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Book ; Online: Serum-IgG responses to SARS-CoV-2 after mild and severe COVID-19 infection

Marklund, Emelie / Leach, Susannah / Gisslén, Magnus

2020

Abstract: SARS-CoV-2 specific serum IgG (AU/ml), as measured by iFlash 1800 chemiluminescent immunoassay (YHLO, China), in 15 patients with severe COVID-19 and 32 patients with mild COVID-19 over >90 days follow-up post symptom onset. SARS-CoV-2 receptor binding ... ...

Abstract	SARS-CoV-2 specific serum IgG (AU/ml), as measured by iFlash 1800 chemiluminescent immunoassay (YHLO, China), in 15 patients with severe COVID-19 and 32 patients with mild COVID-19 over >90 days follow-up post symptom onset. SARS-CoV-2 receptor binding domain specific serum IgM, IgG and IgA in samples collected >75 days post symtom onset from 21 patients with mild or severe COVID-19. Measured by in-house ELISA, results presented as AUC of titration curve.
Keywords	covid19
Publishing date	2020-07-07
Publishing country	eu
Document type	Book ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Book ; Online: Serum-IgG responses to SARS-CoV-2 after mild and severe COVID-19 infection

Marklund, Emelie / Leach, Susannah / Gisslén, Magnus

2020

Abstract	SARS-CoV-2 specific serum IgG (AU/ml), as measured by iFlash 1800 chemiluminescent immunoassay (YHLO, China), in 15 patients with severe COVID-19 and 32 patients with mild COVID-19 over >90 days follow-up post symptom onset. SARS-CoV-2 receptor binding domain specific serum IgM, IgG and IgA in samples collected >75 days post symtom onset from 21 patients with mild or severe COVID-19. Measured by in-house ELISA, results presented as AUC of titration curve.
Keywords	covid19
Publishing date	2020-07-07
Publishing country	eu
Document type	Book ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Plasmablasts in previously immunologically naïve COVID-19 patients express markers indicating mucosal homing and secrete antibodies cross-reacting with SARS-CoV-2 variants and other beta-coronaviruses.

Lundgren, Anna / Leach, Susannah / Axelsson, Hannes / Isakson, Pauline / Nyström, Kristina / Scharf, Lydia / Andersson, Bengt A / Miron, Nicolae / Marklund, Emelie / Andersson, Lars-Magnus / Gisslén, Magnus / Angeletti, Davide / Bemark, Mats

Clinical and experimental immunology

2023 Volume 213, Issue 2, Page(s) 173–189

Abstract: Antigen-specific class-switched antibodies are detected at the same time or even before IgM in serum of non-vaccinated individuals infected with SARS-CoV-2. These derive from the first wave of plasmablasts formed. Hence, the phenotype and specificity of ... ...

Abstract	Antigen-specific class-switched antibodies are detected at the same time or even before IgM in serum of non-vaccinated individuals infected with SARS-CoV-2. These derive from the first wave of plasmablasts formed. Hence, the phenotype and specificity of plasmablasts can reveal information about early B-cell activation. Here we have analyzed B cells and plasmablasts circulating in blood of COVID-19 patients not previously exposed to SARS-CoV-2 during and after disease. We find that during infection with the original Wuhan strain, plasmablasts in blood produce IgA1, IgG1, and IgM, and that most express CCR10 and integrin β1, only some integrin β7, while the majority lack CCR9. Plasmablast-secreted antibodies are reactive to the spike (S) and nucleocapsid (N) proteins of the Wuhan strain as well as later variants of concern, but also bind S proteins from endemic and non-circulating betacoronaviruses. In contrast, after recovery, antibodies produced from memory B cells target variants of SARS-CoV-2 and SARS-CoV-1 but compared to previously non-infected individuals do not show increased binding to endemic coronaviruses. This suggests that the early antibody response to a large extent stems from pre-existing cross-reactive class-switched memory B cells, and that although newly formed memory cells target the novel SARS-CoV-2 virus the numbers of broadly cross-reactive memory B cells do not increase extensively. The observations give insight into the role of pre-existing memory B cells in early antibody responses to novel pathogens and may explain why class-switched antibodies are detected early in the serum of COVID-19 patients.
MeSH term(s)	Humans ; SARS-CoV-2 ; COVID-19 ; Immunoglobulin G ; Immunoglobulin M ; Antibodies, Viral ; Antibodies, Neutralizing
Chemical Substances	Immunoglobulin G ; Immunoglobulin M ; Antibodies, Viral ; Antibodies, Neutralizing
Language	English
Publishing date	2023-04-18
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	218531-3
ISSN	1365-2249 ; 0009-9104 ; 0964-2536
ISSN (online)	1365-2249
ISSN	0009-9104 ; 0964-2536
DOI	10.1093/cei/uxad044
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Article ; Online: Longitudinal single-cell analysis of SARS-CoV-2-reactive B cells uncovers persistence of early-formed, antigen-specific clones.

