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1.
Nat Med ; 27(6): 1012-1024, 2021 06.
Article in English | MEDLINE | ID: covidwho-1472229

ABSTRACT

Age is the dominant risk factor for infectious diseases, but the mechanisms linking age to infectious disease risk are incompletely understood. Age-related mosaic chromosomal alterations (mCAs) detected from genotyping of blood-derived DNA, are structural somatic variants indicative of clonal hematopoiesis, and are associated with aberrant leukocyte cell counts, hematological malignancy, and mortality. Here, we show that mCAs predispose to diverse types of infections. We analyzed mCAs from 768,762 individuals without hematological cancer at the time of DNA acquisition across five biobanks. Expanded autosomal mCAs were associated with diverse incident infections (hazard ratio (HR) 1.25; 95% confidence interval (CI) = 1.15-1.36; P = 1.8 × 10-7), including sepsis (HR 2.68; 95% CI = 2.25-3.19; P = 3.1 × 10-28), pneumonia (HR 1.76; 95% CI = 1.53-2.03; P = 2.3 × 10-15), digestive system infections (HR 1.51; 95% CI = 1.32-1.73; P = 2.2 × 10-9) and genitourinary infections (HR 1.25; 95% CI = 1.11-1.41; P = 3.7 × 10-4). A genome-wide association study of expanded mCAs identified 63 loci, which were enriched at transcriptional regulatory sites for immune cells. These results suggest that mCAs are a marker of impaired immunity and confer increased predisposition to infections.


Subject(s)
Aging/genetics , Communicable Diseases/genetics , Pneumonia/genetics , Sepsis/genetics , Adolescent , Adult , Aged , Aged, 80 and over , Aging/pathology , Biological Specimen Banks , Chromosome Aberrations , Communicable Diseases/complications , Communicable Diseases/microbiology , Digestive System Diseases/epidemiology , Digestive System Diseases/genetics , Digestive System Diseases/microbiology , Female , Genetic Predisposition to Disease , Genome-Wide Association Study , Genotype , Hematologic Neoplasms/complications , Hematologic Neoplasms/genetics , Hematologic Neoplasms/microbiology , Humans , Male , Middle Aged , Mosaicism , Pneumonia/epidemiology , Pneumonia/microbiology , Risk Factors , Sepsis/epidemiology , Sepsis/microbiology , Urogenital Abnormalities/epidemiology , Urogenital Abnormalities/genetics , Urogenital Abnormalities/microbiology , Young Adult
2.
Theranostics ; 11(18): 9133-9161, 2021.
Article in English | MEDLINE | ID: covidwho-1410987

ABSTRACT

During an epidemic or pandemic, the primary task is to rapidly develop precise diagnostic approaches and effective therapeutics. Oligonucleotide aptamer-based pathogen detection assays and control therapeutics are promising, as aptamers that specifically recognize and block pathogens can be quickly developed and produced through simple chemical synthesis. This work reviews common aptamer-based diagnostic techniques for communicable diseases and summarizes currently available aptamers that target various pathogens, including the SARS-CoV-2 virus. Moreover, this review discusses how oligonucleotide aptamers might be leveraged to control pathogen propagation and improve host immune system responses. This review offers a comprehensive data source to the further develop aptamer-based diagnostics and therapeutics specific for infectious diseases.


Subject(s)
Aptamers, Nucleotide , Bacteria/genetics , Communicable Diseases/diagnosis , Molecular Diagnostic Techniques/methods , Viruses/genetics , Aptamers, Nucleotide/pharmacology , Biosensing Techniques , COVID-19 Testing/methods , Communicable Disease Control , Communicable Diseases/microbiology , Communicable Diseases/virology , Enzyme-Linked Immunosorbent Assay/methods , Host-Pathogen Interactions/immunology , Humans , SELEX Aptamer Technique , Virus Internalization
3.
J Mater Chem B ; 9(38): 7878-7908, 2021 10 06.
Article in English | MEDLINE | ID: covidwho-1373457

