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1.
Cells ; 10(12)2021 11 25.
Article in English | MEDLINE | ID: covidwho-1542428

ABSTRACT

Acute respiratory distress syndrome (ARDS) is a serious lung condition characterized by severe hypoxemia leading to limitations of oxygen needed for lung function. In this study, we investigated the effect of anandamide (AEA), an endogenous cannabinoid, on Staphylococcal enterotoxin B (SEB)-mediated ARDS in female mice. Single-cell RNA sequencing data showed that the lung epithelial cells from AEA-treated mice showed increased levels of antimicrobial peptides (AMPs) and tight junction proteins. MiSeq sequencing data on 16S RNA and LEfSe analysis demonstrated that SEB caused significant alterations in the microbiota, with increases in pathogenic bacteria in both the lungs and the gut, while treatment with AEA reversed this effect and induced beneficial bacteria. AEA treatment suppressed inflammation both in the lungs as well as gut-associated mesenteric lymph nodes (MLNs). AEA triggered several bacterial species that produced increased levels of short-chain fatty acids (SCFAs), including butyrate. Furthermore, administration of butyrate alone could attenuate SEB-mediated ARDS. Taken together, our data indicate that AEA treatment attenuates SEB-mediated ARDS by suppressing inflammation and preventing dysbiosis, both in the lungs and the gut, through the induction of AMPs, tight junction proteins, and SCFAs that stabilize the gut-lung microbial axis driving immune homeostasis.


Subject(s)
Arachidonic Acids/therapeutic use , Endocannabinoids/therapeutic use , Gastrointestinal Microbiome , Gastrointestinal Tract/pathology , Lung/pathology , Polyunsaturated Alkamides/therapeutic use , Respiratory Distress Syndrome/drug therapy , Respiratory Distress Syndrome/microbiology , Animals , Arachidonic Acids/pharmacology , Butyrates/metabolism , Cecum/pathology , Cell Separation , Colon/drug effects , Colon/pathology , Discriminant Analysis , Dysbiosis/complications , Dysbiosis/microbiology , Endocannabinoids/pharmacology , Enterotoxins , Female , Gastrointestinal Tract/drug effects , Lymph Nodes/drug effects , Lymph Nodes/pathology , Lymphocyte Activation/drug effects , Mice, Inbred C57BL , Pneumonia/drug therapy , Pneumonia/microbiology , Polyunsaturated Alkamides/pharmacology , Respiratory Distress Syndrome/complications , T-Lymphocytes/drug effects
3.
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
4.
Respir Med ; 188: 106619, 2021 11.
Article in English | MEDLINE | ID: covidwho-1415764

ABSTRACT

BACKGROUND: Invasive fungal infections (IFI) are increasing in prevalence in recent years. In the last few months, the rise of COVID-19 patients has generated a new escalation in patients presenting opportunistic mycoses, mainly by Aspergillus. Candida infections are not being reported yet. OBJECTIVES: We aimed to determine the prevalence of systemic candidiasis in patients admitted to ICUs due to severe pneumonia secondary to SARS-CoV-2 infection and the existence of possible associated risk factors that led these patients to develop candidiasis. PATIENTS/METHODS: We designed a study including patients with a confirmed diagnosis of COVID-19. RESULTS: The prevalence of systemic candidiasis was 14.4%, and the main isolated species were C. albicans and C. parapsilosis. All patients that were tested positive for Candida spp. stayed longer in the ICU in comparison to patients who tested negative. Patients with candidiasis had higher MuLBSTA score and mortality rates and a worse radiological involvement. In our study, Candida spp. isolates were found in patients that were submitted to: tocilizumab, tocilizumab plus systemic steroids, interferon type 1ß and Lopinavir-Ritonavir. CONCLUSIONS: Results suggested a high prevalence of systemic candidiasis in severe COVID-19-associated pneumonia patients. Patients with Candidiasis had the worst clinical outcomes. Treatment with tocilizumab could potentialize the risk to develop systemic candidiasis.


