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Article ; Online: Non-invasive saliva specimens for the diagnosis of COVID-19: caution in mild outpatient cohorts with low prevalence.

Skolimowska, Keira / Rayment, Michael / Jones, Rachael / Madona, Pinglawathee / Moore, Luke S P / Randell, Paul

Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases

2020 Volume 26, Issue 12, Page(s) 1711–1713

MeSH term(s)	Acute Disease ; Adult ; COVID-19/diagnosis ; COVID-19 Nucleic Acid Testing ; Cross-Sectional Studies ; Female ; Humans ; Male ; Middle Aged ; Oropharynx/virology ; Outpatients/statistics & numerical data ; Predictive Value of Tests ; Prevalence ; Prospective Studies ; SARS-CoV-2 ; Saliva/virology ; Sensitivity and Specificity ; United Kingdom ; Viral Load
Keywords	covid19
Language	English
Publishing date	2020-07-18
Publishing country	England
Document type	Letter
ZDB-ID	1328418-6
ISSN	1469-0691 ; 1470-9465 ; 1198-743X
ISSN (online)	1469-0691
ISSN	1470-9465 ; 1198-743X
DOI	10.1016/j.cmi.2020.07.015
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Article ; Online: Reply to Dudoignon et al.

Rawson, Timothy M / Moore, Luke S P / Zhu, Nina / Ranganathan, Nishanthy / Skolimowska, Keira / Gilchrist, Mark / Satta, Giovanni / Cooke, Graham / Holmes, Alison

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

2020 Volume 72, Issue 5, Page(s) 906–908

MeSH term(s)	Anti-Infective Agents ; COVID-19 ; Coinfection ; Coronavirus ; Humans ; SARS-CoV-2
Chemical Substances	Anti-Infective Agents
Language	English
Publishing date	2020-06-16
Publishing country	United States
Document type	Letter ; Research Support, Non-U.S. Gov't ; Comment
ZDB-ID	1099781-7
ISSN	1537-6591 ; 1058-4838
ISSN (online)	1537-6591
ISSN	1058-4838
DOI	10.1093/cid/ciaa767
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Zs.A 1505: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 480: Show issues

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Article ; Online: Bacterial and Fungal Coinfection in Individuals With Coronavirus: A Rapid Review To Support COVID-19 Antimicrobial Prescribing.

Rawson, Timothy M / Moore, Luke S P / Zhu, Nina / Ranganathan, Nishanthy / Skolimowska, Keira / Gilchrist, Mark / Satta, Giovanni / Cooke, Graham / Holmes, Alison

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

2020 Volume 71, Issue 9, Page(s) 2459–2468

Abstract: Background: To explore and describe the current literature surrounding bacterial/fungal coinfection in patients with coronavirus infection.: Methods: MEDLINE, EMBASE, and Web of Science were searched using broad-based search criteria relating to ... ...

