Efficacy of tocilizumab in patients with severe COVID-19: Survival and clinical outcomes

Background: SARS-CoV-2 is associated with a severe inflammatory response contributing to respiratory and systemic manifestations, morbidity, and mortality in patients with coronavirus disease 2019 (COVID-19). Methods: Tocilizumab (TCZ) efficacy on mortality and length of hospital stay was retrospectively evaluated in patients who received TCZ and compared with that in controls with a similar severity of COVID-19. The primary endpoint was survival probability on day 28. The secondary endpoints included survival at day 14 and length of hospital stay. Results: Of the 148 patients included in the study, 62 received TCZ and standard of care, whereas 86 served as a control group and received only standard of care. The two groups were similar, although TCZ-treated patients were more likely to exhibit hypertension (46.7% vs. 29.8%), chronic kidney disease (14.5% vs. 1.1%), and high Charlson score (1.18 vs. 1.00; p = 0.006) and less likely to receive corticosteroid treatment (48.5% vs. 93.0%). TCZ was associated with lower mortality on both day 28 (16.1% vs. 37.2%, p = 0.004) and day 14 (9.7% vs. 24.4%, p = 0.022). The hospital stay was longer in the TCZ-treated than in the control group (15.6 ± 7.59 vs.17.7 ± 7.8 days, p = 0.103). Ten patients (16.0%) in the TCZ-treated group developed infections. Conclusion: TCZ was associated with a lower likelihood of death despite resulting in higher infection rates and a non-significant longer hospital stay

Microbial Natural Products with Antiviral Activities, Including Anti-SARS-CoV-2: A Review

The SARS-CoV-2 virus, which caused the COVID-19 infection, was discovered two and a half years ago. It caused a global pandemic, resulting in millions of deaths and substantial damage to the worldwide economy. Currently, only a few vaccines and antiviral drugs are available to combat SARS-CoV-2. However, there has been an increase in virus-related research, including exploring new drugs and their repurposing. Since discovering penicillin, natural products, particularly those derived from microbes, have been viewed as an abundant source of lead compounds for drug discovery. These compounds treat bacterial, fungal, parasitic, and viral infections. This review incorporates evidence from the available research publications on isolated and identified natural products derived from microbes with anti-hepatitis, anti-herpes simplex, anti-HIV, anti-influenza, anti-respiratory syncytial virus, and anti-SARS-CoV-2 properties. About 131 compounds with in vitro antiviral activity and 1 compound with both in vitro and in vivo activity have been isolated from microorganisms, and the mechanism of action for some of these compounds has been described. Recent reports have shown that natural products produced by the microbes, such as aurasperone A, neochinulin A and B, and aspulvinone D, M, and R, have potent in vitro anti-SARS-CoV-2 activity, targeting the main protease (Mpro). In the near and distant future, these molecules could be used to develop antiviral drugs for treating infections and preventing the spread of disease

Designing an Epitope-Based Peptide Vaccine Derived from RNA-Dependent RNA Polymerase (RdRp) against Dengue Virus Serotype 2

Dengue fever (DF) continues to be one of the tropical and subtropical health concerns. Its prevalence tends to increase in some places in these regions. This disease is caused by the dengue virus (DENV), which is transmitted through the mosquitoes Aedes aegypti and A. albopictus. The treatment of DF to date is only supportive and there is no definitive vaccine to prevent this disease. The non-structural DENV protein, RNA-dependent RNA Polymerase (RdRp), is involved in viral replication. The RdRp-derived peptides can be used in the construction of a universal dengue vaccine. These peptides can be utilized as epitopes to induce immunity. This study was an in silico evaluation of the affinity of the potential epitope for the universal dengue vaccine to dendritic cells and the bonds between the epitope and the dendritic cell receptor. The peptide sequence MGKREKKLGEFGKAKG generated from dengue virus subtype 2 (DENV-2) RdRp was antigenic, did not produce allergies, was non-toxic, and had no homology with the human genome. The potential epitope-based vaccine MGKREKKLGEFGKAKG binds stably to dendritic cell receptors with a binding free energy of −474,4 kcal/mol. This epitope is anticipated to induce an immunological response and has the potential to serve as a universal dengue virus vaccine candidate

