Epidemiological determinants for the spread of COVID-19 in Riyadh Province of Saudi Arabia

Background and objectiveCoronavirus Disease 2019 (COVID-19) has affected millions of individuals all over the world. In addition to the patients' compelling indications, various sociodemographic characteristics were identified to influence infection complications. The purpose of this study was to assess the impact of the aforementioned parameters on the dissemination of COVID-19 among residents of Saudi Arabia's Riyadh region.Materials and methodsIn the Saudi Arabian province of Riyadh, a cross-sectional retrospective analysis of COVID-19 incidences, recoveries, and case-fatality ratio (CFR) was undertaken. The study was carried out by gathering daily COVID-19 records from the ministry of health's official websites between October 2020 and September 2021. The influencing factors were obtained from the statistical authority. Using the SPSS IBM 25 software, the data was examined. The association between demographic factors as well as the presence of comorbidity on the COVID-19 outcome was determined using Spearman's correlation and regression tests. P < 0.05 was considered to indicate the significance of the results.ResultsThe data from the study indicated that the highest number of COVID-19 cases were recorded in June 2021, and peak recovery was observed in July 2021. The CFR declined progressively from October 2020 to just over 1, even when the cases peaked. A significant (p < 0.05) correlation between diabetes and COVID-19 incidences was observed. The recovery rate had a significant (p < 0.05) association with the literacy rate and those aged 14–49 years old. Presences of co-morbidities such as Dyslipidemia, hypertension, diabetes, asthma, stroke and heart failure have negatively affected the recovery from COVID-19 in the population. The CFR is significantly (p < 0.05) associated with people over 60, hypertensive patients, and asthma patients. Regression analysis suggested that the risk of complications due to COVID-19 infection is more in males, people above 60 years age and those suffering from co-morbidities.ConclusionsThe findings of the study indicate an association between several of the characteristics studied, such as gender, age, and comorbidity, and the spread of infection, recovery, and mortality. To restrict the spread of COVID-19 and prevent its complications, effective measures are required to control the modifiable risk factors.     

COVID-19 Pandemic: Insights into Interactions between SARS-CoV-2 Infection and MAFLD

COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become an ongoing global health pandemic. Since 2019, the pandemic continues to cast a long shadow on all aspects of our lives, bringing huge health and economic burdens to all societies. With our in-depth understanding of COVID-19, from the initial respiratory tract to the later gastrointestinal tract and cardiovascular systems, the multiorgan involvement of this infectious disease has been discovered. Metabolic dysfunction-associated fatty liver disease (MAFLD), formerly named nonalcoholic fatty liver disease (NAFLD), is a major health issue closely related to metabolic dysfunctions, affecting a quarter of the world''s adult population. The association of COVID-19 with MAFLD has received increasing attention, as MAFLD is a potential risk factor for SARS-CoV-2 infection and severe COVID-19 symptoms. In this review, we provide an update on the interactions between COVID-19 and MAFLD and its underlying mechanisms.     

Chloroplastic and nuclear diversity of wild beets at a large geographical scale: Insights into the evolutionary history of the Beta section

Historical demographic processes and mating systems are believed to be major factors in the shaping of the intraspecies genetic diversity of plants. Among Caryophyllales, the Beta section of the genus Beta, within the Amaranthaceae/Chenopodiaceae alliance, is an interesting study model with species and subspecies (Beta macrocarpa, Beta patula, Beta vulgaris maritima and B.v. adanensis) differing in geographical distribution and mating system. In addition, one of the species, B. macrocarpa, mainly diploid, varies in its level of ploidy with a tetraploid cytotype described in the Canary Islands and in Portugal. In this study, we analyzed the nucleotide diversity of chloroplastic and nuclear sequences on a representative sampling of species and subspecies of the Beta section (except B. patula). Our objectives were (1) to assess their genetic relationships through phylogenetic and multivariate analyses, (2) relate their genetic diversity to their mating system, and (3) reconsider the ploidy status and the origin of the Canarian Beta macrocarpa.     