Subject(s)
COVID-19/complications , Candidiasis/epidemiology , Coinfection/epidemiology , Pneumonia/epidemiology , Aged , COVID-19/diagnosis , Candida albicans , Candida parapsilosis , Candidiasis/complications , Candidiasis/diagnosis , Coinfection/diagnosis , Critical Care , Female , Humans , Male , Middle Aged , Pneumonia/microbiology , Pneumonia/virology , Prevalence , Prospective Studies , Risk Factors
5.
Microb Drug Resist ; 27(9): 1167-1175, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1406451

ABSTRACT

Background: The aim of this study was to assess the drivers of multidrug-resistant (MDR) bacterial infection development in coronavirus disease 2019 (COVID-19) and its impact on patient outcome. Methods: Retrospective analysis on data from 32 consecutive patients with COVID-19, admitted to our intensive care unit (ICU) from March to May 2020. Outcomes considered were MDR infection and ICU mortality. Results: Fifty percent of patients developed an MDR infection during ICU stay after a median time of 8 [4-11] days. Most common MDR pathogens were carbapenem-resistant Klebsiella pneumoniae and Acinetobacter baumannii, causing bloodstream infections and pneumonia. MDR infections were linked to a higher length of ICU stay (p = 0.002), steroid therapy (p = 0.011), and associated with a lower ICU mortality (odds ratio: 0.439, 95% confidence interval: 0.251-0.763; p < 0.001). Low-dose aspirin intake was associated with both MDR infection (p = 0.043) and survival (p = 0.015). Among MDR patients, mortality was related with piperacillin-tazobactam use (p = 0.035) and an earlier onset of MDR infection (p = 0.042). Conclusions: MDR infections were a common complication in critically ill COVID-19 patients at our center. MDR risk was higher among those dwelling longer in the ICU and receiving steroids. However, MDR infections were not associated with a worse outcome.


Subject(s)
Acinetobacter Infections/mortality , COVID-19/mortality , Drug Resistance, Multiple, Bacterial , Klebsiella Infections/mortality , Opportunistic Infections/mortality , Pneumonia/mortality , SARS-CoV-2/pathogenicity , Acinetobacter Infections/drug therapy , Acinetobacter Infections/microbiology , Acinetobacter Infections/virology , Acinetobacter baumannii/drug effects , Acinetobacter baumannii/growth & development , Acinetobacter baumannii/pathogenicity , Adult , Aged , Anti-Bacterial Agents/therapeutic use , Aspirin/therapeutic use , COVID-19/drug therapy , COVID-19/microbiology , COVID-19/virology , Carbapenems/therapeutic use , Critical Illness , Female , Hospital Mortality , Humans , Intensive Care Units , Klebsiella Infections/drug therapy , Klebsiella Infections/microbiology , Klebsiella Infections/virology , Klebsiella pneumoniae/drug effects , Klebsiella pneumoniae/growth & development , Klebsiella pneumoniae/pathogenicity , Length of Stay/statistics & numerical data , Male , Middle Aged , Opportunistic Infections/drug therapy , Opportunistic Infections/microbiology , Opportunistic Infections/virology , Piperacillin, Tazobactam Drug Combination/therapeutic use , Pneumonia/drug therapy , Pneumonia/microbiology , Pneumonia/virology , Retrospective Studies , SARS-CoV-2/drug effects , SARS-CoV-2/physiology , Steroids/therapeutic use , Survival Analysis , Treatment Outcome
6.
Cells ; 10(8)2021 07 29.
Article in English | MEDLINE | ID: covidwho-1339532

ABSTRACT

Neutrophils act as the first line of defense during infection and inflammation. Once activated, they are able to fulfil numerous tasks to fight inflammatory insults while keeping a balanced immune response. Besides well-known functions, such as phagocytosis and degranulation, neutrophils are also able to release "neutrophil extracellular traps" (NETs). In response to most stimuli, the neutrophils release decondensed chromatin in a NADPH oxidase-dependent manner decorated with histones and granule proteins, such as neutrophil elastase, myeloperoxidase, and cathelicidins. Although primarily supposed to prevent microbial dissemination and fight infections, there is increasing evidence that an overwhelming NET response correlates with poor outcome in many diseases. Lung-related diseases especially, such as bacterial pneumonia, cystic fibrosis, chronic obstructive pulmonary disease, aspergillosis, influenza, and COVID-19, are often affected by massive NET formation. Highly vascularized areas as in the lung are susceptible to immunothrombotic events promoted by chromatin fibers. Keeping this fragile equilibrium seems to be the key for an appropriate immune response. Therapies targeting dysregulated NET formation might positively influence many disease progressions. This review highlights recent findings on the pathophysiological influence of NET formation in different bacterial, viral, and non-infectious lung diseases and summarizes medical treatment strategies.


