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.

Hematological and Biochemical Laboratory Parameters in COVID-19 Patients: A Retrospective Modeling Study of Severity and Mortality Predictors.

Background: It is well known that laboratory markers could help in identifying risk factors of severe illness and predicting outcomes of diseases. Here, we performed a retrospective modeling study of severity and mortality predictors of hematological and biochemical laboratory parameters in Iranian COVID-19 patients. Methods: Data were obtained retrospectively from medical records of 564 confirmed Iranian COVID-19 cases. According to the disease severity, the patients were categorized into two groups (severe or nonsevere), and based on the outcome of the disease, patients were divided into two groups (recovered or deceased). Demographic and laboratory data were compared between groups, and statistical analyses were performed to define predictors of disease severity and mortality in the patients. Results: The study identified a panel of hematological and biochemical markers associated with the severe outcome of COVID-19 and constructed different predictive models for severity and mortality. The disease severity and mortality rate were significantly higher in elderly inpatients, whereas gender was not a determining factor of the clinical outcome. Age-adjusted white blood cells (WBC), platelet cells (PLT), neutrophil-to-lymphocyte ratio (NLR), red blood cells (RBC), hemoglobin (HGB), hematocrit (HCT), erythrocyte sedimentation rate (ESR), mean corpuscular hemoglobin (MCHC), blood urea nitrogen (BUN), and creatinine (Cr) also showed high accuracy in predicting severe cases at the time of hospitalization, and logistic regression analysis suggested grouped hematological parameters (age, WBC, NLR, PLT, HGB, and international normalized ratio (INR)) and biochemical markers (age, BUN, and lactate dehydrogenase (LDH)) as the best models of combined laboratory predictors for severity and mortality. Conclusion: The findings suggest that a panel of several routine laboratory parameters recorded on admission could be helpful for clinicians to predict and evaluate the risk of disease severity and mortality in COVID-19 patients.

Cross-reactivity between Mycobacterium avium subspecies paratuberculosis 4027 peptide and Human IRF5 may contribute to Multiple Sclerosis in Iranian patients.

Background: The etiology of Multiple sclerosis (MS) is complicated and can be affected by several environmental factors, such as Mycobacterium avium subspecies paratuberculosis (MAP) infection in genetically predisposed individuals. The link between MAP and MS depends on host genetic and epigenetic aspects and population-based features that require further investigation. We aimed to study the possible role of MAP in triggering MS using molecular and serological methods. Materials and methods: This case-control study examined 200 blood samples (100 MS patients and 100 HCs) to search for the MAP-specific IS900 gene. In addition, ELISA was conducted to determine the humoral response against MAP_402718-32 and its human IRF5424-434 peptide homolog. Results: The frequency of MAP detection based on the molecular method in MS patients and HCs was 48 % and 13 %, respectively (p < 0.0001). The presence of antibodies against MAP_402718-32 and IRF5424-434 was 55 % and 65 % in MS patients versus 9 % and 7 % in HCs, respectively (p < 0.0001). A good correlation was observed between MAP_4027 and IRF5 antibodies (r = 0.5782, p < 0.0001), indicating that the same antibodies recognized common peptide epitopes. Conclusion: Our research revealed a significant association between MAP and MS, highlighting the possible role of MAP as an important infection trigger factor of MS. It is hypothesized that cross-reactivity between MAP4027 and IRF5 may dysregulate immune homeostasis.

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.

Detection of SARS-CoV-2 genome in the air, surfaces, and wastewater of the referral hospitals, Gorgan, north of Iran.

Background and Objectives: Coronavirus disease 2019 (COVID-19) is a pandemic caused by the novel virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Knowing the virus's behavior and its persistence in different environments are crucial and will lead to the proper management of the disease. In this study, air, surface, and sewage samples were taken from different parts of referral hospitals for COVID-19. Materials and Methods: Air samples were taken with impinger, surface samples with swabs, and sewage samples were taken from the hospital wastewater treatment plant. After viral genome extraction, a real-time RT-PCR test was applied to confirm the presence of SARS-CoV-2 RNA in the collected samples. Results: The virus genome could be traced in the wards and wastewater related to hospitalized COVID-19 patients. Overally, 29%, 16%, and 37.5% of air, surface, and sewage samples were positive for the SARS-CoV-2 genome, respectively. Conclusion: Findings of such studies provide valuable results regarding the degree of contamination of hospital environments and the risk of virus transmission in different environments and among hospital staff and patients.

