Gut microbiota composition reflects disease severity and dysfunctional immune responses in patients with COVID-19

Gut, Год журнала: 2021, Номер 70(4), С. 698 - 706

Опубликована: Янв. 11, 2021

Although COVID-19 is primarily a respiratory illness, there mounting evidence suggesting that the GI tract involved in this disease. We investigated whether gut microbiome linked to disease severity patients with COVID-19, and perturbations composition, if any, resolve clearance of SARS-CoV-2 virus.In two-hospital cohort study, we obtained blood, stool patient records from 100 laboratory-confirmed infection. Serial samples were collected 27 up 30 days after SARS-CoV-2. Gut compositions characterised by shotgun sequencing total DNA extracted stools. Concentrations inflammatory cytokines blood markers measured plasma.Gut composition was significantly altered compared non-COVID-19 individuals irrespective had received medication (p<0.01). Several commensals known immunomodulatory potential such as Faecalibacterium prausnitzii, Eubacterium rectale bifidobacteria underrepresented remained low resolution. Moreover, perturbed exhibited stratification concordant elevated concentrations C reactive protein, lactate dehydrogenase, aspartate aminotransferase gamma-glutamyl transferase.Associations between microbiota levels suggest magnitude possibly via modulating host immune responses. Furthermore, dysbiosis resolution could contribute persistent symptoms, highlighting need understand how microorganisms are inflammation COVID-19.

Язык: Английский

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Towards the sustainable discovery and development of new antibiotics

Nature Reviews Chemistry, Год журнала: 2021, Номер 5(10), С. 726 - 749

Опубликована: Авг. 19, 2021

An ever-increasing demand for novel antimicrobials to treat life-threatening infections caused by the global spread of multidrug-resistant bacterial pathogens stands in stark contrast current level investment their development, particularly fields natural-product-derived and synthetic small molecules. New agents displaying innovative chemistry modes action are desperately needed worldwide tackle public health menace posed antimicrobial resistance. Here, our consortium presents a strategic blueprint substantially improve ability discover develop new antibiotics. We propose both short-term long-term solutions overcome most urgent limitations various sectors research funding, aiming bridge gap between academic, industrial political stakeholders, unite interdisciplinary expertise order efficiently fuel translational pipeline benefit future generations.

Язык: Английский

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Co-infections, secondary infections, and antimicrobial use in patients hospitalised with COVID-19 during the first pandemic wave from the ISARIC WHO CCP-UK study: a multicentre, prospective cohort study

The Lancet Microbe, Год журнала: 2021, Номер 2(8), С. e354 - e365

Опубликована: Июнь 2, 2021

Язык: Английский

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The role of co-infections and secondary infections in patients with COVID-19

Pneumonia, Год журнала: 2021, Номер 13(1)

Опубликована: Апрель 24, 2021

Abstract Background It has been recognised for a considerable time-period, that viral respiratory infections predispose patients to bacterial infections, and these co-infections have worse outcome than either infection on its own. However, it is still unclear what exact roles and/or superinfections play in with COVID-19 infection. Main body This was an extensive review of the current literature regarding SARS-CoV-2 The definitions used were those Centers Disease Control Prevention (US), which defines coinfection as one occurring concurrently initial infection, while are follow previous especially when caused by microorganisms resistant, or become antibiotics earlier. Some researchers envisioned three potential scenarios bacterial/SARS-CoV-2 co-infection; namely, secondary following colonisation, combined viral/bacterial pneumonia, superinfection SARS-CoV-2. There myriad published articles ranging from letters editor systematic reviews meta-analyses describing varying ranges co-infection COVID-19. concomitant described included other viruses, bacteria, including mycobacteria, fungi, well other, more unusual, pathogens. will be seen this review, there often not clear distinction made authors referring to, whether true concomitant/co-infections superinfections. In addition, possible mechanisms interactions between SARS-CoV-2, particularly discussed further. Lastly, impact severity their also described. Conclusion describes rates although two literature. When they occur, appear associated both poorer outcomes.