Evaluation of Bi-Lateral Co-Infections and Antibiotic Resistance Rates among COVID-19 Patients in Lahore, Pakistan

Background and Objective: Bacterial infections are among the major complications of many viral respiratory tract illnesses, such as influenza and coronavirus disease-2019 (COVID-19). These bacterial co-infections are associated with an increase in morbidity and mortality rates. The current observational study was conducted at a tertiary care hospital in Lahore, Pakistan among COVID-19 patients with the status of oxygen dependency to see the prevalence of bacterial co-infections and their antibiotic susceptibility patterns. Materials and Methods: A total of 1251 clinical samples were collected from already diagnosed COVID-19 patients and tested for bacterial identification (cul-tures) and susceptibility testing (disk diffusion and minimum inhibitory concentration) using gold standard diagnostic methods. Results: From the total collected samples, 234 were found positive for different bacterial isolates. The most common isolated bacteria were Escherichia coli (E. coli) (n = 62) and Acinetobacter baumannii (A. baumannii) (n = 47). The E. coli isolates have shown the highest resistance to amoxicillin and ampicillin, while in the case of A. baumannii, the highest resistance was noted against tetracycline. The prevalence of methicillin resistant Staphylococcus aureus (MRSA) was 14.9%, carbapenem resistant Enterobacteriaceae (CRE) was 4.5%, and vancomycin resistant Enterococ-cus (VRE) was 3.96%. Conclusion: The results of the current study conclude that empiric antimicro-bial treatment in critically ill COVID-19 patients may be considered if properly managed within institutional or national level antibiotic stewardship programs, because it may play a protective role in the case of bacterial co-infections, especially when a patient has other AMR risk factors, such as hospital admission within the previous six months

Psychogenetic, genetic and epigenetic mechanisms in Candida auris: Role in drug resistance

In recent years, we are facing the challenge of drug resistance emergence in fungi. The availability of limited antifungals and development of multi-drug resistance in fungal pathogens has become a serious concern in the past years in the health sector. Although several cellular, molecular, and genetic mechanisms have been proposed to explain the drug resistance mechanism in fungi, but a complete understanding of the molecular and genetic mechanisms is still lacking. Besides the genetic mechanism, epigenetic mechanisms are pivotal in the fungal lifecycle and disease biology. However, very little is understood about the role of epigenetic mechanisms in the emergence of multi-drug resistance in fungi, especially in Candida auris (C. auris). The current narrative review summaries the clinical characteristics, genomic organization, and molecular/genetic/epigenetic mechanisms underlying the emergence of drug resistance in C. auris. A very few studies have attempted to evaluate the role of epigenetic mechanisms in C. auris. Furthermore, advanced genetic tools such as the CRISP-Cas9 system can be utilized to elucidate the epigenetic mechanisms and their role in the emergence of multi-drug resistance in C. auris

Application of Artificial Intelligence in Combating High Antimicrobial Resistance Rates

Artificial intelligence (AI) is a branch of science and engineering that focuses on the computational understanding of intelligent behavior. Many human professions, including clinical diagnosis and prognosis, are greatly useful from AI. Antimicrobial resistance (AMR) is among the most critical challenges facing Pakistan and the rest of the world. The rising incidence of AMR has become a significant issue, and authorities must take measures to combat the overuse and incorrect use of antibiotics in order to combat rising resistance rates. The widespread use of antibiotics in clinical practice has not only resulted in drug resistance but has also increased the threat of super-resistant bacteria emergence. As AMR rises, clinicians find it more difficult to treat many bacterial infections in a timely manner, and therapy becomes prohibitively costly for patients. To combat the rise in AMR rates, it is critical to implement an institutional antibiotic stewardship program that monitors correct antibiotic use, controls antibiotics, and generates antibiograms. Furthermore, these types of tools may aid in the treatment of patients in the event of a medical emergency in which a physician is unable to wait for bacterial culture results. AI’s applications in healthcare might be unlimited, reducing the time it takes to discover new antimicrobial drugs, improving diagnostic and treatment accuracy, and lowering expenses at the same time. The majority of suggested AI solutions for AMR are meant to supplement rather than replace a doctor’s prescription or opinion, but rather to serve as a valuable tool for making their work easier. When it comes to infectious diseases, AI has the potential to be a game-changer in the battle against antibiotic resistance. Finally, when selecting antibiotic therapy for infections, data from local antibiotic stewardship programs are critical to ensuring that these bacteria are treated quickly and effectively. Furthermore, organizations such as the World Health Organization (WHO) have underlined the necessity of selecting the appropriate antibiotic and treating for the shortest time feasible to minimize the spread of resistant and invasive resistant bacterial strains

