Repositioning of anti-infective compounds against monkeypox virus core cysteine proteinase: a molecular dynamics study.

Monkeypox virus (MPXV) core cysteine proteinase (CCP) is one of the major drug targets used to examine the inhibitory action of chemical moieties. In this study, an in silico technique was applied to screen 1395 anti-infective compounds to find out the potential molecules against the MPXV-CCP. The top five hits were selected after screening and processed for exhaustive docking based on the docked score of ≤ -9.5 kcal/mol. Later, the top three hits based on the exhaustive-docking score and interaction profile were selected to perform MD simulations. The overall RMSD suggested that two compounds, SC75741 and ammonium glycyrrhizinate, showed a highly stable complex with a standard deviation of 0.18 and 0.23 nm, respectively. Later, the MM/GBSA binding free energies of complexes showed significant binding strength with ΔGTOTAL from -21.59 to -15 kcal/mol. This report reported the potential inhibitory activity of SC75741 and ammonium glycyrrhizinate against MPXV-CCP by competitively inhibiting the binding of the native substrate.

A survey of drive-thru pharmacy services: Evaluating the acceptance and perspectives of community pharmacists in Saudi Arabia.

Background: The practice of dispensing drugs in primary healthcare centers has shifted to community pharmacies in Saudi Arabia. These changes increase demand and mandate improving their services; one such is establishing pharmacy drive-thru services. To explore the effects of drive-thru services on the pharmacy profession, this study aimed to measure community pharmacists' acceptance, perception, and satisfaction regarding drive-thru services. Methods: This cross-sectional study design was conducted in Saudi Arabia between January 2023 and May 2023-comparing the perception, acceptance, and satisfaction of pharmacists who work in a community pharmacy that provides a drive-thru service versus no drive-thru service. Community pharmacists were invited to complete an online questionnaire consisting of four sections developed from previous studies with some modifications. Descriptive statistical analysis and an independent t-test were utilized to test the difference between the two groups (providing drive-thru service vs. non) in their responses. Results: This study included 380 community pharmacists, of whom 33 % provided drive-thru services and 67 % did not. Pharmacists' perceptions of drive-thru services differed significantly. Those with drive-thru services perceived lower convenience for delivering drug information and patient counseling, and they were concerned about the potential impact on their health effects (M = 3.15, SD = 1.34) compared to those without (M = 3.58, SD = 1.10), t (3 7 8) = -3.32, p < 0.01). However, they recognized the convenience of serving sick patients, the elderly, disabled individuals, and mothers with children in cars (M = 3.71, SD = 1.17), which was higher than those without (M = 4.04, SD = 1.21), t (3 7 8) = -2.70, p < 0.01). Regarding the current pharmacy layout suitability, pharmacists with drive-thru services found it more suitable (M = 3.13, SD = 1.14) than those without (M = 2.49, SD = 1.14), t (3 7 8) = 5.1, p < 0.01). However, the two groups had no significant difference in overall satisfaction. Conclusion: Pharmacists working in pharmacies offering drive-thru services recognized certain benefits but also expressed concerns about health effects and decreased convenience for counseling. These findings provide valuable insights for policymakers and pharmacy management, highlighting the nuanced views of pharmacists in adopting drive-thru services.

Bioprospecting of Meliaceae family phytomolecules for the treatment of monkeypox virus infection: a QSAR modeling and MD simulation approach.

Recent monkeypox virus (MPXV) infections show the risk of MPXV transmission that persists today and the significance of surveillance and quick response methods to stop the virus's spread. Currently, the monkeypox virus infection is not specifically treated. In this study, QSAR models were designed using known inhibitors of cysteine proteinase from the vaccinia virus, where the Random Forest model and Ridge model had showed the best correlation between predicted and observed EC50. These models were used to screen Maliaceae family phytochemicals against MPXV cysteine proteinase. The compound, IMPHY010637 was detected in top 5 from both the QSAR screening models and showed best docked score (-8.6 kcal/mol) and thus selected for further investigation. Further, the IMPHY010637 showed interaction with the catalytic residue His241 of the protein as reported in earlier studies. The ADMET analysis of the compound showed the acceptable drug-like properties of IMPHY010637. However, these properties could be improved after experimental validation of protein-ligand binding. Both docked complex and poses created in 100 ns MD simulation of the protein-ligand complex showed the presence of multiple hydrogen bonds. RMSD and conformation analysis showed stable binding of IMPHY010637 with the cysteine proteinase of MPXV at its active site. Compared to the known inhibitor, IMPHY010637 showed better binding with the protein as observed by the PCA and MM/GBSA analysis. This study concluded IMPHY010637 as a potential inhibitor for the cysteine proteinase of MPXV using computational methods that could be tested in in-vitro experiments.Communicated by Ramaswamy H. Sarma.

