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1.
Sensors (Basel) ; 22(20)2022 Oct 19.
Article in English | MEDLINE | ID: covidwho-2082155

ABSTRACT

COVID-19 has infected millions of people worldwide over the past few years. The main technique used for COVID-19 detection is reverse transcription, which is expensive, sensitive, and requires medical expertise. X-ray imaging is an alternative and more accessible technique. This study aimed to improve detection accuracy to create a computer-aided diagnostic tool. Combining other artificial intelligence applications techniques with radiological imaging can help detect different diseases. This study proposes a technique for the automatic detection of COVID-19 and other chest-related diseases using digital chest X-ray images of suspected patients by applying transfer learning (TL) algorithms. For this purpose, two balanced datasets, Dataset-1 and Dataset-2, were created by combining four public databases and collecting images from recently published articles. Dataset-1 consisted of 6000 chest X-ray images with 1500 for each class. Dataset-2 consisted of 7200 images with 1200 for each class. To train and test the model, TL with nine pretrained convolutional neural networks (CNNs) was used with augmentation as a preprocessing method. The network was trained to classify using five classifiers: two-class classifier (normal and COVID-19); three-class classifier (normal, COVID-19, and viral pneumonia), four-class classifier (normal, viral pneumonia, COVID-19, and tuberculosis (Tb)), five-class classifier (normal, bacterial pneumonia, COVID-19, Tb, and pneumothorax), and six-class classifier (normal, bacterial pneumonia, COVID-19, viral pneumonia, Tb, and pneumothorax). For two, three, four, five, and six classes, our model achieved a maximum accuracy of 99.83, 98.11, 97.00, 94.66, and 87.29%, respectively.


Subject(s)
COVID-19 , Deep Learning , Pneumonia, Bacterial , Pneumonia, Viral , Pneumothorax , Humans , COVID-19/diagnosis , SARS-CoV-2 , Artificial Intelligence
2.
Front Cell Infect Microbiol ; 12: 934671, 2022.
Article in English | MEDLINE | ID: covidwho-2032744

ABSTRACT

Pneumonia is one of the leading causes of morbidity and mortality worldwide and Gram-negative bacteria are a major cause of severe pneumonia. Despite advances in diagnosis and treatment, the rise of multidrug-resistant organisms and hypervirulent strains demonstrates that there will continue to be challenges with traditional treatment strategies using antibiotics. Hence, an alternative approach is to focus on the disease tolerance components that mediate immune resistance and enhance tissue resilience. Adaptive immunity plays a pivotal role in modulating these processes, thus affecting the incidence and severity of pneumonia. In this review, we focus on the adaptive T cell responses to pneumonia induced by Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii. We highlight key factors in these responses that have potential for therapeutic targeting, as well as the gaps in current knowledge to be focused on in future work.


Subject(s)
Acinetobacter baumannii , Pneumonia, Bacterial , Anti-Bacterial Agents/pharmacology , Drug Resistance, Multiple, Bacterial , Gram-Negative Bacteria , Humans , Microbial Sensitivity Tests , Pneumonia, Bacterial/drug therapy , Pseudomonas aeruginosa , T-Lymphocytes
3.
Saudi Med J ; 43(9): 1000-1006, 2022 Sep.
Article in English | MEDLINE | ID: covidwho-2030393

ABSTRACT

OBJECTIVES: To investigate the seroprevalence of the community-acquired bacterial that causes atypical pneumonia among confirmed severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) patients. METHODS: In this cohort study, we retrospectively investigated the seroprevalence of Chlamydia pneumoniae, Mycoplasma pneumoniae, and Legionella pneumophila among randomly selected 189 confirmed COVID-19 patients at their time of hospital presentation via commercial immunoglobulin M (IgM) antibodies against these bacteria. We also carried out quantitative measurements of procalcitonin in patients' serum. RESULTS: The seropositivity for L. pneumophila was 12.6%, with significant distribution among patientsolder than 50 years (χ2 test, p=0.009), while those of M. pneumoniae was 6.3% and C. pneumoniae was 2.1%, indicating an overall co-infection rate of 21% among COVID-19 patients. No significant difference (χ2 test, p=0.628) in the distribution of bacterial co-infections existed between male and female patients. Procalcitonin positivity was confirmed amongst 5% of co-infected patients. CONCLUSION: Our study documented the seroprevalence of community-acquired bacteria co-infection among COVID-19 patients. In this study, procalcitonin was an inconclusive biomarker for non-severe bacterial co-infections among COVID-19 patients. Consideration and proper detection of community-acquired bacterial co-infection may minimize misdiagnosis during the current pandemic and positively reflect disease management and prognosis.


