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1. Author Correction: Prospective individual patient data meta-analysis of two randomized trials on convalescent plasma for COVID-19 outpatients

Author

Millat-Martinez, Pere, Gharbharan, Arvind, Alemany, Andrea, Rokx, Casper, Geurtsvankessel, Corine, Papageorgiou, Grigorios, van Geloven, Nan, Jordans, Carlijn, Groeneveld, Geert, Swaneveld, Francis, van der Schoot, Ellen, Corbacho-Monné, Marc, Ouchi, Dan, Piccolo Ferreira, Francini, Malchair, Pierre, Videla, Sebastian, García García, Vanesa, Ruiz-Comellas, Anna, Ramírez-Morros, Anna, Rodriguez Codina, Joana, Amado Simon, Rosa, Grifols, Joan-Ramon, Blanco, Julian, Blanco, Ignacio, Ara, Jordi, Bassat, Quique, Clotet, Bonaventura, Baro, Bàrbara, Troxel, Andrea, Zwaginga, Jaap Jan, Mitjà, Oriol, and Rijnders, Bart J. A.

Published
2024
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4. Prospective individual patient data meta-analysis of two randomized trials on convalescent plasma for COVID-19 outpatients

Author

Millat-Martinez, Pere, Gharbharan, Arvind, Alemany, Andrea, Rokx, Casper, Geurtsvankessel, Corine, Papageorgiou, Grigorios, van Geloven, Nan, Jordans, Carlijn, Groeneveld, Geert, Swaneveld, Francis, van der Schoot, Ellen, Corbacho-Monné, Marc, Ouchi, Dan, Piccolo Ferreira, Francini, Malchair, Pierre, Videla, Sebastian, García García, Vanesa, Ruiz-Comellas, Anna, Ramírez-Morros, Anna, Rodriguez Codina, Joana, Amado Simon, Rosa, Grifols, Joan-Ramon, Blanco, Julian, Blanco, Ignacio, Ara, Jordi, Bassat, Quique, Clotet, Bonaventura, Baro, Bàrbara, Troxel, Andrea, Zwaginga, Jaap Jan, Mitjà, Oriol, and Rijnders, Bart J. A.

Published
2022
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5. Stratification of hospitalized COVID-19 patients into clinical severity progression groups by immuno-phenotyping and machine learning

Author

Mueller, Yvonne M., Schrama, Thijs J., Ruijten, Rik, Schreurs, Marco W. J., Grashof, Dwin G. B., van de Werken, Harmen J. G., Lasinio, Giovanna Jona, Álvarez-Sierra, Daniel, Kiernan, Caoimhe H., Castro Eiro, Melisa D., van Meurs, Marjan, Brouwers-Haspels, Inge, Zhao, Manzhi, Li, Ling, de Wit, Harm, Ouzounis, Christos A., Wilmsen, Merel E. P., Alofs, Tessa M., Laport, Danique A., van Wees, Tamara, Kraker, Geoffrey, Jaimes, Maria C., Van Bockstael, Sebastiaan, Hernández-González, Manuel, Rokx, Casper, Rijnders, Bart J. A., Pujol-Borrell, Ricardo, and Katsikis, Peter D.

Published
2022
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7. Dolutegravir/Lamivudine Is Noninferior to Continuing Dolutegravir- and Non-Dolutegravir-Based Triple-Drug Antiretroviral Therapy in Virologically Suppressed People With Human Immunodeficiency Virus: DUALING Prospective Nationwide Matched Cohort Study

Author

Vasylyev, Marta, primary, Wit, Ferdinand W N M, additional, Jordans, Carlijn C E, additional, Soetekouw, Robin, additional, van Lelyveld, Steven F L, additional, Kootstra, Gert-Jan, additional, Delsing, Corine E, additional, Ammerlaan, Heidi S M, additional, van Kasteren, Marjo E E, additional, Brouwer, Annemarie E, additional, Leyten, Eliane M S, additional, Claassen, Mark A A, additional, Hassing, Robert-Jan, additional, den Hollander, Jan G, additional, van den Berge, Marcel, additional, Roukens, Anna H E, additional, Bierman, Wouter F W, additional, Groeneveld, Paul H P, additional, Lowe, Selwyn H, additional, van Welzen, Berend J, additional, Richel, Olivier, additional, Nellen, Jeannine F, additional, van den Berk, Guido E L, additional, van der Valk, Marc, additional, Rijnders, Bart J A, additional, and Rokx, Casper, additional

Published
2024
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8. Clinical and Virological Outcome of Monoclonal Antibody Therapies Across Severe Acute Respiratory Syndrome Coronavirus 2 Variants in 245 Immunocompromised Patients: A Multicenter Prospective Cohort Study

Author

Huygens, Sammy, primary, GeurtsvanKessel, Corine, additional, Gharbharan, Arvind, additional, Bogers, Susanne, additional, Worp, Nathalie, additional, Boter, Marjan, additional, Bax, Hannelore I, additional, Kampschreur, Linda M, additional, Hassing, Robert-Jan, additional, Fiets, Roel B, additional, Levenga, Henriette, additional, Afonso, Pedro Miranda, additional, Koopmans, Marion, additional, Rijnders, Bart J A, additional, and Oude Munnink, Bas B, additional

Published
2024
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9. Taskforce report on the diagnosis and clinical management of COVID-19 associated pulmonary aspergillosis

Author

Verweij, Paul E., Brüggemann, Roger J. M., Azoulay, Elie, Bassetti, Matteo, Blot, Stijn, Buil, Jochem B., Calandra, Thierry, Chiller, Tom, Clancy, Cornelius J., Cornely, Oliver A., Depuydt, Pieter, Koehler, Philipp, Lagrou, Katrien, de Lange, Dylan, Lass-Flörl, Cornelia, Lewis, Russell E., Lortholary, Olivier, Liu, Peter-Wei Lun, Maertens, Johan, Nguyen, M. Hong, Patterson, Thomas F., Rijnders, Bart J. A., Rodriguez, Alejandro, Rogers, Thomas R., Schouten, Jeroen A., Wauters, Joost, van de Veerdonk, Frank L., and Martin-Loeches, Ignacio

Published
2021
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10. HCV micro-elimination in individuals with HIV in the Netherlands 4 years after universal access to direct-acting antivirals: a retrospective cohort study

