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Article ; Online: Antiviral treatment of COVID-19: which role can clinical parameters play in therapy evaluation?

Hübner, Yannis R / Spuck, Nikolai / Berger, Moritz / Schlabe, Stefan / Rieke, Gereon J / Breitschwerdt, Sven / van Bremen, Kathrin / Strassburg, Christian P / Gonzalez-Carmona, Maria A / Wasmuth, Jan-Christian / Rockstroh, Jürgen K / Boesecke, Christoph / Monin, Malte B

Infection

2023 Volume 51, Issue 6, Page(s) 1855–1861

MeSH term(s)	Humans ; COVID-19 ; Antiviral Agents/therapeutic use ; SARS-CoV-2
Chemical Substances	Antiviral Agents
Language	English
Publishing date	2023-08-09
Publishing country	Germany
Document type	Letter
ZDB-ID	185104-4
ISSN	1439-0973 ; 0300-8126 ; 0173-2129
ISSN (online)	1439-0973
ISSN	0300-8126 ; 0173-2129
DOI	10.1007/s15010-023-02081-0
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Article ; Online: Natural Killer Cell-Mediated Antibody-Dependent Cellular Cytotoxicity Against SARS-CoV-2 After Natural Infection Is More Potent Than After Vaccination.

Rieke, Gereon J / van Bremen, Kathrin / Bischoff, Jenny / ToVinh, Michael / Monin, Malte B / Schlabe, Stefan / Raabe, Jan / Kaiser, Kim M / Finnemann, Claudia / Odainic, Alexandru / Kudaliyanage, Anushka / Latz, Eicke / Strassburg, Christian P / Boesecke, Christoph / Schmidt, Susanne V / Krämer, Benjamin / Rockstroh, Jürgen K / Nattermann, Jacob

The Journal of infectious diseases

2022 Volume 225, Issue 10, Page(s) 1688–1693

Abstract: We compared the ability of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike-specific antibodies to induce natural killer cell-mediated antibody-dependent cellular cytotoxicity (ADCC) in patients with natural infection and vaccinated ... ...

Abstract	We compared the ability of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike-specific antibodies to induce natural killer cell-mediated antibody-dependent cellular cytotoxicity (ADCC) in patients with natural infection and vaccinated persons. Analyzing plasma samples from 39 coronavirus disease 2019 (COVID-19) patients and 11 vaccinated individuals, significant induction of ADCC could be observed over a period of more than 3 months in both vaccinated and recovered individuals. Although plasma antibody concentrations were lower in recovered patients, we found antibodies elicited by natural infection induced a significantly stronger ADCC response compared to those induced by vaccination, which may affect protection conferred by vaccination.
MeSH term(s)	Antibodies, Neutralizing ; Antibodies, Viral ; Antibody-Dependent Cell Cytotoxicity ; COVID-19/prevention & control ; Humans ; Killer Cells, Natural ; SARS-CoV-2 ; Spike Glycoprotein, Coronavirus ; Vaccination
Chemical Substances	Antibodies, Neutralizing ; Antibodies, Viral ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2
Language	English
Publishing date	2022-03-22
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3019-3
ISSN	1537-6613 ; 0022-1899
ISSN (online)	1537-6613
ISSN	0022-1899
DOI	10.1093/infdis/jiac060
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Article: Impaired immunogenicity after vaccination for SARS-CoV-2 in patients with gastrointestinal cancer: does tumor entity matter?

Monin, Malte Benedikt / Gorny, Jens Gabriel / Berger, Moritz / Baier, Leona I / Zhou, Taotao / Mahn, Robert / Sadeghlar, Farsaneh / Möhring, Christian / Boesecke, Christoph / van Bremen, Kahtrin / Rieke, Gereon J / Schlabe, Stefan / Breitschwerdt, Stefan / Marinova, Milka / Schmidt-Wolf, Ingo G H / Strassburg, Christian P / Eis-Hübinger, Anna-Maria / Gonzalez-Carmona, Maria A

Journal of gastrointestinal oncology

2023 Volume 14, Issue 3, Page(s) 1218–1234

Abstract: Background: SARS-CoV-2 immunogenicity in patients with gastrointestinal cancer (GI cancer) following second and third vaccination was analyzed.: Methods: A total of 125 patients under active anticancer therapy or in follow-up care were included in ... ...

