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1.
Int J Nanomedicine ; 16: 6575-6591, 2021.
Article in English | MEDLINE | ID: covidwho-1533527

ABSTRACT

Public awareness of infectious diseases has increased in recent months, not only due to the current COVID-19 outbreak but also because of antimicrobial resistance (AMR) being declared a top-10 global health threat by the World Health Organization (WHO) in 2019. These global issues have spiked the realization that new and more efficient methods and approaches are urgently required to efficiently combat and overcome the failures in the diagnosis and therapy of infectious disease. This holds true not only for current diseases, but we should also have enough readiness to fight the unforeseen diseases so as to avoid future pandemics. A paradigm shift is needed, not only in infection treatment, but also diagnostic practices, to overcome the potential failures associated with early diagnosis stages, leading to unnecessary and inefficient treatments, while simultaneously promoting AMR. With the development of nanotechnology, nanomaterials fabricated as multifunctional nano-platforms for antibacterial therapeutics, diagnostics, or both (known as "theranostics") have attracted increasing attention. In the research field of nanomedicine, mesoporous silica nanoparticles (MSN) with a tailored structure, large surface area, high loading capacity, abundant chemical versatility, and acceptable biocompatibility, have shown great potential to integrate the desired functions for diagnosis of bacterial infections. The focus of this review is to present the advances in mesoporous materials in the form of nanoparticles (NPs) or composites that can easily and flexibly accommodate dual or multifunctional capabilities of separation, identification and tracking performed during the diagnosis of infectious diseases together with the inspiring NP designs in diagnosis of bacterial infections.


Subject(s)
Bacterial Infections , COVID-19 , Nanoparticles , Bacterial Infections/diagnosis , Bacterial Infections/drug therapy , Humans , Porosity , SARS-CoV-2 , Silicon Dioxide
2.
Acc Chem Res ; 54(21): 3991-4000, 2021 11 02.
Article in English | MEDLINE | ID: covidwho-1483068

ABSTRACT

The modern healthcare system faces an unrelenting threat from microorganisms, as evidenced by global outbreaks of new viral diseases, emerging antimicrobial resistance, and the rising incidence of healthcare-associated infections (HAIs). An effective response to these threats requires rapid and accurate diagnostic tests that can identify causative pathogens at the point of care (POC). Such tests could eliminate diagnostic uncertainties, facilitating patient triaging, minimizing the empiric use of antimicrobial drugs, and enabling targeted treatments. Current standard methods, however, often fail to meet the needs of rapid diagnosis in POC settings. Culture-based assays entail long processing times and require specialized laboratory infrastructure; nucleic acid (NA) tests are often limited to centralized hospitals due to assay complexity and high costs. Here we discuss two new POC tests developed in our groups to enable the rapid diagnosis of infection. The first is nanoPCR that takes advantages of core-shell magnetoplasmonic nanoparticles (MPNs): (i) Au shell significantly accelerates thermocycling via volumetric, plasmonic light-to-heat conversion and (ii) a magnetic core enables sensitive in situ fluorescent detection via magnetic clearing. By adopting a Ferris wheel module, the system expedites multisamples in parallel with a minimal setup. When applied to COVID-19 diagnosis, nanoPCR detected SARS-CoV-2 RNA down to 3.2 copy/µL within 17 min. In particular, nanoPCR diagnostics accurately identified COVID-19 cases in clinical samples (n = 150), validating its clinical applicability. The second is a polarization anisotropy diagnostic (PAD) system that exploits the principle of fluorescence polarization (FP) as a detection modality. Fluorescent probes were designed to alter their molecular weight upon recognizing target NAs. This event modulates the probes' tumbling rate (Brownian motion), which leads to changes in FP. The approach is robust against environmental noise and benefits from the ratiometric nature of the signal readout. We applied PAD to detect clinically relevant HAI bacteria (Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Staphylococcus aureus). The PAD assay demonstrated detection sensitivity down to the single bacterium level and determined both drug resistance and virulence status. In summary, these new tests have the potential to become powerful tools for rapid diagnosis in the infectious disease space. They do not require highly skilled personnel or labor-intensive analyses, and the assays are quick and cost-effective. These attributes will make nanoPCR and PAD well-aligned with a POC workflow to aid physicians to initiate prompt and informed patient treatment.


Subject(s)
Bacterial Infections/diagnosis , COVID-19 Testing , COVID-19/diagnosis , Fluorescence Polarization , Nanotechnology , Polymerase Chain Reaction , Fluorescent Dyes/chemistry , Humans , Point-of-Care Systems , RNA, Viral/genetics , SARS-CoV-2/genetics
3.
Crit Care Med ; 49(10): 1664-1673, 2021 10 01.
Article in English | MEDLINE | ID: covidwho-1452743