Investigation of Zika virus methyl transferase inhibitors using steered molecular dynamics.

Zika virus (ZIKV) spread is considered a major public health threat by the World Health Organization (WHO). There are no vaccines or drugs available to control the infection of the Zika virus, therefore a highly effective medicinal molecule is urgently required. In this study, a computationally intensive investigation was performed to identify a potent natural compound that could inhibit the ZIKV NS5 methyltransferase. This research approach is based on target-based drug identification principles where the native inhibitor SAH (S-adenosylhomocysteine) of ZIKV NS5 methyltransferase was selected as a reference. High-throughput virtual screening and tanimoto similarity coefficient were applied to the natural compound library for ranking the potential candidates. The top five compounds were selected for interaction analysis, MD simulation, total binding free energy through MM/GBSA, and steered MD simulation. Among these compounds, Adenosine 5'-monophosphate monohydrate, Tubercidin, and 5-Iodotubercidin showed stable binding to the protein compared to the native compound, SAH. These three compounds also showed less fluctuations in RMSF in contrast to native compound. Additionally, the same interacting residues observed in SAH also made strong interactions with these three compounds. Adenosine 5'-monophosphate monohydrate and 5-Iodotubercidin had greater total binding free energies than the reference ligand. Moreover, the dissociation resistance of all three compounds was equivalent to that of the reference ligand. This study suggested binding properties of three-hit compounds that could be used to develop drugs against Zika virus infections.Communicated by Ramaswamy H. Sarma.

Immunoinformatics-Driven Strategies for Advancing Epitope-Based Vaccine Design for West Nile Virus.

The West Nile virus (WNV) is the causative agent of West Nile disease (WND), which poses a potential risk of meningitis or encephalitis. The aim of the study was to design an epitope-based vaccine for WNV by utilizing computational analyses. The epitope-based vaccine design process encompassed WNV sequence collection, phylogenetic tree construction, and sequence alignment. Computational models identified B-cell and T-cell epitopes, followed by immunological property analysis. Epitopes were then modeled and docked with B-cell receptors, MHC I, and MHC II. Molecular dynamics simulations further explored dynamic interactions between epitopes and receptors. The findings indicated that the B-cell epitope QINHHWHKSGSSIG, along with three T-cell epitopes (FLVHREWFM for MHC I, NPFVSVATANAKVLI for MHC II, and NAYYVMTVGTKTFLV for MHC II), successfully passed the immunological evaluations. These four epitopes were further subjected to docking and molecular dynamics simulation studies. Although each demonstrated favorable affinities with their respective receptors, only NAYYVMTVGTKTFLV displayed a stable interaction with MHC II during MDS analysis, hence emerging as a potential candidate for a WNV epitope-based vaccine. This study demonstrates a comprehensive approach to epitope vaccine design, combining computational analyses, molecular modeling, and simulation techniques to identify potential vaccine candidates for WNV.

Microbiological trends and mortality risk factors of central line-associated bloodstream infections in an academic medical center 2015-2020.