Subject(s)
COVID-19 , Coinfection , Community-Acquired Infections , Pneumonia, Bacterial , Adult , COVID-19/epidemiology , Cohort Studies , Coinfection/epidemiology , Community-Acquired Infections/diagnosis , Community-Acquired Infections/epidemiology , Female , Humans , Immunoglobulin M , Male , Mycoplasma pneumoniae , Pneumonia, Bacterial/epidemiology , Pneumonia, Bacterial/microbiology , Procalcitonin , Retrospective Studies , SARS-CoV-2 , Saudi Arabia/epidemiology , Seroepidemiologic Studies
4.
Sci Rep ; 12(1): 15485, 2022 09 15.
Article in English | MEDLINE | ID: covidwho-2028718

ABSTRACT

Secondary infections have been shown to complicate the clinical course and worsen the outcome of critically ill patients. Severe Coronavirus Disease 2019 (COVID-19) may be accompanied by a pronounced cytokine release, and immune competence of these patients towards most pathogenic antigens remains uncompromised early in the disease. Patients with bacterial sepsis also exhibit excessive cytokine release with systemic hyper-inflammation, however, typically followed by an anti-inflammatory phase, causing immune paralysis. In a second hit immune response model, leukocyte activation capacity of severely ill patients with pneumonia caused by SARS-CoV-2 or by bacteria were compared upon ICU admission and at days 4 and 7 of the ICU stay. Blood cell count and release of the pro-inflammatory cytokines IL-2, IFNγ and TNF were assessed after whole-blood incubation with the potent immune stimulus pokeweed mitogen (PWM). For comparison, patients with bacterial sepsis not originating from pneumonia, and healthy volunteers were included. Lymphopenia and granulocytosis were less pronounced in COVID-19 patients compared to bacterial sepsis patients. After PWM stimulation, COVID-19 patients showed a reduced release of IFNγ, while IL-2 levels were found similar and TNF levels were increased compared to healthy controls. Interestingly, concentrations of all three cytokines were significantly higher in samples from COVID-19 patients compared to samples from patients with bacterial infection. This fundamental difference in immune competence during a second hit between COVID-19 and sepsis patients may have implications for the selection of immune suppressive or enhancing therapies in personalized medicine.


Subject(s)
COVID-19 , Pneumonia, Bacterial , Sepsis , Cytokines , Humans , Immunity , Interleukin-2 , Pokeweed Mitogens , SARS-CoV-2
5.
PLoS Pathog ; 18(9): e1010809, 2022 09.
Article in English | MEDLINE | ID: covidwho-2009723

ABSTRACT

Acinetobacter baumannii is an opportunistic pathogen and an emerging global health threat. Within healthcare settings, major presentations of A. baumannii include bloodstream infections and ventilator-associated pneumonia. The increased prevalence of ventilated patients during the COVID-19 pandemic has led to a rise in secondary bacterial pneumonia caused by multidrug resistant (MDR) A. baumannii. Additionally, due to its MDR status and the lack of antimicrobial drugs in the development pipeline, the World Health Organization has designated carbapenem-resistant A. baumannii to be its priority critical pathogen for the development of novel therapeutics. To better inform the design of new treatment options, a comprehensive understanding of how the host contains A. baumannii infection is required. Here, we investigate the innate immune response to A. baumannii by assessing the impact of infection on host gene expression using NanoString technology. The transcriptional profile observed in the A. baumannii infected host is characteristic of Gram-negative bacteremia and reveals expression patterns consistent with the induction of nutritional immunity, a process by which the host exploits the availability of essential nutrient metals to curtail bacterial proliferation. The gene encoding for lipocalin-2 (Lcn2), a siderophore sequestering protein, was the most highly upregulated during A. baumannii bacteremia, of the targets assessed, and corresponds to robust LCN2 expression in tissues. Lcn2-/- mice exhibited distinct organ-specific gene expression changes including increased transcription of genes involved in metal sequestration, such as S100A8 and S100A9, suggesting a potential compensatory mechanism to perturbed metal homeostasis. In vitro, LCN2 inhibits the iron-dependent growth of A. baumannii and induces iron-regulated gene expression. To elucidate the role of LCN2 in infection, WT and Lcn2-/- mice were infected with A. baumannii using both bacteremia and pneumonia models. LCN2 was not required to control bacterial growth during bacteremia but was protective against mortality. In contrast, during pneumonia Lcn2-/- mice had increased bacterial burdens in all organs evaluated, suggesting that LCN2 plays an important role in inhibiting the survival and dissemination of A. baumannii. The control of A. baumannii infection by LCN2 is likely multifactorial, and our results suggest that impairment of iron acquisition by the pathogen is a contributing factor. Modulation of LCN2 expression or modifying the structure of LCN2 to expand upon its ability to sequester siderophores may thus represent feasible avenues for therapeutic development against this pathogen.


