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Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly contagious virus that uses angiotensin converting enzyme 2 (ACE2), a pivotal member of the renin-angiotensin system (RAS), as its cell-entry receptor. Another member of the RAS, angiotensin II (Ang II), is the major biologically active component in this system. There is growing evidence suggesting that serum miRNAs could serve as prognostic biomarkers for SARS-CoV-2 infection and regulate ACE2 expression. Therefore, the aim of this study is to evaluate the changes in the serum levels of sACE2 and Ang II, as well as the expression level of miR-141-3p and miR-421 in SARS-CoV-2 positive and negative subjects., Methods: In the present study, the serum levels of sACE2 and Ang II were measured in 94 SARS-CoV-2 positive patients and 94 SARS-CoV-2 negative subjects with some symptoms similar to those of SARS-CoV-2 positive patients using the ELISA method. In addition, the expression level of miR-141-3p and miR-421 as ACE2 regulators and biomarkers was evaluated using quantitative real-time PCR (qRT-PCR) method., Results: The mean serum sACE2 concentration in the SARS-CoV-2-positive group was 3.268 ± 0.410 ng/ml, whereas in the SARS-CoV-2 negative group, it was 3.564 ± 0.437 ng/ml. Additionally, the mean serum Ang II level in the SARS-CoV-2 positive and negative groups were 60.67 ± 6.192 ng/L and 67.97 ± 6.837 ng/L, respectively. However, there was no significant difference in the serum levels of sACE2 (P value: 0.516) and Ang II (P value: 0.134) between the SARS-CoV-2 positive and negative groups. Meanwhile, our findings indicated that the expression levels of miR-141-3p and miR-421 in SARS-CoV-2 positive group were significantly lower and higher than SARS-CoV-2 negative group, respectively (P value < 0.001)., Conclusions: Taken together, the results of this study showed that the serum levels of sACE2 and Ang II in SARS-CoV-2 positive and negative subjects were not significantly different, but the expression levels of miR-141-3p and miR-421 were altered in SARS-CoV-2 positive patients which need more investigation to be used as biomarkers for COVID-19 diagnosis., (© 2024. The Author(s).)

Background: This study aims to explore the potential of utilizing the expression levels of cannabinoid receptor 2 (CB2), μ-opioid receptor (MOR), MCP-1, IL-17, IFN-γ, and osteopontin as predictors for the severity of SARS-CoV-2 infection. The overarching goal is to delineate the pathogenic mechanisms associated with SARS-CoV-2., Methods: Using quantitative Real-time PCR, we analyzed the gene expression levels of CB2 and MOR in nasopharynx specimens obtained from patients diagnosed with SARS-CoV-2 infection, with 46 individuals classified as having severe symptoms and 46 as non-severe. Additionally, we measured the circulating levels of MCP-1, IL-17, IFN-γ, and osteopontin using an ELISA assay. We examined the predictive capabilities of these variables and explored their correlations across all patient groups., Results: Our results demonstrated a significant increase in MOR gene expression in the epithelium of patients with severe infection. The expression of CB2 receptor was also elevated in both male and female patients with severe symptoms. Furthermore, we observed concurrent rises in MCP-1, IL-17, IFN-γ, and osteopontin levels in patients, which were linked to disease severity. CB2, MOR, MCP-1, IL-17, IFN-γ, and osteopontin showed strong predictive abilities in distinguishing between patients with varying degrees of SARS-CoV-2 severity. Moreover, we identified a significant correlation between CB2 expression and the levels of MOR, MCP-1, osteopontin, and IFN-γ., Conclusions: These results underline the interconnected nature of molecular mediators in a sequential manner, suggesting that their overexpression may play a role in the development of SARS-CoV-2 infections., (© 2024. The Author(s).)