ABSTRACT

OBJECTIVES: The rapid diagnosis of acute infections and sepsis remains a serious challenge. As a result of limitations in current diagnostics, guidelines recommend early antimicrobials for suspected sepsis patients to improve outcomes at a cost to antimicrobial stewardship. We aimed to develop and prospectively validate a new, 29-messenger RNA blood-based host-response classifier Inflammatix Bacterial Viral Non-Infected version 2 (IMX-BVN-2) to determine the likelihood of bacterial and viral infections. DESIGN: Prospective observational study. SETTING: Emergency Department, Campus Benjamin Franklin, Charité-Universitätsmedizin Berlin, Germany. PATIENTS: Three hundred twelve adult patients presenting to the emergency department with suspected acute infections or sepsis with at least one vital sign change. INTERVENTIONS: None (observational study only). MEASUREMENTS AND MAIN RESULTS: Gene expression levels from extracted whole blood RNA was quantified on a NanoString nCounter SPRINT (NanoString Technologies, Seattle, WA). Two predicted probability scores for the presence of bacterial and viral infection were calculated using the IMX-BVN-2 neural network classifier, which was trained on an independent development set. The IMX-BVN-2 bacterial score showed an area under the receiver operating curve for adjudicated bacterial versus ruled out bacterial infection of 0.90 (95% CI, 0.85-0.95) compared with 0.89 (95% CI, 0.84-0.94) for procalcitonin with procalcitonin being used in the adjudication. The IMX-BVN-2 viral score area under the receiver operating curve for adjudicated versus ruled out viral infection was 0.83 (95% CI, 0.77-0.89). CONCLUSIONS: IMX-BVN-2 demonstrated accuracy for detecting both viral infections and bacterial infections. This shows the potential of host-response tests as a novel and practical approach for determining the causes of infections, which could improve patient outcomes while upholding antimicrobial stewardship.


Subject(s)
Bacterial Infections/diagnosis , RNA, Messenger/analysis , Virus Diseases/diagnosis , Aged , Aged, 80 and over , Area Under Curve , Bacterial Infections/blood , Bacterial Infections/physiopathology , Berlin , Biomarkers/analysis , Biomarkers/blood , Emergency Service, Hospital/organization & administration , Emergency Service, Hospital/statistics & numerical data , Female , Humans , Male , Middle Aged , Prospective Studies , RNA, Messenger/blood , ROC Curve , Virus Diseases/blood , Virus Diseases/physiopathology
4.
Acc Chem Res ; 54(18): 3550-3562, 2021 09 21.
Article in English | MEDLINE | ID: covidwho-1377906

ABSTRACT

Infectious diseases present tremendous challenges to human progress and public health. The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the associated coronavirus disease 2019 (COVID-19) pandemic continue to pose an imminent threat to humanity. These infectious diseases highlight the importance of developing innovative strategies to study disease pathogenesis and protect human health. Although conventional in vitro cell culture and animal models are useful in facilitating the development of effective therapeutics for infectious diseases, models that can accurately reflect human physiology and human-relevant responses to pathogens are still lacking. Microfluidic organs-on-a-chip (organ chips) are engineered microfluidic cell culture devices lined with living cells, which can resemble organ-level physiology with high fidelity by rebuilding tissue-tissue interfaces, mechanical cues, fluidic flow, and the biochemical cellular microenvironment. They present a unique opportunity to bridge the gap between in vitro experimental models and in vivo human pathophysiology and are thus a promising platform for disease studies and drug testing. In this Account, we first introduce how recent progress in organ chips has enabled the recreation of complex pathophysiological features of human infections in vitro. Next, we describe the progress made by our group in adopting organ chips and other microphysiological systems for the study of infectious diseases, including SARS-CoV-2 viral infections and intrauterine bacterial infections. Respiratory symptoms dominate the clinical manifestations of many COVID-19 patients, even involving the systemic injury of many distinct organs, such as the lung, the gastrointestinal tract, and so forth. We thus particularly highlight our recent efforts to explore how lung-on-a-chip and intestine-on-a-chip might be useful in addressing the ongoing viral pandemic of COVID-19 caused by SARS-CoV-2. These organ chips offer a potential platform for studying virus-host interactions and human-relevant responses as well as accelerating the development of effective therapeutics against COVID-19. Finally, we discuss opportunities and challenges in the development of next-generation organ chips, which are urgently needed for developing effective and affordable therapies to combat infectious diseases. We hope that this Account will promote awareness about in vitro organ microphysiological systems for modeling infections and stimulate joint efforts across multiple disciplines to understand emerging and re-emerging pandemic diseases and rapidly identify innovative interventions.


