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Article ; Online: High prevalence group testing in epidemiology with geometrically inspired algorithms.

Schenk, Hannes / Caf, Yasemin / Knabl, Ludwig / Mayerhofer, Christoph / Rauch, Wolfgang

2023 Volume 13, Issue 1, Page(s) 18910

Abstract: Demand for mass surveillance during peak times of the SARS-CoV-2 pandemic caused high workload for clinical laboratories. Efficient and cost conserving testing designs by means of group testing can substantially reduce resources during possible future ... ...

Abstract	Demand for mass surveillance during peak times of the SARS-CoV-2 pandemic caused high workload for clinical laboratories. Efficient and cost conserving testing designs by means of group testing can substantially reduce resources during possible future emergency situations. The novel hypercube algorithm proposed by Mutesa et al. 2021 published in Nature provides methodological proof of concept and points out the applicability to epidemiological testing. In this work, the algorithm is explored and expanded for settings with high group prevalence. Numerical studies investigate the limits of the adapted hypercube methodology, allowing to optimize pooling designs for specific requirements (i.e. number of samples and group prevalence). Hyperparameter optimization is performed to maximize test-reduction. Standard deviation is examined to investigate resilience and precision. Moreover, empirical validation was performed by elaborately pooling SARS-CoV-2 virus samples according to numerically optimized pooling designs. Laboratory experiments with SARS-CoV-2 sample groups, ranging from 50 to 200 items, characterized by group prevalence up to 10%, are successfully processed and analysed. Test-reductions from 50 to 72.5% were achieved in the experimental setups when compared to individual testing. Higher theoretical test-reduction is possible, depending on the number of samples and the group prevalence, indicated by simulation results.
MeSH term(s)	Prevalence ; SARS-CoV-2 ; Algorithms ; Clinical Laboratory Services ; Computer Simulation
Language	English
Publishing date	2023-11-02
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-023-45639-6
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Antifungal susceptibility testing in

Knabl, Ludwig / Lass-Flörl, Cornelia

Expert review of anti-infective therapy

2020 Volume 18, Issue 8, Page(s) 779–787

Abstract: Introduction: Invasive fungal diseases (IFDs) have received attention as an emerging public health threat, are difficult to diagnose and to treat, and are associated with substantial morbidity and mortality. The standard of care in IFD management ... ...

Abstract	Introduction: Invasive fungal diseases (IFDs) have received attention as an emerging public health threat, are difficult to diagnose and to treat, and are associated with substantial morbidity and mortality. The standard of care in IFD management requires an early and targeted antifungal treatment, hence covers - amongst others - species identification and antifungal susceptibility testing (AFST). Areas covered: This review gives an overview of methods currently applied in AFST and highlights promising new tools for shortening the turnaround time focusing on Expert opinion: The performance of the broth microdilution reference methods for AFST is not suitable for daily laboratory practice as they are too labor-intensive and time-consuming. Other conventional approaches such as disk diffusion assays, epsilometer tests, colorimetric or automated approaches are easier in handling, and in part, show good correlations with the reference methods. Promising results for shortening the turnaround time in providing MIC data or resistance detection include matrix-assisted laser desorption/ionization-time of flight mass spectrometer (MALDI-TOF MS) assisted AFST, molecular-based techniques and modified conventional approaches applying direct inoculation methods. These underlying AFST concepts are promising but in part completely different, have their own advantages and disadvantages, and need further clinical validation.
MeSH term(s)	Antifungal Agents/pharmacology ; Candida/drug effects ; Candida/isolation & purification ; Candidiasis, Invasive/diagnosis ; Candidiasis, Invasive/drug therapy ; Candidiasis, Invasive/microbiology ; Drug Resistance, Fungal ; Humans ; Microbial Sensitivity Tests ; Time Factors
Chemical Substances	Antifungal Agents
Language	English
Publishing date	2020-05-05
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2181279-2
ISSN	1744-8336 ; 1478-7210
ISSN (online)	1744-8336
ISSN	1478-7210
DOI	10.1080/14787210.2020.1760841
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Article ; Online: Neutralization Profile after Recovery from SARS-CoV-2 Omicron Infection.

