Epidemiology and clinical features of respiratory syncytial virus (RSV) infection in hospitalized children during the COVID-19 pandemic in Gorgan, Iran.

Background and Aims: Respiratory syncytial virus (RSV) is a leading cause of acute respiratory infection in infants and young children. Given the altered circulation patterns of respiratory viruses during the coronavirus disease pandemic-2019 (COVID-19), the study aimed to evaluate epidemiology and clinical features of RSV infections in hospitalized children during the COVID-19 pandemic in Gorgan, northeastern Iran. Molecular epidemiology studies on respiratory viral infections are necessary to monitor circulating viruses, disease severity, and clinical symptoms, in addition to early warning of new outbreaks. Methods: Overall, 411 respiratory swab samples from hospitalized children from October 2021 to March 2022 were collected at Taleghani Children's Hospital, Gorgan, Iran. The incidence of RSV, as well as the circulating subgroups and genotypes, were investigated and confirmed using PCR methods. Additionally, all samples tested for severe acute respiratory syndrome-associated coronavirus 2 (SARS-CoV-2) and influenza, and demographic and clinical data were analyzed using SPSS software. Results: The share of RSV, SARS-CoV-2, and influenza among hospitalized children with acute lower respiratory infections (ALRI) were 27%, 16.5%, and 4.1%, respectively. The RSV subgroup A (genotype ON1) was dominant over subgroup B (genotype BA9), with more severe clinical symptoms. Compared with the prepandemic era there were high numbers of hospitalized SARS-CoV-2 positive children and low numbers of other respiratory viruses. Despite this, the prevalence of ALRI-related RSV-disease among hospitalized children in our specialized pediatric center was higher than COVID-19 disease in the same cohort. Conclusions: Studying the epidemiology of respiratory viruses and determining the circulating strains can contribute to effective infection control and treatment strategies.

Prevalence of CCR5 Delta 32 Genetic Variant in the Turkmen Population of Golestan Province, Northeast of Iran.

The 32 bp deletion in the chemokine receptor (C-C motif) 5 gene (CCR5Δ32) is a natural loss of function polymorphism that prevents the protein from locating on the cell surface. This genetic variation acts as a double-edge sword in the pathogenesis/defense mechanism of different health conditions, such as viral infections, autoimmune diseases, and cancers. Here, we evaluated the prevalence of the CCR5Δ32 polymorphism in the Turkmen population of Golestan province, northeast of Iran. Blood samples were collected from 400 randomly selected Turkmen populations (199 women and 201 men), and genomic DNA was extracted. Characterization of CCR5Δ32 genotypes was performed by PCR using primers flanking the 32-nucleotide deletion in the CCR5 gene. The amplified DNA fragments were visualized on 2% agarose gel electrophoresis with cybergreen staining under UV light. All individuals were of Turkmen ethnicity and lived in the Golestan province, northeast of Iran. The mean age of all participants was 35.46 years, with a 20-45 year range. All the studied subjects were healthy without any severe conditions such as autoimmune disease and viral infections. All individuals had no history of HIV infection. The PCR product visualization showed that all the samples are at the 330 bp size, which means the CCR5Δ32 allele was utterly absent from the study population. The presence of the CCR5Δ32 allele among Turkmens may be attributed to the admixture with European descent people. We conclude that the CCR5Δ32 polymorphism may be absent in the Iranian Turkmen population, and further studies with a large population are needed.

Polymyxin combination therapy for multidrug-resistant, extensively-drug resistant, and difficult-to-treat drug-resistant gram-negative infections: is it superior to polymyxin monotherapy?

INTRODUCTION: The increasing prevalence of infections with multidrug-resistant (MDR), extensively-drug resistant (XDR) or difficult-to-treat drug resistant (DTR) Gram-negative bacilli (GNB), including Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae, Enterobacter species, and Escherichia coli poses a severe challenge. AREAS COVERED: The rapid growing of multi-resistant GNB as well as the considerable deceleration in development of new anti-infective agents have made polymyxins (e.g. polymyxin B and colistin) a mainstay in clinical practices as either monotherapy or combination therapy. However, whether the polymyxin-based combinations lead to better outcomes remains unknown. This review mainly focuses on the effect of polymyxin combination therapy versus monotherapy on treating GNB-related infections. We also provide several factors in designing studies and their impact on optimizing polymyxin combinations. EXPERT OPINION: An abundance of recent in vitro and preclinical in vivo data suggest clinical benefit for polymyxin-drug combination therapies, especially colistin plus meropenem and colistin plus rifampicin, with synergistic killing against MDR, XDR, and DTR P. aeruginosa, K. pneumoniae and A. baumannii. The beneficial effects of polymyxin-drug combinations (e.g. colistin or polymyxin B + carbapenem against carbapenem-resistant K. pneumoniae and carbapenem-resistant A. baumannii, polymyxin B + carbapenem + rifampin against carbapenem-resistant K. pneumoniae, and colistin + ceftolozan/tazobactam + rifampin against PDR-P. aeruginosa) have often been shown in clinical setting by retrospective studies. However, high-certainty evidence from large randomized controlled trials is necessary. These clinical trials should incorporate careful attention to patient's sample size, characteristics of patient's groups, PK/PD relationships and dosing, rapid detection of resistance, MIC determinations, and therapeutic drug monitoring.