Psychogenetic, genetic and epigenetic mechanisms in Candida auris: Role in drug resistance

In recent years, we are facing the challenge of drug resistance emergence in fungi. The availability of limited antifungals and development of multi-drug resistance in fungal pathogens has become a serious concern in the past years in the health sector. Although several cellular, molecular, and genetic mechanisms have been proposed to explain the drug resistance mechanism in fungi, but a complete understanding of the molecular and genetic mechanisms is still lacking. Besides the genetic mechanism, epigenetic mechanisms are pivotal in the fungal lifecycle and disease biology. However, very little is understood about the role of epigenetic mechanisms in the emergence of multi-drug resistance in fungi, especially in Candida auris (C. auris). The current narrative review summaries the clinical characteristics, genomic organization, and molecular/genetic/epigenetic mechanisms underlying the emergence of drug resistance in C. auris. A very few studies have attempted to evaluate the role of epigenetic mechanisms in C. auris. Furthermore, advanced genetic tools such as the CRISP-Cas9 system can be utilized to elucidate the epigenetic mechanisms and their role in the emergence of multi-drug resistance in C. auris

Evaluation of Hematological, Biochemical Profiles and Molecular Detection of Envelope Gene (gp-41) in Human Immunodeficiency Virus (HIV) among Newly Diagnosed Patients

The Human Immunodeficiency Virus (HIV) is a highly morphic, retrovirus that rapidly evolves through mutation as well as recombination. Because of the immunocompromised status in HIV patients, there is often a higher chance of acquiring different secondary infections followed by liver cirrhosis, hepatitis B & C, and HIV-associated nephropathy. The current study was conducted to see the prevalence of secondary infections, hematological and biochemical markers for liver and renal associated diseases, and to detect the envelope gene (GP41) in newly diagnosed HIV patients. A total of 37 samples were collected from HIV-positive patients registered in different hospital settings under the National AIDS control program. The collected samples were processed for hepatitis B, hepatitis C, hematological analysis, and biochemical analysis. To identify the envelope gene in newly diagnosed HIV patients, polymerase chain reaction (PCR) was performed using four gene-specific primers. The HIV infections were seen more in male as compared to females. A significant decrease in complete blood count was observed in HIV patients when compared to healthy individuals. There was a significant increase in aspartate aminotransferase (AST), alanine aminotransferase (ALT), urea, and creatinine observed in HIV patients. No significant difference was observed in alkaline phosphatase (ALP), total bilirubin, and albumin levels when compared to healthy control. Anemia was observed in 59.4% of HIV patients. A total of three (8.1%) patients were found to be co-infected with hepatitis B and one (2.7 %) was co-infected with hepatitis C. Out of these 37 tested samples, a total of four showed the successful amplification of the envelope gene. This study provides platform for the health care facilitators to regularly monitor the signs, symptoms and clinical biomarkers of HIV-associated infections to prevent toxicity at an early stage to improve the quality of life (QoL) and minimize the mortality rate in HIV patients. Envelope gene mutating frequently results in drug resistance, and thus future research on polymorphism analysis will reveal points of substitutions to improve drug designing

Systematic Review on Pathophysiological Complications in Severe COVID-19 among the Non-Vaccinated and Vaccinated Population

