Severe Acute Respiratory Syndrome Coronavirus Research Articles

The influence of environmental factors on the detection and quantification of SARS-CoV-2 variants in dormitory wastewater at a primarily undergraduate institution.

Testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has been crucial in tracking the spread of the virus and informing public health decisions. SARS-CoV-2 viral RNA is shed by symptomatic and asymptomatic infected individuals, allowing its genetic material to be detected and quantified in wastewater. Here, we used wastewater-based epidemiology to measure SARS-CoV-2 viral RNA from several dormitories on the Appalachian State University campus and examined the impact of sampling methods, target types, environmental factors, and infrastructure variables on quantification. Changes in the quantification of SARS-CoV-2 were observed based on target type, as well as trends for the quantification of the Delta and Omicron variants by sampling method. These results highlight the value of applying the data-inquiry practices used in this study to better contextualize wastewater sampling results.

The Effect of COVID-19 on Neonatal Outcomes in a Community Hospital.

Background: Despite considerable research on pregnancy outcomes affected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the consequences for infants exposed to the virus in utero remain unclear. Methods: A retrospective cohort study was conducted, encompassing 392 mother-infant pairs delivered between April 2020 and July 2021 at a community hospital network in northeastern Pennsylvania, USA. Of these, 198 mothers had a confirmed SARS-CoV-2 infection during pregnancy, while 194 did not. Infant outcomes were compared between the two groups. Results: Pregnant women with a SARS-CoV-2 infection during their gestation exhibited higher rates of obesity (p = 0.04) with higher body mass indices (BMI) (p = 0.01), were more likely to be of Hispanic ethnicity (p = 0.01), and had a history of chronic hypertension (p = 0.05), as well as higher occurrences of postpartum depression (p = 0.01), gestational diabetes (p = 0.05), cesarean section (CS) rates (p< 0.001), and preeclampsia (p = 0.04). Among the infants reviewed, there was no statistical significance difference in developmental milestones at 2, 4, 6, 9, and 12 months of age between infants of parturients who tested positive for coronavirus disease 2019 (COVID-19) and infants of parturients without a positive COVID-19 test result. There was no statistically significant difference between the two groups in developmental outcomes, as measured by Ages and Stages Questionnaire (ASQ) scores at 9 months (p = 0.76) and at 18 months (p = 0.89). Conclusions: This study corroborates the adverse impact of SARS-CoV-2 infection on pregnant women, characterized by increased maternal comorbidities and adverse birth outcomes. No significant disparities in neonatal developmental milestones or growth outcomes were observed at birth; first office visit, or at 1, 2, 4, 6, 9, and 12 months of age.

Ultrasensitive detection of intact SARS-CoV-2 particles in complex biofluids using microfluidic affinity capture.

Measuring virus in biofluids is complicated by confounding biomolecules coisolated with viral nucleic acids. To address this, we developed an affinity-based microfluidic device for specific capture of intact severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Our approach used an engineered angiotensin-converting enzyme 2 to capture intact virus from plasma and other complex biofluids. Our device leverages a staggered herringbone pattern, nanoparticle surface coating, and processing conditions to achieve detection of as few as 3 viral copies per milliliter. We further validated our microfluidic assay on 103 plasma, 36 saliva, and 29 stool samples collected from unique patients with COVID-19, showing SARS-CoV-2 detection in 72% of plasma samples. Longitudinal monitoring in the plasma revealed our device's capacity for ultrasensitive detection of active viral infections over time. Our technology can be adapted to target other viruses using relevant cell entry molecules for affinity capture. This versatility underscores the potential for widespread application in viral load monitoring and disease management.