Rössler, Annika / Knabl, Ludwig / von Laer, Dorothee / Kimpel, Janine

The New England journal of medicine

2022 Volume 386, Issue 18, Page(s) 1764–1766

MeSH term(s)	Antibodies, Neutralizing/immunology ; Antibodies, Viral/immunology ; COVID-19/immunology ; Humans ; SARS-CoV-2/immunology
Chemical Substances	Antibodies, Neutralizing ; Antibodies, Viral
Language	English
Publishing date	2022-03-23
Publishing country	United States
Document type	Letter
ZDB-ID	207154-x
ISSN	1533-4406 ; 0028-4793
ISSN (online)	1533-4406
ISSN	0028-4793
DOI	10.1056/NEJMc2201607
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Article ; Online: High prevalence group testing in epidemiology with geometrically inspired algorithms

Hannes Schenk / Yasemin Caf / Ludwig Knabl / Christoph Mayerhofer / Wolfgang Rauch

Scientific Reports, Vol 13, Iss 1, Pp 1-

2023 Volume 9

Abstract: Abstract Demand for mass surveillance during peak times of the SARS-CoV-2 pandemic caused high workload for clinical laboratories. Efficient and cost conserving testing designs by means of group testing can substantially reduce resources during possible ... ...

Abstract	Abstract Demand for mass surveillance during peak times of the SARS-CoV-2 pandemic caused high workload for clinical laboratories. Efficient and cost conserving testing designs by means of group testing can substantially reduce resources during possible future emergency situations. The novel hypercube algorithm proposed by Mutesa et al. 2021 published in Nature provides methodological proof of concept and points out the applicability to epidemiological testing. In this work, the algorithm is explored and expanded for settings with high group prevalence. Numerical studies investigate the limits of the adapted hypercube methodology, allowing to optimize pooling designs for specific requirements (i.e. number of samples and group prevalence). Hyperparameter optimization is performed to maximize test-reduction. Standard deviation is examined to investigate resilience and precision. Moreover, empirical validation was performed by elaborately pooling SARS-CoV-2 virus samples according to numerically optimized pooling designs. Laboratory experiments with SARS-CoV-2 sample groups, ranging from 50 to 200 items, characterized by group prevalence up to 10%, are successfully processed and analysed. Test-reductions from 50 to 72.5% were achieved in the experimental setups when compared to individual testing. Higher theoretical test-reduction is possible, depending on the number of samples and the group prevalence, indicated by simulation results.
Keywords	Medicine ; R ; Science ; Q
Subject code	000
Language	English
Publishing date	2023-11-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Expression of Tissue Factor and Platelet/Leukocyte Markers on Extracellular Vesicles Reflect Platelet-Leukocyte Interaction in Severe COVID-19.

Eichhorn, Tanja / Weiss, René / Huber, Silke / Ebeyer-Masotta, Marie / Mostageer, Marwa / Emprechtinger, Robert / Knabl, Ludwig / Knabl, Ludwig / Würzner, Reinhard / Weber, Viktoria

International journal of molecular sciences

2023 Volume 24, Issue 23

Abstract: Severe COVID-19 is frequently associated with thromboembolic complications. Increased platelet activation and platelet-leukocyte aggregate formation can amplify thrombotic responses by inducing tissue factor (TF) expression on leukocytes. Here, we ... ...

Abstract	Severe COVID-19 is frequently associated with thromboembolic complications. Increased platelet activation and platelet-leukocyte aggregate formation can amplify thrombotic responses by inducing tissue factor (TF) expression on leukocytes. Here, we characterized TF-positive extracellular vesicles (EVs) and their cellular origin in 12 patients suffering from severe COVID-19 (time course, 134 samples overall) and 25 healthy controls. EVs exposing phosphatidylserine (PS) were characterized by flow cytometry. Their cellular origin was determined by staining with anti-CD41, anti-CD45, anti-CD235a, and anti-CD105 as platelet, leukocyte, red blood cell, and endothelial markers. We further investigated the association of EVs with TF, platelet factor 4 (PF4), C-reactive protein (CRP), and high mobility group box-1 protein (HMGB-1). COVID-19 patients showed higher levels of PS-exposing EVs compared to controls. The majority of these EVs originated from platelets. A higher amount of EVs in patient samples was associated with CRP, HMGB-1, PF4, and TF as compared to EVs from healthy donors. In COVID-19 samples, 16.5% of all CD41
MeSH term(s)	Humans ; Blood Platelets/metabolism ; COVID-19/metabolism ; Extracellular Vesicles/metabolism ; HMGB Proteins/metabolism ; Leukocytes/metabolism ; Thromboplastin/metabolism
Chemical Substances	HMGB Proteins ; Thromboplastin (9035-58-9) ; F3 protein, human
Language	English
Publishing date	2023-11-28
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms242316886
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Article: Robust immune response to the BNT162b mRNA vaccine in an elderly population vaccinated 15 months after recovery from COVID-19.