Author

van der Valk, M., Geerlings, S.E., Goorhuis, A., Hovius, J.W., Lempkes, B., Nellen, F.J.B., van der Poll, T., Prins, J.M., van Vugt, M., Wiersinga, W.J., Wit, F.W.M.N., van Duinen, M., van Eden, J., Hazenberg, A., van Hes, A.M.H., Pijnappel, F.J.J., Smalhout, S.Y., Weijsenfeld, A.M., Jurriaans, S., Back, N.K.T., Zaaijer, H.L., Berkhout, B., Cornelissen, M.T.E., Schinkel, C.J., Wolthers, K.C., Peters, E.J.G., van Agtmael, M.A., Autar, R.S., Bomers, M., Sigaloff, K.C.E., Heitmuller, M., Laan, L.M., Ang, C.W., van Houdt, R., Jonges, M., van den Berge, M., Stegeman, A., Baas, S., Hage de Looff, L., Buiting, A., Reuwer, A., Veenemans, J., Wintermans, B., Pronk, M.J.H., Ammerlaan, H.S.M., van den Bersselaar, D.N.J., de Munnik, E.S., Deiman, B., Jansz, A.R., Scharnhorst, V., Tjhie, J., Wegdam, M.C.A., van Eeden, A., Nellen, J., Brokking, W., Elsenburg, L.J.M., Nobel, H., van Kasteren, M.E.E., Berrevoets, M.A.H., Brouwer, A.E., Adams, A., van Erve, R., de Kruijf-van de Wiel, B.A.F.M., Keelan-Phaf, S., van de Ven, B., Buiting, A.G.M., Murck, J.L., de Vries-Sluijs, T.E.M.S., Bax, H.I., van Gorp, E.C.M., de Jong-Peltenburg, N.C., de Mendonça Melo, M., van Nood, E., Nouwen, J.L., Rijnders, B.J.A., Rokx, C., Schurink, C.A.M., Slobbe, L., Verbon, A., Bassant, N., van Beek, J.E.A., Vriesde, M., van Zonneveld, L.M., de Groot, J., Boucher, C.A.B., Koopmans, M.P.G., van Kampen, J.J.A., Branger, J., Douma, R.A., Cents-Bosma, A.S., Duijf-van de Ven, C.J.H.M., Schippers, E.F., van Nieuwkoop, C., van IJperen, J.M., Geilings, J., van Burgel, N.D., Leyten, E.M.S., van der Hut, G., Gelinck, L.B.S., Mollema, F., Davids-Veldhuis, S., Tearno, C., Wildenbeest, G.S., Heikens, E., Groeneveld, P.H.P., Bouwhuis, J.W., Lammers, A.J.J., Kraan, S., van Hulzen, A.G.W., Kruiper, M.S.M., van der Bliek, G.L., Bor, P.C.J., Debast, S.B., Wagenvoort, G.H.J., Kroon, F.P., de Boer, M.G.J., Jolink, H., Lambregts, M.M.C., Roukens, A.H.E., Scheper, H., Dorama, W., van Holten, N., Claas, E.C.J., Wessels, E., den Hollander, J.G., Brouwer, C.J., Smit, J.V., Struik-Kalkman, D., van Niekerk, T., El Moussaoui, R., Pogany, K., Pontesilli, O., Lowe, S.H., Oude Lashof, A.M.L., Posthouwer, D., van Wolfswinkel, M.E., Ackens, R.P., Burgers, K., Schippers, J., Weijenberg-Maes, B., van Loo, I.H.M., Havenith, T.R.A., van Vonderen, M.G.A., Kampschreur, L.M., Faber, S., Steeman-Bouma, R., Al Moujahid, A., Kootstra, G.J., Delsing, C.E., van der Burg-van de Plas, M., Scheiberlich, L., Kortmann, W., van Twillert, G., Renckens, R., Ruiter-Pronk, D., van Truijen-Oud, F.A., Cohen Stuart, J.W.T., Jansen, E.R., Hoogewerf, M., Rozemeijer, W., van der Reijden, W.A., Sinnige, J.C., Brinkman, K., van den Berk, G.E.L., Blok, W.L., Lettinga, K.D., de Regt, M., Schouten, W.E.M., Stalenhoef, J.E., Veenstra, J., Vrouenraets, S.M.E., Blaauw, H., Geerders, G.F., Kleene, M.J., Kok, M., Knapen, M., van der Meché, I.B., Mulder-Seeleman, E., Toonen, A.J.M., Wijnands, S., Wttewaal, E., Kwa, D., van Crevel, R., Dofferhoff, A.S.M., ter Hofstede, H.J.M., Hoogerwerf, J., Keuter, M., Richel, O., Albers, M., Grintjes-Huisman, K.J.T., de Haan, M., Marneef, M., Strik-Albers, R., Rahamat-Langendoen, J., Stelma, F.F., Burger, D., Gisolf, E.H., Hassing, R.J., Claassen, M., ter Beest, G., van Bentum, P.H.M., Langebeek, N., Tiemessen, R., Swanink, C.M.A., van Lelyveld, S.F.L., Soetekouw, R., van der Prijt, L.M.M., van der Swaluw, J., Bermon, N., Jansen, R., Herpers, B.L., Veenendaal, D., Verhagen, D.W.M., Lauw, F.N., van Broekhuizen, M.C., van Wijk, M., Bierman, W.F.W., Bakker, M., Kleinnijenhuis, J., Kloeze, E., Middel, A., Postma, D.F., Stienstra, Y., Wouthuyzen-Bakker, M., Boonstra, A., de Groot-de Jonge, H., van der Meulen, P.A., de Weerd, D.A., Niesters, H.G.M., van Leer-Buter, C.C., Knoester, M., Hoepelman, A.I.M., Arends, J.E., Barth, R.E., Bruns, A.H.W., Ellerbroek, P.M., Mudrikova, T., Oosterheert, J.J., Schadd, E.M., van Welzen, B.J., Aarsman, K., Griffioen-van Santen, B.M.G., de Kroon, I., van Berkel, M., van Rooijen, C.S.A.M., Schuurman, R., Verduyn-Lunel, F., Wensing, A.M.J., Reiss, P., Zaheri, S., Boyd, A.C., Bezemer, D.O., van Sighem, A.I., Smit, C., Hillebregt, M., de Jong, A., Woudstra, T., Bergsma, D., Meijering, R., van de Sande, L., Rutkens, T., van der Vliet, S., de Groot, L., van den Akker, M., Bakker, Y., El Berkaoui, A., Bezemer, M., Brétin, N., Djoechro, E., Groters, M., Kruijne, E., Lelivelt, K.J., Lodewijk, C., Lucas, E., Munjishvili, L., Paling, F., Peeck, B., Ree, C., Regtop, R., Ruijs, Y., Schoorl, M., Schnörr, P., Scheigrond, A., Tuijn, E., Veenenberg, L., Visser, K.M., Witte, E.C., Smit, Colette, Boyd, Anders, Rijnders, Bart J A, van de Laar, Thijs J W, Leyten, Eliane M, Bierman, Wouter F, Brinkman, Kees, Claassen, Mark A A, den Hollander, Jan, Boerekamps, Anne, Newsum, Astrid M, Schinkel, Janke, Prins, Maria, Arends, Joop E, Op de Coul, Eline L M, van der Valk, Marc, and Reiss, Peter

Published
2021
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11. Clinical and Virological Outcome of Monoclonal Antibody Therapies Across SARS-CoV-2 Variants in 245 Immunocompromised Patients:a multicenter prospective cohort study

Author

Huygens, Sammy, GeurtsvanKessel, Corine, Gharbharan, Arvind, Bogers, Susanne, Worp, Nathalie, Boter, Marjan, Bax, Hannelore I, Kampschreur, Linda M, Hassing, Robert-Jan, Fiets, Roel B, Levenga, Henriette, Afonso, Pedro Miranda, Koopmans, Marion, Rijnders, Bart J A, Oude Munnink, Bas B, Huygens, Sammy, GeurtsvanKessel, Corine, Gharbharan, Arvind, Bogers, Susanne, Worp, Nathalie, Boter, Marjan, Bax, Hannelore I, Kampschreur, Linda M, Hassing, Robert-Jan, Fiets, Roel B, Levenga, Henriette, Afonso, Pedro Miranda, Koopmans, Marion, Rijnders, Bart J A, and Oude Munnink, Bas B

Abstract

Background. Immunocompromised patients (ICPs) have an increased risk for a severe and prolonged COVID-19. SARS-CoV-2 monoclonal antibodies (mAbs) were extensively used in these patients, but data from randomized trials that focus on ICPs are lacking. We evaluated the clinical and virological outcome of COVID-19 in ICPs treated with mAbs across SARS-CoV-2 variants. Methods. In this multicenter prospective cohort study, we enrolled B-cell- and/or T-cell-deficient patients treated with casirivimab/imdevimab, sotrovimab, or tixagevimab/cilgavimab. SARS-CoV-2 RNA was quantified and sequenced weekly, and time to viral clearance, viral genome mutations, hospitalization, and death rates were registered. Results. Two hundred and forty five patients infected with the Delta (50%) or Omicron BA.1, 2, or 5 (50%) variant were enrolled. Sixty-seven percent were vaccinated; 78 treated as outpatients, of whom 2 required hospital admission, but both survived. Of the 159 patients hospitalized at time of treatment, 43 (27%) required mechanical ventilation or died. The median time to viral clearance was 14 days (interquartile range, 7-22); however, it took >30 days in 15%. Resistance-associated spike mutations emerged in 9 patients in whom the median time to viral clearance was 63 days (95% confidence interval, 57-69; P < .001). Spike mutations were observed in 1 of 42 (2.4%) patients after treatment with 2 active mAbs, in 5 of 34 (14.7%) treated with actual monotherapy (sotrovimab), and 3 of 20 (12%) treated with functional monotherapy (ie, tixagevimab/cilgavimab against tixagevimab-resistant variant). Conclusions. Despite treatment with mAbs, morbidity and mortality of COVID-19 in ICPs remained substantial. Combination antiviral therapy should be further explored and may be preferred in severely ICPs.