In silico Evaluation of H1-Antihistamine as Potential Inhibitors of SARS-CoV-2 RNA-dependent RNA Polymerase: Repurposing Study of COVID-19 Therapy.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), from the family Coronaviridae, is the seventh known coronavirus to infect humans and cause acute respiratory syndrome. Although vaccination efforts have been conducted against this virus, which emerged in Wuhan, China, in December 2019 and has spread rapidly around the world, the lack of an Food and Drug Administration-approved antiviral agent has made drug repurposing an important approach for emergency response during the COVID-19 pandemic. The aim of this study was to investigate the potential of H1-antihistamines as antiviral agents against SARS-CoV-2 RNA-dependent RNA polymerase enzyme. Using molecular docking techniques, we explored the interactions between H1-antihistamines and RNA-dependent RNA polymerase (RdRp), a key enzyme involved in viral replication. The three-dimensional structure of 37 H1-antihistamine molecules was drawn and their energies were minimized using Spartan 0.4. Subsequently, we conducted a docking study with Autodock Vina to assess the binding affinity of these molecules to the target site. The docking scores and conformations were then visualized using Discovery Studio. The results examined showed that the docking scores of the H1-antihistamines were between 5.0 and 8.3 kcal/mol. These findings suggested that among all the analyzed drugs, bilastine, fexofenadine, montelukast, zafirlukast, mizolastine, and rupatadine might bind with the best binding energy (< -7.0 kcal/mol) and inhibit RdRp, potentially halting the replication of the virus. This study highlights the potential of H1-antihistamines in combating COVID-19 and underscores the value of computational approaches in rapid drug discovery and repurposing efforts. Finally, experimental studies are required to measure the potency of H1-antihistamines before their clinical use against COVID-19 as RdRp inhibitors.

COVID-19 infection and risk of adverse drug reactions: Cohort study.

During coronavirus disease 2019 (COVID-19), the incidence rate of adverse drug reactions (ADRs) in hospitalized patients seemed higher than before the pandemic. Severe inflammation triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was cited as an explanation. We aimed to determine whether COVID-19 infection was associated with a higher risk of ADRs compared to other infectious diseases. A monocentric historic cohort, "exposed/unexposed" study, was conducted in the university hospital of Saint-Étienne (inclusion period from March 05, 2020 to April 16, 2020 for "COVID-19" and from January to December 2019 for "non-COVID-19"). All ADRs reported in patients' medical records were retrospectively assessed using Bégaud et al.'s algorithm. A multivariable Cox regression was performed to assess the hazard ratio (HR). The incidence rate of 4.64 ADRs per person-month in the "COVID-19" group did not differ from the 3.52 ADRs per person-month in the "non-COVID-19" group (multivariable adjusted HR 1.29, 95% confidence interval [CI], 0.91-1.81, P=0.1436). COVID-19 patients had more hepatobiliary disorders whereas non-COVID-19 patients had more renal and urinary disorders. Classes of drugs mostly involved in ADRs occurrence were antibiotics, followed by antithrombotics in both groups. Compared to patients with no ADR, patients with ADRs had higher C-reactive protein (CRP) levels and a lower estimated glomerular filtration rate (eGFR). In this study, the incidence rate in hospitalized patients with COVID-19 was not statistically different from that in the group with another infection. High CRP levels, as well as low eGFR, were the main risk factors for the occurrence of ADRs and should be considered in further ADR prevention strategies.

Nutritional changes in patients undergoing hemodialysis who develop COVID-19

BackgroundCoronavirus disease 2019 (COVID-19) is known to deteriorate nutrition in the general population. However, the influence of COVID-19 on the nutritional status of patients undergoing maintenance hemodialysis remains unclear.MethodsA retrospective study was conducted in a hospital that had an outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. COVID-19 was diagnosed using an antigen test, and the subjects were divided into COVID-19 and control groups. Data on body mass index, biochemistry measurements, geriatric nutritional risk index (GNRI), functional oral intake scale, and nutritional intake were collected from medical records. A generalized linear mixed model was used to analyze the interaction of time × group for these parameters between the two groups.ResultsThe study included 28 participants, 16 of whom belonged to the COVID-19 group. There were no significant differences in baseline characteristics, except for serum creatinine level, among the groups. In the COVID-19 group, 63% exhibited anorexia and 50% experienced vomiting/nausea. Nutritional support or dietary consultations were provided to nine patients. Significant declines were observed in serum albumin level, total iron binding capacity, energy intake, and GNRI in the COVID-19 group, and these nutritional parameters recovered within 1 month following the resolution of the infection.ConclusionsCOVID-19 deteriorated nutritional status in patients undergoing hemodialysis. More proactive nutritional support may help maintain the nutritional status of patients undergoing hemodialysis during COVID-19 infection and could lead to a better prognosis.

