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1.
N Engl J Med ; 386(9): 861-868, 2022 03 03.
Article in English | MEDLINE | ID: covidwho-1721753

ABSTRACT

Melioidosis, caused by the bacterium Burkholderia pseudomallei, is an uncommon infection that is typically associated with exposure to soil and water in tropical and subtropical environments. It is rarely diagnosed in the continental United States. Patients with melioidosis in the United States commonly report travel to regions where melioidosis is endemic. We report a cluster of four non-travel-associated cases of melioidosis in Georgia, Kansas, Minnesota, and Texas. These cases were caused by the same strain of B. pseudomallei that was linked to an aromatherapy spray product imported from a melioidosis-endemic area.


Subject(s)
Aromatherapy/adverse effects , Burkholderia pseudomallei/isolation & purification , Disease Outbreaks , Melioidosis/epidemiology , Aerosols , Brain/microbiology , Brain/pathology , Burkholderia pseudomallei/genetics , COVID-19/complications , Child, Preschool , Fatal Outcome , Female , Genome, Bacterial , Humans , Lung/microbiology , Lung/pathology , Male , Melioidosis/complications , Middle Aged , Phylogeny , Shock, Septic/microbiology , United States/epidemiology
2.
Int J Mol Sci ; 23(4)2022 Feb 10.
Article in English | MEDLINE | ID: covidwho-1715394

ABSTRACT

Tuberculosis (TB) is one of the ten leading causes of death worldwide. Patients with TB have been observed to suffer from depression and anxiety linked to social variables. Previous experiments found that the substantial pulmonary inflammation associated with TB causes neuroinflammation, neuronal death, and behavioral impairments in the absence of brain infection. Curcumin (CUR) is a natural product with antioxidant, anti-inflammatory and antibacterial activities. In this work, we evaluated the CUR effect on the growth control of mycobacteria in the lungs and the anti-inflammatory effect in the brain using a model of progressive pulmonary TB in BALB/c mice infected with drug-sensitive mycobacteria (strain H37Rv). The results have shown that CUR decreased lung bacilli load and pneumonia of infected animals. Finally, CUR significantly decreased neuroinflammation (expression of TNFα, IFNγ and IL12) and slightly increased the levels of nuclear factor erythroid 2-related to factor 2 (Nrf2) and the brain-derived neurotrophic factor (BDNF) levels, improving behavioral status. These results suggest that CUR has a bactericidal effect and can control pulmonary mycobacterial infection and reduce neuroinflammation. It seems that CUR has a promising potential as adjuvant therapy in TB treatment.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Antitubercular Agents/pharmacology , Brain/microbiology , Curcumin/pharmacology , Lung/microbiology , Tuberculosis, Pulmonary/drug therapy , Tuberculosis/drug therapy , Animals , Brain/metabolism , Brain-Derived Neurotrophic Factor/metabolism , Disease Models, Animal , Inflammation/drug therapy , Inflammation/metabolism , Lung/metabolism , Male , Mice , Mice, Inbred BALB C , Mycobacterium tuberculosis/drug effects , Tuberculosis/metabolism , Tuberculosis, Pulmonary/metabolism
3.
Front Immunol ; 12: 700705, 2021.
Article in English | MEDLINE | ID: covidwho-1686468

ABSTRACT

A novel coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), arose late in 2019, with disease pathology ranging from asymptomatic to severe respiratory distress with multi-organ failure requiring mechanical ventilator support. It has been found that SARS-CoV-2 infection drives intracellular complement activation in lung cells that tracks with disease severity. However, the cellular and molecular mechanisms responsible remain unclear. To shed light on the potential mechanisms, we examined publicly available RNA-Sequencing data using CIBERSORTx and conducted a Ingenuity Pathway Analysis to address this knowledge gap. In complement to these findings, we used bioinformatics tools to analyze publicly available RNA sequencing data and found that upregulation of complement may be leading to a downregulation of T-cell activity in lungs of severe COVID-19 patients. Thus, targeting treatments aimed at the modulation of classical complement and T-cell activity may help alleviate the proinflammatory effects of COVID-19, reduce lung pathology, and increase the survival of COVID-19 patients.


