Afucosylated IgG characterizes enveloped viral responses and correlates with COVID-19 severity

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Abstract

IgG antibodies are crucial for protection against invading pathogens. A highly conserved N-linked glycan within the IgG-Fc tail, essential for IgG function, shows variable composition in humans. Afucosylated IgG variants are already used in anti-cancer therapeutic antibodies for their elevated activity through Fc receptors (FcγRIIIa). Here, we report that afucosylated IgG (~6% of total IgG in humans) are specifically formed against enveloped viruses but generally not against other antigens. This mediates stronger FcγRIIIa responses, but also amplifies brewing cytokine storms and immune-mediated pathologies. Critically ill COVID-19 patients, but not those with mild symptoms, had high levels of afucosylated IgG antibodies against SARS-CoV-2, amplifying pro-inflammatory cytokine release and acute phase responses. Thus, antibody glycosylation plays a critical role in immune responses to enveloped viruses, including COVID-19.

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Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

Chaolin Huang, Yeming Wang, Xingwang Li … (2020)

Summary Background A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV). We report the epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of these patients. Methods All patients with suspected 2019-nCoV were admitted to a designated hospital in Wuhan. We prospectively collected and analysed data on patients with laboratory-confirmed 2019-nCoV infection by real-time RT-PCR and next-generation sequencing. Data were obtained with standardised data collection forms shared by WHO and the International Severe Acute Respiratory and Emerging Infection Consortium from electronic medical records. Researchers also directly communicated with patients or their families to ascertain epidemiological and symptom data. Outcomes were also compared between patients who had been admitted to the intensive care unit (ICU) and those who had not. Findings By Jan 2, 2020, 41 admitted hospital patients had been identified as having laboratory-confirmed 2019-nCoV infection. Most of the infected patients were men (30 [73%] of 41); less than half had underlying diseases (13 [32%]), including diabetes (eight [20%]), hypertension (six [15%]), and cardiovascular disease (six [15%]). Median age was 49·0 years (IQR 41·0–58·0). 27 (66%) of 41 patients had been exposed to Huanan seafood market. One family cluster was found. Common symptoms at onset of illness were fever (40 [98%] of 41 patients), cough (31 [76%]), and myalgia or fatigue (18 [44%]); less common symptoms were sputum production (11 [28%] of 39), headache (three [8%] of 38), haemoptysis (two [5%] of 39), and diarrhoea (one [3%] of 38). Dyspnoea developed in 22 (55%) of 40 patients (median time from illness onset to dyspnoea 8·0 days [IQR 5·0–13·0]). 26 (63%) of 41 patients had lymphopenia. All 41 patients had pneumonia with abnormal findings on chest CT. Complications included acute respiratory distress syndrome (12 [29%]), RNAaemia (six [15%]), acute cardiac injury (five [12%]) and secondary infection (four [10%]). 13 (32%) patients were admitted to an ICU and six (15%) died. Compared with non-ICU patients, ICU patients had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFα. Interpretation The 2019-nCoV infection caused clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus and was associated with ICU admission and high mortality. Major gaps in our knowledge of the origin, epidemiology, duration of human transmission, and clinical spectrum of disease need fulfilment by future studies. Funding Ministry of Science and Technology, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, and Beijing Municipal Science and Technology Commission.

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The pathogenesis and treatment of the `Cytokine Storm' in COVID-19

Qing Ye, Bili Wang, Jianhua Mao (2020)

Summary Cytokine storm is an excessive immune response to external stimuli. The pathogenesis of the cytokine storm is complex. The disease progresses rapidly, and the mortality is high. Certain evidence shows that, during the coronavirus disease 2019 (COVID-19) epidemic, the severe deterioration of some patients has been closely related to the cytokine storm in their bodies. This article reviews the occurrence mechanism and treatment strategies of the COVID-19 virus-induced inflammatory storm in attempt to provide valuable medication guidance for clinical treatment.

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Potent neutralizing antibodies from COVID-19 patients define multiple targets of vulnerability

Philip Brouwer, Tom Caniels, Karlijn van der Straten … (2020)

The rapid spread of SARS-CoV-2 has a significant impact on global health, travel and economy. Therefore, preventative and therapeutic measures are urgently needed. Here, we isolated monoclonal antibodies from three convalescent COVID-19 patients using a SARS-CoV-2 stabilized prefusion spike protein. These antibodies had low levels of somatic hypermutation and showed a strong enrichment in VH1-69, VH3-30-3 and VH1-24 gene usage. A subset of the antibodies were able to potently inhibit authentic SARS-CoV-2 infection as low as 0.007 μg/mL. Competition and electron microscopy studies illustrate that the SARS-CoV-2 spike protein contains multiple distinct antigenic sites, including several receptor-binding domain (RBD) epitopes as well as non-RBD epitopes. In addition to providing guidance for vaccine design, the antibodies described here are promising candidates for COVID-19 treatment and prevention.

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Author and article information

Journal

Journal ID (nlm-ta): Science

Journal ID (iso-abbrev): Science

Journal ID (publisher-id): SCIENCE

Title: Science (New York, N.y.)

