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2.
PLoS One ; 17(3): e0264855, 2022.
Article in English | MEDLINE | ID: covidwho-1736511

ABSTRACT

Since December 2019 the world has been facing the outbreak of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Identification of infected patients and discrimination from other respiratory infections have so far been accomplished by using highly specific real-time PCRs. Here we present a rapid multiplex approach (RespiCoV), combining highly multiplexed PCRs and MinION sequencing suitable for the simultaneous screening for 41 viral and five bacterial agents related to respiratory tract infections, including the human coronaviruses NL63, HKU1, OC43, 229E, Middle East respiratory syndrome coronavirus, SARS-CoV, and SARS-CoV-2. RespiCoV was applied to 150 patient samples with suspected SARS-CoV-2 infection and compared with specific real-time PCR. Additionally, several respiratory tract pathogens were identified in samples tested positive or negative for SARS-CoV-2. Finally, RespiCoV was experimentally compared to the commercial RespiFinder 2SMART multiplex screening assay (PathoFinder, The Netherlands).


Subject(s)
Bacteria/genetics , COVID-19/diagnosis , High-Throughput Nucleotide Sequencing/methods , RNA Viruses/genetics , Respiratory Tract Infections/diagnosis , SARS-CoV-2/genetics , Bacteria/isolation & purification , COVID-19/virology , Coronavirus/genetics , Coronavirus/isolation & purification , DNA, Bacterial/chemistry , DNA, Bacterial/metabolism , Herpesvirus 1, Human/genetics , Herpesvirus 1, Human/isolation & purification , Humans , Multiplex Polymerase Chain Reaction , Nanopores , Orthomyxoviridae/genetics , Orthomyxoviridae/isolation & purification , RNA Viruses/isolation & purification , RNA, Viral/chemistry , RNA, Viral/metabolism , Respiratory Tract Infections/microbiology , Respiratory Tract Infections/virology , SARS-CoV-2/isolation & purification
3.
J Genet Genomics ; 48(9): 803-814, 2021 09 20.
Article in English | MEDLINE | ID: covidwho-1720312

ABSTRACT

Children are less susceptible to coronavirus disease 2019 (COVID-19), and they have manifested lower morbidity and mortality after infection, for which a multitude of mechanisms may be considered. Whether the normal development of the gut-airway microbiome in children is affected by COVID-19 has not been evaluated. Here, we demonstrate that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection alters the upper respiratory tract and the gut microbiomes in nine children. The alteration of the microbiome is dominated by the genus Pseudomonas, and it sustains for up to 25-58 days in different individuals. Moreover, the patterns of alternation are different between the upper respiratory tract and the gut. Longitudinal investigation shows that the upper respiratory tract and the gut microbiomes are extremely variable among children during the course of COVID-19. The dysbiosis of microbiome persists in 7 of 8 children for at least 19-24 days after discharge from the hospital. Disturbed development of both the gut and the upper respiratory microbiomes and prolonged dysbiosis in these nine children imply possible long-term complications after clinical recovery from COVID-19, such as predisposition to the increased health risk in the post-COVID-19 era.


Subject(s)
COVID-19/pathology , Computational Biology/methods , Respiratory Tract Infections/microbiology , Dysbiosis/microbiology , Dysbiosis/pathology , Gastrointestinal Microbiome/physiology , Humans
4.
PLoS Pathog ; 18(2): e1010259, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1690683

ABSTRACT

At the end of 2019 Wuhan witnessed an outbreak of "atypical pneumonia" that later developed into a global pandemic. Metagenomic sequencing rapidly revealed the causative agent of this outbreak to be a novel coronavirus denoted SARS-CoV-2. To provide a snapshot of the pathogens in pneumonia-associated respiratory samples from Wuhan prior to the emergence of SARS-CoV-2, we collected bronchoalveolar lavage fluid samples from 408 patients presenting with pneumonia and acute respiratory infections at the Central Hospital of Wuhan between 2016 and 2017. Unbiased total RNA sequencing was performed to reveal their "total infectome", including viruses, bacteria and fungi. We identified 35 pathogen species, comprising 13 RNA viruses, 3 DNA viruses, 16 bacteria and 3 fungi, often at high abundance and including multiple co-infections (13.5%). SARS-CoV-2 was not present. These data depict a stable core infectome comprising common respiratory pathogens such as rhinoviruses and influenza viruses, an atypical respiratory virus (EV-D68), and a single case of a sporadic zoonotic pathogen-Chlamydia psittaci. Samples from patients experiencing respiratory disease on average had higher pathogen abundance than healthy controls. Phylogenetic analyses of individual pathogens revealed multiple origins and global transmission histories, highlighting the connectedness of the Wuhan population. This study provides a comprehensive overview of the pathogens associated with acute respiratory infections and pneumonia, which were more diverse and complex than obtained using targeted PCR or qPCR approaches. These data also suggest that SARS-CoV-2 or closely related viruses were absent from Wuhan in 2016-2017.


