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Article ; Online: Publisher Correction: Human memory B cells show plasticity and adopt multiple fates upon recall response to SARS-CoV-2.

Zurbuchen, Yves / Michler, Jan / Taeschler, Patrick / Adamo, Sarah / Cervia, Carlo / Raeber, Miro E / Acar, Ilhan E / Nilsson, Jakob / Warnatz, Klaus / Soyka, Michael B / Moor, Andreas E / Boyman, Onur

Nature immunology

2023 Volume 24, Issue 11, Page(s) 1961

Language	English
Publishing date	2023-08-09
Publishing country	United States
Document type	Published Erratum
ZDB-ID	2016987-5
ISSN	1529-2916 ; 1529-2908
ISSN (online)	1529-2916
ISSN	1529-2908
DOI	10.1038/s41590-023-01628-5
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Article ; Online: Human memory B cells show plasticity and adopt multiple fates upon recall response to SARS-CoV-2.

Nature immunology

2023 Volume 24, Issue 6, Page(s) 955–965

Abstract: The B cell response to different pathogens uses tailored effector mechanisms and results in functionally specialized memory B ( ... ...

Abstract	The B cell response to different pathogens uses tailored effector mechanisms and results in functionally specialized memory B (B
MeSH term(s)	Humans ; SARS-CoV-2 ; Memory B Cells ; COVID-19 ; B-Lymphocytes ; B-Lymphocyte Subsets
Language	English
Publishing date	2023-04-27
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2016987-5
ISSN	1529-2916 ; 1529-2908
ISSN (online)	1529-2916
ISSN	1529-2908
DOI	10.1038/s41590-023-01497-y
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Zs.A 5294: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Persistent complement dysregulation with signs of thromboinflammation in active Long Covid.

Cervia-Hasler, Carlo / Brüningk, Sarah C / Hoch, Tobias / Fan, Bowen / Muzio, Giulia / Thompson, Ryan C / Ceglarek, Laura / Meledin, Roman / Westermann, Patrick / Emmenegger, Marc / Taeschler, Patrick / Zurbuchen, Yves / Pons, Michele / Menges, Dominik / Ballouz, Tala / Cervia-Hasler, Sara / Adamo, Sarah / Merad, Miriam / Charney, Alexander W /

Puhan, Milo / Brodin, Petter / Nilsson, Jakob / Aguzzi, Adriano / Raeber, Miro E / Messner, Christoph B / Beckmann, Noam D / Borgwardt, Karsten / Boyman, Onur

Science (New York, N.Y.)

2024 Volume 383, Issue 6680, Page(s) eadg7942

Abstract: Long Covid is a debilitating condition of unknown etiology. We performed multimodal proteomics analyses of blood serum from COVID-19 patients followed up to 12 months after confirmed severe acute respiratory syndrome coronavirus 2 infection. Analysis of > ...

Abstract	Long Covid is a debilitating condition of unknown etiology. We performed multimodal proteomics analyses of blood serum from COVID-19 patients followed up to 12 months after confirmed severe acute respiratory syndrome coronavirus 2 infection. Analysis of >6500 proteins in 268 longitudinal samples revealed dysregulated activation of the complement system, an innate immune protection and homeostasis mechanism, in individuals experiencing Long Covid. Thus, active Long Covid was characterized by terminal complement system dysregulation and ongoing activation of the alternative and classical complement pathways, the latter associated with increased antibody titers against several herpesviruses possibly stimulating this pathway. Moreover, markers of hemolysis, tissue injury, platelet activation, and monocyte-platelet aggregates were increased in Long Covid. Machine learning confirmed complement and thromboinflammatory proteins as top biomarkers, warranting diagnostic and therapeutic interrogation of these systems.
MeSH term(s)	Humans ; Complement Activation ; Complement System Proteins/analysis ; Complement System Proteins/metabolism ; Post-Acute COVID-19 Syndrome/blood ; Post-Acute COVID-19 Syndrome/complications ; Post-Acute COVID-19 Syndrome/immunology ; Thromboinflammation/blood ; Thromboinflammation/immunology ; Biomarkers/blood ; Proteome ; Proteomics ; Male ; Female ; Young Adult ; Adult ; Middle Aged ; Aged
Chemical Substances	Complement System Proteins (9007-36-7) ; Biomarkers ; Proteome
Language	English
Publishing date	2024-01-19
Publishing country	United States
Document type	Journal Article
ZDB-ID	128410-1
ISSN	1095-9203 ; 0036-8075
ISSN (online)	1095-9203
ISSN	0036-8075
DOI	10.1126/science.adg7942
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Zs.A 27: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: T-cell recovery and evidence of persistent immune activation 12 months after severe COVID-19.

