Targeting RNA-dependent RNA polymerase (RdRp), a highly conserved enzyme essential for SARS coronavirus 2 (SARS-CoV-2) replication and transcription, represents a promising antiviral strategy due to its lower mutation rate than structural proteins such as Spike. This study introduces a cell-based assay system for screening potential SARS-CoV-2 RdRp inhibitors, contributing to ongoing efforts to identify effective antiviral agents. The assay utilizes a reporter vector containing the 3' untranslated region (UTR), luciferase reporter gene, and 5' UTR gene, sequentially arranged in reverse under the control of the cytomegalovirus promoter in the pcDNA3.1 vector. Co-transfection with SARS-CoV-2 RdRp resulted an increase in luminescence-based quantification of RdRp activity, achieving a Z-factor of 0.605, indicative of high reproducibility and reliability for high-throughput screening. Established RdRp inhibitors, including remdesivir, molnupiravir, tenofovir, and sofosbuvir, significantly reduced reporter activity, with remdesivir exhibiting the strongest inhibition. A newly identified RdRp inhibitor was further validated through primer extension polymerase and NMPylation assays, along with virus-based experiments, confirming its inhibitory mechanism. These results highlight the utility of this screening system in identifying effective RdRp-targeting antivirals, reinforcing the strategic importance of RdRp inhibition in combating SARS-CoV-2 and emerging variants.

Introduction: Coronavirus (CoV) is an extremely contagious, enveloped positive-single-stranded RNA virus, which has become a global pandemic that causes several illnesses in humans and animals. Hence, it is necessary to investigate viral-induced reactions across diverse hosts. Herein, we propose utilizing naturally secreted extracellular vesicles (EVs), mainly focusing on exosomes to examine virus-host responses following CoV infection. Exosomes are small membrane-bound vesicles originating from the endosomal pathway, which play a pivotal role in intracellular communication and physiological and pathological processes. We suggested that CoV could impact EV formation, content, and diverse immune responses in vitro. Methods: In this study, we infected A-72, which is a canine fibroblast cell line, with a feline coronavirus (FCoV) and canine coronavirus (CCoV) independently in an exosome-free media at 0.001 multiplicity of infection (MOI), with incubation periods of 48 and 72 h. The cell viability was significantly downregulated with increased incubation time following FCoV and CCoV infection, which was identified by performing the 3-(4,5-dimethylthiazo-1-2yl)-2,5-diphenyltetrazolium bromide (MTT) assay. After the infection, EVs were isolated through ultracentrifugation, and the subsequent analysis involved quantifying and characterizing the purified EVs using various techniques. Results: NanoSight particle tracking analysis (NTA) verified that EV dimensions fell between 100 and 200 nm at both incubation periods. At both periods, total protein and RNA levels were significantly upregulated in A-72-derived EVs following FCoV and CCoV infections. However, total DNA levels were gradually upregulated with increased incubation time. Dot blot analysis indicated that the expression levels of ACE2, IL-1β, Flotillin-1, CD63, caspase-8, and Hsp90 were modified in A-72-derived EVs following both CoV infections. Conclusions: Our results indicated that FCoV and CCoV infections could modulate the EV production and content, which could play a role in the development of viral diseases. Investigating diverse animal CoV will provide in-depth insight into host exosome biology during CoV infection. Hence, our findings contribute to the comprehension and characterization of EVs in virus-host interactions during CoV infection.

Background: This study investigated the role of genetic polymorphisms in IFNAR2, OAS1, OAS3, and ACE2 as predictors of Paxlovid treatment response, specifically examining their influence on the clinical course and laboratory parameters of COVID-19 patients. Methods: We analyzed the impact of polymorphisms in genes associated with the interferon pathway (IFNAR2 rs2236757), antiviral response (OAS1 rs10774671, OAS3 rs10735079), and viral entry (ACE2 rs2074192) in individuals treated with Paxlovid. Results: Our findings suggest that genetic variations in these genes may modulate the immune response and coagulation pathways in the context of Paxlovid treatment during COVID-19 infection. Specifically, the IFNAR2 rs2236757 G allele was associated with alterations in inflammatory and coagulation markers, while polymorphisms in OAS1 and OAS3 influenced coagulation parameters. Furthermore, specific genotypes were linked to changes in clinical parameters such as oxygen saturation, leukocyte count, and liver function markers in Paxlovid-treated patients. Conclusions: These results highlight the potential of considering genetic factors in understanding individual responses to COVID-19 treatment with Paxlovid and informing future personalized approaches.

Up to 90% of patients with high-grade serous ovarian cancer (HGSC) will develop resistance to platinum-based chemotherapy, posing substantial therapeutic challenges due to a lack of universally druggable targets. Leveraging BenevolentAI's artificial intelligence (AI)-driven approach to target discovery, we screened potential AI-predicted therapeutic targets mapped to unapproved tool compounds in patient-derived 3D models. This identified TNIK, which is modulated by NCB-0846, as a novel target for platinum-resistant HGSC. Targeting by this compound demonstrated efficacy across both in vitro and ex vivo organoid platinum-resistant models. Additionally, NCB-0846 treatment effectively decreased Wnt activity, a known driver of platinum resistance; however, we found that these effects were not solely mediated by TNIK inhibition. Comprehensive AI, in silico, and in vitro analyses revealed CDK9 as another key target driving NCB-0846's efficacy. Interestingly, TNIK and CDK9 co-expression positively correlated, and chromosomal gains in both served as prognostic markers for poor patient outcomes. Combined knockdown of TNIK and CDK9 markedly diminished downstream Wnt targets and reduced chemotherapy-resistant cell viability. Furthermore, we identified CDK9 as a novel mediator of canonical Wnt activity, providing mechanistic insights into the combinatorial effects of TNIK and CDK9 inhibition and offering a new understanding of NCB-0846 and CDK9 inhibitor function. Our findings identified the TNIK-CDK9 axis as druggable targets mediating platinum resistance and cell viability in HGSC. With AI at the forefront of drug discovery, this work highlights how to ensure that AI findings are biologically relevant by combining compound screens with physiologically relevant models, thus supporting the identification and validation of potential drug targets.

Objective: To assess the perceived risks and impact of the COVID-19 outbreak on radiation therapists in Saudi Arabia. Methods: A questionnaire was distributed to all radiation therapists in the country. The questionnaire contained questions about demographic characteristics, the extent of the pandemic's impact on hospital resources, risk perception, work-life, leadership, and immediate supervision. The questionnaire's reliability was assessed using Cronbach's alpha; >0.7 was considered adequate. Results: Out of the 127 registered radiation therapists, 77 (60.6%) responded; 49 (63.6%) females; and 28 (36.4%) males. The mean age was 36.8 ± 12.5 years. Nine (12%) of the participants had a past experience with pandemics or epidemics. Further, 46 (59.7%) respondents correctly identified the mode of transmission of COVID-19. Approximately, 69% of the respondents perceived COVID-19 as more than a minor risk to their families and 63% to themselves. COVID-19 had an overall negative impact on work at the personal and organizational levels. However, there was a positive attitude toward organizational management during the pandemic in general; positive responses ranged from 66.2% to 82.4%. Ninety-two percent considered protective resources and 70% considered the availability of supportive staff to be adequate. Demographic characteristics were not significantly associated with the perceived risk. Conclusions: Despite the high perception of risk and negative impact on their work, radiation therapists conveyed a positive overall perception regarding resource availability, supervision, and leadership. Efforts should be made to improve their knowledge and appreciate their efforts.

