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1.
J Infect Dev Ctries ; 15(1): 58-68, 2021 Jan 31.
Article in English | MEDLINE | ID: covidwho-1079734

ABSTRACT

INTRODUCTION: SARS-CoV2 pandemic marks the need to pay attention to bacterial pathogens that can complicate the hospital stay of patients in the intensive care unit (ICU). ESKAPE bacteria which includes Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter cloacae are considered the most important, because of their close relationship with the development of ventilator-associated pneumonia (VAP). The aim of this work was to identify and characterize ESKAPE bacteria and to detect their possible clonal spread in medical devices, patients, and medical personnel of the ICU for COVID-19 patients of the Hospital Juarez de Mexico. METHODOLOGY: Genetic identification of ESKAPE bacteria was performed by analyzing the 16S rRNA gene. Resistance assays were performed according to the CLSI guidelines. Assembly of AdeABCRS operon and inhibition assays of pumps efflux in Acinetobacter baumannii isolates were performed. Associated gene involved in biofilm formation (icaA) was performed in isolates belonging to the Staphylococcus genus. Finally, typing by ERIC-PCR and characterization of mobile genetic element SCCmec were done. RESULTS: Heterogeneous distribution of ESKAPE and non-ESKAPE bacteria was detected in various medical devices, patients, and medical personnel. Acinetobacter baumannii and Staphylococcus aureus were the predominant ESKAPE members. The analysis of intergenic regions revealed an important clonal distribution of A. baumannii (AdeABCRS+). Genotyping of SCCmec mobile genetic elements and the icaA gene showed that there is no clonal distribution of S. aureus. CONCLUSIONS: Clonal spread of A. baumannii (AdeABCRS+) highlights the importance of adopting good practices for equipment disinfection, surfaces and management of COVID-19 patients.


Subject(s)
Acinetobacter Infections/transmission , Acinetobacter baumannii/isolation & purification , Cross Infection/prevention & control , Intensive Care Units , Acinetobacter baumannii/pathogenicity , Anti-Bacterial Agents/pharmacology , Biofilms/growth & development , Cross Infection/microbiology , Drug Resistance, Bacterial/genetics , Equipment and Supplies/microbiology , Genotype , Humans , Interspersed Repetitive Sequences , Mexico , Pneumonia, Ventilator-Associated/microbiology
3.
Arch Virol ; 166(3): 935-941, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-1045234

ABSTRACT

Enteric coronaviruses (CoVs) are major pathogens that cause diarrhea in piglets. To date, four porcine enteric CoVs have been identified: transmissible gastroenteritis virus (TGEV), porcine epidemic diarrhea virus (PEDV), porcine deltacoronavirus (PDCoV), and HKU2-like porcine enteric alphacoronavirus (PEAV). In this study, we investigated the replicative capacity of these four enteric CoVs in LLC-PK1 cells, a porcine kidney cell line. The results showed that LLC-PK1 cells are susceptible to all four enteric CoVs, particularly to TGEV and PDCoV infections, indicating that LLC-PK1 cells can be applied to porcine enteric CoV research in vitro, particularly for coinfection studies.


Subject(s)
/growth & development , Gastroenteritis, Transmissible, of Swine/virology , Porcine epidemic diarrhea virus/growth & development , Transmissible gastroenteritis virus/growth & development , Virus Replication/physiology , Animals , Cell Line , Chlorocebus aethiops , Disease Susceptibility , Fluorescent Antibody Technique, Indirect , Intestine, Small/virology , LLC-PK1 Cells , Swine , Swine Diseases/virology , Vero Cells
4.
Antimicrob Resist Infect Control ; 10(1): 11, 2021 01 12.
Article in English | MEDLINE | ID: covidwho-1028830