Background: The role of the lipoxygenase (LOX) and cyclooxygenase (COX) enzymes in maintaining cellular homeostasis and regulating immune responses promoted us in this study to analyze the pattern of changes in 15-lipoxygenase and cyclooxygenase isoforms and their related cytokines in SARS-CoV-2 infection., Methods: 15-LOX-1, 15-LOX-2, COX-1 and COX-2 gene expression levels were determined using qRT-PCR in nasopharynx specimens from patients with severe [N = 40] and non-severe [N = 40] confirmed SARS-CoV-2 infections and healthy controls. Circulating levels of lL-6, lL-10, PGE2, and IFN-γ were measured in patients and healthy controls using ELISA assay. The associations between the measured variables and the patient's clinic-pathological characteristics were assessed for all groups., Results: The expression level of 15-LOX-1 was elevated significantly in male patients with severe infection; although female patients showed a different expression profile. 15-LOX-2 expression level was considerably increased in male patients with severe infection; while changes in its expression remained inconclusive in female patients. The relationship between 15-LOX expression and the male gender was prominent. Both COX isoforms expression showed elevation in male and female patients that were correlated with disease severity. The simultaneous increase in lL-6, PGE2 and IFN-γ levels also decrease in lL-10 in patients with severe infection indicating the possible regulatory network related to the COX and 15-LOX enzymes in the output of the SARS-CoV-2 infection., Conclusion: The results of this study determined the pattern of possible changes in key enzymes of prostaglandin and eicosanoids synthesis pathway and their mediators, which can be helpful in mapping the SARS-CoV-2 pathogenicity and pharmaceutical approaches., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Human orthopneumovirus (HOPV) or respiratory syncytial virus (RSV) is one of the important causes of acute respiratory infections (ARIs) during the cold months of the year worldwide. Many countries have reported an absence of ARIs due to HOPV during the winter of 2020-2021 associated with preventive measures to reduce the spread of SARS-CoV2. However, with the reduction of COVID-19 public health restrictions and the absence of immunity in the community due to the lack of exposure in the previous season, many countries had a delayed HOPV outbreak. Here we reported the impact of COVID-19 on the changing pattern of HOPV infection in Iran., Methods: Throat and nasopharyngeal swab samples were collected from patients (children and adults) with ARIs and sent to the Iran National Influenza Center. After RNA extraction, Real time RT-PCR was performed for HOPV detection., Results: In 260 samples collected from patients with ARIs in three different groups, which included children in March 2021, pilgrims in July 2022, and outpatients during November and December 2022, no HOPV was detected in any group., Conclusions: The lack of HOPV activity in Iran during the winter of 2020-2021 and then the resurgence in spring 2022 and again the absence of activity in summer and autumn 2022 was extraordinary in the HOPV epidemiology, and probably due to the implementation of public health non-pharmaceutical interventions to reduce the spread of SARS-CoV2. Although it is not possible to keep such restrictions, similar methods can be taken to control outbreaks caused by respiratory viruses., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Many evidence suggests that long-lasting infection can develop with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This occurrence has been widely described in immunocompromised individuals. In these patients, ineffective clearance of virus infection provides an opportunity for developing immune escape mutants. This study aimed to characterize SARS-CoV-2 intrahost evolution in five immunocompromised in comparison with five immunocompetent COVID-19 patients during treatment. We performed next-generation sequencing (NGS) on collected two oropharyngeal samples from immunocompromised and immunocompetent COVID-19 patients before and after treatment. In this study, we detected alpha and delta variants of SARS-CoV-2. The most common substitutions in structural proteins in patients with alpha variant were S-ΔY143-144, A570D, D614G and D1118H, and N-R203K and G204R, and in delta variant S-T19R, G142D, E156G, 157-158del, L452R, T478K, D614G, D950N and N-D63G, R203M and D377Y were dominant. The common variations in nonstructural and accessory proteins including nsp3-A488S, P1228L, nsp6-T77A, nsp12-P323L, G671S, nsp13-P77L, NS3-S26L, and NS7a-T120I were detected. Also some infrequent substitutions were seen in immunocompromised and immunocompetent patients. After treatment, nsp12-V166A was emerged as a remdesivir resistance and S-L452M in a patient with common variable immunodeficiency. S-E484Q was detected in a patient with acute lymphoma leukemia. This study showed the possibility of the genetic diversity and development of some new mutations in immunocompromised patients. Therefore, surveillance of these patients to characterize any new variants is necessary., (© 2023 Wiley Periodicals LLC.)

Background: SARS-CoV-2 genomic surveillance is necessary for the detection, monitoring, and evaluation of virus variants, which can have increased transmissibility, disease severity, or other adverse effects. We sequenced 330 SARS-CoV-2 genomes during the sixth wave of the COVID pandemic in Iran and compared them with five previous waves, for identifying SARS-CoV-2 variants, the genomic behavior of the virus, and understanding its characteristics., Methods: After viral RNA extraction from clinical samples collected during the COVID-19 pandemic, next generation sequencing was performed using the Nextseq and Nanopore platforms. The sequencing data were analyzed and compared with reference sequences., Results: In Iran during the first wave, V and L clades were detected. The second wave was recognized by G, GH, and GR clades. Circulating clades during the third wave were GH and GR. In the fourth wave, GRY (alpha variant), GK (delta variant), and one GH clade (beta variant) were detected. All viruses in the fifth wave were in GK clade (delta variant). In the sixth wave, Omicron variant (GRA clade) was circulating., Conclusions: Genome sequencing, a key strategy in genomic surveillance systems, helps to detect and monitor the prevalence of SARS-CoV-2 variants, monitor the viral evolution of SARS-CoV-2, identify new variants for disease prevention, control, and treatment, and also provide information for and conduct public health measures in this area. With this system, Iran could be ready for surveillance of other respiratory virus diseases besides influenza and SARS-CoV-2., Competing Interests: The authors declare no conflicts of interest., (© 2023 The Authors. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.)

