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1. Decoding the historical tale: COVID-19 impact on haematological malignancy patients—EPICOVIDEHA insights from 2020 to 2022

Author

Salmanton-Garcia, J., Marchesi, F., Farina, F., Weinbergerova, B., Itri, F., Davila-Valls, J., Martin-Perez, S., Glenthoj, A., Hersby, D. S., Gomes da Silva, M., Nunes Rodrigues, R., Lopez-Garcia, A., Cordoba, R., Bilgin, Y. M., Falces-Romero, I., El-Ashwah, S., Emarah, Z., Besson, C., Kohn, M., Van Doesum, J., Ammatuna, E., Marchetti, M., Labrador, J., Zambrotta, G. P. M., Verga, L., Jaksic, O., Nucci, M., Piukovics, K., Cabirta-Touzon, A., Jimenez, M., Arellano, E., Espigado, I., Blennow, O., Nordlander, A., Meers, S., van Praet, J., Aiello, T. F., Garcia-Vidal, C., Fracchiolla, N., Sciume, M., Seval, G. C., Zak, P., Buquicchio, C., Tascini, C., Grafe, S. K., Schonlein, M., Adzic-Vukicevic, T., Bonuomo, V., Cattaneo, C., Nizamuddin, S., Cernan, M., Plantefeve, G., Prin, R., Szotkovski, T., Collins, G. P., Dargenio, M., Petzer, V., Wolf, D., Colovic, N., Prezioso, L., Valkovic, T., Passamonti, F., Mendez, G. -A., Sili, U., Vena, A., Bavastro, M., Limongelli, A., Duarte, R. F., Ledoux, M. -P., Cvetanoski, M., Stojanoski, Z., Machado, M., Batinic, J., Magliano, G., Biernat, M. M., Pantic, N., Poulsen, C. B., Cuccaro, A., Del Principe, M. I., Kulasekararaj, A., Ormazabal-Velez, I., Busca, A., Demirkan, F., Ijaz, M., Klimko, N., Stoma, I., Khostelidi, S., Fernandez, N., Omrani, A. S., Bergantim, R., De Jonge, N., Fouquet, G., Navratil, M., Abu-Zeinah, G., Samarkos, M., Maertens, J., De Ramon, C., Guidetti, A., Magyari, F., Gonzalez-Lopez, T. J., Lahmer, T., Finizio, O., Ali, N., Pinczes, L. I., Lavilla-Rubira, E., Romano, A., Merelli, M., Delia, M., Calbacho, M., Meletiadis, J., Antic, D., Hernandez-Rivas, J. -A., Marques de Almeida, J., Al-Khabori, M., Hoenigl, M., Tisi, M. C., Khanna, N., Barac, A., Eisa, N., Di Blasi, R., Lievin, R., Miranda-Castillo, C., Bahr, N. C., Lamure, S., Papa, M. V., Yahya, A., Aujayeb, A., Novak, J., Erben, N., Fernandez-Galan, M., Ribera-Santa Susana, J. -M., Rinaldi, I., Fazzi, R., Piedimonte, M., Dulery, R., Gonzaga, Y., Soto-Silva, A., Sapienza, G., Serris, A., Drgona, Groh, A., Serrano, L., Gavriilaki, E., Tragiannidis, A., Prattes, J., Coppola, N., Otasevic, V., Mladenovic, M., Mitrovic, M., Miskovic, B., Jindra, P., Zompi, S., Sacchi, M. V., Krekeler, C., Infante, M. S., Garcia-Bordallo, D., Colak, G. M., Mayer, J., Nygaard, M., Hanakova, M., Racil, Z., Bonanni, Matteo, Koehler, P., Rahimli, L., Cornely, O. A., Pagano, Livio, Martin-Vallejo, F. J., Zdziarski, P., Zarrinfer, H., Wittig, J., Win, S., Wai-Man, V., Visek, B., Vinh, D. C., Vehreschild, M., Varricchio, G., Tsirigotis, P., Torres-Tienza, A., Tanase, A. D., Tafuri, A., Stamouli, M., Sramek, J., Soussain, C., Shirinova, A., Schubert, J., Schalk, E., Salehi, M. R., Saleh, M., Rosati, G., Roldan, E., Reizine, F., Rego, M., Regalado-Artamendi, I., Popova, M., Pinto, F., Philippe, L., Orth, H. M., Ommen, H. -B., Obr, A., Nunez-Martin-Buitrago, L., Noel, N., Neuhann, J., Nadali, G., Nacov, J. A., Munhoz Alburquerque, A. M., Mitra, M. E., Mikulska, M., Mellinghoff, S., Mechtel, B., Martin-Gonzalez, J. -A., Malak, S., Loureiro-Amigo, J., Lorenzo De La Pena, L., Liberti, G., Landau, M., Lacej, I., Kolditz, M., Kho, C. S., Khedr, R. A., Karthaus, M., Karlsson, L. K., Jimenez-Lorenzo, M. -J., Izuzquiza, M., Hoell-Neugebauer, B., Herbrecht, R., Heath, C. H., Guolo, F., Grothe, J., Giordano, A., Gerasymchuk, S., Garcia-Sanz, R., Garcia-Pouton, N., Funke, V. A. M., Fung, M., Flasshove, C., Fianchi, Luana, Essame, J., Egger, M., Drenou, B., Dragonetti, G., Desole, M., Della Pepa, R., Deau Fischer, B., De Kort, E., De Cabo, E., Danion, F., Daguindau, E., Cushion, T., Cremer, L., Criscuolo, Marianna, Cordini, G., Cingolani, Antonella, Ciceri, F., Chowdhury, F. R., Chelysheva, E., Chauchet, A., Chai, L. Y. A., Ceesay, M. M., Busch, E., Brehon, M., Borducchi, D. M. M., Booth, S., Bologna, S., Berg Venemyr, C., Bailen-Almorox, R., Antoniadou, A., Anastasopoulou, A. N., Altuntas, F., Bonanni M., Pagano L. (ORCID:0000-0001-8287-928X), Fianchi L., Criscuolo M., Cingolani A. (ORCID:0000-0002-3793-2755), Salmanton-Garcia, J., Marchesi, F., Farina, F., Weinbergerova, B., Itri, F., Davila-Valls, J., Martin-Perez, S., Glenthoj, A., Hersby, D. S., Gomes da Silva, M., Nunes Rodrigues, R., Lopez-Garcia, A., Cordoba, R., Bilgin, Y. M., Falces-Romero, I., El-Ashwah, S., Emarah, Z., Besson, C., Kohn, M., Van Doesum, J., Ammatuna, E., Marchetti, M., Labrador, J., Zambrotta, G. P. M., Verga, L., Jaksic, O., Nucci, M., Piukovics, K., Cabirta-Touzon, A., Jimenez, M., Arellano, E., Espigado, I., Blennow, O., Nordlander, A., Meers, S., van Praet, J., Aiello, T. F., Garcia-Vidal, C., Fracchiolla, N., Sciume, M., Seval, G. C., Zak, P., Buquicchio, C., Tascini, C., Grafe, S. K., Schonlein, M., Adzic-Vukicevic, T., Bonuomo, V., Cattaneo, C., Nizamuddin, S., Cernan, M., Plantefeve, G., Prin, R., Szotkovski, T., Collins, G. P., Dargenio, M., Petzer, V., Wolf, D., Colovic, N., Prezioso, L., Valkovic, T., Passamonti, F., Mendez, G. -A., Sili, U., Vena, A., Bavastro, M., Limongelli, A., Duarte, R. F., Ledoux, M. -P., Cvetanoski, M., Stojanoski, Z., Machado, M., Batinic, J., Magliano, G., Biernat, M. M., Pantic, N., Poulsen, C. B., Cuccaro, A., Del Principe, M. I., Kulasekararaj, A., Ormazabal-Velez, I., Busca, A., Demirkan, F., Ijaz, M., Klimko, N., Stoma, I., Khostelidi, S., Fernandez, N., Omrani, A. S., Bergantim, R., De Jonge, N., Fouquet, G., Navratil, M., Abu-Zeinah, G., Samarkos, M., Maertens, J., De Ramon, C., Guidetti, A., Magyari, F., Gonzalez-Lopez, T. J., Lahmer, T., Finizio, O., Ali, N., Pinczes, L. I., Lavilla-Rubira, E., Romano, A., Merelli, M., Delia, M., Calbacho, M., Meletiadis, J., Antic, D., Hernandez-Rivas, J. -A., Marques de Almeida, J., Al-Khabori, M., Hoenigl, M., Tisi, M. C., Khanna, N., Barac, A., Eisa, N., Di Blasi, R., Lievin, R., Miranda-Castillo, C., Bahr, N. C., Lamure, S., Papa, M. V., Yahya, A., Aujayeb, A., Novak, J., Erben, N., Fernandez-Galan, M., Ribera-Santa Susana, J. -M., Rinaldi, I., Fazzi, R., Piedimonte, M., Dulery, R., Gonzaga, Y., Soto-Silva, A., Sapienza, G., Serris, A., Drgona, Groh, A., Serrano, L., Gavriilaki, E., Tragiannidis, A., Prattes, J., Coppola, N., Otasevic, V., Mladenovic, M., Mitrovic, M., Miskovic, B., Jindra, P., Zompi, S., Sacchi, M. V., Krekeler, C., Infante, M. S., Garcia-Bordallo, D., Colak, G. M., Mayer, J., Nygaard, M., Hanakova, M., Racil, Z., Bonanni, Matteo, Koehler, P., Rahimli, L., Cornely, O. A., Pagano, Livio, Martin-Vallejo, F. J., Zdziarski, P., Zarrinfer, H., Wittig, J., Win, S., Wai-Man, V., Visek, B., Vinh, D. C., Vehreschild, M., Varricchio, G., Tsirigotis, P., Torres-Tienza, A., Tanase, A. D., Tafuri, A., Stamouli, M., Sramek, J., Soussain, C., Shirinova, A., Schubert, J., Schalk, E., Salehi, M. R., Saleh, M., Rosati, G., Roldan, E., Reizine, F., Rego, M., Regalado-Artamendi, I., Popova, M., Pinto, F., Philippe, L., Orth, H. M., Ommen, H. -B., Obr, A., Nunez-Martin-Buitrago, L., Noel, N., Neuhann, J., Nadali, G., Nacov, J. A., Munhoz Alburquerque, A. M., Mitra, M. E., Mikulska, M., Mellinghoff, S., Mechtel, B., Martin-Gonzalez, J. -A., Malak, S., Loureiro-Amigo, J., Lorenzo De La Pena, L., Liberti, G., Landau, M., Lacej, I., Kolditz, M., Kho, C. S., Khedr, R. A., Karthaus, M., Karlsson, L. K., Jimenez-Lorenzo, M. -J., Izuzquiza, M., Hoell-Neugebauer, B., Herbrecht, R., Heath, C. H., Guolo, F., Grothe, J., Giordano, A., Gerasymchuk, S., Garcia-Sanz, R., Garcia-Pouton, N., Funke, V. A. M., Fung, M., Flasshove, C., Fianchi, Luana, Essame, J., Egger, M., Drenou, B., Dragonetti, G., Desole, M., Della Pepa, R., Deau Fischer, B., De Kort, E., De Cabo, E., Danion, F., Daguindau, E., Cushion, T., Cremer, L., Criscuolo, Marianna, Cordini, G., Cingolani, Antonella, Ciceri, F., Chowdhury, F. R., Chelysheva, E., Chauchet, A., Chai, L. Y. A., Ceesay, M. M., Busch, E., Brehon, M., Borducchi, D. M. M., Booth, S., Bologna, S., Berg Venemyr, C., Bailen-Almorox, R., Antoniadou, A., Anastasopoulou, A. N., Altuntas, F., Bonanni M., Pagano L. (ORCID:0000-0001-8287-928X), Fianchi L., Criscuolo M., and Cingolani A. (ORCID:0000-0002-3793-2755)

Abstract

Background: The COVID-19 pandemic heightened risks for individuals with hematological malignancies due to compromised immune systems, leading to more severe outcomes and increased mortality. While interventions like vaccines, targeted antivirals, and monoclonal antibodies have been effective for the general population, their benefits for these patients may not be as pronounced. Methods: The EPICOVIDEHA registry (National Clinical Trials Identifier, NCT04733729) gathers COVID-19 data from hematological malignancy patients since the pandemic's start worldwide. It spans various global locations, allowing comprehensive analysis over the first three years (2020–2022). Findings: The EPICOVIDEHA registry collected data from January 2020 to December 2022, involving 8767 COVID-19 cases in hematological malignancy patients from 152 centers across 41 countries, with 42% being female. Over this period, there was a significant reduction in critical infections and an overall decrease in mortality from 29% to 4%. However, hospitalization, particularly in the ICU, remained associated with higher mortality rates. Factors contributing to increased mortality included age, multiple comorbidities, active malignancy at COVID-19 onset, pulmonary symptoms, and hospitalization. On the positive side, vaccination with one to two doses or three or more doses, as well as encountering COVID-19 in 2022, were associated with improved survival. Interpretation: Patients with hematological malignancies still face elevated risks, despite reductions in critical infections and overall mortality rates over time. Hospitalization, especially in ICUs, remains a significant concern. The study underscores the importance of vaccination and the timing of COVID-19 exposure in 2022 for enhanced survival in this patient group. Ongoing monitoring and targeted interventions are essential to support this vulnerable population, emphasizing the critical role of timely diagnosis and prompt treatment in preventing severe

Published
2024

2. Survival in multiple myeloma and SARS-COV-2 infection through the COVID-19 pandemic: Results from the EPICOVIDEHA registry

Author

Musto, P., Salmanton-Garcia, J., Sgherza, N., Bergantim, R., Farina, F., Glenthoj, A., Cengiz Seval, G., Weinbergerova, B., Bonuomo, V., Bilgin, Y. M., van Doesum, J., Jaksic, O., Visek, B., Falces-Romero, I., Marchetti, M., Davila-Valls, J., Martin-Perez, S., Nucci, M., Lopez-Garcia, A., Itri, F., Buquicchio, C., Verga, L., Piukovics, K., Navratil, M., Collins, G. P., Jimenez, M., Fracchiolla, N. S., Labrador, J., Prezioso, L., Rossi, E., Colovic, N., Meers, S., Kulasekararaj, A., Cuccaro, A., Blennow, O., Valkovic, T., Sili, U., Ledoux, M. -P., Batinic, J., Passamonti, F., Machado, M., Duarte, R. F., Poulsen, C. B., Mendez, G. -A., Espigado, I., Demirkan, F., Cernan, M., Cattaneo, C., Petzer, V., Magliano, G., Garcia-Vidal, C., El-Ashwah, S., Gomes-Da-Silva, M., Vena, A., Ormazabal-Velez, I., van Praet, J., Dargenio, M., De-Ramon, C., Del Principe, M. I., Marques-De-Almeida, J., Wolf, D., Szotkowski, T., Obr, A., Colak, G. M., Nordlander, A., Izuzquiza, M., Cabirta, A., Zambrotta, G. P. M., Cordoba, R., Zak, P., Ammatuna, E., Mayer, J., Ilhan, O., Garcia-Sanz, R., Quattrone, Martina, Arellano, E., Nunes-Rodrigues, R., Emarah, Z., Aiello, T. F., Hanakova, M., Racil, Z., Bavastro, M., Limongelli, A., Rahimli, L., Marchesi, F., Cornely, O. A., Pagano, Livio, Quattrone M., Pagano L. (ORCID:0000-0001-8287-928X), Musto, P., Salmanton-Garcia, J., Sgherza, N., Bergantim, R., Farina, F., Glenthoj, A., Cengiz Seval, G., Weinbergerova, B., Bonuomo, V., Bilgin, Y. M., van Doesum, J., Jaksic, O., Visek, B., Falces-Romero, I., Marchetti, M., Davila-Valls, J., Martin-Perez, S., Nucci, M., Lopez-Garcia, A., Itri, F., Buquicchio, C., Verga, L., Piukovics, K., Navratil, M., Collins, G. P., Jimenez, M., Fracchiolla, N. S., Labrador, J., Prezioso, L., Rossi, E., Colovic, N., Meers, S., Kulasekararaj, A., Cuccaro, A., Blennow, O., Valkovic, T., Sili, U., Ledoux, M. -P., Batinic, J., Passamonti, F., Machado, M., Duarte, R. F., Poulsen, C. B., Mendez, G. -A., Espigado, I., Demirkan, F., Cernan, M., Cattaneo, C., Petzer, V., Magliano, G., Garcia-Vidal, C., El-Ashwah, S., Gomes-Da-Silva, M., Vena, A., Ormazabal-Velez, I., van Praet, J., Dargenio, M., De-Ramon, C., Del Principe, M. I., Marques-De-Almeida, J., Wolf, D., Szotkowski, T., Obr, A., Colak, G. M., Nordlander, A., Izuzquiza, M., Cabirta, A., Zambrotta, G. P. M., Cordoba, R., Zak, P., Ammatuna, E., Mayer, J., Ilhan, O., Garcia-Sanz, R., Quattrone, Martina, Arellano, E., Nunes-Rodrigues, R., Emarah, Z., Aiello, T. F., Hanakova, M., Racil, Z., Bavastro, M., Limongelli, A., Rahimli, L., Marchesi, F., Cornely, O. A., Pagano, Livio, Quattrone M., and Pagano L. (ORCID:0000-0001-8287-928X)

Abstract

Patients affected by multiple myeloma (MM) have an increased risk of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection and subsequent coronavirus (20)19 disease (COVID-19)-related death. The changing epidemiological and therapeutic scenarios suggest that there has been an improvement in severity and survival of COVID-19 during the different waves of the pandemic in the general population, but this has not been investigated yet in MM patients. Here we analyzed a large cohort of 1221 patients with MM and confirmed SARS-CoV-2 infection observed between February 2020, and August 2022, in the EPICOVIDEHA registry from 132 centers around the world. Median follow-up was 52 days for the entire cohort and 83 days for survivors. Three-hundred and three patients died (24%) and COVID-19 was the primary reason for death of around 89% of them. Overall survival (OS) was significantly higher in vaccinated patients with both stable and active MM versus unvaccinated, while only a trend favoring vaccinated patients was observed in subjects with responsive MM. Vaccinated patients with at least 2 doses showed a better OS than those with one or no vaccine dose. Overall, according to pandemic waves, mortality rate decreased over time from 34% to 10%. In multivariable analysis, age, renal failure, active disease, hospital, and intensive care unit admission, were independently associated with a higher number of deaths, while a neutrophil count above 0.5 × 109/L was found to be protective. This data suggests that MM patients remain at risk of SARS-CoV-2 infection even in the vaccination era, but their clinical outcome, in terms of OS, has progressively improved throughout the different viral phases of the pandemic.

Published
2024

3. Guideline adherence and survival of patients with candidaemia in Europe: results from the ECMM Candida III multinational European observational cohort study

Author

Hoenigl, M., Salmanton-García, J., Egger, M., Gangneux, J.P., Bicanic, T., Arikan-Akdagli, S., Alastruey-Izquierdo, A., Klimko, N., Barac, A., Özenci, V., Meijer, E.F.J., Khanna, N., Bassetti, M., Rautemaa-Richardson, R., Lagrou, K., Adam, K.M., Akalin, E.H., Akova, M., Arsenijevic, V. Arsic, Aujayeb, A., Blennow, O., Bretagne, S., Danion, F., Denis, B., Jonge, N.A. de, Desoubeaux, G., Drgona, L., Erben, N., Gori, A., Rodríguez, J. García, Garcia-Vidal, C., Giacobbe, D.R., Goodman, A.L., Hamal, P., Hammarström, H., Toscano, C., Lanternier, F., Lass-Flörl, C., Lockhart, D.E.A., Longval, T., Loughlin, L., Matos, T., Mikulska, M., Narayanan, M., Martín-Pérez, S., Prattes, J., Rogers, B., Rahimli, L., Ruiz, M., Roilides, E., Samarkos, M., Scharmann, U., Sili, U., Sipahi, O.R., Sivakova, A., Steinmann, J., Trauth, J., Turhan, O., Praet, J. Van, Vena, A., White, P.L., Willinger, B., Tortorano, A.M., Arendrup, M.C., Koehler, P., Cornely, O.A., Hoenigl, M., Salmanton-García, J., Egger, M., Gangneux, J.P., Bicanic, T., Arikan-Akdagli, S., Alastruey-Izquierdo, A., Klimko, N., Barac, A., Özenci, V., Meijer, E.F.J., Khanna, N., Bassetti, M., Rautemaa-Richardson, R., Lagrou, K., Adam, K.M., Akalin, E.H., Akova, M., Arsenijevic, V. Arsic, Aujayeb, A., Blennow, O., Bretagne, S., Danion, F., Denis, B., Jonge, N.A. de, Desoubeaux, G., Drgona, L., Erben, N., Gori, A., Rodríguez, J. García, Garcia-Vidal, C., Giacobbe, D.R., Goodman, A.L., Hamal, P., Hammarström, H., Toscano, C., Lanternier, F., Lass-Flörl, C., Lockhart, D.E.A., Longval, T., Loughlin, L., Matos, T., Mikulska, M., Narayanan, M., Martín-Pérez, S., Prattes, J., Rogers, B., Rahimli, L., Ruiz, M., Roilides, E., Samarkos, M., Scharmann, U., Sili, U., Sipahi, O.R., Sivakova, A., Steinmann, J., Trauth, J., Turhan, O., Praet, J. Van, Vena, A., White, P.L., Willinger, B., Tortorano, A.M., Arendrup, M.C., Koehler, P., and Cornely, O.A.