ABSTRACT

BACKGROUND: In intensive care units (ICUs) treating patients with Coronavirus disease 2019 (COVID-19) invasive ventilation poses a high risk for aerosol and droplet formation. Surface contamination of severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) or bacteria can result in nosocomial transmission. METHODS: Two tertiary care COVID-19 intensive care units treating 53 patients for 870 patient days were sampled after terminal cleaning and preparation for regular use to treat non-COVID-19 patients. RESULTS: A total of 176 swabs were sampled of defined locations covering both ICUs. No SARS-CoV-2 ribonucleic acid (RNA) was detected. Gram-negative bacterial contamination was mainly linked to sinks and siphons. Skin flora was isolated from most swabbed areas and Enterococcus faecium was detected on two keyboards. CONCLUSIONS: After basic cleaning with standard disinfection measures no remaining SARS-CoV-2 RNA was detected. Bacterial contamination was low and mainly localised in sinks and siphons.


Subject(s)
Bacteria/isolation & purification , Disinfection/methods , Equipment Contamination/statistics & numerical data , Intensive Care Units/statistics & numerical data , Aerosols/analysis , Bacteria/classification , Bacteria/genetics , Bacteria/growth & development , Cross Infection/microbiology , Cross Infection/prevention & control , Cross Infection/virology , Female , Humans , Male , Middle Aged , /isolation & purification , Tertiary Healthcare/statistics & numerical data
6.
Clin Microbiol Infect ; 26(8): 1094.e1-1094.e5, 2020 Aug.
Article in English | MEDLINE | ID: covidwho-1023515

ABSTRACT

OBJECTIVES: To detect possible severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) RNA contamination of inanimate surfaces in areas at high risk of aerosol formation by patients with coronavirus disease 2019 (COVID-19). METHODS: Sampling was performed in the emergency unit and the sub-intensive care ward. SARS-CoV-2 RNA was extracted from swabbed surfaces and objects and subjected to real-time RT-PCR targeting RNA-dependent RNA polymerase and E genes. Virus isolation from positive samples was attempted in vitro on Vero E6 cells. RESULTS: Twenty-six samples were collected and only two were positive for low-level SARS-CoV-2 RNA, both collected on the external surface of continuous positive airway pressure helmets. All transport media were inoculated onto susceptible cells, but none induced a cytopathic effect on day 7 of culture. CONCLUSIONS: Even though daily contact with inanimate surfaces and patient fomites in contaminated areas may be a medium of infection, our data obtained in real-life conditions suggest that it might be less extensive than hitherto recognized.


Subject(s)
Betacoronavirus/growth & development , Fomites/virology , Viral Envelope Proteins/genetics , Animals , Betacoronavirus/genetics , Chlorocebus aethiops , Equipment Contamination , Humans , Intensive Care Units , Microbial Viability , Reverse Transcriptase Polymerase Chain Reaction , Vero Cells , Viral Proteins/genetics
7.
Sheng Wu Gong Cheng Xue Bao ; 36(4): 605-611, 2020 Apr 25.
Article in Chinese | MEDLINE | ID: covidwho-1024807

ABSTRACT

Cyclophilin A (CypA) is a widely distributed and highly conserved protein in organisms. It has peptidyl-prolyl cis/trans isomerase activity and is a receptor for cyclosporin A (CsA). Coronaviruses are enveloped, single-stranded, positive-sense RNA viruses. Seven types of coronaviruses are currently known to infect humans, among which SARS-CoV, MERS-CoV, and SARS-CoV-2 are fatal for humans. It is well established that CypA is essential for the replication of various coronaviruses such as SARS-CoV, CoV-229E, CoV-NL63, and FCoV. Additionally, CsA and its derivatives (ALV, NIM811, etc.) have obvious inhibitory effects on a variety of coronaviruses. These results suggest that CypA is a potential antiviral target and the existing drug CsA might be used as an anti-coronavirus drug. At the end of 2019, SARS-CoV-2 raged in China, which seriously theatern human health and causes huge economic lases. In view of this, we describe the effects of CypA on the replication of coronaviruses and the antiviral activities of its inhibitors, which will provide the scientific basis and ideas for the development of antiviral drugs for SARS-CoV-2.