Abstract	Background: SARS-CoV-2 immunogenicity in patients with gastrointestinal cancer (GI cancer) following second and third vaccination was analyzed. Methods: A total of 125 patients under active anticancer therapy or in follow-up care were included in this prospective study. Seroprevalence of SARS-CoV-2 anti-spike and surrogate neutralization antibodies (NABs) was measured. Results: Four weeks after second vaccination, adequate titers of SARS-CoV-2 anti-spike immunoglobulin G (IgG) [≥282.0 binding antibody units (BAU)/mL] were found in 62.2% of patients under treatment versus 96.3% of patients in follow-up care (P<0.01). Sufficient titers of SARS-CoV-2 surrogate NAB (≥85.0%) were found in 32.7% of patients under treatment versus 70.6% in follow-up care (P<0.01). Titers of SARS-CoV-2 anti-spike IgG were especially low in patients with colorectal cancer (CRC). For SARS-CoV-2 surrogate NAB, patients with hepatocellular carcinoma (HCC) and with pancreaticobiliary cancer showed the lowest titers (P<0.01). SARS-CoV-2 anti-spike IgG and SARS-CoV-2 surrogate NAB were associated with a correlation coefficient of 0.93. Reaching a titer of SARS-CoV-2 anti-spike IgG ≥482.0 BAU/mL, protective levels of SARS-CoV-2 surrogate NAB (≥85.0%) could be assumed. Following booster vaccination, all patients reached effective antibody titers. Conclusions: Patients with active GI cancer showed impaired immunogenicity after second SARS-CoV-2 vaccination which was overcome by booster vaccination. Our findings were tumor-related and pronounced in patients with CRC and HCC. Waning immunity over time and antibody escape phenomena by variant of concern Omicron must be considered in these especially vulnerable patients.
Language	English
Publishing date	2023-06-26
Publishing country	China
Document type	Journal Article
ZDB-ID	2594644-4
ISSN	2219-679X ; 2078-6891
ISSN (online)	2219-679X
ISSN	2078-6891
DOI	10.21037/jgo-22-1065
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Article ; Online: SARS-CoV-2 seroconversions and chains of infection in healthcare professionals in a German maximum care provider (The CoSHeP study).

van Bremen, Kathrin / Monin, Malte / Eis-Hübinger, Anna Maria / Marx, Benjamin / Aldabaggh, Souhaib / Streeck, Hendrik / Wasmuth, Jan-Christian / Menting, Tanja / Schlabe, Stefan / Rieke, Gereon J / Schwarze-Zander, Carolynne / Rockstroh, Jürgen K / Boesecke, Christoph

Infection

2021 Volume 49, Issue 5, Page(s) 1039–1043

Abstract: Introduction: The CoSHeP study provides novel data on SARS-CoV-2 seroconversion rates in healthcare professionals (HP) at risk at the University Hospital Bonn, a maximum healthcare provider in a region of 900.000 inhabitants.: Methods: Single-center, ...