Subject(s)
COVID-19/epidemiology , Disease Outbreaks , Pneumonia/epidemiology , Respiratory Tract Infections/epidemiology , SARS-CoV-2/isolation & purification , Acute Disease , Adolescent , Adult , Aged , Aged, 80 and over , Bronchoalveolar Lavage Fluid/microbiology , COVID-19/virology , China/epidemiology , Cohort Studies , Female , Gene Expression Profiling , Humans , Male , Metagenomics , Middle Aged , Phylogeny , Pneumonia/microbiology , Respiratory Tract Infections/microbiology , Young Adult
5.
Microbiol Spectr ; 10(1): e0155021, 2022 02 23.
Article in English | MEDLINE | ID: covidwho-1685499

ABSTRACT

Mycoplasma pneumoniae is a common pathogen causing respiratory disease in children. We sought to investigate the epidemiology of M. pneumoniae among outpatient children with mild respiratory tract infections (RTIs) during the coronavirus disease 2019 (COVID-19) pandemic. Eligible patients were prospectively enrolled from January 2020 to June 2021. Throat swabs were tested for M. pneumoniae RNA. M. pneumoniae IgM was tested by a colloidal gold assay. Macrolide resistance and the effect of the COVID-19 countermeasures on M. pneumoniae prevalence were assessed. Symptom scores, treatments, and outcomes were evaluated. Eight hundred sixty-two eligible children at 15 centers in China were enrolled. M. pneumoniae was detected in 78 (9.0%) patients. Seasonally, M. pneumoniae peaked in the first spring and dropped dramatically to extremely low levels over time until the next summer. Decreases in COVID-19 prevalence were significantly associated with decreases in M. pneumoniae prevalence (r = 0.76, P = 0.001). The macrolide resistance rate was 7.7%. The overall sensitivity and specificity of the colloidal gold assay used in determining M. pneumoniae infection were 32.1% and 77.9%, respectively. No more benefits for improving the severity of symptoms and outcomes were observed in M. pneumoniae-infected patients treated with a macrolide than in those not treated with a macrolide during follow-up. The prevalences of M. pneumoniae and macrolide resistance in outpatient children with mild RTIs were at low levels in the early stage of the COVID-19 pandemic but may have rebounded recently. The colloidal gold assay for M. pneumoniae IgM may be not appropriate for diagnosis of M. pneumoniae infection. Macrolides should be used with caution among outpatients with mild RTIs. IMPORTANCE This is the first and largest prospective, multicenter, active, population-based surveillance study of the epidemiology of Mycoplasma pneumoniae among outpatient children with mild respiratory tract infections (RTIs) during the COVID-19 pandemic. Nationwide measures like strict face mask wearing and restrictions on population movement implemented to prevent the spread of COVID-19 might also effectively prevent the spread of M. pneumoniae. The prevalence of M. pneumoniae and the proportion of drug-resistant M. pneumoniae isolates in outpatient children with mild RTIs were at low levels in the early stage of the COVID-19 pandemic but may have rebounded recently. The colloidal gold assay for M. pneumoniae IgM may be not appropriate for screening and diagnosis of M. pneumoniae infection. Macrolides should be used with caution among outpatients with mild RTIs.


Subject(s)
Mycoplasma pneumoniae/isolation & purification , Pneumonia, Mycoplasma/microbiology , Respiratory Tract Infections/microbiology , Adolescent , Adult , Anti-Bacterial Agents/therapeutic use , COVID-19/epidemiology , Child , Child, Preschool , China/epidemiology , Drug Resistance, Bacterial , Female , Humans , Infant , Macrolides/therapeutic use , Male , Mycoplasma pneumoniae/genetics , Mycoplasma pneumoniae/physiology , Outpatients/statistics & numerical data , Pneumonia, Mycoplasma/drug therapy , Pneumonia, Mycoplasma/epidemiology , Prospective Studies , Respiratory Tract Infections/drug therapy , Respiratory Tract Infections/epidemiology , Young Adult
7.
PLoS One ; 17(1): e0262057, 2022.
Article in English | MEDLINE | ID: covidwho-1622351