Taeschler, Patrick / Adamo, Sarah / Deng, Yun / Cervia, Carlo / Zurbuchen, Yves / Chevrier, Stéphane / Raeber, Miro E / Hasler, Sara / Bächli, Esther / Rudiger, Alain / Stüssi-Helbling, Melina / Huber, Lars C / Bodenmiller, Bernd / Boyman, Onur / Nilsson, Jakob

Allergy

2022 Volume 77, Issue 8, Page(s) 2468–2481

Abstract: Background: T-cell lymphopenia and functional impairment is a hallmark of severe acute coronavirus disease 2019 (COVID-19). How T-cell numbers and function evolve at later timepoints after clinical recovery remains poorly investigated.: Methods: We ... ...

Abstract	Background: T-cell lymphopenia and functional impairment is a hallmark of severe acute coronavirus disease 2019 (COVID-19). How T-cell numbers and function evolve at later timepoints after clinical recovery remains poorly investigated. Methods: We prospectively enrolled and longitudinally sampled 173 individuals with asymptomatic to critical COVID-19 and analyzed phenotypic and functional characteristics of T cells using flow cytometry, 40-parameter mass cytometry, targeted proteomics, and functional assays. Results: The extensive T-cell lymphopenia observed particularly in patients with severe COVID-19 during acute infection had recovered 6 months after infection, which was accompanied by a normalization of functional T-cell responses to common viral antigens. We detected persisting CD4 Conclusion: Our study suggests that T-cell numbers and function recover in most patients after COVID-19. However, we find evidence of persistent T-cell activation up to 12 months after infection and describe a subgroup of severe COVID-19 patients with persistently low CD8
MeSH term(s)	CD8-Positive T-Lymphocytes ; COVID-19 ; COVID-19 Vaccines ; Humans ; Lymphopenia/etiology ; Lymphopenia/metabolism ; SARS-CoV-2
Chemical Substances	COVID-19 Vaccines
Language	English
Publishing date	2022-06-02
Publishing country	Denmark
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	391933-x
ISSN	1398-9995 ; 0105-4538
ISSN (online)	1398-9995
ISSN	0105-4538
DOI	10.1111/all.15372
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Article ; Online: Immunoglobulin signature predicts risk of post-acute COVID-19 syndrome.

Cervia, Carlo / Zurbuchen, Yves / Taeschler, Patrick / Ballouz, Tala / Menges, Dominik / Hasler, Sara / Adamo, Sarah / Raeber, Miro E / Bächli, Esther / Rudiger, Alain / Stüssi-Helbling, Melina / Huber, Lars C / Nilsson, Jakob / Held, Ulrike / Puhan, Milo A / Boyman, Onur

Nature communications

2022 Volume 13, Issue 1, Page(s) 446

Abstract: Following acute infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) a significant proportion of individuals develop prolonged symptoms, a serious condition termed post-acute coronavirus disease 2019 (COVID-19) syndrome (PACS) or ... ...