The growing societal impact of coronavirus disease 2019 (COVID-19) has underscored the urgent need for innovative strategies to address the ongoing challenges posed by the pandemic. While rapid therapeutic interventions remain critical for short-term mitigation, equally vital is the development of accessible and efficient diagnostic tools to curb viral transmission. In this context, optical sensing technologies have emerged as foundational tools for detection and diagnosis, owing to their rapid response, user-friendliness, and adaptability. These attributes strengthen their indispensable role in identifying severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19. This review systematically outlines the structural components of SARS-CoV-2 virions and their respective biological functions, classifies optical biosensors according to their underlying principles and evaluates the advantages and limitations of each methodology in real-world diagnostic applications. By addressing current detection challenges, these optical platforms not only enhance our capacity to manage SARS-CoV-2 but also establish a framework for deploying optical sensing technologies in future pandemic scenarios.

Obstructive sleep apnea (OSA) is associated with health complications, but its impact on COVID-19 outcomes is not known. This study investigated the association between OSA and outcomes of hospitalized COVID-19 patients.

The Nationwide Inpatient Sample 2020 was searched for adults hospitalized for COVID-19. The outcomes of interest were in-hospital mortality, non-routine discharge, prolonged length of stay (LOS), and complications. Patients with OSA were matched to those without OSA in a 1:4 ratio using propensity score matching (PSM) according to age, sex, and major comorbidities.

After PSM, there were 54,900 adult COVID-19 patients consisting of 10,980 with OSA and 43,920 without OSA. The mean age was 63.2 years and 62.8% were male. Patients with OSA had higher odds of respiratory failure (adjusted OR [aOR] = 1.20, 95% confidence interval [CI]: 1.14-1.25), heart failure (aOR = 1.71, 95% CI: 1.60-1.82), and arrhythmias (aOR = 1.18, 95% CI: 1.08-1.30). Conversely, OSA was associated with lower odds of cerebrovascular accidents (CVAs) (aOR = 0.71, 95% CI: 0.62-0.81, p < 0.001), and a reduced likelihood of in-hospital mortality among patients ≥70 years old (aOR = 0.82, 95% CI: 0.75-0.89, p < 0.001) and males (aOR = 0.79, 95% CI: 0.72-0.88, p < 0.001), but not females.

OSA is associated with higher risks of respiratory failure, heart failure, and arrhythmias in patients hospitalized for COVID-19. However, patients with OSA who are ≥70 years old and those who are male are less likely to have CVAs and in-hospital mortality. These findings underscore the complex relationship between OSA and COVID-19. As the study focused on hospitalized patients, the findings may not apply to mild or asymptomatic COVID-19 cases. Future research should include community-based cohorts and prospective studies to better understand this association.

Effective management of COVID-19 requires clinical tools to treat the disease in addition to preventive vaccines. Several recombinant mAbs and their cocktails have been developed to treat COVID-19 but these have limitations. Here, we evaluate small ankyrin repeat proteins called Ankyrons that were generated to bind with high affinity to the SARS-CoV-2 virus. Ankyrons are ankyrin repeat proteins comprised of repetitions a structural module. Each module consists of a β-turn followed by two antiparallel α-helices. The Ankyrons™ are directly selected in vitro from a highly diverse library of around a trillion clones in ribosome display and like antibodies can bind with high affinity to almost any target. We assessed Ankyrons that were generated against the wild-type SARS-CoV-2 and the Delta (B.1.617.2) and Omicron (BA.1) variants in a binding assay. We determined that all Ankyrons were specific in that they did not bind to MERS. While all Ankyrons bound with high affinity to the variant they were generated against, some also showed cross-reactivity to all three SARS-CoV-2 variants. Binding assays are useful for screening analytes but do not provide information about clinical effectiveness. Therefore, we used a pseudovirus-based neutralization assay to show that five of the Ankyrons evaluated neutralized all three strains of SARS-CoV-2. We have provided a workflow for the evaluation of novel Ankyrons against a viral target. This suggests that Ankyrons could be useful for rapidly developing new research tools for studying other emerging infectious diseases rapidly with the optional further potential for developing Ankyrons into diagnostic and even therapeutic applications.

Hydroxychloroquine and Chloroquine (CQ) and Hydroxychloroquine (HCQ) are antimalarial drugs with well-known anti-inflammatory and antiviral effects used to treat various diseases, with few side effects. After COVID-19 emergence, numerous researches from around the world have examined the potential of using CQ or HCQ as potential treatment of COVID-19. However, conflicting outcomes have been found in COVID-19 clinical trials after treatment with CQ or HCQ. This study aims to evaluate research on CQ and HCQ for COVID-19 treatment and prophylaxis control using bibliometric methods.

We analyzed bibliometric data on HCQ and COVID-19 (HCQ-C19) quantitatively and semantically (2020-2023) using the Scopus database VOSviewer, Bibliometrix, and MS Excel.

Analyses of 7471 original and conference articles revealed that the total number of publications has continually increased. The country producing the most articles in this field was the United States, followed by Italy, India, and Spain. The top-productive authors on HCQ-C19 are Mussini, C., and Raoult, D. (Italy) with 23 and 21 articles, respectively. The top-impactful organization is IHU Méditerranée Infection, France. A Bibliometrix's network analysis based on the co-occurrence of keywords revealed the following themes HCQ-C19, including "clinical research/practice," "COVID-19," "thrombosis," "HCQ," "epidemiology," and "infectious disease."

In conclusion, the analysis reveals a growing interest in HCQ-C19 research. Prominent contributions come from the United States, Italy, India, and Spain. Key themes include clinical research/practice, COVID-19, thrombosis, HCQ, epidemiology, and infectious disease. Future recommendations include conducting well-designed clinical trials and fostering collaborative interdisciplinary efforts.