Subject(s)
Bacterial Infections/diagnosis , COVID-19/diagnosis , Lab-On-A-Chip Devices , Humans
5.
Crit Care ; 25(1): 281, 2021 08 05.
Article in English | MEDLINE | ID: covidwho-1344117

ABSTRACT

BACKGROUND: Procalcitonin (PCT) and C-reactive protein (CRP) were previously shown to have value for the detection of secondary infections in critically ill COVID-19 patients. However, since the introduction of immunomodulatory therapy, the value of these biomarkers is unclear. We investigated PCT and CRP kinetics in critically ill COVID-19 patients treated with dexamethasone with or without tocilizumab, and assessed the value of these biomarkers to detect secondary bacterial infections. METHODS: In this prospective study, 190 critically ill COVID-19 patients were divided into three treatment groups: no dexamethasone, no tocilizumab (D-T-), dexamethasone, no tocilizumab (D+T-), and dexamethasone and tocilizumab (D+T+). Serial data of PCT and CRP were aligned on the last day of dexamethasone treatment, and kinetics of these biomarkers were analyzed between 6 days prior to cessation of dexamethasone and 10 days afterwards. Furthermore, the D+T- and D+T+ groups were subdivided into secondary infection and no-secondary infection groups to analyze differences in PCT and CRP kinetics and calculate detection accuracy of these biomarkers for the occurrence of a secondary infection. RESULTS: Following cessation of dexamethasone, there was a rebound in PCT and CRP levels, most pronounced in the D+T- group. Upon occurrence of a secondary infection, no significant increase in PCT and CRP levels was observed in the D+T- group (p = 0.052 and p = 0.08, respectively). Although PCT levels increased significantly in patients of the D+T+ group who developed a secondary infection (p = 0.0003), this rise was only apparent from day 2 post-infection onwards. CRP levels remained suppressed in the D+T+ group. Receiver operating curve analysis of PCT and CRP levels yielded area under the curves of 0.52 and 0.55, respectively, which are both markedly lower than those found in the group of COVID-19 patients not treated with immunomodulatory drugs (0.80 and 0.76, respectively, with p values for differences between groups of 0.001 and 0.02, respectively). CONCLUSIONS: Cessation of dexamethasone in critically ill COVID-19 patients results in a rebound increase in PCT and CRP levels unrelated to the occurrence of secondary bacterial infections. Furthermore, immunomodulatory treatment with dexamethasone and tocilizumab considerably reduces the value of PCT and CRP for detection of secondary infections in COVID-19 patients.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Bacterial Infections/diagnosis , COVID-19/drug therapy , Coinfection/diagnosis , Dexamethasone/therapeutic use , Aged , C-Reactive Protein/analysis , COVID-19/complications , Critical Illness , Female , Humans , Male , Middle Aged , Netherlands , Procalcitonin/analysis , Prospective Studies
6.
Emerg Med J ; 38(9): 685-691, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1320447

ABSTRACT

BACKGROUND: Guidelines recommend maximal efforts to obtain blood and sputum cultures in patients with COVID-19, as bacterial coinfection is associated with worse outcomes. The aim of this study was to evaluate the yield of bacteriological tests, including blood and sputum cultures, and the association of multiple biomarkers and the Pneumonia Severity Index (PSI) with clinical and microbiological outcomes in patients with COVID-19 presenting to the emergency department (ED). METHODS: This is a substudy of a large observational cohort study (PredictED study). The PredictED included adult patients from whom a blood culture was drawn at the ED of Haga Teaching Hospital, The Netherlands. For this substudy, all patients who tested positive for SARS-CoV-2 by PCR in March and April 2020 were included. The primary outcome was the incidence of bacterial coinfection. We used logistic regression analysis for associations of procalcitonin, C reactive protein (CRP), ferritin, lymphocyte count and PSI score with a severe disease course, defined as intensive care unit admission and/or 30-day mortality. The area under the receiver operating characteristics curve (AUC) quantified the discriminatory performance. RESULTS: We included 142 SARS-CoV-2 positive patients. On presentation, the median duration of symptoms was 8 days. 41 (29%) patients had a severe disease course and 24 (17%) died within 30 days. The incidence of bacterial coinfection was 2/142 (1.4%). None of the blood cultures showed pathogen growth while 6.3% was contaminated. The AUCs for predicting severe disease were 0.76 (95% CI 0.68 to 0.84), 0.70 (0.61 to 0.79), 0.62 (0.51 to 0.74), 0.62 (0.51 to 0.72) and 0.72 (0.63 to 0.81) for procalcitonin, CRP, ferritin, lymphocyte count and PSI score, respectively. CONCLUSION: Blood cultures appear to have limited value while procalcitonin and the PSI appear to be promising tools in helping physicians identify patients at risk for severe disease course in COVID-19 at presentation to the ED.


Subject(s)
Bacterial Infections/diagnosis , Bacteriological Techniques/methods , COVID-19/diagnosis , Coinfection/diagnosis , Adult , Aged , Aged, 80 and over , Bacterial Infections/blood , Bacterial Infections/complications , Bacterial Infections/microbiology , Bacteriological Techniques/statistics & numerical data , C-Reactive Protein/analysis , COVID-19/blood , COVID-19/complications , COVID-19/virology , COVID-19 Nucleic Acid Testing , Coinfection/blood , Coinfection/epidemiology , Coinfection/microbiology , Emergency Service, Hospital , Female , Ferritins/blood , Humans , Incidence , Lymphocyte Count , Male , Middle Aged , Netherlands/epidemiology , Procalcitonin/blood , Prognosis , ROC Curve , Retrospective Studies , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification , Severity of Illness Index
7.
Pediatrics ; 148(4)2021 10.
Article in English | MEDLINE | ID: covidwho-1291386

