Performance of point-of care molecular and antigen-based tests for SARS-CoV-2: a living systematic review and meta-analysis

BackgroundMolecular and antigen point-of-care tests (POCTs) have augmented our ability to rapidly identify and manage SARS-CoV-2 infection. However, their clinical performance varies among individual studies.ObjectivesThe evaluation of the performance of molecular and antigen-based POCTs in confirmed, suspected, or probable COVID-19 cases compared with that of laboratory-based RT-PCR in real-life settings.Data sourcesMEDLINE/PubMed, Scopus, Embase, Web of Science, Cochrane Library, Cochrane COVID-19 study register, and COVID-19 Living Evidence Database from the University of Bern.Study eligibility criteriaPeer-reviewed or preprint observational studies or randomized controlled trials that evaluated any type of commercially available antigen and/or molecular POCTs for SARS-CoV-2, including multiplex PCR panels, approved by the United States Food and Drug Administration, with Emergency Use Authorization, and/or marked with Conformitè Europëenne from European Commission/European Union.ParticipantsClose contacts and/or patients with symptomatic and/or asymptomatic confirmed, suspected, or probable COVID-19 infection of any age.Test/sMolecular and/or antigen-based SARS-CoV-2 POCTs.Reference standardLaboratory-based SARS-CoV-2 RT-PCR.Assessment of risk of biasEligible studies were subjected to quality-control and risk-of-bias assessment using the Quality Assessment of Diagnostic Accuracy Studies 2 tool.Methods of data synthesisSummary sensitivities and specificities with their 95% CIs were estimated using a bivariate model. Subgroup analysis was performed when at least three studies informed the outcome.ResultsA total of 123 eligible publications (97 and 26 studies assessing antigen-based and molecular POCTs, respectively) were retrieved from 4674 initial records. The pooled sensitivity and specificity for 13 molecular-based POCTs were 92.8% (95% CI, 88.9–95.4%) and 97.6% (95% CI, 96.6–98.3%), respectively. The sensitivity of antigen-based POCTs pooled from 138 individual evaluations was considerably lower than that of molecular POCTs; the pooled sensitivity and specificity rates were 70.6% (95% CI, 67.2–73.8%) and 98.9% (95% CI, 98.5–99.2%), respectively.DiscussionFurther studies are needed to evaluate the performance of molecular and antigen-based POCTs in underrepresented patient subgroups and different respiratory samples.     

The hereditary spastic paraplegias

The hereditary spastic paraplegias are a complex group of neurodegenerative conditions which are characterised by slowly progressive lower limb spasticity. This article describes the main clinical features of pure and complicated hereditary spastic paraplegias and summarises recent advances in our understanding of the molecular genetics of these conditions. Received: 2 June 1999 Accepted: 7 August 1999     

A molecular scheme for the reaction between γ-aminobutyric acid and the most abundant chloride channel on crayfish deep extensor abdominal muscle

Single-channel measurements were performed with the aim of constructing a detailed molecular scheme for the reaction between -aminobutyric acid (GABA) and a chloride channel of crayfish deep extensor abdominal muscle (DEAM). GABA was applied in pulses to outside-out patches of muscle membrane, and, based on the dose-response of the peak currents and of their rise times, a linear model with five binding steps has been proposed. Evaluation of the single-channel kinetics indicated at least three open states. Two of them originate most probably from the fully liganded receptor state and are grouped in mixed bursts due to their different life times. The third one appears independently, outside the bursts, and originates from a lower liganded receptor state. Simulations of the dose-responses and the open time distributions with this model led to a set of rate constants which generated relatively optimal fits.     

Molecular epidemiology of nasopharyngeal corynebacteria in healthy adults from an area where diphtheria vaccination has been extensively practiced

In addition to conventional biochemical tests, a DNA probe specific for Corynebacterium diphtheriae was used to characterize 53 cystinase-positive and urease-negative corynebacteria strains isolated from pharyngeal and nasal swabs obtained from 515 healthy adults living in an urban area of central Italy. No Corynebacterium diphtheriae strain was found. Six atypical strains were isolated, which could not be classified in any of the species so far defined in the Corynebacterium genus. These strains appeared to be biochemically close to Corynebacterium pseudodiphtheriticum and genetically close to Corynebacterium diphtheriae, since their DNAs strongly hybridized, under relatively low stringency conditions, with a Corynebacterium diphtheriae-specific probe and since insertion sequences which are usually found in Corynebacterium diphtheriae genomes were also found to be present in their genomes. No one of these six strains was either toxigenic or susceptible to lysogenization by -corynephage carrying the tox gene. Therefore, they do not seem to have any epidemiological relevance as possible hosts for -phages.Corresponding author.     