Subject(s)
COVID-19/genetics , Complement Activation/genetics , Complement System Proteins/genetics , Gene Expression Profiling/methods , Lung/metabolism , T-Lymphocytes/metabolism , COVID-19/immunology , COVID-19/virology , Gene Regulatory Networks/genetics , Humans , Intracellular Space/genetics , Lung/immunology , Lung/microbiology , Lymphocyte Count , SARS-CoV-2/physiology , T-Lymphocyte Subsets/metabolism
4.
Int J Infect Dis ; 117: 233-240, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1670583

ABSTRACT

BACKGROUND: The COVID-19 pandemic has intensified interest in how the infection affects the lung microbiome of critically ill patients and how it contributes to acute respiratory distress syndrome (ARDS). We aimed to characterize the lower respiratory tract mycobiome of critically ill patients with COVID-19 in comparison to patients without COVID-19. METHODS: We performed an internal transcribed spacer 2 (ITS2) profiling with the Illumina MiSeq platform on 26 respiratory specimens from patients with COVID-19 as well as from 26 patients with non-COVID-19 pneumonia. RESULTS: Patients with COVID-19 were more likely to be colonized with Candida spp. ARDS was associated with lung dysbiosis characterized by a shift to Candida species colonization and a decrease of fungal diversity. We also observed higher bacterial phylogenetic distance among taxa in colonized patients with COVID-19. In patients with COVID-19 not colonized with Candida spp., ITS2 amplicon sequencing revealed an increase of Ascomycota unassigned spp. and 1 Aspergillus spp.-positive specimen. In addition, we found that corticosteroid therapy was frequently associated with positive Galactomannan cell wall component of Aspergillus spp. among patients with COVID-19. CONCLUSION: Our study underpins that ARDS in patients with COVID-19 is associated with lung dysbiosis and that an increased density of Ascomycota unassigned spp. is present in patients not colonized with Candida spp.


Subject(s)
COVID-19 , COVID-19/complications , Candida/genetics , Critical Illness , Dysbiosis/complications , Dysbiosis/microbiology , Humans , Lung/microbiology , Pandemics , Phylogeny
5.
Virchows Arch ; 479(1): 97-108, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1574264

ABSTRACT

Between April and June 2020, i.e., during the first wave of pandemic coronavirus disease 2019 (COVID-19), 55 patients underwent long-term treatment in the intensive care unit at the University Hospital of Regensburg. Most of them were transferred from smaller hospitals, often due to the need for an extracorporeal membrane oxygenation system. Autopsy was performed in 8/17 COVID-19-proven patients after long-term treatment (mean: 33.6 days). Autopsy revealed that the typical pathological changes occurring during the early stages of the disease (e.g., thrombosis, endothelitis, capillaritis) are less prevalent at this stage, while severe diffuse alveolar damage and especially coinfection with different fungal species were the most conspicuous finding. In addition, signs of macrophage activation syndrome was detected in 7 of 8 patients. Thus, fungal infections were a leading cause of death in our cohort of severely ill patients and may alter clinical management of patients, particularly in long-term periods of treatment.


Subject(s)
COVID-19/microbiology , Coinfection , Lung Diseases, Fungal/microbiology , Lung/microbiology , Multiple Organ Failure/microbiology , Adult , Aged , COVID-19/drug therapy , COVID-19/mortality , COVID-19/pathology , COVID-19/therapy , Cause of Death , Extracorporeal Membrane Oxygenation , Female , Humans , Intensive Care Units , Lung/pathology , Lung/virology , Lung Diseases, Fungal/mortality , Lung Diseases, Fungal/pathology , Macrophage Activation Syndrome/microbiology , Macrophage Activation Syndrome/pathology , Male , Middle Aged , Multiple Organ Failure/mortality , Multiple Organ Failure/pathology , Multiple Organ Failure/virology , Risk Factors , Time Factors , Treatment Outcome
6.
Int J Mol Sci ; 22(23)2021 Nov 24.
Article in English | MEDLINE | ID: covidwho-1560167