ABSTRACT

Respiratory tract infections (RTIs) are extremely common and can cause gastrointestinal tract symptoms and changes to the gut microbiota, yet these effects are poorly understood. We conducted a systematic review to evaluate the reported evidence of gut microbiome alterations in patients with a RTI compared to healthy controls (PROSPERO: CRD42019138853). We systematically searched Medline, Embase, Web of Science, Cochrane and the Clinical Trial Database for studies published between January 2015 and June 2021. Studies were eligible for inclusion if they were human cohorts describing the gut microbiome in patients with an RTI compared to healthy controls and the infection was caused by a viral or bacterial pathogen. Dual data screening and extraction with narrative synthesis was performed. We identified 1,593 articles and assessed 11 full texts for inclusion. Included studies (some nested) reported gut microbiome changes in the context of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) (n = 5), influenza (H1N1 and H7N9) (n = 2), Tuberculosis (TB) (n = 4), Community-Acquired Pneumonia CAP (n = 2) and recurrent RTIs (rRTI) (n = 1) infections. We found studies of patients with an RTI compared to controls reported a decrease in gut microbiome diversity (Shannon) of 1.45 units (95% CI, 0.15-2.50 [p, <0.0001]) and a lower abundance of taxa (p, 0.0086). Meta-analysis of the Shannon value showed considerable heterogeneity between studies (I2, 94.42). Unbiased analysis displayed as a funnel plot revealed a depletion of Lachnospiraceae, Ruminococcaceae and Ruminococcus and enrichment of Enterococcus. There was an important absence in the lack of cohort studies reporting gut microbiome changes and high heterogeneity between studies may be explained by variations in microbiome methods and confounder effects. Further human cohort studies are needed to understand RTI-induced gut microbiome changes to better understand interplay between microbes and respiratory health.


Subject(s)
Gastrointestinal Microbiome/physiology , Gastrointestinal Tract/microbiology , Respiratory Tract Infections/microbiology , Animals , Bacteria/growth & development , Humans
8.
Br J Gen Pract ; 72(716): e217-e224, 2022 03.
Article in English | MEDLINE | ID: covidwho-1608429

ABSTRACT

BACKGROUND: There is little evidence about the relationship between aetiology, illness severity, and clinical course of respiratory tract infections (RTIs) in primary care. Understanding these associations would aid in the development of effective management strategies for these infections. AIM: To investigate whether clinical presentation and illness course differ between RTIs where a viral pathogen was detected and those where a potential bacterial pathogen was found. DESIGN AND SETTING: Post hoc analysis of data from a pragmatic randomised trial on the effects of oseltamivir in patients with flu-like illness in primary care (n = 3266) in 15 European countries. METHOD: Patient characteristics and their signs and symptoms of disease were registered at baseline. Nasopharyngeal (adults) or nasal and pharyngeal (children) swabs were taken for polymerase chain reaction analysis. Patients were followed up until 28 days after inclusion. Regression models and Kaplan-Meier curves were used to analyse the relationship between aetiology, clinical presentation at baseline, and course of disease including complications. RESULTS: Except for a less prominent congested nose (odds ratio [OR] 0.55, 95% confidence interval [CI] = 0.35 to 0.86) and acute cough (OR 0.42, 95% CI = 0.27 to 0.65) in patients with flu-like illness in whom a possible bacterial pathogen was isolated, there were no clear clinical differences in presentations between those with a possible bacterial aetiology compared with those with a viral aetiology. Also, course of disease and complications were not related to aetiology. CONCLUSION: Given current available microbiological tests and antimicrobial treatments, and outside pandemics such as COVID-19, microbiological testing in primary care patients with flu-like illness seems to have limited value. A wait-and-see policy in most of these patients with flu-like illness seems the best option.