Abstract

Item does not contain fulltext, BACKGROUND: The European Confederation of Medical Mycology (ECMM) collected data on epidemiology, risk factors, treatment, and outcomes of patients with culture-proven candidaemia across Europe to assess how adherence to guideline recommendations is associated with outcomes. METHODS: In this observational cohort study, 64 participating hospitals located in 20 European countries, with the number of eligible hospitals per country determined by population size, included the first ten consecutive adults with culture-proven candidaemia after July 1, 2018, and entered data into the ECMM Candida Registry (FungiScope CandiReg). We assessed ECMM Quality of Clinical Candidaemia Management (EQUAL Candida) scores reflecting adherence to recommendations of the European Society of Clinical Microbiology and Infectious Diseases and the Infectious Diseases Society of America guidelines. FINDINGS: 632 patients with candidaemia were included from 64 institutions. Overall 90-day mortality was 43% (265/617), and increasing age, intensive care unit admission, point increases in the Charlson comorbidity index score, and Candida tropicalis as causative pathogen were independent baseline predictors of mortality in Cox regression analysis. EQUAL Candida score remained an independent predictor of mortality in the multivariable Cox regression analyses after adjusting for the baseline predictors, even after restricting the analysis to patients who survived for more than 7 days after diagnosis (adjusted hazard ratio 1·08 [95% CI 1·04-1·11; p<0·0001] in patients with a central venous catheter and 1·09 [1·05-1·13; p<0·0001] in those without one, per one score point decrease). Median duration of hospital stay was 15 days (IQR 4-30) after diagnosis of candidaemia and was extended specifically for completion of parenteral therapy in 100 (16%) of 621 patients. Initial echinocandin treatment was associated with lower overall mortality and longer duration of hospital stay among survivors than treatment

Published
2023

4. Nirmatrelvir/ritonavir in COVID-19 patients with haematological malignancies: a report from the EPICOVIDEHA registry

Author

Salmanton-Garcia, J., Marchesi, F., Gomes da Silva, M., Farina, F., Davila-Valls, J., Bilgin, Y. M., Glenthoj, A., Falces-Romero, I., Van Doesum, J., Labrador, J., Buquicchio, C., El-Ashwah, S., Petzer, V., Van Praet, J., Schonlein, M., Dargenio, M., Mendez, G. -A., Meers, S., Itri, F., Giordano, A., Pinczes, L. I., Espigado, I., Stojanoski, Z., Lopez-Garcia, A., Prezioso, L., Jaksic, O., Vena, A., Fracchiolla, N. S., Gonzalez-Lopez, T. J., Colovic, N., Delia, M., Weinbergerova, B., Marchetti, M., Marques de Almeida, J., Finizio, O., Besson, C., Biernat, M. M., Valkovic, T., Lahmer, T., Cuccaro, A., Ormazabal-Velez, I., Batinic, J., Fernandez, N., De Jonge, N., Tascini, C., Anastasopoulou, A. N., Dulery, R., Del Principe, M. I., Plantefeve, G., Papa, M. V., Nucci, M., Jimenez, M., Aujayeb, A., Hernandez-Rivas, J. -A., Merelli, M., Cattaneo, C., Blennow, O., Nordlander, A., Cabirta, A., Varricchio, G., Sacchi, M. V., Cordoba, R., Arellano, E., Grafe, S. K., Wolf, D., Emarah, Z., Ammatuna, E., Hersby, D. S., Martin-Perez, S., Nunes Rodrigues, R., Rahimli, L., Pagano, Livio, Cornely, O. A., Piukovics, K., De Ramon, C., Danion, F., Yahya, A., Guidetti, A., Garcia-Vidal, C., Sili, U., Meletiadis, J., De Kort, E., Verga, L., Serrano, L., Erben, N., Di Blasi, R., Tragiannidis, A., Ribera-Santa Susana, J. -M., Ommen, H. -B., Busca, A., Coppola, N., Bergantim, R., Dragonetti, Giulia, Criscuolo, Marianna, Fianchi, Luana, Bonanni, Matteo, Soto-Silva, A., Mikulska, M., Machado, M., Shan Kho, C., Hassan, N., Gavriilaki, E., Cordini, G., Chi, L. Y. A., Eggerer, M., Hoenigl, M., Prattes, J., Jimenez-Lorenzo, M. -J., Zompi, S., Zambrotta, G. P. M., Colak, G. M., Garcia-Pouton, N., Aiello, T. F., Prin, R., Stamouli, M., Samarkos, M., Pagano L. (ORCID:0000-0001-8287-928X), Dragonetti G., Criscuolo M., Fianchi L., Bonanni M., Salmanton-Garcia, J., Marchesi, F., Gomes da Silva, M., Farina, F., Davila-Valls, J., Bilgin, Y. M., Glenthoj, A., Falces-Romero, I., Van Doesum, J., Labrador, J., Buquicchio, C., El-Ashwah, S., Petzer, V., Van Praet, J., Schonlein, M., Dargenio, M., Mendez, G. -A., Meers, S., Itri, F., Giordano, A., Pinczes, L. I., Espigado, I., Stojanoski, Z., Lopez-Garcia, A., Prezioso, L., Jaksic, O., Vena, A., Fracchiolla, N. S., Gonzalez-Lopez, T. J., Colovic, N., Delia, M., Weinbergerova, B., Marchetti, M., Marques de Almeida, J., Finizio, O., Besson, C., Biernat, M. M., Valkovic, T., Lahmer, T., Cuccaro, A., Ormazabal-Velez, I., Batinic, J., Fernandez, N., De Jonge, N., Tascini, C., Anastasopoulou, A. N., Dulery, R., Del Principe, M. I., Plantefeve, G., Papa, M. V., Nucci, M., Jimenez, M., Aujayeb, A., Hernandez-Rivas, J. -A., Merelli, M., Cattaneo, C., Blennow, O., Nordlander, A., Cabirta, A., Varricchio, G., Sacchi, M. V., Cordoba, R., Arellano, E., Grafe, S. K., Wolf, D., Emarah, Z., Ammatuna, E., Hersby, D. S., Martin-Perez, S., Nunes Rodrigues, R., Rahimli, L., Pagano, Livio, Cornely, O. A., Piukovics, K., De Ramon, C., Danion, F., Yahya, A., Guidetti, A., Garcia-Vidal, C., Sili, U., Meletiadis, J., De Kort, E., Verga, L., Serrano, L., Erben, N., Di Blasi, R., Tragiannidis, A., Ribera-Santa Susana, J. -M., Ommen, H. -B., Busca, A., Coppola, N., Bergantim, R., Dragonetti, Giulia, Criscuolo, Marianna, Fianchi, Luana, Bonanni, Matteo, Soto-Silva, A., Mikulska, M., Machado, M., Shan Kho, C., Hassan, N., Gavriilaki, E., Cordini, G., Chi, L. Y. A., Eggerer, M., Hoenigl, M., Prattes, J., Jimenez-Lorenzo, M. -J., Zompi, S., Zambrotta, G. P. M., Colak, G. M., Garcia-Pouton, N., Aiello, T. F., Prin, R., Stamouli, M., Samarkos, M., Pagano L. (ORCID:0000-0001-8287-928X), Dragonetti G., Criscuolo M., Fianchi L., and Bonanni M.

Abstract

Background: Nirmatrelvir/ritonavir treatment decreases the hospitalisation rate in immunocompetent patients with COVID-19, but data on efficacy in patients with haematological malignancy are scarce. Here, we describe the outcome of nirmatrelvir/ritonavir treatment in a large cohort of the latter patients. Methods: This is a retrospective cohort study from the multicentre EPICOVIDEHA registry (NCT04733729) on patients with haematological malignancy, who were diagnosed with COVID-19 between January and September 2022. Patients receiving nirmatrelvir/ritonavir were compared to those who did not. A logistic regression was run to determine factors associated with nirmatrelvir/ritonavir administration in our sample. Mortality between treatment groups was assessed with Kaplan–Meier survival plots after matching all the patients with a propensity score. Additionally, a Cox regression was modelled to detect factors associated with mortality in patients receiving nirmatrelvir/ritonavir. Findings: A total of 1859 patients were analysed, 117 (6%) were treated with nirmatrelvir/ritonavir, 1742 (94%) were treated otherwise. Of 117 patients receiving nirmatrelvir/ritonavir, 80% had received ≥1 anti-SARS-CoV-2 vaccine dose before COVID-19 onset, 13% of which received a 2nd vaccine booster. 5% were admitted to ICU. Nirmatrelvir/ritonavir treatment was associated with the presence of extrapulmonary symptoms at COVID-19 onset, for example anosmia, fever, rhinitis, or sinusitis (aOR 2.509, 95%CI 1.448–4.347) and 2nd vaccine booster (aOR 3.624, 95%CI 1.619–8.109). Chronic pulmonary disease (aOR 0.261, 95%CI 0.093–0.732) and obesity (aOR 0.105, 95%CI 0.014–0.776) were not associated with nirmatrelvir/ritonavir use. After propensity score matching, day-30 mortality rate in patients treated with nirmatrelvir/ritonavir was 2%, significantly lower than in patients with SARS-CoV-2 directed treatment other than nirmatrelvir/ritonavir (11%, p = 0.036). No factor was observed explaining the mort

Published
2023

5. Molnupiravir compared to nirmatrelvir/ritonavir for COVID-19 in high-risk patients with haematological malignancy in Europe. A matched-paired analysis from the EPICOVIDEHA registry

Author

Salmanton-Garcia, J., Marchesi, F., Koehler, P., Weinbergerova, B., Colovic, N., Falces-Romero, I., Buquicchio, C., Farina, F., van Praet, J., Biernat, M. M., Itri, F., Prezioso, L., Tascini, C., Vena, A., Romano, A., Delia, M., Davila-Valls, J., Martin-Perez, S., Lavilla-Rubira, E., Adzic-vukicevic, T., Garcia-Bordallo, D., Lopez-Garcia, A., Criscuolo, Marianna, Petzer, V., Fracchiolla, N. S., Espigado, I., Sili, U., Meers, S., Erben, N., Cattaneo, C., Tragiannidis, A., Gavriilaki, E., Schonlein, M., Mitrovic, M., Pantic, N., Merelli, M., Labrador, J., Hernandez-Rivas, J. -A., Glenthoj, A., Fouquet, G., del Principe, M. I., Dargenio, M., Calbacho, M., Besson, C., Kohn, M., Grafe, S., Hersby, D. S., Arellano, E., Colak, G. M., Wolf, D., Marchetti, M., Nordlander, A., Blennow, O., Cordoba, R., Miskovic, B., Mladenovic, M., Bavastro, M., Limongelli, A., Rahimli, L., Pagano, Livio, Cornely, O. A., Criscuolo M., Pagano L. (ORCID:0000-0001-8287-928X), Salmanton-Garcia, J., Marchesi, F., Koehler, P., Weinbergerova, B., Colovic, N., Falces-Romero, I., Buquicchio, C., Farina, F., van Praet, J., Biernat, M. M., Itri, F., Prezioso, L., Tascini, C., Vena, A., Romano, A., Delia, M., Davila-Valls, J., Martin-Perez, S., Lavilla-Rubira, E., Adzic-vukicevic, T., Garcia-Bordallo, D., Lopez-Garcia, A., Criscuolo, Marianna, Petzer, V., Fracchiolla, N. S., Espigado, I., Sili, U., Meers, S., Erben, N., Cattaneo, C., Tragiannidis, A., Gavriilaki, E., Schonlein, M., Mitrovic, M., Pantic, N., Merelli, M., Labrador, J., Hernandez-Rivas, J. -A., Glenthoj, A., Fouquet, G., del Principe, M. I., Dargenio, M., Calbacho, M., Besson, C., Kohn, M., Grafe, S., Hersby, D. S., Arellano, E., Colak, G. M., Wolf, D., Marchetti, M., Nordlander, A., Blennow, O., Cordoba, R., Miskovic, B., Mladenovic, M., Bavastro, M., Limongelli, A., Rahimli, L., Pagano, Livio, Cornely, O. A., Criscuolo M., and Pagano L. (ORCID:0000-0001-8287-928X)

Abstract

Introduction: Molnupiravir and nirmatrelvir/ritonavir are antivirals used to prevent progression to severe SARS-CoV-2 infections and decrease hospitalisation and mortality rates. Nirmatrelvir/ritonavir was authorised in Europe in December 2021, whereas molnupiravir is not yet licensed in Europe as of February 2022. Molnupiravir may be an alternative to nirmatrelvir/ritonavir because it is associated with fewer drug-drug interactions and contraindications. A caveat for molnupiravir is the mode of action induces viral mutations. Mortality rate reduction with molnupiravir was less pronounced than that with nirmatrelvir/ritonavir in patients without haematological malignancy. Little is known about the comparative efficacy of the two drugs in patients with haematological malignancy at high-risk of severe COVID-19. Thus, molnupiravir and nirmatrelvir/ritonavir were compared in a cohort of patients with haematological malignancies. Methods: Clinical data from patients treated with molnupiravir or nirmatrelvir/ritonavir monotherapy for COVID-19 were retrieved from the EPICOVIDEHA registry. Patients treated with molnupiravir were matched by sex, age (±10 years), and severity of baseline haematological malignancy to controls treated with nirmatrelvir/ritonavir. Results: A total of 116 patients receiving molnupiravir for the clinical management of COVID-19 were matched to an equal number of controls receiving nirmatrelvir/ritonavir. In each of the groups, 68 (59%) patients were male; with a median age of 64 years (interquartile range [IQR] 53-74) for molnupiravir recipients and 64 years (IQR 54-73) for nirmatrelvir/ritonavir recipients; 56.9% (n=66) of the patients had controlled baseline haematological malignancy, 12.9% (n=15) had stable disease, and 30.2% (n=35) had active disease at COVID-19 onset in each group. During COVID-19 infection, one third of patients from each group were admitted to hospital. Although a similar proportion of patients in the two groups were vaccina

Published
2023

6. Age, successive waves, immunization, and mortality in elderly COVID-19 hematological patients: EPICOVIDEHA findings

Author

Rossi, G., Salmanton-Garcia, J., Cattaneo, C., Marchesi, F., Davila-Valls, J., Martin-Perez, S., Itri, F., Lopez-Garcia, A., Glenthoj, A., Da Silva, M. G., Besson, C., Marchetti, M., Weinbergerova, B., Jaksic, O., Jimenez, M., Bilgin, Y. M., Van Doesum, J., Farina, F., Ak, P., Verga, L., Collins, G. P., Bonuomo, V., Praet, J. V., Nucci, M., Meers, S., Espigado, I., Fracchiolla, N. S., Valkovic, T., Poulsen, C. B., Colovic, N., Dragonetti, Giulia, Ledoux, M. -P., Tascini, C., Buquicchio, C., Blennow, O., Passamonti, F., Machado, M., Labrador, J., Duarte, R. F., Schonlein, M., Prezioso, L., Falces-Romero, I., Kulasekararaj, A., Garcia-Vidal, C., Fernandez, N., Abu-Zeinah, G., Ormazabal-Velez, I., Ad ic-Vukicevic, T., Piukovics, K., Stoma, I., Cuccaro, A., Magliano, G., Szotkowski, T., Gonzalez-Lopez, T. -J., El-Ashwah, S., Bergantim, R., Sili, U., Maertens, J., Demirkan, F., De Ramon, C., Petzer, V., Del Principe, M. I., Navratil, M., Dargenio, M., Seval, G. C., Samarkos, M., Racil, Z., Pinczes, L. I., Lahmer, T., Busca, A., Mendez, G. -A., Vena, A., Biernat, M. M., Merelli, M., Calbacho, M., Barac, A., Bavastro, M., Limongelli, A., Ilhan, O., Wolf, D., Colak, G. M., Garcia-Sanz, R., Emarah, Z., Mi kovic, B., Grafe, S. K., Mladenovic, M., Aiello, T. F., Nunez-Martin-Buitrago, L., Nordlander, A., Arellano, E., Zambrotta, G. P. M., Ammatuna, E., Cabirta, A., Sacchi, M. V., Rodrigues, R. N., Hersby, D. S., Hanakova, M., Rahimli, L., Cordoba, R., Cornely, O. A., Pagano, Livio, Marques De, Almeida, Hernandez-Rivas, Marques De Almeida, J., Hernandez-Rivas, J. A., Guidetti, A., Finizio, O., Stojanoski, Z., Cvetanoski, M., Meletiadis, J., De Jonge, N., Antic, D., Ali, N., Tisi, M. C., Serrano, L., Plantefeve, G., Khanna, N., Hoenigl, M., Cernan, M., Miranda-Castillo, C., Fernandez-Galan, M., Serris, A., Erben, N., Dulery, R., Aujayeb, A., Papa, M. V., Novak, J., Delia, M., Sapienza, G., Reizine, F., Omrani, A. S., Di Blasi, R., Lamure, S., Drgona, L., Coppola, N., Batinic, J., Al-Khabori, M., Ribera-Santa Susana, J. -M., Piedimonte, M., Loureiro-Amigo, J., Fouquet, G., Fazzi, R., Danion, F., Schubert, J., Hoell-Neugebauer, B., Bahr, N. C., Yahia, A. O., Torres-Atienza, A., Rinaldi, I., Popova, M., Ommen, H. -B., Mitra, M. E., Mikulska, M., Lacej, I., Khostelidi, S., Win, S., Vinh, D., Saleh, M., Prattes, J., Jindra, P., Guolo, F., Della Pepa, R., Chelysheva, E., Zdziarski, P., Wai-Man, V., Soto-Silva, A., Orth, H. M., Malak, S., Lorenzo De La Pena, L., Kolditz, M., Kho, C. S., Heath, C. H., Groh, A., Gavriilaki, E., Fung, M., Egger, M., De Kort, E., De Cabo, E., Cushion, T., Chowdhury, F. R., Ceesay, M. M., Brehon, M., Varricchio, G., Tafuri, A., Jimenez-Lorenzo, M. -J., Klimko, N., Tsirigotis, P., Antoniadou, A., Vehreschild, M., Dragonetti G., Pagano L. (ORCID:0000-0001-8287-928X), Rossi, G., Salmanton-Garcia, J., Cattaneo, C., Marchesi, F., Davila-Valls, J., Martin-Perez, S., Itri, F., Lopez-Garcia, A., Glenthoj, A., Da Silva, M. G., Besson, C., Marchetti, M., Weinbergerova, B., Jaksic, O., Jimenez, M., Bilgin, Y. M., Van Doesum, J., Farina, F., Ak, P., Verga, L., Collins, G. P., Bonuomo, V., Praet, J. V., Nucci, M., Meers, S., Espigado, I., Fracchiolla, N. S., Valkovic, T., Poulsen, C. B., Colovic, N., Dragonetti, Giulia, Ledoux, M. -P., Tascini, C., Buquicchio, C., Blennow, O., Passamonti, F., Machado, M., Labrador, J., Duarte, R. F., Schonlein, M., Prezioso, L., Falces-Romero, I., Kulasekararaj, A., Garcia-Vidal, C., Fernandez, N., Abu-Zeinah, G., Ormazabal-Velez, I., Ad ic-Vukicevic, T., Piukovics, K., Stoma, I., Cuccaro, A., Magliano, G., Szotkowski, T., Gonzalez-Lopez, T. -J., El-Ashwah, S., Bergantim, R., Sili, U., Maertens, J., Demirkan, F., De Ramon, C., Petzer, V., Del Principe, M. I., Navratil, M., Dargenio, M., Seval, G. C., Samarkos, M., Racil, Z., Pinczes, L. I., Lahmer, T., Busca, A., Mendez, G. -A., Vena, A., Biernat, M. M., Merelli, M., Calbacho, M., Barac, A., Bavastro, M., Limongelli, A., Ilhan, O., Wolf, D., Colak, G. M., Garcia-Sanz, R., Emarah, Z., Mi kovic, B., Grafe, S. K., Mladenovic, M., Aiello, T. F., Nunez-Martin-Buitrago, L., Nordlander, A., Arellano, E., Zambrotta, G. P. M., Ammatuna, E., Cabirta, A., Sacchi, M. V., Rodrigues, R. N., Hersby, D. S., Hanakova, M., Rahimli, L., Cordoba, R., Cornely, O. A., Pagano, Livio, Marques De, Almeida, Hernandez-Rivas, Marques De Almeida, J., Hernandez-Rivas, J. A., Guidetti, A., Finizio, O., Stojanoski, Z., Cvetanoski, M., Meletiadis, J., De Jonge, N., Antic, D., Ali, N., Tisi, M. C., Serrano, L., Plantefeve, G., Khanna, N., Hoenigl, M., Cernan, M., Miranda-Castillo, C., Fernandez-Galan, M., Serris, A., Erben, N., Dulery, R., Aujayeb, A., Papa, M. V., Novak, J., Delia, M., Sapienza, G., Reizine, F., Omrani, A. S., Di Blasi, R., Lamure, S., Drgona, L., Coppola, N., Batinic, J., Al-Khabori, M., Ribera-Santa Susana, J. -M., Piedimonte, M., Loureiro-Amigo, J., Fouquet, G., Fazzi, R., Danion, F., Schubert, J., Hoell-Neugebauer, B., Bahr, N. C., Yahia, A. O., Torres-Atienza, A., Rinaldi, I., Popova, M., Ommen, H. -B., Mitra, M. E., Mikulska, M., Lacej, I., Khostelidi, S., Win, S., Vinh, D., Saleh, M., Prattes, J., Jindra, P., Guolo, F., Della Pepa, R., Chelysheva, E., Zdziarski, P., Wai-Man, V., Soto-Silva, A., Orth, H. M., Malak, S., Lorenzo De La Pena, L., Kolditz, M., Kho, C. S., Heath, C. H., Groh, A., Gavriilaki, E., Fung, M., Egger, M., De Kort, E., De Cabo, E., Cushion, T., Chowdhury, F. R., Ceesay, M. M., Brehon, M., Varricchio, G., Tafuri, A., Jimenez-Lorenzo, M. -J., Klimko, N., Tsirigotis, P., Antoniadou, A., Vehreschild, M., Dragonetti G., and Pagano L. (ORCID:0000-0001-8287-928X)

Abstract

Objectives: Elderly patients with hematologic malignancies face the highest risk of severe COVID-19 outcomes. The infection's impact on different age groups remains unstudied in detail. Methods: We analyzed elderly patients (age groups: 65-70, 71-75, 76-80, and >80 years old) with hematologic malignancies included in the EPICOVIDEHA registry between January 2020 and July 2022. Univariable and multivariable Cox regression models were conducted to identify factors influencing death in COVID-19 patients with hematological malignancy. Results: The study included data from 3,603 elderly patients (aged 65 or older) with hematological malignancy, with a majority being male (58.1%) and a significant proportion having comorbidities. The patients were divided into four age groups, and the analysis assessed COVID-19 outcomes, vaccination status, and other variables in relation to age and pandemic waves. The 90-day survival rate for patients with COVID-19 was 71.2%, with significant differences between groups. The pandemic waves had varying impacts, with the first wave affecting patients over 80 years old, the second being more severe in 65-70, and the third being the least severe in all age groups. Factors contributing to 90-day mortality included age, comorbidities, lymphopenia, active malignancy, acute leukemia, less than three vaccine doses, severe COVID-19, and using only corticosteroids as treatment. Conclusion: These data underscore the heterogeneity of elderly hematological patients, highlight the different impacts of COVID-19 waves and the pivotal importance of vaccination, and may help in planning future healthcare efforts.