Abstract	Background: To explore and describe the current literature surrounding bacterial/fungal coinfection in patients with coronavirus infection. Methods: MEDLINE, EMBASE, and Web of Science were searched using broad-based search criteria relating to coronavirus and bacterial coinfection. Articles presenting clinical data for patients with coronavirus infection (defined as SARS-1, MERS, SARS-CoV-2, and other coronavirus) and bacterial/fungal coinfection reported in English, Mandarin, or Italian were included. Data describing bacterial/fungal coinfections, treatments, and outcomes were extracted. Secondary analysis of studies reporting antimicrobial prescribing in SARS-CoV-2 even in absence of coinfection was performed. Results: 1007 abstracts were identified. Eighteen full texts reporting bacterial/fungal coinfection were included. Most studies did not identify or report bacterial/fungal coinfection (85/140; 61%). Nine of 18 (50%) studies reported on COVID-19, 5/18 (28%) on SARS-1, 1/18 (6%) on MERS, and 3/18 (17%) on other coronaviruses. For COVID-19, 62/806 (8%) patients were reported as experiencing bacterial/fungal coinfection during hospital admission. Secondary analysis demonstrated wide use of broad-spectrum antibacterials, despite a paucity of evidence for bacterial coinfection. On secondary analysis, 1450/2010 (72%) of patients reported received antimicrobial therapy. No antimicrobial stewardship interventions were described. For non-COVID-19 cases, bacterial/fungal coinfection was reported in 89/815 (11%) of patients. Broad-spectrum antibiotic use was reported. Conclusions: Despite frequent prescription of broad-spectrum empirical antimicrobials in patients with coronavirus-associated respiratory infections, there is a paucity of data to support the association with respiratory bacterial/fungal coinfection. Generation of prospective evidence to support development of antimicrobial policy and appropriate stewardship interventions specific for the COVID-19 pandemic is urgently required.
MeSH term(s)	Anti-Infective Agents/therapeutic use ; Antimicrobial Stewardship ; Bacterial Infections/drug therapy ; Bacterial Infections/epidemiology ; Bacterial Infections/microbiology ; COVID-19/drug therapy ; COVID-19/epidemiology ; COVID-19/microbiology ; Coinfection/drug therapy ; Coinfection/epidemiology ; Coinfection/microbiology ; Drug Resistance, Microbial ; Humans ; Mycoses/drug therapy ; Mycoses/epidemiology ; Mycoses/microbiology ; SARS-CoV-2/drug effects
Chemical Substances	Anti-Infective Agents
Keywords	covid19
Language	English
Publishing date	2020-04-27
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1099781-7
ISSN	1537-6591 ; 1058-4838
ISSN (online)	1537-6591
ISSN	1058-4838
DOI	10.1093/cid/ciaa530
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Article: Non-invasive saliva specimens for the diagnosis of COVID-19: caution in mild outpatient cohorts with low prevalence

Skolimowska, Keira / Rayment, Michael / Jones, Rachael / Madona, Pinglawathee / Moore, Luke S P / Randell, Paul

Clin. microbiol. infect

Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #653313
Database	COVID19

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Article ; Online: Non-invasive saliva specimens for the diagnosis of COVID-19

Skolimowska, Keira / Rayment, Michael / Jones, Rachael / Madona, Pinglawathee / Moore, Luke S.P. / Randell, Paul

Clinical Microbiology and Infection ; ISSN 1198-743X

caution in mild outpatient cohorts with low prevalence

2020

Keywords	Microbiology (medical) ; Infectious Diseases ; General Medicine ; covid19
Language	English
Publisher	Elsevier BV
Publishing country	us
Document type	Article ; Online
DOI	10.1016/j.cmi.2020.07.015
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Supervised machine learning to support the diagnosis of bacterial infection in the context of COVID-19.

Rawson, Timothy M / Hernandez, Bernard / Wilson, Richard C / Ming, Damien / Herrero, Pau / Ranganathan, Nisha / Skolimowska, Keira / Gilchrist, Mark / Satta, Giovanni / Georgiou, Pantelis / Holmes, Alison H

JAC-antimicrobial resistance

2021 Volume 3, Issue 1, Page(s) dlab002

Abstract: Background: Bacterial infection has been challenging to diagnose in patients with COVID-19. We developed and evaluated supervised machine learning algorithms to support the diagnosis of secondary bacterial infection in hospitalized patients during the ... ...

Abstract	Background: Bacterial infection has been challenging to diagnose in patients with COVID-19. We developed and evaluated supervised machine learning algorithms to support the diagnosis of secondary bacterial infection in hospitalized patients during the COVID-19 pandemic. Methods: Inpatient data at three London hospitals for the first COVD-19 wave in March and April 2020 were extracted. Demographic, blood test and microbiology data for individuals with and without SARS-CoV-2-positive PCR were obtained. A Gaussian Naive Bayes, Support Vector Machine (SVM) and Artificial Neural Network were trained and compared using the area under the receiver operating characteristic curve (AUCROC). The best performing algorithm (SVM with 21 blood test variables) was prospectively piloted in July 2020. AUCROC was calculated for the prediction of a positive microbiological sample within 48 h of admission. Results: A total of 15 599 daily blood profiles for 1186 individual patients were identified to train the algorithms; 771/1186 (65%) individuals were SARS-CoV-2 PCR positive. Clinically significant microbiology results were present for 166/1186 (14%) patients during admission. An SVM algorithm trained with 21 routine blood test variables and over 8000 individual profiles had the best performance. AUCROC was 0.913, sensitivity 0.801 and specificity 0.890. Prospective testing on 54 patients on admission (28/54, 52% SARS-CoV-2 PCR positive) demonstrated an AUCROC of 0.960 (95% CI: 0.90-1.00). Conclusions: An SVM using 21 routine blood test variables had excellent performance at inferring the likelihood of positive microbiology. Further prospective evaluation of the algorithms ability to support decision making for the diagnosis of bacterial infection in COVID-19 cohorts is underway.
Language	English
Publishing date	2021-02-03
Publishing country	England
Document type	Journal Article
ISSN	2632-1823
ISSN (online)	2632-1823
DOI	10.1093/jacamr/dlab002
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Bacterial and fungal co-infection in individuals with coronavirus: A rapid review to support COVID-19 antimicrobial prescribing