Abstract	Introduction: The CoSHeP study provides novel data on SARS-CoV-2 seroconversion rates in healthcare professionals (HP) at risk at the University Hospital Bonn, a maximum healthcare provider in a region of 900.000 inhabitants. Methods: Single-center, longitudinal observational study investigating rate of SARS-CoV-2 IgG seroconversion in HP at 2 time-points. SARS-CoV-2 IgG was measured with Roche Elecsys Anti-SARS-CoV-2 assay. Results: Overall, 150 HP were included. Median age was 35 (range: 19-68). Main operational areas were intensive care unit (53%, n = 80), emergency room (31%, n = 46), and infectious disease department (16%, n = 24). SARS-CoV-2-IgG was detected in 5 participants (3%) at inclusion in May/June 2020, and in another 11 participants at follow-up (December 2020/ January 2021). Of the 16 seropositive participants, 14 had already known their SARS-CoV-2 infection because they had performed a PCR-test previously triggered by symptoms. Trailing chains of infection by self-assessment, 31% (n = 5) of infections were acquired through private contacts, 25% (n = 4) most likely through semi-private contacts during work. 13% (n = 2) were assumed to result through contact with contagious patients, further trailing was unsuccessful in 31% (n = 5). All five participants positive for SARS-CoV-2 IgG at inclusion remained positive with a median of 7 months after infection. Discussion: Frontline HP caring for hospitalized patients with COVID-19 are at higher risk of SARS-CoV-2 infections. Noteworthy, based upon identified chains of infection most of the infections were acquired in private environment and semi-private contacts during work. The low rate of infection through infectious patients reveals that professional hygiene standards are effective in preventing SARS-CoV-2 infections in HP. Persisting SARS-CoV-2-IgG might indicate longer lasting immunity supporting prioritization of negative HP for vaccination.
MeSH term(s)	Adult ; Antibodies, Viral ; COVID-19 ; Delivery of Health Care ; Health Personnel ; Humans ; SARS-CoV-2 ; Seroconversion
Chemical Substances	Antibodies, Viral
Language	English
Publishing date	2021-06-18
Publishing country	Germany
Document type	Journal Article ; Observational Study
ZDB-ID	185104-4
ISSN	1439-0973 ; 0300-8126 ; 0173-2129
ISSN (online)	1439-0973
ISSN	0300-8126 ; 0173-2129
DOI	10.1007/s15010-021-01641-6
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Article ; Online: Mitochondrial Dysfunction Contributes to Impaired Cytokine Production of CD56bright Natural Killer Cells From Human Immunodeficiency Virus-Infected Individuals Under Effective Antiretroviral Therapy.

ToVinh, Michael / Hörr, Gregor / Dobrikova, Kristiyana / Gotter, Christina / Rommel, Clemens / Hoffmeister, Christoph / Raabe, Jan / Kaiser, Kim M / Finnemann, Claudia / Bischoff, Jenny / Rieke, Gereon J / Wilhelm, Christoph / Schmitt, Vanessa / Möhl, Christoph / Aghabeig, Mansoureh / Schwarze-Zander, Carolynne / Boesecke, Christoph / van Bremen, Kathrin / Wasmuth, Jan Christian /

Strassburg, Christian P / Rockstroh, Jürgen K / Spengler, Ulrich / Krämer, Benjamin / Nattermann, Jacob

The Journal of infectious diseases

2022 Volume 226, Issue 5, Page(s) 901–906

Abstract: Human immunodeficiency virus (HIV) infection is associated with impaired natural killer (NK) cell activity, which is only incompletely restored under antiretroviral therapy. Analyzing the bioenergetics profiles of oxygen consumption, we observed that ... ...

Abstract	Human immunodeficiency virus (HIV) infection is associated with impaired natural killer (NK) cell activity, which is only incompletely restored under antiretroviral therapy. Analyzing the bioenergetics profiles of oxygen consumption, we observed that several parameters were significantly reduced in HIV+ NK cells, indicating a mitochondrial defect. Accordingly, we found HIV+ CD56bright NK cells to display a decreased mitochondrial membrane potential and mitochondrial mass. Both parameters were positively correlated with interferon gamma (IFN-γ) production of NK cells. Finally, we demonstrated that stimulation of HIV+ NK cells with MitoTEMPO, a mitochondria-targeting antioxidant, significantly improved IFN-γ production. We identified mitochondrial dysfunction as a mechanism that contributes to impaired NK cell function.
MeSH term(s)	CD56 Antigen/metabolism ; Cytokines/metabolism ; HIV/metabolism ; HIV Infections/complications ; Humans ; Killer Cells, Natural/metabolism ; Mitochondria/metabolism
Chemical Substances	CD56 Antigen ; Cytokines
Language	English
Publishing date	2022-03-21
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3019-3
ISSN	1537-6613 ; 0022-1899
ISSN (online)	1537-6613
ISSN	0022-1899
DOI	10.1093/infdis/jiac103
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Article ; Online: HIV-Associated Microbial Translocation May Affect Cytokine Production of CD56bright NK Cells via Stimulation of Monocytes.