Published
2023

7. Breakthrough COVID-19 in vaccinated patients with hematologic malignancies: results from the EPICOVIDEHA survey

Author

Pagano, Livio, Salmanton-Garcia, J., Marchesi, F., Blennow, O., Gomes da Silva, M., Glenthoj, A., van Doesum, J., Bilgin, Y. M., Lopez-Garcia, A., Itri, F., Nunes Rodrigues, R., Weinbergerova, B., Farina, F., Dragonetti, Giulia, Berg Venemyr, C., van Praet, J., Jaksic, O., Valkovic, T., Falces-Romero, I., Martin-Perez, S., Jimenez, M., Davila-Valls, J., Schonlein, M., Ammatuna, E., Meers, S., Delia, M., Stojanoski, Z., Nordlander, A., Lahmer, T., Imre Pinczes, L., Buquicchio, C., Piukovics, K., Ormazabal-Velez, I., Fracchiolla, N., Samarkos, M., Mendez, G. -A., Hernandez-Rivas, J. -A., Espigado, I., Cernan, M., Petzer, V., Lamure, S., di Blasi, R., Marques de Almedia, J., Dargenio, M., Biernat, M. M., Sciume, M., de Ramon, C., de Jonge, N., Batinic, J., Aujayeb, A., Marchetti, M., Fouquet, G., Fernandez, N., Zambrotta, G., Sacchi, M. V., Guidetti, A., Demirkan, F., Prezioso, L., Racil, Z., Nucci, M., Mladenovic, M., Lievin, R., Hanakova, M., Grafe, S., Sili, U., Machado, M., Cattaneo, C., Adzic-Vukicevic, T., Verga, L., Labrador, J., Rahimli, L., Bonanni, Matteo, Passamonti, F., Pagliuca, A., Corradini, P., Hoenigl, M., Koehler, P., Busca, A., Cornely, O. A., Serrano, L., Ribera-Santa Susana, J. -M., Meletiadis, J., Tsirigotis, P., Coppola, N., Mikulska, M., Erben, N., Besson, C., Merelli, M., Gonzalez-Lopez, T. -J., Loureiro-Amigo, J., Garcia-Vidal, C., Kort, E. D., Cuccaro, A., Zompi, S., Reizine, F., Finizio, O., Dulery, R., Calbacho, M., Abu-Zeinah, G., Malak, S., Zdziarski, P., Varrichio, G., Tragiannidis, A., Plantefeve, G., Duarte, R., Danion, F., Tisi, M. C., Sakellari, I., Karthaus, M., Groh, A., Fung, M., Emarah, Z., Coronel-Ayala, O. -F., Ann Chai, L. Y., Brehon, M., Bonuomo, V., Wolf, D., Wittig, J., Vehreschild, M., Papa, M. V., Neuhann, J., Jimenez-Lorenzo, M. -J., Grothe, J., Gavriilaki, E., Garcia-Sanz, R., Garcia-Pouton, N., El-Ashwah, S. S., Eggerer, M., Cordoba, R., Colak, G. M., Arellano, E., Hematology, Pagano L., Salmanton-García J., Marchesi F., Blennow O., Gomes da Silva M., Glenthøj A., van Doesum J., Bilgin Y. M. , López-García A., Itri F., et al., and Gilead Sciences

Subjects
Internal Diseases, Clinical Trials and Observations, CELL BIOLOGY, Cardiorespiratory Medicine and Haematology, Sağlık Bilimleri, Fundamental Medical Sciences, Biochemistry, İç Hastalıkları, Clinical Medicine (MED), COVID-19 Testing, BİYOKİMYA VE MOLEKÜLER BİYOLOJİ, Biyokimya, Monoclonal, Klinik Tıp (MED), 03.02. Klinikai orvostan, Viral, Lung, Cancer, BIOMEDICINA I ZDRAVSTVO. Kliničke medicinske znanosti. Interna medicina, Lymphoid Neoplasia, Myeloid Neoplasia, Klinik Tıp, Hücre Biyolojisi, Temel Bilimler, HEMATOLOJİ, Life Sciences, HÜCRE BİYOLOJİSİ, Tıp, MOLECULAR BIOLOGY & GENETICS, Infectious Diseases, Hematologic Neoplasms, Medicine, Natural Sciences, Infection, BIOCHEMISTRY & MOLECULAR BIOLOGY, BIOMEDICINA I ZDRAVSTVO. Kliničke medicinske znanosti. Infektologija, Sitogenetik, Biotechnology, Adult, Clinical Sciences, Immunology, Temel Tıp Bilimleri, Histoloji-Embriyoloji, Life Sciences (LIFE), Molecular Biology and Genetics, Antiviral Agents, Antibodies, Vaccine Related, Paediatrics and Reproductive Medicine, HEMATOLOGY, Biodefense, Yaşam Bilimleri, Health Sciences, Humans, CVOID19, Cytogenetic, Free Research Articles, BIOMEDICINE AND HEALTHCARE. Clinical Medical Sciences. Internal Medicine, Moleküler Biyoloji ve Genetik, Internal Medicine Sciences, İmmünoloji, SARS-CoV-2, Histology and Embryology, Prevention, COVID-19, Dahili Tıp Bilimleri, CLINICAL MEDICINE, BIOMEDICINE AND HEALTHCARE. Clinical Medical Sciences. Infectology, Settore MED/15 - MALATTIE DEL SANGUE, Emerging Infectious Diseases, Good Health and Well Being, Yaşam Bilimleri (LIFE), Hematoloji, Immunization
Abstract

Limited data are available on breakthrough COVID-19 in patients with hematologic malignancy (HM) after anti–severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. Adult patients with HM, ≥1 dose of anti-SARS-CoV-2 vaccine, and breakthrough COVID-19 between January 2021 and March 2022 were analyzed. A total of 1548 cases were included, mainly lymphoid malignancies (1181 cases, 76%). After viral sequencing in 753 cases (49%), the Omicron variant was prevalent (517, 68.7%). Most of the patients received ≤2 vaccine doses before COVID-19 (1419, 91%), mostly mRNA-based (1377, 89%). Overall, 906 patients (59%) received COVID-19-specific treatment. After 30-day follow-up from COVID-19 diagnosis, 143 patients (9%) died. The mortality rate in patients with the Omicron variant was 7.9%, comparable to other variants, with a significantly lower 30-day mortality rate than in the prevaccine era (31%). In the univariable analysis, older age (P < .001), active HM (P < .001), and severe and critical COVID-19 (P = .007 and P < .001, respectively) were associated with mortality. Conversely, patients receiving monoclonal antibodies, even for severe or critical COVID-19, had a lower mortality rate (P < .001). In the multivariable model, older age, active disease, critical COVID-19, and 2-3 comorbidities were correlated with a higher mortality, whereas monoclonal antibody administration, alone (P < .001) or combined with antivirals (P = .009), was protective. Although mortality is significantly lower than in the prevaccination era, breakthrough COVID-19 in HM is still associated with considerable mortality. Death rate was lower in patients who received monoclonal antibodies, alone or in combination with antivirals., EPICOVIDEHA has received funds from Optics COMMIT (COVID-19 Unmet Medical Needs and Associated Research Extension) COVID-19 RFP program by GILEAD Science, United States (Project 2020-8223).

Published
2022

8. S280: B-CELL MALIGNANCIES TREATED WITH TARGETED DRUGS AND SARS-COV-2 INFECTION. A EUROPEAN HEMATOLOGY ASSOCIATION SURVEY (EPICOVIDEHA)

Author

Infante, M. S., primary, Salmanton-García, J., additional, Fernandez-Cruz, A., additional, Marchesi, F., additional, RÁČIL, Z., additional, Hanakova, M., additional, Jaksic, O., additional, Weinbergerova, B., additional, Besson, C., additional, Duarte, R., additional, Itri, F., additional, VALKOVIĆ, T., additional, Busca, A., additional, Guidetti, A., additional, GLENTHØJ, A., additional, Collins, G., additional, Bonuomo, V., additional, Sili, U., additional, Seval, G., additional, Machado, M., additional, Lopez-Garcia, A., additional, Cordoba, R., additional, Blennow, O., additional, Abu-zeinah, G., additional, Lemure, S., additional, Kulasekararaj, A., additional, Falces-Romero, I., additional, Cattaneo, C., additional, Cornely, O. A., additional, Hernandez-Rivas, J.-A., additional, and Pagano, L., additional

Published
2022
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9. An international observational study to assess the impact of the Omicron variant emergence on the clinical epidemiology of COVID-19 in hospitalised patients

Author

Goncalves, BP, Hall, M, Jassat, W, Balan, V, Murthy, S, Kartsonaki, C, Semple, MG, Rojek, A, Baruch, J, Reyes, LF, Dasgupta, A, Dunning, J, Citarella, BW, Pritchard, M, Martin-Quiros, A, Sili, U, Baillie, JK, Aryal, D, Arabi, Y, Rashan, A, Angheben, A, Caoili, J, Carrier, FM, Harrison, EM, Gomez-Junyent, J, Figueiredo-Mello, C, Douglas, JJ, Nor, MBM, Chow, YP, Wong, XC, Bertagnolio, S, Thwin, SS, Streinu-Cercel, A, Salazar, L, Rishu, A, Rangappa, R, Ong, DSY, Hashmi, M, Carson, G, Diaz, J, Fowler, R, Kraemer, MUG, Wils, E-J, Horby, P, Merson, L, Olliaro, PL, Goncalves, BP, Hall, M, Jassat, W, Balan, V, Murthy, S, Kartsonaki, C, Semple, MG, Rojek, A, Baruch, J, Reyes, LF, Dasgupta, A, Dunning, J, Citarella, BW, Pritchard, M, Martin-Quiros, A, Sili, U, Baillie, JK, Aryal, D, Arabi, Y, Rashan, A, Angheben, A, Caoili, J, Carrier, FM, Harrison, EM, Gomez-Junyent, J, Figueiredo-Mello, C, Douglas, JJ, Nor, MBM, Chow, YP, Wong, XC, Bertagnolio, S, Thwin, SS, Streinu-Cercel, A, Salazar, L, Rishu, A, Rangappa, R, Ong, DSY, Hashmi, M, Carson, G, Diaz, J, Fowler, R, Kraemer, MUG, Wils, E-J, Horby, P, Merson, L, and Olliaro, PL

Abstract

BACKGROUND: Whilst timely clinical characterisation of infections caused by novel SARS-CoV-2 variants is necessary for evidence-based policy response, individual-level data on infecting variants are typically only available for a minority of patients and settings. METHODS: Here, we propose an innovative approach to study changes in COVID-19 hospital presentation and outcomes after the Omicron variant emergence using publicly available population-level data on variant relative frequency to infer SARS-CoV-2 variants likely responsible for clinical cases. We apply this method to data collected by a large international clinical consortium before and after the emergence of the Omicron variant in different countries. RESULTS: Our analysis, that includes more than 100,000 patients from 28 countries, suggests that in many settings patients hospitalised with Omicron variant infection less often presented with commonly reported symptoms compared to patients infected with pre-Omicron variants. Patients with COVID-19 admitted to hospital after Omicron variant emergence had lower mortality compared to patients admitted during the period when Omicron variant was responsible for only a minority of infections (odds ratio in a mixed-effects logistic regression adjusted for likely confounders, 0.67 [95% confidence interval 0.61-0.75]). Qualitatively similar findings were observed in sensitivity analyses with different assumptions on population-level Omicron variant relative frequencies, and in analyses using available individual-level data on infecting variant for a subset of the study population. CONCLUSIONS: Although clinical studies with matching viral genomic information should remain a priority, our approach combining publicly available data on variant frequency and a multi-country clinical characterisation dataset with more than 100,000 records allowed analysis of data from a wide range of settings and novel insights on real-world heterogeneity of COVID-19 presentation and clin

Published
2022

10. B-cell malignancies treated with targeted drugs and SARS-CoV-2 infection: A European Hematology Association Survey (EPICOVIDEHA)

Author

Infante, M. S., Salmanton-Garcia, J., Fernandez-Cruz, A., Marchesi, F., Jaksic, O., Weinbergerova, B., Besson, C., Duarte, R. F., Itri, F., Valkovic, T., Szotkovski, T., Busca, A., Guidetti, A., Glenthoj, A., Collins, G. P., Bonuomo, V., Sili, U., Seval, G. C., Machado, M., Cordoba, R., Blennow, O., Abu-Zeinah, G., Lamure, S., Kulasekararaj, A., Falces-Romero, I., Cattaneo, C., Van Doesum, J., Piukovics, K., Omrani, A. S., Magliano, G., Ledoux, M. -P., de Ramon, C., Cabirta, A., Verga, L., Lopez-Garcia, A., Da Silva, M. G., Stojanoski, Z., Meers, S., Lahmer, T., Martin-Perez, S., Davila-Vals, J., Van Praet, J., Samarkos, M., Bilgin, Y. M., Karlsson, L. K., Batinic, J., Nordlander, A., Schonlein, M., Hoenigl, M., Racil, Z., Mladenovic, M., Hanakova, M., Zambrotta, G. P. M., De Jonge, N., Adzic-Vukicevic, T., Nunes-Rodrigues, R., Prezioso, L., Navratil, M., Marchetti, M., Cuccaro, A., Calbacho, M., Giordano, A., Cornely, O. A., Hernandez-Rivas, J. -A., Pagano, Livio, Pagano L. (ORCID:0000-0001-8287-928X), Infante, M. S., Salmanton-Garcia, J., Fernandez-Cruz, A., Marchesi, F., Jaksic, O., Weinbergerova, B., Besson, C., Duarte, R. F., Itri, F., Valkovic, T., Szotkovski, T., Busca, A., Guidetti, A., Glenthoj, A., Collins, G. P., Bonuomo, V., Sili, U., Seval, G. C., Machado, M., Cordoba, R., Blennow, O., Abu-Zeinah, G., Lamure, S., Kulasekararaj, A., Falces-Romero, I., Cattaneo, C., Van Doesum, J., Piukovics, K., Omrani, A. S., Magliano, G., Ledoux, M. -P., de Ramon, C., Cabirta, A., Verga, L., Lopez-Garcia, A., Da Silva, M. G., Stojanoski, Z., Meers, S., Lahmer, T., Martin-Perez, S., Davila-Vals, J., Van Praet, J., Samarkos, M., Bilgin, Y. M., Karlsson, L. K., Batinic, J., Nordlander, A., Schonlein, M., Hoenigl, M., Racil, Z., Mladenovic, M., Hanakova, M., Zambrotta, G. P. M., De Jonge, N., Adzic-Vukicevic, T., Nunes-Rodrigues, R., Prezioso, L., Navratil, M., Marchetti, M., Cuccaro, A., Calbacho, M., Giordano, A., Cornely, O. A., Hernandez-Rivas, J. -A., Pagano, Livio, and Pagano L. (ORCID:0000-0001-8287-928X)

Abstract

Patients with lymphoproliferative diseases (LPD) are vulnerable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Here, we describe and analyze the outcome of 366 adult patients with chronic lymphocytic leukemia (CLL) or non-Hodgkin Lymphoma (NHL) treated with targeted drugs and laboratory-confirmed COVID-19 diagnosed between February 2020 and January 2022. Median follow-up was 70.5 days (IQR 0-609). Most used targeted drugs were Bruton-kinase inhibitors (BKIs) (N= 201, 55%), anti-CD20 other than rituximab (N=61, 16%), BCL2 inhibitors (N=33, 9%) and lenalidomide (N=28, 8%).Only 16.2% of the patients were vaccinated with 2 or more doses of vaccine at the onset of COVID-19. Mortality was 24% (89/366) on day 30 and 36%(134/366) on the last day of follow-up. Age >75 years (p<0.001, HR 1.036), active malignancy (p<0.001, HR 2.215), severe COVID-19 (p=0.017, HR 2.270) and admission to ICU (p<0.001, HR 5.751) were risk factors for mortality at last day of follow up. There was no difference in OS rates in NHL vs CLL patients (p=0.306), nor in patients treated with or without BKIs (p=0.151). Mortality in ICU was 66% (CLL 61%, NHL 76%). Overall mortality rate decreased according to vaccination status, being 39% in unvaccinated patients, 32% and 26% in those having received one or two doses, respectively, and 20% in patients with a booster dose (p=0.245). Overall mortality rate dropped from 41% during the first semester of 2020 to 25% at the last semester of 2021. These results show increased severity and mortality from COVID-19 in LPDs patients treated with targeted drugs.

Published
2022

11. Simultaneous Onset of Haematological Malignancy and COVID: An Epicovideha Survey

Author

Cattaneo, C., Salmanton-Garcia, J., Marchesi, F., El-Ashwah, S., Itri, F., Weinbergerova, B., Gomes Da Silva, M., Dargenio, M., Davila-Valls, J., Martin-Perez, S., Farina, F., Van Doesum, J., Valkovic, T., Besson, C., Poulsen, C. B., Lopez-Garcia, A., Zak, P., Schonlein, M., Piukovics, K., Jaksic, O., Cabirta, A., Ali, N., Sili, U., Fracchiolla, N., Dragonetti, Giulia, Adzic-Vukicevic, T., Marchetti, M., Machado, M., Glenthoj, A., Finizio, O., Demirkan, F., Blennow, O., Tisi, M. C., Omrani, A. S., Navratil, M., Racil, Z., Novak, J., Magliano, G., Jimenez, M., Garcia-Vidal, C., Erben, N., Del Principe, M. I., Buquicchio, C., Bergantim, R., Batinic, J., Al-Khabori, M., Verga, L., Szotkowski, T., Samarkos, M., Ormazabal-Velez, I., Meers, S., Maertens, J., Pinczes, L. I., Hoenigl, M., Drgona, L., Cuccaro, A., Bilgin, Y. M., Aujayeb, A., Rahimli, L., Grafe, S., Sciume, M., Mladenovic, M., Colak, G. M., Sacchi, M. V., Nordlander, A., Berg Venemyr, C., Hanakova, M., Garcia-Pouton, N., Emarah, Z., Zambrotta, G. P. M., Nunes Rodrigues, R., Cordoba, R., Mendez, G. -A., Biernat, M. M., Cornely, O. A., Pagano, Livio, Dragonetti G., Pagano L. (ORCID:0000-0001-8287-928X), Cattaneo, C., Salmanton-Garcia, J., Marchesi, F., El-Ashwah, S., Itri, F., Weinbergerova, B., Gomes Da Silva, M., Dargenio, M., Davila-Valls, J., Martin-Perez, S., Farina, F., Van Doesum, J., Valkovic, T., Besson, C., Poulsen, C. B., Lopez-Garcia, A., Zak, P., Schonlein, M., Piukovics, K., Jaksic, O., Cabirta, A., Ali, N., Sili, U., Fracchiolla, N., Dragonetti, Giulia, Adzic-Vukicevic, T., Marchetti, M., Machado, M., Glenthoj, A., Finizio, O., Demirkan, F., Blennow, O., Tisi, M. C., Omrani, A. S., Navratil, M., Racil, Z., Novak, J., Magliano, G., Jimenez, M., Garcia-Vidal, C., Erben, N., Del Principe, M. I., Buquicchio, C., Bergantim, R., Batinic, J., Al-Khabori, M., Verga, L., Szotkowski, T., Samarkos, M., Ormazabal-Velez, I., Meers, S., Maertens, J., Pinczes, L. I., Hoenigl, M., Drgona, L., Cuccaro, A., Bilgin, Y. M., Aujayeb, A., Rahimli, L., Grafe, S., Sciume, M., Mladenovic, M., Colak, G. M., Sacchi, M. V., Nordlander, A., Berg Venemyr, C., Hanakova, M., Garcia-Pouton, N., Emarah, Z., Zambrotta, G. P. M., Nunes Rodrigues, R., Cordoba, R., Mendez, G. -A., Biernat, M. M., Cornely, O. A., Pagano, Livio, Dragonetti G., and Pagano L. (ORCID:0000-0001-8287-928X)

Abstract

Background: The outcome of patients with simultaneous diagnosis of haematological malignancies (HM) and COVID-19 is unknown and there are no specific treatment guidelines. Methods: We describe the clinical features and outcome of a cohort of 450 patients with simultaneous diagnosis of HM and COVID-19 registered in the EPICOVIDEHA registry between March 2020 to February 2022. Results: Acute leukaemia and lymphoma were the most frequent HM (35.8% and 35.1%, respectively). Overall, 343 (76.2%) patients received treatment for HM, which was delayed for longer than one month since diagnosis in 57 (16.6%). An overall response rate was observed in 140 (40.8%) patients after the first line of treatment. After a median follow-up of 35 days, overall mortality was 177/450 (39.3%); 30-day mortality was significantly higher in patients not receiving HM treatment (42.1%) than in those receiving treatment (27.4%, p = 0.004), either before and/or after COVID-19, or compared to patients receiving HM treatment at least after COVID-19 (15.2%, p < 0.001). Age, severe/critical COVID-19, ≥2 comorbidities, and lack of HM treatment were independent risk factors for mortality, whereas a lymphocyte count >500/mcl at COVID-19 onset was protective. Conclusions: HM treatment should be delivered as soon as possible for patients with simultaneous diagnosis of COVID-19 and HM requiring immediate therapy.

Published
2022

12. Pharmacokinetic characterization of favipiravir in patients with COVID-19 and patient outcome

Author

Filiz Onat, Eryüksel E, Bulut C, Balcan B, Şengel Be, Tigen Et, Toplu A, Karakurt S, Çulpan Y, Oglu Mgi, Güner A, Gülhan R, Ay P, Patsalos P, Elçi A, Korten, Yildizeli So, Karaalp A, Hasan Raci Yananli, Sili U, Hatipoglu M, Kocakaya D, and Ratnaraj N

Subjects
Oncology, medicine.medical_specialty, Text mining, Pharmacokinetics, Coronavirus disease 2019 (COVID-19), business.industry, Internal medicine, medicine, In patient, Favipiravir, business, Outcome (game theory)
Abstract

Favipiravir is one of the repurposed antiviral medications for the treatment of SARS-CoV-2 infection. Since the dosing regimen is a prominent factor for the success of the antiviral therapy, this prospective observational study aimed to characterize the pharmacokinetic characteristics of favipiravir in COVID-19 patients. Adult patients (n=21) hospitalized for mild to moderate COVID-19 with a positive RT-PCR test, and assigned for favipiravir treatment were included. Favipiravir was administered for 5 days, with a loading dose of 3200 mg and a 1200 mg/day maintenance dose. Serial blood samples were collected on Day-2 and Day-4 of the therapy. Laboratory findings of the patients and in-hospital mortality were assessed. Favipiravir concentrations exhibited high variations and a significant decrease during the treatment of COVID-19. The median favipiravir trough concentration (C0-trough) on Day-2 was 21.26 µg/mL whereas it decreased significantly to 1.61 µg/mL on Day-4, the area under the concentration versus time curve decreased from 345.6 µg.h/mL to 108.6 µg.h/mL, respectively. Gender seems significant to affect favipiravir concentrations. Day-2-C0-trough of female patients was significantly higher than male patients. Of the 5 patients that died, 4 were male with a significant increase in ferritin levels from Day-0 to Day-5 compared to surviving patients. In addition, there was a significant decrease in D-dimer and CRP levels in the surviving patients. Our findings indicate that favipiravir concentrations show significant changes during the treatment of COVID-19. Therapeutic drug monitoring may best guide dose adjustments in patients that do not respond to treatment with favipiravir.