Subject(s)
Extracellular Traps/immunology , Neutrophils/immunology , Pneumonia/immunology , COVID-19/immunology , Disease Progression , Humans , Neutrophils/microbiology , Neutrophils/virology , Pneumonia/microbiology , Pneumonia/pathology , Pneumonia/virology
7.
Emerg Microbes Infect ; 10(1): 1515-1518, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1313723

ABSTRACT

We show a shift in the prevalence of respiratory viral pathogens in community-acquired pneumonia patients during the COVID-19 pandemic. Our data support the efficiency of non-pharmaceutical interventions on virus circulation except for rhinoviruses. The consequences of an altered circulation on subsequent winter seasons remain unclear and support the importance of systematic virological surveillance.


Subject(s)
COVID-19/epidemiology , Community-Acquired Infections/epidemiology , Pneumonia/epidemiology , Respiratory Tract Infections/epidemiology , Adult , Aged , Bacteria/classification , Bacteria/genetics , Bacteria/isolation & purification , COVID-19/virology , Community-Acquired Infections/microbiology , Community-Acquired Infections/virology , Female , Germany/epidemiology , Humans , Male , Middle Aged , Pandemics , Pneumonia/microbiology , Pneumonia/virology , Prevalence , Prospective Studies , Respiratory Tract Infections/microbiology , Respiratory Tract Infections/virology , SARS-CoV-2/genetics , SARS-CoV-2/physiology , Viruses/classification , Viruses/genetics , Viruses/isolation & purification , Young Adult
8.
Emerg Microbes Infect ; 10(1): 1418-1428, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1284839

ABSTRACT

Chlamydia psittaci infection in humans, also known as psittacosis, is usually believed to be an uncommon disease which mainly presents as community-acquired pneumonia (CAP). It is usually sporadic, but outbreaks of infection may occasionally occur. In outbreaks, diagnosis and investigations were usually hampered by the non-specificity of laboratory testing methods to identify C. psittaci. In this study, we use metagenomic next-generation sequencing (mNGS) in the diagnosis of a family outbreak of psittacosis under COVID-19. Three members of an extended family of 6 persons developed psittacosis with pneumonia and hepatic involvement with common symptoms of fever and weakness. Two newly purchased pet parrots, which had died successively, were probably the primary source of infection. Imagings show lung consolidations and infiltrates, which are difficult to be differentiated from CAP caused by other common pathogens. mNGS rapidly identified the infecting agent as C. psittaci within 48 h. The results of this work suggest that there are not characteristic clinical manifestations and imagings of psittacosis pneumonia which can differentiate from CAP caused by other pathogens. The use of mNGS can improve accuracy and reduce the delay in the diagnosis of psittacosis especially during the outbreak, which can shorten the course of the disease control. Family outbreak under COVID-19 may be related to the familial aggregation due to the epidemic. To our knowledge, this is the first reported family outbreak of psittacosis in China, and the first reported psittacosis outbreak identified by the method of mNGS in the world.


Subject(s)
Chlamydophila psittaci/genetics , Family , High-Throughput Nucleotide Sequencing , Metagenomics , Pneumonia/microbiology , Psittacosis/diagnostic imaging , Adult , Aged , Animals , COVID-19/epidemiology , China/epidemiology , Chlamydophila psittaci/isolation & purification , Disease Outbreaks , Female , Humans , Male , Metagenome , Middle Aged , Parrots/microbiology , Pneumonia/diagnostic imaging , Psittacosis/microbiology , Psittacosis/transmission , Retrospective Studies , Tomography, X-Ray Computed
10.
Medicine (Baltimore) ; 100(4): e24524, 2021 Jan 29.
Article in English | MEDLINE | ID: covidwho-1218898