ABSTRACT

Infectious diseases caused by bacteria, viruses, and fungi and their global spread pose a great threat to human health. The 2019 World Health Organization report predicted that infection-related mortality will be similar to cancer mortality by 2050. Particularly, the global cumulative numbers of the recent outbreak of coronavirus disease (COVID-19) have reached 110.7 million cases and over 2.4 million deaths as of February 23, 2021. Moreover, the crisis of these infectious diseases exposes the many problems of traditional diagnosis, treatment, and prevention, such as time-consuming and unselective detection methods, the emergence of drug-resistant bacteria, serious side effects, and poor drug delivery. There is an urgent need for rapid and sensitive diagnosis as well as high efficacy and low toxicity treatments. The emergence of nanomedicine has provided a promising strategy to greatly enhance detection methods and drug treatment efficacy. Owing to their unique optical, magnetic, and electrical properties, nanoparticles (NPs) have great potential for the fast and selective detection of bacteria, viruses, and fungi. NPs exhibit remarkable antibacterial activity by releasing reactive oxygen species and metal ions, exerting photothermal effects, and causing destruction of the cell membrane. Nano-based delivery systems can further improve drug permeability, reduce the side effects of drugs, and prolong systemic circulation time and drug half-life. Moreover, effective drugs against COVID-19 are still lacking. Recently, nanomedicine has shown great potential to accelerate the development of safe and novel anti-COVID-19 drugs. This article reviews the fundamental mechanisms and the latest developments in the treatment and diagnosis of bacteria, viruses, and fungi and discusses the challenges and perspectives in the application of nanomedicine.


Subject(s)
Anti-Infective Agents/therapeutic use , Communicable Diseases/drug therapy , Nanomedicine , Anti-Infective Agents/chemistry , COVID-19/diagnosis , COVID-19/drug therapy , COVID-19/virology , Communicable Diseases/diagnosis , Communicable Diseases/microbiology , Communicable Diseases/virology , Drug Carriers/chemistry , Humans , Nanoparticles/chemistry , Reactive Oxygen Species/metabolism , SARS-CoV-2/isolation & purification
4.
Nat Biomed Eng ; 5(7): 643-656, 2021 07.
Article in English | MEDLINE | ID: covidwho-1324420

ABSTRACT

The accurate and timely diagnosis of disease is a prerequisite for efficient therapeutic intervention and epidemiological surveillance. Diagnostics based on the detection of nucleic acids are among the most sensitive and specific, yet most such assays require costly equipment and trained personnel. Recent developments in diagnostic technologies, in particular those leveraging clustered regularly interspaced short palindromic repeats (CRISPR), aim to enable accurate testing at home, at the point of care and in the field. In this Review, we provide a rundown of the rapidly expanding toolbox for CRISPR-based diagnostics, in particular the various assays, preamplification strategies and readouts, and highlight their main applications in the sensing of a wide range of molecular targets relevant to human health.


Subject(s)
CRISPR-Cas Systems/genetics , Communicable Diseases/diagnosis , Nucleic Acid Amplification Techniques/methods , Nucleic Acids/analysis , Communicable Diseases/microbiology , Communicable Diseases/virology , Genetic Diseases, Inborn/diagnosis , Humans , Nucleic Acid Amplification Techniques/economics , Nucleic Acids/metabolism , Point-of-Care Systems , Polymorphism, Single Nucleotide , Sequence Analysis, DNA
6.
Int J Mol Sci ; 22(5)2021 Mar 08.
Article in English | MEDLINE | ID: covidwho-1134168