Published
2021

13. COVID-19 infection in adult patients with hematological malignancies: a European Hematology Association Survey (EPICOVIDEHA)

Author

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, G. P., Farina, F., Cattaneo, C., Cabirta, A., Gomes-Silva, M., Itri, F., van Doesum, J., Ledoux, M. -P., Cernan, M., Jaksic, O., Duarte, R. F., Magliano, G., Omrani, A. S., Fracchiolla, N. S., Kulasekararaj, A., Valkovic, T., Poulsen, C. B., 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, M. I., 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, M. M., Tisi, M. C., Sal, E., Rahimli, L., Colovic, N., Schonlein, M., Calbacho, M., Tascini, C., Miranda-Castillo, C., Khanna, N., Mendez, G. -A., Petzer, V., Novak, J., Besson, C., Dulery, R., Lamure, S., Nucci, M., Zambrotta, G., Zak, P., Seval, G. C., Bonuomo, V., Mayer, J., Lopez-Garcia, A., Sacchi, M. V., 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, L. K., Shapetska, M., Hanakova, M., El-Ashwah, S., Borbenyi, Z., Colak, G. M., Nordlander, A., Dragonetti, G., Maraglino, A. M. E., Rinaldi, A., De Ramon-Sanchez, C., Cornely, O. A., Finizio, O., Fazzi, R., Sapienza, G., Chauchet, A., Van Praet, J., Prattes, J., Dargenio, M., Rossi, C., Shirinova, A., Malak, S., Tafuri, A., Ommen, H. -B., Bologna, S., Khedr, R. A., Choquet, S., Joly, B., Ceesay, M. M., Philippe, L., Kho, C. S., Desole, M., Tsirigotis, P., Otasevic, V., Borducchi, D. M. M., Antoniadou, A., Gaziev, J., Almaslamani, M. A., Garcia-Pouton, N., Paterno, G., Torres-Lopez, A., Tarantini, G., Mellinghoff, S., Grafe, S., Borschel, N., Passweg, J., Merelli, M., Barac, A., Wolf, D., Shaikh, M. U., Thieblemont, C., Bernard, S., Funke, V. A. M., Daguindau, E., Khostelidi, S., Nucci, F. M., Martin-Gonzalez, J. -A., Landau, M., Soussain, C., Laureana, C., Lacombe, K., Kohn, M., Aliyeva, G., Piedimonte, M., Fouquet, G., Rego, M., Hoell-Neugebauer, B., Cartron, G., Pinto, F., Alburquerque, A. M., Passos, J., Yilmaz, A. F., Redondo-Izal, A. -M., Altuntas, F., Heath, C., Kolditz, M., Schalk, E., Guolo, F., Karthaus, M., Della Pepa, R., Vinh, D., Noel, N., Deau Fischer, B., Drenou, B., Mitra, M. E., Meletiadis, J., Bilgin, Y. M., Jindra, P., Espigado, I., Drgona, L., Serris, A., Di Blasi, R., Ali, N., Pagano L. (ORCID:0000-0001-8287-928X), Dragonetti G., 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, G. P., Farina, F., Cattaneo, C., Cabirta, A., Gomes-Silva, M., Itri, F., van Doesum, J., Ledoux, M. -P., Cernan, M., Jaksic, O., Duarte, R. F., Magliano, G., Omrani, A. S., Fracchiolla, N. S., Kulasekararaj, A., Valkovic, T., Poulsen, C. B., 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, M. I., 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, M. M., Tisi, M. C., Sal, E., Rahimli, L., Colovic, N., Schonlein, M., Calbacho, M., Tascini, C., Miranda-Castillo, C., Khanna, N., Mendez, G. -A., Petzer, V., Novak, J., Besson, C., Dulery, R., Lamure, S., Nucci, M., Zambrotta, G., Zak, P., Seval, G. C., Bonuomo, V., Mayer, J., Lopez-Garcia, A., Sacchi, M. V., 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, L. K., Shapetska, M., Hanakova, M., El-Ashwah, S., Borbenyi, Z., Colak, G. M., Nordlander, A., Dragonetti, G., Maraglino, A. M. E., Rinaldi, A., De Ramon-Sanchez, C., Cornely, O. A., Finizio, O., Fazzi, R., Sapienza, G., Chauchet, A., Van Praet, J., Prattes, J., Dargenio, M., Rossi, C., Shirinova, A., Malak, S., Tafuri, A., Ommen, H. -B., Bologna, S., Khedr, R. A., Choquet, S., Joly, B., Ceesay, M. M., Philippe, L., Kho, C. S., Desole, M., Tsirigotis, P., Otasevic, V., Borducchi, D. M. M., Antoniadou, A., Gaziev, J., Almaslamani, M. A., Garcia-Pouton, N., Paterno, G., Torres-Lopez, A., Tarantini, G., Mellinghoff, S., Grafe, S., Borschel, N., Passweg, J., Merelli, M., Barac, A., Wolf, D., Shaikh, M. U., Thieblemont, C., Bernard, S., Funke, V. A. M., Daguindau, E., Khostelidi, S., Nucci, F. M., Martin-Gonzalez, J. -A., Landau, M., Soussain, C., Laureana, C., Lacombe, K., Kohn, M., Aliyeva, G., Piedimonte, M., Fouquet, G., Rego, M., Hoell-Neugebauer, B., Cartron, G., Pinto, F., Alburquerque, A. M., Passos, J., Yilmaz, A. F., Redondo-Izal, A. -M., Altuntas, F., Heath, C., Kolditz, M., Schalk, E., Guolo, F., Karthaus, M., Della Pepa, R., Vinh, D., Noel, N., Deau Fischer, B., Drenou, B., Mitra, M. E., Meletiadis, J., Bilgin, Y. M., Jindra, P., Espigado, I., Drgona, L., Serris, A., Di Blasi, R., Ali, N., Pagano L. (ORCID:0000-0001-8287-928X), and Dragonetti G.

Abstract

Background: Patients with hematological malignancies (HM) are at high risk of mortality from SARS-CoV-2 disease 2019 (COVID-19). A better understanding of risk factors for adverse outcomes may improve clinical management in these patients. We therefore studied baseline characteristics of HM patients developing COVID-19 and analyzed predictors of mortality. Methods: The survey was supported by the Scientific Working Group Infection in Hematology of the European Hematology Association (EHA). Eligible for the analysis were adult patients with HM and laboratory-confirmed COVID-19 observed between March and December 2020. Results: The study sample includes 3801 cases, represented by lymphoproliferative (mainly non-Hodgkin lymphoma n = 1084, myeloma n = 684 and chronic lymphoid leukemia n = 474) and myeloproliferative malignancies (mainly acute myeloid leukemia n = 497 and myelodysplastic syndromes n = 279). Severe/critical COVID-19 was observed in 63.8% of patients (n = 2425). Overall, 2778 (73.1%) of the patients were hospitalized, 689 (18.1%) of whom were admitted to intensive care units (ICUs). Overall, 1185 patients (31.2%) died. The primary cause of death was COVID-19 in 688 patients (58.1%), HM in 173 patients (14.6%), and a combination of both COVID-19 and progressing HM in 155 patients (13.1%). Highest mortality was observed in acute myeloid leukemia (199/497, 40%) and myelodysplastic syndromes (118/279, 42.3%). The mortality rate significantly decreased between the first COVID-19 wave (March–May 2020) and the second wave (October–December 2020) (581/1427, 40.7% vs. 439/1773, 24.8%, p value < 0.0001). In the multivariable analysis, age, active malignancy, chronic cardiac disease, liver disease, renal impairment, smoking history, and ICU stay correlated with mortality. Acute myeloid leukemia was a higher mortality risk than lymphoproliferative diseases. Conclusions: This survey confirms that COVID-19 patients with HM are at high risk of lethal complications. Ho

Published
2021

16. Induction of antigen-specific regulatory T cells following overexpression of a Notch ligand by human B lymphocytes

Author

Vigouroux, S, Yvon, E, Wagner, H, Biagi, E, Dotti, G, Sili, U, Lira, C, Rooney, C, Brenner, M, Brenner, M., BIAGI, ETTORE, Vigouroux, S, Yvon, E, Wagner, H, Biagi, E, Dotti, G, Sili, U, Lira, C, Rooney, C, Brenner, M, Brenner, M., and BIAGI, ETTORE

Abstract

In mice, activation of the Notch pathway in T cells by antigen-presenting cells overexpressing Notch ligands favors differentiation of regulatory T lymphocytes responsible for antigen-specific tolerance. To determine whether this mechanism operates in human T cells, we used Epstein-Barr virus-positive lymphoblastoid cell lines (EBV-LCL) as our (viral) antigen-presenting cells and overexpressed the Notch ligand Jagged-1 (EBV-LCL J1) by adenoviral transduction. The EBV-LCL J1s were cocultured with autologous T cells, and the proliferative and cytotoxic responses to EBV antigens were measured. Transduction had no effect on EBV-LCL expression of major histocompatibility complex (MHC) antigens or of costimulatory molecules CD80, CD86, and CD40. However, we observed a 35% inhibition of proliferation and a >65% reduction in cytotoxic-T-cell activity, and interleukin 10 production was increased ninefold. These EBV-LCL J1-stimulated T lymphocytes act as antigen-specific regulatory cells, since their addition to fresh autologous T cells cultured with autologous nontransduced EBV-LCL cells significantly inhibited both proliferation and cytotoxic effector function. Within the inhibitory population, CD4(+)CD25(+) and CD8(+)CD25(-) T cells had the greatest activity. This inhibition appears to be antigen-specific, since responses to Candida and cytomegalovirus antigens were unaffected. Hence, transgenic expression of Jagged-1 by antigen-presenting cells can induce antigen-specific regulatory T cells in humans and modify immune responses to viral antigens

Published
2003

18. Effect of video camera monitoring feedback on hand hygiene compliance in neonatal intensive care unit, an interventional study

Author

Huseyin Bilgin, Uluhan Sili, Nazli Pazar, Isil Kucuker, Eda Kepenekli, Meral Agirman Yanar, Asli Memisoglu, Eren Ozek, Neill KJ Adhikari, Ruxandra Pinto, Volkan Korten, and Bilgin H., SİLİ U., Pazar N., Kucuker I., Kepenekli E., Yanar M. A., MEMİŞOĞLU A., ÖZEK E., Adhikari N. K., Pinto R., et al.

Subjects
Social Sciences and Humanities, Social Sciences (SOC), Hawthorne effect, Family Medicine, Epidemiology, SOCIAL SCIENCES, GENERAL, SAĞLIK BAKIM BİLİMLERİ VE HİZMETLERİ, Hospital acquired infections, Life Sciences (LIFE), Aile Hekimliği, Glove use, Sağlık Bilimleri, Clinical Medicine (MED), IMMUNOLOGY, Sağlık Politikaları, Sociology, Video camera footage, Yaşam Bilimleri, Health Sciences, Epidemiyoloji, Sosyal ve Beşeri Bilimler, Klinik Tıp (MED), Sosyoloji, Halk, Çevre ve İş Sağlığı, PUBLIC, ENVIRONMENTAL & OCCUPATIONAL HEALTH, Internal Medicine Sciences, Klinik Tıp, İmmünoloji, Temel Bilimler, Health Policy, Public Health, Environmental and Occupational Health, Life Sciences, Dahili Tıp Bilimleri, INFECTIOUS DISEASES, Sosyal Bilimler Genel, CLINICAL MEDICINE, KAMU, ÇEVRE VE İŞ SAĞLIĞI, HEALTH CARE SCIENCES & SERVICES, Tıp, Bulaşıcı hastalıklar, Yaşam Bilimleri (LIFE), BULAŞICI HASTALIKLAR, Medicine, Sosyal Bilimler (SOC), Natural Sciences
Abstract

Background: The purpose of this study was to determine whether use of a video camera surveillance system for hand hygiene (HH) monitoring, video-based education, and feedback could improve the HH compliance in a neonatal intensive care unit (NICU). Methods and materials: This was an interventional before-after trial conducted in a level-III NICU between July 2019 and June 2020. HH compliance was measured using randomly selected video-camera footage in the baseline, intervention, and maintenance periods. After the baseline, an intervention consisting of feedback and education with video scenarios was implemented. The primary outcome was change in HH compliance. The compliance rates were analyzed as an interrupted time series (ITS) with a segmented regression model adjusted for autocorrelation for each study period. Results: We identified a total of 8335 HH indications. There were non significant increases in the total compliance rate (9.0%, 95% CI -2% to 20%) at the time of intervention and in the compliance rate after intervention (0.26%, 95% CI -0.31% to 0.84%) per day. The hand hygiene compliance before patient contact significantly increased (19.8%, 95% CI, 4.8%-34.8%). Incorrect glove use improved non-significantly with the intervention (-3.4%, 95% CI -13.4% to 6.7%). Conclusion: In this study of HH monitoring using video-camera footage combined with an intervention including feedback and education, there were inconsistent improvements in HH compliance. However, these improvements were not sustained in the long term. Frequent feedback and education may be required to sustain high compliance.

Published
2023

19. The effect of immunization with inactivated SARS-CoV-2 vaccine (CoronaVac) and/or SARS-CoV-2 infection on antibody levels, plasmablasts, long-lived-plasma-cells, and IFN-gamma release by natural killer cells

Author

Huseyin Bilgin, Marisa Marku, Sultan Seval Yilmaz, Aysegul Karahasan Yagci, Uluhan Sili, Baris Can, Rabia Can Sarinoglu, Lutfiye Mulazimoglu Durmusoglu, Goncagul Haklar, Onder Sirikci, Emel Eksioglu Demiralp, and Bilgin H., Marku M., Yilmaz S. S., Karahasan Yagci A., Sili U., Can B., Can Sarinoglu R., Mulazimoglu Durmusoglu L., Haklar G., Sirikci O., et al.

Subjects
COVID-19 Vaccines, Plasma Cells, Immunology, Life Sciences (LIFE), Antibodies, Viral, Sağlık Bilimleri, Medical Ecology and Hydroclimatology, Clinical Medicine (MED), Genel İmmünoloji ve Mikrobiyoloji, IFN-gamma, Interferon-gamma, Tıbbi Ekoloji ve Hidroklimatoloji, Araştırma ve Teori, Yaşam Bilimleri, Health Sciences, İncelemeler ve Referanslar (tıbbi), Humans, Klinik Tıp (MED), TIP, ARAŞTIRMA VE DENEYSEL, Internal Medicine Sciences, General Veterinary, İmmünoloji, Klinik Tıp, Research and Theory, General Immunology and Microbiology, SARS-CoV-2, Temel Bilimler, SARS-CoV-2 infection, Vaccination, Public Health, Environmental and Occupational Health, Anti-spike antibody, Life Sciences, COVID-19, Dahili Tıp Bilimleri, CLINICAL MEDICINE, Tıp, Killer Cells, Natural, Infectious Diseases, Yaşam Bilimleri (LIFE), MEDICINE, RESEARCH & EXPERIMENTAL, Reviews and References (medical), Molecular Medicine, Medicine, CoronaVac, Whole virion inactivated vaccine, Natural Sciences
Abstract

Objectives: We evaluated the antibody response, natural killer cell response and B cell phenotypes in healthcare workers (HCW) who are vaccinated with two doses of CoronaVac with or without documented SARS-CoV-2 infection and unvaccinated HCWs with SARS-CoV-2 infection. Methods: HCWs were divided into four groups: vaccine only (VO), vaccine after SARS-CoV-2 infection (VAI), SARS-CoV-2 infection only (IO), and SARS-CoV-2 infection after vaccine (IAV). Anti-SARS-CoV-2 spike protein (Anti-S) antibodies were measured by Elecsys Anti–SARS–CoV–2 S ELISA kit. Memory B cells (CD19+ CD27+ ), plasmablast B cells (CD19+ CD138+ ) and long-lived plasma cells (LLPC; CD138+ CD19- ) were measured by flow cytometry in 74 patients. Interferon gamma (IFN-c) release by natural killer (NK) cells were measured by NKVue Test (NKMAX, Republic of Korea) in 76 patients. RT-PCR was performed with Bio-speedy COVID-19 qPCR detection kit, Version 2 (Bioexen LTD, Istanbul, Turkey). Results: The Anti-S antibodies were detectable in all HCWs (n: 224). The median Anti-S titers (BAU/mL) was significantly higher in VAI (620 25–75% 373–1341) compared to VO (136, 25–75% 85–283) and IO (111, 25–75% 54–413, p < 0.01). VAI group had significantly lower percentage of plasmablasts (2.9; 0– 8.7) compared to VO (6.8; 3.5–12.0) and IO (9.9; 4.7–47.5, p < 0.01) (n:74). Percentage of LLPCs in groups VO, VAI and IO was similar. There was no difference of IFN-c levels between the study groups (n: 76). Conclusion: The antibody response was similar between uninfected vaccinated HCWs and unvaccinated HCWs who had natural infection. HCWs who had two doses of CoronaVac either before or after the natural SARS-CoV-2 infection elicited significantly higher antibody responses compared to uninfected vaccinated HCWs. The lower percentages of plasmablasts in the VAI group may indicate their migration to lymph nodes and initiation of the germinal center reaction phase. IFN-c response did not differ among the groups.

Published
2022

21. COVID-19 infection in adult patients with hematological malignancies:a European Hematology Association Survey (EPICOVIDEHA)