ABSTRACT

ABSTRACT: This study aimed to evaluate the incidence of co-infection with different types of pathogens in patients with hypoxemic pneumonia due to coronavirus disease 2019 (COVID-19) in Reunion Island.This observational study using a prospectively collected database of hypoxemic pneumonia due to COVID-19 cases was conducted at Félix Guyon University Hospital in Reunion Island, France.Between 18 March 2020 and 15 April 2020, 156 patients were admitted to our hospital for COVID-19. A total of 36 patients had hypoxemic pneumonia (23.1%) due to COVID-19. Thirty of these cases (83.3%) were imported by travelers returning mainly from metropolitan France and Spain. Patients were screened for co-infection with other pathogens at admission: 31 (86.1%) by multiplex polymerase chain reaction (PCR) and 16 (44.4%) by cytobacteriological examination of sputum culture. Five patients (13.9%) were found to have co-infection: 1 with influenza virus A H1N1 (pdm09) associated with Branhamella catarrhalis, 1 with Streptococcus pneumoniae associated with Haemophilus influenzae, 1 with Human Coronavirus 229E, 1 with Rhinovirus, and 1 with methicillin-susceptible Staphylococcus aureus. Patients with co-infection had higher D-dimer levels than those without co-infection (1.36 [1.34-2.36] µg/mL vs 0.63 [0.51-1.12] µg/mL, P = .05).The incidence of co-infection in our cohort was higher than expected (13.9%). Three co-infections (with influenza virus A(H1N1) pdm09, Streptococcus pneumoniae, and Staphylococcus aureus) required specific treatment. Patients with hypoxemic pneumonia due to COVID-19 should be screened for co-infection using respiratory cultures or multiplex PCR. Whilst our study has a number of limitations, the results from our study suggest that in the absence of screening, patients should be commenced on treatment for co-infection in the presence of an elevated D-dimer.


Subject(s)
COVID-19/epidemiology , Coinfection/epidemiology , Pneumonia/epidemiology , Pneumonia/microbiology , Adult , Female , France/epidemiology , Humans , Hypoxia , Male , Middle Aged , Retrospective Studies , SARS-CoV-2
11.
BMC Infect Dis ; 21(1): 352, 2021 Apr 15.
Article in English | MEDLINE | ID: covidwho-1191295

ABSTRACT

BACKGROUND: Identifying the causes of community-acquired pneumonia (CAP) is challenging due to the disease's complex etiology and the limitations of traditional microbiological diagnostic methods. Recent advances in next generation sequencing (NGS)-based metagenomics allow pan-pathogen detection in a single assay, and may have significant advantages over culture-based techniques. RESULTS: We conducted a cohort study of 159 CAP patients to assess the diagnostic performance of a clinical metagenomics assay and its impact on clinical management and patient outcomes. When compared to other techniques, clinical metagenomics detected more pathogens in more CAP cases, and identified a substantial number of polymicrobial infections. Moreover, metagenomics results led to changes in or confirmation of clinical management in 35 of 59 cases; these 35 cases also had significantly improved patient outcomes. CONCLUSIONS: Clinical metagenomics could be a valuable tool for the diagnosis and treatment of CAP. TRIAL REGISTRATION: Trial registration number with the Chinese Clinical Trial Registry: ChiCTR2100043628 .


Subject(s)
Community-Acquired Infections/diagnosis , Metagenomics/methods , Pneumonia/diagnosis , Adult , Aged , Aged, 80 and over , Bronchoalveolar Lavage Fluid/microbiology , Cohort Studies , Community-Acquired Infections/microbiology , DNA, Bacterial/chemistry , DNA, Bacterial/metabolism , Female , High-Throughput Nucleotide Sequencing , Humans , Male , Middle Aged , Mycobacterium tuberculosis/genetics , Mycobacterium tuberculosis/isolation & purification , Pneumonia/microbiology , Sequence Analysis, DNA , Sputum/microbiology , Young Adult
12.
Respir Res ; 22(1): 99, 2021 Apr 06.
Article in English | MEDLINE | ID: covidwho-1169963

