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1.
Front Immunol ; 12: 715023, 2021.
Article in English | MEDLINE | ID: covidwho-1477819

ABSTRACT

Emerging evidence has unveiled the secondary infection as one of the mortal causes of post-SARS-CoV-2 infection, but the factors related to secondary bacterial or fungi infection remains largely unexplored. We here systematically investigated the factors that might contribute to secondary infection. By clinical examination index analysis of patients, combined with the integrative analysis with RNA-seq analysis in the peripheral blood mononuclear cell isolated shortly from initial infection, this study showed that the antibiotic catabolic process and myeloid cell homeostasis were activated while the T-cell response were relatively repressed in those with the risk of secondary infection. Further monitoring analysis of immune cell and liver injury analysis showed that the risk of secondary infection was accompanied by severe lymphocytopenia at the intermediate and late stages and liver injury at the early stages of SARS-CoV-2. Moreover, the metagenomics analysis of bronchoalveolar lavage fluid and the microbial culture analysis, to some extent, showed that the severe pneumonia-related bacteria have already existed in the initial infection.


Subject(s)
Bacterial Infections/epidemiology , COVID-19/pathology , Coinfection/epidemiology , Coinfection/mortality , Mycoses/epidemiology , Adult , Aged , Aged, 80 and over , Bacterial Infections/mortality , Bronchoalveolar Lavage Fluid/microbiology , CD4 Lymphocyte Count , Female , Humans , Leukocytes, Mononuclear/immunology , Liver/injuries , Liver/virology , Lymphopenia/immunology , Male , Middle Aged , Mycoses/mortality , Retrospective Studies , Risk Factors , SARS-CoV-2/immunology , T-Lymphocytes/immunology
2.
Nat Microbiol ; 6(10): 1245-1258, 2021 10.
Article in English | MEDLINE | ID: covidwho-1380902

ABSTRACT

Respiratory failure is associated with increased mortality in COVID-19 patients. There are no validated lower airway biomarkers to predict clinical outcome. We investigated whether bacterial respiratory infections were associated with poor clinical outcome of COVID-19 in a prospective, observational cohort of 589 critically ill adults, all of whom required mechanical ventilation. For a subset of 142 patients who underwent bronchoscopy, we quantified SARS-CoV-2 viral load, analysed the lower respiratory tract microbiome using metagenomics and metatranscriptomics and profiled the host immune response. Acquisition of a hospital-acquired respiratory pathogen was not associated with fatal outcome. Poor clinical outcome was associated with lower airway enrichment with an oral commensal (Mycoplasma salivarium). Increased SARS-CoV-2 abundance, low anti-SARS-CoV-2 antibody response and a distinct host transcriptome profile of the lower airways were most predictive of mortality. Our data provide evidence that secondary respiratory infections do not drive mortality in COVID-19 and clinical management strategies should prioritize reducing viral replication and maximizing host responses to SARS-CoV-2.


Subject(s)
Bronchoalveolar Lavage Fluid/microbiology , COVID-19/therapy , Respiration, Artificial , SARS-CoV-2/pathogenicity , Adaptive Immunity , Adult , Aged , Bacteria/classification , Bacteria/genetics , Bacteria/isolation & purification , Bacterial Load , Bronchoalveolar Lavage Fluid/immunology , Bronchoalveolar Lavage Fluid/virology , COVID-19/immunology , COVID-19/microbiology , COVID-19/mortality , Critical Illness , Female , Hospitalization , Humans , Immunity, Innate , Male , Microbiota , Middle Aged , Odds Ratio , Prognosis , Prospective Studies , Respiratory System/immunology , Respiratory System/microbiology , Respiratory System/virology , SARS-CoV-2/immunology , Viral Load
3.
BMC Pulm Med ; 20(1): 233, 2020 Aug 31.
Article in English | MEDLINE | ID: covidwho-1257932