ABSTRACT

The fruit fly, Drosophila melanogaster, has been used to understand fundamental principles of genetics and biology for over a century. Drosophila is now also considered an essential tool to study mechanisms underlying numerous human genetic diseases. In this review, we will discuss how flies can be used to deepen our knowledge of infectious disease mechanisms in vivo. Flies make effective and applicable models for studying host-pathogen interactions thanks to their highly conserved innate immune systems and cellular processes commonly hijacked by pathogens. Drosophila researchers also possess the most powerful, rapid, and versatile tools for genetic manipulation in multicellular organisms. This allows for robust experiments in which specific pathogenic proteins can be expressed either one at a time or in conjunction with each other to dissect the molecular functions of each virulent factor in a cell-type-specific manner. Well documented phenotypes allow large genetic and pharmacological screens to be performed with relative ease using huge collections of mutant and transgenic strains that are publicly available. These factors combine to make Drosophila a powerful tool for dissecting out host-pathogen interactions as well as a tool to better understand how we can treat infectious diseases that pose risks to public health, including COVID-19, caused by SARS-CoV-2.


Subject(s)
Communicable Diseases/immunology , Communicable Diseases/metabolism , Drosophila melanogaster/immunology , Drosophila melanogaster/metabolism , Animals , Communicable Diseases/microbiology , Communicable Diseases/virology , Drosophila melanogaster/microbiology , Drosophila melanogaster/virology , Host-Pathogen Interactions , Immunity, Innate , Signal Transduction , Virulence Factors/metabolism
7.
Pathog Glob Health ; 115(3): 151-167, 2021 05.
Article in English | MEDLINE | ID: covidwho-1082903

ABSTRACT

Before the 20th century many deaths in England, and most likely a majority, were caused by infectious diseases. The focus here is on the biggest killers, plague, typhus, smallpox, tuberculosis, cholera, typhoid, dysentery, childhood infections, pneumonia, and influenza. Many other infectious diseases including puerperal fever, relapsing fever, malaria, syphilis, meningitis, tetanus and gangrene caused thousands of deaths. This review of preventive measures, public health interventions and changes in behavior that reduced the risk of severe infections puts the response to recent epidemic challenges in historical perspective. Two new respiratory viruses have recently caused pandemics: an H1N1 influenza virus genetically related to pig viruses, and a bat-derived coronavirus causing COVID-19. Studies of infectious diseases emerging in human populations in recent decades indicate that the majority were zoonotic, and many of the causal pathogens had a wildlife origin. As hunter-gatherers, humans contracted pathogens from other species, and then from domesticated animals and rodents when they began to live in settled communities based on agriculture. In the modern world of large inter-connected urban populations and rapid transport, the risk of global transmission of new infectious diseases is high. Past and recent experience indicates that surveillance, prevention and control of infectious diseases are critical for global health. Effective interventions are required to control activities that risk dangerous pathogens transferring to humans from wild animals and those reared for food.


Subject(s)
Communicable Disease Control/history , Communicable Diseases/history , Animals , Communicable Diseases/epidemiology , Communicable Diseases/microbiology , Communicable Diseases/virology , History, 15th Century , History, 16th Century , History, 17th Century , History, 18th Century , History, 19th Century , History, 20th Century , History, 21st Century , History, Ancient , History, Medieval , Humans , Public Health/history
8.
Nutrients ; 13(1)2021 Jan 08.
Article in English | MEDLINE | ID: covidwho-1067765

ABSTRACT

Reduced magnesium (Mg) intake is a frequent cause of deficiency with age together with reduced absorption, renal wasting, and polypharmacotherapy. Chronic Mg deficiency may result in increased oxidative stress and low-grade inflammation, which may be linked to several age-related diseases, including higher predisposition to infectious diseases. Mg might play a role in the immune response being a cofactor for immunoglobulin synthesis and other processes strictly associated with the function of T and B cells. Mg is necessary for the biosynthesis, transport, and activation of vitamin D, another key factor in the pathogenesis of infectious diseases. The regulation of cytosolic free Mg in immune cells involves Mg transport systems, such as the melastatin-like transient receptor potential 7 channel, the solute carrier family, and the magnesium transporter 1 (MAGT1). The functional importance of Mg transport in immunity was unknown until the description of the primary immunodeficiency XMEN (X-linked immunodeficiency with Mg defect, Epstein-Barr virus infection, and neoplasia) due to a genetic deficiency of MAGT1 characterized by chronic Epstein-Barr virus infection. This and other research reporting associations of Mg deficit with viral and bacterial infections indicate a possible role of Mg deficit in the recent coronavirus disease 2019 (COVID-19) and its complications. In this review, we will discuss the importance of Mg for the immune system and for infectious diseases, including the recent pandemic of COVID-19.


