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Cerebral venous thrombosis (CVT) is a form of cerebrovascular disorders that is difficult to recognize, it is potentially a life threatening condition and requires timely anticoagulant therapy. In the era of the COVID-19 pandemic, there is a steady increase in CVT (4.2% vs. 0.5-1%). At the same time, mortality in patients with CVT on the background of COVID-19 significantly exceeds the mortality in patients with CVT without COVID-19 (45.5% vs. 15%). Objective(s): to study the clinical course of CVT, to determine the diagnostic value of radiological methods and the significance of genetic risk factors for thrombosis in the development of CVT in young and middle-aged patients against the background of COVID-19. Material and methods. Seven patients were examined: six women (five of them of reproductive age) and one man, aged 26 to 57 years (mean age 37 years). The main clinical and neurological manifestations of CVT, the results of laboratory examination, neuroimaging, and the data of molecular genetic analysis of risk factors for thrombosis were analyzed. Results. The course of COVID-19 was severe in one case, and moderate in the rest of cases. The interval between the onset of COVID-19 symptoms and the development of CVT ranged from 7 to 25 days. In three cases CVT had an acute course and was accompanied by the development of a stroke (in two cases, hemorrhagic stroke was noted, in one case, multifocal ischemic stroke), in other cases, a subacute course of CVT was noted. Genetic risk factors for thrombosis were identified in all patients. Conclusion. The diagnosis of CVT in the era of the COVID-19 pandemic is particularly difficult, since the most common symptom of CVT - headache (90%) - can be regarded as a manifestation of COVID-19. At the same time, timely diagnosis of CVT and immediate initiation of anticoagulant therapy are associated with a relatively favorable prognosis.Copyright © 2023 Ima-Press Publishing House. All rights reserved.
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Background/Objectives: We previously demonstrated that carrying a single pathogenic CFTR allele increases the risk for COVID-19 severity and mortality rate. We now aim to clarify the role of several uncharacterized rare alleles, including complex (cis) alleles, and in trans combinations. Method(s): LASSO logistic regression was used for the association of sets of variants, stratified by MAF, with severity. Immortalized cystic fibrosis bronchial epithelial cell lines and Fischer Rat Thyroid cells were transfected by plasmid carrying specific CFTR mutations. YFP-based assays were used to measure CFTR activity. Result(s): Here we functionally demonstrate that the rare (MAF=0.007) complex G576V/R668C allelemitigates the disease by a gain of function mechanism. Several novel CFTR ultra-rare (MAF <0.001) alleles were proved to have a reduced function;they are associated with disease severity either alone (single or complex alleles) or with another hypomorphic allele in the second chromosome, with a global reduction of CFTR activity between 40 to 72%. Conclusion(s): CFTR is a bidirectional modulator of COVID-19 outcome. At-risk subjects do not have open cystic fibrosis before viral infection and therefore are not easily recognisable in the general population unless a genetic analysis is performed. As the CFTR activity is partially retained, CFTR potentiator drugs could be an option as add-on therapy for at-risk patients.
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Androgen insensitivity syndrome has a wide spectrum of presentations. It results from a mutation in androgen receptor (AR) gene. It ranges from mild androgen insensitivity syndrome (MAIS) which is the mildest form to complete androgen insensitivity syndrome (CAIS). In case of MAIS, the abnormality that can be observed appears to be male infertility and sexual difficulties including premature ejaculation and erectile dysfunction. In this case report, we discuss a case of MAIS in a 37-year-old male who presented with infertility, premature ejaculation, and secondary erectile dysfunction.Copyright © 2023, Ibn Sina Trust. All rights reserved.
