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1.
J Nanobiotechnology ; 19(1): 348, 2021 Oct 30.
Article in English | MEDLINE | ID: covidwho-1486580

ABSTRACT

Viral infections are the most common among diseases that globally require around 60 percent of medical care. However, in the heat of the pandemic, there was a lack of medical equipment and inpatient facilities to provide all patients with viral infections. The detection of viral infections is possible in three general ways such as (i) direct virus detection, which is performed immediately 1-3 days after the infection, (ii) determination of antibodies against some virus proteins mainly observed during/after virus incubation period, (iii) detection of virus-induced disease when specific tissue changes in the organism. This review surveys some global pandemics from 1889 to 2020, virus types, which induced these pandemics, and symptoms of some viral diseases. Non-analytical methods such as radiology and microscopy also are overviewed. This review overlooks molecular analysis methods such as nucleic acid amplification, antibody-antigen complex determination, CRISPR-Cas system-based viral genome determination methods. Methods widely used in the certificated diagnostic laboratory for SARS-CoV-2, Influenza A, B, C, HIV, and other viruses during a viral pandemic are outlined. A comprehensive overview of molecular analytical methods has shown that the assay's sensitivity, accuracy, and suitability for virus detection depends on the choice of the number of regions in the viral open reading frame (ORF) genome sequence and the validity of the selected analytical method.


Subject(s)
Clinical Laboratory Techniques , Virus Diseases/diagnosis , Viruses/isolation & purification , Biosensing Techniques , COVID-19/diagnosis , COVID-19/epidemiology , Humans , Nucleic Acid Amplification Techniques , Pandemics , SARS-CoV-2/genetics , SARS-CoV-2/immunology , SARS-CoV-2/isolation & purification , Viral Proteins/genetics , Viral Proteins/immunology , Virus Diseases/epidemiology , Viruses/classification , Viruses/genetics , Viruses/immunology
2.
Crit Care Med ; 49(10): 1664-1673, 2021 10 01.
Article in English | MEDLINE | ID: covidwho-1452743

ABSTRACT

OBJECTIVES: The rapid diagnosis of acute infections and sepsis remains a serious challenge. As a result of limitations in current diagnostics, guidelines recommend early antimicrobials for suspected sepsis patients to improve outcomes at a cost to antimicrobial stewardship. We aimed to develop and prospectively validate a new, 29-messenger RNA blood-based host-response classifier Inflammatix Bacterial Viral Non-Infected version 2 (IMX-BVN-2) to determine the likelihood of bacterial and viral infections. DESIGN: Prospective observational study. SETTING: Emergency Department, Campus Benjamin Franklin, Charité-Universitätsmedizin Berlin, Germany. PATIENTS: Three hundred twelve adult patients presenting to the emergency department with suspected acute infections or sepsis with at least one vital sign change. INTERVENTIONS: None (observational study only). MEASUREMENTS AND MAIN RESULTS: Gene expression levels from extracted whole blood RNA was quantified on a NanoString nCounter SPRINT (NanoString Technologies, Seattle, WA). Two predicted probability scores for the presence of bacterial and viral infection were calculated using the IMX-BVN-2 neural network classifier, which was trained on an independent development set. The IMX-BVN-2 bacterial score showed an area under the receiver operating curve for adjudicated bacterial versus ruled out bacterial infection of 0.90 (95% CI, 0.85-0.95) compared with 0.89 (95% CI, 0.84-0.94) for procalcitonin with procalcitonin being used in the adjudication. The IMX-BVN-2 viral score area under the receiver operating curve for adjudicated versus ruled out viral infection was 0.83 (95% CI, 0.77-0.89). CONCLUSIONS: IMX-BVN-2 demonstrated accuracy for detecting both viral infections and bacterial infections. This shows the potential of host-response tests as a novel and practical approach for determining the causes of infections, which could improve patient outcomes while upholding antimicrobial stewardship.


Subject(s)
Bacterial Infections/diagnosis , RNA, Messenger/analysis , Virus Diseases/diagnosis , Aged , Aged, 80 and over , Area Under Curve , Bacterial Infections/blood , Bacterial Infections/physiopathology , Berlin , Biomarkers/analysis , Biomarkers/blood , Emergency Service, Hospital/organization & administration , Emergency Service, Hospital/statistics & numerical data , Female , Humans , Male , Middle Aged , Prospective Studies , RNA, Messenger/blood , ROC Curve , Virus Diseases/blood , Virus Diseases/physiopathology
3.
Int J Mol Med ; 47(5)2021 05.
Article in English | MEDLINE | ID: covidwho-1448967

ABSTRACT

Circular RNAs (circRNAs) are a class of non­coding RNAs with a circular, covalent structure that lack both 5' ends and 3' poly(A) tails, which are stable and specific molecules that exist in eukaryotic cells and are highly conserved. The role of circRNAs in viral infections is being increasingly acknowledged, since circRNAs have been discovered to be involved in several viral infections (such as hepatitis B virus infection and human papilloma virus infection) through a range of circRNA/microRNA/mRNA regulatory axes. These findings have prompted investigations into the potential of circRNAs as targets for the diagnosis and treatment of viral infection­related diseases. The aim of the present review was to systematically examine and discuss the role of circRNAs in several common viral infections, as well as their potential as diagnostic markers and therapeutic targets.