ABSTRACT

OBJECTIVES: To determine the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in infants hospitalized for a serious bacterial infection (SBI) evaluation and clinically characterize young infants with SARS-CoV-2 infection. METHODS: A retrospective chart review was conducted on infants <90 days of age hospitalized for an SBI evaluation. The study was conducted at 4 inpatient facilities in New York City from March 15, 2020, to December 15, 2020. RESULTS: We identified 148 SBI evaluation infants who met inclusion criteria. A total of 22 infants (15%) tested positive for SARS-CoV-2 by nasopharyngeal reverse transcription polymerase chain reaction; 31% of infants admitted during periods of high community SARS-CoV-2 circulation tested positive for SARS-CoV-2, compared with 3% when community SARS-CoV-2 circulation was low (P < .001). The mean age of infants with SARS-CoV-2 was higher than that of SARS-CoV-2-negative infants (33 [SD: 17] days vs 23 [SD: 23] days, respectively; P = .03), although no age difference was observed when analysis was limited only to febrile infants. An isolated fever was the most common presentation of SARS-CoV-2 (n = 13; 59%). Admitted infants with SARS-CoV-2 were less likely to have positive urine culture results (n = 1 [5%] versus n = 25 [20%], respectively; P = .002), positive cerebrospinal culture results (n = 0 [0%] versus n = 5 [4%], respectively; P = .02), or be admitted to intensive care (n = 2 [9%] versus n = 47 [37%]; P < .001), compared with infants without SARS-CoV-2. CONCLUSIONS: SARS-CoV-2 was common among young infants hospitalized for an SBI evaluation during periods of high but not low community SARS-CoV-2 circulation in New York City, although most infants did not require intensive care admission.


Subject(s)
Bacterial Infections/diagnosis , COVID-19/diagnosis , COVID-19/epidemiology , Age of Onset , Bacterial Infections/complications , Bacterial Infections/epidemiology , COVID-19/complications , COVID-19 Nucleic Acid Testing , Comorbidity , Female , Fever/microbiology , Fever/virology , Humans , Infant , Infant, Newborn , Male , New York City/epidemiology , Prevalence , Retrospective Studies , SARS-CoV-2
8.
Auris Nasus Larynx ; 48(6): 1176-1180, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1281384

ABSTRACT

OBJECTIVE: In Japan, many otolaryngologists provide primary care for patients with coronavirus disease 2019 (COVID-19). The purpose of this study was to analyze the characteristics of otorhinolaryngological findings in order to improve COVID-19 diagnostic systems in a primary care setting. METHODS: A total of 351 patients (mean age, 36.0 ± 15.4 years) diagnosed with COVID-19 by otolaryngologists who belong to the Japan Otorhinolaryngologists Association were included in the study. A web-based questionnaire was used to collect information regarding the timing of positive identification of COVID-19, the route of infection, symptoms, and findings in the tonsils, nasal cavity, pharynx, ear, and neck. A modified Centor score was calculated for cases in which age, symptoms, and tonsil and neck findings were described. RESULTS: Symptoms included fever (56%), olfactory disturbance (46%), and a sore throat (56%). Of the individuals considered, 63% had ordinary rhinoscopic findings, 21% experienced watery rhinorrhea, and 12% had observable mucosal redness. Further, 87% had ordinary tonsillar findings, 13% displayed tonsillar redness, with enlargement and white mucus observe in 2% and 1% of participants, respectively. A total of 193 patients had a calculated Centor score of 3 points in 2%, and scores of the remaining participants were ≤2 points. CONCLUSION: Of all patients considered, 40% had nasal findings and 4% had purulent nasal discharge. In contrast, only 13% of the patients had tonsillar findings, and no patients had Centor scores ≥4 points. Symptom differentiation from that of bacterial infections is difficult. In areas where COVID-19 is prevalent, the disease should be considered in patients presenting with fever, olfactory disturbances, and sore throat with minimal or no clinical findings in the nasal cavity and pharynx.


Subject(s)
COVID-19/diagnosis , Otorhinolaryngologic Diseases/diagnosis , Symptom Assessment , Adult , Bacterial Infections/diagnosis , COVID-19/complications , COVID-19/epidemiology , Diagnosis, Differential , Female , Health Care Surveys , Humans , Japan/epidemiology , Male , Otolaryngologists , Otorhinolaryngologic Diseases/epidemiology , Otorhinolaryngologic Diseases/virology
10.
Ann Clin Biochem ; 58(5): 520-527, 2021 09.
Article in English | MEDLINE | ID: covidwho-1277833