Recurrent viral RNA positivity and candidiasis findings in hospitalized patients with COVID-19.

Background: The aim of this study was to evaluate reinfection and fungal infections among 785 patients with COVID-19 disease admitted to Baqiyatallah Hospital in Northeastern Iran after the onset of the COVID-19 epidemic. Materials & Methods: In this descriptive-analytic study (20 February-21 July 2020), reinfection and fungal infections among 785 patients were investigated using epidemiological questionnaire, clinical trials, Real-time PCR and CT scan (chest computed tomography) from the hospital HIS (hospital's information system) and collected samples. Results: Reinfection and one oral candidiasis were diagnosed in one 68-year-old man and one 47-year-old man 63 and 42 days after the initial infection, respectively. Conclusion: The research results showed that exposure to COVID-19 may not establish long-term protective immunity to all patients.

Anti-inflammatory effects of curcumin-loaded niosomes on respiratory syncytial virus infection in a mice model.

Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infection in paediatrics. While antivirals are apparent candidates to treat RSV-induced diseases, they have not yet met expectations and have remained in infancy. There is growing evidence to suggest that modulating the exacerbated inflammation during RSV infection can improve disease outcome. Curcumin-loaded niosomes have anti-inflammatory effects against RSV-induced respiratory disease by reducing immune cells' infiltration and inflammatory cytokines' production. This study evaluated the effects of curcumin-loaded niosomes on RSV-induced immunopathology in a mice model. Curcumin-loaded niosomes were prepared using the thin-film hydration method and characterized in vitro. Female Balb/c mice were infected by RSV-A2 and treated daily with curcumin-loaded niosomes. The potential anti-inflammatory effects of curcumin-loaded niosomes were evaluated on day 5 after infection. Using curcumin-loaded niosomes decreased immune cell influx and the inflammatory mediators (MIP-1α, TNF-α and IFN-γ) production in the lung, resulting in alleviated lung pathology following RSV infection. These findings indicate that curcumin-loaded niosomes have anti-inflammatory potential and could be a promising candidate to alleviate RSV-associated immunopathology.

Evaluation of biochemical characteristics of 183 COVID-19 patients: A retrospective study.

INTRODUCTION AND AIM: Coronavirus disease 2019 (COVID-19), with a high mortality rate, has caught the eyes of researchers worldwide and placed a heavy burden on the health care system. Accordingly, this study aimed to evaluate the values of biochemical parameters on the outcomes of COVID-19 patients in Golestan, Iran. MATERIALS AND METHODS: This retrospective study was conducted on 183 COVID-19 patients (i.e., 94 males and 89 females) between March and September 2020. The biochemical parameters and demographic data of the patients (including age, sex, urea, creatinine [Cr], lactate dehydrogenase [LDH], and creatine kinase [CK]) were obtained from electrical medical records. According to the outcome of COVID-19, the patients were categorized into two groups (i.e., death [n = 63] and survival [n = 120] groups), and the biochemical parameters and outcomes of COVID-19 were analyzed. RESULTS: Of the 183 patients, 120 (65.5%) had a non-severe type and recovered from COVID-19, and 63 (34.4%) developed into a critically severe type and died. The mean age of all patients was 56.5 years old. The highest mortality was observed in patients with LDH ≥280. The data obtained by the one-sample t-test showed that there were significantly higher mean values of urea, Cr, CK, and LDH in COVID-19 patients when compared to their reference intervals (P˂0.0001 for all). CONCLUSIONS: Some biochemical parameters are effective in the evaluation of dynamic variations in COVID-19 patients. It can be concluded from the results that biochemical parameters and reinforce LDH may be useful for the evaluation of the COVID-19 outcome.

The effect of carvacrol on respiratory syncytial virus infection in mice model: caution in the use of herbal medicines.