ToVinh, Michael / Hörr, Gregor / Hoffmeister, Christoph / Dobrikova, Kristiyana / Gotter, Christina / Raabe, Jan / Kaiser, Kim M / Ahmad, Sarah / Finnemann, Claudia / Matejec, Eyleen / Hack, Gudrun / Bischoff, Jenny / Rieke, Gereon J / Schwarze-Zander, Carolynne / Boesecke, Christoph / van Bremen, Kathrin / Wasmuth, Jan-Christian / Eis-Hübinger, Anna M / Streeck, Hendrik /

Verhasselt, Hedda L / Oldenburg, Johannes / Strassburg, Christian P / Rockstroh, Jürgen K / Spengler, Ulrich / Krämer, Benjamin / Nattermann, Jacob

The Journal of infectious diseases

2022 Volume 227, Issue 4, Page(s) 577–582

Abstract: The mechanisms involved in HIV-associated natural killer (NK) cell impairment are still incompletely understood. We observed HIV infection to be associated with increased plasma levels of IFABP, a marker for gut epithelial barrier dysfunction, and LBP, a ...

Abstract	The mechanisms involved in HIV-associated natural killer (NK) cell impairment are still incompletely understood. We observed HIV infection to be associated with increased plasma levels of IFABP, a marker for gut epithelial barrier dysfunction, and LBP, a marker for microbial translocation. Both IFABP and LBP plasma concentrations were inversely correlated with NK cell interferon-γ production, suggesting microbial translocation to modulate NK cell functions. Accordingly, we found lipopolysaccharide to have an indirect inhibitory effect on NK cells via triggering monocytes' transforming growth factor-β production. Taken together, our data suggest increased microbial translocation to be involved in HIV-associated NK cell dysfunction.
MeSH term(s)	Humans ; Cytokines ; HIV Infections/metabolism ; HIV Infections/microbiology ; Killer Cells, Natural/metabolism ; Killer Cells, Natural/microbiology ; Killer Cells, Natural/pathology ; Monocytes ; CD56 Antigen ; Intestinal Mucosa/metabolism ; Intestinal Mucosa/pathology
Chemical Substances	Cytokines ; CD56 Antigen ; lipopolysaccharide-binding protein
Language	English
Publishing date	2022-12-13
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3019-3
ISSN	1537-6613 ; 0022-1899
ISSN (online)	1537-6613
ISSN	0022-1899
DOI	10.1093/infdis/jiac485
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Article ; Online: Inducible targeting of cDCs and their subsets in vivo.

Loschko, Jakob / Rieke, Gereon J / Schreiber, Heidi A / Meredith, Matthew M / Yao, Kai-Hui / Guermonprez, Pierre / Nussenzweig, Michel C

Journal of immunological methods

2016 Volume 434, Page(s) 32–38

Abstract: Conventional dendritic cells (cDCs) are essential immune cells linking the innate and adaptive immune system. cDC depletion in mice is an important method to study the function of these cells in vivo. Here we report an inducible in vivo system for cDC ... ...