BACKGROUND: Despite tremendous efforts to prevent central line-associated bloodstream infections, they still remain life-threatening complications among hospitalized patients with significant morbidity and mortality worldwide. The emerging antibiotic-resistant bacteria and other risk factors, including patient comorbidities, complicate patient management. METHODS: A single-center retrospective observational study was conducted at King Fahad Hospital of the University, Eastern Province, Saudi Arabia. Hospitalized patients with confirmed central line-associated bloodstream infections between January 2015 and December 2020 were included. The primary objectives were to investigate the trends in antibiotic susceptibility patterns of the causative agents, coexisting comorbid conditions, and other risk factors associated with mortality. RESULTS: A total of 214 patients with confirmed central line-associated bloodstream infections were included (CLABSI). The overall 30-day mortality rate was 33.6%. The infection rates per 1000 central line days for medical, surgical, and pediatric intensive care units were 4.97, 2.99, and 4.56 per 1000 CL days, respectively. The overall microbiological trends showed a predominance of Gram-negative agents, a steady increase of fungal CLABSI up to 24.0% in 2020, and a high prevalence of multidrug resistance up to 47% of bacterial CLABSI. In addition, the study indicates a significant negative surviving correlation with diabetes mellitus, cardiovascular disease, lung disease, chronic kidney disease, and the presence of ≥ 3 comorbidities (P < 0.05). CONCLUSION: The microbiological trends of the study population demonstrated a steady increase of CLABSI caused by Candida spp. with a predominance of Gram-negative pathogens. Stratifying the patients according to relevant mortality risk factors, including patient comorbidities, will help reduce CLABSI rates and improve patient outcomes.

Pooled rates and demographics of POTS following SARS-CoV-2 infection versus COVID-19 vaccination: Systematic review and meta-analysis.

PURPOSE: To address recent concerns of postural orthostatic tachycardia syndrome (POTS) occurring after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19) vaccination. METHODS: We searched PubMed, Web of Science, and Scopus as of 1st June 2023. We performed a systematic review and meta-analysis of pooled POTS rate in SARS-CoV-2-infected and COVID-19-vaccinated groups from epidemiological studies, followed by subgroup analyses by characteristic. Meta-analysis of risk ratio was conducted to compare POTS rate in infected versus uninfected groups. Meta-analysis of demographics was also performed to compare cases of post-infection and post-vaccination POTS from case reports and series. RESULTS: We estimated the pooled POTS rate of 107.75 (95 % CI: 9.73 to 273.52) and 3.94 (95 % CI: 0 to 16.39) cases per 10,000 (i.e., 1.08 % and 0.039 %) in infected and vaccinated individuals based on 5 and 2 studies, respectively. Meta-regression revealed age as a significant variable influencing 86.2 % variance of the pooled POTS rate in infected population (P < 0.05). Moreover, POTS was 2.12-fold more likely to occur in infected than uninfected individuals (RR = 2.12, 95 % CI: 1.71 to 2.62, P < 0.001). Meta-analyzed demographics for cases of post-infection (n = 43) and post-vaccination (n = 17) POTS found no significant differences in several variables between groups, except that the time from exposure to symptom onset was shorter for cases of post-vaccination POTS (P < 0.05). CONCLUSION: Although evidence is limited for post-vaccination POTS, our study showed that POTS occur more frequently following SARS-CoV-2 infection than COVID-19 vaccination.

Exploration of phytochemical compounds against Marburg virus using QSAR, molecular dynamics, and free energy landscape.

Marburg virus disease (MVD) is caused by the Marburg virus, a one-of-a-kind zoonotic RNA virus from the genus Filovirus. Thus, this current study employed AI-based QSAR and molecular docking-based virtual screening for identifying potential binders against the target protein (nucleoprotein (NP)) of the Marburg virus. A total of 2727 phytochemicals were used for screening, out of which the top three compounds (74977521, 90470472, and 11953909) were identified based on their predicted bioactivity (pIC50) and binding score (< - 7.4 kcal/mol). Later, MD simulation in triplicates and trajectory analysis were performed which showed that 11953909 and 74977521 had the most stable and consistent complex formations and had the most significant interactions with the highest number of hydrogen bonds. PCA (principal component analysis) and FEL (free energy landscape) analysis indicated that these compounds had favourable energy states for most of the conformations. The total binding free energy of the compounds using the MM/GBSA technique showed that 11953909 (ΔGTOTAL = - 30.78 kcal/mol) and 74977521 (ΔGTOTAL = - 30 kcal/mol) had the highest binding affinity with the protein. Overall, this in silico pipeline proposed that the phytochemicals 11953909 and 74977521 could be the possible binders of NP. This study aimed to find phytochemicals inhibiting the protein's function and potentially treating MVD.