ABSTRACT

BACKGROUND: Lower respiratory tract infection (LRIs) is very common both in terms of community-acquired infection and hospital-acquired infection. Sputum and bronchoalveolar lavage fluid (BALF) are the most important specimens obtained from patients with LRI. The choice of antibiotic with which to treat LRI usually depends on the antimicrobial sensitivity of bacteria isolated from sputum and BALF. However, differences in the antimicrobial sensitivity of pathogens isolated from sputum and BALF have not been evaluated. METHODS: A retrospective study was conducted to analyze the differences between sputum and BALF samples in terms of pathogen isolation and antimicrobial sensitivity in hospitalized patients with LRI. RESULTS: Between 2013 and 2015, quality evaluation of sputum samples was not conducted before performing sputum culture; however, between 2016 and 2018, quality evaluation of sputum samples was conducted first, and only quality-assured samples were cultured. The numbers of sputum and BALF in 2013-2015 were 15,549 and 1671, while those in 2016-2018 were 12,055 and 3735, respectively. The results of pathogen culture showed that Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae, Staphylococcus aureus, Hemophilus influenzae, Escherichia coli, Stenotrophomonas maltophilia, and Streptococcus pneumoniae were in the top ten pathogens isolated from sputum and BALF. An antimicrobial susceptibility test showed that the susceptibility of BALF isolates to most antibiotics was higher compared with the susceptibility of sputum isolates, especially after quality control of sputum samples (2016-2018). CONCLUSIONS: Our findings suggest that caution is needed in making therapeutic choices for patients with LRI when using antimicrobial sensitivity results from sputum isolates as opposed to BALF isolates.


Subject(s)
Bacterial Infections/microbiology , Bronchoalveolar Lavage Fluid/microbiology , Microbial Sensitivity Tests , Respiratory System/microbiology , Sputum/microbiology , Anti-Bacterial Agents/therapeutic use , Bacterial Infections/epidemiology , China/epidemiology , Escherichia coli/drug effects , Escherichia coli/isolation & purification , Female , Gram-Negative Bacteria/drug effects , Gram-Negative Bacteria/isolation & purification , Gram-Positive Bacteria/drug effects , Gram-Positive Bacteria/isolation & purification , Hospitals, Teaching , Humans , Male , Retrospective Studies , Staphylococcus aureus/isolation & purification
4.
Mycoses ; 64(9): 980-988, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1273123

ABSTRACT

It is now well known that patients with SARS-CoV-2 infection admitted in ICU and mechanically ventilated are at risk of developing invasive pulmonary aspergillosis (IPA). Nevertheless, symptomatology of IPA is often atypical in mechanically ventilated patients, and radiological aspects in SARS-CoV-2 pneumonia and IPA are difficult to differentiate. In this context, the significance of the presence of Aspergillus in airway specimens (detected by culture, galactomannan antigen or specific PCR) remains to be fully understood. To decipher the relevance of the detection of Aspergillus, we performed a comprehensive review of all published cases of respiratory Aspergillus colonisation and IPA in COVID-19 patients. The comparison of patients receiving or not antifungal treatment allowed us to highlight the most important criteria for the decision to treat. The comparison of surviving and non-surviving patients made it possible to unveil criteria associated with mortality that should be taken into account in the treatment decision.


Subject(s)
Antifungal Agents/therapeutic use , Bronchoalveolar Lavage Fluid/microbiology , COVID-19/microbiology , Cause of Death , Invasive Pulmonary Aspergillosis/diagnosis , Invasive Pulmonary Aspergillosis/drug therapy , Invasive Pulmonary Aspergillosis/mortality , Adult , Aged , Aged, 80 and over , Female , Humans , Intensive Care Units , Male , Middle Aged , SARS-CoV-2
5.
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
6.
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
7.
Mycoses ; 64(9): 1015-1027, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1247256