Abstract	Following acute infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) a significant proportion of individuals develop prolonged symptoms, a serious condition termed post-acute coronavirus disease 2019 (COVID-19) syndrome (PACS) or long COVID. Predictors of PACS are needed. In a prospective multicentric cohort study of 215 individuals, we study COVID-19 patients during primary infection and up to one year later, compared to healthy subjects. We discover an immunoglobulin (Ig) signature, based on total IgM and IgG3 levels, which - combined with age, history of asthma bronchiale, and five symptoms during primary infection - is able to predict the risk of PACS independently of timepoint of blood sampling. We validate the score in an independent cohort of 395 individuals with COVID-19. Our results highlight the benefit of measuring Igs for the early identification of patients at high risk for PACS, which facilitates the study of targeted treatment and pathomechanisms of PACS.
MeSH term(s)	Adult ; Aged ; Antibodies, Viral/blood ; Antibodies, Viral/immunology ; COVID-19/blood ; COVID-19/complications ; COVID-19/diagnosis ; COVID-19/immunology ; Cohort Studies ; Cough/blood ; Cough/complications ; Cough/immunology ; Dyspnea/blood ; Dyspnea/complications ; Dyspnea/immunology ; Fatigue/blood ; Fatigue/complications ; Fatigue/immunology ; Female ; Fever/blood ; Fever/complications ; Fever/immunology ; Humans ; Immunoglobulin G/blood ; Immunoglobulin G/immunology ; Immunoglobulin M/blood ; Immunoglobulin M/immunology ; Male ; Middle Aged ; ROC Curve ; SARS-CoV-2/immunology ; SARS-CoV-2/physiology
Chemical Substances	Antibodies, Viral ; Immunoglobulin G ; Immunoglobulin M
Language	English
Publishing date	2022-01-25
Publishing country	England
Document type	Journal Article ; Multicenter Study ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-021-27797-1
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Article ; Online: Signature of long-lived memory CD8

Adamo, Sarah / Michler, Jan / Zurbuchen, Yves / Cervia, Carlo / Taeschler, Patrick / Raeber, Miro E / Baghai Sain, Simona / Nilsson, Jakob / Moor, Andreas E / Boyman, Onur

Nature

2021 Volume 602, Issue 7895, Page(s) 148–155

Abstract: Immunological memory is a hallmark of adaptive immunity and facilitates an accelerated and enhanced immune response upon re-infection with the same ... ...

Abstract	Immunological memory is a hallmark of adaptive immunity and facilitates an accelerated and enhanced immune response upon re-infection with the same pathogen
MeSH term(s)	Acute Disease ; Antigens, Viral/immunology ; Biomarkers/metabolism ; CD8-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/metabolism ; COVID-19/immunology ; COVID-19/virology ; Cell Proliferation ; Clone Cells/cytology ; Clone Cells/immunology ; Humans ; Interferons/immunology ; Interleukin-7 Receptor alpha Subunit/metabolism ; Leukocyte Common Antigens/metabolism ; Longitudinal Studies ; Mechanistic Target of Rapamycin Complex 1/metabolism ; Memory T Cells/immunology ; Memory T Cells/metabolism ; Receptors, Antigen, T-Cell/metabolism ; Receptors, CCR7/metabolism ; SARS-CoV-2/immunology ; T Cell Transcription Factor 1/metabolism ; Time Factors ; Transcriptome
Chemical Substances	Antigens, Viral ; Biomarkers ; CCR7 protein, human ; IL7R protein, human ; Interleukin-7 Receptor alpha Subunit ; Receptors, Antigen, T-Cell ; Receptors, CCR7 ; T Cell Transcription Factor 1 ; Interferons (9008-11-1) ; Mechanistic Target of Rapamycin Complex 1 (EC 2.7.11.1) ; Leukocyte Common Antigens (EC 3.1.3.48)
Language	English
Publishing date	2021-12-07
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	120714-3
ISSN	1476-4687 ; 0028-0836
ISSN (online)	1476-4687
ISSN	0028-0836
DOI	10.1038/s41586-021-04280-x
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Zs.A 26: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Autoantibodies in COVID-19 correlate with antiviral humoral responses and distinct immune signatures.