Prevalence of Hepatocellular Carcinoma in Hepatitis B Population within Southeast Asia: A Systematic Review and Meta-Analysis of 39,050 Participants.

BACKGROUND AND AIM: Hepatocellular carcinoma (HCC) is a significant complication of hepatitis B and still poses a global public health concern. This systematic review and meta-analysis provide adequate details on the prevalence of HCC in the HBV population within Southeast Asian countries. METHOD: Following the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) criteria, a thorough search for literature discussing the prevalence of HCC in the HBV population within southeast Asia was performed. Eligible studies were subjected to a meta-analysis utilising a DerSimonian and Laird approach and a random effect model. A protocol was registered with PROSPERO (CRD42023423953). RESULT: Our study meticulously recovered 41 articles from seven countries in Southeast Asia, namely Cambodia, Indonesia, Malaysia, the Philippines, Singapore, Thailand, and Vietnam. A total of 39,050 HBV patients and 7479 HCC cases in southeast Asia were analysed. The pooled prevalence of HCC in HBV cases within southeast Asia was 45.8% (95% CI, 34.3-57.8%, I2 = 99.51%, p < 0.001). Singapore (62.5%, CI: 42.4-79.1) had the highest pooled prevalence of HCC in the HBV population compared to Vietnam, with the lowest estimate (22.4%, CI: 9.9-44.9). There was a drop in the pooled prevalence of HCC in HBV from 2016 until now (37.6%, CI: 19.2-60.5). CONCLUSION: The findings of this review reveal a high pooled prevalence of HCC in the HBV population and therefore stir the need for routine screening, management, and surveillance.

Deep and Transfer Learning Approaches for Automated Early Detection of Monkeypox (Mpox) Alongside Other Similar Skin Lesions and Their Classification.

The world faces multiple public health emergencies simultaneously, such as COVID-19 and Monkeypox (mpox). mpox, from being a neglected disease, has emerged as a global threat that has spread to more than 100 nonendemic countries, even as COVID-19 has been spreading for more than 3 years now. The general mpox symptoms are similar to chickenpox and measles, thus leading to a possible misdiagnosis. This study aimed at facilitating a rapid and high-brevity mpox diagnosis. Reportedly, mpox circulates among particular groups, such as sexually promiscuous gay and bisexuals. Hence, selectively vaccinating, isolating, and treating them seems difficult due to the associated social stigma. Deep learning (DL) has great promise in image-based diagnosis and could help in error-free bulk diagnosis. The novelty proposed, the system adopted, and the methods and approaches are discussed in the article. The present work proposes the use of DL models for automated early mpox diagnosis. The performances of the proposed algorithms were evaluated using the data set available in public domain. The data set adopted for the study was meant for both training and testing, the details of which are elaborated. The performances of CNN, VGG19, ResNet 50, Inception v3, and Autoencoder algorithms were compared. It was concluded that CNN, VGG19, and Inception v3 could help in early detection of mpox skin lesions, and Inception v3 returned the best (96.56%) classification accuracy.

Experimental drugs in randomized controlled trials for long-COVID: what's in the pipeline? A systematic and critical review.

INTRODUCTION: Over three years have passed since the emergence of coronavirus disease 2019 (COVID-19), and yet the treatment for long-COVID, a post-COVID-19 syndrome, remains long overdue. Currently, there is no standardized treatment available for long-COVID, primarily due to the lack of funding for post-acute infection syndromes (PAIS). Nevertheless, the past few years have seen a renewed interest in long-COVID research, with billions of dollars allocated for this purpose. As a result, multiple randomized controlled trials (RCTs) have been funded in the quest to find an effective treatment for long-COVID. AREAS COVERED: This systematic review identified and evaluated the potential of current drug treatments for long-COVID, examining both completed and ongoing RCTs. EXPERT OPINION: We identified four completed and 22 ongoing RCTs, investigating 22 unique drugs. However, most drugs were deemed to not have high potential for treating long-COVID, according to three pre-specified domains, a testament to the ordeal of treating long-COVID. Given that long-COVID is highly multifaceted with several proposed subtypes, treatments likely need to be tailored accordingly. Currently, rintatolimod appears to have modest to high potential for treating the myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) subtype, LTY-100 and Treamid for pulmonary fibrosis subtype, and metformin for general long-COVID prevention.