Uncertainty quantification and sensitivity analysis of COVID-19 exit strategies in an individual-based transmission model

Many countries are currently dealing with the COVID-19 epidemic and are searching for an exit strategy such that life in society can return to normal. To support this search, computational models are used to predict the spread of the virus and to assess the efficacy of policy measures before actual implementation. The model output has to be interpreted carefully though, as computational models are subject to uncertainties. These can stem from, e.g., limited knowledge about input parameters values or from the intrinsic stochastic nature of some computational models. They lead to uncertainties in the model predictions, raising the question what distribution of values the model produces for key indicators of the severity of the epidemic. Here we show how to tackle this question using techniques for uncertainty quantification and sensitivity analysis. We assess the uncertainties and sensitivities of four exit strategies implemented in an agent-based transmission model with geographical stratification. The exit strategies are termed Flattening the Curve, Contact Tracing, Intermittent Lockdown and Phased Opening. We consider two key indicators of the ability of exit strategies to avoid catastrophic health care overload: the maximum number of prevalent cases in intensive care (IC), and the total number of IC patient-days in excess of IC bed capacity. Our results show that uncertainties not directly related to the exit strategies are secondary, although they should still be considered in comprehensive analysis intended to inform policy makers. The sensitivity analysis discloses the crucial role of the intervention uptake by the population and of the capability to trace infected individuals. Finally, we explore the existence of a safe operating space. For Intermittent Lockdown we find only a small region in the model parameter space where the key indicators of the model stay within safe bounds, whereas this region is larger for the other exit strategies.     

中国和伊朗新型冠状病毒肺炎流行现状及比较分析

新型冠状病毒肺炎(Coronavirus disease 2019,COVID-19)已造成全球大流行,比较不同国家流行特征是了解该病流行规律的重要内容。为了推进我国提出的一带一路倡议,防止传染病跨境传播,并探讨COVID-19流行规律和不同国家传染病研究方法,本研究对中国和伊朗COVID-19流行特征和影响因素进行比较分析。根据世界卫生组织、国家卫生健康委员会及新闻媒体等提供的数据和信息,采用描述流行病学方法和Pearson相关进行分析,结果显示,截至2020年7月31日24时,中国累计报告确诊病例88122例,占全球报告0.50%,位居28位;同期伊朗确诊304204例,占全球1.73%,位居全球第9位。2020年4月22日伊朗报告累计确诊病例数首次超过中国,中国宁夏回族自治区、北京市、上海市、甘肃省、广东省分别报告有伊朗输入病例。COVID-19流行水平和严重程度伊朗高于中国:伊朗的发病率为371/10万、中国6.29/10万;伊朗的死亡率为20/10万、中国0.33/10万;伊朗的治愈率为86.63%、中国为92.18%;病死率两国水平接近;伊朗平均每日新增确诊病例数1395例,中国404例。中国疫情出现拐点的时间较伊朗早,每日新增确诊病例首次出现下降用时25d(伊朗42d)、每日新增治愈超过新增确诊用时31d(伊朗49d)。伊朗疫情在5月后出现持续反弹,2020年6月4日确诊病例数达反弹峰值(3574例),超过前期的3186例,且在多数时间新增治愈人数低于新增确诊人数。中国和伊朗每日新增确诊、新增治愈病例数趋势形态不同,中国新增治愈病例数趋势图整体延后新增确诊病例,而伊朗新增治愈与新增确诊病例数几乎同步。相关分析显示武汉每日新增确诊病例数在划分的两个阶段与预防控制措施得分均呈正相关(相关系数分别为0.44、0.53),而与当时武汉的气象因素平均气压(百帕)、平均2min风速(米/秒)、平均气温(℃)、平均相对湿度(百分率)、日照时数(时)无相关性;伊朗在疫情的第一阶段呈正相关,第二阶段为负相关。COVID-19在中国和伊朗的流行存在差异,对不同国家流行情况进行比较研究,有助于加深对COVID-19全球大流行的认识。     

Comparative structural analysis of the Erbin PDZ domain and the first PDZ domain of ZO-1. Insights into determinants of PDZ domain specificity