ABSTRACT

BACKGROUND: The variability of Covid-19 severity between patients has driven efforts to identify prognosticating laboratory markers that could aid clinical decision-making. Procalcitonin is classically used as a diagnostic marker in bacterial infections, but its role in predicting Covid-19 disease severity is emerging. We aimed to identify the association between procalcitonin and Covid-19 disease severity in a critical care setting and whether bacterial co-infection is implicated. METHODS: We retrospectively reviewed Covid-19 patients with procalcitonin concentrations measured in a critical care setting at our institution between February and September 2020. Laboratory markers including peak procalcitonin values and a range of bacterial culture results were analysed. Outcomes were the requirement and duration of invasive mechanical ventilation as well as inpatient mortality. RESULTS: In total, 60 patients were included; 68% required invasive mechanical ventilation and 45% died as inpatient. Univariate analysis identified higher peak procalcitonin concentrations significantly associated with both the requirement for invasive mechanical ventilation (OR: 3.2, 95% CI 1.3-9.0, P = 0.02) and inpatient mortality (OR: 2.6, 95% CI 1.1-6.6, P = 0.03). Higher peak procalcitonin concentrations was an independent predictor of mortality on multivariate analysis (OR 3.7, 95% CI 1.1-12.4, P = 0.03). There was a significant positive correlation between increased peak procalcitonin concentrations and duration on invasive mechanical ventilation. No significant difference was found between peak procalcitonin concentrations of patients with positive and negative bacterial cultures. CONCLUSIONS: Elevated procalcitonin concentrations in Covid-19 patients are associated with respiratory failure requiring prolonged invasive mechanical ventilation and inpatient mortality. This association may be independent of bacterial co-infection.


Subject(s)
Bacterial Infections/blood , Bacterial Infections/complications , COVID-19/blood , COVID-19/complications , Procalcitonin/blood , SARS-CoV-2 , Adult , Aged , Bacterial Infections/diagnosis , Biomarkers/blood , COVID-19/epidemiology , Coinfection/blood , Critical Care , England/epidemiology , Female , Humans , Male , Middle Aged , Multivariate Analysis , Pandemics , Prognosis , Respiration, Artificial , Retrospective Studies , Risk Factors , Severity of Illness Index
11.
Eur J Clin Microbiol Infect Dis ; 40(9): 1983-1997, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1263157

ABSTRACT

SARS-CoV-2 antibody assays are used for epidemiological studies and for the assessment of vaccine responses in highly vulnerable patients. So far, data on cross-reactivity of SARS-CoV-2 antibody assays is limited. Here, we compared four enzyme-linked immunosorbent assays (ELISAs; Vircell SARS-CoV-2 IgM/IgA and IgG, Euroimmun SARS-CoV-2 IgA and IgG) for detection of anti-SARS-CoV-2 antibodies in 207 patients with COVID-19, 178 patients with serological evidence of different bacterial infections, 107 patients with confirmed viral respiratory disease, and 80 controls from the pre-COVID-19 era. In COVID-19 patients, the assays showed highest sensitivity in week 3 (Vircell-IgM/A and Euroimmun-IgA: 78.9% each) and after week 7 (Vircell-IgG: 97.9%; Euroimmun-IgG: 92.1%). The antibody indices were higher in patients with fatal disease. In general, IgM/IgA assays had only limited or no benefit over IgG assays. In patients with non-SARS-CoV-2 respiratory infections, IgG assays were more specific than IgM/IgA assays, and bacterial infections were associated with more false-positive results than viral infections. The specificities in bacterial and viral infections were 68.0 and 81.3% (Vircell-IgM/IgA), 84.8 and 96.3% (Euroimmun-IgA), 97.8 and 86.0% (Vircell-IgG), and 97.8 and 99.1% (Euroimmun-IgG), respectively. Sera from patients positive for antibodies against Mycoplasma pneumoniae, Chlamydia psittaci, and Legionella pneumophila yielded particularly high rates of unspecific false-positive results in the IgM/IgA assays, which was revealed by applying a highly specific flow-cytometric assay using HEK 293 T cells expressing the SARS-CoV-2 spike protein. Positive results obtained with anti-SARS-CoV-2 IgM/IgA ELISAs require careful interpretation, especially if there is evidence for prior bacterial respiratory infections.


Subject(s)
Antibodies, Viral/blood , Bacterial Infections/diagnosis , COVID-19 Serological Testing/methods , COVID-19/diagnosis , Respiratory Tract Infections/diagnosis , Antibodies, Bacterial/blood , Bacterial Infections/blood , COVID-19/blood , COVID-19/virology , Enzyme-Linked Immunosorbent Assay , Humans , Immunoglobulin A/blood , Immunoglobulin G/blood , Immunoglobulin M/blood , Respiratory Tract Infections/blood , SARS-CoV-2/immunology , Sensitivity and Specificity , Spike Glycoprotein, Coronavirus/immunology
12.
Arch Pathol Lab Med ; 145(2): 145-167, 2021 02 01.
Article in English | MEDLINE | ID: covidwho-1207907