Subject(s)
COVID-19 , Respiratory Tract Infections , Virus Diseases , Adult , Child , Humans , Pandemics , Respiratory Tract Infections/diagnosis , Respiratory Tract Infections/drug therapy , Respiratory Tract Infections/microbiology , SARS-CoV-2 , Virus Diseases/complications , Virus Diseases/diagnosis , Virus Diseases/epidemiology
9.
Microbiol Spectr ; 9(3): e0016421, 2021 12 22.
Article in English | MEDLINE | ID: covidwho-1599285

ABSTRACT

Respiratory tract infections (RTIs) are ubiquitous among children in the community. A prospective observational study was performed to evaluate the diagnostic performance and quality of at-home parent-collected (PC) nasal and saliva swab samples, compared to nurse-collected (NC) swab samples, from children with RTI symptoms. Children with RTI symptoms were swabbed at home on the same day by a parent and a nurse. We compared the performance of PC swab samples as the test with NC swab samples as the reference for the detection of respiratory pathogen gene targets by reverse transcriptase PCR, with quality assessment using a human gene. PC and NC paired nasal and saliva swab samples were collected from 91 and 92 children, respectively. Performance and interrater agreement (Cohen's κ) of PC versus NC nasal swab samples for viruses combined showed sensitivity of 91.6% (95% confidence interval [CI], 85.47 to 95.73%) and κ of 0.84 (95% CI, 0.79 to 0.88), respectively; the respective values for bacteria combined were 91.4% (95% CI, 86.85 to 94.87%) and κ of 0.85 (95% CI, 0.80 to 0.89). In saliva samples, viral and bacterial sensitivities were lower at 69.0% (95% CI, 57.47 to 79.76%) and 78.1% (95% CI, 71.60 to 83.76%), as were κ values at 0.64 (95% CI, 0.53 to 0.72) and 0.70 (95% CI, 0.65 to 0.76), respectively. Quality assessment for human biological material (18S rRNA) indicated perfect interrater agreement. At-home PC nasal swab samples performed comparably to NC swab samples, whereas PC saliva swab samples lacked sensitivity for the detection of respiratory microbes. IMPORTANCE RTIs are ubiquitous among children. Diagnosis involves a swab sample being taken by a health professional, which places a considerable burden on community health care systems, given the number of cases involved. The coronavirus disease 2019 (COVID-19) pandemic has seen an increase in the at-home self-collection of upper respiratory tract swab samples without the involvement of health professionals. It is advised that parents conduct or supervise swabbing of children. Surprisingly, few studies have addressed the quality of PC swab samples for subsequent identification of respiratory pathogens. We compared NC and PC nasal and saliva swab samples taken from the same child with RTI symptoms, for detection of respiratory pathogens. The PC nasal swab samples performed comparably to NC samples, whereas saliva swab samples lacked sensitivity for the detection of respiratory microbes. Collection of swab samples by parents would greatly reduce the burden on community nurses without reducing the effectiveness of diagnoses.


Subject(s)
Respiratory Tract Infections/diagnosis , Specimen Handling/methods , Adult , Bacteria/genetics , Bacteria/isolation & purification , Child, Preschool , Female , Health Personnel , Humans , Infant , Male , Middle Aged , Nose/microbiology , Nose/virology , Parents , Prospective Studies , Respiratory Tract Infections/microbiology , Respiratory Tract Infections/virology , Saliva , Specimen Handling/standards , Viruses/genetics , Viruses/isolation & purification , Young Adult
10.
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.
Diagn Microbiol Infect Dis ; 102(2): 115576, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1474473

ABSTRACT

The frequencies of 19 respiratory pathogens other than SARS-CoV-2 were assessed in 6,"?>235 Brazilian individuals tested for COVID-19. Overall, only 83 individuals who tested positive for SARS-CoV-2 had codetection of other pathogens. Individuals infected with Rhinovirus/Enterovirus, Human Coronavirus (HCoV)-HKU1, HCoV-NL63, HPIV-4, Influenza A (-H1N1 and other subtypes), Influenza B, Human Respiratory Syncytial Virus and Human Metapneumovirus were less likely to test positive for SARS-CoV-2. Infection with Streptococcys pyogenes, Chlamydophila pneumoniae, Mycoplasma pneumoniae, and Bordetella pertussis were more frequent in individuals who tested negative for SARS-CoV-2, but without significancy. We found 150 individuals infected with ≥2 pathogens other than SARS-CoV-2, only 3 out of whom tested positive for COVID-19. The codetection frequency was low in individuals diagnosed with COVID-19. Other viral infections may provide a cross-reactive, protective immune response against SARS-CoV-2. Screening for bacterial respiratory infections upon COVID-19 testing is important to drive suitable therapeutic approaches and avoid unnecessary antibiotic prescription.