Subject(s)
MicroRNAs/genetics , RNA, Circular/physiology , RNA, Messenger/genetics , Virus Diseases/genetics , Biomarkers/analysis , Humans , RNA, Circular/genetics , Virus Diseases/diagnosis , Virus Diseases/therapy , Virus Diseases/virology
4.
PLoS One ; 16(9): e0258002, 2021.
Article in English | MEDLINE | ID: covidwho-1448576

ABSTRACT

Detecting viruses, which have significant impact on health and the economy, is essential for controlling and combating viral infections. In recent years there has been a focus towards simpler and faster detection methods, specifically through the use of electronic-based detection at the point-of-care. Point-of-care sensors play a particularly important role in the detection of viruses. Tests can be performed in the field or in resource limited regions in a simple manner and short time frame, allowing for rapid treatment. Electronic based detection allows for speed and quantitative detection not otherwise possible at the point-of-care. Such approaches are largely based upon voltammetry, electrochemical impedance spectroscopy, field effect transistors, and similar electrical techniques. Here, we systematically review electronic and electrochemical point-of-care sensors for the detection of human viral pathogens. Using the reported limits of detection and assay times we compare approaches both by detection method and by the target analyte of interest. Compared to recent scoping and narrative reviews, this systematic review which follows established best practice for evidence synthesis adds substantial new evidence on 1) performance and 2) limitations, needed for sensor uptake in the clinical arena. 104 relevant studies were identified by conducting a search of current literature using 7 databases, only including original research articles detecting human viruses and reporting a limit of detection. Detection units were converted to nanomolars where possible in order to compare performance across devices. This approach allows us to identify field effect transistors as having the fastest median response time, and as being the most sensitive, some achieving single-molecule detection. In general, we found that antigens are the quickest targets to detect. We also observe however, that reports are highly variable in their chosen metrics of interest. We suggest that this lack of systematisation across studies may be a major bottleneck in sensor development and translation. Where appropriate, we use the findings of the systematic review to give recommendations for best reporting practice.


Subject(s)
Point-of-Care Systems , Virus Diseases/diagnosis , Electronics , Humans , Virus Diseases/virology
5.
JAMA Netw Open ; 4(9): e2124650, 2021 09 01.
Article in English | MEDLINE | ID: covidwho-1412566

ABSTRACT

Importance: Every year, respiratory viruses exact a heavy burden on Canadian hospitals during winter months. Generalizable seasonal patterns of respiratory virus transmission may estimate the evolution of SARS-CoV-2 or other emerging pathogens. Objective: To describe the annual and biennial variation in respiratory virus seasonality in a northern climate. Design, Setting, and Participants: This cohort study is an epidemiological assessment using population-based surveillance of patients with medically attended respiratory tract infection from 2005 through 2017 in Alberta, Canada. Incident cases of respiratory virus infection and infant respiratory syncytial virus (RSV) hospitalizations in Alberta were extracted from the Data Integration for Alberta Laboratories platform and Alberta Health Services Discharge Abstract Database, respectively. A deterministic susceptible-infected-recovered-susceptible mathematical model with seasonal forcing function was fitted to the data for each virus. The possible future seasonal course of SARS-CoV-2 in northern latitudes was modeled on the basis of these observations. The analysis was conducted between December 15, 2020, and February 10, 2021. Exposures: Seasonal respiratory pathogens. Main Outcomes and Measures: Incidence (temporal pattern) of respiratory virus infections and RSV hospitalizations. Results: A total of 37 719 incident infections with RSV, human metapneumovirus, or human coronaviruses 229E, NL63, OC43, or HKU1 among 35 375 patients (18 069 [51.1%] male; median [interquartile range], 1.29 [0.42-12.2] years) were documented. A susceptible-infected-recovered-susceptible model mirrored the epidemiological data, including a striking biennial variation with alternating severe and mild winter peaks. Qualitative description of the model and numerical simulations showed that strong seasonal contact rate and temporary immunity lasting 6 to 12 months were sufficient to explain biennial seasonality in these various respiratory viruses. The seasonality of 10 212 hospitalizations among children younger than 5 years with RSV was also explored. The median (interquartile range) rate of hospitalizations per 1000 live births was 18.6 (17.6-19.9) and 11.0 (10.4-11.7) in alternating even (severe) and odd (less-severe) seasons, respectively (P = .001). The hazard of admission was higher for children born in severe (even) seasons compared with those born in less-severe (odd) seasons (hazard ratio, 1.68; 95% CI, 1.61-1.75; P < .001). Conclusions and Relevance: In this modeling study of respiratory viruses in Alberta, Canada, the seasonality followed a pattern estimated by simple mathematical models, which may be informative for anticipating future waves of pandemic SARS-CoV-2.