ABSTRACT

Reports of COVID-19 associated pulmonary aspergillosis (CAPA) are rising, but the associated mortality and factors affecting it are not well-characterised. We performed a systematic review including 20 peer-reviewed English language studies reporting mortality in CAPA published till 18 February 2021from PubMed, Ovid SP, Web of Science, Embase and CINHAL. The pooled mortality in CAPA was 51.2% (95% CI: 43.1-61.1, I2  = 38%). The leave one out sensitivity analysis and influential case diagnostics revealed one outlier and its exclusion resulted in a mortality estimate of 54% (95% CI: 45-62). Higher odds of mortality: 2.83 (95% CI: 1.8-4.5) were seen in CAPA compared to controls. No significant difference in various subgroups according to the country of study, the continent of study, income category of country and quality of the included study was seen. None of the host risk factors, mycological test results, therapy for COVID-19 and antifungal therapy affected mortality. Thus, patients with CAPA have a high probability of mortality and early diagnosis with prompt therapy must be ensured to optimally manage these patients. However, more prospective studies with global and multi-centre coordination may help to address CAPA in a better way.


Subject(s)
Bronchoalveolar Lavage Fluid/microbiology , COVID-19/complications , COVID-19/microbiology , Cause of Death , Intensive Care Units/statistics & numerical data , Invasive Pulmonary Aspergillosis/mortality , Adult , Aged , Aged, 80 and over , Antifungal Agents/therapeutic use , COVID-19/epidemiology , Critical Illness/epidemiology , Female , Humans , Invasive Pulmonary Aspergillosis/diagnosis , Invasive Pulmonary Aspergillosis/drug therapy , Invasive Pulmonary Aspergillosis/epidemiology , Male , Middle Aged , SARS-CoV-2
8.
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
9.
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
10.
Sci Rep ; 11(1): 6433, 2021 03 19.
Article in English | MEDLINE | ID: covidwho-1142460

ABSTRACT

In response to the ongoing global pandemic, characterizing the molecular-level host interactions of the new coronavirus SARS-CoV-2 responsible for COVID-19 has been at the center of unprecedented scientific focus. However, when the virus enters the body it also interacts with the micro-organisms already inhabiting the host. Understanding the virus-host-microbiome interactions can yield additional insights into the biological processes perturbed by viral invasion. Alterations in the gut microbiome species and metabolites have been noted during respiratory viral infections, possibly impacting the lungs via gut-lung microbiome crosstalk. To better characterize microbial functions in the lower respiratory tract during COVID-19 infection, we carry out a functional analysis of previously published metatranscriptome sequencing data of bronchoalveolar lavage fluid from eight COVID-19 cases, twenty-five community-acquired pneumonia patients, and twenty healthy controls. The functional profiles resulting from comparing the sequences against annotated microbial protein domains clearly separate the cohorts. By examining the associated metabolic pathways, distinguishing functional signatures in COVID-19 respiratory tract microbiomes are identified, including decreased potential for lipid metabolism and glycan biosynthesis and metabolism pathways, and increased potential for carbohydrate metabolism pathways. The results include overlap between previous studies on COVID-19 microbiomes, including decrease in the glycosaminoglycan degradation pathway and increase in carbohydrate metabolism. The results also suggest novel connections to consider, possibly specific to the lower respiratory tract microbiome, calling for further research on microbial functions and host-microbiome interactions during SARS-CoV-2 infection.


Subject(s)
COVID-19/microbiology , Microbial Interactions , Microbiota , Respiratory System/microbiology , SARS-CoV-2/physiology , Bronchoalveolar Lavage Fluid/microbiology , Humans , Lung/microbiology
11.
PLoS One ; 16(3): e0238825, 2021.
Article in English | MEDLINE | ID: covidwho-1138567