Subject(s)
Bacterial Infections/diagnosis , COVID-19 Testing , COVID-19/diagnosis , Respiratory Tract Infections/diagnosis , SARS-CoV-2/isolation & purification , Adult , Brazil , Cross Reactions , Female , Humans , Male , Mass Screening , Middle Aged , Respiratory Tract Infections/microbiology , Respiratory Tract Infections/virology
12.
BMC Pulm Med ; 21(1): 308, 2021 Sep 28.
Article in English | MEDLINE | ID: covidwho-1439539

ABSTRACT

BACKGROUND: Whether procalcitonin (PCT) or C-reactive protein (CRP) combined with certain clinical characteristics can better distinguish viral from bacterial infections remains unclear. The aim of the study was to assess the ability of PCT or CRP combined with clinical characteristics to distinguish between viral and bacterial infections in hospitalized non-intensive care unit (ICU) adults with lower respiratory tract infection (LRTI). METHODS: This was a post-hoc analysis of a randomized clinical trial previously conducted among LRTI patients. The ability of PCT, CRP and PCT or CRP combined with clinical symptoms to discriminate between viral and bacterial infection were assessed by portraying receiver operating characteristic (ROC) curves among patients with only a viral or a typical bacterial infection. RESULTS: In total, 209 infected patients (viral 69%, bacterial 31%) were included in the study. When using CRP or PCT to discriminate between viral and bacterial LRTI, the optimal cut-off points were 22 mg/L and 0.18 ng/mL, respectively. When the optimal cut-off for CRP (≤ 22 mg/L) or PCT (≤ 0.18 ng/mL) combined with rhinorrhea was used to discriminate viral from bacterial LRTI, the AUCs were 0.81 (95% CI: 0.75-0.87) and 0.80 (95% CI: 0.74-0.86), which was statistically significantly better than when CRP or PCT used alone (p < 0.001). When CRP ≤ 22 mg/L, PCT ≤ 0.18 ng/mL and rhinorrhea were combined, the AUC was 0.86 (95% CI: 0.80-0.91), which was statistically significantly higher than when CRP (≤ 22 mg/L) or PCT (≤ 0.18 ng/mL) was combined with rhinorrhea (p = 0.011 and p = 0.021). CONCLUSIONS: Either CRP ≤ 22 mg/L or PCT ≤ 0.18 ng/mL combined with rhinorrhea could help distinguish viral from bacterial infections in hospitalized non-ICU adults with LRTI. When rhinorrhea was combined together, discrimination ability was further improved.


Subject(s)
C-Reactive Protein/metabolism , Procalcitonin/blood , Respiratory Tract Infections/microbiology , Rhinorrhea/complications , Virus Diseases/diagnosis , Aged , Area Under Curve , Bacterial Infections/diagnosis , Female , Hospitalization , Humans , Male , Middle Aged , ROC Curve , Respiratory Tract Infections/blood , Retrospective Studies , Virus Diseases/blood
13.
Nat Commun ; 12(1): 5026, 2021 08 18.
Article in English | MEDLINE | ID: covidwho-1363491

ABSTRACT

Nationwide prospective surveillance of all-age patients with acute respiratory infections was conducted in China between 2009‒2019. Here we report the etiological and epidemiological features of the 231,107 eligible patients enrolled in this analysis. Children <5 years old and school-age children have the highest viral positivity rate (46.9%) and bacterial positivity rate (30.9%). Influenza virus, respiratory syncytial virus and human rhinovirus are the three leading viral pathogens with proportions of 28.5%, 16.8% and 16.7%, and Streptococcus pneumoniae, Mycoplasma pneumoniae and Klebsiella pneumoniae are the three leading bacterial pathogens (29.9%, 18.6% and 15.8%). Negative interactions between viruses and positive interactions between viral and bacterial pathogens are common. A Join-Point analysis reveals the age-specific positivity rate and how this varied for individual pathogens. These data indicate that differential priorities for diagnosis, prevention and control should be highlighted in terms of acute respiratory tract infection patients' demography, geographic locations and season of illness in China.