Subject(s)
Acinetobacter Infections , Acinetobacter baumannii , Bacteremia , COVID-19 , Pneumonia, Bacterial , Acinetobacter baumannii/genetics , Acinetobacter baumannii/metabolism , Animals , Carbapenems/pharmacology , Humans , Immunity, Innate , Iron/metabolism , Lipocalin-2/genetics , Lipocalin-2/metabolism , Mice , Pandemics , Siderophores/metabolism
6.
Crit Care ; 26(1): 236, 2022 Aug 03.
Article in English | MEDLINE | ID: covidwho-2002213

ABSTRACT

BACKGROUND: The COVID-19 pandemic presented major challenges for critical care facilities worldwide. Infections which develop alongside or subsequent to viral pneumonitis are a challenge under sporadic and pandemic conditions; however, data have suggested that patterns of these differ between COVID-19 and other viral pneumonitides. This secondary analysis aimed to explore patterns of co-infection and intensive care unit-acquired infections (ICU-AI) and the relationship to use of corticosteroids in a large, international cohort of critically ill COVID-19 patients. METHODS: This is a multicenter, international, observational study, including adult patients with PCR-confirmed COVID-19 diagnosis admitted to ICUs at the peak of wave one of COVID-19 (February 15th to May 15th, 2020). Data collected included investigator-assessed co-infection at ICU admission, infection acquired in ICU, infection with multi-drug resistant organisms (MDRO) and antibiotic use. Frequencies were compared by Pearson's Chi-squared and continuous variables by Mann-Whitney U test. Propensity score matching for variables associated with ICU-acquired infection was undertaken using R library MatchIT using the "full" matching method. RESULTS: Data were available from 4994 patients. Bacterial co-infection at admission was detected in 716 patients (14%), whilst 85% of patients received antibiotics at that stage. ICU-AI developed in 2715 (54%). The most common ICU-AI was bacterial pneumonia (44% of infections), whilst 9% of patients developed fungal pneumonia; 25% of infections involved MDRO. Patients developing infections in ICU had greater antimicrobial exposure than those without such infections. Incident density (ICU-AI per 1000 ICU days) was in considerable excess of reports from pre-pandemic surveillance. Corticosteroid use was heterogenous between ICUs. In univariate analysis, 58% of patients receiving corticosteroids and 43% of those not receiving steroids developed ICU-AI. Adjusting for potential confounders in the propensity-matched cohort, 71% of patients receiving corticosteroids developed ICU-AI vs 52% of those not receiving corticosteroids. Duration of corticosteroid therapy was also associated with development of ICU-AI and infection with an MDRO. CONCLUSIONS: In patients with severe COVID-19 in the first wave, co-infection at admission to ICU was relatively rare but antibiotic use was in substantial excess to that indication. ICU-AI were common and were significantly associated with use of corticosteroids. Trial registration ClinicalTrials.gov: NCT04836065 (retrospectively registered April 8th 2021).


Subject(s)
COVID-19 , Coinfection , Pneumonia, Bacterial , Pneumonia, Viral , Adrenal Cortex Hormones/therapeutic use , Adult , Anti-Bacterial Agents/therapeutic use , COVID-19/complications , COVID-19/epidemiology , COVID-19 Testing , Coinfection/drug therapy , Coinfection/epidemiology , Critical Illness , Humans , Intensive Care Units , Pandemics , Pneumonia, Bacterial/drug therapy , Pneumonia, Viral/complications , Pneumonia, Viral/drug therapy , Pneumonia, Viral/epidemiology
7.
NPJ Biofilms Microbiomes ; 8(1): 67, 2022 08 24.
Article in English | MEDLINE | ID: covidwho-2000891