The Coronavirus disease 2019 (COVID-19) pandemic has caused significant global threats, as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is primarily transmitted through airborne droplets and bioaerosols. Healthcare workers are particularly at high risk, yet there is limited research on the presence of SARS-CoV-2 in bioaerosols within healthcare facilities in Malaysia. This study aimed to determine the presence and viability of SARS-CoV-2 and its variants of concern in the air and ventilation systems of designated COVID-19 facilities from December 2021 to February 2022. Samples were collected from two hospitals and one quarantine centre (QC), including medical wards, intensive care units, emergency departments, and QC halls. Air samples were obtained using air samplers, while surface samples were taken from return air grilles. SARS-CoV-2 ribonucleic acid (RNA) and its variants were detected using reverse transcription droplet digital polymerase chain reaction (RT-ddPCR) and PCR-based genotyping, respectively. Results showed that Hospital A had a higher rate (24.6%) of positive samples than Hospital B (8.8%). Surface samples had a higher positivity rate (50.0%) compared to air samples (8.3%). The detected variants included delta (34.7%), a mixture of delta and omicron (8.7%), non-variant of concern (non-VOC) (8.7%), and omicron (4.3%). This study emphasizes the need for strict airborne infection control measures for healthcare workers.

Considering the limited treatment options for acute lung injury (ALI) and pulmonary fibrosis (PF), ozone treatment may be promising as a new immunological agent with its ability to modulate cytokines and interferons. We aimed to investigate the effects of inhaled ozone therapy on both ALI and PF in rat models. A total of 48 albino Wistar male rats were included in the study. Lipopolysaccharide (LPS) was used to induce the ALI model, and bleomycin was used for the PF model. The effects of inhaled ozone (O3) were investigated using the ELISA method. Hematoxylin&eosin staining, Masson's trichrome staining, and immunohistochemical methods were used for histopathological evaluation. The Interleukin-1 beta (IL-1β), Interleukin-6 (IL-6), Tumor Necrosis Factor-alpha (TNF-α), and Nuclear Factor kappa B subunit p65 (NF-κB p65) levels in the ALI + 0.08 ppm O3, ALI + 0.12 ppm O3, PF + 0.08 ppm O3, and PF + 0.12 ppm O3 groups statistically decreased to the same extent and approached the levels of control animals. It was observed that IL-1β, IL-6, TNF-α, and NF-κB p65 levels in lung tissues were significantly and dose-dependently decreased compared to the untreated PF and ALI groups, respectively. While fibrosis was severe in the PF + 0.08 ppm O3 group, it decreased to more moderate levels in the PF + 0.12 ppm O3 group. The cytokine levels confirmed that inhaled ozone protected the lungs from both ALI and the development of PF.

The COVID-19 pandemic has led to the excessive use of antimicrobials in critically ill patients. Infections caused by Acinetobacter baumannii have increased significantly both regionally and globally during the COVID-19 pandemic, posing dramatic challenges for intensive care unit (ICU) patients. This study aimed to determine the prevalence, antimicrobial resistance patterns, presence of selected antimicrobial resistance genes, and genetic diversity of A. baumannii isolates obtained from COVID-19 cases admitted to the ICU at the University Hospital in Iran.

This was a cross-sectional and single-center study comprising patients with A. baumannii infections admitted to the ICU with COVID-19 between April and November 2021. The demographic and clinical data of the patients were collected. Antimicrobial susceptibility testing was conducted based on Clinical Laboratory Standards Institute guidelines. This study used PCR and multiplex PCR to investigate antibiotic resistance genes (ARGs) and global clones (GC), respectively. Genetic diversity was investigated by repetitive element sequence-based PCR (REP-PCR).

The prevalence of A. baumannii coinfection in COVID-19 cases was 8.1% (43/528). More than 90% (39/43) of A. baumannii isolates were resistant to cefepime, ampicillin-sulbactam, gentamicin, trimethoprim-sulfamethoxazole and amikacin. Furthermore, 44.2% (19/43) of isolates were resistant to colistin. There were 91% (39/43) isolates that were extensively drug-resistant (XDR). The most prevalence carbapenem resistance encoding genes were bla -OXA-23 65.1% (29/43) and bla NDM 41.8% (18/43). The most common aminoglycoside resistance genes were aac(6')-Ib 65.1% (28/43) and ant(2)-Ia 46.5% (20/43). Isolates from the prominent Global clone GCII comprised 83.7% (36/43) of total isolates. Genetic fingerprinting using REP-PCR revealed that 39 typeable A. baumannii isolates were categorized into 12 distinct genotypes, of which 72% (28/39) of isolates belonged to one genotype.

The high prevalence of XDR A. baumannii such as carbapenem and colistin-resistant strains, poses a significant concern for the treatment of COVID-19 patients, heightening the risk of therapeutic failure. The data demonstrate the dissemination of a single A. baumannii clone carrying multiple ARGs within our hospital. Regarding the limited therapeutic options, it is crucial to implement effective prevention and containment policies to curb the spread of these strains.

The SARS-CoV-2-induced disease, COVID-19, remains a worldwide public health concern due to its high rate of transmission, even in vaccinated and previously infected people. In the endemic state, it continues to cause significant pathology. To elu- cidate the viral mutational changes and screen the emergence of new variants of concern, we conducted this study in Bangladesh. The viral RNA genomes extracted from 25 ran- domly collected samples of COVID-19-positive patients from March 2021 to February 2022 were sequenced using Illumina COVID Seq protocol and genomic data processing, as well as evaluations performed in DRAGEN COVID Lineage software. In this study, the percentage of Delta, Omicron, and Mauritius variants identified were 88%, 8%, and 4%, respectively. All of the 25 samples had 23,403 A>G (D614G, S gene), 3037 C>T (nsp3), and 14,408 C>T (nsp12) mutations, where 23,403 A>G was responsible for increased transmis- sion. Omicron had the highest number of unique mutations in the spike protein (i.e., sub- stitutions, deletions, and insertions), which may explain its higher transmissibility and immune-evading ability than Delta. A total of 779 mutations were identified, where 691 substitutions, 85 deletions, and 3 insertion mutations were observed. To sum up, our study will enrich the genomic database of SARS-CoV-2, aiding in treatment strategies along with understanding the virus's preferences in both mutation type and mutation site for predicting newly emerged viruses' survival strategies and thus for preparing to coun- teract them.

Background: in the twenty-first century, the emergence of COVID-19 as a highly transmissible pandemic disease caused by SARS-CoV-2 posed a significant threat to humanity. Aims & Objectives: the disease spreads through small respiratory droplets, necessitating the use of various compounds for treatment, with alkaloids being recognized as particularly crucial owing to their diverse pharmaceutical properties. Methodology: in this study, a dataset comprising 100 natural alkaloids obtained from the literature was transformed into 2D chemical structures using Chem Draw 19.1. Subsequently, 3DQSAR studies were conducted on the dataset, resulting in the automatic screening of 50 compounds from the initial pool of 100 compounds. The values of q 2 and r 2 of the validated field-based 3DQSAR model were 0.7186 and 0.971, respectively. The validated atom-based 3DQSAR model has q 2 and r 2 scores of 0.6025 and 0.9845, respectively. Based on the obtained results, 10 compounds with exceptionally active predictive IC50 values were selected for further analysis. Docking experiments were then performed on the selected compounds, and the top three compounds with the highest docking scores were identified as diazepinomicin, (+)-N-methylisococlaurine, and hymenocardine-H. After docking, MM-GBSA was performed on the complexes of diazepinomicin, (+)-N-methylisococlaurine and hymenocardine-H with their corresponding proteins, which resulted in the authentication of the molecular docking scores. MD simulations were also performed to check the flexibility, stability and compactness of these complexes for revalidation of docking scores. Results: finally, ADMET experiments revealed that (+)-N-methylisococlaurine exhibited the most favourable properties among these three compounds.