Scharf, Lydia / Axelsson, Hannes / Emmanouilidi, Aikaterini / Mathew, Nimitha R / Sheward, Daniel J / Leach, Susannah / Isakson, Pauline / Smirnov, Ilya V / Marklund, Emelie / Miron, Nicolae / Andersson, Lars-Magnus / Gisslén, Magnus / Murrell, Ben / Lundgren, Anna / Bemark, Mats / Angeletti, Davide

JCI insight

2023 Volume 8, Issue 1

Abstract: Understanding persistence and evolution of B cell clones after COVID-19 infection and vaccination is crucial for predicting responses against emerging viral variants and optimizing vaccines. Here, we collected longitudinal samples from patients with ... ...

Abstract	Understanding persistence and evolution of B cell clones after COVID-19 infection and vaccination is crucial for predicting responses against emerging viral variants and optimizing vaccines. Here, we collected longitudinal samples from patients with severe COVID-19 every third to seventh day during hospitalization and every third month after recovery. We profiled their antigen-specific immune cell dynamics by combining single-cell RNA-Seq, Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE-Seq), and B cell receptor-Seq (BCR-Seq) with oligo-tagged antigen baits. While the proportion of Spike receptor binding domain-specific memory B cells (MBC) increased from 3 months after infection, the other Spike- and Nucleocapsid-specific B cells remained constant. All patients showed ongoing class switching and sustained affinity maturation of antigen-specific cells, and affinity maturation was not significantly increased early after vaccine. B cell analysis revealed a polyclonal response with limited clonal expansion; nevertheless, some clones detected during hospitalization, as plasmablasts, persisted for up to 1 year, as MBC. Monoclonal antibodies derived from persistent B cell families increased their binding and neutralization breadth and started recognizing viral variants by 3 months after infection. Overall, our findings provide important insights into the clonal evolution and dynamics of antigen-specific B cell responses in longitudinally sampled patients infected with COVID-19.
MeSH term(s)	Humans ; SARS-CoV-2 ; COVID-19 ; B-Lymphocytes ; Plasma Cells ; Clone Cells
Language	English
Publishing date	2023-01-10
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2379-3708
ISSN (online)	2379-3708
DOI	10.1172/jci.insight.165299
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Article ; Online: Correction: Serum-IgG responses to SARS-CoV-2 after mild and severe COVID-19 infection and analysis of IgG non-responders.

Marklund, Emelie / Leach, Susannah / Axelsson, Hannes / Nyström, Kristina / Norder, Heléne / Bemark, Mats / Angeletti, Davide / Lundgren, Anna / Nilsson, Staffan / Andersson, Lars-Magnus / Yilmaz, Aylin / Lindh, Magnus / Liljeqvist, Jan-Åke / Gisslén, Magnus

PloS one

2021 Volume 16, Issue 10, Page(s) e0258401

Abstract: This corrects the article DOI: 10.1371/journal.pone.0241104.]. ...

Abstract	[This corrects the article DOI: 10.1371/journal.pone.0241104.].
Language	English
Publishing date	2021-10-04
Publishing country	United States
Document type	Published Erratum
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0258401
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Article ; Online: Spatio-temporal analysis of prostate tumors in situ suggests pre-existence of treatment-resistant clones.