Rawson, Timothy M / Moore, Luke S P / Zhu, Nina / Ranganathan, Nishanthy / Skolimowska, Keira / Gilchrist, Mark / Satta, Giovanni / Cooke, Graham / Holmes, Alison

Clin. infect. dis

Abstract: BACKGROUND: To explore and describe the current literature surrounding bacterial/fungal co-infection in patients with coronavirus infection. METHODS: MEDLINE, EMBASE, and Web of Science were searched using broad based search criteria relating to ... ...

Abstract	BACKGROUND: To explore and describe the current literature surrounding bacterial/fungal co-infection in patients with coronavirus infection. METHODS: MEDLINE, EMBASE, and Web of Science were searched using broad based search criteria relating to coronavirus and bacterial co-infection. Articles presenting clinical data for patients with coronavirus infection (defined as SARS-1, MERS, SARS-COV-2, and other coronavirus) and bacterial/fungal co-infection reported in English, Mandarin, or Italian were included. Data describing bacterial/fungal co-infections, treatments, and outcomes were extracted. Secondary analysis of studies reporting antimicrobial prescribing in SARS-COV-2 even in the absence of co-infection was performed. RESULTS: 1007 abstracts were identified. Eighteen full texts reported bacterial/fungal co-infection were included. Most studies did not identify or report bacterial/fungal coinfection (85/140;61%). 9/18 (50%) studies reported on COVID-19, 5/18 (28%) SARS-1, 1/18 (6%) MERS, and 3/18 (17%) other coronavirus.For COVID-19, 62/806 (8%) patients were reported as experiencing bacterial/fungal co-infection during hospital admission. Secondary analysis demonstrated wide use of broad-spectrum antibacterials, despite a paucity of evidence for bacterial coinfection. On secondary analysis, 1450/2010 (72%) of patients reported received antimicrobial therapy. No antimicrobial stewardship interventions were described.For non-COVID-19 cases bacterial/fungal co-infection was reported in 89/815 (11%) of patients. Broad-spectrum antibiotic use was reported. CONCLUSIONS: Despite frequent prescription of broad-spectrum empirical antimicrobials in patients with coronavirus associated respiratory infections, there is a paucity of data to support the association with respiratory bacterial/fungal co-infection. Generation of prospective evidence to support development of antimicrobial policy and appropriate stewardship interventions specific for the COVID-19 pandemic are urgently required.
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #154974
Database	COVID19

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Article ; Online: Bacterial and Fungal Coinfection in Individuals With Coronavirus

Rawson, Timothy M / Moore, Luke S P / Zhu, Nina / Ranganathan, Nishanthy / Skolimowska, Keira / Gilchrist, Mark / Satta, Giovanni / Cooke, Graham / Holmes, Alison

Clinical Infectious Diseases ; ISSN 1058-4838 1537-6591

A Rapid Review To Support COVID-19 Antimicrobial Prescribing

2020

Abstract: Abstract Background To explore and describe the current literature surrounding bacterial/fungal coinfection in patients with coronavirus infection. Methods MEDLINE, EMBASE, and Web of Science were searched using broad-based search criteria relating to ... ...