Subject(s)
Respiratory Tract Infections/virology , Seasons , Virus Diseases/diagnosis , Alberta/epidemiology , Cohort Studies , Hospitalization/statistics & numerical data , Humans , Incidence , Respiratory Tract Infections/epidemiology , Statistics, Nonparametric , Virus Diseases/epidemiology
6.
Bioessays ; 43(4): e2000315, 2021 04.
Article in English | MEDLINE | ID: covidwho-1384113

ABSTRACT

The versatile clustered regularly interspaced short palindromic repeats (CRISPR)/Cas system has emerged as a promising technology for therapy and molecular diagnosis. It is especially suited for overcoming viral infections outbreaks, since their effective control relies on an efficient treatment, but also on a fast diagnosis to prevent disease dissemination. The CRISPR toolbox offers DNA- and RNA-targeting nucleases that constitute dual weapons against viruses. They allow both the manipulation of viral and host genomes for therapeutic purposes and the detection of viral nucleic acids in "Point of Care" sensor devices. Here, we thoroughly review recent advances in the use of the CRISPR/Cas system for the treatment and diagnosis of viral deleterious infections such as HIV or SARS-CoV-2, examining their strengths and limitations. We describe the main points to consider when designing CRISPR antiviral strategies and the scientific efforts to develop more sensitive CRISPR-based viral detectors. Finally, we discuss future prospects to improve both applications. Also see the video abstract here: https://www.youtube.com/watch?v=C0z1dLpJWl4.


Subject(s)
Biosensing Techniques/methods , CRISPR-Cas Systems , Virus Diseases/diagnosis , Virus Diseases/therapy , Viruses/genetics , COVID-19/diagnosis , COVID-19/genetics , COVID-19/therapy , Gene Knock-In Techniques , Genome, Viral , Humans , RNA, Guide/genetics
7.
Viruses ; 13(5)2021 05 04.
Article in English | MEDLINE | ID: covidwho-1383920

ABSTRACT

Viral infections are responsible for several chronic and acute diseases in both humans and animals. Despite the incredible progress in human medicine, several viral diseases, such as acquired immunodeficiency syndrome, respiratory syndromes, and hepatitis, are still associated with high morbidity and mortality rates in humans. Natural products from plants or other organisms are a rich source of structurally novel chemical compounds including antivirals. Indeed, in traditional medicine, many pathological conditions have been treated using plant-derived medicines. Thus, the identification of novel alternative antiviral agents is of critical importance. In this review, we summarize novel phytochemicals with antiviral activity against human viruses and their potential application in treating or preventing viral disease.


Subject(s)
Antiviral Agents/pharmacology , Biological Products/pharmacology , Drug Discovery , Animals , Antiviral Agents/chemistry , Antiviral Agents/therapeutic use , Biological Products/chemistry , Biological Products/therapeutic use , DNA Viruses/drug effects , DNA Viruses/physiology , Drug Development , Host-Pathogen Interactions/drug effects , Host-Pathogen Interactions/genetics , Host-Pathogen Interactions/immunology , Humans , RNA Viruses/drug effects , RNA Viruses/physiology , Virus Diseases/diagnosis , Virus Diseases/drug therapy , Virus Diseases/etiology , Virus Diseases/metabolism , Virus Replication/drug effects
8.
Biosensors (Basel) ; 11(9)2021 Aug 28.
Article in English | MEDLINE | ID: covidwho-1374295

ABSTRACT

The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease-19 (COVID-19), has severely influenced public health and economics. For the detection of SARS-CoV-2, clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR associated protein (Cas)-based assays have been emerged because of their simplicity, sensitivity, specificity, and wide applicability. Herein, we have developed a CRISPR-Cas12-based assay for the detection of SARS-CoV-2. In the assay, the target amplicons are produced by isothermal reverse transcription recombinase polymerase amplification (RT-RPA) and recognized by a CRISPR-Cas12a/guide RNA (gRNA) complex that is coupled with the collateral cleavage activity of fluorophore-tagged probes, allowing either a fluorescent measurement or naked-eye detection on a lateral flow paper strip. This assay enables the sensitive detection of SARS-CoV-2 at a low concentration of 10 copies per sample. Moreover, the reliability of the method is verified by using nasal swabs and sputum of COVID-19 patients. We also proved that the current assay can be applied to other viruses, such as Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus (SARS-CoV), with no major changes to the basic scheme of testing. It is anticipated that the CRISPR-Cas12-based assay has the potential to serve as a point-of-care testing (POCT) tool for a wide range of infectious viruses.