Subject(s)
Aging/physiology , COVID-19/metabolism , Communicable Diseases/metabolism , Magnesium Deficiency/complications , Magnesium/metabolism , Aged , COVID-19/etiology , COVID-19/immunology , COVID-19/virology , Cation Transport Proteins/metabolism , Communicable Diseases/immunology , Communicable Diseases/microbiology , Communicable Diseases/virology , Epstein-Barr Virus Infections/metabolism , Female , Humans , Magnesium/immunology , Magnesium Deficiency/immunology , Magnesium Deficiency/metabolism , Male , SARS-CoV-2/immunology , X-Linked Combined Immunodeficiency Diseases/metabolism
9.
Int J Mol Sci ; 22(1)2020 Dec 29.
Article in English | MEDLINE | ID: covidwho-1067750

ABSTRACT

Recently, there has been a growing interest in the medical applications of Cannabis plants. They owe their unique properties to a group of secondary metabolites known as phytocannabinoids, which are specific for this genus. Phytocannabinoids, and cannabinoids generally, can interact with cannabinoid receptors being part of the endocannabinoid system present in animals. Over the years a growing body of scientific evidence has been gathered, suggesting that these compounds have therapeutic potential. In this article, we review the classification of cannabinoids, the molecular mechanisms of their interaction with animal cells as well as their potential application in the treatment of human diseases. Specifically, we focus on the research concerning the anticancer potential of cannabinoids in preclinical studies, their possible use in cancer treatment and palliative medicine, as well as their influence on the immune system. We also discuss their potential as therapeutic agents in infectious, autoimmune, and gastrointestinal inflammatory diseases. We postulate that the currently ongoing and future clinical trials should be accompanied by research focused on the cellular and molecular response to cannabinoids and Cannabis extracts, which will ultimately allow us to fully understand the mechanism, potency, and safety profile of cannabinoids as single agents and as complementary drugs.


Subject(s)
Cannabinoids/pharmacology , Cannabinoids/therapeutic use , Animals , Anti-Infective Agents/pharmacology , Anti-Infective Agents/therapeutic use , Antineoplastic Agents, Phytogenic/pharmacology , Antineoplastic Agents, Phytogenic/therapeutic use , Apoptosis/drug effects , Cannabinoids/chemistry , Cannabis/chemistry , Chemistry Techniques, Synthetic , Communicable Diseases/drug therapy , Communicable Diseases/microbiology , Communicable Diseases/virology , Humans , Immune System/drug effects , Immune System/immunology , Immune System/metabolism , Immunologic Factors/pharmacology , Immunologic Factors/therapeutic use , Neoplasms/drug therapy , Receptors, Cannabinoid/metabolism
10.
mBio ; 12(1)2021 01 12.
Article in English | MEDLINE | ID: covidwho-1030241