Cheminformatics and machine learning approaches for repurposing anti-viral compounds against monkeypox virus thymidylate kinase.

One of the emerging epidemic concerns is Monkeypox disease which is spreading globally. This disease is caused by the monkeypox virus (MPXV), with an increasing global incidence with an outbreak in 2022. One of the novel targets for monkeypox disease is thymidylate kinase, which is involved in pyrimidine metabolism. In this study, docking-based virtual screening and molecular dynamics techniques were employed in addition to the machine learning (ML) model to investigate the potential anti-viral natural small compounds to inhibit thymidylate kinase of MPXV. Several potential hits were identified through high-throughput virtual screening, and further top three candidates were selected, which ranked using the ML model. These three compounds were then examined under molecular dynamics simulation and MM/GBSA-binding free energy analysis. Among these, Chlorhexidine HCl showed high potential for binding to the thymidylate kinase with stable and consistent conformation with RMSD < 0.3 nm. The MM/GBSA analysis also showed the minimum binding free energy (ΔGTOTAL) of -62.41 kcal/mol for this compound. Overall, this study used structure-based drug design complemented by machine learning-guided ligand-based drug design to screen potential hit compounds from the anti-viral natural compound database.

Highlights on the Development, Related Patents, and Prospects of Lenacapavir: The First-in-Class HIV-1 Capsid Inhibitor for the Treatment of Multi-Drug-Resistant HIV-1 Infection.

The multidrug-resistant (MDR) human immunodeficiency virus 1 (HIV-1) infection is an unmet medical need. HIV-1 capsid plays an important role at different stages of the HIV-1 replication cycle and is an attractive drug target for developing therapies against MDR HIV-1 infection. Lenacapavir (LEN) is the first-in-class HIV-1 capsid inhibitor approved by the USFDA, EMA, and Health Canada for treating MDR HIV-1 infection. This article highlights the development, pharmaceutical aspects, clinical studies, patent literature, and future directions on LEN-based therapies. The literature for this review was collected from PubMed, authentic websites (USFDA, EMA, Health Canada, Gilead, and NIH), and the free patent database (Espacenet, USPTO, and Patent scope). LEN has been developed by Gilead and is marketed as Sunlenca (tablet and subcutaneous injection). The long-acting and patient-compliant LEN demonstrated a low level of drug-related mutations, is active against MDR HIV-1 infection, and does not reveal cross-resistance to other anti-HIV drugs. LEN is also an excellent drug for patients having difficult or limited access to healthcare facilities. The literature has established additive/synergistic effects of combining LEN with rilpivirine, cabotegravir, islatravir, bictegravir, and tenofovir. HIV-1 infection may be accompanied by opportunistic infections such as tuberculosis (TB). The associated diseases make HIV treatment complex and warrant drug interaction studies (drug-drug, drug-food, and drug-disease interaction). Many inventions on different aspects of LEN have been claimed in patent literature. However, there is a great scope for developing more inventions related to the drug combination of LEN with anti-HIV/anti-TB drugs in a single dosage form, new formulations, and methods of treating HIV and TB co-infection. Additional research may provide more LEN-based treatments with favorable pharmacokinetic parameters for MDR HIV-1 infections and associated opportunistic infections such as TB.

Performance of CURB-65 and ISARIC 4C mortality scores for hospitalized patients with confirmed COVID-19 infection in Saudi Arabia.