Abstract	Conventional dendritic cells (cDCs) are essential immune cells linking the innate and adaptive immune system. cDC depletion in mice is an important method to study the function of these cells in vivo. Here we report an inducible in vivo system for cDC depletion in which excision of a loxP flanked Stop signal enables expression of the human diphtheria toxin receptor (DTR) under the control of Zbtb46 (zDC(lSlDTR)). cDCs can be specifically depleted by combining zDC(lSlDTR) mice with a Csf1r(Cre) driver line. In addition, we show that zDC(Cre) mice can be used to produce cDC specific conditional knockout mice (Irf8, Irf4, Notch2) which lack specific subsets of cDCs.
MeSH term(s)	Animals ; Bone Marrow Cells/cytology ; Bone Marrow Cells/immunology ; Crosses, Genetic ; Dendritic Cells/cytology ; Dendritic Cells/immunology ; Flow Cytometry/methods ; Heparin-binding EGF-like Growth Factor/immunology ; Humans ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Spleen/immunology
Chemical Substances	Heparin-binding EGF-like Growth Factor
Language	English
Publishing date	2016-07
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	120142-6
ISSN	1872-7905 ; 0022-1759
ISSN (online)	1872-7905
ISSN	0022-1759
DOI	10.1016/j.jim.2016.04.004
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Article ; Online: Impact of COVID-19 on HIV late diagnosis in a specialized German centre.

van Bremen, Kathrin / Monin, Malte / Schlabe, Stefan / Bischoff, Jenny / Rieke, Gereon Jonas / Schwarze-Zander, Carolynne / Wasmuth, Jan-Christian / Rockstroh, Jürgen K / Boesecke, Christoph

HIV medicine

2022 Volume 23, Issue 11, Page(s) 1209–1213

Abstract: Background: The ongoing COVID-19 pandemic has been impeding HIV diagnosis and treatment worldwide. Data on the impact of COVID-19 on late diagnosis (LD) in Germany are lacking. Here we present novel data of a single-centre German HIV cohort assessing LD ...

Abstract	Background: The ongoing COVID-19 pandemic has been impeding HIV diagnosis and treatment worldwide. Data on the impact of COVID-19 on late diagnosis (LD) in Germany are lacking. Here we present novel data of a single-centre German HIV cohort assessing LD during COVID-19. Methods: This is a non-interventional, single-centre retrospective cohort assessing the rate of LD comparing HIV diagnoses pre-COVID-19 with those during the COVID-19 pandemic. New diagnoses between 1 January 2019 and 1 February 2020 were classified as pre-COVID-19, and diagnoses between 1 February 2020 and 1 October 2021 were classified as during COVID-19. Results: Between 1 January 2019 and 1 October 2021, 75 patients presented with newly diagnosed HIV infection, 34 pre-COVID-19 and 41 during COVID-19. LD increased to 83% (n = 34/41) during COVID-19 versus 59% (n = 20/34) pre-COVID-19, and CDC stage C3 rose to 44% (n = 18) versus 27%. Hospitalization rate increased to 49% (n = 20) during COVID-19 versus 29% pre-COVID-19, and 12% (n = 5) presented with HIV-associated neurological disease, whereas none were observed in the pre-COVID-19 group. The incidence of LD (p = 0.020), CD4 count < 350 cells/μL (p = 0.037) and < 200 cells/μL (p = 0.022) were statistically significantly associated with the ongoing COVID-pandemic. An association with HIV transmission risk was borderline significant (p = 0.055). Conclusions: Despite comparable annual rates of new HIV diagnoses, LD has been increasing during the COVID-19 pandemic, resulting in more opportunistic infections and higher hospitalization rates, possibly reflecting pandemic-related shortages in HIV testing and care facilities. Maintaining HIV testing opportunities and access to treatment during a pandemic is crucial so as not to impede WHO elimination goals and so as to prevent an increase in AIDS-related morbidity and mortality.
MeSH term(s)	Humans ; Delayed Diagnosis ; HIV Infections/diagnosis ; HIV Infections/epidemiology ; HIV Infections/complications ; COVID-19/diagnosis ; COVID-19/epidemiology ; Retrospective Studies ; Pandemics
Language	English
Publishing date	2022-10-20
Publishing country	England
Document type	Journal Article
ZDB-ID	2001932-4
ISSN	1468-1293 ; 1464-2662
ISSN (online)	1468-1293
ISSN	1464-2662
DOI	10.1111/hiv.13426
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Article: Inducible targeting of cDCs and their subsets in vivo