ABSTRACT

BACKGROUND: Superinfections, including invasive pulmonary aspergillosis (IPA), are well-known complications of critically ill patients with severe viral pneumonia. Aim of this study was to evaluate the incidence, risk factors and outcome of IPA in critically ill patients with severe COVID-19 pneumonia. METHODS: We prospectively screened 32 critically ill patients with severe COVID-19 pneumonia for a time period of 28 days using a standardized study protocol for oberservation of developement of COVID-19 associated invasive pulmonary aspergillosis (CAPA). We collected laboratory, microbiological, virological and clinical parameters at defined timepoints in combination with galactomannan-antigen-detection from nondirected bronchial lavage (NBL). We used logistic regression analyses to assess if COVID-19 was independently associated with IPA and compared it with matched controls. FINDINGS: CAPA was diagnosed at a median of 4 days after ICU admission in 11/32 (34%) of critically ill patients with severe COVID-19 pneumonia as compared to 8% in the control cohort. In the COVID-19 cohort, mean age, APACHE II score and ICU mortality were higher in patients with CAPA than in patients without CAPA (36% versus 9.5%; p<0.001). ICU stay (21 versus 17 days; p = 0.340) and days of mechanical ventilation (20 versus 15 days; p = 0.570) were not different between both groups. In regression analysis COVID-19 and APACHE II score were independently associated with IPA. INTERPRETATION: CAPA is highly prevalent and associated with a high mortality rate. COVID-19 is independently associated with invasive pulmonary aspergillosis. A standardized screening and diagnostic approach as presented in our study can help to identify affected patients at an early stage.


Subject(s)
COVID-19/complications , Invasive Pulmonary Aspergillosis/etiology , Pneumonia, Viral/complications , Adult , Aged , Aged, 80 and over , Bronchoalveolar Lavage Fluid/microbiology , Bronchoalveolar Lavage Fluid/virology , COVID-19/microbiology , COVID-19/virology , Critical Illness , Female , Galactose/analogs & derivatives , Humans , Intensive Care Units , Invasive Pulmonary Aspergillosis/microbiology , Invasive Pulmonary Aspergillosis/virology , Male , Mannans/metabolism , Middle Aged , Pneumonia, Viral/microbiology , Pneumonia, Viral/virology , Prospective Studies , Respiration, Artificial/methods , SARS-CoV-2/pathogenicity , Superinfection/etiology , Superinfection/microbiology
12.
J Mycol Med ; 31(2): 101124, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1096172

ABSTRACT

Aspergillus infection is a well-known complication of severe influenza and severe acute respiratory syndrome coronavirus (SARS-CoV), and these infections have been related with significant morbidity and mortality even when appropriately diagnosed and treated. Recent studies have indicated that SARS-CoV-2 might increase the risk of invasive pulmonary aspergillosis (IPA). Here, we report the first case of Aspergillus ochraceus in a SARS-CoV-2 positive immunocompetent patient, which is complicated by pulmonary and brain infections. Proven IPA is supported by the positive Galactomannan test, culture-positive, and histopathological evidence. The patient did not respond to voriconazole, and liposomal amphotericin B was added to his anti-fungal regimen. Further studies are needed to evaluate the prevalence of IPA in immunocompetent patients infected with SARS-CoV-2. Consequently, testing for the incidence of Aspergillus species in lower respiratory secretions and Galactomannan test of COVID-19 patients with appropriate therapy and targeted anti-fungal therapy based on the primary clinical suspicion of IPA are highly recommended.


Subject(s)
Aspergillosis/complications , Aspergillus ochraceus/isolation & purification , COVID-19/complications , Invasive Fungal Infections/complications , SARS-CoV-2/isolation & purification , Adult , Amphotericin B/therapeutic use , Antifungal Agents/therapeutic use , Aspergillosis/diagnostic imaging , Aspergillosis/drug therapy , Biomarkers , Brain Abscess/diagnostic imaging , Brain Abscess/etiology , Brain Abscess/microbiology , Bronchoalveolar Lavage Fluid/microbiology , COVID-19/diagnostic imaging , COVID-19 Nucleic Acid Testing , Fatal Outcome , Galactose/analogs & derivatives , Humans , Immunocompetence , Invasive Fungal Infections/diagnostic imaging , Invasive Fungal Infections/drug therapy , Invasive Fungal Infections/microbiology , Lung Diseases, Fungal/complications , Lung Diseases, Fungal/diagnostic imaging , Lung Diseases, Fungal/microbiology , Male , Mannans/blood , Voriconazole/therapeutic use
13.
Medicine (Baltimore) ; 100(1): e24256, 2021 Jan 08.
Article in English | MEDLINE | ID: covidwho-1024164