Background: The COVID-19 pandemic continues with new waves that could persist with the arrival of new SARS-CoV-2 variants. Therefore, the availability of validated and effective triage tools is the cornerstone for proper clinical management. Thus, this study aimed to assess the validity of the ISARIC-4C score as a triage tool for hospitalized COVID-19 patients in Saudi Arabia and to compare its performance with the CURB-65 score. Material and methods: This retrospective observational cohort study was conducted between March 2020 and May 2021 at KFHU, Saudi Arabia, using 542 confirmed COVID-19 patient data on the variables relevant to the application of the ISARIC-4C mortality score and the CURB-65 score. Chi-square and t-tests were employed to study the significance of the CURB-65 score and the ISARIC-4C score variables considering the ICU requirements and the mortality of COVID-19 hospitalized patients. In addition, logistic regression was used to predict the variables related to COVID-19 mortality. In addition, the diagnostic accuracy of both scores was validated by calculating sensitivities, specificities, positive predictive value, negative predictive value, and Youden's J indices (YJI). Results: ROC analysis showed an AUC value of 0.834 [95% CI; 0.800-0.865]) for the CURB-65 score and 0.809 [95% CI; 0.773-0.841]) for the ISARIC-4C score. The sensitivity for CURB-65 and ISARIC-4C is 75% and 85.71%, respectively, while the specificity was 82.31% and 62.66%, respectively. The difference between AUCs was 0.025 (95% [CI; -0.0203-0.0704], p = 0.2795). Conclusion: Study results support external validation of the ISARIC-4C score in predicting the mortality risk of hospitalized COVID-19 patients in Saudi Arabia. In addition, the CURB-65 and ISARIC-4C scores showed comparable performance with good consistent discrimination and are suitable for clinical utility as triage tools for hospitalized COVID-19 patients.

Variants of SARS-CoV-2: Influences on the Vaccines' Effectiveness and Possible Strategies to Overcome Their Consequences.

The immune response elicited by the current COVID-19 vaccinations declines with time, especially among the immunocompromised population. Furthermore, the emergence of novel SARS-CoV-2 variants, particularly the Omicron variant, has raised serious concerns about the efficacy of currently available vaccines in protecting the most vulnerable people. Several studies have reported that vaccinated people get breakthrough infections amid COVID-19 cases. So far, five variants of concern (VOCs) have been reported, resulting in successive waves of infection. These variants have shown a variable amount of resistance towards the neutralising antibodies (nAbs) elicited either through natural infection or the vaccination. The spike (S) protein, membrane (M) protein, and envelope (E) protein on the viral surface envelope and the N-nucleocapsid protein in the core of the ribonucleoprotein are the major structural vaccine target proteins against COVID-19. Among these targets, S Protein has been extensively exploited to generate effective vaccines against COVID-19. Hence, amid the emergence of novel variants of SARS-CoV-2, we have discussed their impact on currently available vaccines. We have also discussed the potential roles of S Protein in the development of novel vaccination approaches to contain the negative consequences of the variants' emergence and acquisition of mutations in the S Protein of SARS-CoV-2. Moreover, the implications of SARS-CoV-2's structural proteins were also discussed in terms of their variable potential to elicit an effective amount of immune response.

Antibodies to Combat Fungal Infections: Development Strategies and Progress.

The finding that some mAbs are antifungal suggests that antibody immunity may play a key role in the defense of the host against mycotic infections. The discovery of antibodies that guard against fungi is a significant advancement because it gives rise to the possibility of developing vaccinations that trigger protective antibody immunity. These vaccines might work by inducing antibody opsonins that improve the function of non-specific (such as neutrophils, macrophages, and NK cells) and specific (such as lymphocyte) cell-mediated immunity and stop or aid in eradicating fungus infections. The ability of antibodies to defend against fungi has been demonstrated by using monoclonal antibody technology to reconsider the function of antibody immunity. The next step is to develop vaccines that induce protective antibody immunity and to comprehend the mechanisms through which antibodies mediate protective effects against fungus.

Regulatory T Cells (Tregs) and COVID-19: Unveiling the Mechanisms, and Therapeutic Potentialities with a Special Focus on Long COVID.