Author

Pagano, Livio, Salmanton-García, Jon, Marchesi, Francesco, Busca, Alessandro, Corradini, Paolo, Hoenigl, Martin, Klimko, Nikolai, Koehler, Philipp, Pagliuca, Antonio, Passamonti, Francesco, Verga, Luisa, Víšek, Benjamin, Ilhan, Osman, Nadali, Gianpaolo, Weinbergerová, Barbora, Córdoba-Mascuñano, Raúl, Marchetti, Monia, Collins, Graham P., Farina, Francesca, Cattaneo, Chiara, Cabirta, Alba, Gomes-Silva, Maria, Itri, Federico, van Doesum, Jaap, Ledoux, Marie-Pierre, Čerňan, Martin, Jakšić, Ozren, Duarte, Rafael F., Magliano, Gabriele, Omrani, Ali S., Fracchiolla, Nicola S., Kulasekararaj, Austin, Valković, Toni, Poulsen, Christian Bjørn, Machado, Marina, Glenthøj, Andreas, Stoma, Igor, Ráčil, Zdeněk, Piukovics, Klára, Navrátil, Milan, Emarah, Ziad, Sili, Uluhan, Maertens, Johan, Blennow, Ola, Bergantim, Rui, García-Vidal, Carolina, Prezioso, Lucia, Guidetti, Anna, del Principe, Maria Ilaria, Popova, Marina, de Jonge, Nick, Ormazabal-Vélez, Irati, Fernández, Noemí, Falces-Romero, Iker, Cuccaro, Annarosa, Meers, Stef, Buquicchio, Caterina, Antić, Darko, Al-Khabori, Murtadha, García-Sanz, Ramón, Biernat, Monika M., Tisi, Maria Chiara, Sal, Ertan, Rahimli, Laman, Čolović, Natasa, Schönlein, Martin, Calbacho, Maria, Tascini, Carlo, Miranda-Castillo, Carolina, Khanna, Nina, Méndez, Gustavo-Adolfo, Petzer, Verena, Novák, Jan, Besson, Caroline, Duléry, Rémy, Lamure, Sylvain, Nucci, Marcio, Zambrotta, Giovanni, Žák, Pavel, Seval, Guldane Cengiz, Bonuomo, Valentina, Mayer, Jiří, López-García, Alberto, Sacchi, Maria Vittoria, Booth, Stephen, Ciceri, Fabio, Oberti, Margherita, Salvini, Marco, Izuzquiza, Macarena, Nunes-Rodrigues, Raquel, Ammatuna, Emanuele, Obr, Aleš, Herbrecht, Raoul, Núñez-Martín-Buitrago, Lucía, Mancini, Valentina, Shwaylia, Hawraa, Sciumè, Mariarita, Essame, Jenna, Nygaard, Marietta, Batinić, Josip, Gonzaga, Yung, Regalado-Artamendi, Isabel, Karlsson, Linda Katharina, Shapetska, Maryia, Hanakova, Michaela, El-Ashwah, Shaimaa, Borbényi, Zita, Çolak, Gökçe Melis, Nordlander, Anna, Dragonetti, Giulia, Maraglino, Alessio Maria Edoardo, Rinaldi, Amelia, De Ramón-Sánchez, Cristina, Cornely, Oliver A., Finizio, Olimpia, Fazzi, Rita, Sapienza, Giuseppe, Chauchet, Adrien, Van Praet, Jens, Prattes, Juergen, Dargenio, Michelina, Rossi, Cédric, Shirinova, Ayten, Malak, Sandra, Tafuri, Agostino, Ommen, Hans-Beier, Bologna, Serge, Khedr, Reham Abdelaziz, Choquet, Sylvain, Joly, Bertrand, Ceesay, M. Mansour, Philippe, Laure, Kho, Chi Shan, Desole, Maximilian, Tsirigotis, Panagiotis, Otašević, Vladimir, Borducchi, Davimar M. M., Antoniadou, Anastasia, Gaziev, Javid, Almaslamani, Muna A., García-Poutón, Nicole, Paterno, Giovangiacinto, Torres-López, Andrea, Tarantini, Giuseppe, Mellinghoff, Sibylle, Gräfe, Stefanie, Börschel, Niklas, Passweg, Jakob, Merelli, Maria, Barać, Aleksandra, Wolf, Dominik, Shaikh, Mohammad Usman, Thiéblemont, Catherine, Bernard, Sophie, Funke, Vaneuza Araújo Moreira, Daguindau, Etienne, Khostelidi, Sofya, Nucci, Fabio Moore, Martín-González, Juan-Alberto, Landau, Marianne, Soussain, Carole, Laureana, Cécile, Lacombe, Karine, Kohn, Milena, Aliyeva, Gunay, Piedimonte, Monica, Fouquet, Guillemette, Rêgo, Mayara, Hoell-Neugebauer, Baerbel, Cartron, Guillaume, Pinto, Fernando, Alburquerque, Ana Munhoz, Passos, Juliana, Yilmaz, Asu Fergun, Redondo-Izal, Ana-Margarita, Altuntaş, Fevzi, Heath, Christopher, Kolditz, Martin, Schalk, Enrico, Guolo, Fabio, Karthaus, Meinolf, Della Pepa, Roberta, Vinh, Donald, Noël, Nicolas, Deau Fischer, Bénédicte, Drenou, Bernard, Mitra, Maria Enza, Meletiadis, Joseph, Bilgin, Yavuz M., Jindra, Pavel, Espigado, Ildefonso, Drgoňa, Ľuboš, Serris, Alexandra, Di Blasi, Roberta, Ali, Natasha, EPICOVIDEHA working group, [missing], Pagano, Livio, Salmanton-Garcia, Jon, Marchesi, Francesco, Busca, Alessandro, Corradini, Paolo, Hoenigl, Martin, Klimko, Nikolai, Koehler, Philipp, Pagliuca, Antonio, Passamonti, Francesco, Verga, Luisa, Visek, Benjamin, Ilhan, Osman, Nadali, Gianpaolo, Weinbergerova, Barbora, Cordoba-Mascunano, Raul, Marchetti, Monia, Collins, Graham P., Farina, Francesca, Cattaneo, Chiara, Cabirta, Alba, Gomes-Silva, Maria, Itri, Federico, van Doesum, Jaap, Ledoux, Marie-Pierre, Cernan, Martin, Jaksic, Ozren, Duarte, Rafael F., Magliano, Gabriele, Omrani, Ali S., Fracchiolla, Nicola S., Kulasekararaj, Austin, Valkovic, Toni, Poulsen, Christian Bjorn, Machado, Marina, Glenthoj, Andreas, Stoma, Igor, Racil, Zdenek, Piukovics, Klara, Navratil, Milan, Emarah, Ziad, Sili, Uluhan, Maertens, Johan, Blennow, Ola, Bergantim, Rui, Garcia-Vidal, Carolina, Prezioso, Lucia, Guidetti, Anna, del Principe, Maria Ilaria, Popova, Marina, de Jonge, Nick, Ormazabal-Velez, Irati, Fernandez, Noemi, Falces-Romero, Iker, Cuccaro, Annarosa, Meers, Stef, Buquicchio, Caterina, Antic, Darko, Al-Khabori, Murtadha, Garcia-Sanz, Ramon, Biernat, Monika M., Tisi, Maria Chiara, Sal, Ertan, Rahimli, Laman, Colovic, Natasa, Schonlein, Martin, Calbacho, Maria, Tascini, Carlo, Miranda-Castillo, Carolina, Khanna, Nina, Mendez, Gustavo-Adolfo, Petzer, Verena, Novak, Jan, Besson, Caroline, Dulery, Remy, Lamure, Sylvain, Nucci, Marcio, Zambrotta, Giovanni, Zak, Pavel, Seval, Guldane Cengiz, Bonuomo, Valentina, Mayer, Jiri, Lopez-Garcia, Alberto, Sacchi, Maria Vittoria, Booth, Stephen, Ciceri, Fabio, Oberti, Margherita, Salvini, Marco, Izuzquiza, Macarena, Nunes-Rodrigues, Raquel, Ammatuna, Emanuele, Obr, Ales, Herbrecht, Raoul, Nunez-Martin-Buitrago, Lucia, Mancini, Valentina, Shwaylia, Hawraa, Sciume, Mariarita, Essame, Jenna, Nygaard, Marietta, Batinic, Josip, Gonzaga, Yung, Regalado-Artamendi, Isabel, Karlsson, Linda Katharina, Shapetska, Maryia, Hanakova, Michaela, El-Ashwah, Shaimaa, Borbenyi, Zita, Colak, Gokce Melis, Nordlander, Anna, Dragonetti, Giulia, Maraglino, Alessio Maria Edoardo, Rinaldi, Amelia, De Ramon-Sanchez, Cristina, Cornely, Oliver A., 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, G. P., Farina, F., Cattaneo, C., Cabirta, A., Gomes-Silva, M., Itri, F., van Doesum, J., Ledoux, M. -P., Cernan, M., Jaksic, O., Duarte, R. F., Magliano, G., Omrani, A. S., Fracchiolla, N. S., Kulasekararaj, A., Valkovic, T., Poulsen, C. B., 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, M. I., 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, M. M., Tisi, M. C., Sal, E., Rahimli, L., Colovic, N., Schonlein, M., Calbacho, M., Tascini, C., Miranda-Castillo, C., Khanna, N., Mendez, G. -A., Petzer, V., Novak, J., Besson, C., Dulery, R., Lamure, S., Nucci, M., Zambrotta, G., Zak, P., Seval, G. C., Bonuomo, V., Mayer, J., Lopez-Garcia, A., Sacchi, M. V., 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, L. K., Shapetska, M., Hanakova, M., El-Ashwah, S., Borbenyi, Z., Colak, G. M., Nordlander, A., Dragonetti, G., Maraglino, A. M. E., Rinaldi, A., De Ramon-Sanchez, C., Cornely, O. A., Finizio, O., Fazzi, R., Sapienza, G., Chauchet, A., Van Praet, J., Prattes, J., Dargenio, M., Rossi, C., Shirinova, A., Malak, S., Tafuri, A., Ommen, H. -B., Bologna, S., Khedr, R. A., Choquet, S., Joly, B., Ceesay, M. M., Philippe, L., Kho, C. S., Desole, M., Tsirigotis, P., Otasevic, V., Borducchi, D. M. M., Antoniadou, A., Gaziev, J., Almaslamani, M. A., Garcia-Pouton, N., Paterno, G., Torres-Lopez, A., Tarantini, G., Mellinghoff, S., Grafe, S., Borschel, N., Passweg, J., Merelli, M., Barac, A., Wolf, D., Shaikh, M. U., Thieblemont, C., Bernard, S., Funke, V. A. M., Daguindau, E., Khostelidi, S., Nucci, F. M., Martin-Gonzalez, J. -A., Landau, M., Soussain, C., Laureana, C., Lacombe, K., Kohn, M., Aliyeva, G., Piedimonte, M., Fouquet, G., Rego, M., Hoell-Neugebauer, B., Cartron, G., Pinto, F., Alburquerque, A. M., Passos, J., Yilmaz, A. F., Redondo-Izal, A. -M., Altuntas, F., Heath, C., Kolditz, M., Schalk, E., Guolo, F., Karthaus, M., Della Pepa, R., Vinh, D., Noel, N., Deau Fischer, B., Drenou, B., Mitra, M. E., Meletiadis, J., Bilgin, Y. M., Jindra, P., Espigado, I., Drgona, L., Serris, A., Di Blasi, R., Ali, N., Stem Cell Aging Leukemia and Lymphoma (SALL), Salvy-Córdoba, Nathalie, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università cattolica del Sacro Cuore = Catholic University of the Sacred Heart [Roma] (Unicatt), University Hospital of Cologne [Cologne], Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, IFO - Istituto Nazionale Tumori Regina Elena [Roma] (IRE), Città della Salute e della Scienza University-Hospital, IRCCS Istituto Nazionale dei Tumori [Milano], University of California [San Diego] (UC San Diego), University of California (UC), Medical University of Graz, Odessa National I.I.Mechnikov University, Faculty of Medicine [Cologne], University Hospital of Cologne [Cologne]-University of Cologne, King's College Hospital (KCH), Universitá degli Studi dell’Insubria = University of Insubria [Varese] (Uninsubria), Dipartimento di Medicina e Chirurgia = School of Medicine and Surgery [Monza], Università degli Studi di Milano-Bicocca = University of Milano-Bicocca (UNIMIB), Faculty of Medicine in Hradec Kralove [Republique Tchèque], Charles University [Prague] (CU), Ankara University School of Medicine [Turkey], Azienda Ospedaliera Universitaria Integrata of Verona, Masaryk University [Brno] (MUNI), Fundación Jiménez Díaz, Fundacion Jimenez Diaz [Madrid] (FJD), Ospedale SS Antonio e Biagio e Cesare Arrigo, Churchill Hospital Oxford Centre for Haematology, IRCCS San Raffaele Scientific Institute [Milan, Italie], ASST Spedali Civili of Brescia, Vall d'Hebron Institute of Oncology [Barcelone] (VHIO), Vall d'Hebron University Hospital [Barcelona], Universitat Autònoma de Barcelona (UAB), Instituto Português de Oncologia de Lisboa Francisco Gentil, Ospedale San Luigi Gonzaga, University Medical Center Groningen [Groningen] (UMCG), Institut de Cancérologie de Strasbourg Europe (ICANS), Palacky University Olomouc, Zagreb School of Medicine [Zagreb, Croatia] (Dubrava University Hospital), University of Zagreb, Hospital Universitario Puerta de Hierro-Majadahonda [Madrid, Spain], ASST Great Metropolitan Niguarda / ASST Grande Ospedale Metropolitano Niguarda [Milan, Italia], Hamad Medical Corporation [Doha, Qatar], Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, University of Rijeka, Croatian Cooperative Group for Hematological Diseases (CROHEM), Zealand University Hospital [Roskilde, Denmark], Hospital General Universitario 'Gregorio Marañón' [Madrid], Department of Clinical Microbiology [Rigshospitalet], Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, Homieĺ State Medical University (GSMU), Institute of Hematology and Blood Transfusion [Prague, Czech Republic], University of Szeged [Szeged], University Hospital Ostrava, Mansoura University [Egypt], Marmara University [Kadıköy - İstanbul], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Karolinska University Hospital [Stockholm], Instituto de Investigação e Inovação em Saúde (I3S), Universidade do Porto = University of Porto, Instituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP), Hospital de São João [Porto], Faculdade de Medicina da Universidade do Porto (FMUP), Clinic Barcelona Hospital Universitari, Department of Public Health and Cell Biology, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy, Pavlov First Saint Petersburg State Medical University [St. Petersburg], Vrije Universiteit Medical Centre (VUMC), Vrije Universiteit Amsterdam [Amsterdam] (VU), Complejo Hospitalario de Navarra, Hospital Universitario Marqués de Valdecilla [Santander], La Paz University Hospital, Azienda Usl Toscana centro [Firenze], AZ Klina, Clinical Center of Serbia (KCS), University of Belgrade [Belgrade], Sultan Qaboos University Hospital, Partenaires INRAE, Hospital Universitario de Salamanca, Servicio de Haematologia, Centro de Investigación del Cáncer-IBMCC (USAL-CSIC), University of Wrocław [Poland] (UWr), San Bortolo Hospital, Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Hospital Universitario 12 de Octubre [Madrid], Azienda Sanitaria Universitaria Friuli Centrale (ASU FC), Universidad Rey Juan Carlos [Madrid] (URJC), University of Basel (Unibas), Innsbruck Medical University = Medizinische Universität Innsbruck (IMU), University Hospital Kralovské Vinohrady, Centre Hospitalier de Versailles André Mignot (CHV), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut de Génétique Moléculaire de Montpellier (IGMM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Département Hématologie biologique [CHRU Montpellier], Pôle Biologie-Pathologie [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Universidade Federal do Estado do Rio de Janeiro (UNIRIO), San Gerardo Hospital of Monza, Oxford NIHR Biomedical Research Centre, IRCCS Ospedale San Raffaele [Milan, Italy], Assi Sette Llaghi Varese, Instituto Português de Oncologia do Porto / Portuguese Oncology Institute of Porto (IPO Porto), University Hospital Olomouc [Czech Republic], ASST Grande Ospedale Metropolitano Niguarda, University Hospital Centre Zagreb, Instituto Nacional do Câncer, Copenhagen University Hospital, Republican Scientific and Practical Center (RSPC) for organ and Tissue Transplantation, Minsk, Republican Scientific and Practical Center (RSPC) for Organ and Transplantation, German Centre for Infection Research (DZIF), Gilead Sciences, Pagano, Livio [0000-0001-8287-928X], Salmanton-García, Jon [0000-0002-6766-8297], Marchesi, Francesco [0000-0001-6353-2272], Busca, Alessandro [0000-0001-5361-5613], Corradini, Paolo [0000-0002-9186-1353], Hoenigl, Martin [0000-0002-1653-2824], Klimko, Nikolay [0000-0001-6095-7531], Koehler, Philipp [0000-0002-7386-7495], Pagliuca, Antonio [0000-0003-2519-0333], Passamonti, Francesco [0000-0001-8068-5289], Verga, Luisa [0000-0003-1142-8435], Víšek, Benjamin [0000-0001-8268-452X], Ilhan, Osman [0000-0003-1665-372X], Weinbergerová, Barbora [0000-0001-6460-2471], Córdoba, Raúl [0000-0002-7654-8836], Marchetti, Monia [0000-0001-7615-0572], Farina, Francesca [0000-0002-5124-6970], Cattaneo, Chiara [0000-0003-0031-3237], Cabirta, Alba [0000-0001-7198-8894], Gomes-Silva, Maria [0000-0002-6993-2450], Itri, Federico [0000-0002-3532-5281], Doesum, Jaap van [0000-0003-0214-3219], Ledoux, Marie-Pierre [0000-0002-3261-3616], Čerňan, Martin [0000-0003-2345-1229], Jakšić, Ozren [0000-0003-4026-285X], Magliano, Gabriel [0000-0002-9129-1530], Omrani, Ali S. [0000-0001-5309-6358], Fracchiolla, Nicola S. [0000-0002-8982-8079], Kulasekararaj, Austin G. [0000-0003-3180-3570], Valković, Toni [0000-0001-6083-8815], Poulsen, Christian Bjørn [0000-0001-9785-1378], Machado, Marina [0000-0002-8370-2248], Glenthøj, Andrea [0000-0003-2082-0738], Stoma, Igor [0000-0003-0483-7329], Ráčil, Zdeněk [0000-0003-3511-4596], Piukovics, Klára [0000-0003-4480-3131], Emarah, Ziad [0000-0003-0622-2598], Sili, Uluhan [0000-0002-9939-9298], Maertens, Johan [0000-0003-4257-5980], Bergantim, Rui [0000-0002-7811-9509], García-Vidal, Carolina [0000-0002-8915-0683], Prezioso, Lucia [0000-0003-1660-4960], Principe, Maria Ilaria del [0000-0002-3958-0669], Popova, Marina [0000-0001-8536-5495], Jonge, Nick de [0000-0002-9901-0887], Ormazabal-Vélez, Irati [0000-0003-1141-5546], Falces-Romero, Iker [0000-0001-5888-7706], Cuccaro, Annarosa [0000-0002-0237-1839], Meers, Stef [0000-0003-1754-2175], Buquicchio, Caterina [0000-0002-3683-5953], Antić, Darko [0000-0002-2608-1342], Al-Khabori, Murtadha [0000-0002-2937-8838], García-Sanz, Ramón [0000-0003-4120-2787], Biernat, Monika [0000-0003-3161-3398], Tisi, Maria Chiara [0000-0001-8231-6700], Sal, Ertan [0000-0003-2761-2675], Rahimli, Laman [0000-0003-2266-445X], Schönlein, Martin [0000-0002-1010-0975], Calbacho, María [0000-0001-8106-4863], Tascini, Carlo [0000-0001-9625-6024], Miranda-Castillo, Carolina [0000-0001-8763-9576], Khanna, Nina [0000-0002-2642-419X], Méndez, Gustavo-Adolfo [0000-0003-0514-7004], Petzer, Verena [0000-0002-9205-1440], Besson, Caroline [0000-0003-4364-7173], Duléry, Rémy [0000-0002-5024-1713], Lamure, Sylvain [0000-0001-5980-305X], Nucci, Marcio [0000-0003-4867-0014], Zambrotta, Giovanni [0000-0002-8612-2994], Žák, Pavel [0000-0003-4465-5343], Cengiz Seval, Guldane [0000-0001-9433-2054], Bonuomo, Valentina [0000-0001-6491-8337], Mayer, Jiří [0000-0003-0567-9887], López-García, Alberto [0000-0002-5354-5261], Sacchi, Maria Vittoria [0000-0001-8133-3357], Booth, Stephen [0000-0003-2687-0234], Ciceri, Fabio [0000-0003-0873-0123], Nunes-Rodrigues, Raquel [0000-0002-8347-4281], Ammatuna, Emanuele [0000-0001-8247-4901], Obr, Aleš [0000-0002-6758-3074], Herbrecht, Raoul [0000-0002-9381-4876], Shwaylia, Hawraa [0000-0002-4098-6092], Sciumè, Mariarita [0000-0001-7958-4966], Essame, Jenna [0000-0003-0926-5577], Batinić, Josip [0000-0001-5595-9911], Gonzaga, Yung [0000-0003-1416-2118], Regalado-Artamendi, Isabel [0000-0002-9673-9015], Karlsson, Linda Katharina [0000-0003-3317-7550], Shapetska, Maryia [0000-0002-1223-9161], El-Ashwah, Shaimaa [0000-0003-2210-1534], Çolak, Gökçe Melis [0000-0002-7662-7454], Dragonetti, Giulia [0000-0003-1775-6333], Rinaldi, Amelia [0000-0002-8211-5076], Ramón, Cristina de [0000-0002-8167-6410], Cornely, Oliver A. [0000-0001-9599-3137], Institut Català de la Salut, [Pagano L] Hematology, Fondazione Policlinico Universitario Agostino Gemelli - IRCCS – Università Cattolica del Sacro Cuore, Rome, Italy. Università Cattolica del Sacro Cuore, Rome, Italy. [Salmanton-García J] Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Excellence Center for Medical Mycology (ECMM), University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany. Cologne Excellence Cluster On Cellular Stress Responses in Aging Associated Diseases (CECAD), University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany. [Marchesi F] Hematology and Stem Cell Transplant Unit, IRCCS Regina Elena National Cancer Institute, Rome, Italy. [Busca A] Stem Cell Transplant Center, AOU Citta’ Della Salute E Della Scienza, Turin, Italy. [Corradini P] University of Milan and Fondazione IRCCS Istituto Nazionale Dei Tumori, Milan, Italy. [Hoenigl M] Division of Infectious Diseases and Global Public Health, Department of Medicine, University of California San Diego, San Diego, CA, USA. Clinical and Translational Fungal Working Group, University of California San Diego, La Jolla, CA, USA. Section of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Medical University of Graz, Graz, Austria. [Cabirta A, Izuzquiza M] Servei d’Hematologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Experimental Hematology, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Departament de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain, Vall d'Hebron Barcelona Hospital Campus, Hematology, Salmanton-García, Jon, Klimko, Nikolay, Víšek, Benjamin, Weinbergerová, Barbora, Córdoba, Raúl, Doesum, Jaap van, Čerňan, Martin, Jakšić, Ozren, Magliano, Gabriel, Kulasekararaj, Austin G., Valković, Toni, Poulsen, Christian Bjørn, Glenthøj, Andrea, Ráčil, Zdeněk, Piukovics, Klára, García-Vidal, Carolina, Principe, Maria Ilaria del, Jonge, Nick de, Ormazabal-Vélez, Irati, Antić, Darko, García-Sanz, Ramón, Biernat, Monika, Schönlein, Martin, Calbacho, María, Méndez, Gustavo-Adolfo, Duléry, Rémy, Žák, Pavel, Cengiz Seval, Guldane, Mayer, Jiří, López-García, Alberto, Obr, Aleš, Sciumè, Mariarita, Batinić, Josip, Çolak, Gökçe Melis, Ramón, Cristina de, and Universidad de Sevilla. Departamento de Medicina

Subjects
[SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Male, Cancer Research, MESH: Registries, Epidemiology, MESH: Hospitalization, Hematological malignancies, Otros calificadores::Otros calificadores::/complicaciones [Otros calificadores], MESH: Aged, 80 and over, MESH: Risk Factors, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Risk Factors, Malalties - Factors de risc, Risk of mortality, Medicine and Health Sciences, virosis::infecciones por virus ARN::infecciones por Nidovirales::infecciones por Coronaviridae::infecciones por Coronavirus [ENFERMEDADES], 80 and over, Medicine, MESH: COVID-19, Registries, Sang - Malalties - Complicacions, RC254-282, Cause of death, BIOMEDICINA I ZDRAVSTVO. Kliničke medicinske znanosti. Interna medicina, MESH: Aged, Aged, 80 and over, Hematology, MESH: Middle Aged, Mortality rate, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Myeloid leukemia, Virus Diseases::RNA Virus Infections::Nidovirales Infections::Coronaviridae Infections::Coronavirus Infections [DISEASES], [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Middle Aged, CANCER, Europe, Hospitalization, Intensive Care Units, Oncology, MESH: Young Adult, Hematologic Neoplasms, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Female, BIOMEDICINA I ZDRAVSTVO. Kliničke medicinske znanosti. Infektologija, Life Sciences & Biomedicine, Adult, medicine.medical_specialty, [SDV.CAN]Life Sciences [q-bio]/Cancer, COVID-19, EHA, Pandemic, Aged, Humans, SARS-CoV-2, Young Adult, técnicas de investigación::métodos epidemiológicos::estadística como asunto::probabilidad::riesgo::factores de riesgo [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], [SDV.CAN] Life Sciences [q-bio]/Cancer, Intensive care, Internal medicine, Diseases of the blood and blood-forming organs, MESH: SARS-CoV-2, neoplasias::neoplasias por localización::neoplasias hematológicas [ENFERMEDADES], Molecular Biology, BIOMEDICINE AND HEALTHCARE. Clinical Medical Sciences. Internal Medicine, pandemic, hematological malignancies, epidemiology, MESH: Humans, Science & Technology, business.industry, Myelodysplastic syndromes, Research, MESH: Adult, Neoplasms::Neoplasms by Site::Hematologic Neoplasms [DISEASES], medicine.disease, BIOMEDICINE AND HEALTHCARE. Clinical Medical Sciences. Infectology, Settore MED/15, MESH: Male, Settore MED/15 - MALATTIE DEL SANGUE, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, COVID-19 (Malaltia) - Diagnòstic, MESH: Intensive Care Units, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk Factors [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], MESH: Europe, RC633-647.5, business, MESH: Female, Other subheadings::Other subheadings::/complications [Other subheadings], MESH: Hematologic Neoplasms
Abstract

Background Patients with hematological malignancies (HM) are at high risk of mortality from SARS-CoV-2 disease 2019 (COVID-19). A better understanding of risk factors for adverse outcomes may improve clinical management in these patients. We therefore studied baseline characteristics of HM patients developing COVID-19 and analyzed predictors of mortality. Methods The survey was supported by the Scientific Working Group Infection in Hematology of the European Hematology Association (EHA). Eligible for the analysis were adult patients with HM and laboratory-confirmed COVID-19 observed between March and December 2020. Results The study sample includes 3801 cases, represented by lymphoproliferative (mainly non-Hodgkin lymphoma n = 1084, myeloma n = 684 and chronic lymphoid leukemia n = 474) and myeloproliferative malignancies (mainly acute myeloid leukemia n = 497 and myelodysplastic syndromes n = 279). Severe/critical COVID-19 was observed in 63.8% of patients (n = 2425). Overall, 2778 (73.1%) of the patients were hospitalized, 689 (18.1%) of whom were admitted to intensive care units (ICUs). Overall, 1185 patients (31.2%) died. The primary cause of death was COVID-19 in 688 patients (58.1%), HM in 173 patients (14.6%), and a combination of both COVID-19 and progressing HM in 155 patients (13.1%). Highest mortality was observed in acute myeloid leukemia (199/497, 40%) and myelodysplastic syndromes (118/279, 42.3%). The mortality rate significantly decreased between the first COVID-19 wave (March–May 2020) and the second wave (October–December 2020) (581/1427, 40.7% vs. 439/1773, 24.8%, p value, EPICOVIDEHA has received funds from Optics COMMITTM (COVID-19 Unmet Medical Needs and Associated Research Extension) COVID-19 RFP program by GILEAD Science, United States (Project 2020-8223).