ABSTRACT

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic has posed multiple challenges to global public health. Clinical features and sequela of SARS-CoV-2 infection include long-term and short-term complications often clinically indistinguishable from bacterial sepsis and acute lung infection. Post-hoc studies of previous SARS outbreaks postulate secondary bacterial infections with microbial dysbiosis. Oral microbial dysbiosis, particularly the altered proportion of Firmicutes and Proteobacteria, observed in other respiratory virus infection, like influenza, has shown to be associated with increased morbidity and mortality. Oropharynx and lung share similar kinds of bacterial species. We hypothesized that alteration in the Human Oropharyngeal Microbiome in SARS-CoV-2 patients can be a clinical indicator of bacterial infection related complications. We made a longitudinal comparison of oropharyngeal microbiome of 20 SARS-CoV-2 patients over a period of 30 days; at three time points, with a 15 days interval; contrasting them with a matched group of 10 healthy controls. Present observation indicates that posterior segment of the oropharyngeal microbiome is a key reservoir for bacteria causing pneumonia and chronic lung infection on SARS-CoV-2 infection. Oropharyngeal microbiome is indeed altered and its α-diversity decreases, indicating reduced stability, in all SARS-CoV-2 positive individuals right at Day-1; i.e. within ~24 h of post clinical diagnosis. The dysbiosis persists long-term (30 days) irrespective of viral clearance and/or administration of antibiotics. There is a severe depletion of commensal bacteria phyla like Firmicutes among the patients and that depletion is compensated by higher proportion of bacteria associated with sepsis and severe lung infection from phyla Proteobacteria. We also found elevated proportions of certain genus that have previously been shown to be causal for lung pneumonia in studies of model organisms and human autopsies' including Stenotrophomonas, Acenetobactor, Enterobactor, Klebsiella and Chryseobacterium that were to be elevated among the cases. We also show that responses to the antibiotics (Azithromycin and Doxycycline) are not uniform for all individuals.


Subject(s)
COVID-19 , Coinfection , Microbiota , Pneumonia, Bacterial , Sepsis , Anti-Bacterial Agents , Bacteria/genetics , Dysbiosis/microbiology , Humans , Oropharynx/microbiology , SARS-CoV-2
9.
PLoS One ; 17(7): e0271450, 2022.
Article in English | MEDLINE | ID: covidwho-1951555

ABSTRACT

BACKGROUND: Around 12-20% of patients with community-acquired pneumonia (CAP) require critical care. Ventilator-associated pneumonia (VAP) is the second cause of nosocomial infection in Paediatric Intensive Care Units (PICU). As far as we know, there are no studies comparing both types of pneumonia in children, thus it remains unclear if there are differences between them in terms of severity and outcomes. OBJECTIVE: The aim was to compare clinical and microbiological characteristics and outcomes of patients with severe CAP and VAP. METHODS: A retrospective descriptive study, including patients diagnosed of VAP and CAP, with a positive respiratory culture and under mechanical ventilation, admitted to the PICU from 2015 to 2019. RESULTS: 238 patients were included; 163 (68.4%) with CAP, and 75 (31.5%) with VAP. Patients with VAP needed longer mechanical ventilation (14 vs. 7 days, p<0.001) and more inotropic support (49.3 vs. 30.7%, p = 0.006). Patients with VAP had higher mortality (12 vs. 2.5%, p = 0.005). Enterobacterales were more involved with VAP than with CAP (48 vs. 9%, p<0.001). Taking into account only the non-drug sensitive microorganisms, patients with VAP tended to have more multidrug-resistant bacteria (30 vs. 10.8%, p = 0.141) than patients with CAP. CONCLUSION: Patients with VAP had worse prognosis than patients with CAP, needing longer mechanical ventilation, more inotropic support and had higher mortality. Patients with VAP were mainly infected by Enterobacterales and had more multidrug resistant microorganisms than patients with CAP.


Subject(s)
Community-Acquired Infections , Pneumonia, Bacterial , Pneumonia, Ventilator-Associated , Child , Community-Acquired Infections/microbiology , Community-Acquired Infections/therapy , Humans , Intensive Care Units, Pediatric , Pneumonia, Bacterial/microbiology , Pneumonia, Bacterial/therapy , Pneumonia, Ventilator-Associated/microbiology , Pneumonia, Ventilator-Associated/therapy , Prognosis , Respiration, Artificial/adverse effects , Respiration, Artificial/statistics & numerical data , Retrospective Studies
10.
PLoS One ; 17(5): e0269005, 2022.
Article in English | MEDLINE | ID: covidwho-1923703

ABSTRACT

BACKGROUND: Inflammatory biomarkers are associated with severity of coronavirus disease 2019 (COVID-19). However, direct comparisons of their utility in COVID-19 versus other respiratory infections are largely missing. OBJECTIVE: We aimed to investigate the prognostic utility of various inflammatory biomarkers in COVID-19 compared to patients with other respiratory infections. MATERIALS AND METHODS: Patients presenting to the emergency department with symptoms suggestive of COVID-19 were prospectively enrolled. Levels of Interleukin-6 (IL-6), c-reactive protein (CRP), procalcitonin, ferritin, and leukocytes were compared between COVID-19, other viral respiratory infections, and bacterial pneumonia. Primary outcome was the need for hospitalisation, secondary outcome was the composite of intensive care unit (ICU) admission or death at 30 days. RESULTS: Among 514 patients with confirmed respiratory infections, 191 (37%) were diagnosed with COVID-19, 227 (44%) with another viral respiratory infection (viral controls), and 96 (19%) with bacterial pneumonia (bacterial controls). All inflammatory biomarkers differed significantly between diagnoses and were numerically higher in hospitalized patients, regardless of diagnoses. Discriminative accuracy for hospitalisation was highest for IL-6 and CRP in all three diagnoses (in COVID-19, area under the curve (AUC) for IL-6 0.899 [95%CI 0.850-0.948]; AUC for CRP 0.922 [95%CI 0.879-0.964]). Similarly, IL-6 and CRP ranged among the strongest predictors for ICU admission or death at 30 days in COVID-19 (AUC for IL-6 0.794 [95%CI 0.694-0.894]; AUC for CRP 0.807 [95%CI 0.721-0.893]) and both controls. Predictive values of inflammatory biomarkers were generally higher in COVID-19 than in controls. CONCLUSION: In patients with COVID-19 and other respiratory infections, inflammatory biomarkers harbour strong prognostic information, particularly IL-6 and CRP. Their routine use may support early management decisions.