Marklund, Maja / Schultz, Niklas / Friedrich, Stefanie / Berglund, Emelie / Tarish, Firas / Tanoglidi, Anna / Liu, Yao / Bergenstråhle, Ludvig / Erickson, Andrew / Helleday, Thomas / Lamb, Alastair D / Sonnhammer, Erik / Lundeberg, Joakim

Nature communications

2022 Volume 13, Issue 1, Page(s) 5475

Abstract: The molecular mechanisms underlying lethal castration-resistant prostate cancer remain poorly understood, with intratumoral heterogeneity a likely contributing factor. To examine the temporal aspects of resistance, we analyze tumor heterogeneity in ... ...

Abstract	The molecular mechanisms underlying lethal castration-resistant prostate cancer remain poorly understood, with intratumoral heterogeneity a likely contributing factor. To examine the temporal aspects of resistance, we analyze tumor heterogeneity in needle biopsies collected before and after treatment with androgen deprivation therapy. By doing so, we are able to couple clinical responsiveness and morphological information such as Gleason score to transcriptome-wide data. Our data-driven analysis of transcriptomes identifies several distinct intratumoral cell populations, characterized by their unique gene expression profiles. Certain cell populations present before treatment exhibit gene expression profiles that match those of resistant tumor cell clusters, present after treatment. We confirm that these clusters are resistant by the localization of active androgen receptors to the nuclei in cancer cells post-treatment. Our data also demonstrates that most stromal cells adjacent to resistant clusters do not express the androgen receptor, and we identify differentially expressed genes for these cells. Altogether, this study shows the potential to increase the power in predicting resistant tumors.
MeSH term(s)	Androgen Antagonists/pharmacology ; Androgen Antagonists/therapeutic use ; Androgens/metabolism ; Clone Cells/metabolism ; Humans ; Male ; Prostatic Neoplasms/drug therapy ; Prostatic Neoplasms/genetics ; Prostatic Neoplasms/metabolism ; Receptors, Androgen/genetics ; Receptors, Androgen/metabolism ; Spatio-Temporal Analysis
Chemical Substances	Androgen Antagonists ; Androgens ; Receptors, Androgen
Language	English
Publishing date	2022-09-17
Publishing country	England
Document type	Journal Article ; 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/s41467-022-33069-3
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Article ; Online: No effect of remdesivir or betamethasone on upper respiratory tract SARS-CoV-2 RNA kinetics in hospitalised COVID-19 patients: a retrospective observational study.

Sourander, Birger / Andersson, Lars-Magnus / Brink, Magnus / Yilmaz, Aylin / Sundell, Nicklas / Marklund, Emelie / Nilsson, Staffan / Lindh, Magnus / Robertson, Josefina / Gisslén, Magnus

Infectious diseases (London, England)

2022 Volume 54, Issue 10, Page(s) 703–712

Abstract: Background: The viral kinetics of SARS-CoV-2 has been considered clinically important. While remdesivir and corticosteroids are recommended for COVID-19 patients requiring oxygen support, there is a limited number of published reports on viral kinetics ... ...