Published
2024

12. Correction: Immunogenicity and reactogenicity of SARS-CoV-2 vaccines in people living with HIV in the Netherlands: A nationwide prospective cohort study

Author

Hensley, Kathryn S., Jongkees, Marlou J., Geers, Daryl, GeurtsvanKessel, Corine H., Mueller, Yvonne M., Dalm, Virgil A. S. H., Papageorgiou, Grigorios, Steggink, Hanka, Gorska, Alicja, Bogers, Susanne, den Hollander, Jan G., Bierman, Wouter F. W., Gelinck, Luc B. S., Schippers, Emile F., Ammerlaan, Heidi S. M., van der Valk, Marc, van Vonderen, Marit G. A., Delsing, Corine E., Gisolf, Elisabeth H., Bruns, Anke H. W., Lauw, Fanny N., Berrevoets, Marvin A. H., Sigaloff, Kim C. E., Soetekouw, Robert, Branger, Judith, de Mast, Quirijn, Lammers, Adriana J. J., Lowe, Selwyn H., de Vries, Rory D., Katsikis, Peter D., Rijnders, Bart J. A., Brinkman, Kees, Roukens, Anna H. E., and Rokx, Casper

Subjects
Biological sciences
Abstract

Author(s): Kathryn S. Hensley, Marlou J. Jongkees, Daryl Geers, Corine H. GeurtsvanKessel, Yvonne M. Mueller, Virgil A. S. H. Dalm, Grigorios Papageorgiou, Hanka Steggink, Alicja Gorska, Susanne Bogers, Jan G. [...]

Published
2023
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13. Clinical and Virological Outcome of Monoclonal Antibody Therapies Across SARS-CoV-2 Variants in 245 Immunocompromised Patients: A Multicenter Prospective Cohort Study.

Author

Huygens, Sammy, GeurtsvanKessel, Corine, Gharbharan, Arvind, Bogers, Susanne, Worp, Nathalie, Boter, Marjan, Bax, Hannelore I, Kampschreur, Linda M, Hassing, Robert-Jan, Fiets, Roel B, Levenga, Henriette, Afonso, Pedro Miranda, Koopmans, Marion, Rijnders, Bart J A, and Munnink, Bas B Oude

Subjects
THERAPEUTIC use of monoclonal antibodies, T-cell lymphoma, MORTALITY, IMMUNIZATION, RESEARCH funding, VIRAL load, PATIENTS, IMMUNOCOMPROMISED patients, HOSPITAL care, HOSPITAL admission & discharge, TREATMENT effectiveness, DESCRIPTIVE statistics, LONGITUDINAL method, ANTIVIRAL agents, RESEARCH, ARTIFICIAL respiration, GENETIC mutation, COVID-19, B cell lymphoma, EVALUATION
Abstract

Background Immunocompromised patients (ICPs) have an increased risk for a severe and prolonged COVID-19. SARS-CoV-2 monoclonal antibodies (mAbs) were extensively used in these patients, but data from randomized trials that focus on ICPs are lacking. We evaluated the clinical and virological outcome of COVID-19 in ICPs treated with mAbs across SARS-CoV-2 variants. Methods In this multicenter prospective cohort study, we enrolled B-cell– and/or T-cell–deficient patients treated with casirivimab/imdevimab, sotrovimab, or tixagevimab/cilgavimab. SARS-CoV-2 RNA was quantified and sequenced weekly, and time to viral clearance, viral genome mutations, hospitalization, and death rates were registered. Results Two hundred and forty five patients infected with the Delta (50%) or Omicron BA.1, 2, or 5 (50%) variant were enrolled. Sixty-seven percent were vaccinated; 78 treated as outpatients, of whom 2 required hospital admission, but both survived. Of the 159 patients hospitalized at time of treatment, 43 (27%) required mechanical ventilation or died. The median time to viral clearance was 14 days (interquartile range, 7–22); however, it took >30 days in 15%. Resistance-associated spike mutations emerged in 9 patients in whom the median time to viral clearance was 63 days (95% confidence interval, 57–69; P <.001). Spike mutations were observed in 1 of 42 (2.4%) patients after treatment with 2 active mAbs, in 5 of 34 (14.7%) treated with actual monotherapy (sotrovimab), and 3 of 20 (12%) treated with functional monotherapy (ie, tixagevimab/cilgavimab against tixagevimab-resistant variant). Conclusions Despite treatment with mAbs, morbidity and mortality of COVID-19 in ICPs remained substantial. Combination antiviral therapy should be further explored and may be preferred in severely ICPs. [ABSTRACT FROM AUTHOR]

Published
2024
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14. Diagnostic Value of Microbial Cell-free DNA Sequencing for Suspected Invasive Fungal Infections: A Retrospective Multicenter Cohort Study.

Author

Huygens, Sammy, Schauwvlieghe, Alexander, Wlazlo, Nick, Moors, Ine, Boelens, Jerina, Reynders, Marijke, Chong, Ga-Lai, Klaassen, Corné H W, and Rijnders, Bart J A

Subjects
CELL-free DNA, MYCOSES, DNA sequencing, NONINVASIVE diagnostic tests, NUCLEOTIDE sequencing
Abstract

Background An early diagnosis and treatment of invasive fungal disease (IFD) is associated with improved outcome, but the moderate sensitivity of noninvasive diagnostic tests makes this challenging. Invasive diagnostic procedures such as bronchoalveolar lavage (BAL) have a higher yield but are not without risk. The detection and sequencing of microbial cell-free DNA (mcfDNA) may facilitate a noninvasive diagnosis. Materials In a prospective observational study, we collected plasma in the 120 hours preceding or following a BAL in patients with hematological malignancies suspected for a pulmonary IFD. The EORTC/MSGERC2020 criteria were used for IFD classification. Sequencing was performed by Karius (Redwood City, CA) using their Karius Test (KT) on plasma and a "research use only test" on BAL fluid if available. Cases with a probable/proven IFD were identified based on standard diagnostic tests on serum and BAL (microscopy, polymerase chain reaction, galactomannan, culture) and used to calculate the sensitivity, specificity, and additional diagnostic value of the KT. Results Of 106 patients enrolled, 39 (37%) had a proven/probable invasive aspergillosis, 7 (7%) a non- Aspergillus IFD, and 4 (4%) a mixed IFD. The KT detected fungal mcfDNA in 29 (28%) patients. Compared with usual diagnostic tests, the sensitivity and specificity were 44.0% (95% confidence interval [CI], 31.2–57.7) and 96.6% (95% CI, 88.5%–99.1%). Sensitivity of the KT was higher in non- Aspergillus IFD (Mucorales :2/3, Pneumocystis jirovecii : 3/5). On BAL, the sensitivity was 72.2% (95% CI, 62.1–96.3), and specificity 83.3% (95% CI, 49.1–87.5). Conclusions Sequencing of mcfDNA may facilitate a noninvasive diagnosis of IFD in particular non- Aspergillus IFD. However, on plasma and similar to currently available diagnostics, it cannot be used as a "rule-out" test. [ABSTRACT FROM AUTHOR]

Published
2024
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15. Effects of potent neutralizing antibodies from convalescent plasma in patients hospitalized for severe SARS-CoV-2 infection

Author

Gharbharan, Arvind, Jordans, Carlijn C. E., GeurtsvanKessel, Corine, den Hollander, Jan G., Karim, Faiz, Mollema, Femke P. N., Stalenhoef – Schukken, Janneke E., Dofferhoff, Anthonius, Ludwig, Inge, Koster, Adrianus, Hassing, Robert-Jan, Bos, Jeannet C., van Pottelberge, Geert R., Vlasveld, Imro N., Ammerlaan, Heidi S. M., van Leeuwen – Segarceanu, Elena M., Miedema, Jelle, van der Eerden, Menno, Schrama, Thijs J., Papageorgiou, Grigorios, te Boekhorst, Peter, Swaneveld, Francis H., Mueller, Yvonne M., Schreurs, Marco W. J., van Kampen, Jeroen J. A., Rockx, Barry, Okba, Nisreen M. A., Katsikis, Peter D., Koopmans, Marion P. G., Haagmans, Bart L., Rokx, Casper, and Rijnders, Bart J. A.