The COVID-19 pandemic has caused havoc all around the world. The causative agent of COVID-19 is the novel form of the coronavirus (CoV) named SARS-CoV-2, which results in immune system disruption, increased inflammation, and acute respiratory distress syndrome (ARDS). T cells have been important components of the immune system, which decide the fate of the COVID-19 disease. Recent studies have reported an important subset of T cells known as regulatory T cells (Tregs), which possess immunosuppressive and immunoregulatory properties and play a crucial role in the prognosis of COVID-19 disease. Recent studies have shown that COVID-19 patients have considerably fewer Tregs than the general population. Such a decrement may have an impact on COVID-19 patients in a number of ways, including diminishing the effect of inflammatory inhibition, creating an inequality in the Treg/Th17 percentage, and raising the chance of respiratory failure. Having fewer Tregs may enhance the likelihood of long COVID development in addition to contributing to the disease's poor prognosis. Additionally, tissue-resident Tregs provide tissue repair in addition to immunosuppressive and immunoregulatory activities, which may aid in the recovery of COVID-19 patients. The severity of the illness is also linked to abnormalities in the Tregs' phenotype, such as reduced expression of FoxP3 and other immunosuppressive cytokines, including IL-10 and TGF-beta. Hence, in this review, we summarize the immunosuppressive mechanisms and their possible roles in the prognosis of COVID-19 disease. Furthermore, the perturbations in Tregs have been associated with disease severity. The roles of Tregs are also explained in the long COVID. This review also discusses the potential therapeutic roles of Tregs in the management of patients with COVID-19.

Inflammatory and vascular biomarkers in post-COVID-19 syndrome: A systematic review and meta-analysis of over 20 biomarkers.

Severe acute respiratory syndrome coronavirus 2 may inflict a post-viral condition known as post-COVID-19 syndrome (PCS) or long-COVID. Studies measuring levels of inflammatory and vascular biomarkers in blood, serum, or plasma of COVID-19 survivors with PCS versus non-PCS controls have produced mixed findings. Our review sought to meta-analyse those studies. A systematic literature search was performed across five databases until 25 June 2022, with an updated search on 1 November 2022. Data analyses were performed with Review Manager and R Studio statistical software. Twenty-four biomarkers from 23 studies were meta-analysed. Higher levels of C-reactive protein (Standardized mean difference (SMD) = 0.20; 95% CI: 0.02-0.39), D-dimer (SMD = 0.27; 95% CI: 0.09-0.46), lactate dehydrogenase (SMD = 0.30; 95% CI: 0.05-0.54), and leukocytes (SMD = 0.34; 95% CI: 0.02-0.66) were found in COVID-19 survivors with PCS than in those without PCS. After sensitivity analyses, lymphocytes (SMD = 0.30; 95% CI: 0.12-0.48) and interleukin-6 (SMD = 0.30; 95% CI: 0.12-0.49) were also significantly higher in PCS than non-PCS cases. No significant differences were noted in the remaining biomarkers investigated (e.g., ferritin, platelets, troponin, and fibrinogen). Subgroup analyses suggested the biomarker changes were mainly driven by PCS cases diagnosed via manifestation of organ abnormalities rather than symptomatic persistence, as well as PCS cases with duration of <6 than ≥6 months. In conclusion, our review pinpointed certain inflammatory and vascular biomarkers associated with PCS, which may shed light on potential new approaches to understanding, diagnosing, and treating PCS.

Incidence and Risk Factors of Colistin-Induced Nephrotoxicity Associated with The International Consensus Guidelines for the Optimal Use of the Polymyxins: A Retrospective Study in a Tertiary Care Hospital, Saudi Arabia.

Background: Colistin is an effective therapy against multidrug-resistant gram-negative bacteria. However, nephrotoxicity is a major issue with its use. Objective: We aimed to evaluate the incidence and the potential risk factors of nephrotoxicity in colistin-treated patients. Methods: A retrospective cohort study was conducted. All adult patients aged 18 years and older who received colistin for ≥72 h were included in the study, while end-stage kidney disease patients requiring dialysis or had renal transplants were excluded. The incidence and severity of acute kidney injury (AKI) were assessed based on the Kidney Disease Improving Global Outcomes (KDIGO). Result: Out of 128 patients who received colistin, 51.56% of them have experienced AKI. The incidence was increased among oldest patients (above 80) and those who did not receive the appropriate dose (p-value = 0.0003). In addition, the median time until the AKI occurred was 10 days after receiving the colistin treatment. Rates of AKI in patients with previous AKI (71.7%) were three times higher than patients who did not previously experience AKI (HR = 2.97, 95% CI [1.8-4.8]). Conclusions: Nephrotoxicity is a significant issue among patients who receive colistin in the hospital, especially among older patients and those who did not receive the appropriate dose. As a result, healthcare providers should play a major role in colistin dosing, especially among the older adult population.