Abstract	Background: The viral kinetics of SARS-CoV-2 has been considered clinically important. While remdesivir and corticosteroids are recommended for COVID-19 patients requiring oxygen support, there is a limited number of published reports on viral kinetics in hospitalised patients with COVID-19 treated with remdesivir or corticosteroids. Methods: We conducted a retrospective study by collecting longitudinal samples from the nasopharynx/throat of 123 hospitalised patients (median age 55 years, 74% male) with COVID-19, to evaluate the effects of remdesivir and corticosteroid treatment on viral RNA levels. The subjects were divided into four groups: those receiving remdesivir ( Results: We found no significant difference in SARS-CoV-2 RNA decline rate or time to SARS-CoV-2 RNA clearance between the groups. Moreover, clinical status at baseline was not correlated with time to viral clearance. Conclusions: Since SARS-CoV-2 RNA kinetics was not affected by treatment, repeated sampling from the upper respiratory tract cannot be used to evaluate treatment response.
MeSH term(s)	Adenosine Monophosphate/analogs & derivatives ; Alanine/analogs & derivatives ; Antiviral Agents/therapeutic use ; Betamethasone/therapeutic use ; COVID-19/drug therapy ; Female ; Humans ; Male ; Middle Aged ; Nasopharynx ; RNA, Viral ; Retrospective Studies ; SARS-CoV-2
Chemical Substances	Antiviral Agents ; RNA, Viral ; remdesivir (3QKI37EEHE) ; Adenosine Monophosphate (415SHH325A) ; Betamethasone (9842X06Q6M) ; Alanine (OF5P57N2ZX)
Language	English
Publishing date	2022-06-16
Publishing country	England
Document type	Journal Article ; Observational Study
ZDB-ID	2839775-7
ISSN	2374-4243 ; 2374-4235
ISSN (online)	2374-4243
ISSN	2374-4235
DOI	10.1080/23744235.2022.2081716
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Article ; Online: Longitudinal single-cell analysis of SARS-CoV-2–reactive B cells uncovers persistence of early-formed, antigen-specific clones

Lydia Scharf / Hannes Axelsson / Aikaterini Emmanouilidi / Nimitha R. Mathew / Daniel J. Sheward / Susannah Leach / Pauline Isakson / Ilya V. Smirnov / Emelie Marklund / Nicolae Miron / Lars-Magnus Andersson / Magnus Gisslén / Ben Murrell / Anna Lundgren / Mats Bemark / Davide Angeletti

JCI Insight, Vol 8, Iss

2023 Volume 1

Abstract	Understanding persistence and evolution of B cell clones after COVID-19 infection and vaccination is crucial for predicting responses against emerging viral variants and optimizing vaccines. Here, we collected longitudinal samples from patients with severe COVID-19 every third to seventh day during hospitalization and every third month after recovery. We profiled their antigen-specific immune cell dynamics by combining single-cell RNA-Seq, Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE-Seq), and B cell receptor–Seq (BCR-Seq) with oligo-tagged antigen baits. While the proportion of Spike receptor binding domain–specific memory B cells (MBC) increased from 3 months after infection, the other Spike- and Nucleocapsid-specific B cells remained constant. All patients showed ongoing class switching and sustained affinity maturation of antigen-specific cells, and affinity maturation was not significantly increased early after vaccine. B cell analysis revealed a polyclonal response with limited clonal expansion; nevertheless, some clones detected during hospitalization, as plasmablasts, persisted for up to 1 year, as MBC. Monoclonal antibodies derived from persistent B cell families increased their binding and neutralization breadth and started recognizing viral variants by 3 months after infection. Overall, our findings provide important insights into the clonal evolution and dynamics of antigen-specific B cell responses in longitudinally sampled patients infected with COVID-19.
Keywords	COVID-19 ; Immunology ; Medicine ; R
Subject code	570
Language	English
Publishing date	2023-01-01T00:00:00Z
Publisher	American Society for Clinical investigation
Document type	Article ; Online
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Article ; Online: Upper Respiratory Tract Levels of Severe Acute Respiratory Syndrome Coronavirus 2 RNA and Duration of Viral RNA Shedding Do Not Differ Between Patients With Mild and Severe/Critical Coronavirus Disease 2019.

Yilmaz, Aylin / Marklund, Emelie / Andersson, Maria / Nilsson, Staffan / Andersson, Lars-Magnus / Lindh, Magnus / Gisslén, Magnus

The Journal of infectious diseases

2020 Volume 223, Issue 1, Page(s) 15–18

Abstract: This study reports longitudinal viral RNA loads from the nasopharynx/throat in patients with mild and severe/critical coronavirus disease 2019 (COVID-19). We also investigated whether the duration of symptoms correlated with the duration of viral RNA ... ...