Published
2021
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16. Immunogenicity and reactogenicity of SARS-CoV-2 vaccines in people living with HIV in the Netherlands: A nationwide prospective cohort study

Author

Hensley, Kathryn S., Jongkees, Marlou J., Geers, Daryl, GeurtsvanKessel, Corine H., Mueller, Yvonne M., Dalm, Virgil A. S. H., Papageorgiou, Grigorios, Steggink, Hanka, Gorska, Alicja, Bogers, Susanne, den Hollander, Jan G., Bierman, Wouter F. W., Gelinck, Luc B. S., Schippers, Emile F., Ammerlaan, Heidi S. M., van der Valk, Marc, van Vonderen, Marit G. A., Delsing, Corine E., Gisolf, Elisabeth H., Bruns, Anke H. W., Lauw, Fanny N., Berrevoets, Marvin A. H., Sigaloff, Kim C. E., Soetekouw, Robert, Branger, Judith, de Mast, Quirijn, Lammers, Adriana J. J., Lowe, Selwyn H., de Vries, Rory D., Katsikis, Peter D., Rijnders, Bart J. A., Brinkman, Kees, Roukens, Anna H. E., and Rokx, Casper

Subjects
Immune response -- Evaluation -- Comparative analysis, HIV patients -- Drug therapy, Biological sciences
Abstract

Background Vaccines can be less immunogenic in people living with HIV (PLWH), but for SARS-CoV-2 vaccinations this is unknown. In this study we set out to investigate, for the vaccines currently approved in the Netherlands, the immunogenicity and reactogenicity of SARS-CoV-2 vaccinations in PLWH. Methods and findings We conducted a prospective cohort study to examine the immunogenicity of BNT162b2, mRNA-1273, ChAdOx1-S, and Ad26.COV2.S vaccines in adult PLWH without prior COVID-19, and compared to HIV-negative controls. The primary endpoint was the anti-spike SARS-CoV-2 IgG response after mRNA vaccination. Secondary endpoints included the serological response after vector vaccination, anti-SARS-CoV-2 T-cell response, and reactogenicity. Between 14 February and 7 September 2021, 1,154 PLWH (median age 53 [IQR 44-60] years, 85.5% male) and 440 controls (median age 43 [IQR 33-53] years, 28.6% male) were included in the final analysis. Of the PLWH, 884 received BNT162b2, 100 received mRNA-1273, 150 received ChAdOx1-S, and 20 received Ad26.COV2.S. In the group of PLWH, 99% were on antiretroviral therapy, 97.7% were virally suppressed, and the median CD4+ T-cell count was 710 cells/[mu]L (IQR 520-913). Of the controls, 247 received mRNA-1273, 94 received BNT162b2, 26 received ChAdOx1-S, and 73 received Ad26.COV2.S. After mRNA vaccination, geometric mean antibody concentration was 1,418 BAU/mL in PLWH (95% CI 1322-1523), and after adjustment for age, sex, and vaccine type, HIV status remained associated with a decreased response (0.607, 95% CI 0.508-0.725, p 300 BAU/mL, whilst in PLWH this response rate was 93.6%. In PLWH vaccinated with mRNA-based vaccines, higher antibody responses were predicted by CD4+ T-cell count 250-500 cells/[mu]L (2.845, 95% CI 1.876-4.314, p 500 cells/[mu]L (2.936, 95% CI 1.961-4.394, p 50 copies/mL was associated with a reduced response (0.454, 95% CI 0.286-0.720, p = 0.001). Increased IFN-[gamma], CD4+ T-cell, and CD8+ T-cell responses were observed after stimulation with SARS-CoV-2 spike peptides in ELISpot and activation-induced marker assays, comparable to controls. Reactogenicity was generally mild, without vaccine-related serious adverse events. Due to the control of vaccine provision by the Dutch National Institute for Public Health and the Environment, there were some differences between vaccine groups in the age, sex, and CD4+ T-cell counts of recipients. Conclusions After vaccination with BNT162b2 or mRNA-1273, anti-spike SARS-CoV-2 antibody levels were reduced in PLWH compared to HIV-negative controls. To reach and maintain the same serological responses as HIV-negative controls, additional vaccinations are probably required. Trial registration The trial was registered in the Netherlands Trial Register (NL9214). https://www.trialregister.nl/trial/9214., Author(s): Kathryn S. Hensley 1, Marlou J. Jongkees 1, Daryl Geers 2, Corine H. GeurtsvanKessel 2, Yvonne M. Mueller 3, Virgil A. S. H. Dalm 3,4, Grigorios Papageorgiou 5, Hanka [...]

Published
2022
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17. Review of influenza-associated pulmonary aspergillosis in ICU patients and proposal for a case definition: an expert opinion

Author

Verweij, Paul E., Rijnders, Bart J. A., Brüggemann, Roger J. M., Azoulay, Elie, Bassetti, Matteo, Blot, Stijn, and Calandra, Thierry

Subjects
Astellas Pharma Inc., Gilead Sciences Inc., Pfizer Inc., Merck Sharp & Dohme Corp., Biological products industry -- Health aspects -- Usage, Pulmonary aspergillosis -- Care and treatment, Medical research -- Usage -- Health aspects, Medicine, Experimental -- Usage -- Health aspects, Influenza -- Care and treatment, Medical colleges -- Health aspects -- Usage, Epidemiology -- Usage -- Health aspects, Hospital patients -- Care and treatment, Pharmaceutical industry -- Health aspects -- Usage, Health care industry
Abstract

Purpose Invasive pulmonary aspergillosis is increasingly reported in patients with influenza admitted to the intensive care unit (ICU). Classification of patients with influenza-associated pulmonary aspergillosis (IAPA) using the current definitions for invasive fungal diseases has proven difficult, and our aim was to develop case definitions for IAPA that can facilitate clinical studies. Methods A group of 29 international experts reviewed current insights into the epidemiology, diagnosis and management of IAPA and proposed a case definition of IAPA through a process of informal consensus. Results Since IAPA may develop in a wide range of hosts, an entry criterion was proposed and not host factors. The entry criterion was defined as a patient requiring ICU admission for respiratory distress with a positive influenza test temporally related to ICU admission. In addition, proven IAPA required histological evidence of invasive septate hyphae and mycological evidence for Aspergillus. Probable IAPA required the detection of galactomannan or positive Aspergillus culture in bronchoalveolar lavage (BAL) or serum with pulmonary infiltrates or a positive culture in upper respiratory samples with bronchoscopic evidence for tracheobronchitis or cavitating pulmonary infiltrates of recent onset. The IAPA case definitions may be useful to classify patients with COVID-19-associated pulmonary aspergillosis (CAPA), while awaiting further studies that provide more insight into the interaction between Aspergillus and the SARS-CoV-2-infected lung. Conclusion A consensus case definition of IAPA is proposed, which will facilitate research into the epidemiology, diagnosis and management of this emerging acute and severe Aspergillus disease, and may be of use to study CAPA., Author(s): Paul E. Verweij [sup.1] [sup.2], Bart J. A. Rijnders [sup.3], Roger J. M. Brüggemann [sup.2] [sup.4], Elie Azoulay [sup.5], Matteo Bassetti [sup.6] [sup.7], Stijn Blot [sup.8] [sup.9], Thierry Calandra [...]

Published
2020
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18. Treatment of acute hepatitis C genotypes 1 and 4 with 8 weeks of grazoprevir plus elbasvir (DAHHS2): an open-label, multicentre, single-arm, phase 3b trial

Author

Boerekamps, Anne, De Weggheleire, Anja, van den Berk, Guido E, Lauw, Fanny N, Claassen, Mark A A, Posthouwer, Dirk, Bierman, Wouter F, Hullegie, Sebastiaan J, Popping, Stephanie, van de Vijver, David A C M, Dofferhoff, Anthonius S M, Kootstra, Gert Jan, Leyten, Eliane M, den Hollander, Jan, van Kasteren, Marjo E, Soetekouw, Robert, Ammerlaan, Heidi S M, Schinkel, Janke, Florence, Eric, Arends, Joop E, and Rijnders, Bart J A

Published
2019
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21. Screening for Hepatitis C Virus Reinfection Using a Behaviour-Based Risk Score among Men Who Have Sex with Men with HIV: Results from a Case–Control Diagnostic Validation Study

Author

Hage, Kris, primary, van de Kerkhof, Marita, additional, Boyd, Anders, additional, Carson, Joanne M., additional, Newsum, Astrid M., additional, Matser, Amy, additional, van der Valk, Marc, additional, Brinkman, Kees, additional, Arends, Joop E., additional, Lauw, Fanny N., additional, Rijnders, Bart J. A., additional, van Eeden, Arne, additional, Martinello, Marianne, additional, Matthews, Gail V., additional, Schinkel, Janke, additional, and Prins, Maria, additional

Published
2023
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23. The S230R Integrase Substitution Associated With Virus Load Rebound During Dolutegravir Monotherapy Confers Low-Level Resistance to Integrase Strand-Transfer Inhibitors

Author

Pham, Hanh T., Labrie, Lydia, Wijting, Ingeborg E. A., Hassounah, Said, Lok, Ka Yee, Portna, Inna, Goring, Mark E., Han, Yingshan, Lungu, Cynthia, van der Ende, Marchina E., Brenner, Bluma G., Boucher, Charles A., Rijnders, Bart J. A., van Kampen, Jeroen J. A., Mesplède, Thibault, and Wainberg, Mark A.