Abstract	Abstract Background To explore and describe the current literature surrounding bacterial/fungal coinfection in patients with coronavirus infection. Methods MEDLINE, EMBASE, and Web of Science were searched using broad-based search criteria relating to coronavirus and bacterial coinfection. Articles presenting clinical data for patients with coronavirus infection (defined as SARS-1, MERS, SARS-CoV-2, and other coronavirus) and bacterial/fungal coinfection reported in English, Mandarin, or Italian were included. Data describing bacterial/fungal coinfections, treatments, and outcomes were extracted. Secondary analysis of studies reporting antimicrobial prescribing in SARS-CoV-2 even in absence of coinfection was performed. Results 1007 abstracts were identified. Eighteen full texts reporting bacterial/fungal coinfection were included. Most studies did not identify or report bacterial/fungal coinfection (85/140; 61%). Nine of 18 (50%) studies reported on COVID-19, 5/18 (28%) on SARS-1, 1/18 (6%) on MERS, and 3/18 (17%) on other coronaviruses. For COVID-19, 62/806 (8%) patients were reported as experiencing bacterial/fungal coinfection during hospital admission. Secondary analysis demonstrated wide use of broad-spectrum antibacterials, despite a paucity of evidence for bacterial coinfection. On secondary analysis, 1450/2010 (72%) of patients reported received antimicrobial therapy. No antimicrobial stewardship interventions were described. For non–COVID-19 cases, bacterial/fungal coinfection was reported in 89/815 (11%) of patients. Broad-spectrum antibiotic use was reported. Conclusions Despite frequent prescription of broad-spectrum empirical antimicrobials in patients with coronavirus-associated respiratory infections, there is a paucity of data to support the association with respiratory bacterial/fungal coinfection. Generation of prospective evidence to support development of antimicrobial policy and appropriate stewardship interventions specific for the COVID-19 pandemic is urgently required.
Keywords	Microbiology (medical) ; Infectious Diseases ; covid19
Language	English
Publisher	Oxford University Press (OUP)
Publishing country	uk
Document type	Article ; Online
DOI	10.1093/cid/ciaa530
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Altered ratio of IFN-γ/IL-10 in patients with drug resistant Mycobacterium tuberculosis and HIV- Tuberculosis Immune Reconstitution Inflammatory Syndrome.

Skolimowska, Keira H / Rangaka, Molebogeng X / Meintjes, Graeme / Pepper, Dominique J / Seldon, Ronnett / Matthews, Kerryn / Wilkinson, Robert J / Wilkinson, Katalin A

PloS one

2012 Volume 7, Issue 10, Page(s) e46481

Abstract: We have described a clinical relationship between HIV-Tuberculosis Immune Reconstitution Inflammatory Syndrome (TB-IRIS) and anti-tubercular drug resistance. Here we studied the immune response of TB-IRIS patients from whom a drug-resistant (n = 11) or ... ...

Abstract	We have described a clinical relationship between HIV-Tuberculosis Immune Reconstitution Inflammatory Syndrome (TB-IRIS) and anti-tubercular drug resistance. Here we studied the immune response of TB-IRIS patients from whom a drug-resistant (n = 11) or drug-susceptible (n = 25) Mycobacterium tuberculosis (MTB) strain was isolated after presenting with TB-IRIS. ELISpot analysis and multiplex cytokine analysis of the supernatant collected from peripheral blood mononuclear cells stimulated overnight with the heat-killed H37Rv MTB laboratory strain was used. Although there was no statistical difference in IFN-gamma ELISpot responses between the two groups, the results point towards higher bacterial load in the drug-resistant patients, possibly due to failed therapy. The ratio between secreted IFN-gamma/IL-10 and IL-2/IL-10 was significantly lower in TB-IRIS patients in whom the cause of TB was a drug-resistant strain compared to those with a fully sensitive strain (p = 0.02). Since host immune responses are dependent on the bacterial load, we hypothesise that the impaired cytokine balance is likely to be caused by the poorly controlled bacterial growth in these patients.
MeSH term(s)	Adult ; Enzyme-Linked Immunosorbent Assay ; Female ; HIV Infections/blood ; Humans ; Immune Reconstitution Inflammatory Syndrome/blood ; Interferon-gamma/blood ; Interleukin-10/blood ; Male ; Tuberculosis, Multidrug-Resistant/blood
Chemical Substances	Interleukin-10 (130068-27-8) ; Interferon-gamma (82115-62-6)
Language	English
Publishing date	2012-10-10
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0046481
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Cytotoxic mediators in paradoxical HIV-tuberculosis immune reconstitution inflammatory syndrome.