The unrelenting emergence of SARS-CoV-2 variants has significantly challenged the efficacy of existing COVID-19 vaccines. Enhancing the stability and immunogenicity of the spike protein is critical for improving vaccine performance and addressing variant-driven immune evasion.

We developed an mRNA-based vaccine, RV-1730, encoding the Delta variant spike protein with the S6P mutation to enhance stability and immunogenicity. The vaccine's immunogenicity and protective efficacy were evaluated in preclinical models, including monovalent (RV-1730) and bivalent (RV-1731) formulations targeting the Delta and BA.1 variants. Additionally, the effectiveness of RV-1730 as a heterologous booster following primary vaccination with BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna-NIAID) was assessed.

RV-1730 elicited significantly stronger B and T cell responses and more durable neutralizing antibodies compared to S2P-based vaccines. The bivalent RV-1731 vaccine demonstrated broad neutralizing activity against emerging variants, including XBB1.5 and JN.1. Importantly, RV-1730, when used as a heterologous booster following initial immunization with BNT162b2 or mRNA-1273, significantly enhanced neutralizing antibody titers against multiple variants, including Delta and Omicron. Both RV-1730 and RV-1731 provided superior protection in preclinical models, indicating enhanced efficacy due to the S6P mutation.

The incorporation of the S6P mutation into the Delta variant spike protein significantly enhances the immunogenicity and efficacy of mRNA-based COVID-19 vaccines. The strong performance of RV-1730 as a heterologous booster and the broad-spectrum activity of the bivalent RV-1731 vaccine underscore their potential as versatile and effective vaccination strategies against SARS-CoV-2 and its evolving variants.

The COVID-19 pandemic has caused significant mortality and morbidity for millions of people. Severe Acute Respiratory Syndrome-2 (SARS-CoV-2) virus is capable of causing severe and fatal diseases. We evaluated the antiviral properties of Aspergillus tamarii SP73-EGY isolate extract against low pathogenic coronavirus (229E), Adeno-7- and Herpes-2 viruses. The extract showed a high selectivity index (SI = 43.4) and a significant inhibition of 229E (IC50 = 8.205 μg/ml). It was stronger than the drug control, remdesivir (IC50 = 38.2 μg/ml, SI = 7.29). However, the extract showed minimal efficacy against Adeno-7- and Herpes-2-Viruses (IC50 = 22.52, 47.79 μg/ml, and SI = 6.75, 5.08, respectively). It exhibited profound efficacy against the highly pathogenic SARS-CoV-2 (IC50 = 8.306 μg/ml, SI = 42.2). Kojic acid, the primary component of the extract, showed substantial antiviral activity against SARS-CoV-2 (IC50 = 23.4 μg/ml, SI = 5.6), Remdesivir (IC50 = 4.55 μg/ml, SI = 61.45). Therefore, the extract demonstrated the most notable antiviral characteristics against coronavirus infection. Co-infecting microorganisms may contribute to immune system deterioration and airway injury caused by SARS-CoV-2. The extract showed significant efficacy against E. coli and P. aeruginosa, with an inhibition range of 3.5-10 mm at a concentration of 200 mg/ml. A molecular docking study showed that hexadecanoic, Kojic, octanoic acids, and 4(4-Methylbenzylidene)cyclohexane-1,3-dione have stronger binding affinity to the SARS-CoV-2 Mpro than Remdesivir. Molecular dynamics simulations were employed to examine the structural stability and flexibility of these complexes. This confirmed the high binding affinities of Kojic acid and 4(4-Methylbenzylidene)cyclohexane-1,3-dione, thereby proving their potential as novel anti-SARS-CoV-2.

It has been demonstrated that COVID-19 vaccines confer significant protection, but temporal decay in the vaccine-induced antibodies has been reported; therefore, a third booster dose was considered. Human leukocyte antigen (HLA) class II molecules act as antigen presenting structures, play critical roles in the formation of an efficient antibody response. The current study aimed to evaluate the anti-receptor binding domain (RBD) antibody response after the booster dose of SpikoGen® vaccine in individuals with a history of Sinopharm primary vaccination series and its association with HLA-DQB1 and -DRB alleles.

Whole blood samples were drawn from 95 eligible individuals before and three weeks after the booster dose of SpikoGen®. Quantitative measurement of anti-RBD IgG and qualitative assessment of anti-RBD IgA was performed using the ELISA method and HLA-DQB1 and -DRB loci were genotyped by low-resolution SSP-PCR method.

A significant increase was observed in the anti-RBD IgG antibodies after the booster dose of SpikoGen® (baseline: 1.82 ± 0.55 GMT, after: 2.28 ± 0.36 GMT)(P < 0.0001). The median fold change of anti-RBD IgG antibodies for DRB1*14 positive individuals (3.96 (1.47-31.75)) was significantly higher than DRB1*14 negative people (1.18 (1.08-1.34))(P = 0.008). In addition, the median fold change of anti-RBD IgG antibodies for DQB1*04 positive individuals (1.39 (1.21-3.43)) was higher than those which were DQB1*04 negative (1.18 (1.08-1.34)), however it was marginally significant (P = 0.060). The seroconversion incidence for anti-RBD IgA antibodies was 68.42 %.

In conclusion, our study showed that the booster dose of SpikoGen® can elicit a robust anti-RBD antibody response which was positively associated with DRB1*14 allele.

A significant number of deaths and disabilities worldwide are brought on by inflammatory lung diseases. Many inflammatory lung disorders, including chronic respiratory emphysema, resistant asthma, resistance to steroids, and coronavirus-infected lung infections, have severe variants for which there are no viable treatments; as a result, new treatment alternatives are needed. Here, we emphasize how oxidative imbalance contributes to the emergence of provocative lung problems that are challenging to treat. Endogenic antioxidant systems are not enough to avert free radical-mediated damage due to the induced overproduction of ROS. Pro-inflammatory mediators are then produced due to intracellular signaling events, which can harm the tissue and worsen the inflammatory response. Overproduction of ROS causes oxidative stress, which causes lung damage and various disease conditions. Invasive microorganisms or hazardous substances that are inhaled repeatedly can cause an excessive amount of ROS to be produced. By starting signal transduction pathways, increased ROS generation during inflammation may cause recurrent DNA damage and apoptosis and activate proto-oncogenes. This review provides information about new targets for conducting research in related domains or target factors to prevent, control, or treat such inflammatory oxidative stress-induced inflammatory lung disorders.