Subject(s)
Antiviral Agents/pharmacology , Coronavirus Infections , Coronavirus/drug effects , Coronavirus/growth & development , Cyclophilin A/antagonists & inhibitors , Cyclosporine/pharmacology , Cyclosporine/therapeutic use , Pandemics , Pneumonia, Viral , Antiviral Agents/therapeutic use , Betacoronavirus/drug effects , Betacoronavirus/growth & development , Coronavirus Infections/drug therapy , Coronavirus Infections/epidemiology , Coronavirus Infections/virology , Cyclosporine/chemistry , Humans , Pneumonia, Viral/drug therapy , Pneumonia, Viral/epidemiology , Pneumonia, Viral/virology , SARS Virus/drug effects , SARS Virus/growth & development , Virus Replication/drug effects
9.
Viruses ; 12(12)2020 12 17.
Article in English | MEDLINE | ID: covidwho-993595

ABSTRACT

Plant viruses are commonly vectored by flying or crawling animals, such as aphids and beetles, and cause serious losses in major agricultural and horticultural crops. Controlling virus spread is often achieved by minimizing a crop's exposure to the vector, or by reducing vector numbers with compounds such as insecticides. A major, but less obvious, factor not controlled by these measures is Homo sapiens. Here, we discuss the inconvenient truth of how humans have become superspreaders of plant viruses on both a local and a global scale.


Subject(s)
Crops, Agricultural/virology , Plant Diseases/virology , Virus Diseases/transmission , Animals , Climate Change , Disease Vectors , Humans , Plant Diseases/prevention & control , Plant Viruses/growth & development
10.
Virology ; 554: 75-82, 2021 02.
Article in English | MEDLINE | ID: covidwho-989370

ABSTRACT

Human population growth, climate change, and globalization are accelerating the emergence of novel pathogenic viruses. In the past two decades alone, three such members of the coronavirus family have posed serious threats, spurring intense efforts to understand their biology as a way to identify targetable vulnerabilities. Coronaviruses use a programmed -1 ribosomal frameshift (-1 PRF) mechanism to direct synthesis of their replicase proteins. This is a critical switch in their replication program that can be therapeutically targeted. Here, we discuss how nearly half a century of research into -1 PRF have provided insight into the virological importance of -1 PRF, the molecular mechanisms that drive it, and approaches that can be used to manipulate it towards therapeutic outcomes with particular emphasis on SARS-CoV-2.


Subject(s)
Antiviral Agents/pharmacology , Coronavirus/drug effects , Coronavirus/genetics , Frameshifting, Ribosomal/drug effects , Antiviral Agents/chemistry , Antiviral Agents/therapeutic use , Coronavirus/growth & development , Coronavirus/physiology , Coronavirus Infections/drug therapy , Frameshifting, Ribosomal/genetics , Frameshifting, Ribosomal/physiology , Gene Expression Regulation, Viral , Humans , Mutation , Nucleic Acid Conformation , RNA, Viral/chemistry , RNA, Viral/genetics , RNA, Viral/metabolism , /genetics , /physiology , Virus Replication
11.
Molecules ; 25(11)2020 Jun 11.
Article in English | MEDLINE | ID: covidwho-981163

ABSTRACT

Flavonoids are widely used as phytomedicines. Here, we report on flavonoid phytomedicines with potential for development into prophylactics or therapeutics against coronavirus disease 2019 (COVID-19). These flavonoid-based phytomedicines include: caflanone, Equivir, hesperetin, myricetin, and Linebacker. Our in silico studies show that these flavonoid-based molecules can bind with high affinity to the spike protein, helicase, and protease sites on the ACE2 receptor used by the severe acute respiratory syndrome coronavirus 2 to infect cells and cause COVID-19. Meanwhile, in vitro studies show potential of caflanone to inhibit virus entry factors including, ABL-2, cathepsin L, cytokines (IL-1ß, IL-6, IL-8, Mip-1α, TNF-α), and PI4Kiiiß as well as AXL-2, which facilitates mother-to-fetus transmission of coronavirus. The potential for the use of smart drug delivery technologies like nanoparticle drones loaded with these phytomedicines to overcome bioavailability limitations and improve therapeutic efficacy are discussed.