Published
2021

22. Induction of antigen-specific regulatory T cells following overexpression of a Notch ligand by human B lymphocytes

Author

Ettore Biagi, Cecilia Lira, Cliona M. Rooney, Stephane Vigouroux, Malcolm K. Brenner, Hans Joachim Wagner, Uluhan Sili, Gianpietro Dotti, Eric Yvon, Vigouroux, S, Yvon, E, Wagner, H, Biagi, E, Dotti, G, Sili, U, Lira, C, Rooney, C, and Brenner, M

Subjects
Adult, Herpesvirus 4, Human, T-Lymphocytes, Immunology, Lymphocyte Activation, Microbiology, Immunophenotyping, Interleukin 21, hemic and lymphatic diseases, Virology, Immune Tolerance, Intercellular Signaling Peptides and Protein, Humans, Cytotoxic T cell, Serrate-Jagged Proteins, IL-2 receptor, Antigen-presenting cell, Antigens, Viral, Membrane Protein, Calcium-Binding Protein, CD86, B-Lymphocytes, CD40, biology, Receptors, Notch, Calcium-Binding Proteins, B-Lymphocyte, Membrane Proteins, Cell biology, Insect Science, Interleukin 12, biology.protein, Intercellular Signaling Peptides and Proteins, Pathogenesis and Immunity, Immunologic Memory, Jagged-1 Protein, CD80, Human
Abstract

In mice, activation of the Notch pathway in T cells by antigen-presenting cells overexpressing Notch ligands favors differentiation of regulatory T lymphocytes responsible for antigen-specific tolerance. To determine whether this mechanism operates in human T cells, we used Epstein-Barr virus-positive lymphoblastoid cell lines (EBV-LCL) as our (viral) antigen-presenting cells and overexpressed the Notch ligand Jagged-1 (EBV-LCL J1) by adenoviral transduction. The EBV-LCL J1s were cocultured with autologous T cells, and the proliferative and cytotoxic responses to EBV antigens were measured. Transduction had no effect on EBV-LCL expression of major histocompatibility complex (MHC) antigens or of costimulatory molecules CD80, CD86, and CD40. However, we observed a 35% inhibition of proliferation and a >65% reduction in cytotoxic-T-cell activity, and interleukin 10 production was increased ninefold. These EBV-LCL J1-stimulated T lymphocytes act as antigen-specific regulatory cells, since their addition to fresh autologous T cells cultured with autologous nontransduced EBV-LCL cells significantly inhibited both proliferation and cytotoxic effector function. Within the inhibitory population, CD4+CD25+and CD8+CD25−T cells had the greatest activity. This inhibition appears to be antigen-specific, since responses toCandidaand cytomegalovirus antigens were unaffected. Hence, transgenic expression of Jagged-1 by antigen-presenting cells can induce antigen-specific regulatory T cells in humans and modify immune responses to viral antigens.

Published
2003

23. Dexamethasone treatment for COVID-19 is related to increased mortality in hematologic malignancy patients: results from the EPICOVIDEHA registry.

Author

Aiello TF, Salmanton-Garcia J, Marchesi F, Weinbergerova B, Glenthoj A, Van Praet J, Farina F, Davila-Valls J, Martin-Perez S, El-Ashwah S, Schonlein M, Falces-Romero I, Labrador J, Sili U, Buquicchio C, Vena A, Plantefeve G, Petzer V, Biernat MM, Lahmer T, Espigado I, Van Doesum J, Blennow O, Piukovics K, Tascini C, Samarkos M, Bilgin YM, Fianchi L, Itri F, Valković T, Fracchiolla NS, Dargenio M, Jimenez M, Magyari F, Lopez-Garcia A, Prezioso L, Čolović N, Shumilov E, Abu-Zeinah G, Krekeler C, Lavilla-Rubira E, Papa MV, Gonzalez-Lopez TJ, Pinczes LI, Demirkan F, Ali N, Besson C, Fouquet G, Romano A, Hernandez-Rivas JA, Del Principe MI, Aujayeb A, Merelli M, Lamure S, De Almeida JM, Da Silva MG, Eisa N, Meletiadis J, Rinaldi I, Finizio O, Jaksic O, Delia M, Nizamuddin S, Marchetti M, Ijaz M, Machado M, Bailen-Almorox R, Čerňan M, Coppola N, Gavriilaki E, Cattaneo C, Groh A, Stojanoski Z, Erben N, Pantic N, Mendez GA, Di Blasi R, Meers S, De Ramon C, Bahr NC, Emarah Z, Varricchio G, Cvetanoski M, Garcia-Sanz R, Mitrovic M, Lievin R, Hanakova M, Račil Z, Vehreschild M, Tragiannidis A, Rodrigues RN, Garcia-Bordallo D, Cordoba R, Cabirta A, Nordlander A, Ammatuna E, Arellano E, Wolf D, Prin R, Limongelli A, Bavastro M, Colak GM, Grafe S, Hersby DS, Rahimli L, Cornely OA, Garcia-Vidal C, Pagano L, and Study Group E

Subjects
Humans, Male, Female, Aged, Middle Aged, Adult, Aged, 80 and over, Dexamethasone therapeutic use, Hematologic Neoplasms mortality, Hematologic Neoplasms drug therapy, Registries, COVID-19 mortality, COVID-19 complications, SARS-CoV-2 isolation & purification, COVID-19 Drug Treatment
Published
2024
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24. Clinical Pharmacist-Led Medication Review in Hospitalized Confirmed or Probable Patients with COVID-19 During the First Wave of COVID-19 Pandemic.

Author

Ünder D, Enver C, Demirci MY, Ayhan YE, Özgan B, İlerler EE, Okuyan B, Ertürk Şengel B, Kocakaya D, Sili U, Tükenmez Tigen E, Karakurt S, Korten V, and Sancar M

Abstract

Objectives: Drug-related problems (DRPs) result in serious problems among hospitalized patients, high rates of morbidity and mortality, and increased healthcare costs. This study aimed to identify DRPs by clinical pharmacist-led medication review in hospitalized probable patients with coronavirus disease-2019 (COVID-19) during the first wave of the COVID-19 pandemic., Materials and Methods: This retrospective cross-sectional study was conducted at the COVID-19 inpatient services of a tertiary university hospital in Türkiye for 3 months (between March 2020 and June 2020) and included hospitalized confirmed or probable COVID-19 patients. The World Health Organization and Turkish Ministry of Health Guidelines case definitions were used to define confirmed and probable COVID-19 patients. Six clinical pharmacy residents provided medication review services during their education and training. DRPs were classified based on the Pharmaceutical Care Network Europe V9.00. The physician's acceptance rate of clinical pharmacists' recommendations was assessed., Results: Among 202 hospitalized patients with probable or confirmed COVID-19, 132 (65.3%) had at least one drug-related problem. Two hundred and sixty-four DRPs were identified. Drug selection (85.6%) and dose selection (9.2%) were the most common causes of these problems. Among the 80 clinical pharmacist interventions, 48.8% were accepted by the physicians., Conclusion: Clinical pharmacists identified a significant number of DRPs during the COVID-19 pandemic, particularly those related to drug interactions and drug safety, such as adverse drug reactions. This study highlights the importance of detecting and responding to DRPs in the COVID-19 pandemic., Competing Interests: Conflict of Interest: The authors have no relevant financial or non-financial interests to disclose.

Published
2024
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25. The clinical features, treatment and prognosis of neutropenic fever and Coronavirus disease 2019 results of the multicentre teos study.

Author

Başkol Elik D, Kaya Ş, Alkan S, Demirdal T, Sener A, Kaya S, Güzel Tunçcan Ö, Kayaaslan B, Güner R, Eser F, Kahraman H, Birengel S, Sarıcaoğlu EM, Eroğlu E, Çölkesen F, Öztürk E, Berk Cam H, Mermutluoğlu Ç, Özer Balin Ş, Sincan G, Altın N, Sili U, Suntur BM, Arslan Gülen T, Deveci B, Saba R, İncecik Ş, Eser Karlıdağ G, Hakko E, Akdağ D, Erdem HA, Sipahi H, Çicek C, Taşbakan MS, Taşbakan M, Pullukçu H, Yamazhan T, Arda B, Ulusoy S, and Sipahi OR

Subjects
Humans, Female, Retrospective Studies, SARS-CoV-2, Prognosis, Shock, Septic, COVID-19, Neutropenia
Abstract

This multicentre (22 centres in Turkey) retrospective cohort study aimed to assess the clinical outcomes of patients with neutropenic fever and SARS-CoV-2 positivity. Study period was 15 March 2020-15 August 2021. A total of 170 cases (58 female, aged 59 ± 15.5 years) that fulfilled the inclusion criteria were included in the study. One-month mortality rate (OMM) was 44.8%. The logistic regression analysis showed the following significant variables for the mentioned dependent variables: (i) achieving PCR negativity: receiving a maximum of 5 days of favipiravir (p = 0.005, OR 5.166, 95% CI 1.639-16.280); (ii) need for ICU: receiving glycopeptide therapy at any time during the COVID-19/FEN episode (p = 0.001, OR 6.566, 95% CI 2.137-20.172), the need for mechanical ventilation (p < 0.001, OR 62.042, 95% CI 9.528-404.011); (iii) need for mechanical ventilation: failure to recover from neutropenia (p < 0.001, OR 17.869, 95% CI 3.592-88.907), receiving tocilizumab therapy (p = 0.028, OR 32.227, 95% CI 1.469-707.053), septic shock (p = 0.001, OR 15.4 96% CI 3.164-75.897), and the need for ICU (p < 0.001, OR 91.818, 95% CI 15.360-548.873), (iv) OMM: [mechanical ventilation (p = 0.001, OR 19.041, 95% CI 3.229-112.286) and septic shock (p = 0.010, OR 5.589,95% CI 1.509-20.700)]. Although it includes a relatively limited number of patients, our findings suggest that COVID-19 and FEN are associated with significant mortality and morbidity., (© 2024. The Author(s).)

Published
2024
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26. Early empiric antibiotic use in COVID-19 patients: results from the international VIRUS registry.

Author

Sili U, Tekin A, Bilgin H, Khan SA, Domecq JP, Vadgaonkar G, Segu SS, Rijhwani P, Raju U, Surapaneni KM, Zabolotskikh I, Gomaa D, Goodspeed VM, and Ay P

Subjects
Humans, Anti-Bacterial Agents therapeutic use, Azithromycin therapeutic use, Ceftriaxone therapeutic use, Registries, COVID-19, Community-Acquired Infections drug therapy
Abstract

Objectives: COVID-19 escalated inappropriate antibiotic use. We determined the distribution of pathogens causing community-acquired co-infections, the rate, and factors associated with early empiric antibiotic (EEAB) treatment among hospitalized COVID-19 patients., Methods: The Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study (VIRUS) COVID-19 Registry including 68,428 patients from 28 countries enrolled between January 2020 and October 2021 were screened. After exclusions, 7830 patients were included in the analysis. Azithromycin and/or other antibiotic treatment given within the first 3 days of hospitalization was investigated. Univariate and multivariate analyses were performed to determine factors associated with EEAB use., Results: The majority (6214, 79.4%) of patients received EEAB, with azithromycin combination being the most frequent (3146, 40.2%). As the pandemic advanced, the proportion of patients receiving EEAB regressed from 84.4% (786/931) in January-March 2020 to 65.2% (30/46) in April-June 2021 (P < 0.001). Beta-lactams, especially ceftriaxone was the most commonly used antibiotic. Staphylococcus aureus was the most commonly isolated pathogen. Multivariate analysis showed geographical location and pandemic timeline as the strongest independent predictors of EEAB use., Conclusions: EEAB administration decreased as pandemic advanced, which may be the result of intensified antimicrobial stewardship efforts. Our study provides worldwide goals for antimicrobial stewardship programs in the post-COVID-19 era., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Published
2024
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27. Age, successive waves, immunization, and mortality in elderly COVID-19 hematological patients: EPICOVIDEHA findings.

Author

Rossi G, Salmanton-García J, Cattaneo C, Marchesi F, Dávila-Valls J, Martín-Pérez S, Itri F, López-García A, Glenthøj A, Gomes da Silva M, Besson C, Marchetti M, Weinbergerová B, Jaksic O, Jiménez M, Bilgin YM, Van Doesum J, Farina F, Žák P, Verga L, Collins GP, Bonuomo V, Van Praet J, Nucci M, Meers S, Espigado I, Fracchiolla NS, Valković T, Poulsen CB, Čolović N, Dragonetti G, Ledoux MP, Tascini C, Buquicchio C, Blennow O, Passamonti F, Machado M, Labrador J, Duarte RF, Schönlein M, Prezioso L, Falces-Romero I, Kulasekararaj A, Garcia-Vidal C, Fernández N, Abu-Zeinah G, Ormazabal-Vélez I, Adžić-Vukičević T, Piukovics K, Stoma I, Cuccaro A, Magliano G, Szotkowski T, González-López TJ, El-Ashwah S, Bergantim R, Sili U, Maertens J, Demirkan F, De Ramón C, Petzer V, Del Principe MI, Navrátil M, Dargenio M, Seval GC, Samarkos M, Ráčil Z, Pinczés LI, Lahmer T, Busca A, Méndez GA, Vena A, Biernat MM, Merelli M, Calbacho M, Barać A, Bavastro M, Limongelli A, Ilhan O, Wolf D, Çolak GM, García-Sanz R, Emarah Z, Mišković B, Gräfe SK, Mladenović M, Aiello TF, Núñez-Martín-Buitrago L, Nordlander A, Arellano E, Zambrotta GPM, Ammatuna E, Cabirta A, Sacchi MV, Nunes Rodrigues R, Hersby DS, Hanakova M, Rahimli L, Cordoba R, Cornely OA, and Pagano L

Subjects
Aged, Humans, Male, Aged, 80 and over, Female, Vaccination, Immunization, COVID-19, Lymphopenia, Hematologic Neoplasms complications
Abstract

Objectives: Elderly patients with hematologic malignancies face the highest risk of severe COVID-19 outcomes. The infection's impact on different age groups remains unstudied in detail., Methods: We analyzed elderly patients (age groups: 65-70, 71-75, 76-80, and >80 years old) with hematologic malignancies included in the EPICOVIDEHA registry between January 2020 and July 2022. Univariable and multivariable Cox regression models were conducted to identify factors influencing death in COVID-19 patients with hematological malignancy., Results: The study included data from 3,603 elderly patients (aged 65 or older) with hematological malignancy, with a majority being male (58.1%) and a significant proportion having comorbidities. The patients were divided into four age groups, and the analysis assessed COVID-19 outcomes, vaccination status, and other variables in relation to age and pandemic waves. The 90-day survival rate for patients with COVID-19 was 71.2%, with significant differences between groups. The pandemic waves had varying impacts, with the first wave affecting patients over 80 years old, the second being more severe in 65-70, and the third being the least severe in all age groups. Factors contributing to 90-day mortality included age, comorbidities, lymphopenia, active malignancy, acute leukemia, less than three vaccine doses, severe COVID-19, and using only corticosteroids as treatment., Conclusion: These data underscore the heterogeneity of elderly hematological patients, highlight the different impacts of COVID-19 waves and the pivotal importance of vaccination, and may help in planning future healthcare efforts., Competing Interests: Declarations of competing interest The authors have no competing interests to declare., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Published
2023
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28. Factors Associated with 28-day Critical Illness Development During the First Wave of COVID-19.

Author

Sili U, Ay P, Bilgin H, Topuzoğlu A, Tükenmez-Tigen E, Ertürk-Şengel B, Yağçı-Çağlayık D, Balcan B, Kocakaya D, Olgun-Yıldızeli Ş, Gül F, Bilgili B, Can-Sarınoğlu R, Karahasan-Yağcı A, Mülazimoğlu-Durmuşoğlu L, Eryüksel E, Odabaşı Z, Direskeneli H, Karakurt S, and Korten V

Abstract

Objective: This study aimed to define the predictors of critical illness development within 28 days postadmission during the first wave of the COVID-19 pandemic., Materials and Methods: We conducted a prospective cohort study including 477 PCR-positive COVID-19 patients admitted to a tertiary care hospital in Istanbul from March 12 to May 12, 2020., Results: The most common presenting symptoms were cough, dyspnea, and fatigue. Critical illness developed in 45 (9.4%; 95% CI=7.0%-12.4%) patients. In the multivariable analysis, age (hazard ratio (HR)=1.05, p <0.001), number of comorbidities (HR=1.33, p =0.02), procalcitonin ≥0.25 µg/L (HR=2.12, p =0.03) and lactate dehydrogenase (LDH) ≥350 U/L (HR=2.04, p =0.03) were independently associated with critical illness development. The World Health Organization (WHO) ordinal scale for clinical improvement on admission was the strongest predictor of critical illness (HR=4.15, p <0.001). The patients hospitalized at the end of the study period had a much better prognosis compared to the patients hospitalized at the beginning (HR=0.14; p =0.02). The C-index of the model was 0.92., Conclusion: Age, comorbidity number, the WHO scale, LDH, and procalcitonin were independently associated with critical illness development. Mortality from COVID-19 seemed to be decreasing as the first wave of the pandemic advanced., Graphic Abstract: Graphic Abstract., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Infectious Diseases and Clinical Microbiology.)

Published
2023
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29. Breakthrough COVID-19 in vaccinated patients with hematologic malignancies: results from the EPICOVIDEHA survey.

Author

Pagano L, Salmanton-García J, Marchesi F, Blennow O, Gomes da Silva M, Glenthøj A, van Doesum J, Bilgin YM, López-García A, Itri F, Nunes Rodrigues R, Weinbergerová B, Farina F, Dragonetti G, Berg Venemyr C, van Praet J, Jaksic O, Valković T, Falces-Romero I, Martín-Pérez S, Jiménez M, Dávila-Valls J, Schönlein M, Ammatuna E, Meers S, Delia M, Stojanoski Z, Nordlander A, Lahmer T, Imre Pinczés L, Buquicchio C, Piukovics K, Ormazabal-Vélez I, Fracchiolla N, Samarkos M, Méndez GA, Hernández-Rivas JÁ, Espigado I, Cernan M, Petzer V, Lamure S, di Blasi R, Marques de Almedia J, Dargenio M, Biernat MM, Sciumè M, de Ramón C, de Jonge N, Batinić J, Aujayeb A, Marchetti M, Fouquet G, Fernández N, Zambrotta G, Sacchi MV, Guidetti A, Demirkan F, Prezioso L, Ráčil Z, Nucci M, Mladenović M, Liévin R, Hanáková M, Gräfe S, Sili U, Machado M, Cattaneo C, Adžić-Vukičević T, Verga L, Labrador J, Rahimli L, Bonanni M, Passamonti F, Pagliuca A, Corradini P, Hoenigl M, Koehler P, Busca A, and Cornely OA

Subjects
Adult, Humans, SARS-CoV-2, COVID-19 Testing, Antibodies, Monoclonal, Antiviral Agents, Antibodies, Viral, COVID-19 epidemiology, COVID-19 prevention & control, Hematologic Neoplasms complications, Hematologic Neoplasms therapy
Abstract

Limited data are available on breakthrough COVID-19 in patients with hematologic malignancy (HM) after anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. Adult patients with HM, ≥1 dose of anti-SARS-CoV-2 vaccine, and breakthrough COVID-19 between January 2021 and March 2022 were analyzed. A total of 1548 cases were included, mainly lymphoid malignancies (1181 cases, 76%). After viral sequencing in 753 cases (49%), the Omicron variant was prevalent (517, 68.7%). Most of the patients received ≤2 vaccine doses before COVID-19 (1419, 91%), mostly mRNA-based (1377, 89%). Overall, 906 patients (59%) received COVID-19-specific treatment. After 30-day follow-up from COVID-19 diagnosis, 143 patients (9%) died. The mortality rate in patients with the Omicron variant was 7.9%, comparable to other variants, with a significantly lower 30-day mortality rate than in the prevaccine era (31%). In the univariable analysis, older age (P < .001), active HM (P < .001), and severe and critical COVID-19 (P = .007 and P < .001, respectively) were associated with mortality. Conversely, patients receiving monoclonal antibodies, even for severe or critical COVID-19, had a lower mortality rate (P < .001). In the multivariable model, older age, active disease, critical COVID-19, and 2-3 comorbidities were correlated with a higher mortality, whereas monoclonal antibody administration, alone (P < .001) or combined with antivirals (P = .009), was protective. Although mortality is significantly lower than in the prevaccination era, breakthrough COVID-19 in HM is still associated with considerable mortality. Death rate was lower in patients who received monoclonal antibodies, alone or in combination with antivirals., (© 2022 by The American Society of Hematology.)

Published
2022
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30. Simultaneous Onset of Haematological Malignancy and COVID: An Epicovideha Survey.

Author

Cattaneo C, Salmanton-García J, Marchesi F, El-Ashwah S, Itri F, Weinbergerová B, Gomes Da Silva M, Dargenio M, Dávila-Valls J, Martín-Pérez S, Farina F, Van Doesum J, Valković T, Besson C, Poulsen CB, López-García A, Žák P, Schönlein M, Piukovics K, Jaksic O, Cabirta A, Ali N, Sili U, Fracchiolla N, Dragonetti G, Adžić-Vukičević T, Marchetti M, Machado M, Glenthøj A, Finizio O, Demirkan F, Blennow O, Tisi MC, Omrani AS, Navrátil M, Ráčil Z, Novák J, Magliano G, Jiménez M, Garcia-Vidal C, Erben N, Del Principe MI, Buquicchio C, Bergantim R, Batinić J, Al-Khabori M, Verga L, Szotkowski T, Samarkos M, Ormazabal-Vélez I, Meers S, Maertens J, Pinczés LI, Hoenigl M, Drgoňa Ľ, Cuccaro A, Bilgin YM, Aujayeb A, Rahimli L, Gräfe S, Sciumè M, Mladenović M, Çolak GM, Sacchi MV, Nordlander A, Berg Venemyr C, Hanáková M, García-Poutón N, Emarah Z, Zambrotta GPM, Nunes Rodrigues R, Cordoba R, Méndez GA, Biernat MM, Cornely OA, and Pagano L

Abstract

Background: The outcome of patients with simultaneous diagnosis of haematological malignancies (HM) and COVID-19 is unknown and there are no specific treatment guidelines. Methods: We describe the clinical features and outcome of a cohort of 450 patients with simultaneous diagnosis of HM and COVID-19 registered in the EPICOVIDEHA registry between March 2020 to February 2022. Results: Acute leukaemia and lymphoma were the most frequent HM (35.8% and 35.1%, respectively). Overall, 343 (76.2%) patients received treatment for HM, which was delayed for longer than one month since diagnosis in 57 (16.6%). An overall response rate was observed in 140 (40.8%) patients after the first line of treatment. After a median follow-up of 35 days, overall mortality was 177/450 (39.3%); 30-day mortality was significantly higher in patients not receiving HM treatment (42.1%) than in those receiving treatment (27.4%, p = 0.004), either before and/or after COVID-19, or compared to patients receiving HM treatment at least after COVID-19 (15.2%, p < 0.001). Age, severe/critical COVID-19, ≥2 comorbidities, and lack of HM treatment were independent risk factors for mortality, whereas a lymphocyte count >500/mcl at COVID-19 onset was protective. Conclusions: HM treatment should be delivered as soon as possible for patients with simultaneous diagnosis of COVID-19 and HM requiring immediate therapy.