Subject(s)
Bacteria/isolation & purification , Bacterial Infections/microbiology , Respiratory Tract Infections/microbiology , Respiratory Tract Infections/virology , Virus Diseases/virology , Viruses/isolation & purification , Adolescent , Adult , Bacteria/classification , Bacteria/genetics , Bacterial Infections/epidemiology , Child , Child, Preschool , China/epidemiology , Female , Humans , Infant , Male , Prospective Studies , Respiratory Tract Infections/epidemiology , Seasons , Virus Diseases/epidemiology , Viruses/classification , Viruses/genetics , Young Adult
14.
Diagn Microbiol Infect Dis ; 102(1): 115558, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1446562

ABSTRACT

The primary objectives were to determine the prevalence of and identify variables associated with respiratory bacterial co-infection in COVID-19 inpatients. Secondary outcomes included length of stay and in-hospital mortality. Eighty-two (11.2%) of 735 COVID-19 inpatients had respiratory bacterial co-infection. Fifty-seven patients met inclusion criteria and were matched to three patients lacking co-infection (N = 228 patients). Patients with co-infection were more likely to receive antibiotics [57 (100%) vs 130 (76%), P < 0.0001] and for a longer duration [19 (13-33) vs 8 (4-13) days, P < 0.0001]. The multi-variable logistic regression model revealed risk factors of respiratory bacterial co-infection to be admission from SNF/LTAC/NH (AOR 6.8, 95% CI 2.6-18.2), severe COVID-19 (AOR 3.03, 95% CI 0.78-11.9), and leukocytosis (AOR 3.03, 95% CI 0.99-1.16). Although respiratory bacterial co-infection is rare in COVID-19 inpatients, antibiotic use is common. Early recognition of respiratory bacterial coinfection predictors in COVID-19 inpatients may improve empiric antibiotic prescribing.


Subject(s)
Bacterial Infections/complications , COVID-19/complications , Coinfection , Respiratory Tract Infections/complications , SARS-CoV-2 , Aged , Female , Humans , Inpatients , Male , Middle Aged , Respiratory Tract Infections/microbiology , Risk Factors
15.
Am J Respir Crit Care Med ; 204(12): 1379-1390, 2021 12 15.
Article in English | MEDLINE | ID: covidwho-1430274

ABSTRACT

Rationale: Alteration of human respiratory microbiota had been observed in coronavirus disease (COVID-19). How the microbiota is associated with the prognosis in COVID-19 is unclear. Objectives: To characterize the feature and dynamics of the respiratory microbiota and its associations with clinical features in patients with COVID-19. Methods: We conducted metatranscriptome sequencing on 588 longitudinal oropharyngeal swab specimens collected from 192 patients with COVID-19 (including 39 deceased patients) and 95 healthy controls from the same geographic area. Meanwhile, the concentration of 27 cytokines and chemokines in plasma was measured for patients with COVID-19. Measurements and Main Results: The upper respiratory tract (URT) microbiota in patients with COVID-19 differed from that in healthy controls, whereas deceased patients possessed a more distinct microbiota, both on admission and before discharge/death. The alteration of URT microbiota showed a significant correlation with the concentration of proinflammatory cytokines and mortality. Specifically, Streptococcus-dominated microbiota was enriched in recovered patients, and showed high temporal stability and resistance against pathogens. In contrast, the microbiota in deceased patients was more susceptible to secondary infections and became more deviated from the norm after admission. Moreover, the abundance of S. parasanguinis on admission was significantly correlated with prognosis in nonsevere patients (lower vs. higher abundance, odds ratio, 7.80; 95% CI, 1.70-42.05). Conclusions: URT microbiota dysbiosis is a remarkable manifestation of COVID-19; its association with mortality suggests it may reflect the interplay between pathogens, symbionts, and the host immune status. Whether URT microbiota could be used as a biomarker for diagnosis and prognosis of respiratory diseases merits further investigation.


Subject(s)
COVID-19/microbiology , COVID-19/mortality , Microbiota , Respiratory Tract Infections/microbiology , Respiratory Tract Infections/mortality , Adult , Aged , COVID-19/epidemiology , Female , Humans , Male , Middle Aged , Prognosis , SARS-CoV-2
16.
Appl Biochem Biotechnol ; 194(2): 671-693, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1375835

