Partial sequence conservation of SARS-CoV-2 NSP-2, NSP-12, and Spike in stool samples from Abadan, Iran.

Since the onset of the coronavirus disease 2019 (COVID-19) pandemic, the clinical manifestations of the virus have undergone many changes. Recently, there have been many reports on gastrointestinal symptoms in COVID-19 patients. This study is aimed to perform a detailed phylogenetic study and assessment of different SNVs in the RNA genome of viruses isolated from fecal samples of patients with COVID-19 who have gastrointestinal symptoms, which can help better understand viral pathogenesis. In the present study, 20 fecal samples were collected by written consent from COVID-19 patients. According to the manufacturer's protocol, virus nucleic acid was extracted from stool samples and the SARS-CoV-2 genome presence in stool samples was confirmed by RT-PCR assay. Three viral genes, S, nsp12, and nsp2, were amplified using the reverse transcription polymerase chain reaction (RT-PCR) method and specific primers. Multiple sequencing alignment (MSA) was performed in the CLC word bench, and a phylogenetic tree was generated by MEGA X based on the neighbor-joining method. Of all cases, 11 (55%) were males. The mean age of the patients was 33.6 years. Diabetes (70%) and blood pressure (55%) were the most prevalent comorbidities. All 20 patients were positive for SARS-CoV-2 infection in respiratory samples. Molecular analysis investigation among 20 stool samples revealed that the SARS-CoV-2 genome was found among 10 stool samples; only three samples were used for sequencing. The polymorphism and phylogenetic analysis in SARS-CoV-2 showed great similarity among all of the evaluated genes with the Wuhan reference sequence and all of the current variants of concern (VOCs). The current study represents a great similarity in polymorphism and phylogenetic analysis of the SARS-CoV-2 isolates with the Wuhan reference sequence and all of the current VOC in the particular evaluated partial sequences of S, nsp12, and nsp2.

Monkeypox virus replication underlying circadian rhythm networks.

The mammalian brain has an endogenous central circadian clock that regulates central and peripheral cellular activities. At the molecular level, this day-night cycle induces the expression of upstream and downstream transcription factors that influence the immune system and the severity of viral infections over time. In addition, there are also circadian effects on host tolerance pathways. This stimulates adaptation to normal changes in environmental conditions and requirements (including light and food). These rhythms influence the pharmacokinetics and efficacy of therapeutic drugs and vaccines. The importance of circadian systems in regulating viral infections and the host response to viruses is currently of great importance for clinical management. With the knowledge gained from the COVID-19 pandemic, it is important to address any outbreak of viral infection that could become endemic and to quickly focus research on any knowledge gaps. For example, responses to booster vaccination COVID-19 may have different time-dependent patterns during circadian cycles. There may be a link between reactivation of latently infected viruses and regulation of circadian rhythms. In addition, mammals may show different seasonal antiviral responses in winter and summer. This article discusses the importance of the host circadian clock during monkeypox infection and immune system interactions.

The role of SARS-CoV-2 accessory proteins in immune evasion.

Many questions on the SARS-CoV-2 pathogenesis remain to answer. The SARS-CoV-2 genome encodes some accessory proteins that are essential for infection. Notably, accessory proteins of SARS-CoV-2 play significant roles in affecting immune escape and viral pathogenesis. Therefore SARS-CoV-2 accessory proteins could be considered putative drug targets. IFN-I and IFN-III responses are the primary mechanisms of innate antiviral immunity in infection clearance. Previous research has shown that SARS-CoV-2 suppresses IFN-ß by infecting host cells via ORF3a, ORF3b, ORF6, ORF7a, ORF7b, ORF8, and ORF9b. Furthermore, ORF3a, ORF7a, and ORF7b have a role in blocking IFNα signaling, and ORF8 represses IFNß signaling. The ORF3a, ORF7a, and ORF7b disrupt the STAT1/2 phosphorylation. ORF3a, ORF6, ORF7a, and ORF7b could prevent the ISRE promoter activity. The main SARS-CoV-2 accessory proteins involved in immune evasion are discussed here for comprehensive learning on viral entry, replication, and transmission in vaccines and antiviral development.