Subject(s)
Bacterial Proteins/metabolism , CRISPR-Associated Proteins/metabolism , Endodeoxyribonucleases/metabolism , Middle East Respiratory Syndrome Coronavirus/isolation & purification , SARS Virus/isolation & purification , SARS-CoV-2/isolation & purification , Virus Diseases/diagnosis , CRISPR-Cas Systems , Fluorescent Dyes/chemistry , Humans , Middle East Respiratory Syndrome Coronavirus/genetics , Nose/virology , Point-of-Care Testing , RNA, Guide/chemistry , RNA, Guide/genetics , Reverse Transcriptase Polymerase Chain Reaction , SARS Virus/genetics , SARS-CoV-2/genetics , Sensitivity and Specificity , Sputum/virology
10.
J Gen Virol ; 102(8)2021 08.
Article in English | MEDLINE | ID: covidwho-1369239

ABSTRACT

Viruses may exploit the cardiovascular system to facilitate transmission or within-host dissemination, and the symptoms of many viral diseases stem at least in part from a loss of vascular integrity. The microvascular architecture is comprised of an endothelial cell barrier ensheathed by perivascular cells (pericytes). Pericytes are antigen-presenting cells (APCs) and play crucial roles in angiogenesis and the maintenance of microvascular integrity through complex reciprocal contact-mediated and paracrine crosstalk with endothelial cells. We here review the emerging ways that viruses interact with pericytes and pay consideration to how these interactions influence microvascular function and viral pathogenesis. Major outcomes of virus-pericyte interactions include vascular leakage or haemorrhage, organ tropism facilitated by barrier disruption, including viral penetration of the blood-brain barrier and placenta, as well as inflammatory, neurological, cognitive and developmental sequelae. The underlying pathogenic mechanisms may include direct infection of pericytes, pericyte modulation by secreted viral gene products and/or the dysregulation of paracrine signalling from or to pericytes. Viruses we cover include the herpesvirus human cytomegalovirus (HCMV, Human betaherpesvirus 5), the retrovirus human immunodeficiency virus (HIV; causative agent of acquired immunodeficiency syndrome, AIDS, and HIV-associated neurocognitive disorder, HAND), the flaviviruses dengue virus (DENV), Japanese encephalitis virus (JEV) and Zika virus (ZIKV), and the coronavirus severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2; causative agent of coronavirus disease 2019, COVID-19). We touch on promising pericyte-focussed therapies for treating the diseases caused by these important human pathogens, many of which are emerging viruses or are causing new or long-standing global pandemics.


Subject(s)
Cell Physiological Phenomena , Disease Susceptibility , Host-Pathogen Interactions , Pericytes/virology , Virus Diseases/metabolism , Virus Diseases/virology , Animals , Cell Communication , Dengue Virus/physiology , Disease Management , Endothelial Cells/virology , Endothelium/metabolism , Endothelium/virology , HIV/physiology , Humans , Paracrine Communication , SARS-CoV-2/physiology , Virus Diseases/diagnosis , Virus Diseases/therapy , Virus Physiological Phenomena
11.
ACS Appl Mater Interfaces ; 13(26): 30295-30305, 2021 Jul 07.
Article in English | MEDLINE | ID: covidwho-1337092

ABSTRACT

As viruses have been threatening global public health, fast diagnosis has been critical to effective disease management and control. Reverse-transcription quantitative polymerase chain reaction (RT-qPCR) is now widely used as the gold standard for detecting viruses. Although a multiplex assay is essential for identifying virus types and subtypes, the poor multiplicity of RT-qPCR makes it laborious and time-consuming. In this paper, we describe the development of a multiplex RT-qPCR platform with hydrogel microparticles acting as independent reactors in a single reaction. To build target-specific particles, target-specific primers and probes are integrated into the particles in the form of noncovalent composites with boron nitride nanotubes (BNNTs) and carbon nanotubes (CNTs). The thermal release characteristics of DNA, primer, and probe from the composites of primer-BNNT and probe-CNT allow primer and probe to be stored in particles during particle production and to be delivered into the reaction. In addition, BNNT did not absorb but preserved the fluorescent signal, while CNT protected the fluorophore of the probe from the free radicals present during particle production. Bicompartmental primer-incorporated network (bcPIN) particles were designed to harness the distinctive properties of two nanomaterials. The bcPIN particles showed a high RT-qPCR efficiency of over 90% and effective suppression of non-specific reactions. 16-plex RT-qPCR has been achieved simply by recruiting differently coded bcPIN particles for each target. As a proof of concept, multiplex one-step RT-qPCR was successfully demonstrated with a simple reaction protocol.