Post-COVID-19 neurogenic lower urinary tract dysfunction in pediatrics: A case series of clinical manifestations resembling Elsberg syndrome

Background: Among the numerous complications associated with post-coronavirus disease 2019 (COVID-19) syndrome, neurogenic lower urinary tract dysfunction (NLUTD) has been rarely reported, particularly in the pediatric population. Case Presentation: This report presented three pediatric cases of NLUTD that developed following severe acute respiratory syndrome coronavirus 2 infection, with clinical features resembling Elsberg syndrome. These cases were notable for the severity of their urinary symptoms, which required specialized and individualized bladder management strategies. This case series aims to raise awareness of this emerging clinical condition, which may be underdiagnosed in children recovering from COVID-19. Pediatricians, general practitioners, and urologists should be vigilant in considering NLUTD as a potential diagnosis in children presenting with new or unexplained urinary symptoms. Early diagnosis and timely management are crucial to address these symptoms effectively and prevent potential complications, such as irreversible upper urinary tract damage or long-term bladder dysfunction. Conclusion: Further investigations are warranted to clarify the pathophysiological mechanisms underlying post-COVID-19 NLUTD. Moreover, long-term follow-up studies are needed to better understand the natural history and implications of this condition in the pediatric population, as well as to develop effective strategies for prevention and treatment.

Uncovering Antiviral Potential of Cistus ladanifer Extracts Against HSV-1 and SARS-CoV-2 by In Vitro and In Silico Analysis.

Infectious diseases remain a major global health concern. Cistus ladanifer, a plant commonly employed in Moroccan traditional medicine, has been identified as a potential antiviral candidate. This study aimed to evaluate the antiviral activity of C. ladanifer extracts in vitro and in silico against two respiratory viruses: Herpes simplex virus and the severe acute respiratory syndrome coronavirus 2 variants of concern Delta and Omicron. Toxic prediction of the main compounds identified by Gas Chromatography-Mass Spectrometry from Cistus ladanifer was performed in silico via ProTox-II software. Molecular docking was subsequently performed via Maestro version 11.5 software from Schrödinger to gain a comprehensive understanding of their biological activity. The extracts were subjected to in vitro antiviral screening against the selected strains via real-time RT‒qPCR. Our docking estimation supported the in vitro results, and a diverse array of compounds extracted from Cistus ladanifer demonstrated significant antiviral activity with a low toxicity profile. Accordingly, in vitro data revealed a dose-dependent effect of the studied extracts, with particular efficacy against the Omicron variant. With the antiviral evaluation and docking outcomes in hand, we suggest a plausible mechanism of action for these compounds through further investigation into the effectiveness of Cistus ladanifer against other respiratory viruses.

Post-COVID metabolic enzyme alterations in K18-hACE2 mice exacerbate alcohol-induced liver injury through transcriptional regulation.

Coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), poses a significant threat to global public health. Despite reports of liver injury during viral disease, the occurrence and detailed mechanisms underlying the development of secondary exogenous liver injury, particularly in relation to changes in metabolic enzymes, remain to be fully elucidated. Therefore, this study was aimed to investigate the mechanisms underlying SARS-CoV-2-induced molecular alterations in hepatic metabolism and the consequent secondary liver injury resulting from alcohol exposure. We investigated the potential effects of SARS-CoV-2 infection on alcohol-induced liver injury in Keratin 18 promoter-human angiotensin converting enzyme 2 (K18-hACE2) transgenic mice. Mice were intranasally infected with 1×102 PFU of SARS-CoV-2. Following a 14 d recovery period from infection, the recovered mice were orally administered alcohol at 6 g/kg. Prior SARS-CoV-2 infection aggravated alcohol-induced liver injury based on increased alanine aminotransferase levels and cytoplasmic vacuolation. Interestingly, infected mice exhibited lower blood alcohol levels and higher levels of acetaldehyde, a toxic alcohol metabolite, compared to uninfected mice after the same period of alcohol consumption. Along with alterations of several metabolic process-related terms identified through RNA sequencing, notably, upregulation of cytochrome P450 2E1 (CYP2E1) and CYP1A2 was observed in infected mice compared to control value prior to alcohol exposure, with no significant impact of SARS-CoV-2 on intestinal damage. Tumor necrosis factor-alpha persistently showed upregulated expression in the infected mice; it also enhanced aryl hydrocarbon receptor and Sp1 expressions and their binding activity to Cyp1a2 and Cyp2e1 promoters, respectively, in hepatocytes, promoting the upregulation of their transcription. Our findings suggest that SARS-CoV-2 infection exacerbates alcohol-induced liver injury through the transcriptional activation of Cyp1a2 and Cyp2e1, providing valuable insights for the development of clinical recommendations on long COVID.