ABSTRACT

Despite being nearly 10 months into the COVID-19 (coronavirus disease 2019) pandemic, the definitive animal host for SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), the causal agent of COVID-19, remains unknown. Unfortunately, similar problems exist for other betacoronaviruses, and no vouchered specimens exist to corroborate host species identification for most of these pathogens. This most basic information is critical to the full understanding and mitigation of emerging zoonotic diseases. To overcome this hurdle, we recommend that host-pathogen researchers adopt vouchering practices and collaborate with natural history collections to permanently archive microbiological samples and host specimens. Vouchered specimens and associated samples provide both repeatability and extension to host-pathogen studies, and using them mobilizes a large workforce (i.e., biodiversity scientists) to assist in pandemic preparedness. We review several well-known examples that successfully integrate host-pathogen research with natural history collections (e.g., yellow fever, hantaviruses, helminths). However, vouchering remains an underutilized practice in such studies. Using an online survey, we assessed vouchering practices used by microbiologists (e.g., bacteriologists, parasitologists, virologists) in host-pathogen research. A much greater number of respondents permanently archive microbiological samples than archive host specimens, and less than half of respondents voucher host specimens from which microbiological samples were lethally collected. To foster collaborations between microbiologists and natural history collections, we provide recommendations for integrating vouchering techniques and archiving of microbiological samples into host-pathogen studies. This integrative approach exemplifies the premise underlying One Health initiatives, providing critical infrastructure for addressing related issues ranging from public health to global climate change and the biodiversity crisis.


Subject(s)
Biomedical Research/standards , Communicable Diseases/pathology , Natural History/standards , Zoonoses/pathology , Animals , Biodiversity , Biomedical Research/trends , COVID-19/pathology , COVID-19/virology , Communicable Diseases/microbiology , Communicable Diseases/parasitology , Communicable Diseases/virology , Host-Pathogen Interactions , Humans , Museums/standards , SARS-CoV-2/classification , SARS-CoV-2/physiology , Specimen Handling , Zoonoses/microbiology , Zoonoses/parasitology , Zoonoses/virology
11.
Nutrients ; 13(1)2021 Jan 08.
Article in English | MEDLINE | ID: covidwho-1016214

ABSTRACT

Reduced magnesium (Mg) intake is a frequent cause of deficiency with age together with reduced absorption, renal wasting, and polypharmacotherapy. Chronic Mg deficiency may result in increased oxidative stress and low-grade inflammation, which may be linked to several age-related diseases, including higher predisposition to infectious diseases. Mg might play a role in the immune response being a cofactor for immunoglobulin synthesis and other processes strictly associated with the function of T and B cells. Mg is necessary for the biosynthesis, transport, and activation of vitamin D, another key factor in the pathogenesis of infectious diseases. The regulation of cytosolic free Mg in immune cells involves Mg transport systems, such as the melastatin-like transient receptor potential 7 channel, the solute carrier family, and the magnesium transporter 1 (MAGT1). The functional importance of Mg transport in immunity was unknown until the description of the primary immunodeficiency XMEN (X-linked immunodeficiency with Mg defect, Epstein-Barr virus infection, and neoplasia) due to a genetic deficiency of MAGT1 characterized by chronic Epstein-Barr virus infection. This and other research reporting associations of Mg deficit with viral and bacterial infections indicate a possible role of Mg deficit in the recent coronavirus disease 2019 (COVID-19) and its complications. In this review, we will discuss the importance of Mg for the immune system and for infectious diseases, including the recent pandemic of COVID-19.


Subject(s)
Aging/physiology , COVID-19/metabolism , Communicable Diseases/metabolism , Magnesium Deficiency/complications , Magnesium/metabolism , Aged , COVID-19/etiology , COVID-19/immunology , COVID-19/virology , Cation Transport Proteins/metabolism , Communicable Diseases/immunology , Communicable Diseases/microbiology , Communicable Diseases/virology , Epstein-Barr Virus Infections/metabolism , Female , Humans , Magnesium/immunology , Magnesium Deficiency/immunology , Magnesium Deficiency/metabolism , Male , SARS-CoV-2/immunology , X-Linked Combined Immunodeficiency Diseases/metabolism
12.
Commun Dis Intell (2018) ; 442020 Oct 25.
Article in English | MEDLINE | ID: covidwho-962054