Published
2022
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31. Improved Clinical Outcome of COVID-19 in Hematologic Malignancy Patients Receiving a Fourth Dose of Anti-SARS-CoV-2 Vaccine: An EPICOVIDEHA Report.

Author

Salmanton-García J, Marchesi F, Glenthøj A, Bilgin YM, van Praet J, Dávila-Valls J, Martín-Pérez S, Labrador J, van Doesum J, Falces-Romero I, Farina F, Schönlein M, Chanut M, Petzer V, Espigado I, Dargenio M, Aujayeb A, Sili U, Serrano L, Pinczés LI, de Jonge N, Soto-Silva A, Buquicchio C, Prezioso L, Marchetti M, Meers S, Busca A, Corradini P, Hoenigl M, Koehler P, Rahimli L, Çolak GM, Arellano E, Wolf D, Gräfe S, Ammatuna E, Berg Venemyr C, Cornely OA, and Pagano L

Published
2022
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32. An international observational study to assess the impact of the Omicron variant emergence on the clinical epidemiology of COVID-19 in hospitalised patients.

Author

Gonçalves BP, Hall M, Jassat W, Balan V, Murthy S, Kartsonaki C, Semple MG, Rojek A, Baruch J, Reyes LF, Dasgupta A, Dunning J, Citarella BW, Pritchard M, Martín-Quiros A, Sili U, Baillie JK, Aryal D, Arabi Y, Rashan A, Angheben A, Caoili J, Carrier FM, Harrison EM, Gómez-Junyent J, Figueiredo-Mello C, Douglas JJ, Mat Nor MB, Chow YP, Wong XC, Bertagnolio S, Thwin SS, Streinu-Cercel A, Salazar L, Rishu A, Rangappa R, Ong DSY, Hashmi M, Carson G, Diaz J, Fowler R, Kraemer MUG, Wils EJ, Horby P, Merson L, and Olliaro PL

Subjects
Humans, COVID-19 epidemiology, COVID-19 virology, SARS-CoV-2 genetics
Abstract

Background: Whilst timely clinical characterisation of infections caused by novel SARS-CoV-2 variants is necessary for evidence-based policy response, individual-level data on infecting variants are typically only available for a minority of patients and settings., Methods: Here, we propose an innovative approach to study changes in COVID-19 hospital presentation and outcomes after the Omicron variant emergence using publicly available population-level data on variant relative frequency to infer SARS-CoV-2 variants likely responsible for clinical cases. We apply this method to data collected by a large international clinical consortium before and after the emergence of the Omicron variant in different countries., Results: Our analysis, that includes more than 100,000 patients from 28 countries, suggests that in many settings patients hospitalised with Omicron variant infection less often presented with commonly reported symptoms compared to patients infected with pre-Omicron variants. Patients with COVID-19 admitted to hospital after Omicron variant emergence had lower mortality compared to patients admitted during the period when Omicron variant was responsible for only a minority of infections (odds ratio in a mixed-effects logistic regression adjusted for likely confounders, 0.67 [95% confidence interval 0.61-0.75]). Qualitatively similar findings were observed in sensitivity analyses with different assumptions on population-level Omicron variant relative frequencies, and in analyses using available individual-level data on infecting variant for a subset of the study population., Conclusions: Although clinical studies with matching viral genomic information should remain a priority, our approach combining publicly available data on variant frequency and a multi-country clinical characterisation dataset with more than 100,000 records allowed analysis of data from a wide range of settings and novel insights on real-world heterogeneity of COVID-19 presentation and clinical outcome., Funding: Bronner P. Gonçalves, Peter Horby, Gail Carson, Piero L. Olliaro, Valeria Balan, Barbara Wanjiru Citarella, and research costs were supported by the UK Foreign, Commonwealth and Development Office (FCDO) and Wellcome [215091/Z/18/Z, 222410/Z/21/Z, 225288/Z/22/Z]; and Janice Caoili and Madiha Hashmi were supported by the UK FCDO and Wellcome [222048/Z/20/Z]. Peter Horby, Gail Carson, Piero L. Olliaro, Kalynn Kennon and Joaquin Baruch were supported by the Bill & Melinda Gates Foundation [OPP1209135]; Laura Merson was supported by University of Oxford's COVID-19 Research Response Fund - with thanks to its donors for their philanthropic support. Matthew Hall was supported by a Li Ka Shing Foundation award to Christophe Fraser. Moritz U.G. Kraemer was supported by the Branco Weiss Fellowship, Google.org, the Oxford Martin School, the Rockefeller Foundation, and the European Union Horizon 2020 project MOOD (#874850). The contents of this publication are the sole responsibility of the authors and do not necessarily reflect the views of the European Commission. Contributions from Srinivas Murthy, Asgar Rishu, Rob Fowler, James Joshua Douglas, François Martin Carrier were supported by CIHR Coronavirus Rapid Research Funding Opportunity OV2170359 and coordinated out of Sunnybrook Research Institute. Contributions from Evert-Jan Wils and David S.Y. Ong were supported by a grant from foundation Bevordering Onderzoek Franciscus; and Andrea Angheben by the Italian Ministry of Health "Fondi Ricerca corrente-L1P6" to IRCCS Ospedale Sacro Cuore-Don Calabria. The data contributions of J.Kenneth Baillie, Malcolm G. Semple, and Ewen M. Harrison were supported by grants from the National Institute for Health Research (NIHR; award CO-CIN-01), the Medical Research Council (MRC; grant MC&#95;PC&#95;19059), and by the NIHR Health Protection Research Unit (HPRU) in Emerging and Zoonotic Infections at University of Liverpool in partnership with Public Health England (PHE) (award 200907), NIHR HPRU in Respiratory Infections at Imperial College London with PHE (award 200927), Liverpool Experimental Cancer Medicine Centre (grant C18616/A25153), NIHR Biomedical Research Centre at Imperial College London (award IS-BRC-1215-20013), and NIHR Clinical Research Network providing infrastructure support. All funders of the ISARIC Clinical Characterisation Group are listed in the appendix., Competing Interests: BG, MH, WJ, VB, CK, AR, JB, LR, AD, JD, BC, MP, US, JB, DA, YA, AR, JC, EH, CF, MM, YC, XW, SB, ST, LS, AR, RR, DO, MH, GC, JD, MK, EW, PH, LM, PO No competing interests declared, SM declares receiving salary support from the Health Research Foundation and Innovative Medicines Canada Chair in Pandemic Preparedness Research, MS reports grants from DHSC National Institute of Health Research UK, from the Medical Research Council UK, and from the Health Protection Research Unit in Emerging & Zoonotic Infections, University of Liverpool, supporting the conduct of the study; other interest in Integrum Scientific LLC, Greensboro, NC, USA, outside the submitted work, AM declares consulting fees for Gilead and MSD, presentation fees for GILEAD, Pfizer and MSD, support for attending ECCMID from Gilead, and advisory board fees for MSD and Gilead, AA declares support from Italian Ministry of Health - "Fondi Ricerca Corrente" Line1 Project 5 to IRCCS Sacro Cuore - Don Calabria Hospital, FC declares a grant from the Canadian Institute of Health Research, JG declares support by Pfizer, Angelini and MSD to attend meetings (registration to meetings only), JD declares personal fees from lectures from Sunovion and Merck and consulting fees from Pfizer, AS has been an investigator in COVID-19 clinical trials by Algernon Pharmaceuticals, Atea Pharmaceuticals, Regeneron Pharmaceuticals, Diffusion Pharmaceuticals, Celltrion, Inc and Atriva Therapeutics, outside the scope of the submitted work, RF declares a peer reviewed research grant from the Canadian Institutes of Health Research, See Appendix 1 for competing interests for group author members, (© 2022, Gonçalves et al.)

Published
2022
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33. B-cell malignancies treated with targeted drugs and SARS-CoV-2 infection: A European Hematology Association Survey (EPICOVIDEHA).

Author

Infante MS, Salmanton-García J, Fernández-Cruz A, Marchesi F, Jaksic O, Weinbergerová B, Besson C, Duarte RF, Itri F, Valković T, Szotkovski T, Busca A, Guidetti A, Glenthøj A, Collins GP, Bonuomo V, Sili U, Seval GC, Machado M, Cordoba R, Blennow O, Abu-Zeinah G, Lamure S, Kulasekararaj A, Falces-Romero I, Cattaneo C, Van Doesum J, Piukovics K, Omrani AS, Magliano G, Ledoux MP, de Ramon C, Cabirta A, Verga L, López-García A, Da Silva MG, Stojanoski Z, Meers S, Lahmer T, Martín-Pérez S, Dávila-Vals J, Van Praet J, Samarkos M, Bilgin YM, Karlsson LK, Batinić J, Nordlander A, Schönlein M, Hoenigl M, Ráčil Z, Mladenović M, Hanakova M, Zambrotta GPM, De Jonge N, Adžić-Vukičević T, Nunes-Rodrigues R, Prezioso L, Navrátil M, Marchetti M, Cuccaro A, Calbacho M, Giordano A, Cornely OA, Hernández-Rivas JÁ, and Pagano L

Abstract

Patients with lymphoproliferative diseases (LPD) are vulnerable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Here, we describe and analyze the outcome of 366 adult patients with chronic lymphocytic leukemia (CLL) or non-Hodgkin Lymphoma (NHL) treated with targeted drugs and laboratory-confirmed COVID-19 diagnosed between February 2020 and January 2022. Median follow-up was 70.5 days (IQR 0-609). Most used targeted drugs were Bruton-kinase inhibitors (BKIs) (N= 201, 55%), anti-CD20 other than rituximab (N=61, 16%), BCL2 inhibitors (N=33, 9%) and lenalidomide (N=28, 8%).Only 16.2% of the patients were vaccinated with 2 or more doses of vaccine at the onset of COVID-19. Mortality was 24% (89/366) on day 30 and 36%(134/366) on the last day of follow-up. Age >75 years (p<0.001, HR 1.036), active malignancy (p<0.001, HR 2.215), severe COVID-19 (p=0.017, HR 2.270) and admission to ICU (p<0.001, HR 5.751) were risk factors for mortality at last day of follow up. There was no difference in OS rates in NHL vs CLL patients (p=0.306), nor in patients treated with or without BKIs (p=0.151). Mortality in ICU was 66% (CLL 61%, NHL 76%). Overall mortality rate decreased according to vaccination status, being 39% in unvaccinated patients, 32% and 26% in those having received one or two doses, respectively, and 20% in patients with a booster dose (p=0.245). Overall mortality rate dropped from 41% during the first semester of 2020 to 25% at the last semester of 2021. These results show increased severity and mortality from COVID-19 in LPDs patients treated with targeted drugs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest of this work., (Copyright © 2022 Infante, Salmanton-García, Fernández-Cruz, Marchesi, Jaksic, Weinbergerová, Besson, Duarte, Itri, Valković, Szotkovski, Busca, Guidetti, Glenthøj, Collins, Bonuomo, Sili, Seval, Machado, Cordoba, Blennow, Abu-Zeinah, Lamure, Kulasekararaj, Falces-Romero, Cattaneo, Van Doesum, Piukovics, Omrani, Magliano, Ledoux, de Ramon, Cabirta, Verga, López-García, Da Silva, Stojanoski, Meers, Lahmer, Martín-Pérez, Dávila-Vals, Van Praet, Samarkos, Bilgin, Karlsson, Batinić, Nordlander, Schönlein, Hoenigl, Ráčil, Mladenović, Hanakova, Zambrotta, De Jonge, Adžić-Vukičević, Nunes-Rodrigues, Prezioso, Navrátil, Marchetti, Cuccaro, Calbacho, Giordano, Cornely, Hernández-Rivas and Pagano.)

Published
2022
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34. The Association of Latitude and Altitude with COVID-19 Symptoms: A VIRUS: COVID-19 Registry Analysis.

Author

Tekin A, Qamar S, Bansal V, Surani S, Singh R, Sharma M, LeMahieu AM, Hanson AC, Schulte PJ, Bogojevic M, Deo N, Sanghavi DK, Cartin-Ceba R, Jain NK, Christie AB, Sili U, Anderson HL, Denson JL, Khanna AK, Zabolotskikh IB, La Nou AT, Akhter M, Mohan SK, Dodd KW, Retford L, Boman K, Kumar VK, Walkey AJ, Gajic O, Domecq JP, and Kashyap R

Abstract

Background: Better delineation of COVID-19 presentations in different climatological conditions might assist with prompt diagnosis and isolation of patients., Objectives: To study the association of latitude and altitude with COVID-19 symptomatology., Methods: This observational cohort study included 12267 adult COVID-19 patients hospitalized between 03/2020 and 01/2021 at 181 hospitals in 24 countries within the SCCM Discovery VIRUS: COVID-19 Registry. The outcome was symptoms at admission, categorized as respiratory, gastrointestinal, neurological, mucocutaneous, cardiovascular, and constitutional. Other symptoms were grouped as atypical. Multivariable regression modeling was performed, adjusting for baseline characteristics. Models were fitted using generalized estimating equations to account for the clustering., Results: The median age was 62 years, with 57% males. The median age and percentage of patients with comorbidities increased with higher latitude. Conversely, patients with comorbidities decreased with elevated altitudes. The most common symptoms were respiratory (80%), followed by constitutional (75%). Presentation with respiratory symptoms was not associated with the location. After adjustment, at lower latitudes (<30º), patients presented less commonly with gastrointestinal symptoms ( p< .001, odds ratios for 15º, 25º, and 30º: 0.32, 0.81, and 0.98, respectively). Atypical symptoms were present in 21% of the patients and showed an association with altitude ( p= .026, odds ratios for 75, 125, 400, and 600 meters above sea level: 0.44, 0.60, 0.84, and 0.77, respectively)., Conclusions: We observed geographic variability in symptoms of COVID-19 patients. Respiratory symptoms were most common but were not associated with the location. Gastrointestinal symptoms were less frequent in lower latitudes. Atypical symptoms were associated with higher altitude., Competing Interests: Dr. Salim Surani is the Co-Editor of the journal Open Respiratory Medicine Journal., (© 2022 Tekin et al.)

Published
2022
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35. Pharmacokinetic characterization of favipiravir in patients with COVID-19.

Author

Gülhan R, Eryüksel E, Gülçebi İdriz Oğlu M, Çulpan Y, Toplu A, Kocakaya D, Tigen E, Ertürk Şengel B, Sili U, Olgun Yıldızeli Ş, Balcan MB, Elçi A, Bulut C, Karaalp A, Yananlı HR, Güner AE, Hatipoğlu M, Karakurt S, Korten V, Ratnaraj N, Patsalos P, Ay P, and Onat F

Subjects
Adult, Amides adverse effects, Antiviral Agents adverse effects, Female, Humans, Male, Pyrazines adverse effects, Treatment Outcome, COVID-19 Drug Treatment
Abstract

This prospective observational study describes the pharmacokinetic characteristics of favipiravir in adult patients hospitalized for mild to moderate COVID-19 with a positive RT-PCR test. Favipiravir was administered for 5 days, with a loading dose of 3200 mg and a maintenance dose of 1200 mg/day. Serial blood samples were collected on Day 2 and Day 4 of the therapy. Laboratory findings of the patients (n = 21) and in-hospital mortality were recorded. Favipiravir concentrations exhibited substantial variability and a significant decrease during the treatment of COVID-19. The median favipiravir trough concentration (C 0-trough ) on Day 2 was 21.26 (interquartile range [IQR], 8.37-30.78) μg/mL, whereas it decreased significantly to 1.61 (IQR, 0.00-6.41) μg/mL on Day 4, the area under the concentration-time curve decreased by 68.5%. Day 2 C 0-trough of female patients was higher than male patients. Our findings indicate that favipiravir concentrations show significant variability during the treatment of COVID-19 and therapeutic drug monitoring may be necessary to maintain targeted concentrations., (© 2022 British Pharmacological Society.)

Published
2022
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36. COVID-19 in vaccinated adult patients with hematological malignancies: preliminary results from EPICOVIDEHA.

Author

Pagano L, Salmanton-García J, Marchesi F, López-García A, Lamure S, Itri F, Gomes-Silva M, Dragonetti G, Falces-Romero I, van Doesum J, Sili U, Labrador J, Calbacho M, Bilgin YM, Weinbergerová B, Serrano L, Ribera-Santa Susana JM, Malak S, Loureiro-Amigo J, Glenthøj A, Córdoba-Mascuñano R, Nunes-Rodrigues R, González-López TJ, Karlsson LK, Jiménez-Lorenzo MJ, Hernández-Rivas JÁ, Jaksic O, Ráčil Z, Busca A, Corradini P, Hoenigl M, Klimko N, Koehler P, Pagliuca A, Passamonti F, and Cornely OA

Subjects
Adult, Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, 2019-nCoV Vaccine mRNA-1273 administration & dosage, BNT162 Vaccine administration & dosage, COVID-19 immunology, COVID-19 mortality, COVID-19 prevention & control, Hematologic Neoplasms immunology, Hematologic Neoplasms mortality, SARS-CoV-2 immunology
Published
2022
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37. COVID-19 infection in adult patients with hematological malignancies: a European Hematology Association Survey (EPICOVIDEHA).

Author

Pagano L, Salmanton-García J, Marchesi F, Busca A, Corradini P, Hoenigl M, Klimko N, Koehler P, Pagliuca A, Passamonti F, Verga L, Víšek B, Ilhan O, Nadali G, Weinbergerová B, Córdoba-Mascuñano R, Marchetti M, Collins GP, Farina F, Cattaneo C, Cabirta A, Gomes-Silva M, Itri F, van Doesum J, Ledoux MP, Čerňan M, Jakšić O, Duarte RF, Magliano G, Omrani AS, Fracchiolla NS, Kulasekararaj A, Valković T, Poulsen CB, Machado M, Glenthøj A, Stoma I, Ráčil Z, Piukovics K, Navrátil M, Emarah Z, Sili U, Maertens J, Blennow O, Bergantim R, García-Vidal C, Prezioso L, Guidetti A, Del Principe MI, Popova M, de Jonge N, Ormazabal-Vélez I, Fernández N, Falces-Romero I, Cuccaro A, Meers S, Buquicchio C, Antić D, Al-Khabori M, García-Sanz R, Biernat MM, Tisi MC, Sal E, Rahimli L, Čolović N, Schönlein M, Calbacho M, Tascini C, Miranda-Castillo C, Khanna N, Méndez GA, Petzer V, Novák J, Besson C, Duléry R, Lamure S, Nucci M, Zambrotta G, Žák P, Seval GC, Bonuomo V, Mayer J, López-García A, Sacchi MV, Booth S, Ciceri F, Oberti M, Salvini M, Izuzquiza M, Nunes-Rodrigues R, Ammatuna E, Obr A, Herbrecht R, Núñez-Martín-Buitrago L, Mancini V, Shwaylia H, Sciumè M, Essame J, Nygaard M, Batinić J, Gonzaga Y, Regalado-Artamendi I, Karlsson LK, Shapetska M, Hanakova M, El-Ashwah S, Borbényi Z, Çolak GM, Nordlander A, Dragonetti G, Maraglino AME, Rinaldi A, De Ramón-Sánchez C, and Cornely OA

Subjects
Adult, Aged, Aged, 80 and over, COVID-19 diagnosis, COVID-19 epidemiology, COVID-19 therapy, Europe epidemiology, Female, Hematologic Neoplasms epidemiology, Hematologic Neoplasms therapy, Hospitalization, Humans, Intensive Care Units, Male, Middle Aged, Registries, Risk Factors, SARS-CoV-2 isolation & purification, Young Adult, COVID-19 complications, Hematologic Neoplasms complications
Abstract

Background: Patients with hematological malignancies (HM) are at high risk of mortality from SARS-CoV-2 disease 2019 (COVID-19). A better understanding of risk factors for adverse outcomes may improve clinical management in these patients. We therefore studied baseline characteristics of HM patients developing COVID-19 and analyzed predictors of mortality., Methods: The survey was supported by the Scientific Working Group Infection in Hematology of the European Hematology Association (EHA). Eligible for the analysis were adult patients with HM and laboratory-confirmed COVID-19 observed between March and December 2020., Results: The study sample includes 3801 cases, represented by lymphoproliferative (mainly non-Hodgkin lymphoma n = 1084, myeloma n = 684 and chronic lymphoid leukemia n = 474) and myeloproliferative malignancies (mainly acute myeloid leukemia n = 497 and myelodysplastic syndromes n = 279). Severe/critical COVID-19 was observed in 63.8% of patients (n = 2425). Overall, 2778 (73.1%) of the patients were hospitalized, 689 (18.1%) of whom were admitted to intensive care units (ICUs). Overall, 1185 patients (31.2%) died. The primary cause of death was COVID-19 in 688 patients (58.1%), HM in 173 patients (14.6%), and a combination of both COVID-19 and progressing HM in 155 patients (13.1%). Highest mortality was observed in acute myeloid leukemia (199/497, 40%) and myelodysplastic syndromes (118/279, 42.3%). The mortality rate significantly decreased between the first COVID-19 wave (March-May 2020) and the second wave (October-December 2020) (581/1427, 40.7% vs. 439/1773, 24.8%, p value < 0.0001). In the multivariable analysis, age, active malignancy, chronic cardiac disease, liver disease, renal impairment, smoking history, and ICU stay correlated with mortality. Acute myeloid leukemia was a higher mortality risk than lymphoproliferative diseases., Conclusions: This survey confirms that COVID-19 patients with HM are at high risk of lethal complications. However, improved COVID-19 prevention has reduced mortality despite an increase in the number of reported cases., (© 2021. The Author(s).)

Published
2021
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38. Frequency and associated factors for carbapenem-non-susceptible Bacteroides fragilis group bacteria colonization in hospitalized patients: Case control study in a university hospital in Turkey.