Subject(s)
Hydrogels/chemistry , Multiplex Polymerase Chain Reaction/methods , Nanotubes, Carbon/chemistry , RNA, Viral/analysis , Reverse Transcriptase Polymerase Chain Reaction/methods , Boron Compounds/chemistry , Coronavirus/chemistry , DNA Primers/chemistry , DNA, Single-Stranded/chemistry , Fluorescent Dyes/chemistry , Graphite/chemistry , Influenza A virus/chemistry , Newcastle disease virus/chemistry , Proof of Concept Study , RNA, Viral/chemistry , Virus Diseases/diagnosis
12.
Small ; 17(45): e2100692, 2021 11.
Article in English | MEDLINE | ID: covidwho-1323911

ABSTRACT

Viral infection is one of the leading causes of mortality worldwide. The growth of globalization significantly increases the risk of virus spreading, making it a global threat to future public health. In particular, the ongoing coronavirus disease 2019 (COVID-19) pandemic outbreak emphasizes the importance of devices and methods for rapid, sensitive, and cost-effective diagnosis of viral infections in the early stages by which their quick and global spread can be controlled. Micro and nanoscale technologies have attracted tremendous attention in recent years for a variety of medical and biological applications, especially in developing diagnostic platforms for rapid and accurate detection of viral diseases. This review addresses advances of microneedles, microchip-based integrated platforms, and nano- and microparticles for sampling, sample processing, enrichment, amplification, and detection of viral particles and antigens related to the diagnosis of viral diseases. Additionally, methods for the fabrication of microchip-based devices and commercially used devices are described. Finally, challenges and prospects on the development of micro and nanotechnologies for the early diagnosis of viral diseases are highlighted.


Subject(s)
COVID-19 , Virus Diseases , Humans , Nanotechnology , Pandemics , SARS-CoV-2 , Virus Diseases/diagnosis
13.
Anal Chim Acta ; 1159: 338384, 2021 May 15.
Article in English | MEDLINE | ID: covidwho-1279519

ABSTRACT

Viruses are the causing agents for many relevant diseases, including influenza, Ebola, HIV/AIDS, and COVID-19. Its rapid replication and high transmissibility can lead to serious consequences not only to the individual but also to collective health, causing deep economic impacts. In this scenario, diagnosis tools are of significant importance, allowing the rapid, precise, and low-cost testing of a substantial number of individuals. Currently, PCR-based techniques are the gold standard for the diagnosis of viral diseases. Although these allow the diagnosis of different illnesses with high precision, they still present significant drawbacks. Their main disadvantages include long periods for obtaining results and the need for specialized professionals and equipment, requiring the tests to be performed in research centers. In this scenario, biosensors have been presented as promising alternatives for the rapid, precise, low-cost, and on-site diagnosis of viral diseases. This critical review article describes the advancements achieved in the last five years regarding electrochemical biosensors for the diagnosis of viral infections. First, genosensors and aptasensors for the detection of virus and the diagnosis of viral diseases are presented in detail regarding probe immobilization approaches, detection methods (label-free and sandwich), and amplification strategies. Following, immunosensors are highlighted, including many different construction strategies such as label-free, sandwich, competitive, and lateral-flow assays. Then, biosensors for the detection of viral-diseases-related biomarkers are presented and discussed, as well as point of care systems and their advantages when compared to traditional techniques. Last, the difficulties of commercializing electrochemical devices are critically discussed in conjunction with future trends such as lab-on-a-chip and flexible sensors.


Subject(s)
Biosensing Techniques , Electrochemical Techniques , Virus Diseases/diagnosis , Viruses/isolation & purification , Humans , Immunoassay
14.
Biochim Biophys Acta Mol Basis Dis ; 1867(10): 166198, 2021 10 01.
Article in English | MEDLINE | ID: covidwho-1263225

ABSTRACT

Some maternal infections, contracted before or during pregnancy, can be transmitted to the fetus, during gestation (congenital infection), during labor and childbirth (perinatal infection) and through breastfeeding (postnatal infection). The agents responsible for these infections can be viruses, bacteria, protozoa, fungi. Among the viruses most frequently responsible for congenital infections are Cytomegalovirus (CMV), Herpes simplex 1-2, Herpes virus 6, Varicella zoster. Moreover Hepatitis B and C virus, HIV, Parvovirus B19 and non-polio Enteroviruses when contracted during pregnancy may involve the fetus or newborn at birth. Recently, new viruses have emerged, SARS-Cov-2 and Zika virus, of which we do not yet fully know the characteristics and pathogenic power when contracted during pregnancy. Viral infections in pregnancy can damage the fetus (spontaneous abortion, fetal death, intrauterine growth retardation) or the newborn (congenital anomalies, organ diseases with sequelae of different severity). Some risk factors specifically influence the incidence of transmission to the fetus: the timing of the infection in pregnancy, the order of the infection, primary or reinfection or chronic, the duration of membrane rupture, type of delivery, socio-economic conditions and breastfeeding. Frequently infected neonates, symptomatic at birth, have worse outcomes than asymptomatic. Many asymptomatic babies develop long term neurosensory outcomes. The way in which the virus interacts with the maternal immune system, the maternal-fetal interface and the placenta explain these results and also the differences that are observed from time to time in the fetal­neonatal outcomes of maternal infections. The maternal immune system undergoes functional adaptation during pregnancy, once thought as physiological immunosuppression. This adaptation, crucial for generating a balance between maternal immunity and fetus, is necessary to promote and support the pregnancy itself and the growth of the fetus. When this adaptation is upset by the viral infection, the balance is broken, and the infection can spread and lead to the adverse outcomes previously described. In this review we will describe the main viral harmful infections in pregnancy and the potential mechanisms of the damages on the fetus and newborn.