Subject(s)
COVID-19 , Pneumonia, Bacterial , Respiratory Tract Infections , Biomarkers , C-Reactive Protein/metabolism , COVID-19/diagnosis , Humans , Interleukin-6 , Pneumonia, Bacterial/diagnosis , Prospective Studies
11.
APMIS ; 130(9): 590-596, 2022 Sep.
Article in English | MEDLINE | ID: covidwho-1909331

ABSTRACT

Ferritin, the central iron storage protein, has attracted attention as a biomarker of severe COVID-19. Few studies have investigated regulators of iron metabolism in the context of COVID-19. The aim was to evaluate biomarkers for iron metabolism in the acute phase response to community-acquired pneumonia (CAP) caused by SARS-CoV-2 compared with CAP caused by bacteria or influenza virus in hospitalized patients. A cross-sectional study of 164 patients from the Surviving Pneumonia Cohort recruited between January 8, 2019 and May 26, 2020. Blood samples were collected at admission and analyzed for levels of C-reactive protein (CRP), ferritin, soluble transferrin receptor, erythroferrone, and hepcidin. Median (IQR) hepcidin was higher in SARS-CoV-2 with 143.8 (100.7-180.7) ng/mL compared with bacterial and influenza infection with 78.8 (40.1-125.4) and 53.5 (25.2-125.8) ng/mL, respectively. The median ferritin level was more than 2-fold higher in patients with SARS-CoV-2 compared with the other etiologies (p < 0.001). Patients with SARS-CoV-2 had lower levels of erythroferrone and CRP compared with those infected with bacteria. Higher levels of hepcidin and lower levels of erythroferrone despite lower CRP levels among patients with SARS-CoV-2 compared with those infected with bacteria indicate alterations in iron metabolism in patients with SARS-CoV-2 infection.


Subject(s)
COVID-19 , Community-Acquired Infections , Influenza, Human , Pneumonia, Bacterial , Pneumonia, Viral , Biomarkers/blood , C-Reactive Protein/metabolism , COVID-19/complications , Community-Acquired Infections/blood , Community-Acquired Infections/diagnosis , Cross-Sectional Studies , Ferritins , Hepcidins/metabolism , Humans , Influenza, Human/complications , Iron/metabolism , Pneumonia, Bacterial/blood , Pneumonia, Bacterial/diagnosis , Pneumonia, Viral/blood , Pneumonia, Viral/diagnosis , SARS-CoV-2
12.
Adv Ther ; 39(7): 3061-3071, 2022 07.
Article in English | MEDLINE | ID: covidwho-1906545

ABSTRACT

The COVID-19 pandemic has drawn considerable attention to viral pneumonia from clinicians, public health authorities, and the general public. With dozens of viruses able to cause pneumonia in humans, differentiating viral from bacterial pneumonia can be very challenging in clinical practice using traditional diagnostic methods. Precision medicine is a medical model in which decisions, practices, interventions, and therapies are adapted to the individual patient on the basis of their predicted response or risk of disease. Precision medicine approaches hold promise as a way to improve outcomes for patients with viral pneumonia. This review describes the latest advances in the use of precision medicine for diagnosing and treating viral pneumonia in adults and discusses areas where further research is warranted.


