CMMC: FPC_20_22_Cornely, Oliver A

Abstract

In patients, a variety of risk factors predispose for different invasive fungal infections. Common invasive fungal infections are invasive candidiasis, invasive aspergillosis, and mucormycosis. Patients with well-defined profound immunosuppression are at high risk for invasive aspergillosis and mucormycosis, whereas invasive candidiasis occurs in immunocompetent patients, too.
Current standard diagnostics for invasive fungal infections such as blood culture, bronchoalveolar lavage, tissue biopsies and serological assays are sensitive to errors, sometimes unspecific, invasive and often contraindicated. The lack of reliable diagnostics along with high mortality lead to complex treatment strategies by means of prophylaxis, fever-driven, diagnosis-driven, and targeted treatment approaches.
With the development of the antigen-reactive T cell assay a non-invasive diagnostic allows fast and valid identification of pathogens to genus and species level when standard tests remain negative or patients’ comorbidities forbid invasive diagnostics.
We use peripheral blood mononuclear cells (PBMCs) from patients’ full blood and challenge them with fungal lysates. If the PBMCs encounter a repetitive fungal challenge, we identify fungus-reactive CD4+ T cells in the patient’s blood via flow cytometry.
The current project is advanced to further bacterial and fungal pathogens for clinical diagnostics and to investigate the cellular immune response in cooperation with the AG Klinische Mikrobiomforschung (PD Dr. M. Vehreschild) and AG Immunologie der HIV-Infektion (PD Dr. C. Lehmann).

Clinical/medical relevance and sustainability in disease understanding

Invasive fungal infections are associated with high morbidity and mortality in immunosuppressed and immunocompetent patients. With the development of new diagnostic tools, we want to overcome the problem of false negative standard diagnostics to facilitate targeted treatment and thus improve patient outcome.We receive patient samples from multiple sites in Germany through our FungiResearch network (http://fungiresearch.uni-koeln.de) and act as the lab of the European Excellence Center of Medical Mycology (https://www.ecmm.info).

Publications as of June 2022

Blennow O, Salmanton-Garcia J, Nowak P, Itri F, Van Doesum J, Lopez-Garcia A, Farina F, Jaksic O, Pinczes LI, Bilgin YM, Falces-Romero I, Jimenez M, Ormazabal-Velez I, Weinbergerova B, Dulery R, Stojanoski Z, Lahmer T, Fernandez N, Hernandez-Rivas JA, Petzer V, De Jonge N, Glenthoj A, De Ramon C, Biernat MM, Fracchiolla N, Aujayeb A, Van Praet J, Schonlein M, Mendez GA, Cattaneo C, Guidetti A, Sciume M, Ammatuna E, Cordoba R, Garcia-Pouton N, Grafe S, Cabirta A, Wolf D, Nordlander A, Garcia-Sanz R, Delia M, Berg Venemyr C, Brones C, Di Blasi R, De Kort E, Meers S, Lamure S, Serrano L, Merelli M, Coppola N, Bergantim R, Besson C, Kohn M, Petiti J, Garcia-Vidal C, Dargenio M, Danion F, Machado M, Bailen-Almorox R, Hoenigl M, Dragonetti G, Chai LYA, Kho CS, Bonanni M, Lievin R, Marchesi F, Cornely OA, and Pagano L (2022). Outcome of infection with omicron SARS-CoV-2 variant in patients with hematological malignancies: An EPICOVIDEHA survey report. Am J Hematol. doi:10.1002/ajh.26626.