Taeschler, Patrick / Cervia, Carlo / Zurbuchen, Yves / Hasler, Sara / Pou, Christian / Tan, Ziyang / Adamo, Sarah / Raeber, Miro E / Bächli, Esther / Rudiger, Alain / Stüssi-Helbling, Melina / Huber, Lars C / Brodin, Petter / Nilsson, Jakob / Probst-Müller, Elsbeth / Boyman, Onur

Allergy

2022 Volume 77, Issue 8, Page(s) 2415–2430

Abstract: Background: Several autoimmune features occur during coronavirus disease 2019 (COVID-19), with possible implications for disease course, immunity, and autoimmune pathology. In this study, we longitudinally screened for clinically relevant systemic ... ...

Abstract	Background: Several autoimmune features occur during coronavirus disease 2019 (COVID-19), with possible implications for disease course, immunity, and autoimmune pathology. In this study, we longitudinally screened for clinically relevant systemic autoantibodies to assess their prevalence, temporal trajectory, and association with immunity, comorbidities, and severity of COVID-19. Methods: We performed highly sensitive indirect immunofluorescence assays to detect antinuclear antibodies (ANA) and antineutrophil cytoplasmic antibodies (ANCA), along with serum proteomics and virome-wide serological profiling in a multicentric cohort of 175 COVID-19 patients followed up to 1 year after infection, eleven vaccinated individuals, and 41 unexposed controls. Results: Compared with healthy controls, similar prevalence and patterns of ANA were present in patients during acute COVID-19 and recovery. However, the paired analysis revealed a subgroup of patients with transient presence of certain ANA patterns during acute COVID-19. Furthermore, patients with severe COVID-19 exhibited a high prevalence of ANCA during acute disease. These autoantibodies were quantitatively associated with higher SARS-CoV-2-specific antibody titers in COVID-19 patients and in vaccinated individuals, thus linking autoantibody production to increased antigen-specific humoral responses. Notably, the qualitative breadth of antibodies cross-reactive with other coronaviruses was comparable in ANA-positive and ANA-negative individuals during acute COVID-19. In autoantibody-positive patients, multiparametric characterization demonstrated an inflammatory signature during acute COVID-19 and alterations of the B-cell compartment after recovery. Conclusion: Highly sensitive indirect immunofluorescence assays revealed transient autoantibody production during acute SARS-CoV-2 infection, while the presence of autoantibodies in COVID-19 patients correlated with increased antiviral humoral immune responses and inflammatory immune signatures.
MeSH term(s)	Antibodies, Antineutrophil Cytoplasmic ; Antibodies, Antinuclear ; Antiviral Agents ; Autoantibodies ; COVID-19 ; Humans ; Immunity, Humoral ; SARS-CoV-2
Chemical Substances	Antibodies, Antineutrophil Cytoplasmic ; Antibodies, Antinuclear ; Antiviral Agents ; Autoantibodies
Language	English
Publishing date	2022-04-08
Publishing country	Denmark
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	391933-x
ISSN	1398-9995 ; 0105-4538
ISSN (online)	1398-9995
ISSN	0105-4538
DOI	10.1111/all.15302
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Article ; Online: Fate and plasticity of SARS-CoV-2-specific B cells during memory and recall response in humans

Zurbuchen, Yves / Michler, Jan / Taeschler, Patrick / Adamo, Sarah / Cervia, Carlo / Raeber, Miro Emanuel / Acar, Ilhan Erkin / Nilsson, Jakob / Soyka, Michael B. / Moor, Andreas E. / Boyman, Onur

bioRxiv

Abstract: B cell responses to different pathogens recruit tailored effector mechanisms, resulting in functionally specialized subsets. For human memory B cells (MBCs), these include CD21+ resting, CD21-CD27+ activated, and CD21-CD27- atypical cells. Whether these ... ...