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The recent COVID-19 pandemic has once again caught the attention of people on the probable zoonotic transmission from animals to humans, but the role of companion animals in the coronavirus (CoV) epidemiology still remains unknown. The present study was aimed to investigate epidemiology and molecular characterizations of CoVs from companion animals in Chengdu city, Southwest China. 523 clinical samples from 393 animals were collected from one veterinary hospital between 2020 and 2021, and the presence of CoVs was detected by end-point PCR using pan-CoV assay targeting the RdRp gene. Partial and complete S genes were sequenced for further genotyping and genetic diversity analysis. A total of 162 (31.0%, 162/523) samples and 146 (37.2%, 146/393) animals were tested positive for CoVs. The positive rate in rectal swabs was higher than that in eye/nose/mouth swabs and ascitic fluid but was not statistically different between clinically healthy and diseased ones. Genotyping identified twenty-two feline enteric coronavirus (FCoV) I, four canine enteric coronavirus (CECoV) I, fourteen CECoV IIa, and one CECoV IIb, respectively. Eight complete S genes, including one canine respiratory coronavirus (CRCoV) strain, were successfully obtained. FCoV strains (F21071412 and F21061627) were more closely related to CECoV strains than CRCoV, and C21041821-2 showed potential recombination event. In addition, furin cleavage site between S1 and S2 was identified in two strains. The study supplemented epidemiological information and natural gene pool of CoVs from companion animals. Further understanding of other functional units of CoVs is needed, so as to contribute to the prevention and control of emerging infectious diseases.
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Objectives: to determine the clinical and genetic determinants of the severe course of COVID-19 in pregnant women in order to identify a risk group and search for therapeutic targets. Materials and methods. 21 patients (group 1) with a severe course of COVID-19 who required intensive care in the Anesthesiology and Intensive Care Unit (AICU) and 126 pregnant women with moderate severity treated in the Infectious-Obstetrics Unit (IOCU) were examined (group 2). Genomic DNA for molecular genetic analysis of gene variants ACE (I/D, rs 4340), PGR (Alu insertion), ESR1 (A351G, rs 9340799), PON1 (C108T, rs 705379) was isolated from the peripheral blood of patients using a commercial Quick-DNA Miniprep Plus Kit (Zymo Research, USA). Variants of ACE and PGR genes were determined using allele-specific polymerase chain reaction;polymerase chain reaction followed by restriction analysis was used to determine ESR1 and PON1 gene variants. Results. Severe course of COVID-19 is observed in 18.2% of pregnant women, critical condition in 7.5%. A third of AICU patients are over 35 years old. Somatic anamnesis was complicated in 23.8% of patients;thyroid gland pathology (14.3%) and varicose disease (19.0%) prevailed. A significant factor in the severe course of COVID-19 is obesity of the III-IV degree in 28.5% cases. The severe course of the disease was associated with complications of pregnancy (oligohydramnios - 52.4%, ahydramnios - 14.3%, fetal growth retardation syndrome - 33.3%, circulatory disorders - 57.1%, fetal distress - 47.6%, preeclampsia - 14.3%), labor (caesarean section - 57.1%, premature birth - 28.6%), disorders of newborns state (asphyxia - 35.6%). These patients are characterized by anemia (58.7%), thrombocytopenia (23.8%), leukocytosis (33.3%), lymphopenia (90.5%), a shift of the leukocyte formula to the left (an increase of rod-nuclear leukocytes by 85.7%). There were significantly increased levels of transaminases: alanine aminotransferase in 47.6%, aspartate aminotransferase in 76.2%. Prothrombotic changes are indicated by a decrease in prothrombin time and activated partial thromboplastin time in 66.7%, which is confirmed by an increase in D-dimer in 85.7% of patients up to the maximum 15,000 ng/ml in 9.5% of women. An increase in inflammation markers (C-reactive protein and interleukin-6 in all AICU patients, procalcitonin in 66.7%) is a reflection of the destructive effect of inflammatory processes. The genetic determinants of the severe course of COVID-19 in pregnant women can be the ID genotype of the ACE I/D rs4340 polymorphism (81.0%), the T2/T2 PROGINS genotype (19.0%), the ESR1 A351G rs9340799 GG genotype (28.5%). Conclusions. The use of separate clinical, laboratory and genetic indicators in pregnant women with COVID-19 will contribute to the selection of the risk group of a coronavirus severe course and the determination of targets of therapeutic impact.Copyright © 2022 Trylyst. All rights reserved.