Published
2018

25. Declining Hepatitis C Virus (HCV) Incidence in Dutch Human Immunodeficiency Virus-Positive Men Who Have Sex With Men After Unrestricted Access to HCV Therapy

Author

Boerekamps, Anne, van den Berk, Guido E., Lauw, Fanny N., Leyten, Eliane M., van Kasteren, Marjo E., van Eeden, Arne, Posthouwer, Dirk, Claassen, Mark A., Dofferhoff, Anton S., Verhagen, Dominique W. M., Bierman, Wouter F., Lettinga, Kamilla D., Kroon, Frank P., Delsing, Corine E., Groeneveld, Paul H., Soetekouw, Robert, Peters, Edgar J., Hullegie, Sebastiaan J., Popping, Stephanie, van de Vijver, David A. M. C., Boucher, Charles A., Arends, Joop E., and Rijnders, Bart J.

Published
2018

26. Invasive aspergillosis in patients admitted to the intensive care unit with severe influenza: a retrospective cohort study

Author

Schauwvlieghe, Alexander F A D, Rijnders, Bart J A, Philips, Nele, Verwijs, Rosanne, Vanderbeke, Lore, Van Tienen, Carla, Lagrou, Katrien, Verweij, Paul E, Van de Veerdonk, Frank L, Gommers, Diederik, Spronk, Peter, Bergmans, Dennis C J J, Hoedemaekers, Astrid, Andrinopoulou, Eleni-Rosalina, van den Berg, Charlotte H S B, Juffermans, Nicole P, Hodiamont, Casper J, Vonk, Alieke G, Depuydt, Pieter, Boelens, Jerina, and Wauters, Joost

Published
2018
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27. Hyperimmune Globulin for Severely Immunocompromised Patients Hospitalized With Coronavirus Disease 2019

Author

Huygens, Sammy, Hofsink, Quincy, Nijhof, Inger S., Goorhuis, Abraham, Kater, Arnon P., Te Boekhorst, Peter A.W., Swaneveld, Francis, Novotný, Věra M.J., Bogers, Susanne, Welkers, Matthijs R.A., Papageorgiou, Grigorios, Rijnders, Bart J., Heijmans, Jarom, Graduate School, Clinical Haematology, Infectious diseases, APH - Aging & Later Life, APH - Global Health, AII - Infectious diseases, Experimental Immunology, AII - Cancer immunology, CCA - Cancer biology and immunology, Medical Microbiology and Infection Prevention, General Internal Medicine, Internal Medicine, Hematology, Virology, and Epidemiology

Subjects
Infectious Diseases, SDG 3 - Good Health and Well-being, Immunology and Allergy, COVID-19, plasma-derived antibody therapy, anti-SARS-CoV-2 hyperimmune globulin, severely immunocompromised state, B-cell dysfunction
Abstract

Background The aim of this randomized, controlled trial is to determine whether antisevere acute respiratory syndrome coronavirus 2 hyperimmune globulin (COVIG) protects against severe coronavirus disease 2019 (COVID-19) in severely immunocompromised, hospitalized, COVID-19 patients. Methods Patients were randomly assigned to receive COVIG or intravenous immunoglobulin (IVIG) without SARS-CoV-2 antibodies. Results Severe COVID-19 was observed in 2 of 10 (20%) patients treated with COVIG compared to 7 of 8 (88%) in the IVIG control group (P = .015, Fisher’s exact test). Conclusions Antisevere acute respiratory syndrome coronavirus 2 hyperimmune globulin may be a valuable treatment in severely immunocompromised, hospitalized, COVID-19 patients and should be considered when no monoclonal antibody therapies are available.

Published
2023

29. Is hepatitis C virus elimination possible among people living with HIV and what will it take to achieve it?

Author

Martin, Natasha K, Boerekamps, Anne, Hill, Andrew M, and Rijnders, Bart J A

Subjects
HIV patients -- Health aspects, Antiviral agents -- Dosage and administration, Hepatitis C -- Risk factors -- Patient outcomes -- Prevention -- Drug therapy, Health
Abstract

Introduction: The World Health Organization targets for hepatitis C virus (HCV) elimination include a 90% reduction in new infections by 2030. Our objective is to review the modelling evidence and cost data surrounding feasibility of HCV elimination among people living with HIV (PLWH), and identify likely components for elimination. We also discuss the real-world experience of HCV direct acting antiviral (DAA) scale-up and elimination efforts in the Netherlands. Methods: We review modelling evidence of what intervention scale-up is required to achieve WHO HCV elimination targets among HIV-infected (HIV+) people who inject drugs (PWID) and men who have sex with men (MSM), review cost-effectiveness of HCV therapy among PLWH and discuss economic implications of elimination. We additionally use the real-world experience of DAA scale-up in the Netherlands to illustrate the promise and potential challenges of HCV elimination strategies in MSM. Finally, we summarize key components of the HCV elimination response among PWLH. Results and discussion: Modelling indicates HCV elimination among HIV+ MSM and PWID is potentially achievable but requires combination treatment and either harm reduction or behavioural risk reductions. Preliminary modelling indicates elimination among HIV+ PWID will require elimination efforts among PWID more broadly. Treatment for PLWH and high-risk populations (PWID and MSM) is cost-effective in high-income countries, but costs of DAAs remain a barrier to scale-up worldwide despite the potential low production price ($50 per 12 week course). In the Netherlands, universal DAA availability led to rapid uptake among HIV+ MSM in 2015/16, and a 50% reduction in acute HCV incidence among HIV+ MSM from 2014 to 2016 was observed. In addition to HCV treatment, elimination among PLWH globally also likely requires regular HCV testing, development of low-cost accurate HCV diagnostics, reduced costs of DAA therapy, broad treatment access without restrictions, close monitoring for HCV reinfection and retreatment, and harm reduction and/or behavioural interventions. Conclusions: Achieving WHO HCV Elimination targets is potentially achievable among HIV-infected populations. Among HIV+ PWID, it likely requires HCV treatment scale-up combined with harm reduction for both HIV+ and HIV- populations. Among HIV+ MSM, elimination likely requires both HCV treatment and behaviour risk reduction among the HIV+ MSM population, the latter of which to date has not been observed. Lower HCV diagnostic and treatment costs will be key to ensuring scale-up of HCV testing and treatment without restriction, enabling elimination. Keywords: HCV; treatment; elimination; modelling, 1 | INTRODUCTION Viral hepatitis was the seventh leading cause of death worldwide in 2013, increasing from the tenth leading cause in 2010 [1]. The vast majority of morbidity and [...]