ABSTRACT

BACKGROUND: COVID-19 pneumonia has been associated with severe acute hypoxia, sepsis-like states, thrombosis and chronic sequelae including persisting hypoxia and fibrosis. The molecular hypoxia response pathway has been associated with such pathologies and our recent observations on anti-hypoxic and anti-inflammatory effects of whole aqueous extract of Adhatoda Vasica (AV) prompted us to explore its effects on relevant preclinical mouse models. METHODS: In this study, we tested the effect of whole aqueous extract of AV, in murine models of bleomycin induced pulmonary fibrosis, Cecum Ligation and Puncture (CLP) induced sepsis, and siRNA induced hypoxia-thrombosis phenotype. The effect on lung of AV treated naïve mice was also studied at transcriptome level. We also determined if the extract may have any effect on SARS-CoV2 replication. RESULTS: Oral administration AV extract attenuates increased airway inflammation, levels of transforming growth factor-ß1 (TGF-ß1), IL-6, HIF-1α and improves the overall survival rates of mice in the models of pulmonary fibrosis and sepsis and rescues the siRNA induced inflammation and associated blood coagulation phenotypes in mice. We observed downregulation of hypoxia, inflammation, TGF-ß1, and angiogenesis genes and upregulation of adaptive immunity-related genes in the lung transcriptome. AV treatment also reduced the viral load in Vero cells infected with SARS-CoV2. CONCLUSION: Our results provide a scientific rationale for this ayurvedic herbal medicine in ameliorating the hypoxia-hyperinflammation features and highlights the repurposing potential of AV in COVID-19-like conditions.


Subject(s)
Anti-Inflammatory Agents/pharmacology , COVID-19/drug therapy , Drug Repositioning , Hypoxia/drug therapy , Justicia , Lung/drug effects , Plant Extracts/pharmacology , Pneumonia/prevention & control , Pulmonary Fibrosis/drug therapy , Sepsis/drug therapy , Animals , Anti-Inflammatory Agents/isolation & purification , Bleomycin , COVID-19/metabolism , COVID-19/virology , Cecum/microbiology , Cecum/surgery , Cytokines/genetics , Cytokines/metabolism , Disease Models, Animal , Hypoxia/genetics , Hypoxia/metabolism , Hypoxia-Inducible Factor 1, alpha Subunit/genetics , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Hypoxia-Inducible Factor-Proline Dioxygenases/genetics , Hypoxia-Inducible Factor-Proline Dioxygenases/metabolism , Inflammation Mediators/metabolism , Justicia/chemistry , Ligation , Lung/metabolism , Lung/microbiology , Lung/pathology , Male , Mice, Inbred BALB C , Mice, Inbred C57BL , Plant Extracts/isolation & purification , Pneumonia/genetics , Pneumonia/metabolism , Pneumonia/microbiology , Pulmonary Fibrosis/chemically induced , Pulmonary Fibrosis/genetics , Pulmonary Fibrosis/metabolism , RNA Interference , RNA, Small Interfering/genetics , RNA, Small Interfering/metabolism , Sepsis/genetics , Sepsis/metabolism , Sepsis/microbiology , Transcriptome
14.
Respiration ; 99(9): 739-747, 2020.
Article in English | MEDLINE | ID: covidwho-934161

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) has become a global emerging infectious disease. OBJECTIVES: To analyze the initial clinical characteristics of COVID-19 suspected and confirmed patients on admission in order to find out which kinds may be more likely to get positive nucleic acid testing results, and to explore the risk factors associated with all-cause death. METHODS: Medical records from 309 highly suspected cases with pneumonia were collected from February 13, 2020, to March 14, 2020, in a COVID-19-designated hospital of Wuhan. The majority of the clinical data were collected on the first day of hospital admission. RESULTS: Of 309 patients with median age 64 years (interquartile ranges [IQR], 53-72 years), 111 patients (35.9%) were confirmed by nucleic acid testing (median age 64 years, IQR: 56-71 years; 48 males). Of those 111 patients, 13 (11.7%) patients died. In multivariate analysis, factors associated with positive testing included fatigue (odds ratios [OR] = 3.14; 95% confidence interval [CI]: 1.88-5.24, p < 0.001), cough (OR = 0.55; 95% CI: 0.32-0.95, p = 0.032), no less than 1 comorbidity (OR = 1.77; 95% CI: 1.06-2.98, p = 0.030), and severe pneumonia (OR = 2.67; 95% CI: 1.20-5.97, p = 0.016). Furthermore, age, dyspnea, noneffective antibiotic treatment, white blood cell, lymphocyte, platelets, and organ dysfunction (e.g., higher lactate dehydrogenase) were significantly associated with all-cause in-hospital death in patients with COVID-19. CONCLUSION: Patients with severe forms of this disease were more likely to get positive results. Age and organ dysfunction were associated with a greater risk of death.