ABSTRACT

Streptococcus pneumoniae is an important causative organism of respiratory tract infections. Although periodontal bacteria have been shown to influence respiratory infections such as aspiration pneumonia, the synergistic effect of S. pneumoniae and Porphyromonas gingivalis, a periodontopathic bacterium, on pneumococcal infections is unclear. To investigate whether P. gingivalis accelerates pneumococcal infections, we tested the effects of inoculating P. gingivalis culture supernatant (PgSup) into S. pneumoniae-infected mice. Mice were intratracheally injected with S. pneumoniae and PgSup to induce pneumonia, and lung histopathological sections and the absolute number and frequency of neutrophils and macrophages in the lung were analyzed. Proinflammatory cytokine/chemokine expression was examined by qPCR and ELISA. Inflammatory cell infiltration was observed in S. pneumoniae-infected mice and S. pnemoniae and PgSup mixed-infected mice, and mixed-infected mice showed more pronounced inflammation in lung. The ratios of monocytes/macrophages and neutrophils were not significantly different between the lungs of S. pneumoniae-infected mice and those of mixed-infected mice. PgSup synergistically increased TNF-α expression/production and IL-17 production compared with S. pneumoniae infection alone. We demonstrated that PgSup enhanced inflammation in pneumonia caused by S. pneumoniae, suggesting that virulence factors produced by P. gingivalis are involved in the exacerbation of respiratory tract infections such as aspiration pneumonia.


Subject(s)
Bacteroidaceae Infections/complications , Inflammation/pathology , Lung/pathology , Neutrophil Infiltration/immunology , Pneumonia, Pneumococcal/pathology , Porphyromonas gingivalis/physiology , Streptococcus pneumoniae/physiology , Animals , Bacteroidaceae Infections/microbiology , Chemokines/metabolism , Cytokines/metabolism , Inflammation/etiology , Lung/immunology , Lung/metabolism , Lung/microbiology , Mice , Mice, Inbred C57BL , Pneumonia, Pneumococcal/epidemiology , Pneumonia, Pneumococcal/metabolism , Pneumonia, Pneumococcal/microbiology
7.
Front Immunol ; 12: 656419, 2021.
Article in English | MEDLINE | ID: covidwho-1506563

ABSTRACT

Tuberculosis (TB) is the global health problem with the second highest number of deaths from a communicable disease after COVID-19. Although TB is curable, poor health infrastructure, long and grueling TB treatments have led to the spread of TB pandemic with alarmingly increasing multidrug-resistant (MDR)-TB prevalence. Alternative host modulating therapies can be employed to improve TB drug efficacies or dampen the exaggerated inflammatory responses to improve lung function. Here, we investigated the adjunct therapy of natural immune-modulatory compound berberine in C57BL/6 mouse model of pulmonary TB. Berberine treatment did not affect Mtb growth in axenic cultures; however, it showed increased bacterial killing in primary murine bone marrow-derived macrophages and human monocyte-derived macrophages. Ad libitum berberine administration was beneficial to the host in combination with rifampicin and isoniazid. Berberine adjunctive treatment resulted in decreased lung pathology with no additive or synergistic effects on bacterial burdens in mice. Lung immune cell flow cytometry analysis showed that adjunctive berberine treatment decreased neutrophil, CD11b+ dendritic cell and recruited interstitial macrophage numbers. Late onset of adjunctive berberine treatment resulted in a similar phenotype with consistently reduced numbers of neutrophils both in lungs and the spleen. Together, our results suggest that berberine can be supplemented as an immunomodulatory agent depending on the disease stage and inflammatory status of the host.


Subject(s)
Antitubercular Agents/therapeutic use , Berberine/therapeutic use , Immunologic Factors/therapeutic use , Isoniazid/therapeutic use , Rifampin/therapeutic use , Tuberculosis, Pulmonary/drug therapy , Animals , Antitubercular Agents/pharmacology , Berberine/pharmacology , Cytokines/immunology , Dendritic Cells/drug effects , Drug Therapy, Combination , Female , Humans , Immunologic Factors/pharmacology , Isoniazid/pharmacology , Lung/drug effects , Lung/immunology , Lung/microbiology , Lung/pathology , Macrophages/drug effects , Macrophages/immunology , Male , Mice, Inbred C3H , Mice, Inbred C57BL , Mycobacterium tuberculosis/drug effects , Mycobacterium tuberculosis/growth & development , Neutrophils/drug effects , Neutrophils/immunology , Rifampin/pharmacology , Spleen/drug effects , Spleen/immunology , Spleen/microbiology , Tuberculosis, Pulmonary/immunology , Tuberculosis, Pulmonary/microbiology , Tuberculosis, Pulmonary/pathology
8.
Toxins (Basel) ; 12(4)2020 04 02.
Article in English | MEDLINE | ID: covidwho-1453289