Subject(s)
Antiviral Agents/pharmacology , Betacoronavirus/drug effects , Coronavirus Infections/drug therapy , Coronavirus OC43, Human/drug effects , Flavonoids/pharmacology , Peptidyl-Dipeptidase A/chemistry , Pneumonia, Viral/drug therapy , Spike Glycoprotein, Coronavirus/chemistry , Animals , Antiviral Agents/chemistry , Betacoronavirus/chemistry , Betacoronavirus/growth & development , Binding Sites , Chloroquine/chemistry , Chloroquine/pharmacology , Coronavirus Infections/genetics , Coronavirus OC43, Human/chemistry , Coronavirus OC43, Human/growth & development , Drug Carriers/administration & dosage , Drug Carriers/chemistry , Flavonoids/chemistry , Humans , Interleukins/antagonists & inhibitors , Interleukins/chemistry , Interleukins/genetics , Interleukins/metabolism , Leukocytes, Mononuclear/drug effects , Leukocytes, Mononuclear/virology , Lung/drug effects , Lung/pathology , Lung/virology , Mice , Molecular Docking Simulation , Nanoparticles/administration & dosage , Nanoparticles/chemistry , Pandemics , Peptidyl-Dipeptidase A/genetics , Peptidyl-Dipeptidase A/metabolism , Phytotherapy/methods , Pneumonia, Viral/genetics , Primary Cell Culture , Protein Binding , Protein Interaction Domains and Motifs , Protein-Tyrosine Kinases/antagonists & inhibitors , Protein-Tyrosine Kinases/chemistry , Protein-Tyrosine Kinases/genetics , Protein-Tyrosine Kinases/metabolism , Spike Glycoprotein, Coronavirus/antagonists & inhibitors , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/metabolism , Thermodynamics , Virus Internalization/drug effects
12.
Clin Microbiol Rev ; 34(1)2020 12 16.
Article in English | MEDLINE | ID: covidwho-962931

ABSTRACT

Patients and physicians worldwide are facing tremendous health care hazards that are caused by the ongoing severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2) pandemic. Remdesivir (GS-5734) is the first approved treatment for severe coronavirus disease 2019 (COVID-19). It is a novel nucleoside analog with a broad antiviral activity spectrum among RNA viruses, including ebolavirus (EBOV) and the respiratory pathogens Middle East respiratory syndrome coronavirus (MERS-CoV), SARS-CoV, and SARS-CoV-2. First described in 2016, the drug was derived from an antiviral library of small molecules intended to target emerging pathogenic RNA viruses. In vivo, remdesivir showed therapeutic and prophylactic effects in animal models of EBOV, MERS-CoV, SARS-CoV, and SARS-CoV-2 infection. However, the substance failed in a clinical trial on ebolavirus disease (EVD), where it was inferior to investigational monoclonal antibodies in an interim analysis. As there was no placebo control in this study, no conclusions on its efficacy in EVD can be made. In contrast, data from a placebo-controlled trial show beneficial effects for patients with COVID-19. Remdesivir reduces the time to recovery of hospitalized patients who require supplemental oxygen and may have a positive impact on mortality outcomes while having a favorable safety profile. Although this is an important milestone in the fight against COVID-19, approval of this drug will not be sufficient to solve the public health issues caused by the ongoing pandemic. Further scientific efforts are needed to evaluate the full potential of nucleoside analogs as treatment or prophylaxis of viral respiratory infections and to develop effective antivirals that are orally bioavailable.