Published
2018
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31. BCG Vaccination of Health Care Workers Does Not Reduce SARS-CoV-2 Infections nor Infection Severity or Duration: a Randomized Placebo-Controlled Trial

Author

Claus, Juana, primary, ten Doesschate, Thijs, additional, Gumbs, Cheyenne, additional, van Werkhoven, Cornelis H., additional, van der Vaart, Thomas W., additional, Janssen, Axel B., additional, Smits, Gaby, additional, van Binnendijk, Rob, additional, van der Klis, Fiona, additional, van Baarle, Debbie, additional, Paganelli, Fernanda L., additional, Leavis, Helen, additional, Verhagen, Lilly M., additional, Joosten, Simone A., additional, Bonten, Marc J. M., additional, Netea, Mihai G., additional, van de Wijgert, Janneke H. H. M., additional, Boersma, Wim G., additional, Bulut, Özlem, additional, van Crevel, Reinout, additional, Debisarun, Priya A., additional, Hoogerwerf, Jacobien, additional, de Jonge, Marien, additional, Kerckhoffs, Angele P. M., additional, Knol, Edward, additional, Koopman, Jan Pieter R., additional, Kuiper, Vincent P., additional, Lalmohamed, Arief, additional, Moorlag, Simone J. C. F. M., additional, Nierkens, Stefan, additional, van Nieuwkoop, Cees, additional, 10 Oever, Jaap, additional, Ottenhoff, Tom H. M., additional, Paternotte, Nienke, additional, Rijnders, Bart J. A., additional, Roukens, Anna H. E., additional, Taks, Esther, additional, Top, Janetta, additional, Veerman, Karin M., additional, Voss, Andreas, additional, and Willems, Rob, additional

Published
2023
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32. Early, very high-titre convalescent plasma therapy in clinically vulnerable individuals with mild COVID-19 (COVIC-19): protocol for a randomised, open-label trial

Author

Desmarets, Maxime, primary, Hoffmann, Simone, additional, Vauchy, Charline, additional, Rijnders, Bart J A, additional, Toussirot, Eric, additional, Durrbach, Antoine, additional, Körper, Sixten, additional, Schrezenmeier, Eva, additional, van der Schoot, C Ellen, additional, Harvala, Heli, additional, Brunotte, Gaëlle, additional, Appl, Thomas, additional, Seifried, Erhard, additional, Tiberghien, Pierre, additional, Bradshaw, Daniel, additional, Roberts, David J, additional, Estcourt, Lise J, additional, and Schrezenmeier, Hubert, additional

Published
2023
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33. The BAF complex inhibitor pyrimethamine reverses HIV-1 latency in people with HIV-1 on antiretroviral therapy

Author

Prins, Henrieke A. B., primary, Crespo, Raquel, additional, Lungu, Cynthia, additional, Rao, Shringar, additional, Li, Letao, additional, Overmars, Ronald J., additional, Papageorgiou, Grigorius, additional, Mueller, Yvonne M., additional, Stoszko, Mateusz, additional, Hossain, Tanvir, additional, Kan, Tsung Wai, additional, Rijnders, Bart J. A., additional, Bax, Hannelore I., additional, van Gorp, Eric C. M., additional, Nouwen, Jan L., additional, de Vries-Sluijs, Theodora E. M. S., additional, Schurink, Carolina A. M., additional, de Mendonça Melo, Mariana, additional, van Nood, Els, additional, Colbers, Angela, additional, Burger, David, additional, Palstra, Robert-Jan, additional, van Kampen, Jeroen J. A., additional, van de Vijver, David A. M. C., additional, Mesplède, Thibault, additional, Katsikis, Peter D., additional, Gruters, Rob A., additional, Koch, Birgit C. P., additional, Verbon, Annelies, additional, Mahmoudi, Tokameh, additional, and Rokx, Casper, additional

Published
2023
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34. Clinical Impact of Polymerase Chain Reaction–based Aspergillus and Azole Resistance Detection in Invasive Aspergillosis: A Prospective Multicenter Study

Author

Huygens, Sammy, primary, Dunbar, Albert, additional, Buil, Jochem B, additional, Klaassen, Corné H W, additional, Verweij, Paul E, additional, van Dijk, Karin, additional, de Jonge, Nick, additional, Janssen, Jeroen J W M, additional, van der Velden, Walter J F M, additional, Biemond, Bart J, additional, Bart, Aldert, additional, Bruns, Anke H W, additional, Haas, Pieter-Jan A, additional, Demandt, Astrid M P, additional, Oudhuis, Guy, additional, von dem Borne, Peter, additional, van der Beek, Martha T, additional, Klein, Saskia K, additional, Godschalk, Peggy, additional, Span, Lambert F R, additional, Postma, Douwe F, additional, Kampinga, Greetje A, additional, Maertens, Johan, additional, Lagrou, Katrien, additional, Mercier, Toine, additional, Moors, Ine, additional, Boelens, Jerina, additional, Selleslag, Dominik, additional, Reynders, Marijke, additional, Zandijk, Willemien, additional, Doorduijn, Jeanette K, additional, Cornelissen, Jan J, additional, Schauwvlieghe, Alexander F A D, additional, and Rijnders, Bart J A, additional

Published
2023
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35. Low Hepatitis C Virus Prevalence among Men Who Have Sex with Men Attending Public Health Services in The Netherlands

Author

Popping, Stephanie, Haspels, Sabine, Gotz, Hannelore M., van der Meijden, W. C.J.P.M., van den Elshout, Mark, Rijnders, Bart J., Popping, Stephanie, Haspels, Sabine, Gotz, Hannelore M., van der Meijden, W. C.J.P.M., van den Elshout, Mark, and Rijnders, Bart J.

Abstract

The hepatitis C virus (HCV) prevalence is high among men who have sex with men (MSM) with HIV in the Netherlands. Large reductions in HCV incidence among MSM with HIV, however, have occurred since treatment with direct-acting antivirals. Over the years, a broader understanding of the HCV epidemic has shown that HCV infections are not solely restricted to MSM with HIV, but they also occur among HIV-negative MSM. Currently, HCV testing among HIV-negative MSM is only provided for PrEP users and is not part of routine sexually transmitted infection (STI) screening among HIV-negative MSM who are not using PrEP. In this study, we screened 1885 HIV-negative MSM who did not participate in a PrEP program, with over 1966 STI screening visits at four different public health clinic sites. Among the 1885 MSM, only one person had a new HCV infection, resulting in a 0.05% (95% confidence interval 0.0–0.3) incidence. Based on our findings, we can conclude that systematic HCV testing at STI clinics may not yield significant benefits for this particular population.

Published
2023

36. Clinical Impact of Polymerase Chain Reaction-Based Aspergillus and Azole Resistance Detection in Invasive Aspergillosis:A Prospective Multicenter Study

Author

Huygens, S, Dunbar, Albert, Buil, Jochem B, Klaassen, Corné H W, Verweij, Paul E, van Dijk, Karin, de Jonge, Nick, Janssen, Jeroen J W M, van der Velden, Walter J F M, Biemond, Bart J, Bart, Aldert, Bruns, Anke H W, Haas, Pieter-Jan A, Demandt, Astrid M P, Oudhuis, Guy, von dem Borne, Peter, van der Beek, Martha T, Klein, Saskia K, Godschalk, Peggy, Span, Lambert F R, Postma, Douwe F, Kampinga, Greetje A, Maertens, Johan, Lagrou, Katrien, Mercier, Toine, Moors, Ine, Boelens, Jerina, Selleslag, Dominik, Reynders, Marijke, Zandijk, Willemien, Doorduijn, Jeanette K, Cornelissen, Jan J, Schauwvlieghe, Alexander F A D, Rijnders, Bart J A, Huygens, S, Dunbar, Albert, Buil, Jochem B, Klaassen, Corné H W, Verweij, Paul E, van Dijk, Karin, de Jonge, Nick, Janssen, Jeroen J W M, van der Velden, Walter J F M, Biemond, Bart J, Bart, Aldert, Bruns, Anke H W, Haas, Pieter-Jan A, Demandt, Astrid M P, Oudhuis, Guy, von dem Borne, Peter, van der Beek, Martha T, Klein, Saskia K, Godschalk, Peggy, Span, Lambert F R, Postma, Douwe F, Kampinga, Greetje A, Maertens, Johan, Lagrou, Katrien, Mercier, Toine, Moors, Ine, Boelens, Jerina, Selleslag, Dominik, Reynders, Marijke, Zandijk, Willemien, Doorduijn, Jeanette K, Cornelissen, Jan J, Schauwvlieghe, Alexander F A D, and Rijnders, Bart J A

Abstract

BACKGROUND: Invasive aspergillosis (IA) by a triazole-resistant Aspergillus fumigatus is associated with high mortality. Real-time resistance detection will result in earlier initiation of appropriate therapy. METHODS: In a prospective study, we evaluated the clinical value of the AsperGenius polymerase chain reaction (PCR) assay in hematology patients from 12 centers. This PCR assay detects the most frequent cyp51A mutations in A. fumigatus conferring azole resistance. Patients were included when a computed tomography scan showed a pulmonary infiltrate and bronchoalveolar fluid (BALf) sampling was performed. The primary end point was antifungal treatment failure in patients with azole-resistant IA. RESULTS: Of 323 patients enrolled, complete mycological and radiological information was available for 276 (94%), and probable IA was diagnosed in 99/276 (36%). Sufficient BALf for PCR testing was available for 293/323 (91%). Aspergillus DNA was detected in 116/293 (40%) and A. fumigatus DNA in 89/293 (30%). The resistance PCR was conclusive in 58/89 (65%) and resistance detected in 8/58 (14%). Two had a mixed azole-susceptible/azole-resistant infection. In the 6 remaining patients, treatment failure was observed in 1. Galactomannan positivity was associated with mortality (P = .004) while an isolated positive Aspergillus PCR was not (P = .83). CONCLUSIONS: Real-time PCR-based resistance testing may help to limit the clinical impact of triazole resistance. In contrast, the clinical impact of an isolated positive Aspergillus PCR on BALf seems limited. The interpretation of the EORTC/MSGERC PCR criterion for BALf may need further specification (eg, minimum cycle threshold value and/or PCR positive on >1 BALf sample).