ABSTRACT

Bacterial toxins play a key role in the pathogenesis of lung disease. Based on their structural and functional properties, they employ various strategies to modulate lung barrier function and to impair host defense in order to promote infection. Although in general, these toxins target common cellular signaling pathways and host compartments, toxin- and cell-specific effects have also been reported. Toxins can affect resident pulmonary cells involved in alveolar fluid clearance (AFC) and barrier function through impairing vectorial Na+ transport and through cytoskeletal collapse, as such, destroying cell-cell adhesions. The resulting loss of alveolar-capillary barrier integrity and fluid clearance capacity will induce capillary leak and foster edema formation, which will in turn impair gas exchange and endanger the survival of the host. Toxins modulate or neutralize protective host cell mechanisms of both the innate and adaptive immunity response during chronic infection. In particular, toxins can either recruit or kill central players of the lung's innate immune responses to pathogenic attacks, i.e., alveolar macrophages (AMs) and neutrophils. Pulmonary disorders resulting from these toxin actions include, e.g., acute lung injury (ALI), the acute respiratory syndrome (ARDS), and severe pneumonia. When acute infection converts to persistence, i.e., colonization and chronic infection, lung diseases, such as bronchitis, chronic obstructive pulmonary disease (COPD), and cystic fibrosis (CF) can arise. The aim of this review is to discuss the impact of bacterial toxins in the lungs and the resulting outcomes for pathogenesis, their roles in promoting bacterial dissemination, and bacterial survival in disease progression.


Subject(s)
Bacteria/pathogenicity , Bacterial Infections/microbiology , Bacterial Toxins/metabolism , Lung/microbiology , Respiratory Tract Infections/microbiology , Adaptive Immunity , Animals , Bacteria/immunology , Bacteria/metabolism , Bacterial Infections/immunology , Bacterial Infections/metabolism , Bacterial Infections/pathology , Disease Progression , Host-Pathogen Interactions , Humans , Immunity, Innate , Lung/immunology , Lung/metabolism , Lung/pathology , Respiratory Tract Infections/immunology , Respiratory Tract Infections/metabolism , Respiratory Tract Infections/pathology , Signal Transduction
11.
Int J Biol Sci ; 17(13): 3305-3319, 2021.
Article in English | MEDLINE | ID: covidwho-1372133

ABSTRACT

An inflammatory cytokine storm is considered an important cause of death in severely and critically ill COVID-19 patients, however, the relationship between the SARS-CoV-2 spike (S) protein and the host's inflammatory cytokine storm is not clear. Here, the qPCR results indicated that S protein induced a significantly elevated expression of multiple inflammatory factor mRNAs in peripheral blood mononuclear cells (PBMCs), whereas RS-5645 ((4-(thiophen-3-yl)-1-(p-tolyl)-1H-pyrrol-3-yl)(3,4,5-trimethoxyphenyl)methanone) attenuated the expression of the most inflammatory factor mRNAs. RS-5645 also significantly reduced the cellular ratios of CD45+/IFNγ+, CD3+/IFNγ+, CD11b+/IFNγ+, and CD56+/IFNγ+ in human PBMCs. In addition, RS-5645 effectively inhibited the activation of inflammatory cells and reduced inflammatory damage to lung tissue in mice. Sequencing results of 16S rRNA v3+v4 in mouse alveolar lavage fluid showed that there were 494 OTUs overlapping between the alveolar lavage fluid of mice that underwent S protein+ LPS-combined intervention (M) and RS-5645-treated mice (R), while R manifested 64 unique OTUs and M exhibited 610 unique OTUs. In the alveoli of group R mice, the relative abundances of microorganisms belonging to Porphyromonas, Rothia, Streptococcus, and Neisseria increased significantly, while the relative abundances of microorganisms belonging to Psychrobacter, Shimia, and Sporosarcina were significantly diminished. The results of KEGG analysis indicated that the alveolar microbiota of mice in the R group can increase translation and reduce the activity of amino acid metabolism pathways. COG analysis results indicated that the abundance of proteins involved in ribosomal structure and biogenesis related to metabolism was augmented in the alveolar microbiota of the mice in the R group, while the abundance of proteins involved in secondary metabolite biosynthesis was significantly reduced. Therefore, our research results showed that RS-5645 attenuated pulmonary inflammatory cell infiltration and the inflammatory storm induced by the S protein and LPS by modulating the pulmonary microbiota.