Subject(s)
Congenital Abnormalities/etiology , Infectious Disease Transmission, Vertical , Pregnancy Complications, Infectious , Virus Diseases/complications , Animals , COVID-19/complications , COVID-19/diagnosis , COVID-19/prevention & control , COVID-19/transmission , Congenital Abnormalities/diagnosis , Congenital Abnormalities/prevention & control , Cytomegalovirus/isolation & purification , Cytomegalovirus Infections/complications , Cytomegalovirus Infections/diagnosis , Cytomegalovirus Infections/prevention & control , Cytomegalovirus Infections/transmission , Female , Humans , Pregnancy , Pregnancy Complications, Infectious/diagnosis , Pregnancy Complications, Infectious/prevention & control , Pregnancy Outcome , SARS-CoV-2/isolation & purification , Virus Diseases/diagnosis , Virus Diseases/prevention & control , Virus Diseases/transmission , Zika Virus/isolation & purification , Zika Virus Infection/complications , Zika Virus Infection/diagnosis , Zika Virus Infection/prevention & control , Zika Virus Infection/transmission
15.
J Med Virol ; 93(2): 1119-1125, 2021 02.
Article in English | MEDLINE | ID: covidwho-1206810

ABSTRACT

Following the announcement of the first coronavirus disease 2019 (COVID-19) case on 11 March 2020 in Turkey, we aimed to report the coinfection rates, and the clinical, laboratory, radiological distinctive features of viral pneumonia caused by viruses other than severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A cross-sectional study was conducted between 18 and 31 March 2020. COVID-19 suspected cases admitted to pandemic policlinic, who had nasopharyngeal swab specimens tested for both SARS-CoV-2 and other respiratory viral pathogens, were included. Among 112 patients, SARS-CoV-2 was detected in 34 patients (30%). Among the non-SARS-CoV-2 viruses (n = 25, 22%), metapneumovirus (n = 10) was the most frequent agent. There were two coinfections with SARS-CoV-2. Sputum was less in the SARS-CoV-2 group (P = .003). The leukocyte, lymphocyte, and thrombocyte count and C-reactive protein levels were the lowest in the SARS-CoV-2 group (P < .001, P = .04, P < .001, P = .007, respectively). Peripheral involvement (80% vs 20%; P ≤ .001), pure ground-glass opacity (65% vs 33%; P = .04), apicobasal gradient (60% vs 40%; P = .08), involvement of greater than or equal to three lobes (80% vs 40%; odds ratio: 6.0; 95% confidence interval: 1.33-27.05; P = .02), and consolidation with accompanying ground-glass opacity (4% vs 33%; P = .031) were more common in SARS-CoV-2 group. Some clinical, laboratory, and radiological findings may help in the differential diagnosis of non-SARS-CoV-2 viruses from COVID-19. However, coinfections may occur, and a non-SARS-CoV-2 pathogen positivity does not exclude accompanying COVID-19.


Subject(s)
Pneumonia, Viral/diagnosis , Virus Diseases/diagnosis , Viruses/isolation & purification , Adult , Aged , COVID-19/epidemiology , Coinfection/diagnosis , Coinfection/virology , Cross-Sectional Studies , Diagnosis, Differential , Hospitalization , Humans , Middle Aged , Nasopharynx/virology , Pneumonia, Viral/epidemiology , Sputum/virology , Tomography, X-Ray Computed , Turkey/epidemiology , Virus Diseases/epidemiology , Viruses/classification , Viruses/genetics
16.
Int J Mol Sci ; 22(8)2021 Apr 17.
Article in English | MEDLINE | ID: covidwho-1206368

ABSTRACT

Viral infections cause a host of fatal diseases and seriously affect every form of life from bacteria to humans. Although most viral infections can receive appropriate treatment thereby limiting damage to life and livelihood with modern medicine and early diagnosis, new types of viral infections are continuously emerging that need to be properly and timely treated. As time is the most important factor in the progress of many deadly viral diseases, early detection becomes of paramount importance for effective treatment. Aptamers are small oligonucleotide molecules made by the systematic evolution of ligands by exponential enrichment (SELEX). Aptamers are characterized by being able to specifically bind to a target, much like antibodies. However, unlike antibodies, aptamers are easily synthesized, modified, and are able to target a wider range of substances, including proteins and carbohydrates. With these advantages in mind, many studies on aptamer-based viral diagnosis and treatments are currently in progress. The use of aptamers for viral diagnosis requires a system that recognizes the binding of viral molecules to aptamers in samples of blood, serum, plasma, or in virus-infected cells. From a therapeutic perspective, aptamers target viral particles or host cell receptors to prevent the interaction between the virus and host cells or target intracellular viral proteins to interrupt the life cycle of the virus within infected cells. In this paper, we review recent attempts to use aptamers for the diagnosis and treatment of various viral infections.