ABSTRACT

ABSTRACT: Brochoalvelolar lavages (BALs) from patients suffering from hospitalized infections with SARS-CoV-2, other corona viruses (human coronavirus (HCoV)-229E, HCoV-OC43, HCoV-NL63, and HCoV-HKU1), Influenza virus type A and B, Haemophilus influenzae and Pneumocystis jirovecii were compared cytopathologically.The aim of the study was to evaluate if the cellular profile detectable in BAL may be specific for the respective pathogens and could lead to diagnosis of COVID-19 even in the absence of PCR results.Differential cytology and flow cytometry datasets of 62 patients were observed and compared.We observed a significant association between individual cell pattern changes and the causing pathogen, but no general cell distribution pattern.The cytology pattern of the BAL fluid in COVID-19 is not specific enough to use it as a sole diagnostic criterion, although it may support clinical decision making.


Subject(s)
Bronchoalveolar Lavage Fluid/virology , COVID-19/diagnosis , Coronavirus/isolation & purification , Haemophilus influenzae/isolation & purification , Orthomyxoviridae/isolation & purification , Pneumonia, Viral/virology , SARS-CoV-2/isolation & purification , Adult , Aged , Aged, 80 and over , Bronchoalveolar Lavage , Bronchoalveolar Lavage Fluid/microbiology , Female , Flow Cytometry , Humans , Male , Middle Aged , Pneumocystis carinii/isolation & purification
14.
Diagn Microbiol Infect Dis ; 99(1): 115183, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-1023526

ABSTRACT

The FilmArray® Pneumonia Plus (FA-PP) panel can provide rapid identifications and semiquantitative results for many pathogens. We performed a prospective single-center study in 43 critically ill patients with coronavirus disease 2019 (COVID-19) in which we performed 96 FA-PP tests and cultures of blind bronchoalveolar lavage (BBAL). FA-PP detected 1 or more pathogens in 32% (31/96 of samples), whereas culture methods detected at least 1 pathogen in 35% (34/96 of samples). The most prevalent bacteria detected were Pseudomonas aeruginosa (n = 14) and Staphylococcus aureus (n = 11) on both FA-PP and culture. The FA-PP results from BBAL in critically ill patients with COVID-19 were consistent with bacterial culture findings for bacteria present in the FA-PP panel, showing sensitivity, specificity, and positive and negative predictive value of 95%, 99%, 82%, and 100%, respectively. Median turnaround time for FA-PP was 5.5 h, which was significantly shorter than for standard culture (26 h) and antimicrobial susceptibility testing results (57 h).


Subject(s)
Bacteria/isolation & purification , Bacteriological Techniques/methods , COVID-19/complications , Multiplex Polymerase Chain Reaction/methods , Pneumonia, Bacterial/diagnosis , Aged , Bacteria/classification , Bacteria/genetics , Bronchoalveolar Lavage Fluid/microbiology , Critical Illness , Female , Humans , Male , Middle Aged , Pneumonia, Bacterial/microbiology , SARS-CoV-2 , Sensitivity and Specificity , Time Factors
15.
Rev Iberoam Micol ; 38(1): 16-18, 2021.
Article in English | MEDLINE | ID: covidwho-947431