Molecular detection of genetic defects in congenital adrenal hyperplasia due to 21-hydroxylase deficiency: A study of 27 families

Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase (21-OHase) deficiency is inherited as an autosomal recessive trait. Patients can present with the salt wasting, simple virilizing or a non-classical form of the disease. The gene for P450C21, the enzyme carrying 21-OHase activity, has been mapped to the major histocompatibility complex on chromosome 6p. Using molecular hybridisation techniques we have studied the genetic defect in 27 families with one or more affected off-spring diagnosed and treated at the University Hospital of Essen. DNA samples were digested with restriction endonucleaseTaqI,PvuII,BglII, andEcoRI and analysed by Southern blot hybridisation with the cDNA probe pC21/3c. Eleven of 40 haplotypes associated with the salt wasting form were found to have a large deletion of 30 kb affecting the 5 end of the active 21-OHase gene and the 3 end of the closely linked pseudogene. Results in another 11 cases are compatible with gene conversion; 18 cases were not informative. The 30 kb deletion was associated with a combination of the HLA antigens Bw47 and DR7 in 7 of 11 cases. In the haplotypes with gene conversion, no linkage disequilibrium to HLA antigens was found. No apparent gene alterations were detected in simple virilizing and non-classical haplotypes. The direct detection of the genetic defect in 55% of the salt wasting haplotypes may help to improve predictive testing in families with CAH.     

肾上腺脑白质营养不良的分子诊断（附2例报告）

目的 探讨肾上腺脑白质营养不良(ALD)的分子诊断方法。方法 在临床诊断的基础上，从2名患者外周血提取白细胞总RNA，进行反转录后，用PCR方法分四段扩增ALD基因编码区。纯化PCR产物，并对其进行序列测定。查出突变位点后，对患者家系成员的基因组DNA进行PCR-限制性酶切分析。结果 患者A的ALD基因第280位密码子发生CGC→CTC改变，使原来编码的精氨酸被亮氨酸取代(R280L突变)；患者B的ALD基因第508位密码子发生了CCC→CTC改变，使正常的脯氨酸被亮氨酸替换(P508L突变)。两个突变通过酶切分析和家系调查得到进一步确证。结论 建立了ALD的分子诊断技术，并在中国人ALD患者发现了两个新的ALD基因突变。     

细胞因子网络--抗银屑病药物的分子免疫学靶位

从分子免疫学的角度阐述了细胞因子异常、细胞因子网络失衡等与银屑病发病的关系，并介绍了针对细胞因子网络设计抗银屑病药物的研究现状，为人们寻找抗银屑病药物提供新线索。     

Role of Clostridium perfringens phospholipase C in the pathogenesis of gas gangrene.

Gas gangrene is an acute and devastating infection most frequently caused by Clostridium perfringens and characterized by severe myonecrosis, intravascular leukocyte accumulation, and significant thrombosis. Several lines of evidence indicate that C. perfringens phospholipase C (Cp-PLC), also called alpha-toxin, is the major virulence factor in this disease. This toxin is a Zn²⁺ metalloenzyme with lecithinase and sphingomyelinase activities. Its three dimensional structure shows two domains, an N-terminal domain which contains the active site, and a C-terminal domain required for the Ca²⁺dependent interaction with membranes. Cp-PLC displays several biological activities: it increases capillary permeability, induces platelet aggregation, hemolysis, myonecrosis, decreases cardiac contractility, and is lethal. Experiments with genetically engineered Cp-PLC variants have revealed that the sphingomyelinase activity and the C-terminal domain are required for toxicity. The myotoxicity of Cp-PLC is largely dependent on its membrane damaging effect. In addition, it has been suggested that the alterations in the blood flow induced by this toxin also contribute to muscle damage. In gas gangrene, Cp-PLC dysregulates transduction pathways in endothelial cells, platelets and neutrophils leading to the uncontrolled production of several intercellular mediators and adhesion molecules. Thus, Cp-PLC alters the traffic of neutrophils to the infected tissue and promotes thrombotic events, enhancing the conditions for anaerobic growth.     

乳腺癌骨髓微转移状况与ER PR VEGF 及Cath-D等因子的关系

目的:检测乳腺癌骨髓组织CK19 mRNA的表达,判断骨髓微转移状况,探讨其与各因子的关系.方法:采用RT-PCR法(一步法)检测骨髓组织中CK19 mRNA表达;用免疫组化SP法检测乳腺癌组织中ER、PR、Cath-D、C-erbB-2及VEGF的表达.结果:102例乳腺癌患者骨髓组织CK19 mRNA表达阳性率56.9%.骨髓CK19 mRNA表达随乳腺癌组织中ER及PR蛋白表达增强而降低(P＜0.05,P＜0.01);随Cath-D、VEGF蛋白表达增强而呈增高趋势(P＜0.005,P＜0.05);但与C-erbB-2表达状况无关.结论:乳腺癌骨髓微转移与癌组织中某些生物学因子表达有关;这些因子决定癌细胞的生物学行为.     

男性胰腺实性-假乳头状瘤2例临床病理观察

目的探讨胰腺实性-假乳头状瘤(SPT)的临床病理特征及了解分子病理学研究进展。方法2例SPT分别作HE、PAS、免疫组织化学(S—P法)染色观察。结果2例SPT男性患者均有腹部包块及腹痛症状。术后均无复发。肿块体积较大，囊实性相间。镜下瘤细胞围绕纤维血管形成特征性的假乳头结构，并可见退行性变、出血和泡沫细胞。免疫组化结果：2例AACT、ACT、Cga和Syn均为阳性，PR、ER、Ck和Ins均为阴性，1例Vim为阳性。结论胰腺SPT为具有独特临床病理特征的低度恶性肿瘤。