We report a structural comparison of the first PDZ domain of ZO-1 (ZO1-PDZ1) and the PDZ domain of Erbin (Erbin-PDZ). Although the binding profile of Erbin-PDZ is extremely specific ([D/E][T/S]WV(COOH)), that of ZO1-PDZ1 is similar ([R/K/S/T][T/S][W/Y][V/I/L](COOH)) but broadened by increased promiscuity for three of the last four ligand residues. Consequently, the biological function of ZO-1 is also broadened, as it interacts with both tight and adherens junction proteins, whereas Erbin is restricted to adherens junctions. Structural analyses reveal that the differences in specificity can be accounted for by two key differences in primary sequence. A reduction in the size of the hydrophobic residue at the base of the site(0) pocket enables ZO1-PDZ1 to accommodate larger C-terminal residues. A single additional difference alters the specificity of both site(-1) and site(-3). In ZO1-PDZ1, an Asp residue makes favorable interactions with both Tyr(-1) and Lys/Arg(-3). In contrast, Erbin-PDZ contains an Arg at the equivalent position, and this side chain cannot accommodate either Tyr(-1) or Lys/Arg(-3) but, instead, interacts favorably with Glu/Asp(-3). We propose a model for ligand recognition that accounts for interactions extending across the entire binding site but that highlights several key specificity switches within the PDZ domain fold.     

Rapid sequence change and geographical spread of human parvovirus B19: comparison of B19 virus evolution in acute and persistent infections

Parvovirus B19 is a common human pathogen maintained by horizontal transmission between acutely infected individuals. However, B19 virus can also be detected in tissues throughout the life of the host, although little is understood about the nature of such persistence. In the current study, we created large VP1/2 sequence data sets of plasma- and tissue (autopsy)-derived variants of B19 virus with known sample dates to compare the rates of sequence change in exogenous virus populations with those in persistently infected individuals. By using linear regression and likelihood-based methods (such as the BEAST program), we found that plasma-derived B19 virus showed a substitution rate of 4 x 10(-4) and an unconstrained (synonymous)-substitution rate of 18 x 10(-4) per site per year, several times higher than previously estimated and within the range of values for mammalian RNA viruses. The underlying high mutation frequency implied by these substitution rates may enable rapid adaptive changes that are more commonly ascribed to RNA virus populations. These revised estimates predict that the last common ancestor for currently circulating genotype 1 variants of B19 virus existed around 1956 to 1959, fitting well with previous analyses of the B19 virus "bioportfolio" that support a complete cessation of genotype 2 infections and their replacement by genotype 1 infections in the 1960s. In contrast, the evolution of B19 virus amplified from tissue samples was best modeled by using estimated dates of primary infection rather than sample dates, consistent with slow or absent sequence change during persistence. Determining what epidemiological or biological factors led to such a complete and geographically extensive population replacement over this short period is central to further understanding the nature of parvovirus evolution.     

COVID-19 pandemic and patients with cancer: The protocol of a Clinical Oncology center in Tehran,Iran

AimTo provide recommendations for the management of patients with cancer in the COVID-19 era.BackgroundThe current global pandemic of COVID-19 has severely impacted global healthcare systems. Several groups of people are considered high-risk for SARS-CoV-2 infection, including patients with cancer. Therefore, protocols for the better management of these patients during this viral pandemic are necessary. So far, several protocols have been presented regarding the management of patients with cancer during the COVID-19 pandemic. However, none of them points to a developing country with limited logistics and facilities.MethodsIn this review, we have provided a summary of recommendations on the management of patients with cancer during the COVID-19 pandemic based on our experience in Shohada-e Tajrish Hospital, Iran.ResultsWe recommend that patients with cancer should be managed in an individualized manner during the COVID-19 pandemic.ConclusionsOur recommendation provides a guide for oncology centers of developing countries for better management of cancer.     