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The root of Isatis tinctoria L. is highly appreciated as a Traditional Chinese herbal medicine for the prevention and adjuvant treatment of respiratory diseases caused by coronaviruses viruses such as SARS and COVID-19. I. tinctoria hairy root cultures (ITHRCs) provide a better alternative to field cultivation for the production of antiviral flavonoids. For the first time, ITHRCs were exposed to different colors of LED lights i.e., red, green, blue, red/green/blue (1/1/1, RGB), and white, in an attempt to promote the root growth and enhance the production of bioactive flavonoids. Results revealed that the biomass productivity (7.15 ± 0.63 g/L) in ITHRCs with an initial inoculum size of 0.2% cultured for 50 days under blue light increased by 1.86-fold relative to that under dark (control), and yields of rutin (320.49 ± 27.56 μg/g DW), quercetin (388.75 ± 9.17 μg/g DW), kaempferol (787.90 ± 83.43 μg/g DW), and isorhamnetin (269.11 ± 20.08 μg/g DW) increased by 4.15-fold, 9.31-fold, 9.09-fold, and 2.88-fold as compared with control, respectively. Interestingly, the emergence of adventitious buds was noticed in ITHRCs under all light treatments. Additionally, the enhanced densities of chloroplasts and root hairs were found in blue-light grown ITHRCs as against control, which might account for the elevated biomass productivity. Moreover, blue light induced oxidative stress in ITHRCs in terms of the overproduction of oxidation products and the enhancement of antioxidant enzyme activity. Furthermore, blue light significantly activated photoreceptor (CRY1) and key regulator of light signaling (HY5), thus leading to the up-regulated expression of MYB4 and structural genes (such as CHS and FLS) responsible for flavonoid biosynthesis. And, the transcriptional activation of CUC1 was likely related to the formation of adventitious buds in ITHRCs. Overall, the simple supplementation of blue LED light makes ITHRCs more attractive as plant factories for obtaining higher productivity of biomass and medicinally important flavonoids. © 2023 Elsevier B.V.
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Spitzoid melanoma is very rare tumour in the pediatric population, with clinical and non-uniform behaviour, different from adult melanoma [1]. It can be difficult to differentiate an atypical Spitz nevus from a Spitzoid melanoma, resulting in diagnostic problems. In addition, in our clinical case, the COVID-19pandemiccaused significant delays both in the diagnosis and in the surgical treatment of our patient. We present the clinical case of a 4-year-old child suffering from a localized polypoid cutaneous neoformation on the dorsum of the left hand, which started immediately before the lockdown and steadily increased during the COVID-19 pandemic. After a general clinical framing, the child underwent an excisional biopsy at our Department of Plastic and Reconstructive Surgery, at the Policlinico of Foggia. Subsequently, two independent anatomic pathology groups examined the specimen. Definitive diagnosis was made only after careful genetic analysis in combination with supporting histological and immunohistochemical examinations. This clinical case shows how during the pandemic we have been facing advanced forms of tumours, compared to the previous period and highlight show an interdisciplinary and multicenter collaboration allowed a quick diagnosis of certainty, demonstrating the utility of molecular pathology as a fundamental aid in clinical/surgical practice. © 2022 The Authors
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Case Report: Atypical Hemolytic Uremic Syndrome (atypical HUS) is a rare and severe form of thrombotic microangiopathy (TMA) characterized by thrombocytopenia, intravascular hemolysis, and acute kidney injury with an incidence of 1 per million.1 Dysregulation and overactivation of the complement alternative pathway due to genetic mutations have been detected in 40-60% of patients with sporadic or familial atypical HUS.2,4 Triggers include viral illness, pregnancy, malignancy, sepsis, or sporadically with no known inciting event.1 Atypical HUS is a severe disease with a 2-10% risk of mortality, 33% risk of end-stage renal failure, and 50% chance of relapse.5 A 24-year-old female with prior history of atypical HUS at the age of 16 (with response to plasmapheresis) presented to the ER with a 5-day history of fever, chills, sore