Lee, Hye Kyung / Knabl, Ludwig / Knabl, Ludwig / Kapferer, Sebastian / Pateter, Birgit / Walter, Mary / Furth, Priscilla A / Hennighausen, Lothar

medRxiv : the preprint server for health sciences

2021

Abstract: Knowledge about the impact of prior SARS-CoV-2 infection of the elderly on mRNA vaccination response is needed to appropriately address the need for booster vaccination in this vulnerable population. To address this, we investigated antibody and genomic ... ...

Abstract	Knowledge about the impact of prior SARS-CoV-2 infection of the elderly on mRNA vaccination response is needed to appropriately address the need for booster vaccination in this vulnerable population. To address this, we investigated antibody and genomic immune responses in 16 elderly (avg. 81 yrs.) individuals that had received a single booster dose of BNT162b vaccine 15 months after recovering from COVID-19. Spike-specific IgG antibody levels increased in each of the study participants from an average of 710 U/ml prior to the vaccination to more than 40,000 U/ml within ten weeks after the vaccination. In contrast, anti-spike-specific IgG antibody levels averaged 2,190 U/ml in 14 healthy SARS-CoV-2-naïve individuals (avg. 58 yrs.) ten weeks after the second dose of BNT162b. RNA-seq conducted on PBMCs demonstrated the activation of interferon-activated genetic programs in both cohorts within one day. Unlike their transient induction in the younger naïve population, persistent activity and the initiation of additional cell cycle regulated programs were obtained in the older COVID-19 recovered population. Here we show that the elderly, a high-risk population, can mount a strong antibody and a persistent molecular immune response upon receiving a single dose of mRNA vaccine 15 months after recovery from COVID-19.
Language	English
Publishing date	2021-09-12
Publishing country	United States
Document type	Preprint
DOI	10.1101/2021.09.08.21263284
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Article ; Online: Durability of Cross-Neutralizing Antibodies 5.5 Months After Bivalent Coronavirus Disease 2019 Vaccine Booster.

Rössler, Annika / Knabl, Ludwig / Netzl, Antonia / Bante, David / Borena, Wegene / von Laer, Dorothee / Smith, Derek J / Kimpel, Janine

The Journal of infectious diseases

2023 Volume 229, Issue 3, Page(s) 644–647

Abstract: We analyzed neutralizing antibodies in samples from ancestral + BA.1 and ancestral + BA.4/5 boosted individuals, collected around 5.5 months after booster. Titers of neutralizing antibodies generally decreased compared to a time point early after the ... ...

Abstract	We analyzed neutralizing antibodies in samples from ancestral + BA.1 and ancestral + BA.4/5 boosted individuals, collected around 5.5 months after booster. Titers of neutralizing antibodies generally decreased compared to a time point early after the bivalent booster immunization. This was more pronounced for individuals without infection history and for recently emerged Omicron variants.
MeSH term(s)	Humans ; Broadly Neutralizing Antibodies ; COVID-19 Vaccines ; COVID-19/prevention & control ; SARS-CoV-2 ; Antibodies, Neutralizing ; Antibodies, Viral
Chemical Substances	Broadly Neutralizing Antibodies ; COVID-19 Vaccines ; Antibodies, Neutralizing ; Antibodies, Viral
Language	English
Publishing date	2023-11-28
Publishing country	United States
Document type	Journal Article
ZDB-ID	3019-3
ISSN	1537-6613 ; 0022-1899
ISSN (online)	1537-6613
ISSN	0022-1899
DOI	10.1093/infdis/jiad472
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Article ; Online: Limited cross-variant immune response from SARS-CoV-2 Omicron BA.2 in naïve but not previously infected outpatients.

Lee, Hye Kyung / Knabl, Ludwig / Walter, Mary / Furth, Priscilla A / Hennighausen, Lothar

iScience

2022 Volume 25, Issue 11, Page(s) 105369

Abstract: Omicron is currently the dominant SARS-CoV-2 variant and several sublineages have emerged. Questions remain about the impact of previous SARS-CoV-2 exposure on cross-variant immune responses elicited by the SARS-CoV-2 Omicron sublineage BA.2 compared to ... ...