The COVID-19 pandemic has spurred significant endeavors to devise treatments to combat SARS-CoV-2. A limited array of small-molecule antiviral drugs, specifically monoclonal antibodies and interferon therapy, have been sanctioned to treat COVID-19. These treatments typically necessitate administration within ten days of symptom onset. There have been reported reductions in the effectiveness of these medications due to mutations in non-structural protein genes, particularly against Omicron subvariants. This underscores the pressing requirement for healthcare systems to continually monitor pathogen variability and its impact on the efficacy of prevention and treatments.

This review aimed to comprehend the therapeutic benefits and recent progress of nMAbs for preventing and treating the Omicron variant of SARS-CoV-2.

Neutralizing monoclonal antibodies (nMAbs) provide a treatment avenue for severely affected individuals, especially those at high risk for whom vaccination is not viable. With their specific epitope affinity, they pose no significant risk of severe adverse effects. The degree of reduction in neutralization varies significantly across different monoclonal antibodies and variant combinations. For instance, Sotrovimab maintained its neutralization effectiveness against Omicron BA.1, but exhibited diminished efficacy against BA.2, BA.4, BA.5, and BA.2.12.1.

Bebtelovimab has been observed to preserve its efficacy against all subtypes of the Omicron variant. Subsequently, WKS13, mAb-39, 19n01, F61-d2 cocktail, etc., have become effective. This review has highlighted the therapeutic implications of nMAbs in SARS-CoV-2 Omicron treatment and the progress of COVID-19 drug discovery.

Post-COVID-19 syndrome (PCS) is a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection-associated chronic condition characterized by long-term violations of physical and mental health. People with type 2 diabetes (T2D) are at high risk for severe COVID-19 and PCS.

The current study aimed to define the predictors of PCS development in people with T2D for further planning of preventive measures and improving patient outcomes.

The data were collected through the national survey targeting persons with T2D concerning the history of COVID-19 course and signs and symptoms that developed during or after COVID-19 and continued for more than 12 weeks and were not explained by an alternative diagnosis. In total, 469 patients from different regions of Ukraine were enrolled in the study. Among them, 227 patients reported PCS development (main group), while 242 patients did not claim PCS symptoms (comparison group). Stepwise multivariate logistic regression and probabilistic neural network (PNN) models were used to select independent risk factors.

Based on the survey data, 8 independent factors associated with the risk of PCS development in T2D patients were selected: newly diagnosed T2D (OR 4.86; 95% CI 2.55-9.28; p<0.001), female sex (OR 1.29; 95% CI 0.86-1.94; p=0.220), COVID-19 severity (OR 1.35 95% CI 1.05-1.70; p=0.018), myocardial infarction (OR 2.42 95% CI 1.26-4.64; p=0.002) and stroke (OR 3.68 95% CI 1.70-7.96; p=0.001) in anamnesis, HbA1c above 9.2% (OR 2.17 95% CI 1.37-3.43; p=0.001), and the use of insulin analogs (OR 2.28 95% CI 1.31-3.94; p=0.003) vs human insulin (OR 0.67 95% CI 0.39-1.15; p=0.146). Although obesity aggravated COVID-19 severity, it did not impact PCS development. In ROC analysis, the 8-factor multilayer perceptron (MLP) model exhibited better performance (AUC 0.808; 95% CІ 0.770-0.843), allowing the prediction of the risk of PCS development with a sensitivity of 71.4%, specificity of 76%, PPV of 73.6% and NPV of 73.9%.

Patients who were newly diagnosed with T2D, had HbA1c above 9.2%, had previous cardiovascular or cerebrovascular events, and had severe COVID-19 associated with mechanical lung ventilation were at high risk for PCS.

The risk of coronavirus (COVID-19) can be affected by the presence of certain chronic conditions. It is unknown if individuals with severe hereditary alpha-1-antitrypsin deficiency (AATD) faced an increased risk of severe COVID-19 infection during the pandemic and if COPD in this population affected the risk of severe COVID-19 outcomes.

Our aim was to investigate COVID-19 outcomes in individuals with severe AATD and to identify if COPD was a risk factor for severe disease.

Between 2021-2023 we interviewed 863 individuals with severe AATD (phenotype PiZZ) included in the Swedish National AATD Registry. Details on COVID-19 outcomes were collected. Cox regression models were used to assess risk of mild and severe COVID-19 by presence of COPD.

Of 863 subjects with severe AATD, 231 reported COVID-19 infection (208 mild and 23 severe COVID-19). Subjects with severe COVID-19 were older, had lower FEV1 values, were more likely ever-smokers and had more comorbidities compared to those with mild COVID-19. Subjects with COPD had over a 5-fold increased risk of severe COVID-19 compared to those without COPD (HR 5.43 (95% CI 1.61-18.27, p=0.006). After adjusting for potential confounders including smoking habits the risk remained significant (HR 3.72 (95% CI 1.04-13.23, p=0.043)).

Most patients with severe AATD exhibit mild symptoms of COVID-19 infection, managing them in the community. Patients who also have COPD are at increased risk of severe COVID-19 infection.

This study explores the capability of thiazoles as potent inhibitors of SARS-CoV-2 Mpro. Seventeen thiazoles (1-17) were screened for their linking affinity with the active site of SARS-CoV-2 Mpro and compared with the FDA-recommended antiviral drugs, Remdesivir and Baricitinib. Density Functional Theory (DFT) calculations provided electronic and energetic properties of these ligands, shedding light on their stability and reactivity. Molecular docking analysis revealed that thiazole derivatives exhibited favorable linking affinities with various functional sites of SARS-CoV-2 proteins, including spike receptor-linking zone, nucleocapsid protein N-terminal RNA linking zone, and Mpro. Notably, compounds 3, 10, and 12 displayed the best interaction with 6LZG as compared to FDA-approved antiviral drugs Remdesivir and Baricitinib, while compounds 1, 10, and 8 exhibited strong linking with 6 M3 M and also better than Remdesivir and Baricitinib. Additionally, compounds 3, 1, and 6 showed promising interactions with 6LU7 but only compound 3 performed better than Baricitinib. An ADME (Absorption, Distribution, Metabolism, and Excretion) study provided insights into the pharmacokinetics and drug-likeness of these compounds, with all ligands demonstrating good physicochemical characteristics, lipophilicity, water solubility, pharmacokinetics, drug-likeness, and medicinal chemistry attributes. The results suggest that these selected thiazole derivatives hold promise as potential candidates for further drug development.