Язык: Английский

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Bacterial Coinfections in Coronavirus Disease 2019

Trends in Microbiology, Год журнала: 2021, Номер 29(10), С. 930 - 941

Опубликована: Апрель 8, 2021

Bacterial coinfections occur in <4% of patients who are hospitalized with COVID-19 and usually caused by S. aureus, pneumoniae, H. influenzae.Empirical antibacterial therapy diagnostic testing for bacterial pathogens indicated only those critical illness, severe immunosuppression, radiographic findings suggestive a pneumonia, or multiple laboratory parameters compatible infection.Hospital-acquired infections common among prolonged hospitalization COVID-19, hospital-acquired pneumonia is most commonly P. aeruginosa, Klebsiella spp., aureus.Carbapenem-resistant Gram-negative being increasingly reported requiring intensive care. increase the severity respiratory viral were frequent causes mortality influenza pandemics but have not been well characterized coronavirus disease 2019 (COVID-19). The aim this review was to identify frequency microbial etiologies that present upon admission hospital during COVID-19. We found yield routine tests low. When did occur, Staphylococcus Streptococcus Haemophilus influenzae atypical bacteria rare. Although uncommon admission, frequently occurred hospitalization, Pseudomonas aureus pathogens. Antibacterial unnecessary clinicians should be vigilant nosocomial infections. Severe acute syndrome 2 (SARS-CoV-2) cause devastating pandemic has led more than 100 million cases deaths globally span 12 monthsi. Pandemics plagued humans throughout history now becoming common. Influenza responsible 1918 resulted ~50 worldwide, recently 1957, 1968, 2009 [1.Morens D.M. et al.Pandemic Joins History's Pandemic Legion.mBio. 2020; 11e00812-20Crossref PubMed Scopus (106) Google Scholar]. In 2003, near-pandemic (SARS-CoV) occurred, closely followed emergence another lethal coronavirus, Middle East (MERS-CoV), 2012 [2.Memish Z.A. al.Middle syndrome.Lancet. 395: 1063-1077Abstract Full Text PDF (306) coinfection complication many tract leads significantly increased morbidity [3.Gupta R.K. al.Bacterial planning.Emerg. Infect. Dis. 2008; 14: 1187-1192Crossref During pandemic, significant contributor nearly all deaths, upper such as β-hemolytic streptococci, influenzae, [4.Morens al.Predominant role death influenza: implications preparedness.J. 198: 962-970Crossref (1245) also occurring 18–30% admitted care unit (ICU) up 55% published autopsy series [5.Martín-Loeches I. al.Community-acquired critically ill A (H1N1) virus.Chest. 2011; 139: 555-562Abstract (146) Scholar, 6.Rice T.W. al.Critical illness from virus United States.Crit. Care Med. 2012; 40: 1487-1498Crossref (282) 7.Gill J.R. al.Pulmonary pathologic fatal A/H1N1 infections.Arch. Pathol. Lab. 2010; 134: 235-243Crossref associated risk shock failure, ICU length stay, Scholar,6.Rice coronaviruses SARS-CoV MERS-CoV clearly defined because relatively small numbers cases, multicenter study ICUs Saudi Arabia identified 19% MERS had [8.Arabi Y.M. al.Critically Respiratory Syndrome: retrospective cohort study.Crit. 2017; 45: 1683-1695Crossref (133) high clinical significance other novel raises concern could an important SARS-CoV-2 infection. initial reports described presentations outcomes [9.Guan W.J. al.Clinical characteristics China.N. Engl. J. 382: 1708-1720Crossref (20519) Scholar,10.Goyal Covid-19 New York City.N. 2372-2374Crossref (1602) Scholar], few focused on microbiological coinfections. Furthermore, these distinguish secondary acquired hospital. Thus, reviews complicating relied limited data [11.Rawson T.M. fungal co-infection individuals coronavirus: rapid support antimicrobial prescribing.Clin. 71: 2459-2468PubMed Scholar,12.Lansbury L. al.Co-infections people COVID-19: systematic meta-analysis.J. 81: 266-275Abstract (1028) However, since reports, numerous studies patients, thus our understanding evolved. Therefore, focus highlight frequency, factors, etiologies, separating hospital, evaluate diagnostics, assess multidrug-resistant (MDR) infections, provide practical guidance clinicians. reviewed publications which primary objective ten evaluated minimum (Table 1), fewer 4% documented [13.Vaughn V.M. al.Empiric community-onset multi-hospital study.Clin. (Published online August 21, 2020. https://doi.org/10.1093/cid/ciaa1239)Google 14.Wang al.An observational empirical antibiotic presenting hospitals North West London.J. Antimicrob. Chemother. 2021; 76: 796-803Crossref (65) 15.Garcia-Vidal C. al.Incidence co-infections superinfections Microbiol. 