Published
2023

37. Hyperimmune Globulin for Severely Immunocompromised Patients Hospitalized With Coronavirus Disease 2019:A Randomized, Controlled Trial

Author

Huygens, Sammy, Hofsink, Quincy, Nijhof, Inger S., Goorhuis, Abraham, Kater, Arnon P., Te Boekhorst, Peter A.W., Swaneveld, Francis, Novotný, Věra M.J., Bogers, Susanne, Welkers, Matthijs R.A., Papageorgiou, Grigorios, Rijnders, Bart J., Heijmans, Jarom, Huygens, Sammy, Hofsink, Quincy, Nijhof, Inger S., Goorhuis, Abraham, Kater, Arnon P., Te Boekhorst, Peter A.W., Swaneveld, Francis, Novotný, Věra M.J., Bogers, Susanne, Welkers, Matthijs R.A., Papageorgiou, Grigorios, Rijnders, Bart J., and Heijmans, Jarom

Abstract

BACKGROUND: The aim of this randomized, controlled trial is to determine whether antisevere acute respiratory syndrome coronavirus 2 hyperimmune globulin (COVIG) protects against severe coronavirus disease 2019 (COVID-19) in severely immunocompromised, hospitalized, COVID-19 patients. METHODS: Patients were randomly assigned to receive COVIG or intravenous immunoglobulin (IVIG) without SARS-CoV-2 antibodies. RESULTS: Severe COVID-19 was observed in 2 of 10 (20%) patients treated with COVIG compared to 7 of 8 (88%) in the IVIG control group (P = .015, Fisher's exact test). CONCLUSIONS: Antisevere acute respiratory syndrome coronavirus 2 hyperimmune globulin may be a valuable treatment in severely immunocompromised, hospitalized, COVID-19 patients and should be considered when no monoclonal antibody therapies are available.

Published
2023

38. Clinical Characteristics and Outcomes of Immunocompromised Patients With Coronavirus Disease 2019 Caused by the Omicron Variant:A Prospective, Observational Study

Author

Malahe, S Reshwan K, Hoek, Rogier A S, Dalm, Virgil A S H, Broers, Annoek E C, den Hoed, Caroline M, Manintveld, Olivier C, Baan, Carla C, van Deuzen, Charlotte M, Papageorgiou, Grigorios, Bax, Hannelore I, Van Kampen, Jeroen J, Hellemons, Merel E, Kho, Marcia M L, de Vries, Rory D, Molenkamp, Richard, Reinders, Marlies E J, Rijnders, Bart J A, Malahe, S Reshwan K, Hoek, Rogier A S, Dalm, Virgil A S H, Broers, Annoek E C, den Hoed, Caroline M, Manintveld, Olivier C, Baan, Carla C, van Deuzen, Charlotte M, Papageorgiou, Grigorios, Bax, Hannelore I, Van Kampen, Jeroen J, Hellemons, Merel E, Kho, Marcia M L, de Vries, Rory D, Molenkamp, Richard, Reinders, Marlies E J, and Rijnders, Bart J A

Abstract

BACKGROUND: Illness after infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant is less severe compared with previous variants. Data on the disease burden in immunocompromised patients are lacking. We investigated the clinical characteristics and outcomes of immunocompromised patients with coronavirus disease 2019 (COVID-19) caused by Omicron. METHODS: Organ transplant recipients, patients on anti-CD20 therapy, and allogenic hematopoietic stem cell transplantation recipients infected with the Omicron variant were included. Characteristics of consenting patients were collected and patients were contacted regularly until symptom resolution. To identify possible risk factors for hospitalization, a univariate logistic analysis was performed. RESULTS: 114 consecutive immunocompromised patients were enrolled. Eighty-nine percent had previously received 3 mRNA vaccinations. While only 1 patient died, 23 (20%) were hospitalized for a median of 11 days. A low SARS-CoV-2 immunoglobulin G (IgG) antibody response (<300 BAU [binding antibody units]/mL) at diagnosis, being older, being a lung transplant recipient, having more comorbidities, and having a higher frailty score were associated with hospital admission (all P < .01). At the end of follow-up, 25% had still not fully recovered. Of the 23 hospitalized patients, 70% had a negative and 92% had a low IgG (<300 BAU/mL) antibody response at admission. Sotrovimab was administered to 17 of these patients, and 1 died. CONCLUSIONS: While the mortality in immunocompromised patients infected with Omicron was low, hospital admission was frequent and the duration of symptoms often prolonged. In addition to vaccination, other interventions are needed to limit the morbidity from COVID-19 in immunocompromised patients.

Published
2023

41. Clinical impact of PCR-based Aspergillus and azole resistance detection in invasive aspergillosis. A prospective multicenter study

Author

Huygens, S, Dunbar, Albert, Buil, Jochem B, Klaassen, Corné H W, Verweij, Paul E, van Dijk, Karin, de Jonge, Nick, Janssen, Jeroen J W M, van der Velden, Walter J F M, Biemond, Bart J, Bart, Aldert, Bruns, Anke H W, Haas, Pieter-Jan A, Demandt, Astrid M P, Oudhuis, Guy, von dem Borne, Peter, van der Beek, Martha T, Klein, Saskia K, Godschalk, Peggy, Span, Lambert F R, Postma, Douwe F, Kampinga, Greetje A, Maertens, Johan, Lagrou, Katrien, Mercier, Toine, Moors, Ine, Boelens, Jerina, Selleslag, Dominik, Reynders, Marijke, Zandijk, Willemien, Doorduijn, Jeanette K, Cornelissen, Jan J, Schauwvlieghe, Alexander F A D, Rijnders, Bart J A, Internal Medicine, Medical Microbiology & Infectious Diseases, and Hematology

Abstract

BACKGROUND: Invasive aspergillosis(IA) by a triazole resistant Aspergillus fumigatus is associated with a high mortality. Real-time resistance detection will result in earlier initiation of appropriate therapy. METHODS: In a prospective study in the Netherlands and Belgium, we evaluated the clinical value of the multiplex AsperGenius®PCR in hematology patients from 12 centers. This PCR detects the most frequent cyp51A mutations in A. fumigatus conferring azole-resistance. Patients were included when a CT-scan showed a pulmonary infiltrate and bronchoalveolar lavage(BALf) sampling was performed. The primary endpoint was antifungal treatment failure in patients with azole-resistant IA. Patients with mixed azole-susceptible/resistant infections were excluded. RESULTS: Of 323 patients enrolled, complete mycological and radiological information was available in 276/323(94%) and probable IA diagnosed in 99/276(36%). Sufficient BALf for PCR testing was available in 293/323(91%). Aspergillus DNA was detected in 116/293(40%) and A.fumigatus DNA in 89/293(30%). The resistance PCR was conclusive in 58/89(65%) and resistance detected in 8/58(14%). Two had a mixed azole-susceptible/resistant infection. In the 6 remaining patients, treatment failure was observed in one. Galactomannan positivity was associated with higher mortality(p=0.004). In contrast, mortality of patients with an isolated positive Aspergillus PCR was comparable to those with a negative PCR(p=0.83). CONCLUSIONS: Real-time PCR-based resistance testing may help to limit the clinical impact of triazole resistance. In contrast, the clinical impact of an isolated positive Aspergillus PCR on BALf seems limited. The interpretation of the EORTC/MSGERC PCR criterion for BALf may need further specification (e.g. minimum Ct-value and/or PCR positive on >1 BALf sample).