Letter to the Editor Regarding "An Overview on Serology and Molecular Tests for COVID-19: An Important Challenge of the Current Century (doi: 10.22034/iji.2021.88660.1894.)".

Recently in a review article by Mansourabadi et al. published in the Iranian Journal of Immunology, the authors described the serological and molecular tests for COVID-19 (1). The mentioned review considered helicase (Hel) as a structural protein of SARS-CoV-2 (1). However, based on evidence, the genome of novel coronavirus is approximately 30kb in length and encodes only four structural proteins, including spike (S), envelope (E), membrane (M), and nucleoprotein (N) (2, 3), although helicase (NSP13) as a nonstructural protein such as RNA-dependent RNA polymerases (NSP12) encoded by the ORF region and is involved in the replication of the virus (3).In addition, authors reported that hemagglutinin esterase could be used as a favorite target for SARS-CoV-2 Real-time PCR (1); however, scientific evidence shows that SARS-CoV-2 as a betacoronavirus lineage B like SARS-CoV lacks hemagglutinin esterase (4-6); thus this protein cannot be a target for detection of SARS-CoV-2.

Comment on Alfassam et al. Development of a Colorimetric Tool for SARS-CoV-2 and Other Respiratory Viruses Detection Using Sialic Acid Fabricated Gold Nanoparticles. Pharmaceutics 2021, 13, 502.

In a published article in Pharmaceutics, researchers developed a sialic acid (SA) stabilized Au nanoparticle system based on SA's binding ability that exists on the surface of lungs epithelial cells. The authors reported that many respiratory viruses including influenza, Middle-East respiratory syndrome (MERS-CoV), and the current coronavirus (SARS-CoV-2) bind to SA as one of the main binding targets of the surface protein hemagglutinin (HA).

Monkeypox virus neurological manifestations in comparison to other orthopoxviruses.

Viral infectious diseases have various neurological manifestations, whether they are epidemic or pandemic in nature. Nonspecific encephalopathy is the most common central nervous system (CNS) manifestation. The spectrum of nervous evidence varies for viral pathogens. Some infectious viruses, such as the Ebola virus, exhibit direct neurotropism. Others, such as the Rift Valley fever virus, have the potential for neurotropism. Direct neurotropism is unknown in monkeypox virus, SARS-CoV-2, MERS-CoV, and even smallpox. As seen in the COVID-19, there may be evidence of para-infectious neurological syndrome. There have only been a few reports of neurological diseases caused by monkeypox infection. Future efforts to prevent the spread of infectious disease surges can reduce mortality complications, the therapeutic burden on the health-care system, and prevent further spread. This study describes the clinical and neurological complications of monkeypox infection, particularly encephalitis, as well as the laboratory diagnosis of these cases.

Ribosome Profiling: A Useful Approach to Discover Hidden Corners of SARS-CoV-2.

Following SARS-CoV-2 China epidemic in the December 2019, researches have attended to the genome of novel coronavirus. Hidden corners of SARS-CoV-2, maybe a shiny way to discover its pathogenicity and virulence. To design therapeutic agents, it is critical to map the complete repertoire of viral-translated proteins. Ribosome profiling is considered as a snapshot of all active ribosomes in a cell at a specific time point.

Worldwide prevalence of fungal coinfections among COVID-19 patients: a comprehensive systematic review and meta-analysis.

Microbial coinfections can increase the morbidity and mortality rates of viral respiratory diseases. Therefore, this study aimed to determine the pooled prevalence of fungal coinfections in coronavirus disease 2019 (COVID-19) patients. Web of Science, Medline, Scopus, and Embase were searched without language restrictions to identify the related research on COVID-19 patients with fungal coinfections from December 1, 2019, to December 30, 2020. A random-effects model was used for analysis. The sample size included 2,246 patients from 8 studies. The pooled prevalence of fungal coinfections was 12.60%. The frequency of fungal subtype coinfections was 3.71% for Aspergillus, 2.39% for Candida, and 0.39% for other. The World Health Organization's Regional Office for Europe and Regional Office for Southeast Asia had the highest (23.28%) and lowest (4.53%) estimated prevalence of fungal coinfection, respectively. Our findings showed a high prevalence of fungal coinfections in COVID-19 cases, which is a likely contributor to mortality in COVID-19 patients. Early identification of fungal pathogens in the laboratory for COVID-19 patients can lead to timely treatment and prevention of further damage by this hidden infection.