Subject(s)
COVID-19 , Pneumonia, Bacterial , Pneumonia, Viral , Humans , Pandemics , Pneumonia, Bacterial/diagnosis , Pneumonia, Viral/drug therapy , Pneumonia, Viral/therapy , Precision Medicine/methods
13.
J Intensive Care Med ; 37(11): 1486-1492, 2022 Nov.
Article in English | MEDLINE | ID: covidwho-1896260

ABSTRACT

Background: Historically, procalcitonin(PCT) has been used as a predictor of bacterial infection and to guide antibiotic therapy in hospitalized patients. The purpose of this study was to determine PCT's diagnostic utility in predicting secondary bacterial pneumonia in critically ill patients with severe COVID-19 pneumonia. Methods: A retrospective cohort study was conducted in COVID-19 adults admitted to the ICU between March 2020, and March 2021. All included patients had a PCT level within 72 h of presentation and serum creatinine of <1.5mg/dL. A PCT threshold of 0.5ng/mL was used to compare patients with high( ≥ 0.5ng/mL) versus low(< 0.5ng/mL) PCT. Bacterial pneumonia was defined by positive respiratory culture. A receiver operating characteristics (ROC) curve was utilized to evaluate PCT as a diagnostic test for bacterial pneumonia, with an area under the curve(AUC) threshold of 0.7 to signify an accurate diagnostic test. A multivariable model was constructed to identify variables associated with in-hospital mortality. Results: There were 165 patients included: 127 low PCT versus 38 high PCT. There was no significant difference in baseline characteristics, vital signs, severity of disease, or outcomes among low versus high PCT groups (all p > 0.05). While there was no difference in bacterial pneumonia in low versus high groups (34(26.8%) versus 12(31.6%), p = 0.562), more patients in the high PCT group had bacteremia (19(15%) versus 11(28.9%), p = 0.050). Sensitivity was 26.1% and specificity was 78.2% for PCT to predict bacterial pneumonia coinfection in ICU patients with COVID-19 pneumonia. ROC yielded an AUC 0.54 (p = 0.415). After adjusting for LDH>350U/L and creatinine in multivariable regression, PCT did not enhance performance of the regression model. Conclusions: PCT offers little to no predictive utility in diagnosing concomitant bacterial pneumonia in critically ill patients with COVID-19 nor in predicting increased severity of disease or worse outcomes including mortality.


Subject(s)
COVID-19 , Pneumonia, Bacterial , Adult , Anti-Bacterial Agents , Biomarkers , COVID-19/complications , Calcitonin , Creatinine , Critical Illness , Humans , Pneumonia, Bacterial/complications , Pneumonia, Bacterial/diagnosis , Procalcitonin , ROC Curve , Retrospective Studies
14.
Proc Natl Acad Sci U S A ; 119(25): e2121778119, 2022 06 21.
Article in English | MEDLINE | ID: covidwho-1890409

ABSTRACT

Community-acquired pneumonia (CAP) has been brought to the forefront of global health priorities due to the COVID-19 pandemic. However, classification of viral versus bacterial pneumonia etiology remains a significant clinical challenge. To this end, we have engineered a panel of activity-based nanosensors that detect the dysregulated activity of pulmonary host proteases implicated in the response to pneumonia-causing pathogens and produce a urinary readout of disease. The nanosensor targets were selected based on a human protease transcriptomic signature for pneumonia etiology generated from 33 unique publicly available study cohorts. Five mouse models of bacterial or viral CAP were developed to assess the ability of the nanosensors to produce etiology-specific urinary signatures. Machine learning algorithms were used to train diagnostic classifiers that could distinguish infected mice from healthy controls and differentiate those with bacterial versus viral pneumonia with high accuracy. This proof-of-concept diagnostic approach demonstrates a way to distinguish pneumonia etiology based solely on the host proteolytic response to infection.


Subject(s)
COVID-19 , Community-Acquired Infections , Gene Expression Profiling , Peptide Hydrolases , Pneumonia, Bacterial , Animals , Biosensing Techniques , COVID-19/genetics , Community-Acquired Infections/classification , Community-Acquired Infections/genetics , Community-Acquired Infections/virology , Disease Models, Animal , Humans , Machine Learning , Mice , Nanoparticles , Peptide Hydrolases/genetics , Pneumonia, Bacterial/classification , Pneumonia, Bacterial/genetics
15.
J Clin Microbiol ; 60(7): e0017422, 2022 07 20.
Article in English | MEDLINE | ID: covidwho-1874497

ABSTRACT

COVID-19 is associated with prolonged hospitalization and a high risk of intubation, which raises concern for bacterial coinfection and antimicrobial resistance. Previous research has shown a wide range of bacterial pneumonia rates for COVID-19 patients in a variety of clinical and demographic settings, but none have compared hospitalized COVID-19 patients to patients testing negative for severe acute respiratory syndrome coronavirus (SARS-CoV-2) in similar care settings. We performed a retrospective cohort study on hospitalized patients with COVID-19 testing from March 10th, 2020 to December 31st, 2020. A total of 19,219 patients were included, of which 3,796 tested positive for SARS-CoV-2. We found a 2.6-fold increase (P < 0.001) in respiratory culture ordering in COVID-19 patients. On a per-patient basis, COVID-19 patients were 1.5-fold more likely than non-COVID patients to have positive respiratory cultures (46.8% versus 30.9%, P < 0.001), which was primarily driven by patients requiring intubation. Among patients with pneumonia, a significantly higher proportion of COVID-19 patients had ventilator-associated pneumonia (VAP) relative to non-COVID patients (86.3% versus 70.8%, P < 0.001), but a lower proportion had community-acquired (11.2% vs 25.5%, P < 0.01) pneumonia. There was also a significantly higher proportion of respiratory cultures positive for methicillin-resistant Staphylococcus aureus, Klebsiella pneumoniae, and antibiotic-resistant organisms in COVID-19 patients. Increased rates of respiratory culture ordering for COVID-19 patients therefore appear to be clinically justified for patients requiring intubation, but further research is needed to understand how SARS-CoV-2 increases the risk of VAP.