BACKGROUND AND OBJECTIVES: Respiratory syncytial virus (RSV) is one of the most common viruses associated with acute lower respiratory tract infections in infants, young children, and the elderly. Due to a lack of effective anti-viral drugs or vaccines, using an immunomodulatory strategy is probably the best option to decrease the burden of RSV disease. Here, we studied carvacrol as a known immunomodulator on RSV infection outcome in a mice model. MATERIALS AND METHODS: Balb/c mice were infected by intranasal inoculation of RSV-A2, and treatment started daily 24 h after infection. Mice were sacrificed on day five after infection and experimental analyses were performed to study airway immune cell influx, CD4 and CD8 subtypes, cytokine/chemokine secretion, lung histopathology, and viral load. RESULTS: Results showed that using carvacrol enhanced immune cell influx, cytokine/chemokine production, and virus titer, and aggravated lung pathology. Our result showed that carvacrol administration increased viral titer compared to the RSVPBS group. Also, carvacrol significantly induced IFN-γ production and did not induce IL-10 production. Besides, carvacrol non-significantly increased lymphocytes and monocytes count but did not affect the neutrophil count. CONCLUSION: Carvacrol at the concentration of 80 (mg/kg) did not show immunomodulatory activity to alleviate the RSV infection outcome. Further research is needed to uncover the effects of the carvacrol intervention on virus replication and immune responses following RSV infection. Many herbal remedies in use contain carvacrol. However, the use of herbal remedies to treat viral respiratory infections such as RSV has to be performed with caution.

Epidemiological and clinical characteristics of the COVID-19 epidemic and associated factors for mortality in Golestan province, Iran: a retrospective cohort study.

BACKGROUND: We aimed to further clarify the epidemiological and clinical characteristics of 2019-nCoV pneumonia and risk factors associated for mortality. METHODS: In this study, we included inpatient with acute respiratory distress syndrome at Golestan Hospitals who had been discharged or had died in 2020. Epidemiological, and clinical data were extracted from electronic medical records and compared between recovered and died cases. We used multiple logistic regression methods to explore the risk factors associated with in-hospital death. RESULTS: Overall 2,835 acute respiratory distress syndrome patients were included in this study, and 874 (30.83%) were positive for 2019-nCoV. Five hundred and sixty-three patients (19.86%) died, 1,687 patients (59.51%) were recovered. Of the total deaths, only 288 (10.15%) were attributed to COVID-19. The most common symptoms at onset of illness were respiratory distress [1,795 (63.32%)], fever [1,601 (56.47%)], dry cough [1,595 (56.26%)], sore throat [445 (15.70%)], and myalgia [342 (12.06%)]. One thousand and twelve (35.7%) had 1 or more coexisting medical conditions. In multiple logistic regression analysis, risk factors associated with the death included older age [OR (Odds Ratio) = 1.03; 95% CI; 1.02-1.04], blood oxygen level (SPO2 < 93%) (OR = 2.44; 95% CI; 1.79-3.31), comorbidities (OR = 2.15; 95% CI; 1.62-2.84), respiratory distress (OR = 1.74; 95% CI; 1.28-2.37), and headache (OR = 0.44 95% CI; 0.21-0.92). CONCLUSIONS: The 2019-nCoV infection caused collections of severe respiratory illness and was associated to a high ratio of hospitalization in ICU and high mortality. Older age and comorbidities were associated with more risk of death among patients with 2019-nCoV.

A case series of pediatric COVID-19 with complicated symptoms in Iran.

People in different age groups are susceptible to SARS-CoV-2 infection as a newly emerging virus. However, the clinical course, symptoms and disease outcome vary from case to case. Although COVID-19 is usually milder in children than adults, some studies reported nonspecific symptoms. Here, we report eight pediatric cases of COVID-19 admitted in the Taleghani Children Hospital in Gorgan city, north of Iran, with complicated symptoms. The current case series poses several challenges to the pediatricians regarding the pediatric cases of COVID-19. As most literature relating to adults are not always transferable to children, clinicians should be warned about such presentations among children with COVID-19.

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.

Association between blood groups and COVID-19 outcome in Iranian patients.