15-Lipoxygenase and its metabolites in the pathogenesis of breast cancer: A double-edged sword.

15-lipoxygenase is one of the key enzymes for the metabolism of unsaturated fatty acids that its manipulation has been proposed recently as a new molecular target for regulating cancer cell growth. Aberrant expression of 15-lipoxygenase enzyme seems to play an indicative role in the pathology of different cancer types, tumor progression, metastasis, or apoptosis. Based on the fact that breast cancer is one of the most common cancers that imposes a burden of mortality in women also, on the other hand, evidence in experimental models and human studies indicate the emerging role of the 15-lipoxygenase pathway in breast cancer pathogenesis, we present a review of recent findings related to the role of 15- lipoxygenase enzyme and metabolites in breast cancer growth, apoptosis, metastasis, and invasion as well as their local and circulating expression pattern in patients with breast cancer. Our review supports the emerging role of 15- lipoxygenase in molecular and cellular processes regulating breast tumor cell fate with both positive and negative effects.

Functional variation (Q63R) in the cannabinoid CB2 receptor may affect the severity of COVID-19: a human study and molecular docking.

Evidence supports a role of host genetic diversity in the clinical course of coronavirus disease 2019 (COVID-19). Variation in the cannabinoid CB2 receptor gene (CNR2) could affect the regulatory action of endocannabinoids on the immune system, resulting in an increased risk of various inflammatory diseases. The present study investigated the relationship between the CNR2-Q63R variant and COVID-19 severity. A total of 200 Iranian COVID-19 patients were enrolled in the study and genotyped using a TaqMan assay. The co-dominant, dominant, recessive, over-dominant, and additive inheritance models were analyzed using SNPStats software. In silico molecular docking was also performed to simulate the effects of the Q63R variation on CB2 binding with a ligand and with the G-protein. A significant difference in the Q63R allele and genotype distribution was found between expired and discharged COVID-19 patients in co-dominant, recessive, and additive inheritance models. The molecular docking results showed that the predicted structure of mutant CB2 (63R type) could not bind to the G-protein in the correct position. The data indicated that the Q63R variation in the CNR2 gene may affect the severity of COVID-19. Identification of genes related to susceptibility and severity of COVID-19 may lead to specific targets for drug repurposing or development.

COVID-19: Why does disease severity vary among individuals?

The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is responsible for the current pandemic, coronavirus disease 2019 (COVID-19). While all people are susceptible to the SARS-CoV-2 infection, the nature and severity of the disease vary significantly among individuals and populations. Importantly, reported disease burdens and case fatality rates differ considerably from country to country. There are, however, still uncertainties about the severity of the disease among individuals or the reason behind a more severe disease in some cases. There is a strong possibility that the severity of this disease depends on a complicated interaction between the host, virus, and environment, which leads to different clinical outcomes. The objective of this article is to point out the essential influential factors related to the host, virus, and environment affecting the clinical outcome of COVID-19.

Neutrophils in respiratory syncytial virus infection: From harmful effects to therapeutic opportunities.

Respiratory syncytial virus (RSV) is an important infectious agent in infants and young children. In most cases, RSV infection only causes mild disease, but in some, it requires invasive ventilation. Although antiviral drugs are obvious candidates to treat viral illness, and some have shown antiviral effects in humans, antivirals such as GS-5806, ALX-0171 and ALS-8176 have not yet met their expectations. Since the inappropriate or dysregulated immune response against RSV leads to harmful immune pathology, a robust immune cascade is probably underway by the time patients reach the hospital. RSV infection is associated with a strong neutrophil influx into the airway. It not clear if these cells contribute to antiviral defence or to lung pathology. This article discusses the protective and harmful roles of neutrophils during RSV infection and provides an overview of mechanisms by which neutrophil function could be targeted to prevent tissue injury and preserve homeostasis.

Respiratory syncytial virus infection: why does disease severity vary among individuals?

Introduction: Respiratory syncytial virus (RSV) is the most common cause of acute lower respiratory tract infections in infancy. While many infants are infected with RSV, the nature and severity of the disease vary among individuals. RSV causes bronchiolitis, pneumonia, and asthma exacerbation. However, most children infected with RSV have only mild upper airways disease and may be asymptomatic.Areas covered: Despite efforts to elucidate mechanisms for the various clinical responses to RSV infection, they remain largely unknown, suggesting that susceptibility and disease are influenced by multiple intrinsic and extrinsic factors. This article reviews the available literature on the field of RSV disease severity and discusses important factors associated to susceptibility and different disease outcome.Expert opinion: The severity of RSV-induced illness is a phenomenon that depends on a variety of graded mechanisms of interaction between the host, virus, and environment. This may lead to differences in the intensity of immune response in the lung and different courses of the disease. By characterizing, classifying, and grading the affecting factors in high-risk patients versus those who do not fall ill by RSV, we may find therapies or point to disease-limiting medications.