Abstract	Omicron is currently the dominant SARS-CoV-2 variant and several sublineages have emerged. Questions remain about the impact of previous SARS-CoV-2 exposure on cross-variant immune responses elicited by the SARS-CoV-2 Omicron sublineage BA.2 compared to BA.1. Here we show that without previous history of COVID-19, BA.2 infection induces a reduced immune response against all variants of concern (VOC) compared to BA.1 infection. The absence of ACE2 binding in sera of previously naïve BA.1 and BA.2 patients indicates a lack of meaningful neutralization. In contrast, anti-spike antibody levels and neutralizing activity greatly increased in the BA.1 and BA.2 patients with a previous history of COVID-19. Transcriptome analyses of peripheral immune cells showed significant differences in immune response and specific antibody generation between BA.1 and BA.2 patients as well as significant differences in the expression of specific immune genes. In summary, prior infection status significantly impacts the innate and adaptive immune response against VOC following BA.2 infection.
Language	English
Publishing date	2022-10-14
Publishing country	United States
Document type	Journal Article
ISSN	2589-0042
ISSN (online)	2589-0042
DOI	10.1016/j.isci.2022.105369
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Article: Limited cross-variant immune response from SARS-CoV-2 Omicron BA.2 in naïve but not previously infected outpatients.

Lee, Hye Kyung / Knabl, Ludwig / Walter, Mary / Furth, Priscilla A / Hennighausen, Lothar

medRxiv : the preprint server for health sciences

2022

Abstract: Omicron is currently the dominant SARS-CoV-2 variant and several sublineages have emerged. Questions remain about the impact of previous SARS-CoV-2 exposure on cross-variant immune responses elicited by BA.2 infection compared to BA.1. Here we show that ... ...

Abstract	Omicron is currently the dominant SARS-CoV-2 variant and several sublineages have emerged. Questions remain about the impact of previous SARS-CoV-2 exposure on cross-variant immune responses elicited by BA.2 infection compared to BA.1. Here we show that without previous history of COVID-19, BA.2 infection induces a reduced immune response against all variants of concern (VOC) compared to BA.1 infection. The absence of ACE2 binding in sera of previously naïve BA.1 and BA.2 patients indicates a lack of meaningful neutralization. In contrast, anti-spike antibody levels and neutralizing activity greatly increased in the BA.1 and BA.2 patients with a previous history of COVID-19. Transcriptome analyses of peripheral immune cells showed significant differences in immune response and specific antibody generation between BA.1 and BA.2 patients as well as significant differences in expression of specific immune genes. In summary, prior infection status significantly impacts the innate and adaptive immune response against VOC following BA.2 infection.
Language	English
Publishing date	2022-05-26
Publishing country	United States
Document type	Preprint
DOI	10.1101/2022.04.07.22273565
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Article: Machine Learning to Identify Critical Biomarker Profiles in New SARS-CoV-2 Variants.

Schatz, Christoph / Knabl, Ludwig / Lee, Hye Kyung / Seeboeck, Rita / von Laer, Dorothee / Lafon, Eliott / Borena, Wegene / Mangge, Harald / Prüller, Florian / Qerimi, Adelina / Wilflingseder, Doris / Posch, Wilfried / Haybaeck, Johannes

Microorganisms

2024 Volume 12, Issue 4

Abstract: The global dissemination of SARS-CoV-2 resulted in the emergence of several variants, including Alpha, Alpha + E484K, Beta, and Omicron. Our research integrated the study of eukaryotic translation factors and fundamental components in general protein ... ...

Abstract	The global dissemination of SARS-CoV-2 resulted in the emergence of several variants, including Alpha, Alpha + E484K, Beta, and Omicron. Our research integrated the study of eukaryotic translation factors and fundamental components in general protein synthesis with the analysis of SARS-CoV-2 variants and vaccination status. Utilizing statistical methods, we successfully differentiated between variants in infected individuals and, to a lesser extent, between vaccinated and non-vaccinated infected individuals, relying on the expression profiles of translation factors. Additionally, our investigation identified common causal relationships among the translation factors, shedding light on the interplay between SARS-CoV-2 variants and the host's translation machinery.
Language	English
Publishing date	2024-04-15
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2720891-6
ISSN	2076-2607
ISSN	2076-2607
DOI	10.3390/microorganisms12040798
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