HIF-1A Gene Polymorphisms are Associated With Clinical and Biochemical Parameters in COVID-19 Patients in Serbian Population.

The hypoxia-inducible factor-1 alpha (HIF-1 alpha) is a major regulator of adaptive response to hypoxia, common in patients with severe coronavirus disease 2019 (COVID-19). In addition, HIF-1 alpha regulates the expression of the most important proteins necessary for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection of cells. The study included 129 hospitalized COVID-19 patients. Genotypes of HIF-1A gene polymorphisms rs11549465 and rs2057482 were determined by the RT-PCR method. We have observed lower mean platelet counts in carriers of HIF-1A rs11549465CC genotype (p = .050) and a significant association of thrombocytopenia with rs11549465CC/rs2057482CT HIF-1A genotypes combination (p = .037) in the group of patients under the age of 40. HIF-1A rs11549465CC genotype and rs11549465CC/rs2057482CT genotype combination could be predictive markers for thrombocytopenia in COVID-19 patients. Identification of such predictive markers for severe disease may contribute to a more efficient response of health systems to the SARS-CoV-2 pandemic.

Potential of mRNA therapy in the treatment of cardiovascular diseases

The outbreak of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), alarmed the global community due to the significant loss of human lives during the pandemic. However, as the saying goes, every cloud has a silver lining. A positive aspect of this recent pandemic has been that it stimulated scientists to create vaccines against SARS-CoV-2, accelerating the emergence of new therapeutic agents based on messenger ribonucleic acid (mRNA). Numerous mRNA therapeutic products are currently in development, with dozens at various clinical trial stages. These products have facilitated significant changes in the paradigm of medical therapy, including the treatment of cardiovascular diseases (CVD). Although most of these cardiovascular mRNA therapeutics are still in preclinical development, phase IIa trials for myocardial ischemia therapy have already been completed with encouraging results. The scope of mRNA therapy for CVD is extremely broad, potentially even limitless, with ongoing research including conditions like myocardial ischemia, heart failure, arrhythmias, hypercholesterolemia, and occlusive arterial diseases. Moreover, mRNA can be used to enhance the effectiveness of cell therapies. In the future, researchers predict that mRNA therapies will not only replace some existing biopharmaceuticals and pharmacotherapy methods but also be applied to treat previously considered untreatable cardiovascular diseases.

Environmental Dissemination of SARS-CoV-2: An Analysis Employing Crassphage and Next-Generation Sequencing Protocols.

This study aimed to investigate the dissemination of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in water samples obtained during the coronavirus disease 2019 pandemic period, employing cross-assembly phage (crAssphage) as a fecal contamination biomarker and next-generation sequencing protocols to characterize SARS-CoV-2 variants. Raw wastewater and surface water (stream and sea) samples were collected for over a month in Rio de Janeiro, Brazil.Ultracentrifugation and negatively charged membrane filtration were employed for viral concentration of the wastewater and surface water samples, respectively. Viruses were detected and quantified by (RT-)qPCR applying TaqMan® system protocols. SARS-CoV-2 RNA signals were detected in 92.5% (37/40) of the wastewater samples and in 31.25% (10/32) of the stream water samples, but not in seawater samples. CrAssphage was detected in 100% of the wastewater samples, 93.75% (30/32) of the stream samples, and in 2/4 of the seawater samples. CrAssphage detection and high concentrations in stream surface waters (median 8.95 log10 gc/L) revealed diffuse contamination by domestic wastewater in a region with high sanitary coverage. The correlations detected between SARS-CoV-2 data and the moving averages of clinical cases per capita over the sampling period were moderate to strong when applying a 13-day offset, regardless of normalization by crAssphage data or not. Sequencing of the receptor-binding domain of the spike protein confirmed the detection of SARS-CoV-2, but did not characterize the circulating variant. On the other hand, the whole genome sequencing protocol identified circulation of the Gamma variant, corroborating the sampling period clinical data.