27: 83-88Abstract (585) 16.Karami Z. al.Few empiric use early phase results multicentre Netherlands.Infect. (Lond). 53: 102-110Crossref (108) 17.Hughes UK secondary-care setting.Clin. 26: 1395-1399Abstract (431) 18.Lehmann C.J. al.Community experience.Clin. July 1, https://doi.org/10.1093/cid/ciaa902)Google 19.Adler al.Low rate COVID-19.Lancet Microbe. 1e62Abstract (48) 20.Cheng L.S.-K. prescribing practice adults experience single cluster.Ther. Adv. 72049936120978095Google 21.Fu Y. al.Secondary 2019.Open Forum 5ofaa220Crossref Scholar].Table 1Bacterial Coinfections Patients Admitted Hospital COVID-19RefsLocationNo. patientsPrevalence coinfectionProportion received therapy[13.Vaughn Scholar]Michigan, USA (38 hospitals)17053.5%57% (median: 3 days)[14.Wang Scholar]London, England (2 hospitals)13962.7%98%aThe denominator proportion includes 37 randomly selected without coinfection.[15.Garcia-Vidal Scholar]Barcelona, Spain (1 hospital)9892.5%NR[16.Karami Scholar]The Netherlands (4 hospitals)9250.8%60% days)[17.Hughes hospitals)8363.2%NR[18.Lehmann Scholar]Chicago, hospital)3211.2%69%[19.Adler Scholar]Liverpool, hospital)1952.6%NR[20.Cheng Scholar]Hong Kong hospital)1472.7%35%bOf 35% antibiotics, 37% them 1 week.[21.Fu Scholar]Hangzhou, China hospital)1010%NR[22.Elabbadi A. pneumonia.Infection. https://doi.org/10.1007/s15010-020-01553-xCrossref (60) Scholar]Paris, France hospital)101 (ICU only)19.8%58%Abbreviations: ICU, unit; No., number; NR, reported.a coinfection.b Of week. Open table new tab Abbreviations: reported. Despite low prevalence coinfection, majority therapy. For example, 1705 38 Michigan hospitals, 57% median days (interquartile range: 2–6 days); however, 3.5% infection 15% agents targeting methicillin-resistant (MRSA) aeruginosa. wide disparities between treated actually highlights substantial patients. Antibiotic overuse driven uncertainty around course infectious disease, extrapolation experiences [23.Chertow D.S. Memoli M.J. grand rounds review.JAMA. 2013; 309: 275-282Crossref (315) surge lack effective therapies SARS-CoV-2. As knowledge grows, factors essential so can target high-risk Advanced age comorbidities, chronic kidney diabetes, heart some Leukocytosis two largest studies, white blood cell (WBC) counts higher compared (median approximately 10.0×109 11.3×109 cells/μl versus 7×109 cells/μl, respectively) Scholar,14.Wang Wang colleagues absolute neutrophil count 9.2×109 5.5×109 (P <0.0001) [14.Wang Vaughn procalcitonin levels leukocytosis, neutrophilia, elevated do sufficient sensitivity, specificity, positive predictive value accurately diagnose stand-alone al. level >0.5 ng/ml 9.3% Conversely, negative values WBC <8.8×109 <6.8×109 ≤0.5 ≥98%. While overall rare they 6–29% Scholar,22.Elabbadi Scholar,24.Kolenda al.Assessment 2-positive units using conventional culture BioFire, FilmArray Pneumonia Panel Plus Assay.Open 7ofaa484Crossref (42) 25.Soriano M.C. incidence co-infection, ICU-acquired COVID-19.J. 82: e20-e21Abstract (36) 26.Stevenson D.R. al.Improving stewardship critically-ill COVID-19.Clin. October 11, https://doi.org/10.1093/cid/ciaa1559)Crossref (5) 27.Contou D. French ICU.Ann. Intensive Care. 10: 119Crossref (199) 28.Dudoignon E. patients: case series.Clin. 72: 905-906Crossref (64) may related increasing cultures [17.Hughes likely Scholar,29.Caméléna F. al.Performance multiplex polymerase chain reaction panel identifying causing COVID-19.Diagn. 99115183Crossref Scholar,30.Rothe K. al.Rates light stewardship.Eur. Clin. 859-869Crossref (83) Clinicians face difficult challenge deciding treat Figure illustrates recommended approach diagnosing management recommend pursing microbiologic initiating ill, severely immunocompromised, coinfection. warranted, we β-lactam when coverage bacteria, and/or MRSA warranted. Studies demonstrated 1.2–4.2% 2) Scholar,17.Hughes Scholar,19.Adler at least half represent skin contaminants 31.Sepulveda al.Bacteremia utilization City.J. 58e00875-20Crossref (128) 32.Yu bloodstream contamination rates COVID-19.PLoS One. 15e0242533Crossref (37) perhaps part due technical challenges healthcare personnel collecting while wearing personal protective equipment (PPE) required Hospitals City (NYC) noted peak analyzed same time previous year, times overwhelmed capacity instruments [31.Sepulveda Moreover, shown lower [32.Yu initiation therapy, routinely ordered Instead, selectively suspicion would include whom initiated.Table 2Yield Diagnostic Tests Coinfection Presenting COVID-19Blood cultures: contaminants.RefsYield pathogenYield contaminant[13.Vaughn Scholar]31/1063 (2.9%)Not reported[14.Wang Scholar]12/969 (1.2%)65/969 (6.7%)[17.Hughes Scholar]21/643 (