throat, nausea, vomiting, and dark urine. She tested positive for COVID-19. The exam revealed scleral icterus and scattered petechiae. Labs demonstrated nadir hemoglobin (Hgb) of 9.2 g/dL, platelet count of 52 000k/uL, haptoglobin < 30 mg/dL, peak LDH 1128U/L and creatinine 4.62 mg/dL. Urinalysis is consistent with hemoglobinuria. Schistocytes were noted on the peripheral smear. Rapid streptococcal antigen test and C3, C4, and IgA levels were unremarkable. Chest X-Ray, X-ray KUB, and ultrasound abdomen were unremarkable. The pregnancy test was negative. ADAMTS13 was >100%. Genetic analysis after the initial episode at age 16 revealed autosomal recessive inheritance c.193A > c gene mutations in C3. The patient received IV fluids, ceftriaxone for cystitis, and two units of Fresh Frozen Plasma. She initiated treatment with eculizumab. She also received the MENVEO and meningitis B vaccine per protocol due to the risk of meningitis from terminal complement deficiencies. After 4 infusions of eculizumab, patient's labs improved to platelet count of 307 000 k/uL, Hgb 12.2 g/ dL (nadir 9.2 g/dL), haptoglobin 78 mg/dL normalization of LDH and improved creatinine. Atypical HUS is a rare form of TMAwith mutations in C3 noted in 5% of cases. Complement cascade dysfunction leads to endothelial deposits and microvasculature damage. The resulting prothrombotic state causes obstructive microvascular thrombi predominantly affecting the kidneys but can cause multiorgan dysfunction. The SARS-CoV-2 virus may precipitate atypical HUS relapse due to endothelial damage and complement activation further intensified in patients with existing complement aberrations. Plasma exchange remains a standard of care for atypical HUS, as it effectively removes the antibodies and other proteins. Eculizumab a humanized monoclonal IgG antibody binds to complement proteins, preventing cleavage into C5a and C5b blocking C5b-9(MAC) activation. In patients with CFH, CFI, C3, and CFB mutations, eculizumab is the preferred intervention. Copyright © 2023 Southern Society for Clinical Investigation.
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Background. SARS-CoV-2 E gene PCRs have been widely used as the first-line assay with a higher sensitivity than those targeting N or RdRp gene. Given the currently available primers and probes were designed at the onset of the pandemic, it is unknown whether the SARS-CoV-2 VOCs have accumulated significant mutations that may affect E gene PCRs. In this study we aim to perform a comprehensive genetic analysis of SARS-CoV-2 E gene sequences to evaluate the impact of the emerging VOCs on E gene PCR performance. Methods. 600 whole-genome sequences of 7 species of human coronaviruses (HCoVs) were retrieved from GenBank and GISAID, including Sarbecoviruses (SARS-CoV-2 variants B1.1.7, B1.351, P.1, B.1.617.2 and B.1.1.529, and SARS-CoV), Embecovirus (OC43, HKU1), Merbecovirus (MERS) and Alphacoronaviruses (229E, NL63). The E gene sequences were retrieved from fulllength genomes of corresponding viruses and aligned by ClustalW multiple alignment. Phylogenetic, conservation and mutation analyses analysis of the enrolled sequences was performed. Results. E gene-based phylogenetic analysis yielded HCoVs typing results consistent with whole genome typing, suggesting E gene is a reliable locus for phylogenetic analysis and typing of HCoVs. Four pan-Sarbecovirus conserved E gene regions were identified with 100% conserved nucleotide similarity among SARS-CoV-2 and its VOCs, as well as SARS-CoV. These regions have appropriate G/C content which may be suitable for primer/probe design for E gene-based pan-Sarbecovirus screening assay. No significant E mutations were found in 137 retrieved SARS-CoV-2 and its VOCs. Interestingly, two novel variations, C26299U and T26354A, were identified in two of our SARS-CoV-2 strains. The latter variation occurred at the 3' end of the target region of the widely used Charite/Berlin (WHO) probe. This variant may lead to a potential failure of the first-line E gene PCR. Conclusion. Our data shed light on the genetic diversity and conservation of E gene of SARS-CoV-2 and may be beneficial for future primer/probe design for novel first-line assay or SARS-CoV-2-specific E gene PCR. SARS-CoV-2 VOCs have not accumulated significant mutations in E gene so far. The impact of novel E gene variations C26299U and T26354A on molecular diagnostic testing warrants further investigation.