Exploiting the Electrostatic Binding of Ruthenium Hexamine Molecular Redox Nanowires onto DNA/OGCN Biohybrid Electrodes toward the Electrochemical Detection of COVID-19.

The Coronavirus Disease 2019 (COVID-19) recently emerged as a life-threatening global pandemic that has ravaged millions of lives. The affected patients are known to frequently register numerous comorbidities induced by COVID-19 such as diabetes, asthma, cardiac arrest, hypertension, and neurodegenerative diseases, to name a few. The expensiveness and probability of false negative results of conventional screening tests often delay timely diagnosis and treatment. In such cases, the deployment of a suitable biosensing platform can readily expedite the rapid diagnosis process for enhanced patient outcomes. We report the development of an electrochemical genosensor based on DNA/OGCN (DNA/oxygenated graphitic carbon nitride) nanohybrids for the quantification of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) DNA─the key biomarker for COVID-19. This is achieved by exploiting the molecular nanowire-formation capability of the [Ru(NH3)6]2+/3+ redox probe onto the DNA phosphate backbone via electrostatic interactions. The microstructural characterization of OGCN was performed using scanning electron microscopy (SEM) coupled with an energy-dispersive X-ray (EDX) module, X-ray diffraction (XRD), and Fourier transform infrared spectroscopy. The electrochemical analyses were performed using cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS), while the analytical performance of the sensor was evaluated using square wave voltammetry (SWV). The developed sensor exhibited a wide linear detection range within 10 fM-10 μM, with a limit of detection (LoD) of ∼7.23 fM with a high degree of selectivity toward SARS-CoV-2 target DNA, thereby indicating its potential to be employed in a point-of-care scenario toward providing affordable healthcare to the global populace.

Alzheimer's disease and infectious agents: a comprehensive review of pathogenic mechanisms and microRNA roles.

Alzheimer's Disease (AD) is the most prevalent type of dementia and is characterized by the presence of senile plaques and neurofibrillary tangles. There are various theories concerning the causes of AD, but the connection between viral and bacterial infections and their potential role in the pathogenesis of AD has become a fascinating area of research for the field. Various viruses such as Herpes simplex virus 1 (HSV-1), Epstein-Barr virus (EBV), Cytomegalovirus (CMV), influenza viruses, and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), as well as bacteria such as Chlamydia pneumoniae (CP), Helicobacter pylori (HP), Porphyromonas gingivalis (P. gingivalis), Spirochetes and eukaryotic unicellular parasites (e.g., Toxoplasma gondii), have been linked to AD due to their ability to activate the immune system, induce inflammation and increase oxidative stress, thereby leading to cognitive decline and AD. In addition, microRNAs (miRNAs) might play a crucial role in the pathogenesis mechanisms of these pathogens since they are utilized to target various protein-coding genes, allowing for immune evasion, maintaining latency, and suppressing cellular signaling molecules. Also, they can regulate gene expression in human cells. This article provides an overview of the association between AD and various infectious agents, with a focus on the mechanisms by which these pathogens may be related to the pathogenesis of AD. These findings suggest important areas for further research to be explored in future studies.

Characteristics of humoral responses to the first coronavirus disease booster vaccine and breakthrough infection in central China: a multicentre, prospective, longitudinal cohort study.