Subject(s)
COVID-19/epidemiology , Cough/physiopathology , Fatigue/physiopathology , Hospital Mortality , Pneumonia/epidemiology , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , Alanine Transaminase/metabolism , Anti-Bacterial Agents/therapeutic use , Aspartate Aminotransferases/metabolism , C-Reactive Protein/metabolism , COVID-19/diagnosis , COVID-19/metabolism , COVID-19/physiopathology , COVID-19 Nucleic Acid Testing , COVID-19 Serological Testing , Cause of Death , Child , Child, Preschool , China/epidemiology , Cohort Studies , Comorbidity , Creatine Kinase/metabolism , Female , Fever/physiopathology , Fibrin Fibrinogen Degradation Products/metabolism , Hospitalization , Humans , Immunoglobulin G , Immunoglobulin M , Infant , Infant, Newborn , L-Lactate Dehydrogenase/metabolism , Male , Middle Aged , Multivariate Analysis , Pneumonia/drug therapy , Pneumonia/microbiology , Pneumonia/physiopathology , Retrospective Studies , Risk Factors , SARS-CoV-2 , Serum Albumin/metabolism , Severity of Illness Index , Treatment Failure , Young Adult
15.
Influenza Other Respir Viruses ; 14(2): 142-149, 2020 03.
Article in English | MEDLINE | ID: covidwho-830213

ABSTRACT

BACKGROUND: In this study, we evaluated the diagnostic potential and clinical impact of an automated multiplex PCR platform (the FilmArray Respiratory Panel; FA-RP), specially designed for pathogen detection in respiratory tract infections in adults with unexplained pneumonia (UP). METHODS: A total of 112 UP patients in Shanghai, China, were enrolled prospectively and assessed using the FA-RP from October 2016 to March 2018. We examined the test results and their influence on clinical decisions. Furthermore, as a control group, we retrospectively obtained the clinical data of 70 UP patients between October 2014 and March 2016 (before the FA-RP was available). The two patient groups were compared with respect to factors, including general antimicrobial use and defined daily dose (DDD) numbers. RESULTS: Between October 2016 and March 2018, the positive rate obtained using FA-RP for UP was 76.8%. The primary pathogens in adults with UP were Influenza A/B (47.3%, 53/112). Compared with the patients before FA-RP was available, patients who underwent FA-RP testing had higher rates of antiviral drug use and antibiotic de-escalation during clinical treatment. FA-RP significantly decreased the total DDDs of antibiotic or antifungal drugs DDDs by 7 days after admission (10.6 ± 2.5 vs 14.1 ± 8.8, P < .01). CONCLUSIONS: The FA-RP is a rapid and sensitive nucleic acid amplification test method for UP diagnosis in adults. The application of FA-RP may lead to a more accurately targeted antimicrobial treatment and reduced use of antibiotic/antifungal drugs.


Subject(s)
Multiplex Polymerase Chain Reaction/methods , Pneumonia/virology , Respiratory Tract Infections/diagnosis , Adult , Aged , Anti-Bacterial Agents/therapeutic use , Antiviral Agents/therapeutic use , China , Female , Hospitalization , Humans , Male , Middle Aged , Molecular Diagnostic Techniques/methods , Pneumonia/drug therapy , Pneumonia/microbiology , RNA, Viral/genetics , Respiratory Tract Infections/drug therapy , Respiratory Tract Infections/microbiology , Respiratory Tract Infections/virology , Viruses/genetics , Viruses/isolation & purification
16.
Pharmacol Ther ; 217: 107663, 2021 01.
Article in English | MEDLINE | ID: covidwho-713921

ABSTRACT

While the world is grappling with the consequences of a global pandemic related to SARS-CoV-2 causing severe pneumonia, available evidence points to bacterial infection with Streptococcus pneumoniae as the most common cause of severe community acquired pneumonia (SCAP). Rapid diagnostics and molecular testing have improved the identification of co-existent pathogens. However, mortality in patients admitted to ICU remains staggeringly high. The American Thoracic Society and Infectious Diseases Society of America have updated CAP guidelines to help streamline disease management. The common theme is use of timely, appropriate and adequate antibiotic coverage to decrease mortality and avoid drug resistance. Novel antibiotics have been studied for CAP and extend the choice of therapy, particularly for those who are intolerant of, or not responding to standard treatment, including those who harbor drug resistant pathogens. In this review, we focus on the risk factors, microbiology, site of care decisions and treatment of patients with SCAP.