Introduction The COVID-19 pandemic originated in Wuhan, China, and swiftly spread across all continents. The respiratory system is the most affected in people who acquire sickness as a result of SARS-CoV-2. However, the virus can also affect other systems. The COVID-19 pandemic has become one of the most fatal infectious diseases in the recent past. Patients present with symptoms of fever, cough, tiredness, loss of taste or smell, sore throat, headache, and diarrhea. Objective This study intends to evaluate how COVID-19 has shown its effects on the well-being of the liver by collecting and correlating the data of the liver enzymes and inflammatory markers among hospitalized COVID-19 patients with age- and sex-matched healthy controls.  Materials and methods A retrospective case-control study that included 200 patients diagnosed and hospitalized with COVID-19 was compared with an equal number of age- and sex-matched healthy control groups without COVID-19 at RVM Institute of Medical Sciences and Research Centre (RVMIMS & RC), a tertiary care teaching hospital in Siddipet, Telangana, India. Liver function tests (LFTs) and inflammatory markers were evaluated in both groups.  Results Out of 200 patients, 179 (89.5%) had elevated alanine transaminase (ALT), 191 (95.5%) had elevated aspartate aminotransferase (AST), 33 (16.5%) had elevated alkaline phosphatase (ALP), and 183 (91.5%) showed elevated D-dimer levels. All the patients had elevated interleukin-6 (IL-6) and C-reactive protein (CRP) levels. Conclusion COVID-19 patients have exhibited elevations in liver enzyme panels and inflammatory markers. Further research and follow-up studies may aid in understanding the role of the well-being of the liver in patients affected by COVID-19. Considering the emergence of newer COVID-19 strains, we recommend LFT to patients who test positive for the virus to monitor prognosis and guide treatment protocols through this study.

Identifying nutritional risk in COVID-19 patients poses a challenge due to the unique qualities of every nutritional screening instrument. The objective was to assess the efficacy of six nutritional scores, including the Nutritional Risk Screening 2002 (NRS-2002) score, the NUTRIC (nutrition risk in the critically ill) score, the modified NUTRIC score, the prognostic nutritional index (PNI), controlling nutritional status (CONUT) score, TCB index (TCBI), predicting prognosis of COVID-19 patients.

Clinical data were collected from COVID-19 patients admitted to the First Affiliated Hospital of Wenzhou Medical University between December 2022 and February 2023. Participants in this research were divided into two groups: all patients and those specifically from the intensive care unit (ICU). Each group was further stratified into two groups: survivors and non-survivors.

506 COVID-19 patients and 190 COVID-19 patients in intensive care unit (ICU) were evaluated. In all COVID-19 patients, we found that NRS-2002 (p < 0.001) and TCBI (p = 0.002) were statistically significant independent predictors in multivariate analyses, while APACHE II score (p = 0,048) and the mNUTRIC score (p = 0.025) were statistically significant independent predictors in multivariate analyses in ICU patients. The NRS-2002 demonstrated a higher AUC value (0.687) than other nutritional scores in all patients, with an optimum cut-off value of 3, translating into a corresponding sensitivity of 66.2% and specificity of 68.7%. With an optimum cut-off value of 4, the mNUTRIC score demonstrated a higher AUC value (0.884) in ICU patients, resulting in a sensitivity of 88.4% and a specificity of 76.9%. By using the discrimination and clinical application (DCA) curve, NRS-2002 demonstrated the greatest net benefit in all patients, while NUTRIC score and mNUTRIC score offered the more significant overall advantage than other nutritional scores in ICU patients. Kaplan-Meier analyses showed lower survival rates in patients in low nutritional risk.

Malnutrition was common in COVID-19 patients. The mNUTRIC score and NRS-2002 were, respectively, more effctive scoring systems of prognosis in all COVID-19 patients and severe or critical COVID-19 patients of the intensive care unit (ICU).

A novel series of substituted benzofuran-tethered triazolylcarbazoles was synthesized in good to high yields (65-89%) via S-alkylation of benzofuran-based triazoles with 2-bromo-N-(9-ethyl-9H-carbazol-3-yl)acetamide. The inhibitory potency of the synthesized compounds against SARS-CoV-2 was evaluated by enacting molecular docking against its three pivotal proteins, namely, Mpro (main protease; PDB ID: 6LU7), the spike glycoprotein (PDB ID: 6WPT), and RdRp (RNA-dependent RNA polymerase; PDB ID: 6M71). The docking results indicated strong binding affinities between SARS-CoV-2 proteins and the synthesized compounds, which were thereby expected to obstruct the function of SARS proteins. Among the synthesized derivatives, the compounds 9e, 9h, 9i, and 9j exposited the best binding scores of -8.77, -8.76, -8.87, and -8.85 Kcal/mol against Mpro, respectively, -6.69, -6.54, -6.44, and -6.56 Kcal/mol against the spike glycoprotein, respectively, and -7.61, -8.10, -8.01, and -7.54 Kcal/mol against RdRp, respectively. Furthermore, the binding scores of 9b (-8.83 Kcal/mol) and 9c (-8.92 Kcal/mol) against 6LU7 are worth mentioning. Regarding the spike glycoprotein, 9b, 9d, and 9f expressed high binding energies of -6.43, -6.38, and -6.41 Kcal/mol, accordingly. Correspondingly, the binding affinity of 9g (-7.62 Kcal/mol) against RdRp is also noteworthy. Furthermore, the potent compounds were also subjected to ADMET analysis to evaluate their pharmacokinetic properties, suggesting that the compounds 9e, 9h, 9i, and 9j exhibited comparable values. These potent compounds may be selected as inhibitory agents and provide a pertinent context for further investigations.

Exosomes, which are small extracellular vesicles, are of particular interest in studies on SARS-CoV-2 infection because of their crucial role in intercellular communication. These vesicles are released by several cell types and are rich in "cargo" such as proteins, lipids, and nucleic acids, which are vital for regulating immune response and viral pathogenesis. Exosomes have been reported to be involved in viral transmission, immune escape mechanisms, and illness development in SARS-CoV-2 infection. This review examines the current research on the contribution of exosomes to the interplay between the virus and host cells, highlighting their potential as diagnostic biomarkers and therapeutic targets in combating COVID-19.

Since the onset of the coronavirus disease 2019 (COVID-19) pandemic, remarkable advances have been made in vaccine development to reduce mortality. However, therapeutic interventions for COVID-19 are comparatively limited despite these intensive efforts. Furthermore, the rapid mutation capability of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a characteristic of its RNA structure, has led to the emergence of multiple variants, necessitating a shift from a predominantly vaccine-centric approach to one that encompasses therapeutic strategies. 6'-Hydroxy justicidin B (6'-HJB), an arylnaphthalene lignan isolated from Justicia procumbens, a traditional Chinese medicine, is known for its antiviral properties.

The aim of the present study was to assess the effectiveness and safety of 6'-HJB against SARS-CoV-2 in order to determine its potential as a therapeutic agent against COVID-19.

The efficacy of 6'-HJB was evaluated both in vitro using Vero and Calu-3 cell lines and in vivo using ferrets. The safety assessment included toxicokinetics, safety pharmacology, and Good Laboratory Practice (GLP)-compliant toxicity evaluations following single- and repeated-dose toxicity studies in dogs.