Aim: Many factors have been speculated to explain the COVID-19 complex clinical phenotype. Due to the inconsistent data published on blood groups and COVID-19, we conducted a study on Iranian patients to further assess this association. Materials & methods: This retrospective study was conducted on data collected from confirmed COVID-19 hospitalized patients during March and December 2020 in a referral hospital for COVID-19, 5 Azar Hospital, Gorgan, north of Iran. A total of 1554 confirmed COVID-19 cases were enrolled in the study with blood group (ABO and Rh), demographic, and clinical data available. Results: Of 1554 patients, 1267 and 287 cases had recovered and deceased (due to COVID-19) outcomes, respectively. Most of the cases had O+ (29.6%), the least number had AB- (0.5%), and most of the deceased cases had O+ blood types (31.4%). Logistic regression analysis revealed that groups A- and B- had higher and groups B+, AB+, O+ and O- had lower odds of death than the A+ group. Conclusion: This study indicates that blood types may be related to the clinical outcome of COVID-19. Further studies with a large cohort for multiple people are required to validate this association.

Case Report: Detection of SARS-CoV-2 From Cerebrospinal Fluid in a 34-Month-Old Child With Encephalitis.

Novel coronavirus (severe acute respiratory syndrome-coronavirus-2: SARS-CoV-2), which arose from Wuhan, China, has rapidly spread to other countries and developed into a pandemic. Although the respiratory manifestations of SARS-CoV-2 are well-documented, there is a considerable challenge regarding the direct and/or indirect infection in other organs. Several preliminary reports confirmed neurological manifestations in the SARS-CoV-2-infected patients. Here, we report the detection of SARS-CoV-2 from the nasopharyngeal swab and cerebrospinal fluid (CSF) in a 34-month-old child with encephalitis. This finding expands the spectrum of the neurological manifestations associated with SARS-CoV-2 infection.

Hyperglycemia results in decreased immune cell infiltration and increased viral load in the lung in a mouse model of RSV infection.

Respiratory Syncytial virus (RSV) infection is a feared disease in vulnerable populations with impaired immune responses. There is currently no vaccine against RSV and young children along with elderly people are at increased risk of severe or sometimes life-threatening RSV infection. Hyperglycemia with immunomodulatory patterns can impact on infectious disease outcomes and immune system responses in diabetic patients. Even though research continues to uncover the complex mechanisms underlying RSV immunopathogenesis and diabetes mellitus disease separately, limited information is available about interaction between these two phenomena. Here, we evaluated the influence of hyperglycemia as the hallmark of diabetes mellitus disease on the pathogenesis and immunopathogenesis of RSV in a mouse model. In this experiment, hyperglycemia was induced by intraperitoneal injection of Streptozotocin (STZ), and after diabetes confirmation, mice were infected with RSV-A2, and the immune responses were followed for 5 days until the mice were sacrificed. Analyses on airway immune cell influx, T-Lymphocyte subtypes, cytokines secretion, lung histopathology, and viral load were conducted. Our results showed that hyperglycemia resulted in reduced lung immune cells infiltration totally and it was associated with decreased pathological damage of the lung. Following RSV infection in hyperglycemic mice, the ratio of CD4/CD8 T-Lymphocytes due to CD8+ depletion, increased. Furthermore, the level of IFN-γ and IL-17A cytokines decreased, whereas IL-10 showed an upward trend and the viral load increased in hyperglycemic mice compared with normoglycemic mice. In conclusion, these findings indicate that hyperglycemia can ameliorate and downregulate RSV-induced inflammatory and antiviral responses, and result in increment of viral load.

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.

COVID-19 in Pediatrics: Demographic, Clinical, Laboratory, and Radiological Characteristics of Infected Patients With SARS-CoV-2.

The COVID-19 disease usually leads to mild infectious disease in children, but some develop serious complications. Here, we describe the characteristics of children with COVID-19 in northern Iran, the Golestan province. Ninety-one confirmed cases were enrolled in the study, aged 0-18 years. Demographic, clinical, comorbidity, laboratory, and radiological data were compared based on the disease severity (admitted to intensive care unit (ICU) or not) and disease outcome (recovered or deceased). Sixteen (17.5%) cases were hospitalized in ICU, and 8/91 (8.8%) deceased. Fever and cough were the most common clinical symptoms. Among all symptoms notified there were no significant differences between severe and milder cases, or between those who deceased and recovered. Failure to thrive (FTT), malignant disease and neurological disease were significantly more prevalent in severe cases as was frequently reported comorbidities. Laterality, ground-glass opacity, and lung consolidation were the most common findings in chest computed tomography. The data confirms that the COVID-19 disease has various presentations in children, and clinical, laboratory, and radiological findings may help predict the development of severe forms of COVID-19 among children.