Loschko, Jakob / Gereon J. Rieke / Heidi A. Schreiber / Kai-Hui Yao / Matthew M. Meredith / Michel C. Nussenzweig / Pierre Guermonprez

Journal of Immunological Methods. 2016 July, v. 434

2016

Abstract	Conventional dendritic cells (cDCs) are essential immune cells linking the innate and adaptive immune system. cDC depletion in mice is an important method to study the function of these cells in vivo. Here we report an inducible in vivo system for cDC depletion in which excision of a loxP flanked Stop signal enables expression of the human diphtheria toxin receptor (DTR) under the control of Zbtb46 (zDClSlDTR). cDCs can be specifically depleted by combining zDClSlDTR mice with a Csf1rCre driver line. In addition, we show that zDCCre mice can be used to produce cDC specific conditional knockout mice (Irf8, Irf4, Notch2) which lack specific subsets of cDCs.
Keywords	adaptive immunity ; dendritic cells ; humans ; knockout mutants ; mice
Language	English
Dates of publication	2016-07
Size	p. 32-38.
Publishing place	Elsevier B.V.
Document type	Article
ZDB-ID	120142-6
ISSN	1872-7905 ; 0022-1759
ISSN (online)	1872-7905
ISSN	0022-1759
DOI	10.1016/j.jim.2016.04.004
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Article ; Online: Absence of MHC class II on cDCs results in microbial-dependent intestinal inflammation.

Loschko, Jakob / Schreiber, Heidi A / Rieke, Gereon J / Esterházy, Daria / Meredith, Matthew M / Pedicord, Virginia A / Yao, Kai-Hui / Caballero, Silvia / Pamer, Eric G / Mucida, Daniel / Nussenzweig, Michel C

The Journal of experimental medicine

2016 Volume 213, Issue 4, Page(s) 517–534

Abstract: Conventional dendritic cells (cDCs) play an essential role in host immunity by initiating adaptive T cell responses and by serving as innate immune sensors. Although both innate and adaptive functions of cDCs are well documented, their relative ... ...

Abstract	Conventional dendritic cells (cDCs) play an essential role in host immunity by initiating adaptive T cell responses and by serving as innate immune sensors. Although both innate and adaptive functions of cDCs are well documented, their relative importance in maintaining immune homeostasis is poorly understood. To examine the significance of cDC-initiated adaptive immunity in maintaining homeostasis, independent of their innate activities, we generated a cDC-specific Cre mouse and crossed it to a floxed MHC class II (MHCII) mouse. Absence of MHCII on cDCs resulted in chronic intestinal inflammation that was alleviated by antibiotic treatment and entirely averted under germ-free conditions. Uncoupling innate and adaptive functions of cDCs revealed that innate immune functions of cDCs are insufficient to maintain homeostasis and antigen presentation by cDCs is essential for a mutualistic relationship between the host and intestinal bacteria.
MeSH term(s)	Animals ; Antigen Presentation ; Chronic Disease ; Colitis/genetics ; Colitis/immunology ; Colitis/microbiology ; Dendritic Cells/immunology ; Dendritic Cells/pathology ; Histocompatibility Antigens Class II/genetics ; Histocompatibility Antigens Class II/immunology ; Immunity, Innate ; Inflammation/genetics ; Inflammation/immunology ; Inflammation/microbiology ; Mice ; Mice, Transgenic
Chemical Substances	Histocompatibility Antigens Class II
Language	English
Publishing date	2016-04-04
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	218343-2
ISSN	1540-9538 ; 0022-1007
ISSN (online)	1540-9538
ISSN	0022-1007
DOI	10.1084/jem.20160062
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