Marchesi F, Salmanton-Garcia J, Emarah Z, Piukovics K, Nucci M, Lopez-Garcia A, Racil Z, Farina F, Popova M, Zompi S, Audisio E, Ledoux MP, Verga L, Weinbergerova B, Szotkovski T, Da Silva MG, Fracchiolla N, De Jonge N, Collins G, Marchetti M, Magliano G, Garcia-Vidal C, Biernat MM, Van Doesum J, Machado M, Demirkan F, Al-Khabori M, Zak P, Visek B, Stoma I, Mendez GA, Maertens J, Khanna N, Espigado I, Dragonetti G, Fianchi L, Del Principe MI, Cabirta A, Ormazabal-Velez I, Jaksic O, Buquicchio C, Bonuomo V, Batinic J, Omrani AS, Lamure S, Finizio O, Fernandez N, Falces-Romero I, Blennow O, Bergantim R, Ali N, Win S, Van Praet J, Tisi MC, Shirinova A, Schonlein M, Prattes J, Piedimonte M, Petzer V, Navratil M, Kulasekararaj A, Jindra P, Sramek J, Glenthoj A, Fazzi R, De Ramon-Sanchez C, Cattaneo C, Calbacho M, Bahr NC, El-Ashwah S, Cordoba R, Hanakova M, Zambrotta G, Sciume M, Booth S, Rodrigues RN, Sacchi MV, Garcia-Pouton N, Martin-Gonzalez JA, Khostelidi S, Grafe S, Rahimli L, Ammatuna E, Busca A, Corradini P, Hoenigl M, Klimko N, Koehler P, Pagliuca A, Passamonti F, Cornely OA, and Pagano L (2022). COVID-19 in adult acute myeloid leukemia patients: a long-term followup study from the European Hematology Association survey (EPICOVIDEHA). Haematologica. doi:10.3324/haematol.2022.280847.

Mellinghoff SC, Thelen M, Bruns C, Garcia-Marquez M, Hartmann P, Lammertz T, Lehmann J, Nowag A, Stemler J, Wennhold K, Cornely OA, von Bergwelt-Baildon MS, and Schlosser HA (2022). T-cells of invasive candidiasis patients show patterns of T-cell-exhaustion suggesting checkpoint blockade as treatment option. J Infect84, 237-247. doi:10.1016/j.jinf.2021.12.009.

Pagano L, Salmanton-Garcia J, Marchesi F, Lopez-Garcia A, Lamure S, Itri F, Gomes-Silva M, Dragonetti G, Falces-Romero I, van Doesum J, Sili U, Labrador J, Calbacho M, Bilgin YM, Weinbergerova B, Serrano L, Ribera-Santa Susana JM, Malak S, Loureiro-Amigo J, Glenthoj A, Cordoba-Mascunano R, Nunes-Rodrigues R, Gonzalez-Lopez TJ, Karlsson LK, Jimenez-Lorenzo MJ, Hernandez-Rivas JA, Jaksic O, Racil Z, Busca A, Corradini P, Hoenigl M, Klimko N, Koehler P, Pagliuca A, Passamonti F, and Cornely OA (2022). COVID-19 in vaccinated adult patients with hematological malignancies: preliminary results from EPICOVIDEHA. Blood139, 1588-1592. doi:10.1182/blood.2021014124.

Seidel D, Simon M, Sprute R, Lubnow M, Evert K, Speer C, Seessle J, Khatamzas E, Merle U, Behrens C, Blau IW, Enghard P, Haas CS, Steinmann J, Kurzai O, and Cornely OA (2022). Results from a national survey on COVID-19-associated mucormycosis in Germany: 13 patients from six tertiary hospitals. Mycoses65, 103-109. doi:10.1111/myc.13379.

Grothe J, Sprute R, and Cornely OA (2022). Comment on: Nephrotoxicity of continuous amphotericin B in critically ill patients with abdominal sepsis: a retrospective analysis with propensity score matching. J Antimicrob Chemother. doi:10.1093/jac/dkac098.

Publications 2021

Banck JC, Mueller N, Mellinghoff SC, Thelen M, Fraccaroli A, Blumenberg V, Koehler P, Kunz WG, Rudelius M, Schrotzlmair F, Subklewe M, Schlosser HA, Tischer J, Cornely OA, Lindner LH, and von Bergwelt-Baildon M (2021). Immune Checkpoint Blockade for Aspergillosis and Mucormycosis Coinfection. Hemasphere5, e530. doi:10.1097/HS9.0000000000000530.

Joachim A, Dewald F, Suarez I, Zemlin M, Lang I, Stutz R, Marthaler A, Bosse HM, Lubke N, Munch J, Bernard MA, Jeltsch K, Tonshoff B, Weidner N, Krausslich HG, Birzele L, Hubner J, Schmied P, Meyer-Buhn M, Horemheb-Rubio G, Cornely OA, Haverkamp H, Wiesmuller G, Fatkenheuer G, Hero B, Kaiser R, Dotsch J, Rybniker J, and group BFs (2021). Pooled RT-qPCR testing for SARS-CoV-2 surveillance in schools - a cluster randomised trial. EClinicalMedicine39, 101082. doi:10.1016/j.eclinm.2021.101082.