Subject(s)
Antiviral Agents/therapeutic use , Aptamers, Nucleotide/therapeutic use , Virus Diseases/diagnosis , Virus Diseases/drug therapy , Animals , DNA Viruses/drug effects , Humans , RNA Viruses/drug effects , Viral Proteins/drug effects , Virion/drug effects
17.
EBioMedicine ; 67: 103352, 2021 May.
Article in English | MEDLINE | ID: covidwho-1205123

ABSTRACT

BACKGROUND: Precise differential diagnosis between acute viral and bacterial infections is important to enable appropriate therapy, avoid unnecessary antibiotic prescriptions and optimize the use of hospital resources. A systems view of host response to infections provides opportunities for discovering sensitive and robust molecular diagnostics. METHODS: We combine blood transcriptomes from six independent datasets (n = 756) with a knowledge-based human protein-protein interaction network, identifies subnetworks capturing host response to each infection class, and derives common response cores separately for viral and bacterial infections. We subject the subnetworks to a series of computational filters to identify a parsimonious gene panel and a standalone diagnostic score that can be applied to individual samples. We rigorously validate the panel and the diagnostic score in a wide range of publicly available datasets and in a newly developed Bangalore-Viral Bacterial (BL-VB) cohort. FINDING: We discover a 10-gene blood-based biomarker panel (Panel-VB) that demonstrates high predictive performance to distinguish viral from bacterial infections, with a weighted mean AUROC of 0.97 (95% CI: 0.96-0.99) in eleven independent datasets (n = 898). We devise a new stand-alone patient-wise score (VB10) based on the panel, which shows high diagnostic accuracy with a weighted mean AUROC of 0.94 (95% CI 0.91-0.98) in 2996 patient samples from 56 public datasets from 19 different countries. Further, we evaluate VB10 in a newly generated South Indian (BL-VB, n = 56) cohort and find 97% accuracy in the confirmed cases of viral and bacterial infections. We find that VB10 is (a) capable of accurately identifying the infection class in culture-negative indeterminate cases, (b) reflects recovery status, and (c) is applicable across different age groups, covering a wide spectrum of acute bacterial and viral infections, including uncharacterized pathogens. We tested our VB10 score on publicly available COVID-19 data and find that our score detected viral infection in patient samples. INTERPRETATION: Our results point to the promise of VB10 as a diagnostic test for precise diagnosis of acute infections and monitoring recovery status. We expect that it will provide clinical decision support for antibiotic prescriptions and thereby aid in antibiotic stewardship efforts. FUNDING: Grand Challenges India, Biotechnology Industry Research Assistance Council (BIRAC), Department of Biotechnology, Govt. of India.


Subject(s)
Bacterial Infections/diagnosis , Biomarkers/blood , Computational Biology/methods , Virus Diseases/diagnosis , Adult , Bacterial Infections/blood , Bacterial Infections/genetics , Databases, Factual , Decision Support Systems, Clinical , Diagnosis, Differential , Female , Gene Expression Profiling , Humans , India , Male , Middle Aged , Observational Studies as Topic , Predictive Value of Tests , Protein Interaction Maps , Virus Diseases/blood , Virus Diseases/genetics
18.
Biosensors (Basel) ; 11(4)2021 Apr 15.
Article in English | MEDLINE | ID: covidwho-1186891

ABSTRACT

The rapid spread of epidemic diseases (i.e., coronavirus disease 2019 (COVID-19)) has contributed to focus global attention on the diagnosis of medical conditions by ultrasensitive detection methods. To overcome this challenge, increasing efforts have been driven towards the development of single-molecule analytical platforms. In this context, recent progress in plasmonic biosensing has enabled the design of novel detection strategies capable of targeting individual molecules while evaluating their binding affinity and biological interactions. This review compiles the latest advances in plasmonic technologies for monitoring clinically relevant biomarkers at the single-molecule level. Functional applications are discussed according to plasmonic sensing modes based on either nanoapertures or nanoparticle approaches. A special focus was devoted to new analytical developments involving a wide variety of analytes (e.g., proteins, living cells, nucleic acids and viruses). The utility of plasmonic-based single-molecule analysis for personalized medicine, considering technological limitations and future prospects, is also overviewed.