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Background: to date, more than 243 million COVID-19 cases have been diagnosed globally, with 4.94 million deaths, 489.000 new cases and 8.474 deaths per day. In Italy there are currently 4.73 million cases and 132.000 deaths. It is well known that the entry of the SARS- CoV-2 virus into cells is mediated by the binding between the virus Spike-glycoprotein (S) and the membrane ACE2-receptor (ACE2-R). When SARS-CoV-2 binds to ACE2-R, with subsequent membrane fusion and virus entry into the cell, a down-regulation of these receptors occurs. ACE2 -R downregulation plays a crucial role in the pulmonary and systemic inflammatory response. A serious clinical course appears to be associated with some factors such as age, previous pathologies and comorbidities. However, also a dysregulation of the RAA system linked to a different expression of ACE-2 R and TMPRSS2 gene polymorphisms and different serum levels of soluble ACE2 (sACE2), could be associated with abnormal inflammatory and immune response to SARS-CoV-2 infection. Aim of the Study: we aimed to verify whether there is an association between the clinical course of COVID-19 patients (pts) and the presence of more frequent ACE2 and TMPRSS2 single-nucleotide polymorphisms (SNPs) and if sACE2 levels are related to specific ACE2 and TMPRSS2 polymorphic variants. Method(s): we consecutively enrolled subjects with previous documented SARS-CoV-2 infection and divided our sample into three groups: pts with asymptomatic course;pts with symptomatic course but without the need for hospitalization for COVID-19;pts with severe symptomatic course requiring hospitalization in intensive care unit. Data about age, clinical course, comorbidities, and therapies were collected. Blood samples were taken for the genetic analysis of the most frequent SNPs of the ACE2-R and TMPRSS2 detected in Italian population, in particular genotypic variants TTand CC of ACE2 SNPs 1 and 5 (rate of 5% and 14% respectively) and genotypic variants TTand CC of TMPRSS2 SNPs 2 and 3 (rate of 50% and 30% respective). Result(s): among 178 pts enrolled up to March 2022, we have so far analyzed the genetic polymorphisms of 74 pts.;21 (28%) were hospitalized for COVID-19, 38 (51%) had symptomatic course without hospitalization and 15 (21%) were completely pauci-asymptomatics. Serum concentrations of sACE2 and distribution of polymorphic variants in the three groups are summarized in Table 1. We found that sACE2 levels were higher in genotypic variant CC of SNP 1 of TMPRSS2 gene (Table 2). Considering that a high concentration of sACE2 outlines a proinflammatory condition, it could be hypothesized that the CC genotype may be a predisposing condition to the cytokine storm of COVID-19. Perspective(s): Genetic analysis of ACE2 and TMPRSS2 SNPs will help to clarify the relationship between these polymorphic variant, sACE2 levels, risk of SARS-CoV2 infection and severity of clinical presentation of COVID-19 in patients with or without CV diseases.
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Snake soup continues to be an iconic tradition in Cantonese culture. Yet little is known about the relationship between snake soup consumption in Hong Kong, wild snake populations, and the communities depending on this tradition for their livelihoods. We applied an interdisciplinary approach including interviews with shopkeepers and genetic analyses of snake meat samples to determine the species consumed in Hong Kong, their source locations, and shopkeepers' views on the future of the industry. We genetically identified the common rat snake Ptyas mucosa, widely distributed throughout East and Southeast Asia, and the Javan spitting cobra Naja sputatrix, endemic to Indonesia, as the species most commonly consumed, which was consistent with interview responses. According to interviews, snakes had mostly been imported from mainland China in the past, but now tend to be sourced from Southeast Asia, particularly Indonesia. Interviews also revealed a pessimistic outlook on the continuation of this tradition because of various factors, including a lasting yet misinformed association of snakes with the 2002–2003 outbreak of severe acute respiratory syndrome. Given the COVID-19 pandemic and China's ensuing ban on the consumption of terrestrial wildlife, Hong Kong's snake soup industry will probably continue to rely on Southeast Asian sources to persist. Given the cultural and conservation issues surrounding this tradition, further research on the economic, ecological and social consequences of snake consumption is needed to examine the broader implications of snake soup and similar industries in the region.