ABSTRACT

CONTEXT.­: Point-of-care testing (POCT) is inherently spatial, that is, performed where needed, and intrinsically temporal, because it accelerates decision-making. POCT efficiency and effectiveness have the potential to facilitate antimicrobial resistance (AMR) detection, decrease risks of coinfections for critically ill patients with coronavirus infectious disease 2019 (COVID-19), and improve the cost-effectiveness of health care. OBJECTIVES.­: To assess AMR identification by using POCT, describe the United States AMR Diagnostic Challenge, and improve global standards of care for infectious diseases. DATA SOURCES.­: PubMed, World Wide Web, and other sources were searched for papers focusing on AMR and POCT. EndNote X9.1 (Clarivate Analytics) consolidated abstracts, URLs, and PDFs representing approximately 500 articles were assessed for relevance. Panelist insights at Tri•Con 2020 in San Francisco and finalist POC technologies competing for a US $20,000,000 AMR prize are summarized. CONCLUSIONS.­: Coinfections represent high risks for COVID-19 patients. POCT potentially will help target specific pathogens, refine choices for antimicrobial drugs, and prevent excess morbidity and mortality. POC assays that identify patterns of pathogen resistance can help tell us how infected individuals spread AMR, where geospatial hotspots are located, when delays cause death, and how to deploy preventative resources. Shared AMR data "clouds" could help reduce critical care burden during pandemics and optimize therapeutic options, similar to use of antibiograms in individual hospitals. Multidisciplinary health care personnel should learn the principles and practice of POCT, so they can meet needs with rapid diagnostic testing. The stakes are high. Antimicrobial resistance is projected to cause millions of deaths annually and cumulative financial loses in the trillions by 2050.


Subject(s)
COVID-19/microbiology , Coinfection/microbiology , Drug Resistance, Bacterial , Drug Resistance, Fungal , Microbial Sensitivity Tests/methods , Point-of-Care Systems , Awards and Prizes , Bacterial Infections/diagnosis , Bacterial Infections/microbiology , COVID-19/diagnosis , COVID-19/mortality , Coinfection/diagnosis , Humans , Microbial Sensitivity Tests/standards , Mycoses/diagnosis , Mycoses/microbiology , Point-of-Care Systems/standards , Spatial Analysis , United States/epidemiology
13.
EBioMedicine ; 67: 103352, 2021 May.
Article in English | MEDLINE | ID: covidwho-1205123

ABSTRACT

BACKGROUND: Precise differential diagnosis between acute viral and bacterial infections is important to enable appropriate therapy, avoid unnecessary antibiotic prescriptions and optimize the use of hospital resources. A systems view of host response to infections provides opportunities for discovering sensitive and robust molecular diagnostics. METHODS: We combine blood transcriptomes from six independent datasets (n = 756) with a knowledge-based human protein-protein interaction network, identifies subnetworks capturing host response to each infection class, and derives common response cores separately for viral and bacterial infections. We subject the subnetworks to a series of computational filters to identify a parsimonious gene panel and a standalone diagnostic score that can be applied to individual samples. We rigorously validate the panel and the diagnostic score in a wide range of publicly available datasets and in a newly developed Bangalore-Viral Bacterial (BL-VB) cohort. FINDING: We discover a 10-gene blood-based biomarker panel (Panel-VB) that demonstrates high predictive performance to distinguish viral from bacterial infections, with a weighted mean AUROC of 0.97 (95% CI: 0.96-0.99) in eleven independent datasets (n = 898). We devise a new stand-alone patient-wise score (VB10) based on the panel, which shows high diagnostic accuracy with a weighted mean AUROC of 0.94 (95% CI 0.91-0.98) in 2996 patient samples from 56 public datasets from 19 different countries. Further, we evaluate VB10 in a newly generated South Indian (BL-VB, n = 56) cohort and find 97% accuracy in the confirmed cases of viral and bacterial infections. We find that VB10 is (a) capable of accurately identifying the infection class in culture-negative indeterminate cases, (b) reflects recovery status, and (c) is applicable across different age groups, covering a wide spectrum of acute bacterial and viral infections, including uncharacterized pathogens. We tested our VB10 score on publicly available COVID-19 data and find that our score detected viral infection in patient samples. INTERPRETATION: Our results point to the promise of VB10 as a diagnostic test for precise diagnosis of acute infections and monitoring recovery status. We expect that it will provide clinical decision support for antibiotic prescriptions and thereby aid in antibiotic stewardship efforts. FUNDING: Grand Challenges India, Biotechnology Industry Research Assistance Council (BIRAC), Department of Biotechnology, Govt. of India.


Subject(s)
Bacterial Infections/diagnosis , Biomarkers/blood , Computational Biology/methods , Virus Diseases/diagnosis , Adult , Bacterial Infections/blood , Bacterial Infections/genetics , Databases, Factual , Decision Support Systems, Clinical , Diagnosis, Differential , Female , Gene Expression Profiling , Humans , India , Male , Middle Aged , Observational Studies as Topic , Predictive Value of Tests , Protein Interaction Maps , Virus Diseases/blood , Virus Diseases/genetics
14.
Curr Res Transl Med ; 69(2): 103289, 2021 05.
Article in English | MEDLINE | ID: covidwho-1179993

ABSTRACT

Elevated PCT level in COVID-19 was associated with higher risk of severe disease and higher risk of overall mortality. An increased PCT level of PCT in COVID-19 patients especially in severe cases would be assumed as bacterial coinfection. Could PCT level increase in SARS-CoV-2 infection without bacterial coinfection? Several SARS-CoV-2 proteins activate STAT3-dependent transcriptional pathways particularly in monocytes, that could lead to increased PCT production. STAT3α isoform could cause increased ACE2 expression, resulting more SARS-CoV-2 infected cells and further production of PCT.