Insights into the structural stability of nuclear matrix ribonucleoprotein,LMG160: thermodynamic and spectroscopic analysis

Low-mobility group nonhistone chromatin protein, LMG_160, is a nuclear matrix ribonucleoprotein particle (RNP) which has a RNA molecule with approximately 300 bases. In this study, structural stability of the intact LMG₁₆₀ (I-LMG₁₆₀) was investigated at different ionic strength and in the absence of its RNA moiety (T-LMG₁₆₀) employing spectroscopic and thermodynamic techniques. The UV absorption spectra showed hypochromicity and red shift under increasing ionic strength for both forms of LMG₁₆₀ but in different extents. The fluorescence emission intensity was decreased as ionic strength was increased and the Stern–Volmer quenching constant (K_sv) for T-LMG₁₆₀ was 3.7 times less than for I-LMG₁₆₀. In the absence of sodium chloride, I-LMG₁₆₀ exhibited a very stable structure against the temperature change compared to T-LMG₁₆₀. The thermodynamic parameters showed that the positive values of ΔH_m and ΔS_m increased by increasing ionic strength in both forms of LMG₁₆₀. Removal of the RNA moiety altered secondary structure: as T-LMG₁₆₀ showed more helical content than I-LMG₁₆₀. From the results, it is concluded that I-LMG₁₆₀ is more sensitive to alteration of environment and the RNA has an important role in this RNP conformation. Also, interaction of both I- and T-LMG₁₆₀ with sodium chloride is entropy driven and is usually accompanied by surface hydrophobicity.     

COVID-19 one year later: a retrospect of CRISPR-Cas system in combating COVID-19

Coronavirus disease 2019 (COVID-19), an infectious disease caused by Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has posed a persistent global threat. The transmission of SARS-CoV-2 is wide and swift. Rapid detection of the viral RNA and effective therapy are imperative to prevent the worldwide spread of the new infectious disease. Clustered Regularly-Interspaced Short Palindromic Repeats (CRISPR)- CRISPR-associated protein (Cas) system is an RNA-directed adaptive immune system, and it has been transformed into a gene editing tool. Applications of CRISPR-Cas system involves in many fields, such as human gene therapy, drug discovery and disease diagnosis. Under the background of COVID-19 pandemic, CRISPR-Cas system shows hidden capacity to fight the emergency in many aspects. This review will focus on the role of gene editing in COVID-19 diagnosis and treatment. We will describe the potential use of CRISPR-Cas-based system in combating COVID-19, from diagnosis to treatment. Furthermore, the limitation and perspectives of this novel technology are also evaluated.     

Spatial analysis of vicariance: a method for using direct geographical information in historical biogeography

Based on Hovenkamp’s ideas on historical biogeography, we present a method for analysis of taxon history, spatial analysis of vicariance, which uses observed distributions as data, thus requiring neither predefined areas nor assumptions of hierarchical relations between areas. The method is based on identifying sister nodes with disjunct (allopatric/vicariant) distributions. To do this across the tree, internal nodes are assigned distributions (as the sum of the distributions of the descendant nodes). When distributions are less than ideal, ignoring the distribution of the problematic node(s) when assigning a distribution to their ancestors may allow us to consider additional sister nodes (i.e. those resulting from splits basal to the problematic node) as having disjunct distributions. The optimality criterion seeks to find the best (possibly weighted) compromise between the maximum possible number of disjunct sister nodes and the minimum number of eliminated distributions. The method can also take overlap into account. The methodology presented is implemented in VIP, a computer program available at http://www.zmuc.dk/public/phylogeny/vip . © The Willi Hennig Society 2011.     

Insights into the pathways of spread and potential origins of Dothistroma septosporum in Britain

Dothistroma needle blight (DNB) is a disease caused by two fungi, Dothistroma septosporum and Dothistroma pini, that has resulted in significant damage to pine forests worldwide. Analysis of 1194 British Dothistroma isolates revealed that only D. septosporum occurred in Britain; D. pini was not detected. The genetic diversity, population structure, and reproductive mode of D. septosporum in Britain were investigated using species-specific mating type markers and eleven microsatellite markers, revealing 382 multilocus haplotypes. Comparison of clustering methods (STRUCTURE, BAPS, DAPC) as well as spatial principal component analysis (sPCA) showed some differences between the methods but similar groupings. A clear north-south cline was found with attributes consistent with a native fungus. Other groups were most probably introduced, with one nearly exclusive lodgepole pine group exhibiting links with Canada. Evidence for the movement of specific multilocus haplotypes via nursery stock as well as across borders is provided and the implications discussed.     