Pooled Prevalence Estimate of Ocular Manifestations in COVID-19 Patients: A Systematic Review and Meta-Analysis.

Background: There are reports of ocular tropism due to respiratory viruses such as severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). Various studies have shown ocular manifestation in coronavirus disease-2019 (COVID-19) patients. We aimed to identify ophthalmic manifestations in COVID-19 patients and establish an association between ocular symptoms and SARS-CoV-2 infection. Methods: A systematic search of Medline, Scopus, Web of Science, Embase, and Cochrane Library was conducted for publications from December 2019 to April 2021. The search included MeSH terms such as SARS-CoV-2 and ocular manifestations. The pooled prevalence estimate (PPE) with 95% confidence interval (CI) was calculated using binomial distribution and random effects. The meta-regression method was used to examine factors affecting heterogeneity between studies. Results: Of the 412 retrieved articles, 23 studies with a total of 3,650 COVID-19 patients were analyzed. The PPE for any ocular manifestations was 23.77% (95% CI: 15.73-31.81). The most prevalent symptom was dry eyes with a PPE of 13.66% (95% CI: 5.01-25.51). The PPE with 95% CI for conjunctival hyperemia, conjunctival congestion/conjunctivitis, and ocular pain was 13.41% (4.65-25.51), 9.14% (6.13-12.15), and 10.34% (4.90-15.78), respectively. Only two studies reported ocular discomfort and diplopia. The results of meta-regression analysis showed that age and sample size had no significant effect on the prevalence of any ocular manifestations. There was no significant publication bias in our meta-analysis. Conclusion: There is a high prevalence of ocular manifestations in COVID-19 patients. The most common symptoms are dry eyes, conjunctival hyperemia, conjunctival congestion/conjunctivitis, ocular pain, irritation/itching/burning sensation, and foreign body sensation.

CRISPR-Cas System: A Promising Diagnostic Tool for Covid-19.

More than a year has passed since the beginning of the 2019 novel coronavirus diseases (COVID-19) pandemic which has created massive problems globally affecting all aspects of people's life. Due to the emergence of new strains of the SARS-CoV-2, pandemic risk still remains, despite the start of vaccination. Therefore, rapid diagnostic tests are essential to control infection, improve clinical care and stop the spread of the disease. Recently CRISPR-based diagnostic tools have facilitated rapid diagnostic. Here, we review the diagnostic applications of CRISPR-Cas system in COVID-19.

Target genes used for biosensor development in COVID-19 diagnosis.

In a published review entitled "COVID-19 diagnosis -A review of current methods", the authors considered hemagglutinin esterase as one of the structural proteins of SARS-CoV-2 and also they did not represent ORF3b, ORF9b, and ORF9c in SARS-CoV-2 genome structure. However, according to the scientific evidence, among coronaviruses only some betacoronaviruses (Embecovirus subgenera) contain HE, and the genome of most of the coronaviruses such as SARS-CoV-2, SARS-CoV, and MERS-CoV lack the HE gene. In addition, the genome of SARS-CoV-2 contains several accessory proteins ORFs including ORF3a, ORF3b, ORF6, ORF7a, ORF7b, ORF8, ORF9b, ORF9c, and ORF10.

A multicenter retrospective study of clinical features, laboratory characteristics, and outcomes of 166 hospitalized children with coronavirus disease 2019 (COVID-19): A preliminary report from Iranian Network for Research in Viral Diseases (INRVD).