Subject(s)
Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Antiviral Agents/pharmacology , Coronavirus Infections/drug therapy , Hemorrhagic Fever, Ebola/drug therapy , Pneumonia, Viral/drug therapy , Severe Acute Respiratory Syndrome/drug therapy , Adenosine Monophosphate/pharmacokinetics , Adenosine Monophosphate/pharmacology , Alanine/pharmacokinetics , Alanine/pharmacology , Antiviral Agents/pharmacokinetics , Betacoronavirus/drug effects , Betacoronavirus/growth & development , Betacoronavirus/pathogenicity , Clinical Trials as Topic , Compassionate Use Trials/methods , Coronavirus Infections/mortality , Coronavirus Infections/pathology , Coronavirus Infections/virology , Drug Administration Schedule , Ebolavirus/drug effects , Ebolavirus/growth & development , Ebolavirus/pathogenicity , Hemorrhagic Fever, Ebola/mortality , Hemorrhagic Fever, Ebola/pathology , Hemorrhagic Fever, Ebola/virology , Humans , Middle East Respiratory Syndrome Coronavirus/drug effects , Middle East Respiratory Syndrome Coronavirus/growth & development , Middle East Respiratory Syndrome Coronavirus/pathogenicity , Pandemics , Patient Safety , Pneumonia, Viral/mortality , Pneumonia, Viral/pathology , Pneumonia, Viral/virology , SARS Virus/drug effects , SARS Virus/growth & development , SARS Virus/pathogenicity , Severe Acute Respiratory Syndrome/mortality , Severe Acute Respiratory Syndrome/pathology , Severe Acute Respiratory Syndrome/virology , Survival Analysis , Treatment Outcome
13.
Sensors (Basel) ; 20(22)2020 Nov 11.
Article in English | MEDLINE | ID: covidwho-918244

ABSTRACT

Greenhouses and indoor farming systems play an important role in providing fresh and nutritious food for the growing global population. Farms are becoming larger and greenhouse growers need to make complex decisions to maximize production and minimize resource use while meeting market requirements. However, highly skilled labor is increasingly lacking in the greenhouse sector. Moreover, extreme events such as the COVID-19 pandemic, can make farms temporarily less accessible. This highlights the need for more autonomous and remote-control strategies for greenhouse production. This paper describes and analyzes the results of the second "Autonomous Greenhouse Challenge". In this challenge, an experiment was conducted in six high-tech greenhouse compartments during a period of six months of cherry tomato growing. The primary goal of the greenhouse operation was to maximize net profit, by controlling the greenhouse climate and crop with AI techniques. Five international teams with backgrounds in AI and horticulture were challenged in a competition to operate their own compartment remotely. They developed intelligent algorithms and use sensor data to determine climate setpoints and crop management strategy. All AI supported teams outperformed a human-operated greenhouse that served as reference. From the results obtained by the teams and from the analysis of the different climate-crop strategies, it was possible to detect challenges and opportunities for the future implementation of remote-control systems in greenhouse production.


Subject(s)
Artificial Intelligence , Coronavirus Infections/epidemiology , Lycopersicon esculentum/growth & development , Pandemics , Pneumonia, Viral/epidemiology , Agriculture/trends , Betacoronavirus/pathogenicity , Climate , Humans
15.
Antimicrob Resist Infect Control ; 9(1): 167, 2020 10 29.
Article in English | MEDLINE | ID: covidwho-895032

ABSTRACT

OBJECTIVES: We performed an environmental sampling study to investigate the environmental contamination of SARS-CoV-2 by COVID-19 patients with prolonged PCR positive status of clinical samples. METHODS: We sampled the air from rooms for nine COVID-19 patients with illness or positive PCR > 30 days, before and after nasopharyngeal/oropharyngeal swabbing and before and after nebulization treatment. We also sampled patients' surroundings and healthcare workers' personal protection equipment (PPE) in a non-ICU ward. SARS-CoV-2 was detected by PCR. RESULTS: Eighty-eight samples were collected from high-touch surfaces and floors in patient rooms and toilets, with only the bedsheets of two patients and one toilet positive for SARS-CoV-2. All air samples (n = 34) were negative for SARS-CoV-2. Fifty-five samples collected from PPE were all negative. CONCLUSION: Contamination of near-patient surroundings was uncommon for COVID-19 patients with prolonged PCR positive status if environmental cleaning/disinfection were performed rigorously. Airborne transmission of SARS-CoV-2 was unlikely in these non-ICU settings.