Subject(s)
COVID-19 , Coinfection , Methicillin-Resistant Staphylococcus aureus , Pneumonia, Bacterial , COVID-19 Testing , Coinfection/epidemiology , Hospitals, Urban , Humans , New York City/epidemiology , Pneumonia, Bacterial/epidemiology , Retrospective Studies , SARS-CoV-2
16.
Pediatr Infect Dis J ; 41(5): e208-e215, 2022 05 01.
Article in English | MEDLINE | ID: covidwho-1831448

ABSTRACT

BACKGROUND: Bacterial pneumonia imparts a major morbidity and mortality burden on children living with HIV, yet effective prevention and treatment options are underutilized. We explored clinical factors associated with severe recurrent bacterial pneumonia among children living with HIV. METHODS: Children enrolled in the TREAT Asia Pediatric HIV Observational Database were included if they started antiretroviral therapy (ART) on or after January 1st, 2008. Factors associated with severe recurrent bacterial pneumonia were assessed using competing-risk regression. RESULTS: A total of 3,944 children were included in the analysis; 136 cases of severe recurrent bacterial pneumonia were reported at a rate of 6.5 [95% confidence interval (CI): 5.5-7.7] events per 1,000 patient-years. Clinical factors associated with severe recurrent bacterial pneumonia were younger age [adjusted subdistribution hazard ratio (aHR): 4.4 for <5 years versus ≥10 years, 95% CI: 2.2-8.4, P < 0.001], lower weight-for-age z-score (aHR: 1.5 for <-3.0 versus >-2.0, 95% CI: 1.1-2.3, P = 0.024), pre-ART diagnosis of severe recurrent bacterial pneumonia (aHR: 4.0 versus no pre-ART diagnosis, 95% CI: 2.7-5.8, P < 0.001), past diagnosis of symptomatic lymphoid interstitial pneumonitis or chronic HIV-associated lung disease, including bronchiectasis (aHR: 4.8 versus no past diagnosis, 95% CI: 2.8-8.4, P < 0.001), low CD4% (aHR: 3.5 for <10% versus ≥25%, 95% CI: 1.9-6.4, P < 0.001) and detectable HIV viral load (aHR: 2.6 versus undetectable, 95% CI: 1.2-5.9, P = 0.018). CONCLUSIONS: Children <10-years-old and those with low weight-for-age, a history of respiratory illness, low CD4% or poorly controlled HIV are likely to gain the greatest benefit from targeted prevention and treatment programs to reduce the burden of bacterial pneumonia in children living with HIV.


Subject(s)
Anti-HIV Agents , HIV Infections , Pneumonia, Bacterial , Anti-HIV Agents/therapeutic use , CD4 Lymphocyte Count , Child , HIV Infections/drug therapy , Humans , Pneumonia, Bacterial/complications , Pneumonia, Bacterial/drug therapy , Pneumonia, Bacterial/epidemiology
17.
Reumatol Clin (Engl Ed) ; 18(9): 546-550, 2022 Nov.
Article in English | MEDLINE | ID: covidwho-1747606

ABSTRACT

INTRODUCTION: Lung Ultrasound is an accessible, low-cost technique that has demonstrated its usefulness in the prognostic stratification of COVID-19 patients. In addition, according to previous studies, it can guide us towards the potential aetiology, especially in epidemic situations such as the current one. PATIENTS AND METHODS: 40 patients were prospectively recruited, 30 with confirmed SARS-CoV-2 pneumonia and 10 with community-acquired pneumonia (CAP). The patients included underwent both a chest X-ray and ultrasound. RESULTS: There were no differences in the 2 groups in terms of clinical and laboratory characteristics. The main ultrasound findings in the SARS-CoV-2 group were the presence of confluent B lines and subpleural consolidations and hepatinization in the CAP group. Pleural effusion was more frequent in the CAP group. There were no normal lung ultrasound exams. Analysis of the area under the curve (AUC) curves showed an area under the curve for Lung Ultrasound of 89.2% (95% CI: 75%.0-100%, p < .001) in the identification of SARS-CoV-2 pneumonia. The cut-off value for the lung score of 10 had a sensitivity of 93.3% and a specificity of 80.0% (p < .001). DISCUSSION: The combination of the findings of the Lung Ultrasound, with a Lung Score greater than 10, added to the rest of the additional tests, can be an excellent tool to predict the aetiology of the pneumonia.