COVID-19 in schools: Mitigating classroom clusters in the context of variable transmission

Widespread school closures occurred during the COVID-19 pandemic. Because closures are costly and damaging, many jurisdictions have since reopened schools with control measures in place. Early evidence indicated that schools were low risk and children were unlikely to be very infectious, but it is becoming clear that children and youth can acquire and transmit COVID-19 in school settings and that transmission clusters and outbreaks can be large. We describe the contrasting literature on school transmission, and argue that the apparent discrepancy can be reconciled by heterogeneity, or “overdispersion” in transmission, with many exposures yielding little to no risk of onward transmission, but some unfortunate exposures causing sizeable onward transmission. In addition, respiratory viral loads are as high in children and youth as in adults, pre- and asymptomatic transmission occur, and the possibility of aerosol transmission has been established. We use a stochastic individual-based model to find the implications of these combined observations for cluster sizes and control measures. We consider both individual and environment/activity contributions to the transmission rate, as both are known to contribute to variability in transmission. We find that even small heterogeneities in these contributions result in highly variable transmission cluster sizes in the classroom setting, with clusters ranging from 1 to 20 individuals in a class of 25. None of the mitigation protocols we modeled, initiated by a positive test in a symptomatic individual, are able to prevent large transmission clusters unless the transmission rate is low (in which case large clusters do not occur in any case). Among the measures we modeled, only rapid universal monitoring (for example by regular, onsite, pooled testing) accomplished this prevention. We suggest approaches and the rationale for mitigating these larger clusters, even if they are expected to be rare.     

Insights into structural and regulatory roles of Sec16 in COPII vesicle formation at ER exit sites

COPII-coated buds are formed at endoplasmic reticulum exit sites (ERES) to mediate ER-to-Golgi transport. Sec16 is an essential factor in ERES formation, as well as in COPII-mediated traffic in vivo. Sec16 interacts with multiple COPII proteins, although the functional significance of these interactions remains unknown. Here we present evidence that full-length Sec16 plays an important role in regulating Sar1 GTPase activity at the late steps of COPII vesicle formation. We show that Sec16 interacts with Sec23 and Sar1 through its C-terminal conserved region and hinders the ability of Sec31 to stimulate Sec23 GAP activity toward Sar1. We also find that purified Sec16 alone can self-assemble into homo-oligomeric complexes on a planar lipid membrane. These features ensure prolonged COPII coat association within a preformed Sec16 cluster, which may lead to the formation of ERES. Our results indicate a mechanistic relationship between COPII coat assembly and ERES formation.     

Allopatric speciation in the desert: diversification of cichlids at their geographical and ecological range limit in Iran

Collated electrofishing data from wadeable riffles of boreal rivers in Finland revealed a substantial shift in the fish assemblage composition, accompanied by a decline in total fish density and a reduction in species richness from early summer to late autumn. As the major changes in fish assemblages, the density of cyprinids decreased sharply from June towards autumn, whereas salmonids peaked in September. These shifts were considered to originate mainly from spawning migrations, fish movements to winter refuge habitat and other temperature-related responses of rheophilic versus eurytopic fish species. Temporal change in fish assemblages induced a prominent variation in the monthly fish-based index values used for bioassessment. The proportion of sampled sites classified as high or good in ecological status within the Water Framework Directive (WFD) based on fish increased from 25.9% in July to 68.3% in October. These results, combined with the observed timing of young of the year (0+) fish recruitment to electrofishing catch, suggest that sampling of fish in boreal rivers for WFD monitoring should be restricted to a considerably shorter period than the prevailing practice in order to avoid temporal bias.     