Subject(s)
Anti-Inflammatory Agents/pharmacology , COVID-19/immunology , Cytokine Release Syndrome/prevention & control , Lipopolysaccharides/pharmacology , Lung/microbiology , Microbiota/drug effects , SARS-CoV-2/pathogenicity , Spike Glycoprotein, Coronavirus/physiology , Animals , Antigens, CD/immunology , COVID-19/virology , Cytokine Release Syndrome/immunology , Disease Models, Animal , Humans , Interferon-gamma/immunology , Male , Mice , Mice, Inbred BALB C
12.
mBio ; 12(4): e0177721, 2021 08 31.
Article in English | MEDLINE | ID: covidwho-1360545

ABSTRACT

Viral infection of the respiratory tract can be associated with propagating effects on the airway microbiome, and microbiome dysbiosis may influence viral disease. Here, we investigated the respiratory tract microbiome in coronavirus disease 2019 (COVID-19) and its relationship to disease severity, systemic immunologic features, and outcomes. We examined 507 oropharyngeal, nasopharyngeal, and endotracheal samples from 83 hospitalized COVID-19 patients as well as non-COVID patients and healthy controls. Bacterial communities were interrogated using 16S rRNA gene sequencing, and the commensal DNA viruses Anelloviridae and Redondoviridae were quantified by qPCR. We found that COVID-19 patients had upper respiratory microbiome dysbiosis and greater change over time than critically ill patients without COVID-19. Oropharyngeal microbiome diversity at the first time point correlated inversely with disease severity during hospitalization. Microbiome composition was also associated with systemic immune parameters in blood, as measured by lymphocyte/neutrophil ratios and immune profiling of peripheral blood mononuclear cells. Intubated patients showed patient-specific lung microbiome communities that were frequently highly dynamic, with prominence of Staphylococcus. Anelloviridae and Redondoviridae showed more frequent colonization and higher titers in severe disease. Machine learning analysis demonstrated that integrated features of the microbiome at early sampling points had high power to discriminate ultimate level of COVID-19 severity. Thus, the respiratory tract microbiome and commensal viruses are disturbed in COVID-19 and correlate with systemic immune parameters, and early microbiome features discriminate disease severity. Future studies should address clinical consequences of airway dysbiosis in COVID-19, its possible use as biomarkers, and the role of bacterial and viral taxa identified here in COVID-19 pathogenesis. IMPORTANCE COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection of the respiratory tract, results in highly variable outcomes ranging from minimal illness to death, but the reasons for this are not well understood. We investigated the respiratory tract bacterial microbiome and small commensal DNA viruses in hospitalized COVID-19 patients and found that each was markedly abnormal compared to that in healthy people and differed from that in critically ill patients without COVID-19. Early airway samples tracked with the level of COVID-19 illness reached during hospitalization, and the airway microbiome also correlated with immune parameters in blood. These findings raise questions about the mechanisms linking SARS-CoV-2 infection and other microbial inhabitants of the airway, including whether the microbiome might regulate severity of COVID-19 disease and/or whether early microbiome features might serve as biomarkers to discriminate disease severity.


Subject(s)
Bacteria/classification , Dysbiosis/microbiology , Lung/microbiology , Nasopharynx/microbiology , Oropharynx/microbiology , SARS-CoV-2/immunology , Adult , Aged , Aged, 80 and over , Anelloviridae/classification , Anelloviridae/genetics , Anelloviridae/isolation & purification , Bacteria/genetics , Bacteria/isolation & purification , COVID-19/pathology , Female , Humans , Lymphocyte Count , Male , Microbiota , Middle Aged , RNA, Ribosomal, 16S/genetics , Severity of Illness Index
14.
Cells ; 10(6)2021 06 10.
Article in English | MEDLINE | ID: covidwho-1264420

