics and the development of mutation-tolerant anti-infective drugs to strengthen global health and combat evolving pathogens is urgently needed. While spike proteins on viral surfaces are attractive targets for preventing viral entry, they mutate frequently, making it difficult to develop effective therapeutics. Here, we used a structure-guided strategy to engineer an inhibitor peptide against the SARS-CoV-2 spike, called CeSPIACE, with mutation-tolerant and potent binding ability against all variants to enhance affinity for the invariant architecture of the receptor-binding domain (RBD). High-resolution structures of the peptide complexed with mutant RBDs revealed a mechanism of mutation-tolerant inhibition. CeSPIACE bound major mutant RBDs with picomolar affinity and inhibited infection by SARS-CoV-2 variants in VeroE6/TMPRSS2 cells (IC50 4 pM to 13 nM) and demonstrated potent in vivo efficacy by inhalation administration in hamsters. Mutagenesis analyses to address mutation risks confirmed tolerance against existing and/or potential future mutations of the RBD. Our strategy of engineering mutation-tolerant inhibitors may be applicable to other infectious diseases.

Recently, previously known viruses have changed their pathogenicity and encompassed new types of host populations. An example of such an infection is that caused by SARS-CoV, belonging to the "well-known" coronavirus family. Another group of viruses that are of great importance to the human population are the herpes viruses. Due to increasing viral resistance to existing antiviral drugs, plant extracts are attracting increasing interest due to their complex composition and their simultaneous attack of different viral targets. Based on the above, we tested the antiviral potential of water-alcoholic extract obtained from a commercial sample of the plant Cistus incanus L. against the enveloped viruses SvHA1, SvHA2 (ACV resistant) and HCoV 229E. The results showed both complete inhibition of the intracellular stages of the viral replication and a strong effect on extracellular virions in the three viral models. In a study of the effect on the replication of SvHA 2, the calculated selectivity index was over 10. From the experiments on the virucidal effects on the two herpes viruses, it was found that the viral titer of the samples decreased by about 4 lg compared to the control sample. The extract is of interest for introduction into practice.

Selenium (Se), a critically essential trace element, plays a crucial role in diverse physiological processes within the human body, such as oxidative stress response, inflammation regulation, apoptosis, and lipid metabolism. Organ fibrosis, a pathological condition caused by various factors, has become a significant global health issue. Numerous studies have demonstrated the substantial impact of Se on fibrotic diseases. This review delves into the latest research advancements in Se and Se-related biological agents for alleviating fibrosis in the heart, liver, lungs, and kidneys, detailing their mechanisms of action within fibrotic pathways. Additionally, the article summa-rizes some of the anti-fibrotic drugs currently in clinical trials for the aforementioned organ fibroses.

To map evidence of organizational support for healthcare professionals who worked in hospitals during the pandemic.

This is a scoping review, based on the framework established by Joanna Briggs Institute and the PRISMA-ScR protocol, registered in the Open Science Framework, under DOI: 10.17605/OSF.IO/2P7B4. Materials that presented evidence of organizational support measures offered to hospital healthcare professionals in the context of the pandemic were included. The databases CINAHL (Ebsco), EMBASE (Elsevier), LILACS (VHL), PubMed (NLM/NCBI), Science Direct (Elsevier), Academic Search Premier (Ebsco), PSYCiNFO (APA), SCOPUS (Elsevier), in addition to official websites of leading healthcare institutions with publications on the topic.

After pre-selection of 716 materials, 60 studies were included; whose results addressed the topics: financial support, in-service education, material resources and physical structure, psychological support, the role of leadership, and other institutional support measures.

The pandemic scenario brought advances in relation to organizational support measures adopted in hospital institutions, highlighting the importance of investments in workplace support policies, not only during the pandemic period. Such actions can positively contribute to the provision of safe care for workers and patients.

Electronic health records (EHRs) facilitate the accessibility and sharing of patient data among various health care providers, contributing to more coordinated and efficient care.

This study aimed to summarize the evolution of secondary use of EHRs and their interoperability in medical research over the past 25 years.

We conducted an extensive literature search in the PubMed, Scopus, and Web of Science databases using the keywords Electronic health record and Electronic medical record in the title or abstract and Medical research in all fields from 2000 to 2024. Specific terms were applied to different time periods.

The review yielded 2212 studies, all of which were then screened and processed in a structured manner. Of these 2212 studies, 2102 (93.03%) were included in the review analysis, of which 1079 (51.33%) studies were from 2000 to 2009, 582 (27.69%) were from 2010 to 2019, 251 (11.94%) were from 2020 to 2023, and 190 (9.04%) were from 2024.

The evolution of EHRs marks an important milestone in health care's journey toward integrating technology and medicine. From early documentation practices to the sophisticated use of artificial intelligence and big data analytics today, EHRs have become central to improving patient care, enhancing public health surveillance, and advancing medical research.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and severe acute respiratory syndrome coronavirus (SARS-CoV) exhibit differences in their inflammatory responses and pulmonary damage, yet the specific mechanisms remain unclear. Here, we discovered that the SARS-CoV-2 nucleocapsid (N) protein inhibits the activation of the nuclear factor-κB (NF-κB) pathway and downstream signal transduction by impeding the assembly of the transforming growth factor β-activated kinase1 (TAK1)-TAK1 binding protein 2/3 (TAB2/3) complex. In contrast, the SARS-CoV N protein does not impact the NF-κB pathway. By comparing the amino acid sequences of the SARS-CoV-2 and SARS-CoV N proteins, we identified Glu-290 and Gln-349 as critical residues in the C-terminal domain (CTD) of the SARS-CoV-2 N protein, essential for its antagonistic function. These findings were further validated in a SARS-CoV-2 trans-complementation system using cellular and animal models. Our results reveal the distinctions in inflammatory responses triggered by SARS-CoV-2 and SARS-CoV, highlighting the significance of specific amino acid alterations in influencing viral pathogenicity.

The molecular mechanisms regulating coronavirus pathogenesis are complex, including virus-host interactions associated with replication and innate immune control. However, some genetic and epigenetic conditions associated with comorbidities increase the risk of hospitalization and can prove fatal in infected patients. This systematic review will provide insight into host genetic and epigenetic factors that interfere with COVID-19 expression in light of available evidence.

This study conducted a systematic review to examine the genetic and epigenetic susceptibility to COVID-19 using a comprehensive approach. Through systematic searches and applying relevant keywords across prominent online databases, including Scopus, PubMed, Web of Science, and Science Direct, we compiled all pertinent papers and reports published in English between December 2019 and June 2023.

The findings reveal that the host's HLA genotype plays a substantial role in determining how viral protein antigens are showcased and the subsequent immune system reaction to these antigens. Within females, genes responsible for immune system regulation are found on the X chromosome, resulting in reduced viral load and inflammation levels when contrasted with males. Possessing blood group A may contribute to an increased susceptibility to contracting COVID-19 as well as a heightened risk of mortality associated with the disease. The capacity of SARS-CoV-2 involves inhibiting the antiviral interferon (IFN) reactions, resulting in uncontrolled viral multiplication.

There is a notable absence of research into the gender-related predisposition to infection, necessitating a thorough examination. According to the available literature, a significant portion of individuals affected by the ailment or displaying severe ramifications already had suppressed immune systems, categorizing them as a group with elevated risk.