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These proceedings contain 78 articles focusing on the following themes: asthma immunology;SARS-COV-2;neuroimmunoendocrinology and immunopharmacology;immunology of infectious and parasitic diseases;immunogenetics, genomics and proteomics;and immunodeficiency and immunopathology.
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Background: Currently, the prothrombogenic status in Covid-19 infection and the possible influence of genetic polymorphism of the hemostasis system are widely discussed. Aim(s): The aim of the study was to evaluate the molecular and genetic features of the hemostasis system in patients with Covid-19 Methods: The study was performed on the basis of the regional center for antithrombotic therapy Arkhangelsk.A molecular genetic analysis was performed for the presence of prothrombogenic mutations in patients (n = 100) with Covid-19 in a covid hospital. Result(s): Polymorphism in the F I G/A-455 (fibrinogen) gene was found in 43% of patients (homozygote -6%, heterozygote -37%), polymorphism in the ITG B3 1565 T>C gene -in 38% (26% -heterozygous carrier and 12% -homozygous). In our study, a mutation in the prothrombin F II gene G20210-A (heterozygous allelic variant -2%) and a "true" prothrombogenic mutation of factor V (Leid) were found with the lowest (6% -heterozygous state). Next, we analyzed the dependence of genetic polymorphism of hemostasis system factors F II 20210 G>A, F V 1691 G>A, PAI-1 675 5G>4G and thrombinemia levels in patients with COVID-19. The level of fibrinogen (>6.0 g/l;p < 0.05) was statistically significantly higher in the groups of patients with prothrombogenic polymorphism in the genes of coagulation factor V (F V), coagulation factor II (F II), PAI-1 for the entire period of hospitalization. Upon admission, the levels of D-dimer and fibrinogen were statistically significantly higher in patients with a mutation in the F II gene. Conclusion(s): When treating Covid-19, it is advisable to take into account the presence of molecular genetic markers of prothrombogenic status in a patient.
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Objective To understand the epidemiology and etiology of a cluster of cases with gastroenteritis in a nursing home in Anning district of Lanzhou, and to provide a scientific evidence for the prevention and control of norovirus diarrhea in community nursing centers. Methods From January 28 to February 4 2021, an epidemiological investigation was conducted on all diarrhea cases, nursing staff and chefs in a nursing home in Anning district, Lanzhou city.Samples of patients′ anal swabs, feces, vomitus were collected for norovirus detection by real-time fluorescent PCR.ORF1/ORF2 junction region of norovirus in some selected positive samples（Ct value ≤ 25） was sequenced.MEGA-X software was used to construct a phylogenetic tree for genetic evolution analysis using the neighboring method. Results The first case was confirmed on January20,2021,and the number of cases peaked during January 25and 29.A total of 58clinically diagnosed cases were reported,57were older people,with an incidence of（57/360,15.83%）.Diarrhea（50/58,86.21%）,vomiting（35/58,60.34%）,nausea（13/58,22.41%）and abdominal pain（6/58,10.34%）were common symptoms,all cases were mild.Fifty-three asymptomatic cases were detected among chefs,housekeepers and nurses.A total of 163specimens were tested,the positive rate of norovirus GⅡwas 49.08%（80/163）.The positive rate of fecal samples collected from nurses,chefs and housekeepers was 48.62%（53/109）,and was11.11%（2/18）in environmental surface swabs.The possibility of other pathogenic infections such as SARS-CoV-2was ruled out by further tests.Thirteen positive samples were selected for sequencing,and 9were successfully sequenced,they were all recombinant GⅡ.4Sydney＿2012 [P16]genotypes,forming an independent cluster,while in a large evolutionary branch with the 2020GⅡ.10 [P16]and 2019GⅡ.2 [P16]virus strains in Lanzhou city,showing a relative close genetic connection. Conclusions GⅡ.4Sydney＿2012[P16]genotype of norovirus is found to be causative pathogen of this outbreak,and close contact is the main reason of the outbreak and persistence of the infection,so asymptomatic infections of norovirus play an important role in the disease spreading.Therefore,public health management in nursing homes and other centralized nursing facilities should be strengthened especially for asymptomatic workers in order to prevent virus transmission.