Subject(s)
Biosensing Techniques/methods , Virus Diseases/diagnosis , Biomarkers/analysis , Biomarkers/metabolism , Biosensing Techniques/instrumentation , COVID-19/diagnosis , COVID-19/virology , Humans , Nanoparticles/chemistry , Nucleic Acids/analysis , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification , Single-Cell Analysis , Surface Plasmon Resonance , Virus Diseases/virology
19.
PLoS Negl Trop Dis ; 14(10): e0008699, 2020 10.
Article in English | MEDLINE | ID: covidwho-932350

ABSTRACT

Surveillance of highly pathogenic viruses circulating in both human and animal populations is crucial to unveil endemic infections and potential zoonotic reservoirs. Monitoring the burden of disease by serological assay could be used as an early warning system for imminent outbreaks as an increased seroprevalance often precedes larger outbreaks. However, the multitude of highly pathogenic viruses necessitates the need to identify specific antibodies against several targets from both humans as well as from potential reservoir animals such as bats. In order to address this, we have developed a broadly reactive multiplex microsphere immunoassay (MMIA) for the detection of antibodies against several highly pathogenic viruses from both humans and animals. To this aim, nucleoproteins (NP) of Ebola virus (EBOV), Marburg virus (MARV) and nucleocapsid proteins (NP) of Crimean-Congo haemorrhagic fever virus, Rift Valley fever virus and Dobrava-Belgrade hantavirus were employed in a 5-plex assay for IgG detection. After optimisation, specific binding to each respective NP was shown by testing sera from humans and non-human primates with known infection status. The usefulness of our assay for serosurveillance was shown by determining the immune response against the NP antigens in a panel of 129 human serum samples collected in Guinea between 2011 and 2012 in comparison to a panel of 88 sera from the German blood bank. We found good agreement between our MMIA and commercial or in-house reference methods by ELISA or IIFT with statistically significant higher binding to both EBOV NP and MARV NP coupled microspheres in the Guinea panel. Finally, the MMIA was successfully adapted to detect antibodies from bats that had been inoculated with EBOV- and MARV- virus-like particles, highlighting the versatility of this technique and potentially enabling the monitoring of wildlife as well as human populations with this assay. We were thus able to develop and validate a sensitive and broadly reactive high-throughput serological assay which could be used as a screening tool to detect antibodies against several highly pathogenic viruses.


Subject(s)
Antibodies, Viral/blood , Immunoassay/methods , Microspheres , Nucleocapsid Proteins/immunology , Virus Diseases/veterinary , Animals , Chiroptera , Humans , Primates , Virus Diseases/diagnosis , Virus Diseases/virology
20.
Influenza Other Respir Viruses ; 15(4): 478-487, 2021 07.
Article in English | MEDLINE | ID: covidwho-1171118

ABSTRACT

BACKGROUND: Physical distancing and facemask use are worldwide recognized as effective non-pharmaceutical interventions (NPIs) against the coronavirus disease-2019 (COVID-19). Since January 2020, Taiwan has introduced both NPIs but their effectiveness on non-COVID-19 respiratory viruses (NCRVs) remain underexplored. METHODS: This retrospective observational study examined electronic records at a tertiary hospital in northern Taiwan from pre-COVID (January-December 2019) to post-COVID period (January-May 2020). Patients with respiratory syndromes were tested for both enveloped (eg, influenza virus and seasonal coronavirus) and non-enveloped RVs (eg, enterovirus and rhinovirus) using multiplex reverse transcription polymerase chain reaction assays. Monthly positivity rates of NCRVs among adult and pediatric patients were analyzed with comparison between pre- and post-COVID periods. RESULTS: A total of 9693 patients underwent 12 127 multiplex RT-PCR tests. The average positivity rate of NCRVs reduced by 11.2% (25.6% to 14.4%) after nationwide PHIs. Despite the COVID-19 pandemic, the most commonly identified enveloped and non-enveloped viruses were influenza virus and enterovirus/rhinovirus, respectively. Observed reduction in NCRV incidence was predominantly contributed by enveloped NCRVs including influenza viruses. We did not observe epidemiological impacts of NPIs on non-enveloped viruses but an increasing trend in enterovirus/rhinovirus test positivity rate among pediatric patients. Our data were validated using Taiwan's national notification database. CONCLUSIONS: Our frontline investigation suggests that the current NPIs in Taiwan might not effectively control the transmission of non-enveloped respiratory viruses, despite their protective effects against influenza and seasonal coronavirus. Health authorities may consider using hydrogen peroxide or chloride-based disinfectants as additional preventative strategies against non-enveloped respiratory viruses in the post-COVID-19 era.


Subject(s)
Communicable Disease Control/methods , Respiratory Tract Infections/prevention & control , Virus Diseases/prevention & control , Adult , COVID-19/epidemiology , COVID-19/prevention & control , Child , Humans , Masks , Middle Aged , Multiplex Polymerase Chain Reaction , Physical Distancing , Respiratory Tract Infections/diagnosis , Respiratory Tract Infections/epidemiology , Retrospective Studies , SARS-CoV-2 , Species Specificity , Taiwan/epidemiology , Tertiary Care Centers , Viral Envelope Proteins/genetics , Viral Envelope Proteins/metabolism , Virus Diseases/diagnosis , Virus Diseases/epidemiology , Viruses/classification , Viruses/genetics , Viruses/isolation & purification
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