ABSTRACT

The growth of respiratory diseases, as witnessed through the SARS and COVID-19 outbreaks, and antimicrobial-resistance together pose a serious threat to humanity. One reason for antimicrobial resistance is formation of bacterial biofilms. In this study the sulphated polysaccharides from green algae Chlamydomonas reinhardtii (Cr-SPs) is tested for its antibacterial and antibiofilm potential against Klebsiella pneumoniae and Serratia marcescens. Agar cup assay clearly indicated the antibacterial potential of Cr-SPs. Minimum inhibitory concentration (MIC50) of Cr-SPs against Klebsiella pneumoniae was found to be 850 µg/ml, and it is 800 µg/ml in Serratia marcescens. Time-kill and colony-forming ability assays suggest the concentration-dependent bactericidal potential of Cr-SPs. Cr-SPs showed 74-100% decrease in biofilm formation in a concentration-dependent manner by modifying the cell surface hydrophobic properties of these bacteria. Cr-SPs have also distorted preformed-biofilms by their ability to interact and destroy the extra polymeric substance and eDNA of the matured biofilm. Scanning electron microscopy analysis showed that Cr-SPs effectively altered the morphology of these bacterial cells and distorted the bacterial biofilms. Furthermore reduced protease, urease and prodigiosin pigment production suggest that Cr-SPs interferes the quorum sensing mechanism in these bacteria. The current study paves way towards developing Cr-SPs as a control strategy for treatment of respiratory tract infections.


Subject(s)
Biofilms/drug effects , Polysaccharides/pharmacology , Quorum Sensing/drug effects , Respiratory Tract Infections/drug therapy , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Biofilms/growth & development , COVID-19/drug therapy , COVID-19/virology , Chlorophyta/chemistry , Humans , Klebsiella pneumoniae/growth & development , Klebsiella pneumoniae/pathogenicity , Microbial Sensitivity Tests , Polysaccharides/chemistry , Respiratory Tract Infections/microbiology , SARS-CoV-2/drug effects , Serratia marcescens/growth & development , Serratia marcescens/pathogenicity
17.
Sci Rep ; 11(1): 16355, 2021 08 11.
Article in English | MEDLINE | ID: covidwho-1354115

ABSTRACT

Rapid diagnostic tests are tools of paramount impact both for improving patient care and in antimicrobial management programs. Particularly in the case of respiratory infections, it is of great importance to quickly confirm/exclude the involvement of pathogens, be they bacteria or viruses, while obtaining information about the presence/absence of a genetic target of resistance to modulate antibiotic therapy. In this paper, we present our experiences with the use of the Biofire® FilmArray® Pneumonia Panel Plus (FAPP; bioMérieux; Marcy l'Etoile, France) to assess coinfection in COVID-19 patients. A total of 152 respiratory samples from consecutive patients were examined, and 93 (61%) were found to be FAPP positive, with the detection of bacteria and/or viruses. The patients were 93 males and 59 females with an average age of 65 years who were admitted to our hospital due to moderate/severe acute respiratory symptoms. Among the positive samples were 52 from sputum (SPU) and 41 from bronchoalveolar lavage (BAL). The most representative species was S. aureus (most isolates were mecA positive; 30/44, 62%), followed by gram-negative pathogens such as P. aeruginosa, K. pneumoniae, and A. baumannii. Evidence of a virus was rare. Cultures performed from BAL and SPU samples gave poor results. Most of the discrepant negative cultures were those in which FAPP detected pathogens with a microbial count ≤ 105 CFU/mL. H. influenzae was one of the most common pathogens lost by the conventional method. Despite the potential limitations of FAPP, which detects a defined number of pathogens, its advantages of rapid detection combined with predictive information regarding the antimicrobial resistance of pathogens through the detection of some relevant markers of resistance could be very useful for establishing empirical targeted therapy for the treatment of patients with respiratory failure. In the COVID era, we understand the importance of using antibiotics wisely to curb the phenomenon of antibiotic resistance.


Subject(s)
COVID-19/complications , Coinfection , Diagnostic Tests, Routine , Respiratory Tract Infections/complications , Respiratory Tract Infections/diagnosis , Aged , Female , Humans , Male , Multiplex Polymerase Chain Reaction/methods , Respiratory Tract Infections/microbiology , Respiratory Tract Infections/virology
18.
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
19.
Int J Mol Sci ; 22(8)2021 Apr 08.
Article in English | MEDLINE | ID: covidwho-1299441