Subject(s)
Betacoronavirus/isolation & purification , Coronavirus Infections/virology , Personal Protective Equipment , Pneumonia, Viral/virology , Betacoronavirus/growth & development , Clinical Laboratory Techniques , Coronavirus Infections/diagnosis , Disinfection/methods , Environmental Microbiology , Environmental Monitoring/methods , Health Personnel , Hospitals , Humans , Pandemics/prevention & control , Patients' Rooms , Pneumonia, Viral/diagnosis , Polymerase Chain Reaction , RNA, Viral/isolation & purification
16.
BMC Res Notes ; 13(1): 497, 2020 Oct 27.
Article in English | MEDLINE | ID: covidwho-895028

ABSTRACT

OBJECTIVE: Nigeria bears 25% of global malaria burden despite concerted efforts towards its control and elimination. The emergence of drug resistance to first line drugs, artemisinin combination therapies (ACTs), indicates an urgent need for continuous molecular surveillance of drug resistance especially in high burden countries where drug interventions are heavily relied on. This study describes mutations in Plasmodium falciparum genes associated with drug resistance in malaria; Pfk13, Pfmdr1, PfATPase6 and Pfcrt in isolates obtained from 83 symptomatic malaria patients collected in August 2014, aged 1-61 years old from South-west Nigeria. RESULTS: Two Pfmdr1, N86 and Y184 variants were present at a prevalence of 56% and 13.25% of isolates respectively. There was one synonymous (S679S) and two non-synonymous (M699V, S769M) mutations in the PATPase6 gene, while Pfcrt genotype (CVIET), had a prevalence of 45%. The Pfk13 C580Y mutant allele was suspected by allelic discrimination in two samples with mixed genotypes although this could not be validated with independent isolation or additional methods. Our findings call for robust molecular surveillance of antimalarial drug resistance markers in west Africa especially with increased use of antimalarial drugs as prophylaxis for Covid-19.


Subject(s)
Artemether, Lumefantrine Drug Combination/therapeutic use , Calcium-Transporting ATPases/genetics , Malaria, Falciparum/drug therapy , Membrane Transport Proteins/genetics , Multidrug Resistance-Associated Proteins/genetics , Mutation , Plasmodium falciparum/drug effects , Protozoan Proteins/genetics , Adolescent , Adult , Antimalarials/therapeutic use , Artemisinins/therapeutic use , Child , Child, Preschool , Coronavirus Infections/epidemiology , Coronavirus Infections/prevention & control , Drug Resistance/genetics , Female , Gene Expression , Genotype , Humans , Infant , Malaria, Falciparum/epidemiology , Malaria, Falciparum/parasitology , Middle Aged , Molecular Epidemiology , Nigeria/epidemiology , Pandemics/prevention & control , Plasmodium falciparum/genetics , Plasmodium falciparum/growth & development , Pneumonia, Viral/epidemiology , Pneumonia, Viral/prevention & control
17.
Nat Commun ; 11(1): 5503, 2020 10 30.
Article in English | MEDLINE | ID: covidwho-894393