The anti-SARS-CoV-2 efficacy of 6'-HJB was evaluated through dose-response curve (DRC) analysis using immunofluorescence; 6'-HJB demonstrated superior inhibition of SARS-CoV-2 growth and lower cytotoxicity than remdesivir. In SARS-CoV-2-infected ferret, 6'-HJB showed efficacy comparable to that of the positive control, Truvada. Further GLP toxicity studies corroborated the safety profile of 6'-HJB. Single-dose and 4-week repeated oral toxicity studies in Beagle dogs demonstrated minimal harmful effects at the highest dosages. The lethal dose of 6'-HJB exceeded 2,000 mg kg-1 in Beagle dogs. Toxicokinetic and GLP safety pharmacology studies demonstrated no adverse effects of 6'-HJB on metabolic processes, respiratory or central nervous systems, or cardiac functions.

This research highlights both the antiviral efficacy and safety profile of 6'-HJB, underscoring its potential as a novel COVID-19 treatment option. The potential of 6'-HJB was demonstrated using modern scientific methodologies and standards.

COVID-19, caused by SARS-CoV-2, triggers a complex immune response, with T regulatory cells (Tregs) playing a crucial role in maintaining immune homeostasis and preventing excessive inflammation. The current study investigates the function of T regulatory cells during COVID-19 infection and the subsequent recovery period, emphasizing their impact on immune regulation and inflammation control. We conducted a comprehensive analysis of Treg subpopulations in peripheral blood samples from COVID-19 patients at different stages: acute infection, early convalescence, and long-term recovery. Flow cytometry was employed to quantify Tregs including "naïve", central memory (CM), effector memory (EM), and terminally differentiated CD45RA+ effector cells (TEMRA). Additionally, the functional state of the Tregs was assessed by the expression of purinergic signaling molecules (CD39, CD73). Cytokine profiles were assessed through multiplex analysis. Our findings indicate a significant decrease in the number of Tregs during the acute phase of COVID-19, which correlates with heightened inflammatory markers and increased disease severity. Specifically, we found a decrease in the relative numbers of "naïve" and an increase in EM Tregs, as well as a decrease in the absolute numbers of "naïve" and CM Tregs. During the early convalescent period, the absolute counts of all Treg populations tended to increase, accompanied by a reduction in pro-inflammatory cytokines. Despite this, one year after recovery, the decreased subpopulations of regulatory T cells had not yet reached the levels observed in healthy donors. Finally, we observed the re-establishment of CD39 expression in all Treg subsets; however, there was no change in CD73 expression among Tregs. Understanding these immunological changes across different T regulatory subsets and adenosine signaling pathways offers important insights into the disease's pathogenesis and provides a broader view of immune system dynamics during recovery.

After the easing of COVID-19 restrictions, peaks of common infectious diseases surpassed pre-pandemic levels, raising questions about causes and ways to monitor these changes. A proposed measure, the Pathogen Population Density (PPD) score, could help track these shifts. PPD refers to the concentration of infectious agents within a population at a given time and location, serving as a potential indicator of infection levels in susceptible individuals at the population level. It is likely that PPD remains relatively stable within a specific community, as an equilibrium forms between infections and susceptibility. During the pandemic, nonpharmaceutical interventions (NPIs) led to a reduction in infectious diseases, possibly lowering population immunity and decreasing the PPD score. Once NPIs were lifted, the PPD score likely increased sharply due to a larger pool of susceptible individuals, causing more primary infections and stronger recurrent infections, faster transmission, and more severe pathogenic outcomes at the individual level. Monitoring the PPD score over time could help predict when infection peaks will occur. PPD is influenced by factors such as public health strategies, vaccination programs, and the behavior of high-risk individuals. As a quantitative measure, PPD has the potential to serve as a valuable predictive and monitoring tool, helping public health officials anticipate and track changes in infectious disease dynamics. It could be an effective tool for managing future outbreaks or pandemics and serve as a communication tool between scientists and the public to understand the emergence of new disease peaks.

The dynamic evolution of SARS-CoV-2 variants necessitates ongoing advancements in therapeutic strategies. Despite the promise of monoclonal antibody (mAb) therapies like bebtelovimab, concerns persist regarding resistance mutations, particularly single-to-multipoint mutations in the receptor-binding domain (RBD). Our study addresses this by employing interface-guided computational protein design to predict potential bebtelovimab-resistance mutations. Through extensive physicochemical analysis, mutational preferences, precision-recall metrics, protein-protein docking, and energetic analyses, combined with all-atom, and coarse-grained molecular dynamics (MD) simulations, we elucidated the structural-dynamics-binding features of the bebtelovimab-RBD complexes. Identification of susceptible RBD residues under positive selection pressure, coupled with validation against bebtelovimab-escape mutations, clinically reported resistance mutations, and viral genomic sequences enhances the translational significance of our findings and contributes to a better understanding of the resistance mechanisms of SARS-CoV-2.

Infection with the SARS-CoV-2 virus may induce some complications among people who experience mild to moderate respiratory illness and some of them recover without requiring special treatment. Albeit, some individuals become seriously reached risk points and require special medical attention especially older people and people who suffer from chronic diseases. Serum and whole blood samples were collected from confirmed infected persons with SARS CoV-2 by real-time PCR and the control group. All lab. Investigations were performed using Cobas 6000. Significant differences were noted between patients compared to the control group in the Mean ± SD of IL-6 (76.06 ± 7.60 vs 3.61 ± 0.296 pg/ml), Procalcitonin (0.947 ± 0.117 vs 0.061 ± 0.007 ng/ml), CRP (125.3 ± 7.560 vs 4.027 ± 0.251 mg/dl), ALT (154.8 ± 30.47 vs 49.75 ± 2.977 IU/L) and AST (70.83 ± 9.215 vs 27.23 ± 1.767) respectively. While other parameters were also showed significant differences were noted between patients compared to the control group for D-Dimmer, PT, PTT, LDH, Ferritin, WBC, Lymphocyte and Creatinine. The results reached that the effect of SARS CoV-2 and cytokine storm was clear on the body's organs through vital biomarker investigations that were performed in this study.