Abstract	B cell responses to different pathogens recruit tailored effector mechanisms, resulting in functionally specialized subsets. For human memory B cells (MBCs), these include CD21+ resting, CD21-CD27+ activated, and CD21-CD27- atypical cells. Whether these subsets follow deterministic or interconnected fates is unknown. We demonstrate in COVID-19 patients that single clones of SARS-CoV-2-specific MBCs followed multiple fates with distinctive phenotypic and functional characteristics. 6-12 months after infection, most circulating MBCs were CD21+ resting cells, which also accumulated in peripheral lymphoid organs where they acquired markers of tissue residency. Conversely, at acute infection and following SARS-CoV-2-specific immunization, CD21- MBCs became the predominant subsets, with atypical MBCs expressing high T-bet, inhibitory molecules, and distinct chemokine receptors. B cell receptor sequencing allowed tracking of individual MBC clones differentiating into CD21+, CD21-CD27+, and CD21-CD27- cell fates. Collectively, single MBC clones can adopt functionally different trajectories, thus contributing to immunity to infection.
Keywords	covid19
Language	English
Publishing date	2022-10-07
Publisher	Cold Spring Harbor Laboratory
Document type	Article ; Online
DOI	10.1101/2022.10.07.511336
Database	COVID19

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Article ; Online: Immunoglobulin signature predicts risk of post-acute COVID-19 syndrome

Carlo Cervia / Yves Zurbuchen / Patrick Taeschler / Tala Ballouz / Dominik Menges / Sara Hasler / Sarah Adamo / Miro E. Raeber / Esther Bächli / Alain Rudiger / Melina Stüssi-Helbling / Lars C. Huber / Jakob Nilsson / Ulrike Held / Milo A. Puhan / Onur Boyman

Nature Communications, Vol 13, Iss 1, Pp 1-

2022 Volume 12

Abstract: Studying a prospective cohort, the authors develop and validate a predictive score for post-acute COVID-19 syndrome, also known as long-COVID. This score relies on an immunoglobulin signature and is independent of timepoint of blood sampling. ...

Abstract	Studying a prospective cohort, the authors develop and validate a predictive score for post-acute COVID-19 syndrome, also known as long-COVID. This score relies on an immunoglobulin signature and is independent of timepoint of blood sampling.
Keywords	Science ; Q
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: CD8+ T cell signature in acute SARS-CoV-2 infection identifies memory precursors

Adamo, Sarah / Michler, Jan / Zurbuchen, Yves / Cervia, Carlo / Taeschler, Patrick / Raeber, Miro E. / Baghai Sain, Simona / Nilsson, Jakob / Moor, Andreas / Boyman, Onur

bioRxiv

Abstract: Immunological memory is a hallmark of adaptive immunity and facilitates an accelerated and enhanced immune response upon re-infection with the same pathogen. Since the outbreak of the ongoing coronavirus disease 19 (COVID-19) pandemic, a key question has ...

Abstract	Immunological memory is a hallmark of adaptive immunity and facilitates an accelerated and enhanced immune response upon re-infection with the same pathogen. Since the outbreak of the ongoing coronavirus disease 19 (COVID-19) pandemic, a key question has focused on whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cells stimulated during acute infection give rise to long-lived memory T cells. Using spectral flow cytometry combined with cellular indexing of transcriptomes and T cell receptor (TCR) sequencing we longitudinally characterize individual SARS-CoV-2-specific CD8+ T cells of COVID-19 patients from acute infection to one year into recovery and find a distinct signature identifying long-lived memory CD8+ T cells. SARS-CoV-2-specific memory CD8+ T cells persisting one year after acute infection re-express CD45RA and interleukin-7 receptor alpha (CD127), upregulate T cell factor-1 (TCF1), and maintain low CCR7, thus resembling CD45RA+ effector-memory T (TEMRA) cells. Tracking individual clones of SARS-CoV-2-specific CD8+ T cells, we reveal that an interferon signature marks clones giving rise to long-lived cells, whereas prolonged proliferation and mammalian target of rapamycin (mTOR) signaling are associated with clone contraction and disappearance. Collectively, we identify a transcriptional signature differentiating short- from long-lived memory CD8+ T cells following an acute virus infection in humans.
Keywords	covid19
Language	English
Publishing date	2021-07-22
Publisher	Cold Spring Harbor Laboratory
Document type	Article ; Online
DOI	10.1101/2021.07.22.453029
Database	COVID19

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