Язык: Английский

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Antibiotics in treatment of COVID-19 complications: a review of frequency, indications, and efficacy

Journal of Infection and Public Health, Год журнала: 2021, Номер 14(5), С. 570 - 576

Опубликована: Фев. 9, 2021

To report available information in the literature regarding frequency, indications, types of antibiotic usage, duration, and their efficacy Covid-19 infected patients. The search was conducted on April 30 May 7, 2020, using Ovid database Google search. Patients' characteristics, clinical outcomes, as well selected characteristics use (indication, class used, rates bacterial secondary co-infection, duration treatment) were analyzed. Nineteen studies reporting data from 2834 patients included. Mean rate 74.0 % cases. Half reported occurrence a co-infection or complication (10 studies). Amongst latter, at least 17.6 who received antibiotics had infections. Pooled 4 show that half receiving not severe nor critical. Detailed lack most articles. present review found major amongst hospitalized patients, mainly an empirical setting. There is no proven this practice. Further research to determine relevant indications for critical view significant mortality associated with infections these rising antimicrobial resistance.

Язык: Английский

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Few bacterial co-infections but frequent empiric antibiotic use in the early phase of hospitalized patients with COVID-19: results from a multicentre retrospective cohort study in The Netherlands

Infectious Diseases, Год журнала: 2020, Номер 53(2), С. 102 - 110

Опубликована: Окт. 24, 2020

Background Knowledge on bacterial co-infections in COVID-19 is crucial to use antibiotics appropriately. Therefore, we aimed determine the incidence of co-infections, antibiotic and application antimicrobial stewardship principles hospitalized patients with COVID-19.Methods We performed a retrospective observational study four hospitals (1 university, 2 non-university teaching, 1 non-teaching hospital) Netherlands from March May 2020 including consecutive PCR-confirmed COVID-19. Data first microbiological investigations obtained at discretion physician week hospital admission were collected.Results Twelve (1.2%) 925 included had documented co-infection (75.0% pneumonia) within week. Microbiological testing was 749 (81%) patients: sputum cultures 105 (11.4%), blood 711 (76.9%), pneumococcal urinary antigen 202 (21.8%), Legionella 199 (21.5%) patients, clear variation between hospitals. On presentation 556 (60.1%; range 33.3–73.4%) received for median duration days (IQR 1–4). Intravenous oral switch 41 413 (9.9%) who intravenous treatment >48 h. Mean adherence local guideline empiric therapy day average 60.3% (range 45.3%–74.7%).Conclusions are rare, while abundant. This implies that should be withheld. has potential dramatically reduce current overuse pandemic.