ABSTRACT

BACKGROUND: Patients with severe viral pneumonia are likely to receive high-dose immunomodulatory drugs to prevent clinical worsening. Aspergillus species have been described as frequent secondary pneumonia agents in severely ill influenza patients receiving steroids. COVID-19 patients admitted to Intensive Care Unit (ICU) are receiving steroids as part of their treatment and they share clinical characteristics with other patients with severe viral pneumonias. COVID-19 patients receiving steroids should be considered a putative risk group of invasive aspergillosis. CASE REPORT: We are reporting a SARS-CoV-2/Aspergillus section Fumigati coinfection in an elderly intubated patient with a history of pulmonary embolism treated with corticosteroids. The diagnosis was made following the ad hoc definitions described for patients admitted to ICU with severe influenza, including clinical criteria (fever for 3 days refractory to the appropriate antibiotic therapy, dyspnea, pleural friction rub, worsening of respiratory status despite antibiotic therapy and need of ventilator support), a radiological criterion (pulmonary infiltrate) and a mycological criterion (several positive galactomannan tests on serum with ratio ≥0.5). In addition, Aspergillus section Fumigati DNA was found in serum and blood samples. These tests were positive 4 weeks after the patient was admitted to the ICU. The patient received voriconazole and after two month in ICU his respiratory status improved; he was discharged after 6 weeks of antifungal treatment. CONCLUSIONS: Severely ill COVID-19 patients would be considered a new aspergillosis risk group. Galactomannan and Aspergillus DNA detection would be useful methods for Aspergillus infection diagnosis as they allow avoiding the biosafety issues related to these patients.


Subject(s)
Aspergillus fumigatus/isolation & purification , COVID-19/complications , COVID-19/drug therapy , Coinfection/diagnosis , Immunocompetence , Immunosuppressive Agents/adverse effects , Invasive Pulmonary Aspergillosis/complications , Methylprednisolone/adverse effects , SARS-CoV-2/isolation & purification , Acetaminophen/therapeutic use , Aged , Anti-Infective Agents/therapeutic use , Bronchoalveolar Lavage Fluid/microbiology , COVID-19/diagnosis , COVID-19/therapy , COVID-19/virology , COVID-19 Nucleic Acid Testing , Coinfection/microbiology , Coinfection/therapy , Coinfection/virology , Combined Modality Therapy , Diagnosis, Differential , Drug Therapy, Combination , Enoxaparin/therapeutic use , Galactose/analogs & derivatives , Humans , Hydroxychloroquine/therapeutic use , Immunosuppressive Agents/therapeutic use , Intubation, Intratracheal , Invasive Pulmonary Aspergillosis/diagnosis , Invasive Pulmonary Aspergillosis/microbiology , Invasive Pulmonary Aspergillosis/therapy , Male , Mannans/blood , Methylprednisolone/therapeutic use , Nasopharynx/virology , Pneumonia, Mycoplasma/diagnosis , Pseudomonas aeruginosa/isolation & purification , Real-Time Polymerase Chain Reaction , Respiration, Artificial , Staphylococcus aureus/isolation & purification , Trachea/microbiology
16.
J Clin Microbiol ; 59(1)2020 12 17.
Article in English | MEDLINE | ID: covidwho-889848