The long-term immunogenicity, adverse effects, influencing factors, and protection from booster vaccines remain unclear. Specifically, little is known regarding the humoral immunity and breakthrough infections associated with COVID-19 booster immunization. Therefore, we evaluated the immunogenicity, reactogenicity, influencing factors, and protective effects of the first coronavirus disease booster vaccine 23 months before and after implementation of dynamic zero epidemic control measures among healthcare staff. We prospectively included 389 healthcare staff members in China with negative pre-enrolment severe acute respiratory syndrome coronavirus 2 test results. Neutralising serum antibodies were evaluated every two months till 23 months post-booster vaccination. Breakthrough infection was recorded or confirmed by SARS-CoV-2 specific PCR testing via throat swabs from participants before and after dynamic zero epidemic control measures. At 15-30 days after vaccination, the mean concentration of the booster vaccine was 6.4 times above initial concentrations. Poorer antibody responses by booster vaccine correlated with male sex, longer post-booster duration, same-manufacturer vaccines, post-routine epidemic control measures implementation and intervals >210 days between primary and booster vaccinations. Higher breakthrough rates were associated with longer post-booster durations and post-routine epidemic control measures implementation but not associated with levels of neutralising antibodies after booster vaccination from participants. Adverse reactions were non-serious. These booster vaccine doses induced rapid, robust antibody responses, maintained for only 6-7 months. Neutralizing antibodies induced by breakthrough infection with SARS-CoV-2 were weaker than those induced by the first COVID-19 booster vaccine, predicting that antibodies induced by SARS-CoV-2 may be very different from those of other known infectious pathogens.

Membrane-Active Singlet Oxygen Photogenerators as a Paradigm for Broad-Spectrum Antivirals: The Case of Halogenated (BOron)-DIPYrromethenes.

Enveloped viruses, such as flaviviruses and coronaviruses, are pathogens of significant medical concern that cause severe infections in humans. Some photosensitizers are known to possess virucidal activity against enveloped viruses, targeting their lipid bilayer. Here we report a series of halogenated difluoroboron-dipyrromethene (BODIPYs) photosensitizers with strong virus-inactivating activity. Our structure-activity relationship analysis revealed that BODIPY scaffolds with a heavy halogen atom demonstrate significant efficacy against both tick-borne encephalitis virus (TBEV; Flaviviridae family) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; Coronaviridae family) along with high singlet oxygen quantum yields. Moreover, select compounds also inactivated other enveloped viruses, such as herpes simplex virus type 1 and monkeypox virus. The nature and length of the alkyl side chain notably influenced the virus-inactivating activity of BODIPY molecules. Furthermore, molecular dynamics studies highlighted the critical importance of the positioning of the chromophore moiety within the lipid bilayer. As membrane-targeting photosensitizers, BODIPYs interact directly with virus particles, causing damage to the viral envelope membranes. Thus, TBEV pretreated with BODIPY was completely noninfective for lab mice. Consequently, BODIPY-based photosensitizers hold potential either as broad-spectrum virus-inactivating antivirals against a variety of phylogenetically unrelated enveloped viruses or as potent inactivators of viruses for the development of vaccines for preventing life-threatening emerging viral diseases.

Outcomes of a Structured Olfactory and Gustatory Rehabilitation Program in Children with Post-COVID-19 Smell and Taste Disturbances

Background/Objectives: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is closely related to SARS-CoV and uses angiotensin-converting enzyme 2 as its cellular receptor. In early 2020, reports emerged linking CoV disease 2019 (COVID-19) to olfactory and gustatory disturbances. These disturbances could be attributed to virus-induced damage to olfactory neurons or immune responses, thereby affecting sensory functions. This randomized controlled trial aimed to evaluate the effectiveness of a structured orofacial rehabilitation program in improving smell (olfaction) and taste (gustation) sensations in children post-COVID-19. Methods: Forty children recovering from COVID-19 in government hospitals in Saudi Arabia were included and randomly assigned to the control group or the experimental group. The orofacial program included (a) facilitation of olfactory function using the 40-item modified Arabic version of the University of Pennsylvania Smell Identification Test (UPSIT); (b) assessment of gustatory function using taste strips with four varying concentrations; and (c) orofacial myofunctional therapy. The intervention was applied three times a week and lasted for 3 months. Results: The experimental group showed a significantly greater improvement in UPSIT scores (median change of 24.1%) than the control group (14.7%; p = 0.010). However, no significant difference was found in the taste strip test scores among the groups or between male and female participants. Conclusions: This study suggests that a structured orofacial rehabilitation program could enhance olfactory and gustatory functions in children recovering from COVID-19.

Shattering the Amyloid Illusion: The Microbial Enigma of Alzheimer's Disease Pathogenesis-From Gut Microbiota and Viruses to Brain Biofilms.