Wilkinson, Katalin A / Walker, Naomi F / Meintjes, Graeme / Deffur, Armin / Nicol, Mark P / Skolimowska, Keira H / Matthews, Kerryn / Tadokera, Rebecca / Seldon, Ronnett / Maartens, Gary / Rangaka, Molebogeng X / Besra, Gurdyal S / Wilkinson, Robert J

Journal of immunology (Baltimore, Md. : 1950)

2015 Volume 194, Issue 4, Page(s) 1748–1754

Abstract: Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) frequently complicates combined antiretroviral therapy and antituberculosis therapy in HIV-1-coinfected tuberculosis patients. The immunopathological mechanisms underlying TB- ... ...

Abstract	Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) frequently complicates combined antiretroviral therapy and antituberculosis therapy in HIV-1-coinfected tuberculosis patients. The immunopathological mechanisms underlying TB-IRIS are incompletely defined, and improved understanding is required to derive new treatments and to reduce associated morbidity and mortality. We performed longitudinal and cross-sectional analyses of human PBMCs from paradoxical TB-IRIS patients and non-IRIS controls (HIV-TB-coinfected patients commencing antiretroviral therapy who did not develop TB-IRIS). Freshly isolated PBMC stimulated with heat-killed Mycobacterium tuberculosis H37Rv (hkH37Rv) were used for IFN-γ ELISPOT and RNA extraction. Stored RNA was used for microarray and RT-PCR, whereas corresponding stored culture supernatants were used for ELISA. Stored PBMC were used for perforin and granzyme B ELISPOT and flow cytometry. There were significantly increased IFN-γ responses to hkH37Rv in TB-IRIS, compared with non-IRIS PBMC (p = 0.035). Microarray analysis of hkH37Rv-stimulated PBMC indicated that perforin 1 was the most significantly upregulated gene, with granzyme B among the top five (log2 fold difference 3.587 and 2.828, respectively), in TB-IRIS. Downstream experiments using RT-PCR, ELISA, and ELISPOT confirmed the increased expression and secretion of perforin and granzyme B. Moreover, granzyme B secretion reduced in PBMC from TB-IRIS patients during corticosteroid treatment. Invariant NKT cell (CD3(+)Vα24(+)) proportions were higher in TB-IRIS patients (p = 0.004) and were a source of perforin. Our data implicate the granule exocytosis pathway in TB-IRIS pathophysiology. Further understanding of the immunopathogenesis of this condition will facilitate development of specific diagnostic and improved therapeutic options.
MeSH term(s)	Adult ; Coinfection ; Cross-Sectional Studies ; Enzyme-Linked Immunosorbent Assay ; Female ; Flow Cytometry ; Granzymes/biosynthesis ; Granzymes/immunology ; HIV Infections/complications ; HIV Infections/immunology ; Humans ; Immune Reconstitution Inflammatory Syndrome/etiology ; Immune Reconstitution Inflammatory Syndrome/immunology ; Interferon-gamma/biosynthesis ; Interferon-gamma/immunology ; Leukocytes, Mononuclear/immunology ; Longitudinal Studies ; Male ; Oligonucleotide Array Sequence Analysis ; Perforin/biosynthesis ; Perforin/immunology ; Real-Time Polymerase Chain Reaction ; Tuberculosis/complications ; Tuberculosis/immunology
Chemical Substances	Perforin (126465-35-8) ; Interferon-gamma (82115-62-6) ; Granzymes (EC 3.4.21.-)
Language	English
Publishing date	2015-01-14
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3056-9
ISSN	1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
ISSN (online)	1550-6606
ISSN	0022-1767 ; 1048-3233 ; 1047-7381
DOI	10.4049/jimmunol.1402105
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