ABSTRACT

Pneumonia due to respiratory infection with most prominently bacteria, but also viruses, fungi, or parasites is the leading cause of death worldwide among all infectious disease in both adults and infants. The introduction of modern antibiotic treatment regimens and vaccine strategies has helped to lower the burden of bacterial pneumonia, yet due to the unavailability or refusal of vaccines and antimicrobials in parts of the global population, the rise of multidrug resistant pathogens, and high fatality rates even in patients treated with appropriate antibiotics pneumonia remains a global threat. As such, a better understanding of pathogen virulence on the one, and the development of innovative vaccine strategies on the other hand are once again in dire need in the perennial fight of men against microbes. Recent data show that the secretome of bacteria consists not only of soluble mediators of virulence but also to a significant proportion of extracellular vesicles-lipid bilayer-delimited particles that form integral mediators of intercellular communication. Extracellular vesicles are released from cells of all kinds of organisms, including both Gram-negative and Gram-positive bacteria in which case they are commonly termed outer membrane vesicles (OMVs) and membrane vesicles (MVs), respectively. (O)MVs can trigger inflammatory responses to specific pathogens including S. pneumonia, P. aeruginosa, and L. pneumophila and as such, mediate bacterial virulence in pneumonia by challenging the host respiratory epithelium and cellular and humoral immunity. In parallel, however, (O)MVs have recently emerged as auspicious vaccine candidates due to their natural antigenicity and favorable biochemical properties. First studies highlight the efficacy of such vaccines in animal models exposed to (O)MVs from B. pertussis, S. pneumoniae, A. baumannii, and K. pneumoniae. An advanced and balanced recognition of both the detrimental effects of (O)MVs and their immunogenic potential could pave the way to novel treatment strategies in pneumonia and effective preventive approaches.


Subject(s)
Bacteria/metabolism , Bacterial Outer Membrane/metabolism , Extracellular Vesicles/metabolism , Pneumonia, Bacterial/microbiology , Adaptive Immunity , Animals , Antigens, Bacterial/immunology , Bacteria/immunology , Bacterial Outer Membrane/immunology , Bacterial Vaccines/immunology , Host-Pathogen Interactions/immunology , Humans , Pneumonia, Bacterial/immunology , Pneumonia, Bacterial/prevention & control , Respiratory Mucosa/immunology , Respiratory Mucosa/microbiology , Respiratory Tract Infections/immunology , Respiratory Tract Infections/microbiology , Respiratory Tract Infections/prevention & control , Virulence
20.
Sci Rep ; 11(1): 13580, 2021 06 30.
Article in English | MEDLINE | ID: covidwho-1291169

ABSTRACT

In the DECODE project, data were collected from 3,114 surveys filled by symptomatic patients RT-qPCR tested for SARS-CoV-2 in a single university centre in March-September 2020. The population demonstrated balanced sex and age with 759 SARS-CoV-2( +) patients. The most discriminative symptoms in SARS-CoV-2( +) patients at early infection stage were loss of taste/smell (OR = 3.33, p < 0.0001), body temperature above 38℃ (OR = 1.67, p < 0.0001), muscle aches (OR = 1.30, p = 0.0242), headache (OR = 1.27, p = 0.0405), cough (OR = 1.26, p = 0.0477). Dyspnea was more often reported among SARS-CoV-2(-) (OR = 0.55, p < 0.0001). Cough and dyspnea were 3.5 times more frequent among SARS-CoV-2(-) (OR = 0.28, p < 0.0001). Co-occurrence of cough, muscle aches, headache, loss of taste/smell (OR = 4.72, p = 0.0015) appeared significant, although co-occurrence of two symptoms only, cough and loss of smell or taste, means OR = 2.49 (p < 0.0001). Temperature > 38℃ with cough was most frequent in men (20%), while loss of taste/smell with cough in women (17%). For younger people, taste/smell impairment is sufficient to characterise infection, whereas in older patients co-occurrence of fever and cough is necessary. The presented study objectifies the single symptoms and interactions significance in COVID-19 diagnoses and demonstrates diverse symptomatology in patient groups.


Subject(s)
COVID-19/diagnosis , COVID-19/epidemiology , Respiratory Tract Infections/diagnosis , Respiratory Tract Infections/epidemiology , SARS-CoV-2 , Symptom Assessment/statistics & numerical data , Academic Medical Centers/statistics & numerical data , Adolescent , Adult , Aged , Aged, 80 and over , Ageusia/etiology , COVID-19/complications , Child , Child, Preschool , Cough/etiology , Diagnosis, Differential , Dyspnea/etiology , Female , Fever/etiology , Headache/etiology , Humans , Infant , Male , Middle Aged , Odds Ratio , Olfaction Disorders/etiology , Pilot Projects , Poland/epidemiology , Respiratory Tract Infections/complications , Respiratory Tract Infections/microbiology , Surveys and Questionnaires , Symptom Assessment/classification , Young Adult
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