Subject(s)
Community-Acquired Infections/drug therapy , Community-Acquired Infections/microbiology , Disease Management , Intensive Care Units , Pneumonia/drug therapy , Pneumonia/microbiology , Community-Acquired Infections/mortality , Drug Resistance, Multiple, Bacterial , Guidelines as Topic , Humans , Pneumonia/mortality
17.
Gastroenterology ; 159(4): 1302-1310.e5, 2020 Oct.
Article in English | MEDLINE | ID: covidwho-621434

ABSTRACT

BACKGROUND & AIMS: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects intestinal cells, and might affect the intestinal microbiota. We investigated changes in the fecal fungal microbiomes (mycobiome) of patients with SARS-CoV-2 infection during hospitalization and on recovery. METHODS: We performed deep shotgun metagenomic sequencing analysis of fecal samples from 30 patients with coronavirus disease 2019 (COVID-19) in Hong Kong, from February 5 through May 12, 2020. Fecal samples were collected 2 to 3 times per week from time of hospitalization until discharge. We compared fecal mycobiome compositions of patients with COVID-19 with those from 9 subjects with community-acquired pneumonia and 30 healthy individuals (controls). We assessed fecal mycobiome profiles throughout time of hospitalization until clearance of SARS-CoV-2 from nasopharyngeal samples. RESULTS: Patients with COVID-19 had significant alterations in their fecal mycobiomes compared with controls, characterized by enrichment of Candia albicans and a highly heterogeneous mycobiome configuration, at time of hospitalization. Although fecal mycobiomes of 22 patients with COVID-19 did not differ significantly from those of controls during times of hospitalization, 8 of 30 patients with COVID-19 had continued significant differences in fecal mycobiome composition, through the last sample collected. The diversity of the fecal mycobiome of the last sample collected from patients with COVID-19 was 2.5-fold higher than that of controls (P < .05). Samples collected at all timepoints from patients with COVID-19 had increased proportions of opportunistic fungal pathogens, Candida albicans, Candida auris, and Aspergillus flavus compared with controls. Two respiratory-associated fungal pathogens, A. flavus and Aspergillus niger, were detected in fecal samples from a subset of patients with COVID-19, even after clearance of SARS-CoV-2 from nasopharyngeal samples and resolution of respiratory symptoms. CONCLUSIONS: In a pilot study, we found heterogeneous configurations of the fecal mycobiome, with enrichment of fungal pathogens from the genera Candida and Aspergillus, during hospitalization of 30 patients with COVID-19 compared with controls. Unstable gut mycobiomes and prolonged dysbiosis persisted in a subset of patients with COVID-19 up to 12 days after nasopharyngeal clearance of SARS-CoV-2. Studies are needed to determine whether alterations in intestinal fungi contribute to or result from SARS-CoV-2 infection, and the effects of these changes in disease progression.


Subject(s)
Coronavirus Infections/microbiology , Feces/microbiology , Fungi/isolation & purification , Gastrointestinal Microbiome , Mycobiome , Pneumonia, Viral/microbiology , Adult , Aged , Aspergillus flavus/genetics , Aspergillus flavus/isolation & purification , Aspergillus niger/genetics , Aspergillus niger/isolation & purification , Betacoronavirus , COVID-19 , Candida/genetics , Candida/isolation & purification , Candida albicans/genetics , Candida albicans/isolation & purification , Case-Control Studies , Community-Acquired Infections/microbiology , DNA, Fungal/analysis , Female , Fungi/genetics , Humans , Male , Metagenomics , Middle Aged , Nasopharynx/virology , Pandemics , Patient Discharge , Pneumonia/microbiology , SARS-CoV-2 , Time Factors , Young Adult
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