Background: Human coronaviruses (HCoVs) 229E, OC43, HKU1, and NL63 are common viruses that continuously circulate in the human population. Previous studies showed the circulation of HCoVs during the cold months in Iran. We studied the circulation of HCoVs during coronavirus disease 2019 (COVID-19) pandemic to find the impact of pandemic on the circulation of these viruses., Methods: As a cross-sectional survey conducted during 2021 to 2022, of all throat swabs sent to Iran National Influenza Center from patients with severe acute respiratory infection, 590 samples were selected to test for HCoVs using one-step real-time RT-PCR., Results: Overall, 28 out of 590 (4.7%) tested samples were found to be positive for at least one HCoVs. HCoV-OC43 was the most common (14/590 or 2.4%), followed by HCoV-HKU1 (12/590 or 2%) and HCoV-229E (4/590 or 0.6%), while HCoV-NL63 was not detected. HCoVs were detected in patients of all ages and throughout the study period with peaks in the cold months of the year., Conclusions: Our multicenter survey provides insight into the low circulation of HCoVs during the COVID-19 pandemic in Iran in 2021/2022. Hygiene habits and social distancing measures might have important role in decreasing of HCoVs transmission. We believe that surveillance studies are needed to track the pattern of HCoVs distributions and detect changes in the epidemiology of such viruses to set out strategies in order to timely control the future outbreaks of HCoVs throughout the nation., Competing Interests: The authors declare no conflicts of interest., (© 2023 The Authors. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.)

SARS-COV-2 is responsible for the current worldwide pandemic, which started on December 2019 in Wuhan, China. On March 2020 World Health Organization announced COVID-19 as the new pandemic. Some SARS-COV-2 variants have increased transmissibility, cause more severe disease (e.g., increased hospitalizations or deaths), are resistant to antibodies produced by the previous infection or vaccination, and there is more difficulty in treatment and diagnosis of them. World Health Organization considered them as SARS-CoV-2 variants of concern. The introductory reproduction rate (R 0 ) is an epidemiologic index of the transmissibility of the virus, defined as the average number of persons infected by the virus after known contact with an infectious person in a susceptible population. An R 0  > 1 means that the virus is spreading exponentially, and R 0  < 1, means that the outbreak is subsiding. In various studies, the estimated R and VOC growth rates were reported to be greater than the ancestral strains. However, it was also a low level of concordance between the estimated Rt of the same variant in different studies. It is because the R of a variant not only dependent on the biological and intrinsic factors of the virus but also several parameters can affect the R0, including the duration of contagiousness and the likelihood of infection per contact. Evaluation of changes in SARS-CoV-2 has shown that the rate of human-to-human transmission of this virus has increased. Like other viruses with non-human sources which succeeded in surviving in the human population, SARS-CoV-2 has gradually adapted to the human population, and its ability to transmit from human to human has increased. Of course, due to the continuous changes in this virus, it is crucial to survey the rate of transmission of the virus over time., (© 2023. The Author(s).)

Acute respiratory infections (ARIs) are one of the leading causes of illness and death among community members worldwide. Viral infections are the most common agents estimated to be involved in these patients. This study aimed to investigate the prevalence of human respiratory syncytial virus (hRSV) and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) among children with ARIs. This study evaluated the presence of SARS-CoV-2 and hRSV in 168 throat and nasopharyngeal swab samples using real-time RT-PCR. All samples were collected from children under 5 years old with ARIs who attended Children's Medical Center, Tehran, Iran, and sent to the Iranian National Influenza Center with appropriate conditions in 2021. Chi-square and Fisher's exact tests were used for comparison of the data of the prevalence of hRSV and SARS-CoV-2 infections among children. Of 168 patients examined, 95 (57%) were male and 73 (43%) female. Out of them, 47 (28%) cases were younger than 1 year old and 121 cases (72%) were 1-5 years old. The most common clinical manifestations of patients were cough (78%), nausea (31%), diarrhea (27%), and fever (18%). Among 168 patients, no hRSV was detected, while the SARS-CoV-2 genome was identified in 16 (9.5%) patients. Among 16 positive cases of SARS-CoV-2, 8 (50%) were under 1 year old and 8 positive cases were 1-5 years old. This study was performed at cold months of the year but due to the coronavirus disease 2019 pandemic and adherence to health protocols, school closures, and virtual classes, no cases of hRSV infections were identified., (© 2022 Wiley Periodicals LLC.)