Author

Ulger Toprak N, Akgul O, Bilgin H, Ozaydin AN, Altinkanat Gelmez G, Sayin E, Sili U, Korten V, and Soyletir G

Subjects
Adult, Bacteroides Infections drug therapy, Case-Control Studies, Hospitals, University, Humans, Meropenem, Microbial Sensitivity Tests, Risk Factors, Turkey epidemiology, beta-Lactamases, Anti-Bacterial Agents therapeutic use, Bacteroides Infections microbiology, Bacteroides fragilis drug effects, Bacteroides fragilis genetics, Carbapenems pharmacology, Drug Resistance, Bacterial
Abstract

Purpuse: The carbapenem-resistant Bacteroides fragilis group (CR-BFG) bacteria have been reported in several countries recently with increasing global attention. The high incidence of CR-BFG isolated from our hospitalized patients has become an important problem. Therefore, we aimed to determine the frequency and associated factors for intestinal colonization by carbapenem-non-susceptible BFG (CNS-BFG) among adult patients hospitalized at intensive care units, neurosurgery and internal medicine wards in our hospital., Methods: Rectal swabs (n = 1200), collected from 766 patients between February 2014 and March 2015, were inoculated onto kanamycin-vancomycin-leaked blood agar containing 0.125 mg/L meropenem. The isolates were identified by MALDI-TOF MS. Susceptibility testing was performed by agar dilution method. The carbapenemase gene (cfiA) was detected by PCR. Logistic regression analysis was used to evaluate the associated factors for intestinal colonization by CNS-BFG., Results: A total 180 non-duplicate BFG isolates were obtained from 164 patients. Ten different species, including Parabacteroides distasonis (n = 46, 25.6%), and Bacteroides fragilis (n = 30; 16.6%), were identified. Twenty-five percent of the isolates were non-susceptible to meropenem (MIC >2 mg/L). The highest prevalence of meropenem resistant strains (MIC >8 mg/L) was detected among B. fragilis (n = 12), followed by Parabacteroides spp. (n = 4). All but one B. fragilis strains were cfiA gene positive. Hospital admission, increasing Charlson score, use of antibiotics; including carbapenems in past three months, colonization with other accompanying carbapenem-resistant Gram negative bacteria (Enterobacteriaceae, Acinetobacter baumannii and Pseudomonas aeruginosa), and having undergone surgical operations were significantly associated with RCS- BFG colonization., Conclusions: The high carriage rate of CNS-BFG in hospitalized patients may lead to worse clinical outcomes, such as serious infections and mortality, and deserves attention., Competing Interests: Declaration of competing interest No conflict of interest was declared by the authors., (Copyright © 2021 Indian Association of Medical Microbiologists. Published by Elsevier B.V. All rights reserved.)

Published
2021
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39. The Association of Thyroid Hormone Changes with Inflammatory Status and Prognosis in COVID-19.

Author

Dincer Yazan C, Ilgin C, Elbasan O, Apaydin T, Dashdamirova S, Yigit T, Sili U, Karahasan Yagci A, Sirikci O, Haklar G, and Gozu H

Abstract

Background: COVID-19 infection may have multiorgan effects in addition to effects on the lungs and immune system. Recently, studies have found thyroid function abnormalities in COVID-19 cases which were interpreted as euthyroid sick syndrome (ESS) or destructive thyroiditis. Therefore, in this study, we aimed to evaluate the thyroid function status and thyroid autoimmunity in COVID-19 patients. Material and Method . 205 patients were included. The medical history and laboratory parameters at admission were collected from medical records. Serum thyroid-stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3), thyroid peroxidase antibody, and thyroglobulin antibody were measured, and patients were classified according to thyroid function status., Results: 34.1% of the patients were euthyroid. Length of hospitalization ( p < 0.001), rate of oxygen demand ( p < 0.001), and intensive care unit (ICU) admission ( p =0.022) were lower, and none of the euthyroid patients died. 108 (52.6%) patients were classified to have ESS, 57 were classified as mild, and 51 were moderate. The inflammatory parameters were higher in patients with moderate ESS. In cluster analysis, a high-risk group with a lower median FT3 value (median = 2.34 ng/L; IQR = 0.86), a higher median FT4 value (median = 1.04 ng/dL; IQR = 0.33), and a lower median TSH value (median = 0.62 mIU/L; IQR = 0.59) included 8 of 9 died patients and 25 of the 31 patients that were admitted to ICU. Discussion . Length of hospitalization, oxygen demand, ICU admission, and mortality were lower in euthyroid patients. Moreover, none of the euthyroid patients died. In conclusion, evaluation of thyroid function tests during COVID-19 infection may give information about the prognosis of disease., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Ceyda Dincer Yazan et al.)

Published
2021
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40. Untreated herpes simplex virus encephalitis without a fatal outcome.

Author

Kaya A, Kurt AF, Sili U, Kaya SY, Şahin Z, Sar M, and Aygün G

Subjects
Adult, Delayed Diagnosis, Encephalitis, Herpes Simplex diagnostic imaging, Encephalitis, Herpes Simplex pathology, Encephalitis, Herpes Simplex virology, Female, Herpesvirus 1, Human growth & development, Herpesvirus 1, Human pathogenicity, Humans, Magnetic Resonance Imaging, Temporal Lobe diagnostic imaging, Temporal Lobe pathology, Temporal Lobe virology, Treatment Outcome, Acyclovir therapeutic use, Antiviral Agents therapeutic use, Encephalitis, Herpes Simplex drug therapy, Herpesvirus 1, Human drug effects, Temporal Lobe drug effects
Abstract

Herpes simplex virus encephalitis (HSE) is the most common sporadic fatal encephalitis. Although timely administered acyclovir treatment decreases mortality, neuropsychiatric sequelae is still common among survivors. Magnetic resonance imaging is frequently utilized for the diagnosis of HSE, which typically involves temporal lobe(s) and can be mixed with brain tumors involving the same area. Here, we report a case of HSE, who received acyclovir with a delay of 90 days because of presumptive tumor diagnosis and survived with minimal sequelae.

Published
2021
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41. Tuberculosis and COVID-19: An overlapping situation during pandemic.

Author

Can Sarınoğlu R, Sili U, Eryuksel E, Olgun Yildizeli S, Cimsit C, and Karahasan Yagci A

Subjects
Adult, Aged, COVID-19, COVID-19 Testing, COVID-19 Vaccines, Clinical Laboratory Techniques, Coinfection, Coronavirus Infections complications, Female, Humans, Male, Pandemics, Pneumonia, Viral complications, Real-Time Polymerase Chain Reaction, SARS-CoV-2, Tomography, X-Ray Computed, Tuberculosis complications, Tuberculosis diagnostic imaging, Betacoronavirus genetics, Coronavirus Infections diagnosis, Pneumonia, Viral diagnosis, Tuberculosis diagnosis
Abstract

Introduction: The novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the coronavirus disease 2019 (COVID-19). First COVID-19 case was detected in March, 10, 2020 in Turkey and as of May, 18, 2020 148,067 cases have been identified and 4096 citizens have died. Tuberculosis (TB) is a worldwide public health concern, incidence of tuberculosis (per 100,000 people) in Turkey was reported at 14, 1 in 2018. During pandemic COVID-19 was the main concern in every clinic and as we discuss here overlapping respiratory diseases may result in delaying of the diagnosis and treatment., Methodology: There were 4605 respiratory samples examined between March 23 and May 18 for COVID-19 and 185 samples for Mycobacterium tuberculosis in our laboratory. The Xpert Ultra assay was performed for the diagnosis of pulmonary tuberculosis; SARS-CoV-2 RNA was determined by real-time PCR (RT-PCR) analysis in combined nasopharyngeal and deep oropharyngeal swabs of suspected cases of COVID-19., Results: Both of SARS-CoV-2 and M. tuberculosis tests were requested on the clinical and radiological grounds in 30 patients. Here we discussed 2 patients who were both COVID-19 and TB positive. One patient already diagnosed with tuberculosis become COVID-19 positive during hospitalization and another patient suspected and treated for COVID-19 received the final diagnosis of pulmonary TB and Human Immunodeficiency Virus infection., Conclusions: We want to emphasize that while considering COVID-19 primarily during these pandemic days, we should not forget one of the "great imitators", tuberculosis within differential diagnoses., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2020 Rabia Can Sarınoğlu, Uluhan Sili, Emel Eryuksel, Sehnaz Olgun Yildizeli, Cagatay Cimsit, Aysegul Karahasan Yagci.)

Published
2020
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42. Hand hygiene knowledge, perception and practice of healthcare workers in a Turkish university hospital intensive care unit.

Author

Sili U, Ay P, Bilgin H, Hidiroglu S, and Korten V

Subjects
Adult, Cross-Sectional Studies, Female, Humans, Intensive Care Units, Male, Surveys and Questionnaires, Turkey, Young Adult, Hand Hygiene methods, Health Knowledge, Attitudes, Practice, Health Personnel, Hospitals, University, Professional Competence
Abstract

Introduction: While improvement of hand hygiene (HH) compliance is considered as the best approach to reduce healthcare-associated infections, the instructional interventions in HH among healthcare workers of intensive care unit (ICU) of our hospital was not successful enough. The following study was conducted to evaluate HH knowledge, perception, practice and effectiveness of the trainings among healthcare workers of ICU in our hospital., Methodology: A cross-sectional study was conducted in the ICU containing 8 medical and 16 surgical beds with 284 filled questionnaires about HH knowledge and 1187 observed opportunities for HH compliance., Results: Overall observed HH compliance rate was 40.6%; lowest compliance was 21.7% for "before clean/aseptic procedure" indication and highest compliance was 68.6% for "after touching a patient" indication. Although > 90% healthcare workers correctly identified the World Health Organization's five indications for HH, 82 - 85% failed to recognize non-indications, i.e. when it was not necessary to perform HH. Our study showed that 15.1% of healthcare workers neither received nor felt the need for HH training., Conclusions: Despite regular HH trainings, healthcare workers could not differentiate when HH was not required which suggested failure to understand HH rationale. This may explain poor HH compliance rates. A systematic study is needed in order to find out the reasons behind of this noncompliance and improve HH training methods for educating healthcare workers., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2019 Uluhan Sili, Pinar Ay, Huseyin Bilgin, Seyhan Hidiroglu, Volkan Korten.)

Published
2019
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43. A qualitative study of hand hygiene compliance among health care workers in intensive care units.

Author

Ay P, Teker AG, Hidiroglu S, Tepe P, Surmen A, Sili U, Korten V, and Karavus M

Subjects
Adult, Female, Humans, Intensive Care Units standards, Male, Middle Aged, Attitude of Health Personnel, Cross Infection prevention & control, Guideline Adherence standards, Hand Hygiene standards, Infection Control standards, Personnel, Hospital standards
Abstract

Introduction: Studies indicate that adherence to hand hygiene guidelines is at suboptimal levels. We aimed to explore the reasons for poor hand hygiene compliance., Methodology: A qualitative study based on the Theory of Planned Behavior as a framework in explaining compliance, consisting four focus group discussions and six in-depth interviews., Results: Participants mostly practiced hand hygiene depending on the sense of "dirtiness" and "cleanliness". Some of the participants indicated that on-job training delivered by the infection control team changed their perception of "emotionally" based hand hygiene to "indication" based. Direct observations and individual feedback on one-to-one basis were the core of this training. There was low social cohesiveness and a deep polarization between the professional groups that led one group accusing the other for not being compliant., Conclusions: The infection control team should continue delivering one-to-one trainings based on observation and immediate feedback. But there is need to base this training model on a structured behavioral modification program and test its efficacy through a quasi-experimental design. Increasing social cohesiveness and transforming the blaming culture to a collaborative safety culture is also crucial to improve compliance. High workload, problems related to work-flow and turnover should be addressed., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2019 Pinar Ay, Ayse Gulsen Teker, Seyhan Hidiroglu, Pinar Tepe, Aysen Surmen, Uluhan Sili, Volkan Korten, Melda Karavus.)

Published
2019
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44. Successful treatment of an invasive fungal infection caused by Talaromyces sp. with voriconazole.

Author

Sili U, Bilgin H, Masania R, Eryuksel E, Cimsit NC, Ayranci G, Richardson M, and Korten V

Abstract

Invasive fungal infections (IFI) are on the rise due to increasing numbers of immunosuppressed and critically ill patients. A malignant-looking pulmonary nodule in an immunosuppressed patient may indeed be caused by a fungal organism. We report a patient, who was eventually diagnosed with an IFI caused by an agent of hyalohyphomycosis, Talaromyces sp. determined via molecular methods and succesfully treated with voriconazole.

Published
2015
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45. Compliance of healthcare workers with hand hygiene practices in neonatal and pediatric intensive care units: overt observation.

Author

Karaaslan A, Kepenekli Kadayifci E, Atıcı S, Sili U, Soysal A, Çulha G, Pekru Y, and Bakır M

Abstract

Background. The objective of this study was to assess the compliance of hand hygiene (HH) of healthcare workers (HCWs) in the neonatal and pediatric intensive care unit in a tertiary university hospital in Istanbul. Methods. An observational study was conducted on the compliance of HH for the five World Health Organization (WHO) indications. HCWs were observed during routine patient care in day shift. The authors also measured the technique of HH through hand washing or hand hygiene with alcohol-based disinfectant. Results. A total of 704 HH opportunities were identified during the observation period. Overall compliance was 37.0% (261/704). Compliance differed by role: nurses (41.4%) and doctors (31.9%) [P = 0.02, OR: 1.504, CI 95%: 1.058-2.137]. HCWs were more likely to use soap and water (63.6%) compared to waterless-alcohol-based hand hygiene (36.3%) [P < 0.05]. Conclusion. Adherence to hand hygiene practice and use of alcohol-based disinfectant was found to be very low. Effective education programs that improve adherence to hand hygiene and use of disinfectants may be helpful to increase compliance.

Published
2014
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46. Production of good manufacturing practice-grade cytotoxic T lymphocytes specific for Epstein-Barr virus, cytomegalovirus and adenovirus to prevent or treat viral infections post-allogeneic hematopoietic stem cell transplant.

Author

Sili U, Leen AM, Vera JF, Gee AP, Huls H, Heslop HE, Bollard CM, and Rooney CM

Subjects
Antigen-Presenting Cells immunology, Antigen-Presenting Cells transplantation, Cell Line, Transformed, Cell Proliferation, Cytotoxicity, Immunologic, HLA Antigens immunology, Humans, Phosphoproteins immunology, T-Lymphocytes, Cytotoxic transplantation, Transplantation, Homologous adverse effects, Viral Matrix Proteins immunology, Virus Diseases therapy, Adenoviridae immunology, Cell Culture Techniques, Cytomegalovirus immunology, Hematopoietic Stem Cell Transplantation adverse effects, Herpesvirus 4, Human immunology, T-Lymphocytes, Cytotoxic immunology, Virus Diseases etiology
Abstract

Infections with a range of common community viruses remain a major cause of mortality and morbidity after allogeneic hematopoietic stem cell transplantation. T cells specific for cytomegalovirus (CMV), Epstein-Barr virus (EBV) and adenoviruses can safely prevent and infections with these three most common culprits, but the manufacture of individual T cell lines for each virus would be prohibitive in terms of time and cost. We have demonstrated that T cells specific for all three viruses can be manufactured in a single culture using monocytes and EBV-transformed B lymphoblastoid cell lines (LCLs), both transduced with an adenovirus vector expressing pp65 of CMV, as antigen-presenting cells. Trivirus-specific T cell lines produced from healthy stem cell donors could prevent and treat infections with all three viruses, not only in the designated recipient, but in unrelated, partially-HLA-matched third party recipients. We now provide the details and logistics of T cell manufacture.

Published
2012
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47. Monoculture-derived T lymphocytes specific for multiple viruses expand and produce clinically relevant effects in immunocompromised individuals.

Author

Leen AM, Myers GD, Sili U, Huls MH, Weiss H, Leung KS, Carrum G, Krance RA, Chang CC, Molldrem JJ, Gee AP, Brenner MK, Heslop HE, Rooney CM, and Bollard CM

Subjects
Adenoviridae metabolism, Adolescent, Adult, CD4-Positive T-Lymphocytes virology, CD8-Positive T-Lymphocytes virology, Cells, Cultured, Child, Child, Preschool, Cytomegalovirus metabolism, Female, Herpesvirus 4, Human metabolism, Humans, Immunophenotyping, Male, Middle Aged, T-Lymphocytes metabolism, CD4-Positive T-Lymphocytes cytology, CD8-Positive T-Lymphocytes cytology, Cell Culture Techniques methods, Immune System Diseases blood, Immune System Diseases therapy
Abstract

Immunocompromised individuals are at high risk for life-threatening diseases, especially those caused by cytomegalovirus (CMV), Epstein-Barr virus (EBV) and adenovirus. Conventional therapeutics are primarily active only against CMV, and resistance is frequent. Adoptive transfer of polyclonal cytotoxic T lymphocytes (CTLs) specific for CMV or EBV seems promising, but it is unclear whether this strategy can be extended to adenovirus, which comprises many serotypes. In addition, the preparation of a specific CTL line for each virus in every eligible individual would be impractical. Here we describe genetic modification of antigen-presenting cell lines to facilitate the production of CD4(+) and CD8(+) T lymphocytes specific for CMV, EBV and several serotypes of adenovirus from a single cell culture. When administered to immunocompromised individuals, the single T lymphocyte line expands into multiple discrete virus-specific populations that supply clinically measurable antiviral activity. Monoculture-derived multispecific CTL infusion could provide a safe and efficient means to restore virus-specific immunity in the immunocompromised host.

Published
2006
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48. A comparison of gene transfer and antigen-loaded dendritic cells for the generation of CD4+ and CD8+ cytomegalovirus-specific T cells in HLA-A2+ and HLA-A2- donors.

Author

Foster AE, Bradstock KF, Sili U, Marangolo M, Rooney CM, and Gottlieb DJ

Subjects
Blood Donors, Cells, Cultured, Cytomegalovirus genetics, Humans, Phosphoproteins genetics, Transduction, Genetic, Viral Matrix Proteins genetics, CD4-Positive T-Lymphocytes immunology, CD8-Positive T-Lymphocytes immunology, Cytomegalovirus immunology, Dendritic Cells immunology, HLA-A2 Antigen immunology, Phosphoproteins immunology, Viral Matrix Proteins immunology
Abstract

Dendritic cells have been used effectively to select for human cytomegalovirus (CMV)-specific T cells for immunotherapy applications. The ability to process and present relevant major histocompatibility complex class I and II peptides to T cells makes them ideal for selecting CD4+ and CD8+ T cells regardless of HLA tissue type. This study compared the generation of CMV-specific T cells by using dendritic cells loaded with either CMV pp65495-503 peptide or CMV lysate or transduced with adenovirus encoding the pp65 gene (Ad5pp65GFP) for the generation of CD4+ and CD8+ CMV-specific T cells in HLA-A2+ and HLA-A2 - donors. In HLA-A2+ donors, CD8+ tetramer+ T cells increased with all antigens but were greatest in peptide- and Ad5pp65GFP-stimulated T cells. The CD4+ /CD8+ ratio in the stimulated T-cell cultures proved to be dependent on the antigen used. CMV lysate-stimulated cells were primarily CD4+, whereas peptide- and Ad5pp65GFP-stimulated cultures were mostly CD8+. Analysis of cells from lysate-stimulated or gene-transduced-stimulated cultures showed expansion of CMV-specific CD4+ T cells, indicating that major histocompatibility complex class II peptides were present in both antigens. Furthermore, CMV-specific T cells were generated from HLA-A2 - donors by using Ad5pp65GFP transduction or CMV lysate stimulation and were able to recognize a pp65 peptide restricted to the HLA-B35 allele. These data indicate that either CMV lysate or adenovirus encoding CMV antigenic genes may be useful for the generation of both CD4+ and CD8+ CMV-specific T cells in donors irrespective of HLA tissue type and may be applicable to clinical immunotherapy.

Published
2004
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49. Conserved CTL epitopes on the adenovirus hexon protein expand subgroup cross-reactive and subgroup-specific CD8+ T cells.

Author

Leen AM, Sili U, Vanin EF, Jewell AM, Xie W, Vignali D, Piedra PA, Brenner MK, and Rooney CM

Subjects
Alleles, Amino Acid Sequence, Animals, Capsid Proteins chemistry, Cells, Cultured, Conserved Sequence, Epitope Mapping, Epitopes, T-Lymphocyte chemistry, HLA-A Antigens genetics, HLA-A Antigens immunology, Humans, Mice, Molecular Sequence Data, Peptides chemistry, Peptides immunology, Adenoviridae immunology, Capsid Proteins immunology, Cross Reactions immunology, Epitopes, T-Lymphocyte immunology, T-Lymphocytes, Cytotoxic immunology
Abstract

Adenoviruses often cause lethal infections in immunocompromised individuals. Adoptive transfer of immune T cells offers a therapeutic option, but this strategy has been hindered by the paucity of information on molecular targets of cellular immunity and by the immunologic heterogeneity of the 51 human adenoviruses, which are grouped from A to F on the basis of genome size, composition, homology, and organization. Clonal analysis of the adenovirus-specific cytotoxic T lymphocyte (CTL) responses of seropositive individuals identified 5 novel CD8(+) T-cell epitopes, all located in conserved regions of the capsid protein hexon. Reactive T cells were cross-reactive between 2 to 4 groups, while no T cells specific for a single subgroup were detected. Thus, by exploiting these peptide targets, it is possible to prepare a T-cell population capable of reacting with most adenoviruses that cause disease in immunocompromised patients.

Published
2004
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50. Fiber-modified adenoviruses generate subgroup cross-reactive, adenovirus-specific cytotoxic T lymphocytes for therapeutic applications.

Author

Leen AM, Sili U, Savoldo B, Jewell AM, Piedra PA, Brenner MK, and Rooney CM

Subjects
Adenoviridae classification, Adenoviridae genetics, Adenoviridae Infections etiology, Adenoviridae Infections prevention & control, Adenoviridae Infections therapy, CD4-Positive T-Lymphocytes immunology, CD8-Positive T-Lymphocytes immunology, Cell Line, Cross Reactions, Dendritic Cells immunology, Genetic Vectors, Hematopoietic Stem Cell Transplantation adverse effects, Humans, Immunologic Memory, In Vitro Techniques, T-Lymphocytes, Cytotoxic transplantation, Adenoviridae immunology, Immunotherapy, Adoptive methods, T-Lymphocytes, Cytotoxic immunology
Abstract

Adenovirus (Ad) infections are responsible for considerable morbidity and mortality, particularly in pediatric hematopoietic stem cell transplant (HSCT) recipients. To date there is no therapy. The present study was motivated by the potential for using adoptive immunotherapy as either prophylaxis or treatment for Ad infections and associated diseases. The authors have developed a protocol to reactivate Ad-specific memory T cells from peripheral blood mononuclear cells (PBMCs) using a clinical-grade adenoviral vector. Such lines contain a specific CD4 and CD8 T-cell component and are capable of recognizing and lysing target cells infected with wild-type Ad serotypes from different Ad groups. Furthermore, the frequency of Ad-specific precursors can be determined in PBMCs ex vivo and used as a means to assess changes in Ad-specific T-cell memory responses after infusion. This is the first report of a simple and reproducible method to activate and expand Ad-specific cytotoxic T lymphocytes (CTLs), which should be protective against the range of different Ad subtypes that affect transplant recipients.

Published
2004
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