Published
2023

42. Erratum: Correction: Immunogenicity and reactogenicity of SARS-CoV-2 vaccines in people living with HIV in the Netherlands: A nationwide prospective cohort study (PLoS medicine (2022) 19 10 (e1003979))

Author

Hensley, Kathryn S., Jongkees, Marlou J., Geers, Daryl, GeurtsvanKessel, Corine H., Mueller, Yvonne M., Dalm, Virgil A. S. H., Papageorgiou, Grigorios, Steggink, Hanka, Gorska, Alicja, Bogers, Susanne, den Hollander, Jan G., Bierman, Wouter F. W., Gelinck, Luc B. S., Schippers, Emile F., Ammerlaan, Heidi S. M., van der Valk, Marc, van Vonderen, Marit G. A., Delsing, Corine E., Gisolf, Elisabeth H., Bruns, Anke H. W., Lauw, Fanny N., Berrevoets, Marvin A. H., Sigaloff, Kim C. E., Soetekouw, Robert, Branger, Judith, de Mast, Quirijn, Lammers, Adriana J. J., Lowe, Selwyn H., de Vries, Rory D., Katsikis, Peter D., Rijnders, Bart J. A., Brinkman, Kees, Roukens, Anna H. E., Rokx, Casper, Infectious diseases, and AII - Infectious diseases

Abstract

[This corrects the article DOI: 10.1371/journal.pmed.1003979.].

Published
2023

43. Erratum:Immunogenicity and reactogenicity of SARS-CoV-2 vaccines in people living with HIV in the Netherlands: A nationwide prospective cohort study (PLoS Med (2022) 19:10 (e1003979) DOI: 10.1371/journal.pmed.1003979)

Author

Hensley, Kathryn S., Jongkees, Marlou J., Geers, Daryl, GeurtsvanKessel, Corine H., Mueller, Yvonne M., Dalm, Virgil A. S. H., Papageorgiou, Grigorios, Steggink, Hanka, Gorska, Alicja, Bogers, Susanne, den Hollander, Jan G., Bierman, Wouter F. W., Gelinck, Luc B. S., Schippers, Emile F., Ammerlaan, Heidi S. M., van der Valk, Marc, van Vonderen, Marit G. A., Delsing, Corine E., Gisolf, Elisabeth H., Bruns, Anke H. W., Lauw, Fanny N., Berrevoets, Marvin A. H., Sigaloff, Kim C. E., Soetekouw, Robert, Branger, Judith, de Mast, Quirijn, Lammers, Adriana J. J., Lowe, Selwyn H., de Vries, Rory D., Katsikis, Peter D., Rijnders, Bart J. A., Brinkman, Kees, Roukens, Anna H. E., Rokx, Casper, and Internal medicine

Abstract

Fig 3 panel B contains a mislabeled axis. The label ‘Pre—HIV negative’ should be ‘Post—HIV negative.’ Please see the correct Fig 3 below.

Published
2023

45. Immunogenicity of an Additional mRNA-1273 SARS-CoV-2 Vaccination in People With HIV With Hyporesponse After Primary Vaccination

Author

Jongkees, Marlou J, primary, Geers, Daryl, additional, Hensley, Kathryn S, additional, Huisman, Wesley, additional, GeurtsvanKessel, Corine H, additional, Bogers, Susanne, additional, Gommers, Lennert, additional, Papageorgiou, Grigorios, additional, Jochems, Simon P, additional, den Hollander, Jan G, additional, Schippers, Emile F, additional, Ammerlaan, Heidi S M, additional, Bierman, Wouter F W, additional, van der Valk, Marc, additional, Berrevoets, Marvin A H, additional, Soetekouw, Robert, additional, Langebeek, Nienke, additional, Bruns, Anke H W, additional, Leyten, Eliane M S, additional, Sigaloff, Kim C E, additional, van Vonderen, Marit G A, additional, Delsing, Corine E, additional, Branger, Judith, additional, Katsikis, Peter D, additional, Mueller, Yvonne M, additional, de Vries, Rory D, additional, Rijnders, Bart J A, additional, Brinkman, Kees, additional, Rokx, Casper, additional, and Roukens, Anna H E, additional

Published
2022
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47. Coronavirus Disease 2019 Convalescent Plasma Outpatient Therapy to Prevent Outpatient Hospitalization: A Meta-Analysis of Individual Participant Data From 5 Randomized Trials.

Author

Levine, Adam C, Fukuta, Yuriko, Huaman, Moises A, Ou, Jiangda, Meisenberg, Barry R, Patel, Bela, Paxton, James H, Hanley, Daniel F, Rijnders, Bart J A, Gharbharan, Arvind, Rokx, Casper, Zwaginga, Jaap Jan, Alemany, Andrea, Mitjà, Oriol, Ouchi, Dan, Millat-Martinez, Pere, Durkalski-Mauldin, Valerie, Korley, Frederick K, Dumont, Larry J, and Callaway, Clifton W

Subjects
MEDICAL databases, RELATIVE medical risk, META-analysis, MEDICAL information storage & retrieval systems, CONFIDENCE intervals, IMMUNOGLOBULINS, SYSTEMATIC reviews, PREVENTIVE health services, CONVALESCENT plasma, HOSPITAL care, DESCRIPTIVE statistics, MEDLINE, COVID-19 pandemic, OUTPATIENT services in hospitals, COMORBIDITY
Abstract

Background Outpatient monoclonal antibodies are no longer effective and antiviral treatments for coronavirus disease 2019 (COVID-19) disease remain largely unavailable in many countries worldwide. Although treatment with COVID-19 convalescent plasma (CCP) is promising, clinical trials among outpatients have shown mixed results. Methods We conducted an individual participant data meta-analysis from outpatient trials to assess the overall risk reduction for all-cause hospitalizations by day 28 in transfused participants. Relevant trials were identified by searching Medline, Embase, medRxiv, World Health Organization COVID-19 Research Database, Cochrane Library, and Web of Science from January 2020 to September 2022. Results Five included studies from 4 countries enrolled and transfused 2620 adult patients. Comorbidities were present in 1795 (69%). The virus neutralizing antibody dilutional titer levels ranged from 8 to 14 580 in diverse assays. One hundred sixty of 1315 (12.2%) control patients were hospitalized, versus 111 of 1305 (8.5%) CCP-treated patients, yielding a 3.7% (95% confidence interval [CI], 1.3%–6.0%; P =.001) absolute risk reduction and 30.1% relative risk reduction for all-cause hospitalization. The hospitalization reduction was greatest in those with both early transfusion and high titer with a 7.6% absolute risk reduction (95% CI, 4.0%–11.1%; P =.0001) accompanied by at 51.4% relative risk reduction. No significant reduction in hospitalization was seen with treatment >5 days after symptom onset or in those receiving CCP with antibody titers below the median titer. Conclusions Among outpatients with COVID-19, treatment with CCP reduced the rate of all-cause hospitalization and may be most effective when given within 5 days of symptom onset and when antibody titer is higher. [ABSTRACT FROM AUTHOR]

Published
2023
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48. Hyperimmune Globulin for Severely Immunocompromised Patients Hospitalized With Coronavirus Disease 2019: A Randomized, Controlled Trial

Author

Huygens, Sammy, primary, Hofsink, Quincy, additional, Nijhof, Inger S, additional, Goorhuis, Abraham, additional, Kater, Arnon P, additional, te Boekhorst, Peter A W, additional, Swaneveld, Francis, additional, Novotný, Věra M J, additional, Bogers, Susanne, additional, Welkers, Matthijs R A, additional, Papageorgiou, Grigorios, additional, Rijnders, Bart J, additional, and Heijmans, Jarom, additional

Published
2022
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49. Clinical Characteristics and Outcomes of Immunocompromised Patients With Coronavirus Disease 2019 Caused by the Omicron Variant: A Prospective, Observational Study

Author

Malahe, S Reshwan K, primary, Hoek, Rogier A S, additional, Dalm, Virgil A S H, additional, Broers, Annoek E C, additional, den Hoed, Caroline M, additional, Manintveld, Olivier C, additional, Baan, Carla C, additional, van Deuzen, Charlotte M, additional, Papageorgiou, Grigorios, additional, Bax, Hannelore I, additional, Van Kampen, Jeroen J, additional, Hellemons, Merel E, additional, Kho, Marcia M L, additional, de Vries, Rory D, additional, Molenkamp, Richard, additional, Reinders, Marlies E J, additional, and Rijnders, Bart J A, additional

Published
2022
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