Purpose: Whole genome sequencing of SARS-CoV2 is important to find useful information about the viral lineages, variants of interests and variants of concern. As there are not enough data about the circulating SARS-CoV2 variants in Iran, we sequenced 54 SARS-CoV2 genomes during the 5 waves of pandemic in Iran., Methods: After viral RNA extraction from clinical samples collected during the COVID-19 pandemic, next generation sequencing was performed using the Nextseq platform. The sequencing data were analyzed and compared with reference sequences., Results: During the 1st wave, V and L clades were detected. The second wave was recognized by G, GH and GR clades. Circulating clades during the 3rd wave were GH and GR. In the fourth wave GRY (alpha variant), GK (delta variant) and one GH clade (beta variant) were detected. All viruses in the fifth wave were in clade GK (delta variant). There were different mutations in all parts of the genomes but Spike-D614G, NSP12-P323L, N-R203K and N-G204R were the most frequent mutants in these studied viruses., Conclusions: These findings display the significance of SARS-CoV2 monitoring to help on time detection of possible variants for pandemic control and vaccination plans., Competing Interests: The authors have declared that no competing interests exist.

The SARS-CoV-2 virus has been rapidly spreading globally since December 2019, triggering a pandemic, soon after its emergence. While Iran was among the first countries confronted with rapid spread of virus in February 2020, no real-time SARS-CoV-2 whole-genome tracking in early phase of outbreak was performed in the country. To address this issue, we provided 50 whole-genome sequences of viral isolates ascertained from different geographical locations in Iran during March-July 2020. The corresponding analysis on origins, transmission dynamics and genetic diversity of SARS-CoV-2 virus, represented at least two introductions of the virus into the country, constructing two major clusters defined as B.4 and B.1*. The first entry of the virus might have occurred around very late 2019/early 2020, as suggested by the time to the most recent common ancestor, followed by a rapid community transmission that led to dominancy of B.4 lineage in early epidemic till the end of June. Gradually, reduction in dominancy of B.4 occurred possibly as a result of other entries of the virus, followed by surge of B.1* lineages, as of mid-May. Remarkably, variation tracking of the virus indicated the increase in frequency of D614G mutation, along with B.1* lineages, which showed continuity till October 2020. The increase in frequency of D614G mutation and B.1* lineages from mid-May onwards predicts a rapid viral transmission that may push the country into a critical health situation followed by a considerable change in composition of viral lineages circulating in the country., (© 2021 Wiley-VCH GmbH.)

Intrauterine viruses can infect the decidua and placenta and cause adverse effects on the fetus during gestation. This review discusses the contribution of various viral infections to miscarriage and the molecular mechanisms by which viruses can cause devastating effects on healthy fetuses and induce miscarriage. Severe acute respiratory syndrome coronavirus 2 as newly emerged coronavirus was considered here, due to the concerns about its role during pregnancy and inducing miscarriage, as well. In this narrative review, an extensive literature search was conducted to find all studies investigating viral infections in miscarriage and their molecular mechanisms published over the past 20 years. The results of various studies investigating the roles of 20 viral infections in miscarriage are presented. Then, the mechanisms of pregnancy loss in viral infections were addressed, including alteration of trophoblast invasion and placental dysfunction, inducing excessive maternal immune response, and inducing apoptosis in the placental tissue. Viruses may cause pregnancy loss through different mechanisms and our knowledge about these mechanisms can be helpful for controlling or preventing viral infections and achieving a successful pregnancy., (© 2021 Japanese Teratology Society.)

Background: In late December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), the causative agent of coronavirus disease 2019 (COVID-19), spread to almost all countries worldwide. The outbreak of this virus has been confirmed on 19th February, 2020, in Iran., Objective: The aim of this study was to investigate the time of viral RNA clearance in swab and serum samples of COVID-19 patients having received different medications. We also evaluated different factors that may affect viral RNA persistence in patients infected by SARS-CoV-2., Methods: In March 2020, twenty-one hospitalized COVID-19 patients participated in this prospective study. All patients received antiviral agents in their routine care. Throat swabs and blood samples were obtained from all patients in different intervals, including day 3 or 5, day 7, day 10, and finally, 14 days after the first positive real-time RT-PCR (rRT-PCT) test., Results: The median time from the symptom onset (SO) to the first negative rRT-PCR results for throat swabs and serum samples of COVID-19 patients was 18 and 14 days, respectively. These times were more significant in patients with lymphopenia, oxygen saturation ≤ 90%, and comorbidity., Conclusion: This preliminary study highlights that SASR-CoV-2 RNA was not detectable in the upper respiratory tract for longer than three weeks. In addition, SARS-CoV-2 may persist for a long period of time in the respiratory than in the serum samples. This study supports the idea that in limited resource settings, the patients should be tested earlier than three weeks for discharge management., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)