Abstract	This study reports longitudinal viral RNA loads from the nasopharynx/throat in patients with mild and severe/critical coronavirus disease 2019 (COVID-19). We also investigated whether the duration of symptoms correlated with the duration of viral RNA shedding. A total of 56 patients were included. The highest viral loads occurred early after onset of symptoms. Neither the viral RNA loads in the upper respiratory tract nor the time to viral RNA clearance differed between patients with mild or severe/critical disease. There was a moderate correlation between number of days with symptoms and number of days with viral RNA shedding in patients with mild COVID-19.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; COVID-19/diagnosis ; Female ; Humans ; Male ; Middle Aged ; Nasopharynx/virology ; Pharynx/virology ; RNA, Viral/analysis ; Sweden ; Viral Load ; Virus Shedding ; Young Adult
Chemical Substances	RNA, Viral
Keywords	covid19
Language	English
Publishing date	2020-10-05
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/jiaa632
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Article ; Online: Longitudinal Follow Up of Immune Responses to SARS-CoV-2 in Health Care Workers in Sweden With Several Different Commercial IgG-Assays, Measurement of Neutralizing Antibodies and CD4

Marklund, Emelie / Leach, Susannah / Nyström, Kristina / Lundgren, Anna / Liljeqvist, Jan-Åke / Nilsson, Staffan / Yilmaz, Aylin / Andersson, Lars-Magnus / Bemark, Mats / Gisslén, Magnus

Frontiers in immunology

2021 Volume 12, Page(s) 750448

Abstract: Background: The risk of SARS-CoV-2 infection among health care workers (HCWs) is a concern, but studies that conclusively determine whether HCWs are over-represented remain limited. Furthermore, methods used to confirm past infection vary and the ... ...

Abstract	Background: The risk of SARS-CoV-2 infection among health care workers (HCWs) is a concern, but studies that conclusively determine whether HCWs are over-represented remain limited. Furthermore, methods used to confirm past infection vary and the immunological response after mild COVID-19 is still not well defined. Method: 314 HCWs were recruited from a Swedish Infectious Diseases clinic caring for COVID-19 patients. IgG antibodies were measured using two commercial assays (Abbot Architect nucleocapsid (N)-assay and YHLO iFlash-1800 N and spike (S)-assays) at five time-points, from March 2020 to January 2021, covering two pandemic waves. Seroprevalence was assessed in matched blood donors at three time-points. More extensive analyses were performed in 190 HCWs in September/October 2020, including two additional IgG-assays (DiaSorin LiaisonXL S1/S2 and Abbot Architect receptor-binding domain (RBD)-assays), neutralizing antibodies (NAbs), and CD4 Findings: Seroprevalence was higher among HCWs compared to sex and age-matched blood donors at all time-points. Seropositivity increased from 6.4% to 16.3% among HCWs between May 2020 and January 2021, compared to 3.6% to 11.9% among blood donors. We found significant correlations and high levels of agreement between NAbs and all four commercial IgG-assays. At 200-300 days post PCR-verified infection, there was a wide variation in sensitivity between the commercial IgG-assays, ranging from <30% in the N-assay to >90% in the RBD-assay. There was only moderate agreement between NAbs and CD4 Conclusions: HCWs in COVID-19 patient care in Sweden have been infected with SARS-CoV-2 at a higher rate compared to blood donors. We demonstrate substantial variation between different IgG-assays and propose that multiple serological targets should be used to verify past infection. Our data suggest that CD4
MeSH term(s)	Adult ; Aged ; Antibodies, Neutralizing/immunology ; Antibodies, Viral/immunology ; CD4-Positive T-Lymphocytes/immunology ; COVID-19/immunology ; Female ; Follow-Up Studies ; Health Personnel ; Humans ; Immunity/immunology ; Immunoglobulin G/immunology ; Male ; Middle Aged ; Pandemics/prevention & control ; SARS-CoV-2/immunology ; Seroepidemiologic Studies ; Sweden ; Young Adult
Chemical Substances	Antibodies, Neutralizing ; Antibodies, Viral ; Immunoglobulin G
Language	English
Publishing date	2021-11-02
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2021.750448
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