ABSTRACT

The implications of the microbiome on Coronavirus disease 2019 (COVID-19) prognosis has not been thoroughly studied. In this study we aimed to characterize the lung and blood microbiome and their implication on COVID-19 prognosis through analysis of peripheral blood mononuclear cell (PBMC) samples, lung biopsy samples, and bronchoalveolar lavage fluid (BALF) samples. In all three tissue types, we found panels of microbes differentially abundant between COVID-19 and normal samples correlated to immune dysregulation and upregulation of inflammatory pathways, including key cytokine pathways such as interleukin (IL)-2, 3, 5-10 and 23 signaling pathways and downregulation of anti-inflammatory pathways including IL-4 signaling. In the PBMC samples, six microbes were correlated with worse COVID-19 severity, and one microbe was correlated with improved COVID-19 severity. Collectively, our findings contribute to the understanding of the human microbiome and suggest interplay between our identified microbes and key inflammatory pathways which may be leveraged in the development of immune therapies for treating COVID-19 patients.


Subject(s)
COVID-19/diagnosis , Leukocytes, Mononuclear/microbiology , Lung/microbiology , Microbiota/physiology , Bronchoalveolar Lavage Fluid/microbiology , Bronchoalveolar Lavage Fluid/virology , COVID-19/immunology , COVID-19/microbiology , COVID-19/virology , Case-Control Studies , Humans , Leukocytes, Mononuclear/virology , Liquid Biopsy , Lung/pathology , Lung/virology , Microbiota/genetics , Microbiota/immunology , Prognosis , RNA, Bacterial/analysis , RNA, Fungal/analysis , RNA-Seq , SARS-CoV-2/physiology
15.
Crit Care ; 25(1): 197, 2021 06 07.
Article in English | MEDLINE | ID: covidwho-1261277

ABSTRACT

BACKGROUND: Hospitalized patients with COVID-19 admitted to the intensive care unit (ICU) and requiring mechanical ventilation are at risk of ventilator-associated bacterial infections secondary to SARS-CoV-2 infection. Our study aimed to investigate clinical features of Staphylococcus aureus ventilator-associated pneumonia (SA-VAP) and, if bronchoalveolar lavage samples were available, lung bacterial community features in ICU patients with or without COVID-19. METHODS: We prospectively included hospitalized patients with COVID-19 across two medical ICUs of the Fondazione Policlinico Universitario A. Gemelli IRCCS (Rome, Italy), who developed SA-VAP between 20 March 2020 and 30 October 2020 (thereafter referred to as cases). After 1:2 matching based on the simplified acute physiology score II (SAPS II) and the sequential organ failure assessment (SOFA) score, cases were compared with SA-VAP patients without COVID-19 (controls). Clinical, microbiological, and lung microbiota data were analyzed. RESULTS: We studied two groups of patients (40 COVID-19 and 80 non-COVID-19). COVID-19 patients had a higher rate of late-onset (87.5% versus 63.8%; p = 0.01), methicillin-resistant (65.0% vs 27.5%; p < 0.01) or bacteremic (47.5% vs 6.3%; p < 0.01) infections compared with non-COVID-19 patients. No statistically significant differences between the patient groups were observed in ICU mortality (p = 0.12), clinical cure (p = 0.20) and microbiological eradication (p = 0.31). On multivariable logistic regression analysis, SAPS II and initial inappropriate antimicrobial therapy were independently associated with ICU mortality. Then, lung microbiota characterization in 10 COVID-19 and 16 non-COVID-19 patients revealed that the overall microbial community composition was significantly different between the patient groups (unweighted UniFrac distance, R2 0.15349; p < 0.01). Species diversity was lower in COVID-19 than in non COVID-19 patients (94.4 ± 44.9 vs 152.5 ± 41.8; p < 0.01). Interestingly, we found that S. aureus (log2 fold change, 29.5), Streptococcus anginosus subspecies anginosus (log2 fold change, 24.9), and Olsenella (log2 fold change, 25.7) were significantly enriched in the COVID-19 group compared to the non-COVID-19 group of SA-VAP patients. CONCLUSIONS: In our study population, COVID-19 seemed to significantly affect microbiological and clinical features of SA-VAP as well as to be associated with a peculiar lung microbiota composition.