Subject(s)
Bacterial Infections/diagnosis , COVID-19/diagnosis , Coinfection/diagnosis , Procalcitonin/blood , SARS-CoV-2/immunology , Bacterial Infections/blood , Bacterial Infections/complications , Biomarkers/blood , COVID-19/blood , COVID-19/complications , COVID-19/immunology , Coinfection/blood , Coinfection/complications , Humans , Immunity/physiology , Monocytes/metabolism , Monocytes/virology , Predictive Value of Tests , Procalcitonin/metabolism , STAT3 Transcription Factor/metabolism , Severity of Illness Index , Signal Transduction/immunology
16.
PLoS One ; 16(4): e0249668, 2021.
Article in English | MEDLINE | ID: covidwho-1170006

ABSTRACT

OBJECTIVE: To understand the clinical characteristics of COVID-19 patients with clinically diagnosed bacterial co-infection (CDBC), and therefore contributing to their early identification and prognosis estimation. METHOD: 905 COVID-19 patients from 7 different centers were enrolled. The demography data, clinical manifestations, laboratory results, and treatments were collected accordingly for further analyses. RESULTS: Around 9.5% of the enrolled COVID-19 patients were diagnosed with CDBC. Older patients or patients with cardiovascular comorbidities have increased CDBC probability. Increased body temperature, longer fever duration, anhelation, gastrointestinal symptoms, illness severity, intensive care unit attending, ventilation treatment, glucocorticoid therapy, longer hospitalization time are correlated to CDBC. Among laboratory results, increased white blood cell counting (mainly neutrophil), lymphocytopenia, increased procalcitonin, erythrocyte sedimentation rate, C-reaction protein, D-dimer, blood urea nitrogen, lactate dehydrogenase, brain natriuretic peptide, myoglobin, blood sugar and decreased albumin are also observed, indicating multiple system functional damage. Radiology results suggested ground glass opacity mixed with high density effusion opacities and even pleural effusion. CONCLUSION: The aged COVID-19 patients with increased inflammatory indicators, worse lymphopenia and cardiovascular comorbidities are more likely to have clinically diagnosed bacterial co-infection. Moreover, they tend to have severer clinical manifestations and increased probability of multiple system functional damage.


Subject(s)
Bacterial Infections , COVID-19/epidemiology , Coinfection , Adult , Aged , Bacterial Infections/diagnosis , Bacterial Infections/epidemiology , Coinfection/diagnosis , Coinfection/epidemiology , Comorbidity , Early Diagnosis , Female , Humans , Male , Middle Aged , Prognosis , Severity of Illness Index
17.
Eur J Clin Microbiol Infect Dis ; 40(10): 2227-2234, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1139366

ABSTRACT

Because the diagnosis of co/superinfection in COVID-19 patients is challenging, empirical antibiotic therapy is frequently initiated until microbiological analysis results. We evaluated the performance and the impact of the BioFire® FilmArray® Pneumonia plus Panel on 112 respiratory samples from 67 COVID-19 ICU patients suspected of co/superinfections. Globally, the sensitivity and specificity of the test were 89.3% and 99.1%, respectively. Positive tests led to antibiotic initiation or adaptation in 15% of episodes and de-escalation in 4%. When negative, 28% of episodes remained antibiotic-free (14% no initiation, 14% withdrawal). Rapid multiplex PCRs can help to improve antibiotic stewardship by administering appropriate antibiotics earlier and avoiding unnecessary prescriptions.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Bacteria/isolation & purification , Bacterial Infections/drug therapy , COVID-19/complications , Multiplex Polymerase Chain Reaction/methods , Aged , Antimicrobial Stewardship , Bacteria/classification , Bacteria/drug effects , Bacteria/genetics , Bacterial Infections/diagnosis , Bacterial Infections/microbiology , COVID-19/virology , Female , Hospitalization , Humans , Intensive Care Units/statistics & numerical data , Male , Middle Aged , Retrospective Studies , SARS-CoV-2/genetics , SARS-CoV-2/physiology
18.
Pediatr Infect Dis J ; 40(4): e159-e161, 2021 04 01.
Article in English | MEDLINE | ID: covidwho-1132631

ABSTRACT

Multisystem inflammatory syndrome in children following severe acute respiratory syndrome coronavirus 2 infection is characterized by fever, elevated inflammatory markers, and multisystem organ involvement. Presentations are variable but often include gastrointestinal symptoms. We describe 5 children with fever and gastrointestinal symptoms initially concerning for multisystem inflammatory syndrome in children who were ultimately diagnosed with bacterial enteritis, highlighting the diagnostic challenges presented by the severe acute respiratory syndrome coronavirus 2 pandemic.