ABSTRACT

The spread of SARS-CoV-2 in Beijing before May, 2020 resulted from transmission following both domestic and global importation of cases. Here we present genomic surveillance data on 102 imported cases, which account for 17.2% of the total cases in Beijing. Our data suggest that all of the cases in Beijing can be broadly classified into one of three groups: Wuhan exposure, local transmission and overseas imports. We classify all sequenced genomes into seven clusters based on representative high-frequency single nucleotide polymorphisms (SNPs). Genomic comparisons reveal higher genomic diversity in the imported group compared to both the Wuhan exposure and local transmission groups, indicating continuous genomic evolution during global transmission. The imported group show region-specific SNPs, while the intra-host single nucleotide variations present as random features, and show no significant differences among groups. Epidemiological data suggest that detection of cases at immigration with mandatory quarantine may be an effective way to prevent recurring outbreaks triggered by imported cases. Notably, we also identify a set of novel indels. Our data imply that SARS-CoV-2 genomes may have high mutational tolerance.


Subject(s)
Betacoronavirus/growth & development , Coronavirus Infections/virology , Pneumonia, Viral/virology , Adult , Beijing/epidemiology , Coronavirus Infections/epidemiology , Female , Genome, Viral , Genomics , Genotype , Humans , Male , Middle Aged , Mutation , Pandemics , Phylogeny , Pneumonia, Viral/epidemiology , Polymorphism, Single Nucleotide , Travel , Young Adult
18.
Nat Commun ; 11(1): 5493, 2020 10 30.
Article in English | MEDLINE | ID: covidwho-894389

ABSTRACT

The relationship between SARS-CoV-2 viral load and risk of disease progression remains largely undefined in coronavirus disease 2019 (COVID-19). Here, we quantify SARS-CoV-2 viral load from participants with a diverse range of COVID-19 disease severity, including those requiring hospitalization, outpatients with mild disease, and individuals with resolved infection. We detected SARS-CoV-2 plasma RNA in 27% of hospitalized participants, and 13% of outpatients diagnosed with COVID-19. Amongst the participants hospitalized with COVID-19, we report that a higher prevalence of detectable SARS-CoV-2 plasma viral load is associated with worse respiratory disease severity, lower absolute lymphocyte counts, and increased markers of inflammation, including C-reactive protein and IL-6. SARS-CoV-2 viral loads, especially plasma viremia, are associated with increased risk of mortality. Our data show that SARS-CoV-2 viral loads may aid in the risk stratification of patients with COVID-19, and therefore its role in disease pathogenesis should be further explored.


Subject(s)
Betacoronavirus/isolation & purification , Coronavirus Infections/virology , Pneumonia, Viral/virology , Adult , Aged , Antibodies, Viral/blood , Betacoronavirus/genetics , Betacoronavirus/growth & development , Biomarkers/blood , C-Reactive Protein , Coronavirus Infections/blood , Coronavirus Infections/mortality , Coronavirus Infections/pathology , Female , Hospitalization , Humans , Inflammation/blood , Inflammation/virology , Interleukin-6/blood , Longitudinal Studies , Massachusetts/epidemiology , Middle Aged , Pandemics , Pneumonia, Viral/blood , Pneumonia, Viral/mortality , Pneumonia, Viral/pathology , RNA, Viral/blood , Severity of Illness Index , Viral Load , Viremia/blood , Viremia/virology
19.
Immunol Lett ; 217: 25-30, 2020 01.
Article in English | MEDLINE | ID: covidwho-888577