Koehler FC, Blomberg L, Brehm TT, Buttner S, Cornely OA, Degen O, Di Cristanziano V, Dolff S, Eberwein L, Hoxha E, Hoyer-Allo KJR, Rudolf S, Spath MR, Wanken M, Muller RU, and Burst V (2021). Development and design of the Hantavirus registry - HantaReg - for epidemiological studies, outbreaks and clinical studies on hantavirus disease. Clin Kidney J14, 2365-2370. doi:10.1093/ckj/sfab053.

Meinberger D, Koch M, Roth A, Hermes G, Stemler J, Cornely OA, Streichert T, and Klatt AR (2021). Analysis of IgM, IgA, and IgG isotype antibodies Directed against SARS-CoV-2 spike glycoprotein and ORF8 in the course of COVID-19. Sci Rep11, 8920. doi:10.1038/s41598-021-88356-8.

Pagano L, Salmanton-Garcia J, Marchesi F, Busca A, Corradini P, Hoenigl M, Klimko N, Koehler P, Pagliuca A, Passamonti F, Verga L, Visek B, Ilhan O, Nadali G, Weinbergerova B, Cordoba-Mascunano R, Marchetti M, Collins GP, Farina F, Cattaneo C, Cabirta A, Gomes-Silva M, Itri F, van Doesum J, Ledoux MP, Cernan M, Jaksic O, Duarte RF, Magliano G, Omrani AS, Fracchiolla NS, Kulasekararaj A, Valkovic T, Poulsen CB, Machado M, Glenthoj A, Stoma I, Racil Z, Piukovics K, Navratil M, Emarah Z, Sili U, Maertens J, Blennow O, Bergantim R, Garcia-Vidal C, Prezioso L, Guidetti A, Del Principe MI, Popova M, de Jonge N, Ormazabal-Velez I, Fernandez N, Falces-Romero I, Cuccaro A, Meers S, Buquicchio C, Antic D, Al-Khabori M, Garcia-Sanz R, Biernat MM, Tisi MC, Sal E, Rahimli L, Colovic N, Schonlein M, Calbacho M, Tascini C, Miranda-Castillo C, Khanna N, Mendez GA, Petzer V, Novak J, Besson C, Dulery R, Lamure S, Nucci M, Zambrotta G, Zak P, Seval GC, Bonuomo V, Mayer J, Lopez-Garcia A, Sacchi MV, Booth S, Ciceri F, Oberti M, Salvini M, Izuzquiza M, Nunes-Rodrigues R, Ammatuna E, Obr A, Herbrecht R, Nunez-Martin-Buitrago L, Mancini V, Shwaylia H, Sciume M, Essame J, Nygaard M, Batinic J, Gonzaga Y, Regalado-Artamendi I, Karlsson LK, Shapetska M, Hanakova M, El-Ashwah S, Borbenyi Z, Colak GM, Nordlander A, Dragonetti G, Maraglino AME, Rinaldi A, De Ramon-Sanchez C, Cornely OA, and group Ew (2021). COVID-19 infection in adult patients with hematological malignancies: a European Hematology Association Survey (EPICOVIDEHA). J Hematol Oncol14, 168. doi:10.1186/s13045-021-01177-0.

Sprute R, Cornely OA, Chen SC, Seidel D, Schuetz AN, and Zhang SX (2021). All You Need To Know and More about the Diagnosis and Management of Rare Yeast Infections. mBio12, e0159421. doi:10.1128/mBio.01594-21.

Sprute R, Salmanton-Garcia J, Sal E, Malaj X, Falces-Romero I, Hatvani L, Heinemann M, Klimko N, Lopez-Soria L, Meletiadis J, Shruti M, Steinmann J, Seidel D, Cornely OA, and Stemler J (2021). Characterization and outcome of invasive infections due to Paecilomyces variotii: analysis of patients from the FungiScope(R) registry and literature reports. J Antimicrob Chemother76, 765-774. doi:10.1093/jac/dkaa481.

Sprute R, Salmanton-Garcia J, Sal E, Malaj X, Racil Z, Ruiz de Alegria Puig C, Falces-Romero I, Barac A, Desoubeaux G, Kindo AJ, Morris AJ, Pelletier R, Steinmann J, Thompson GR, Cornely OA, Seidel D, Stemler J, and FungiScope EIWG (2021). Invasive infections with Purpureocillium lilacinum: clinical characteristics and outcome of 101 cases from FungiScope(R) and the literature. J Antimicrob Chemother76, 1593-1603. doi:10.1093/jac/dkab039.