BACKGROUND: The objectives of this study were to analyze the clinical features and laboratory profiles and risk factors associated with critical illness of children with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: One hundred and sixty-six coronavirus disease 2019 (COVID-19) Iranian pediatric patients were recruited through a collaborative research network between March and May 2020. Demographics, clinical, laboratory, and radiological results were obtained from patient files. RESULTS: Of 166 patients, 102 (61%) and 64 (39%) were males and females, respectively. Ninety-six (57.8%) and 70 (42.2%), had moderate and severe conditions, respectively. Thirty (18%) of patients died. The common symptoms were fever (73%), cough (54%), and shortness of breath, headache decrease in neutrophil and platelet counts; increase values in lactate dehydrogenase, decrease in the blood pH and HCO3 were significantly associated with the disease severity. 54% and 56% of patients showed abnormal radiographic appearance in Chest X-ray and in chest computed tomography scan, respectively. Sixty-one (36.7%) of patients were referred to intensive care unit (ICU). The coexistence of comorbidity was the main factor associated with ICU admission, shock, arrhythmia, acute kidney injury, acute respiratory distress syndrome, acute cardiac injury, and death. CONCLUSIONS: We describe a higher than previously recognized rate of COVID-19 mortality in Iranian pediatric patients. Epidemiological factors, such as the relatively high case fatality rate in the country and the presence of underlying diseases were the main factors for the high death rate.

Worldwide prevalence of microbial agents' coinfection among COVID-19 patients: A comprehensive updated systematic review and meta-analysis.

BACKGROUND: To provide information about pathogens' coinfection prevalence with SARS-CoV-2 could be a real help to save patients' lives. This study aims to evaluate the pathogens' coinfection prevalence among COVID-19 patients. METHOD: In order to find all of the relevant articles, we used systematic search approach. Research-based databases including PubMed, Web of Science, Embase, and Scopus, without language restrictions, were searched to identify the relevant bacterial, fungal, and viral coinfections among COVID-19 cases from December 1, 2019, to August 23, 2021. In order to dig deeper, other scientific repositories such as Medrxiv were probed. RESULTS: A total of 13,023 studies were found through systematic search. After thorough analysis, only 64 studies with 61,547 patients were included in the study. The most common causative agents of coinfection among COVID-19 patients were bacteria (pooled prevalence: 20.97%; 95% CI: 15.95-26.46; I2 : 99.9%) and less frequent were virus coinfections (pooled prevalence: 12.58%; 95% CI: 7.31-18.96; I2 : 98.7%). The pooled prevalence of fungal coinfections was also 12.60% (95% CI: 7.84-17.36; I2 : 98.3%). Meta-regression analysis showed that the age sample size and WHO geographic region did not influenced heterogeneity. CONCLUSION: We identified a high prevalence of pathogenic microorganism coinfection among COVID-19 patients. Because of this rate of coinfection empirical use of antibacterial, antifungal, and antiviral treatment are advisable specifically at the early stage of COVID-19 infection. We also suggest running simultaneously diagnostic tests to identify other microbiological agents' coinfection with SARS-CoV-2.

The role of lipids in the pathophysiology of coronavirus infections.

Coronaviruses, which have been known to cause diseases in animals since the 1930s, utilize cellular components during their replication cycle. Lipids play important roles in viral infection, as coronaviruses target cellular lipids and lipid metabolism to modify their host cells to become an optimal environment for viral replication. Therefore, lipids can be considered as potential targets for the development of antiviral agents. This review provides an overview of the roles of cellular lipids in different stages of the life cycle of coronaviruses.

Severe acute respiratory syndrome coronavirus 2 and respiratory syncytial virus coinfection in children.

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has infected many people around the world. Children are considered an important target group for SARS-CoV-2, as well as other viral infections such as respiratory syncytial virus infection. Both SARS-CoV-2 and respiratory syncytial virus can affect the respiratory tract. Coinfection of SARS-CoV-2 and respiratory syncytial virus can pose significant challenges in terms of diagnosis and treatment in children. This review compares the symptoms, diagnostic methods, and treatment of COVID-19 and respiratory syncytial virus infection in children.