Insights into the structural perturbations of spliced variants of CD44: a modeling and simulation approach

Transient interactions between cancer stem cells and components of the tumor microenvironment initiate various signaling pathways crucial for carcinogenesis. Predominant hyaluronan (HA) receptor, CD44 is structurally and functionally one of the most variable cell surface receptors having the potential to generate a diverse repertory of CD44 isoforms by alternative splicing of variant exons and post-translational modifications. A structurally distinctive variant of CD44, CD44v10, has an inevitable role in malignant progression, invasion, and metastasis. This can be attributed to the binding of HA with CD44v10, which demonstrates a completely different behavioral pattern as compared to the other spliced variants of CD44 molecule. Absence of a comprehensively predicted crystal structure of human CD44s and CD44v10 is an impediment in understanding the resultant structural alterations caused by the binding of HA. Thus, in this study, we aim to predict the CD44s and CD44v10 structures to their closest native confirmation and study the HA binding-induced structural perturbations using homology modeling, molecular docking, and MD simulation approach. The results depicted that modeled 3D structures of CD44s and CD44v10 isoforms were found to be stable throughout MD simulations; however, a substantial decrease was observed in the binding affinity of HA with CD44v10 (?5.355 kcal/mol) as compared to CD44s. Furthermore, loss and gain of several H-bonds and hydrophobic interactions in CD44v10–HA complex during the simulation process not only elucidated the reason for decreased binding affinity for HA but also prompted toward the plausible role of HA-induced structural perturbations in occurrence and progression of carcinogenesis.     

Prevalence and determinants of healthcare avoidance during the COVID-19 pandemic: A population-based cross-sectional study

BackgroundDuring the Coronavirus Disease 2019 (COVID-19) pandemic, the number of consultations and diagnoses in primary care and referrals to specialist care declined substantially compared to prepandemic levels. Beyond deferral of elective non-COVID-19 care by healthcare providers, it is unclear to what extent healthcare avoidance by community-dwelling individuals contributed to this decline in routine healthcare utilisation. Moreover, it is uncertain which specific symptoms were left unheeded by patients and which determinants predispose to healthcare avoidance in the general population. In this cross-sectional study, we assessed prevalence of healthcare avoidance during the pandemic from a patient perspective, including symptoms that were left unheeded, as well as determinants of healthcare avoidance.Methods and findingsOn April 20, 2020, a paper COVID-19 survey addressing healthcare utilisation, socioeconomic factors, mental and physical health, medication use, and COVID-19–specific symptoms was sent out to 8,732 participants from the population-based Rotterdam Study (response rate 73%). All questionnaires were returned before July 10, 2020. By hand, prevalence of healthcare avoidance was subsequently verified through free text analysis of medical records of general practitioners. Odds ratios (ORs) for avoidance were determined using logistic regression models, adjusted for age, sex, and history of chronic diseases. We found that 1,142 of 5,656 included participants (20.2%) reported having avoided healthcare. Of those, 414 participants (36.3%) reported symptoms that potentially warranted urgent evaluation, including limb weakness (13.6%), palpitations (10.8%), and chest pain (10.2%). Determinants related to avoidance were older age (adjusted OR 1.14 [95% confidence interval (CI) 1.08 to 1.21]), female sex (1.58 [1.38 to 1.82]), low educational level (primary education versus higher vocational/university 1.21 [1.01 to 1.46), poor self-appreciated health (per level decrease 2.00 [1.80 to 2.22]), unemployment (versus employed 2.29 [1.54 to 3.39]), smoking (1.34 [1.08 to 1.65]), concern about contracting COVID-19 (per level increase 1.28 [1.19 to 1.38]) and symptoms of depression (per point increase 1.13 [1.11 to 1.14]) and anxiety (per point increase 1.16 [1.14 to 1.18]). Study limitations included uncertainty about (perceived) severity of the reported symptoms and potentially limited generalisability given the ethnically homogeneous study population.ConclusionsIn this population-based cross-sectional study, 1 in 5 individuals avoided healthcare during lockdown in the COVID-19 pandemic, often for potentially urgent symptoms. Healthcare avoidance was strongly associated with female sex, fragile self-appreciated health, and high levels of depression and anxiety. These results emphasise the need for targeted public education urging these vulnerable patients to timely seek medical care for their symptoms to mitigate major health consequences.

Marije J. Splinter and colleagues assess the prevalence of healthcare avoidance during the COIVD-19 pandemic and investigate related determinants