Subject(s)
COVID-19 , Pneumonia, Bacterial , Humans , Pandemics , SARS-CoV-2 , COVID-19/diagnostic imaging , Lung/diagnostic imaging , Pneumonia, Bacterial/diagnostic imaging
19.
Am J Respir Crit Care Med ; 205(11): 1271-1280, 2022 06 01.
Article in English | MEDLINE | ID: covidwho-1698208

ABSTRACT

A dramatic global reduction in the incidence of common seasonal respiratory viral infections has resulted from measures to limit the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the pandemic. This has been accompanied by falls reaching 50% internationally in the incidence of acute exacerbations of preexisting chronic respiratory diseases that include asthma, chronic obstructive pulmonary disease, and cystic fibrosis. At the same time, the incidence of acute bacterial pneumonia and sepsis has fallen steeply worldwide. Such findings demonstrate the profound impact of common respiratory viruses on the course of these global illnesses. Reduced transmission of common respiratory bacterial pathogens and their interactions with viruses appear also as central factors. This review summarizes pandemic changes in exacerbation rates of asthma, chronic obstructive pulmonary disease, cystic fibrosis, and pneumonia. We draw attention to the substantial body of knowledge about respiratory virus infections in these conditions, and that it has not yet translated into clinical practice. Now that the large scale of benefits that could be gained by managing these pathogens is unmistakable, we suggest that the field merits substantial academic and industrial investment. We consider how pandemic-inspired measures for prevention and treatment of common infections should become a cornerstone for managing respiratory diseases.


Subject(s)
Asthma , COVID-19 , Cystic Fibrosis , Pneumonia, Bacterial , Pulmonary Disease, Chronic Obstructive , Respiratory Tract Infections , Virus Diseases , Viruses , Asthma/epidemiology , Cystic Fibrosis/complications , Cystic Fibrosis/epidemiology , Humans , Pandemics/prevention & control , Pulmonary Disease, Chronic Obstructive/epidemiology , Pulmonary Disease, Chronic Obstructive/microbiology , Pulmonary Disease, Chronic Obstructive/prevention & control , Respiratory Tract Infections/epidemiology , SARS-CoV-2
20.
Commun Dis Intell (2018) ; 462022 Feb 16.
Article in English | MEDLINE | ID: covidwho-1689523

ABSTRACT

BACKGROUND: Concerns have been raised internationally, regarding possible increased antimicrobial use during the COVID-19 pandemic and the potential impact on antimicrobial resistance. This analysis aimed to investigate hospital usage rates of broad-spectrum antibacterial agents used to treat community-acquired pneumonia (CAP) and/or hospital-acquired pneumonia (HAP) in Australian principal referral hospitals during 2020. Secondly, usage rates in Victoria were compared with equivalent national rates. METHODS: Monthly antimicrobial dispensing data for all 31 Australian principal referral hospitals were analysed for the period January 2019 to December 2020. Grams of antimicrobial agents used were converted into the World Health Organization (WHO) assigned metric 'Defined Daily Dose' (DDD). Using the hospital activity metric Occupied Bed Days (OBD), a standardised usage density rate was calculated (in units of DDD / 1,000 OBD). RESULTS: The typical expected seasonal trend in aggregate usage rates, for antibacterials used in the treatment of CAP, was not evident in 2020. Overall usage of doxycycline, azithromycin, amoxicillin and cefuroxime decreased in principal referral hospitals compared to 2019. Aggregated monthly usage rates for broad-spectrum agents used to treat HAP increased nationally, on average, by 5.0% in 2020 compared to 2019. Victoria's second COVID-19 wave (July-October 2020) coincided with higher usage rates of antibacterials used for CAP. CONCLUSION: Public health interventions introduced to limit the spread of SARS-CoV-2 infections may have had unintended benefits on other respiratory infection rates. The drop in hospital usage of antibacterials typically used to treat CAP suggests that the number of cases of pneumonia acquired in the community requiring hospitalisation was markedly reduced in 2020.


Subject(s)
Anti-Infective Agents , COVID-19 , Pneumonia, Bacterial , Hospitals , Humans , Pandemics , Pneumonia, Bacterial/drug therapy , Pneumonia, Bacterial/epidemiology , Referral and Consultation , SARS-CoV-2 , Victoria
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