ABSTRACT

COVID-19-associated pulmonary aspergillosis (CAPA) was recently reported as a potential infective complication affecting critically ill patients with acute respiratory distress syndrome following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, with incidence rates varying from 8 to 33% depending on the study. However, definitive diagnosis of CAPA is challenging. Standardized diagnostic algorithms and definitions are lacking, clinicians are reticent to perform aerosol-generating bronchoalveolar lavages for galactomannan testing and microscopic and cultural examination, and questions surround the diagnostic sensitivity of different serum biomarkers. Between 11 March and 14 July 2020, the UK National Mycology Reference Laboratory received 1,267 serum and respiratory samples from 719 critically ill UK patients with COVID-19 and suspected pulmonary aspergillosis. The laboratory also received 46 isolates of Aspergillus fumigatus from COVID-19 patients (including three that exhibited environmental triazole resistance). Diagnostic tests performed included 1,000 (1-3)-ß-d-glucan and 516 galactomannan tests on serum samples. The results of this extensive testing are presented here. For a subset of 61 patients, respiratory specimens (bronchoalveolar lavage specimens, tracheal aspirates, and sputum samples) in addition to serum samples were submitted and subjected to galactomannan testing, Aspergillus-specific PCR, and microscopy and culture. The incidence of probable/proven and possible CAPA in this subset of patients was approximately 5% and 15%, respectively. Overall, our results highlight the challenges in biomarker-driven diagnosis of CAPA, especially when only limited clinical samples are available for testing, and the importance of a multimodal diagnostic approach involving regular and repeat testing of both serum and respiratory samples.


Subject(s)
Antigens, Fungal/blood , Aspergillus fumigatus/isolation & purification , Invasive Pulmonary Aspergillosis/diagnosis , Invasive Pulmonary Aspergillosis/epidemiology , Adult , Aged , Aged, 80 and over , Aspergillus fumigatus/drug effects , Bronchoalveolar Lavage Fluid/microbiology , COVID-19/etiology , Critical Illness , Female , Galactose/analogs & derivatives , Humans , Invasive Pulmonary Aspergillosis/complications , Invasive Pulmonary Aspergillosis/drug therapy , Male , Mannans/blood , Middle Aged , Proteoglycans , Real-Time Polymerase Chain Reaction , SARS-CoV-2 , United Kingdom , beta-Glucans/blood
19.
Intensive Care Med ; 46(8): 1524-1535, 2020 Aug.
Article in English | MEDLINE | ID: covidwho-615887

ABSTRACT

PURPOSE: Invasive pulmonary aspergillosis is increasingly reported in patients with influenza admitted to the intensive care unit (ICU). Classification of patients with influenza-associated pulmonary aspergillosis (IAPA) using the current definitions for invasive fungal diseases has proven difficult, and our aim was to develop case definitions for IAPA that can facilitate clinical studies. METHODS: A group of 29 international experts reviewed current insights into the epidemiology, diagnosis and management of IAPA and proposed a case definition of IAPA through a process of informal consensus. RESULTS: Since IAPA may develop in a wide range of hosts, an entry criterion was proposed and not host factors. The entry criterion was defined as a patient requiring ICU admission for respiratory distress with a positive influenza test temporally related to ICU admission. In addition, proven IAPA required histological evidence of invasive septate hyphae and mycological evidence for Aspergillus. Probable IAPA required the detection of galactomannan or positive Aspergillus culture in bronchoalveolar lavage (BAL) or serum with pulmonary infiltrates or a positive culture in upper respiratory samples with bronchoscopic evidence for tracheobronchitis or cavitating pulmonary infiltrates of recent onset. The IAPA case definitions may be useful to classify patients with COVID-19-associated pulmonary aspergillosis (CAPA), while awaiting further studies that provide more insight into the interaction between Aspergillus and the SARS-CoV-2-infected lung. CONCLUSION: A consensus case definition of IAPA is proposed, which will facilitate research into the epidemiology, diagnosis and management of this emerging acute and severe Aspergillus disease, and may be of use to study CAPA.


Subject(s)
Aspergillus/isolation & purification , Betacoronavirus , Coronavirus Infections/complications , Influenza, Human/complications , Intensive Care Units , Pneumonia, Viral/complications , Pulmonary Aspergillosis , Antifungal Agents/therapeutic use , Bronchoalveolar Lavage Fluid/chemistry , Bronchoalveolar Lavage Fluid/microbiology , COVID-19 , Galactose/analogs & derivatives , Humans , Mannans/analysis , Pandemics , Pulmonary Aspergillosis/diagnosis , Pulmonary Aspergillosis/etiology , Pulmonary Aspergillosis/prevention & control , SARS-CoV-2
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