Subject(s)
COVID-19/complications , Pneumonia, Ventilator-Associated/microbiology , Staphylococcal Infections/etiology , Staphylococcus aureus/isolation & purification , Aged , Anti-Bacterial Agents/therapeutic use , Bronchoalveolar Lavage Fluid/microbiology , COVID-19/mortality , COVID-19/therapy , Female , Hospital Mortality , Hospitalization , Humans , Intensive Care Units , Italy , Logistic Models , Lung/microbiology , Male , Middle Aged , Organ Dysfunction Scores , Pneumonia, Ventilator-Associated/drug therapy , Pneumonia, Ventilator-Associated/etiology , Prospective Studies , Respiration, Artificial , Staphylococcal Infections/drug therapy
16.
JAMA ; 325(18): 1841-1851, 2021 05 11.
Article in English | MEDLINE | ID: covidwho-1237391

ABSTRACT

Importance: Alteration in lung microbes is associated with disease progression in idiopathic pulmonary fibrosis. Objective: To assess the effect of antimicrobial therapy on clinical outcomes. Design, Setting, and Participants: Pragmatic, randomized, unblinded clinical trial conducted across 35 US sites. A total of 513 patients older than 40 years were randomized from August 2017 to June 2019 (final follow-up was January 2020). Interventions: Patients were randomized in a 1:1 allocation ratio to receive antimicrobials (n = 254) or usual care alone (n = 259). Antimicrobials included co-trimoxazole (trimethoprim 160 mg/sulfamethoxazole 800 mg twice daily plus folic acid 5 mg daily, n = 128) or doxycycline (100 mg once daily if body weight <50 kg or 100 mg twice daily if ≥50 kg, n = 126). No placebo was administered in the usual care alone group. Main Outcomes and Measures: The primary end point was time to first nonelective respiratory hospitalization or all-cause mortality. Results: Among the 513 patients who were randomized (mean age, 71 years; 23.6% women), all (100%) were included in the analysis. The study was terminated for futility on December 18, 2019. After a mean follow-up time of 13.1 months (median, 12.7 months), a total of 108 primary end point events occurred: 52 events (20.4 events per 100 patient-years [95% CI, 14.8-25.9]) in the usual care plus antimicrobial therapy group and 56 events (18.4 events per 100 patient-years [95% CI, 13.2-23.6]) in the usual care group, with no significant difference between groups (adjusted HR, 1.04 [95% CI, 0.71-1.53; P = .83]. There was no statistically significant interaction between the effect of the prespecified antimicrobial agent (co-trimoxazole vs doxycycline) on the primary end point (adjusted HR, 1.15 [95% CI 0.68-1.95] in the co-trimoxazole group vs 0.82 [95% CI, 0.46-1.47] in the doxycycline group; P = .66). Serious adverse events occurring at 5% or greater among those treated with usual care plus antimicrobials vs usual care alone included respiratory events (16.5% vs 10.0%) and infections (2.8% vs 6.6%); adverse events of special interest included diarrhea (10.2% vs 3.1%) and rash (6.7% vs 0%). Conclusions and Relevance: Among adults with idiopathic pulmonary fibrosis, the addition of co-trimoxazole or doxycycline to usual care, compared with usual care alone, did not significantly improve time to nonelective respiratory hospitalization or death. These findings do not support treatment with these antibiotics for the underlying disease. Trial Registration: ClinicalTrials.gov Identifier: NCT02759120.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Doxycycline/therapeutic use , Idiopathic Pulmonary Fibrosis/drug therapy , Trimethoprim, Sulfamethoxazole Drug Combination/therapeutic use , Aged , Anti-Bacterial Agents/adverse effects , Doxycycline/adverse effects , Female , Hospitalization , Humans , Idiopathic Pulmonary Fibrosis/mortality , Lung/microbiology , Male , Middle Aged , Respiratory Function Tests , Respiratory Tract Infections/prevention & control , Treatment Outcome , Trimethoprim, Sulfamethoxazole Drug Combination/adverse effects
17.
Sci Rep ; 11(1): 10103, 2021 05 12.
Article in English | MEDLINE | ID: covidwho-1226438