Publisher: American Association for the Advancement of Science

ISSN (Print): 0036-8075

ISSN (Electronic): 1095-9203

Publication date (Electronic): 23 December 2020

Electronic Location Identifier: eabc8378

Affiliations

[1 ]Department of Experimental Immunohematology, Sanquin Research, Amsterdam, Netherlands, and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands.

[2 ]Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, Netherlands.

[3 ]Department of Rheumatology and Clinical Immunology, Amsterdam UMC, Amsterdam Rheumatology and Immunology Center, Amsterdam, Netherlands.

[4 ]Department of Experimental Immunology, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands.

[5 ]Department of Medical Biochemistry, Experimental Vascular Biology, Amsterdam UMC, Cardiovascular Sciences, Amsterdam Infection and Immunity Institute, University of Amsterdam, Amsterdam, Netherlands.

[6 ]Finnish Red Cross Blood Service, Helsinki, Finland.

[7 ]Department of Medical Microbiology, Amsterdam UMC, Amsterdam Infection and Immunity Institute, University of Amsterdam, Amsterdam, Netherlands.

[8 ]Department of Immunopathology, Sanquin Research, Amsterdam, Netherlands, and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands.

[9 ]Amsterdam Rheumatology and Immunology Center, Reade, Amsterdam, Netherlands.

[10 ]Weill Medical College of Cornell University, New York, USA.

[11 ]Department of Intensive Care Medicine, Amsterdam UMC (Location AMC), University of Amsterdam, Amsterdam, Netherlands.

[12 ]Department of Blood-borne Infections, Sanquin, Amsterdam, Netherlands.

Author notes

[*]

These authors contributed equally to this work.

[†]

Amsterdam UMC COVID-19 biobank study group collaborators and affiliations are listed in the supplementary materials.

[‡ ]Corresponding author. Email: g.vidarsson@ 123456sanquin.nl

Author information

Mads Delbo Larsen https://orcid.org/0000-0002-1985-5901

Erik L. de Graaf https://orcid.org/0000-0002-2208-831X

H. Rosina Plomp https://orcid.org/0000-0003-4520-3103

Willianne Hoepel https://orcid.org/0000-0003-1495-4545

Hung-Jen Chen https://orcid.org/0000-0001-6341-8170

Remco Visser https://orcid.org/0000-0002-5846-7223

Tonći Šuštić https://orcid.org/0000-0003-0559-6803

Steven W. de Taeye https://orcid.org/0000-0001-7915-9230

Arthur E. H. Bentlage https://orcid.org/0000-0002-7924-554X

Suvi Toivonen https://orcid.org/0000-0002-9059-3027

Philip J.M. Brouwer https://orcid.org/0000-0002-2902-7739

Chiara Elisabeth Geyer https://orcid.org/0000-0002-9113-3292

Ninotska I. L. Derksen https://orcid.org/0000-0002-0189-2675

Gertjan Wolbink https://orcid.org/0000-0003-1924-7460

Menno de Winther https://orcid.org/0000-0002-4038-6636

Rogier W. Sanders https://orcid.org/0000-0002-2324-8573

Marit J. van Gils https://orcid.org/0000-0003-3422-8161

Alexander P. J. Vlaar https://orcid.org/0000-0002-3453-7186

Theo Rispens https://orcid.org/0000-0001-9600-1312

Jeroen den Dunnen https://orcid.org/0000-0002-7199-8619

Hans L. Zaaijer https://orcid.org/0000-0003-0773-7315

Manfred Wuhrer https://orcid.org/0000-0002-0814-4995

Gestur Vidarsson https://orcid.org/0000-0001-5621-003X

Article

Publisher ID: abc8378

DOI: 10.1126/science.abc8378

PMC ID: 7919849

PubMed ID: 33361116

SO-VID: ab50fea9-cba9-499d-803b-5b9c673cfb32

Copyright © Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY).

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This is an open-access article distributed under the terms of the Creative Commons Attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

History

Date received : 16 May 2020

Date revision received : 12 October 2020

Date accepted : 18 December 2020

Funding

Funded by: doi http://dx.doi.org/10.13039/100009425, Landsteiner Foundation for Blood Transfusion Research;

Award ID: 1229

Funded by: doi http://dx.doi.org/10.13039/100009425, Landsteiner Foundation for Blood Transfusion Research;

Award ID: 1908

Funded by: doi http://dx.doi.org/10.13039/100010663, H2020 European Research Council;

Award ID: 722095

Funded by: doi http://dx.doi.org/10.13039/100011102, Seventh Framework Programme;

Award ID: 278535

Funded by: ZonMW;

Award ID: 10430 01 201 0008

Funded by: ZonMW;

Award ID: 10430 01 201 0021

Funded by: Amsterdam Infection and Immunity Institute;

Award ID: 24175

Funded by: Netherlands Organization for Scientific Research (VICI);

Funded by: Marie Skłodowska-Curie;

Award ID: 847551

Funded by: Amsterdam Infection and Immunity Institute;

Award ID: 24184

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Afucosylated IgG characterizes enveloped viral responses and correlates with COVID-19 severity

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Novel Coronavirus Disease COVID-19

Most cited references 38

Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

The pathogenesis and treatment of the `Cytokine Storm' in COVID-19

Potent neutralizing antibodies from COVID-19 patients define multiple targets of vulnerability

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Cited by 153

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