For decades, Alzheimer's Disease (AD) research has focused on the amyloid cascade hypothesis, which identifies amyloid-beta (Aβ) as the primary driver of the disease. However, the consistent failure of Aβ-targeted therapies to demonstrate efficacy, coupled with significant safety concerns, underscores the need to rethink our approach to AD treatment. Emerging evidence points to microbial infections as environmental factors in AD pathoetiology. Although a definitive causal link remains unestablished, the collective evidence is compelling. This review explores unconventional perspectives and emerging paradigms regarding microbial involvement in AD pathogenesis, emphasizing the gut-brain axis, brain biofilms, the oral microbiome, and viral infections. Transgenic mouse models show that gut microbiota dysregulation precedes brain Aβ accumulation, emphasizing gut-brain signaling pathways. Viral infections like Herpes Simplex Virus Type 1 (HSV-1) and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) may lead to AD by modulating host processes like the immune system. Aβ peptide's antimicrobial function as a response to microbial infection might inadvertently promote AD. We discuss potential microbiome-based therapies as promising strategies for managing and potentially preventing AD progression. Fecal microbiota transplantation (FMT) restores gut microbial balance, reduces Aβ accumulation, and improves cognition in preclinical models. Probiotics and prebiotics reduce neuroinflammation and Aβ plaques, while antiviral therapies targeting HSV-1 and vaccines like the shingles vaccine show potential to mitigate AD pathology. Developing effective treatments requires standardized methods to identify and measure microbial infections in AD patients, enabling personalized therapies that address individual microbial contributions to AD pathogenesis. Further research is needed to clarify the interactions between microbes and Aβ, explore bacterial and viral interplay, and understand their broader effects on host processes to translate these insights into clinical interventions.

Short-Time Preamplification-Assisted One-Pot CRISPR Nucleic Acid Detection Method with Portable Self-Heating Equipment for Point-of-Care Diagnosis.

Infectious diseases, especially respiratory infections, have been significant threats to human health. Therefore, it is essential to develop rapid, portable, and highly sensitive diagnostic methods for their control. Herein, a short-time preamplified, one-pot clustered regularly interspaced short palindromic repeats (CRISPR) nucleic acid detection method (SPOC) is developed by combining the rapid recombinase polymerase amplification (RPA) with CRISPR-Cas12a to reduce the mutual interference and achieve facile and rapid molecular diagnosis. SPOC can reduce the detection time and stably detect up to 1 copy/μL of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA without affecting the detection sensitivity. A highly sensitive one-pot assay integrated with reverse transcription RPA is achieved by wrapping paraffin with a specific melting point on the lyophilized CRISPR reagent surface. A self-heating pack is designed based on thermodynamic principles to melt the paraffin and release CRISPR reagents, enabling low-cost and time-saving detection. Notably, the designed system, coupled with RNA extraction-free technology, can achieve "sample-in-answer-out" detection of the SARS-CoV-2 Orf1ab gene within 22 min using smartphone imaging. The developed assay is validated on 12 clinical samples, and the results 100% correlate with real-time polymerase chain reaction. SPOC is time-saving, is easy to operate, and can eliminate centrifugal and complex hardware devices, satisfying the demand for point-of-care diagnostics in resource-constrained settings.

Advancements in Structural Basis of Covalent Inhibitors Targeting SARS-CoV-2 Essential Proteins.

Covalent inhibitors play a pivotal role in the development of pharmaceutical therapies, as they form stable, irreversible bonds with target biomolecules, leading to prolonged therapeutic effects and enhanced efficacy. Since covalent inhibitors first appeared in the late 1800s, the field has become innovative rapidly, and covalent inhibitors now account for around 30% of all marketed therapeutics. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes the pandemic of Coronavirus Disease 2019 (COVID-19). SARS-CoV-2 needs to be cured with a medicine that is beneficial and with the least side effects. It is necessary to formulate drug candidates to treat this pathogen. The predominance of covalent medications will be briefly discussed in this review, followed by an introduction to their methods of action, as well as more thorough discussions of the safe and effective covalent enzyme inhibitors against SARS-CoV-2. Our main concern is to study covalent inhibitors which are mainly involved in blocking the viral entry of the virus SARS-CoV-2 into the host cell along with its replication and translation process. In the development of anti-SARS-CoV-2 medicines researchers can use those reported drugs as prospective candidates.