Introduction: The COVID-19 virus has impacted people worldwide, causing significant changes in their lifestyles. Since the emergence of the epidemic, attempts have begun to prepare a vaccine that can eliminate the virus and restore balance to life in the entire world. Over the past two years, countries and specialized companies have competed to obtain a license from the World Health Organization for the vaccines that were discovered. After the appearance of vaccines in the health community, comparisons and fears of their side effects began, but people don't get an answer to the question of which is the best vaccine. Methods: IEEE Xplore, ScienceDirect, the New England Journal of Medicine, Google Scholar, and PubMed databases were searched for literature on the COVID-19 vaccine and its side effects. we surveyed the literature on the COVID-19 vaccine's side effects and the sorts of side effects observed after vaccination. Depending on data from the literature, we compared these vaccines in terms of side effects, then we analyzed the gaps and obstacles of previous studies and made proposals to process these gaps in future studies. Results: Overall, 17 studies were included in this scoping systematic review as they fulfilled the criteria specified, the majority of which were cross-sectional and retrospective cross-sectional studies. Most of the side effects were mild, self-limiting, and common. Thus, they usually resolve within 1-3 days after vaccination. Factors associated with higher side effects included advanced age, allergic conditions, those taking other medications (particularly immunosuppressive ones), those with a history of type II diabetes, heart disease, hypertension, COVID-19 infection, and female sex. Our meta-analyses also found that mRNA vaccines looked to be more effective, while inactivated vaccinations had fewer side effects. Conclusion: This review shows that the COVID-19 vaccine is safe to administer and induces protection.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had led to a global pandemic since December 2019. SARS-CoV-2 is a single-stranded RNA virus, which mutates at a higher rate. Multiple works had been done to study nonsynonymous mutations, which change protein sequences. However, there is little study on the effects of SARS-CoV-2 synonymous mutations, which may affect viral fitness. This study aims to predict the effect of synonymous mutations on the SARS-CoV-2 genome.

A total of 26645 SARS-CoV-2 genomic sequences retrieved from Global Initiative on Sharing all Influenza Data (GISAID) database were aligned using MAFFT. Then, the mutations and their respective frequency were identified. Multiple RNA secondary structures prediction tools, namely RNAfold, IPknot++ and MXfold2 were applied to predict the effect of the mutations on RNA secondary structure and their base pair probabilities was estimated using MutaRNA. Relative synonymous codon usage (RSCU) analysis was also performed to measure the codon usage bias (CUB) of SARS-CoV-2.

A total of 150 synonymous mutations were identified. The synonymous mutation identified with the highest frequency is C3037U mutation in the nsp3 of ORF1a. Of these top 10 highest frequency synonymous mutations, C913U, C3037U, U16176C and C18877U mutants show pronounced changes between wild type and mutant in all 3 RNA secondary structure prediction tools, suggesting these mutations may have some biological impact on viral fitness. These four mutations show changes in base pair probabilities. All mutations except U16176C change the codon to a more preferred codon, which may result in higher translation efficiency.

Synonymous mutations in SARS-CoV-2 genome may affect RNA secondary structure, changing base pair probabilities and possibly resulting in a higher translation rate. However, lab experiments are required to validate the results obtained from prediction analysis.

The impact of coronavirus disease 2019 (COVID-19) history on Crohn's disease (CD) is unknown. This investigation aimed to examine the effect of COVID-19 history on the disease course, oral-gut microbiota, and serum metabolomics in patients with CD. In this study, oral-gut microbiota and serum metabolomic profiles in 30 patients with CD and a history of mild COVID-19 (positive group, PG), 30 patients with CD without COVID-19 history (negative group, NG), and 60 healthy controls (HC) were assessed using 16S rDNA sequencing and targeted metabolomics. During follow-up, the CD activity index showed a stronger decrease in the PG than in the NG (p = 0.0496). PG patients demonstrated higher α-diversity and distinct β-diversity clustering in both salivary and fecal microbiota compared to NG and HC individuals. Notably, the gut microbiota composition in the PG patients showed a significantly greater similarity to that of HC than NG individuals. The interaction between oral and intestinal microbiota in the PG was reduced. Moreover, serum metabolome analysis revealed significantly increased anti-inflammatory metabolites, including short-chain fatty acids and N-Acetylserotonin, among PG patients; meanwhile, inflammation-related metabolites such as arachidonic acid were significantly reduced in this group. Our data suggest that the gut microbiota mediates a potential beneficial effect of a mild COVID-19 history in CD patients.

The COVID-19 pandemic underscores the need for accurate prognostic tools to predict patient outcomes. This study evaluates the effectiveness of four prominent COVID-19 prediction scores-PAINT, ISARIC4C, CHIS, and COVID-GRAM-at two critical time points: at admission and seven days post-symptom onset, to assess their utility in predicting mortality among hospitalized patients. Conducted at the Clinical Emergency Hospital Pius Brînzeu in Timișoara, this retrospective analysis included adult patients hospitalized with confirmed SARS-CoV-2 infection. Eligible patients had complete data for the scores at both time points. Statistical analysis involved ROC curves and logistic regression to assess the scores' predictive accuracy for mortality. The study included 215 patients, split into 139 survivors and 76 non-survivors. At admission, the PAINT, ISARIC4C, CHIS, and COVID-GRAM scores significantly differentiated between the survival outcomes (p < 0.0001). The best cutoff values at admission were 6.26 for PAINT, 7.95 for ISARIC4C, 5.58 for CHIS, and 0.63 for COVID-GRAM, corresponding to sensitivities of 85.47%, 80.56%, 88.89%, and 83.33% and specificities of 77.34%, 82.12%, 75.01%, and 78.45%, respectively. By day seven, the cutoff values increased, indicating deteriorating conditions in patients who eventually succumbed to the virus. The hazard ratios at admission for exceeding these cutoffs were significant: PAINT (HR = 3.45), ISARIC4C (HR = 2.89), CHIS (HR = 4.02), and COVID-GRAM (HR = 3.15), highlighting the scores' abilities to predict severe outcomes. One week post symptom onset, these scores' predictive values and corresponding hazard ratios increased, further validating their prognostic significance over time. The evaluated COVID-19 prediction scores robustly predict mortality at admission and become more predictive by the seventh day of symptom onset. These findings support the use of these scores in clinical settings to facilitate early identification and intervention for high-risk patients, potentially improving patient outcomes during the ongoing global health crisis.

Background: Coronavirus Disease-2019 (COVID-19) has posed formidable challenges to healthcare systems. Exploring novel biomarkers that can provide valuable prognostic insights, particularly in critically ill patients, has a significant importance. Against this backdrop, our study aims to elucidate the associations between serum chloride levels and clinical outcomes. Methods: A total of 499 patients were enrolled into the study. The serum chloride levels of patients upon hospital admission were recorded and then categorized into three groups (hypochloremia, normochloremia, and hyperchloremia) for the evaluation of clinical outcomes. Additionally, serum C-reactive protein, procalcitonin, and D-dimer measurements were recorded for further evaluation. Results: A total of 390 (78.1%) patients tested positive for COVID-19 via polymerase chain reaction testing. Non-contrast thorax computed tomography scans were indicative of COVID-19 compatibility for all patients. A total of 210 (42%) patients were female and 289 (58%) were male. A total of 214 (42.8%) patients necessitated tocilizumab intervention; 250 (50.1%) were at an intensive care unit (ICU), with 166 (66.4%) of them receiving tocilizumab. A total of 65 (13%) patients died, 40 (61.5%) of whom received tocilizumab; 41 (63%) were in the ICU. Serum chloride levels upon admission were markedly lower and elevated D-dimer levels were apparent in tocilizumab users, patients requiring ICU care, and patients who died. Conclusions: our findings provide robust evidence supporting the value of serum chloride levels as a prognostic biomarker in critically ill COVID-19 patients.