ABSTRACT

In a previous work we demonstrated that inhibition of mouse indoleamine 2,3-dioxygenase (IDO) by methyltryptophan (MT) exacerbated the pathological actions of mouse hepatitis virus (MHV-A59) infection, suggesting that tryptophan (TRP) catabolism was involved in viral effects. Since there is a second enzyme that dioxygenates TRP, tryptophan-2, 3-dioxygenase (TDO), which is mainly located in liver, we decided to study its role in our model of MHV-infection. Results showed that in vivo TDO inhibition by LM10, a derivative of 3-(2-(pyridyl) ethenyl) indole, resulted in a decrease of anti- MHV Ab titers induced by the virus infection. Besides, a reduction of some alarmin release, i.e, uric acid and high-mobility group box1 protein (HMGB1), was observed. Accordingly, since alarmin liberation was related to the expression of autoantibodies (autoAb) to fumarylacetoacetate hydrolase (FAH), these autoAb also diminished. Moreover, PCR results indicated that TDO inhibition did not abolish viral replication. Furthermore, histological liver examination did not reveal strong pathologies, whereas mouse survival was hundred percent in control as well as in MHV-infected mice treated with LM10. Data presented in this work indicate that in spite of the various TDO actions already described, specific TDO blockage could also restrain some MHV actions, mainly suppressing autoimmune reactions. Such results should prompt further experiments with various viruses to confirm the possible use of a TDO inhibitor such as LM-10 to treat either viral infections or even autoimmune diseases triggered by a viral infection.


Subject(s)
Autoimmune Diseases/enzymology , Autoimmunity/drug effects , Coronavirus Infections/enzymology , Coronavirus Infections/immunology , Liver/enzymology , Murine hepatitis virus/immunology , Tryptophan Oxygenase/antagonists & inhibitors , Tryptophan Oxygenase/metabolism , Alarmins/metabolism , Animals , Autoantibodies/drug effects , Autoantibodies/immunology , Autoimmune Diseases/drug therapy , Autoimmune Diseases/immunology , Autoimmune Diseases/virology , Coronavirus Infections/drug therapy , Coronavirus Infections/virology , Female , HMGB1 Protein/blood , HMGB1 Protein/metabolism , Hydrolases/immunology , Indoles/therapeutic use , Liver/drug effects , Liver/immunology , Liver/pathology , Mice , Mice, Inbred BALB C , Murine hepatitis virus/drug effects , Murine hepatitis virus/growth & development , Tryptophan/metabolism , Tryptophan Oxygenase/genetics , Uric Acid/blood , Uric Acid/metabolism , Virus Replication/drug effects , Virus Replication/immunology
20.
Emerg Microbes Infect ; 9(1): 2433-2445, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-872909

ABSTRACT

Severe acute respiratory syndrome CoV-2 (SARS-CoV-2) is currently causing a worldwide pandemic with high morbidity and mortality. Development of animal models that recapitulate important aspects of coronavirus disease 2019 (COVID-19) is critical for the evaluation of vaccines and antivirals, and understanding disease pathogenesis. SARS-CoV-2 has been shown to use the same entry receptor as SARS-CoV-1, human angiotensin-converting enzyme 2 (hACE2) [1-3]. Due to amino acid differences between murine and hACE2, inbred mouse strains fail to support high titer viral replication of SARS-CoV-2 virus. Therefore, a number of transgenic and knock-in mouse models, as well as viral vector-mediated hACE2 delivery systems have been developed. Here we compared the K18-hACE2 transgenic model to adenovirus-mediated delivery of hACE2 to the mouse lung. We show that K18-hACE2 mice replicate virus to high titers in the nasal turbinates, lung and brain, with high lethality, and cytokine/chemokine production. In contrast, adenovirus-mediated delivery results in viral replication to lower titers limited to the nasal turbinates and lung, and no clinical signs of infection. The K18-hACE2 model provides a stringent model for testing vaccines and antivirals, whereas the adenovirus delivery system has the flexibility to be used across multiple genetic backgrounds and modified mouse strains.


Subject(s)
Betacoronavirus/growth & development , Coronavirus Infections/pathology , Peptidyl-Dipeptidase A/genetics , Pneumonia, Viral/pathology , SARS Virus/growth & development , Virus Replication/genetics , A549 Cells , Adenoviridae/genetics , Animals , Betacoronavirus/metabolism , Cell Line , Chlorocebus aethiops , Disease Models, Animal , Female , Humans , Lung/pathology , Lung/virology , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Mice, Transgenic , Pandemics , SARS Virus/metabolism , Vero Cells , Virus Attachment
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