ABSTRACT

COVID-19 infection may predispose to secondary bacterial infection which is associated with poor clinical outcome especially among critically ill patients. We aimed to characterize the lower respiratory tract bacterial microbiome of COVID-19 critically ill patients in comparison to COVID-19-negative patients. We performed a 16S rRNA profiling on bronchoalveolar lavage (BAL) samples collected between April and May 2020 from 24 COVID-19 critically ill subjects and 24 patients with non-COVID-19 pneumonia. Lung microbiome of critically ill patients with COVID-19 was characterized by a different bacterial diversity (PERMANOVA on weighted and unweighted UniFrac Pr(> F) = 0.001) compared to COVID-19-negative patients with pneumonia. Pseudomonas alcaligenes, Clostridium hiranonis, Acinetobacter schindleri, Sphingobacterium spp., Acinetobacter spp. and Enterobacteriaceae, characterized lung microbiome of COVID-19 critically ill patients (LDA score > 2), while COVID-19-negative patients showed a higher abundance of lung commensal bacteria (Haemophilus influenzae, Veillonella dispar, Granulicatella spp., Porphyromonas spp., and Streptococcus spp.). The incidence rate (IR) of infections during COVID-19 pandemic showed a significant increase of carbapenem-resistant Acinetobacter baumannii (CR-Ab) infection. In conclusion, SARS-CoV-2 infection and antibiotic pressure may predispose critically ill patients to bacterial superinfection due to opportunistic multidrug resistant pathogens.


Subject(s)
Bacteria/isolation & purification , COVID-19/microbiology , Dysbiosis/microbiology , Lung/microbiology , Aged , Bronchoalveolar Lavage Fluid/microbiology , COVID-19/diagnosis , Critical Illness , Dysbiosis/complications , Female , Humans , Male , Microbiota , Middle Aged , SARS-CoV-2/isolation & purification
18.
PLoS One ; 16(4): e0250728, 2021.
Article in English | MEDLINE | ID: covidwho-1207636

ABSTRACT

Among 197 COVID-19 patients hospitalized in ICU, 88 (44.7%) experienced at least one bacterial infection, with pneumonia (39.1%) and bloodstream infections (15,7%) being the most frequent. Unusual findings include frequent suspicion of bacterial translocations originating from the digestive tract as well as bacterial persistence in the lungs despite adequate therapy.


Subject(s)
Bacterial Infections/complications , COVID-19/complications , Pneumonia, Bacterial/complications , Aged , Bacterial Infections/epidemiology , COVID-19/epidemiology , Female , France/epidemiology , Hospitalization , Humans , Intensive Care Units , Lung/microbiology , Lung/virology , Male , Middle Aged , Pneumonia, Bacterial/epidemiology
20.
Clin Immunol ; 226: 108725, 2021 05.
Article in English | MEDLINE | ID: covidwho-1174146

ABSTRACT

Worldwide, scientists are looking for specific treatment for COVID-19. Apart from the antiviral approach, the interventions to support healthy immune responses to the virus are feasible through diet, nutrition, and lifestyle approaches. This narrative review explores the recent studies on dietary, nutritional, and lifestyle interventions that influence the microbiota-mediated immunomodulatory effects against viral infections. Cumulative studies reported that the airway microbiota and SARS-CoV-2 leverage each other and determine the pathogen-microbiota-host responses. Cigarette smoking can disrupt microbiota abundance. The composition and diversification of intestinal microbiota influence the airway microbiota and the innate and adaptive immunity, which require supports from the balance of macro- and micronutrients from the diet. Colorful vegetables supplied fermentable prebiotics and anti-inflammatory, antioxidant phytonutrients. Fermented foods and beverages support intestinal microbiota. In sensitive individuals, the avoidance of the high immunoreactive food antigens contributes to antiviral immunity. This review suggests associations between airway and intestinal microbiota, antiviral host immunity, and the influences of dietary, nutritional, and lifestyle interventions to prevent the clinical course toward severe COVID-19.


Subject(s)
COVID-19/diet therapy , COVID-19/immunology , Gastrointestinal Microbiome/immunology , Host Microbial Interactions/immunology , Lung/immunology , Adaptive Immunity , Anti-Inflammatory Agents/pharmacology , Antioxidants/pharmacology , COVID-19/microbiology , COVID-19/prevention & control , Humans , Immunity, Innate , Life Style , Lung/microbiology , Lung/pathology , Lung/virology , Prebiotics/administration & dosage , Probiotics/pharmacology , Probiotics/therapeutic use , SARS-CoV-2/pathogenicity
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