ABSTRACT

Abstract: Strict physical distancing measures and border controls have been introduced in the Northern Territory (NT), and across Australia, to reduce the spread of coronavirus disease 2019 (COVID-19). These measures have been associated with reduced incidence of other respiratory illnesses such as influenza. It is currently unclear what effect these measures have on non-respiratory communicable diseases. The incidence of notifiable non-respiratory communicable diseases within the NT, from 15 March to 15 May 2020, the period of most restrictive physical distancing, was monitored and is here compared with two control periods: (i) the 4 months immediately prior and (ii) the same two-month period from the preceding 5 years. During the study period, there was a decline in incidence of communicable enteric illnesses, particularly in shigellosis and rotavirus where person-to-person spread is the main transmission route. There was an increase in chlamydial conjunctivitis in areas with endemic trachoma, which is under further investigation. There was no observed increase in conditions associated with crowding, such as those related to group A streptococcal infection.


Subject(s)
COVID-19/epidemiology , COVID-19/prevention & control , Communicable Diseases/epidemiology , Physical Distancing , COVID-19/transmission , COVID-19/virology , Communicable Diseases/microbiology , Humans , Incidence , Northern Territory/epidemiology , Pandemics/prevention & control , SARS-CoV-2/isolation & purification
14.
Biosens Bioelectron ; 169: 112592, 2020 Dec 01.
Article in English | MEDLINE | ID: covidwho-747238

ABSTRACT

Global health and food security constantly face the challenge of emerging human and plant diseases caused by bacteria, viruses, fungi, and other pathogens. Disease outbreaks such as SARS, MERS, Swine Flu, Ebola, and COVID-19 (on-going) have caused suffering, death, and economic losses worldwide. To prevent the spread of disease and protect human populations, rapid point-of-care (POC) molecular diagnosis of human and plant diseases play an increasingly crucial role. Nucleic acid-based molecular diagnosis reveals valuable information at the genomic level about the identity of the disease-causing pathogens and their pathogenesis, which help researchers, healthcare professionals, and patients to detect the presence of pathogens, track the spread of disease, and guide treatment more efficiently. A typical nucleic acid-based diagnostic test consists of three major steps: nucleic acid extraction, amplification, and amplicon detection. Among these steps, nucleic acid extraction is the first step of sample preparation, which remains one of the main challenges when converting laboratory molecular assays into POC tests. Sample preparation from human and plant specimens is a time-consuming and multi-step process, which requires well-equipped laboratories and skilled lab personnel. To perform rapid molecular diagnosis in resource-limited settings, simpler and instrument-free nucleic acid extraction techniques are required to improve the speed of field detection with minimal human intervention. This review summarizes the recent advances in POC nucleic acid extraction technologies. In particular, this review focuses on novel devices or methods that have demonstrated applicability and robustness for the isolation of high-quality nucleic acid from complex raw samples, such as human blood, saliva, sputum, nasal swabs, urine, and plant tissues. The integration of these rapid nucleic acid preparation methods with miniaturized assay and sensor technologies would pave the road for the "sample-in-result-out" diagnosis of human and plant diseases, especially in remote or resource-limited settings.


Subject(s)
Communicable Diseases/diagnosis , Lab-On-A-Chip Devices , Nucleic Acids/isolation & purification , Plant Diseases , Point-of-Care Systems , Betacoronavirus/isolation & purification , COVID-19 , Chemical Fractionation/instrumentation , Chemical Fractionation/methods , Communicable Diseases/microbiology , Communicable Diseases/parasitology , Communicable Diseases/virology , Coronavirus Infections/diagnosis , Coronavirus Infections/virology , Equipment Design , Humans , Nucleic Acid Amplification Techniques/instrumentation , Nucleic Acid Amplification Techniques/methods , Nucleic Acids/blood , Nucleic Acids/urine , Pandemics , Plant Diseases/microbiology , Plant Diseases/parasitology , Plant Diseases/virology , Pneumonia, Viral/diagnosis , Pneumonia, Viral/virology , SARS-CoV-2
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