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COVID-19 disease is caused by a novel type of SARS-CoV-2 virus which was firstly described in Chinese Wuhan in December 2019. It is highly infectious disease manifested with fever, respiratory problems, muscle pains and tiredness. Up to now, no efficient medicine has been available, that is why research is focused on development of a vaccine. The vaccine research was launched immediately when the pandemic broke out. The main goal of vaccination against COVID-19 will be prevention of infection outbreak, prevention of reinfection, long-term protective effect and efficiency of vaccination in case of next potential waves of infection. The primary questions are if the effective vaccine against COVID-19 will be developed, how long it will take and who will be the first. The first pandemic disease caused by a novel SARS coronavirus emerged almost 20 years ago, the next MERS coronavirus disease 8 years ago and no effective vaccine against these diseases has been available so far. Presently, 179 candidate vaccines at minimum are at different stages of their development and 18 vaccines are at the stage of clinical evaluation. The surface S glycoprotein SARS-CoV-2 virus is considered the most promising vaccine antigen. Other options are the use of the whole virion or subunit S1 carrier. Currently, four types of potential vaccines have been developed. Whole virion vaccines (attenuated or killed vaccine) vector vaccines (most often using replicating or non-replicating viral vector) protein vaccines (subunit adjuvant vaccine or vaccine based on virus-like particles) and DNA, RNA vaccine. The key moment will be confirmation of the novel vaccine efficiency at the phase 3 of a clinical trial. Despite pressure and efforts to speed up the development of the vaccine, it is realistic to count on the possible vaccine in the year 2021 the earliest and the question is when it can be available in the Czech Republic. Copyright © 2020, Medakta s.r.o.. All rights reserved.
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RNA viruses have the characteristics of a high mutation rate. New Coronavirus (SARS-CoV-2), as a RNA virus, has been mutated to some extent since the outbreak of New Coronavirus pneumonia (COVID-19). It is of great significance to study the evolution and variation of novel coronavirus genes to analyze the source of virus infection and understand the evolution of viruses. This research is based on the Novel Coronavirus 2019 database at the National Genomics Data Center. We combined macro and micro. We used the phylogenetic tree to analyze the gene fragments of the virus, constructed an evolutionary tree with a depth of 301, searched the root node of the tree to find the source of the virus in the data set and used spectral clustering to analyze the degree of novel Coronavirus variation in each country and the clustering results were visualized to make them easier to observe. The experimental results show that the strain sample at the top of the evolutionary tree originated in New Zealand based on the existing data. In the evolutionary tree, the evolutionary process of the virus can be divided into three branches. After clustering the virus source data and constructing the visual map of the variation degree of SARS-COV-2, we found that the viruses in South Africa, New Zealand and other countries had a higher degree of variation, and the viruses in Australia, the United States and other countries have a relatively lower degree of virus variation. © 2022 IEEE.
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Objective To understand the genomic characteristics of SARS-CoV-2 from 40 imported cases with confirmed COVID-19 in Sichuan during January and March 2022. Methods Total viral RNA was extracted from respiratory samples of 182 confirmed COVID-19 cases who entered China through Chendu International Airport from January to March 2022.Mutation nucleic acid detection kit was used to identify the mutant strains and Illumina sequencing platform was applied for whole genome sequence（WGS） of virus.SARS-CoV-2 reference sequences were downloaded from NCBI database for genetic evolution and antigen variation analysis.The Nextclade and Pangolin online virus analysis platform were used to determine the virus family and type,and to analyze the mutation loci of the virus.The phylogenetic tree was constructed,along with the epidemiological data of cases to analyze the source and correlation of viruses. Results Among 182 imported COVID-19 cases,B.1.617.2 mutations were identified in 3 cases and B.1.1.529 mutations were detected in 57 cases.A total of 40 SARS-CoV-2 whole genome sequences with coverage>95% were obtained in this study.Nextclade typing analysis showed that 3 sequences belonged to 21J（Delta）,5 sequences belonged to 21K（Omicron）and the remaining 32 sequences belonged to 21L（Omicron）.Pangolin typing analysis showed that the 3 sequences of 21J（Delta）belonged to AY.4,AY.109and B.1.617.2,the 5sequences of 21K（Omicron）all belonged to BA.1.1,and the remaining 32 sequences of 21L（Omicron）belonged to BA.2.Our sequence results were99.7% consistency with the Omicron variants sequences in current GISAID database.Compared with the reference sequence strain Wuhan-Hu-1（NC＿045512.2）,45,47and 42nucleotide variation sites and 36,25 and 36amino acid variation sites were found in the 3 sequences of 21J（Delta）.There were average 59（26-64）nucleotide mutation sites and 48（10-53）amino acid mutation sites in the 5sequences of 21K（Omicron）.The median number of nucleotide mutation sites of 71（66-76）and amino acid mutation sites of 53（40-56）were identified in the 32sequences of 21L（Omicron）.Phylogenetic tree analysis showed that 40SARS-CoV-2WGSs were all related to the current variants of concern（VOC）. Conclusions Continuous sequencing of SARS-CoV-2whole genome from imported cases with confirmed COVID-19is of great significance for the prevention and control of the outbreak and prevalence of local epidemic caused by imported viruses in Sichuan.