Язык: Английский

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Economic Burden of COVID-19: A Systematic Review

ClinicoEconomics and Outcomes Research, Год журнала: 2022, Номер Volume 14, С. 293 - 307

Опубликована: Апрель 1, 2022

Objective: To review and qualitatively synthesize the evidence related to economic burden of COVID-19, including healthcare resource utilization costs. Methods: A systematic studies that assessed [eg, direct costs, productivity, macroeconomic impact due non-pharmaceutical interventions (NPIs) equity] COVID-19 was conducted by searches in EMBASE, MEDLINE, MEDLINE-IN-PROCESS, The Cochrane Library, as well manual unpublished research for period between January 2020 February 2021. Single reviewer data extraction confirmed independently a second reviewer. Results: screening process resulted total 27 studies: 25 individual publications, 2 literature reviews, narrower scopes, fulfilled inclusion criteria. patients diagnosed with more severe were associated higher main drivers costs consistent across countries included ICU admission, in-hospital use such mechanical ventilation, which lead increase $2082.65 ± 345.04 $2990.76 545.98. most frequently reported indirect productivity losses. On average, older incurred when compared younger age groups. An estimation 20% infection rate based on Monte Carlo simulation United States led medical cost $163.4 billion over course pandemic. Conclusion: pandemic has generated considerable general population. Preventative measures NPIs only have partial success lowering Implementing additional preventative large-scale vaccination is vital reducing decreased GDP Keywords: covid-19, Impact, symptom Burden, health Economics, vaccines,

Язык: Английский

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Infectious Diseases Society of America Guidelines on the Treatment and Management of Patients With COVID-19 (September 2022)

Clinical Infectious Diseases, Год журнала: 2022, Номер 78(7), С. e250 - e349

Опубликована: Сен. 5, 2022

Abstract There are many pharmacologic therapies that being used or considered for treatment of coronavirus disease 2019 (COVID-19), with rapidly changing efficacy and safety evidence from trials. The objective was to develop evidence-based, rapid, living guidelines intended support patients, clinicians, other healthcare professionals in their decisions about management patients COVID-19. In March 2020, the Infectious Diseases Society America (IDSA) formed a multidisciplinary guideline panel infectious pharmacists, methodologists varied areas expertise regularly review make recommendations persons process approach followed rapid recommendation development checklist. prioritized questions outcomes. A systematic peer-reviewed grey literature conducted at regular intervals. Grading Recommendations Assessment, Development, Evaluation (GRADE) assess certainty recommendations. Based on most recent search 31 May 2022, IDSA has made 32 following groups/populations: pre- postexposure prophylaxis, ambulatory mild-to-moderate disease, hospitalized mild-to-moderate, severe but not critical, critical disease. As these guidelines, can be found online at: https://idsociety.org/COVID19guidelines. At inception its work, expressed overarching goal recruited into ongoing Since then, trials were provided much-needed COVID-19 therapies. still remain unanswered as pandemic evolved, which we hope future answer.

Язык: Английский

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Fighting Antibiotic Resistance in Hospital-Acquired Infections: Current State and Emerging Technologies in Disease Prevention, Diagnostics and Therapy

Frontiers in Microbiology, Год журнала: 2021, Номер 12

Опубликована: Июль 21, 2021

Rising antibiotic resistance is a global threat that projected to cause more deaths than all cancers combined by 2050. In this review, we set summarize the current state of resistance, and give an overview emerging technologies aimed escape pre-antibiotic era recurrence. We conducted comprehensive literature survey &gt;150 original research review articles indexed in Web Science using “antimicrobial resistance,” “diagnostics,” “therapeutics,” “disinfection,” “nosocomial infections,” “ESKAPE pathogens” as key words. discuss impact nosocomial infections on spread multi-drug resistant bacteria, over existing developing strategies for faster diagnostics infectious diseases, novel approaches therapy finally hospital disinfection prevent MDR bacteria spread.

Язык: Английский

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