COVID-19, caused by SARS-CoV-2, is one of the longest viral pandemics in the history of mankind, which have caused millions of deaths globally and induced severe deformities in the sur-vivals. For instance, fibrosis and cavities in the infected lungs of COVID-19 are some of the complications observed in infected patients post COVID-19 recovery. These health abnormalities, including is multiple organ failure—the most striking pathological features of COVID-19—have been linked with diverse distribution of ACE2 receptor. Additionally, several health complications reports were reported after administration of COVID-19 vaccines in healthy individuals, but clinical or molecular pathways causing such complications are not yet studied in detail. Thus, the present systematic review established the comparison of health complication noted in vaccinated and non-vaccinated individuals (COVID-19 infected patients) to identify the association between vaccination and the multiorgan failure based on the data obtained from case studies, research articles, clinical trials/Cohort based studies and review articles published between 2020–2022. This review also in-cludes the biological rationale behind the COVID-19 infection and its subsequent symptoms and effects including multiorgan failure. In addition, multisystem inflammatory syndrome (MIS) has been informed in individuals post vaccination that resulted in multiorgan failure but, no direct cor-relation of vaccination with MIS has been established. Similarly, hemophagocytic lymphohistiocyto-sis (HLH) also noted to cause multiorgan failure in some individuals following full vaccination. Furthermore, severe complications were recorded in elderly patients (+40 years of age), indicates that older age individuals are higher risk by COVID-19 and post vaccination, but available literature is not sufficient to comply with any conclusive statements on relationship between vaccination and multiorgan failure

Seroprevalence, Risk Factors and Maternal–Fetal Outcomes of <i>Toxoplasma gondii</i> in Pregnant Women from WHO Eastern Mediterranean Region: Systematic Review and Meta-Analysis

Background: The protozoan parasite Toxoplasma gondii may cause serious illness in the immunocompromised. The Toxoplasma gondii seropositive prevalence in pregnant women in WHO Eastern Mediterranean Region countries is inconsistent in the literature and it is associated with outcomes that have not be fully elucidated, hence the need for a better understanding of the pooled seroprevalence and associated maternal and fetal outcomes. Objective: The objective was to conduct a systematic literature review and determine the pooled prevalence of WHO Eastern Mediterranean Regional countries’ pregnant women’s seroprevalence of Toxoplasma gondii and the maternal–fetal outcomes. Methods: This quantitative study examined WHO Eastern Mediterranean countries’ maternal–fetal outcomes and Toxoplasma gondii prevalence in pregnant women. The targeted population was pregnant women, while the primary outcome was seropositivity of Toxoplasma gondii, while other outcomes such as maternal and fetal associations and risk factors were determined PubMed, SCOPUS, MEDLINE, and Index Medicus for the Eastern Mediterranean Region (IMEMR) databases were searched up until 30 January 2023. The search terms used were “Toxoplasma gondii” OR “Toxoplasma infection” AND “Pregnant woman” or pregnan* OR Antenatal OR Prenatal OR Gravidity OR Parturition OR Maternal AND WHO Eastern Mediterranean Region). OpenMeta-Analyst and Jamovi were used to analyze the generated data. Results: In total, 95 of 2947 articles meeting the inclusion criteria examined Toxoplasma gondii prevalence in pregnant women from WHO Eastern Mediterranean countries. The pooled prevalence of Toxoplasma gondii in pregnant women was 36.5% (95%CI: 32.6–40.4) with a median value of 35.64%, range values of 1.38–75.30%, with 99.61% heterogeneity. The pooled seroprevalence of IgG of Toxoplasma gondii was 33.5% (95%CI: 29.8–37.2) with a median value of 33.51%, and a range values of 1.38–69.92%; the pooled seroprevalence of IgM was 3.6% (95%CI: 3.1–4.1)) with a median value of 3.62 and range values of 0.20–17.47%, while cases of pooled seroprevalence of both IgG and IgM positivity was 3.0% (95%CI: 1.9–4.4) with a median value of 2.05 and a range values of 0.05–16.62%. Of the Toxoplasma gondii seropositive women, 1281/3389 (34.8%) 174/1765 (32.9%), 1311/3101 (43.7%), and 715/1683 (40.8%) of them had contact with cats, drank unprocessed milk, ate raw or undercooked meat and ate unwashed raw vegetables, respectively. The maternal–fetal outcomes associated with Toxoplasma gondii seropositivity were a history of abortions, miscarriage, stillbirth, intrauterine fetal death, and premature birth, which were found in 868/2990 (32.5%), 112/300 (36.1%), 111/375 (25.7%), 3/157 (1.9%) and 96/362 (20.1%) of women who tested positive for Toxoplasma gondii antibodies. Conclusion: The study found a high proportion of Toxoplasma gondii seroprevalence in pregnant women in the WHO Eastern Mediterranean Region, which may be linked to poor outcomes for mothers and their babies. Thus, pregnant women require monitoring and comprehensive prevention strategies for Toxoplasma gondii infection