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BackgroundWe present a case of alpha-fucosidosis, a lysosomal storage disorder, from Egypt. The report also includes a brief review of the COVID-19 and lysosomal storage diseases relationship.Case presentationA female patient aged 18 years, diagnosed with type II fucosidosis, based on the cutaneous signs, characteristic facies, and systemic symptoms, and diagnosis was confirmed using genetic analysis. The patient died from COVID-19 pneumonia during the COVID-19 pandemic after getting the infection from her father and being hospitalized.ConclusionsPatients with lysosomal storage diseases with local or systemic immune suppression may be predisposed to respiratory complications of COVID-19. Intense care with protective guidelines should be applied to those patients.
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Rotavirus (RV) viroplasms are cytosolic inclusions where both virus genome replication and primary steps of virus progeny assembly take place. A stabilized microtubule cytoskeleton and lipid droplets are required for the viroplasm formation, which involves several virus proteins. The viral spike protein VP4 has not previously been shown to have a direct role in viroplasm formation. However, it is involved with virus-cell attachment, endocytic internalization, and virion morphogenesis. Moreover, VP4 interacts with actin cytoskeleton components, mainly in processes involving virus entrance and egress, and thereby may have an indirect role in viroplasm formation. In this study, we used reverse genetics to construct a recombinant RV, rRV/VP4-BAP, that contains a biotin acceptor peptide (BAP) in the K145-G150 loop of the VP4 lectin domain, permitting live monitoring. The recombinant virus was replication competent but showed a reduced fitness. We demonstrate that rRV/VP4-BAP infection, as opposed to rRV/wt infection, did not lead to a reorganized actin cytoskeleton as viroplasms formed were insensitive to drugs that depolymerize actin and inhibit myosin. Moreover, wild-type (wt) VP4, but not VP4-BAP, appeared to associate with actin filaments. Similarly, VP4 in coexpression with NSP5 and NSP2 induced a significant increase in the number of viroplasm-like structures. Interestingly, a small peptide mimicking loop K145-G150 rescued the phenotype of rRV/VP4-BAP by increasing its ability to form viroplasms and hence improve virus progeny formation. Collectively, these results provide a direct link between VP4 and the actin cytoskeleton to catalyze viroplasm assembly. IMPORTANCE The spike protein VP4 participates in diverse steps of the rotavirus (RV) life cycle, including virus-cell attachment, internalization, modulation of endocytosis, virion morphogenesis, and virus egress. Using reverse genetics, we constructed for the first time a recombinant RV, rRV/VP4-BAP, harboring a heterologous peptide in the lectin domain (loop K145-G150) of VP4. The rRV/VP4-BAP was replication competent but with reduced fitness due to a defect in the ability to reorganize the actin cytoskeleton, which affected the efficiency of viroplasm assembly. This defect was rescued by adding a permeable small-peptide mimicking the wild-type VP4 loop K145-G150. In addition to revealing a new role of VP4, our findings suggest that rRV harboring an engineered VP4 could be used as a new dual vaccination platform providing immunity against RV and additional heterologous antigens.