Theobald SJ, Simonis A, Georgomanolis T, Kreer C, Zehner M, Eisfeld HS, Albert MC, Chhen J, Motameny S, Erger F, Fischer J, Malin JJ, Grab J, Winter S, Pouikli A, David F, Boll B, Koehler P, Vanshylla K, Gruell H, Suarez I, Hallek M, Fatkenheuer G, Jung N, Cornely OA, Lehmann C, Tessarz P, Altmuller J, Nurnberg P, Kashkar H, Klein F, Koch M, and Rybniker J (2021). Long-lived macrophage reprogramming drives spike protein-mediated inflammasome activation in COVID-19. EMBO Mol Med13, e14150. doi:10.15252/emmm.202114150.

Schumacher S, Salmanton-Garcia J, Cornely OA, and Mellinghoff SC (2021). Increasing influenza vaccination coverage in healthcare workers: a review on campaign strategies and their effect. Infection49, 387-399. doi:10.1007/s15010-020-01555-9.

Publications 2020

Aguilar RC, Salmanton-Garcia J, Carney J, Boll B, Kochanek M, Jazmati N, Cornely OA, and Vehreschild M (2020). Clostridioides difficile infections in the intensive care unit: a monocentric cohort study. Infection 48, 421-7.
Augustin M, Schommers P, Suarez I, Koehler P, Gruell H, Klein F, Maurer C, Langerbeins P, Priesner V, Schmidt-Hellerau K, Malin JJ, Stecher M, Jung N, Wiesmuller G, Meissner A, Zweigner J, Langebartels G, Kolibay F, Suarez V, Burst V, Valentin P, Schedler D, Cornely OA, Hallek M, Fatkenheuer G, Rybniker J, and Lehmann C (2020). Rapid response infrastructure for pandemic preparedness in a tertiary care hospital: lessons learned from the COVID-19 outbreak in Cologne, Germany, February to March 2020. Euro Surveill 25.
Bacher P, Rosati E, Esser D, Martini GR, Saggau C, Schiminsky E, Dargvainiene J, Schroder I, Wieters I, Khodamoradi Y, Eberhardt F, Vehreschild M, Neb H, Sonntagbauer M, Conrad C, Tran F, Rosenstiel P, Markewitz R, Wandinger KP, Augustin M, Rybniker J, Kochanek M, Leypoldt F, Cornely OA, Koehler P, Franke A, and Scheffold A (2020). Low-Avidity CD4(+) T Cell Responses to SARS-CoV-2 in Unexposed Individuals and Humans with Severe COVID-19. Immunity 53, 1258-71 e5.
Cornely FB, Cornely OA, Salmanton-Garcia J, Koehler FC, Koehler P, Seifert H, Wingen-Heimann S, and Mellinghoff SC (2020). Attributable mortality of candidemia after introduction of echinocandins. Mycoses 63, 1373-81.
Salmanton-Garcia J, Koehler P, Kindo A, Falces-Romero I, Garcia-Rodriguez J, Racil Z, Chen SC, Klimko N, Desoubeaux G, Thompson Gr, III, Benitez-Penuela MA, Rodriguez JY, Sheppard DC, Hoenigl M, Le Govic Y, Badali H, Baddley JW, Chander J, Ingram PR, Pakstis DL, Mellinghoff SC, Atici S, Cesaro S, Chakrabarti A, Dupont D, Gonzalez GM, Hatvani L, Herbrecht R, Klyasova G, Lass-Florl C, Mares M, Mullane K, Vinh DC, Wisplinghoff H, Lackner M, Cornely OA, Seidel D, and group EIw (2020). Needles in a haystack: Extremely rare invasive fungal infections reported in FungiScope()-Global Registry for Emerging Fungal Infections. The Journal of infection 81, 802-15.
Schommers P, Gruell H, Abernathy ME, Tran MK, Dingens AS, Gristick HB, Barnes CO, Schoofs T, Schlotz M, Vanshylla K, Kreer C, Weiland D, Holtick U, Scheid C, Valter MM, van Gils MJ, Sanders RW, Vehreschild JJ, Cornely OA, Lehmann C, Fatkenheuer G, Seaman MS, Bloom JD, Bjorkman PJ, and Klein F (2020). Restriction of HIV-1 Escape by a Highly Broad and Potent Neutralizing Antibody. Cell 180, 471-89 e22.