Subject(s)
Bacterial Infections/diagnosis , Enteritis/diagnosis , Systemic Inflammatory Response Syndrome/diagnosis , Bacterial Infections/microbiology , Biomarkers , Child , Child, Preschool , Diagnosis, Differential , Diagnostic Errors , Enteritis/microbiology , Female , Hospitalization , Humans , Male , Symptom Assessment
19.
J Med Virol ; 93(5): 2883-2889, 2021 May.
Article in English | MEDLINE | ID: covidwho-1082475

ABSTRACT

INTRODUCTION: The rate of bacterial coinfection with SARS-CoV-2 is poorly defined. The decision to administer antibiotics early in the course of SARS-CoV-2 infection depends on the likelihood of bacterial coinfection. METHODS: We performed a retrospective chart review of all patients admitted through the emergency department with confirmed SARS-CoV-2 infection over a 6-week period in a large healthcare system in the United States. Blood and respiratory culture results were abstracted and adjudicated by multiple authors. The primary outcome was the rate of bacteremia. We secondarily looked to define clinical or laboratory features associated with bacteremia. RESULTS: There were 542 patients admitted with confirmed SARS-CoV-2 infection, with an average age of 62.8 years. Of these, 395 had blood cultures performed upon admission, with six true positive results (1.1% of the total population). An additional 14 patients had positive respiratory cultures treated as true pathogens in the first 72 h. Low blood pressure and elevated white blood cell count, neutrophil count, blood urea nitrogen, and lactate were statistically significantly associated with bacteremia. Clinical outcomes were not statistically significantly different between patients with and without bacteremia. CONCLUSIONS: We found a low rate of bacteremia in patients admitted with confirmed SARS-CoV-2 infection. In hemodynamically stable patients, routine antibiotics may not be warranted in this population.


Subject(s)
Bacterial Infections/epidemiology , COVID-19/epidemiology , Coinfection/epidemiology , Emergency Service, Hospital/statistics & numerical data , Anti-Bacterial Agents/therapeutic use , Bacteremia/diagnosis , Bacteremia/epidemiology , Bacteremia/therapy , Bacterial Infections/diagnosis , Bacterial Infections/therapy , COVID-19/diagnosis , COVID-19/therapy , Coinfection/diagnosis , Coinfection/therapy , Female , Hospitalization , Hospitals , Humans , Indiana/epidemiology , Male , Middle Aged , Retrospective Studies , Risk Factors , SARS-CoV-2/isolation & purification , Treatment Outcome
20.
Clin Chem Lab Med ; 59(3): 599-607, 2021 02 23.
Article in English | MEDLINE | ID: covidwho-1067439

ABSTRACT

OBJECTIVES: Severe coronavirus disease 2019 (COVID-19) is associated with a dysregulated immune state. While research has focused on the hyperinflammation, little research has been performed on the compensatory anti-inflammatory response. The aim of this study was to evaluate the anti-inflammatory cytokine response to COVID-19, by assessing interleukin-10 (IL-10) and IL-10/lymphocyte count ratio and their association with outcomes. METHODS: Adult patients presenting to the emergency department (ED) with laboratory-confirmed COVID-19 were recruited. The primary endpoint was maximum COVID-19 severity within 30 days of index ED visit. RESULTS: A total of 52 COVID-19 patients were enrolled. IL-10 and IL-10/lymphocyte count were significantly higher in patients with severe disease (p<0.05), as well as in those who developed severe acute kidney injury (AKI) and new positive bacterial cultures (all p≤0.01). In multivariable analysis, a one-unit increase in IL-10 and IL-10/lymphocyte count were associated with 42% (p=0.031) and 32% (p=0.013) increased odds, respectively, of severe COVID-19. When standardized to a one-unit standard deviations scale, an increase in the IL-10 was a stronger predictor of maximum 30-day severity and severe AKI than increases in IL-6 or IL-8. CONCLUSIONS: The hyperinflammatory response to COVID-19 is accompanied by a simultaneous anti-inflammatory response, which is associated with poor outcomes and may increase the risk of new positive bacterial cultures. IL-10 and IL-10/lymphocyte count at ED presentation were independent predictors of COVID-19 severity. Moreover, elevated IL-10 was more strongly associated with outcomes than pro-inflammatory IL-6 or IL-8. The anti-inflammatory response in COVID-19 requires further investigation to enable more precise immunomodulatory therapy against SARS-CoV-2.


Subject(s)
COVID-19/diagnosis , Interleukin-10/metabolism , Acute Kidney Injury/blood , Acute Kidney Injury/complications , Acute Kidney Injury/diagnosis , Adult , Aged , Bacterial Infections/blood , Bacterial Infections/complications , Bacterial Infections/diagnosis , COVID-19/blood , COVID-19/complications , Cohort Studies , Emergency Service, Hospital , Female , Hospitalization , Humans , Interleukin-10/blood , Lymphocyte Count , Male , Middle Aged , Prognosis
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