ArticleScience translational medicine2021
High titers and low fucosylation of early human anti-SARS-CoV-2 IgG promote inflammation by alveolar macrophages.
Article in Science translational medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06968442 (SARS-CoV-2 Antibody-mediated Inflammatory Responses by Macrophages in Individuals With and Without Obesity), which is not on this map. Cited by 153 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
SARS-CoV-2 Antibody-mediated Inflammatory Responses by Macrophages in Individuals With and Without Obesity
Who cites it
153 citing papers in PubMed, 247 citations in OpenAlex.
- SARS-CoV-2 Immune Complex-Mediated Neutrophil Activation.Open forum infectious diseases · 2025Trial
- Fostamatinib for Hospitalized Adults With COVID-19 and Hypoxemia: A Randomized Clinical Trial.JAMA network open · 2024Trial
- Spleen tyrosine kinase inhibition restores myeloid homeostasis in COVID-19.Science advances · 2023Trial
- Nucleocapsid-specific antibody function is associated with therapeutic benefits from COVID-19 convalescent plasma therapy.Cell reports. Medicine · 2022Trial
- Fostamatinib for the Treatment of Hospitalized Adults With Coronavirus Disease 2019: A Randomized Trial.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2022Trial
- Vaccination-first immune priming shapes a sustained mRNA vaccine-induced IgG4 class switch that associates with SARS-CoV-2 breakthrough infection risk.Scientific reports · 2026Article
- Subclinical exposure to Streptococcus pyogenes drives the development of long-lived homologous immunity.Nature communications · 2026Article
- Xenosialylation as immunological chimerism: a host-centered unifying model for viral and post-vaccination immune complications.European cytokine network · 2026Review
- Atypical B cells and inflammatory profiles delineate immunity to influenza vaccination in First Nations and non-Indigenous people with chronic multimorbidity.Nature communications · 2026Article
- SYK Signalling in NLRP3 Inflammasome-Mediated Response of Murine Microglia Activated by Immune Complexes Formed of Viral Proteins and Specific IgG.European journal of immunology · 2026Article
- Antibody-Dependent Immune Complex Signaling and Inflammatory Cytokine Responses in Acute Febrile Illness: A Mechanistic Study in Arboviral and Leptospiral Infection.Open forum infectious diseases · 2026Article
- Selection of Functional Glycoforms in Anti-SARS-CoV-2 Human IgG1 Monoclonal Antibodies by FcγRIIIa Affinity Chromatography and Mass Spectrometry.Journal of medicinal chemistry · 2026Article
- Transfer of IgG from long COVID patients induces symptomology in mice.Cell reports. Medicine · 2026Article
- Antigen-specific IgG glycosylation profiles in hamsters and macaques following COVID-19 vaccination.iScience · 2026Article
- Building better antibody responses: The interplay of infection, vaccination, and immune imprinting.PNAS nexus · 2026Review
- A microbiota-dependent bile acid reprograms alveolar macrophages to control lung inflammation.Signal transduction and targeted therapy · 2026Article
- Fc-mediated antibody functions are associated with disease severity in COVID-19.Frontiers in immunology · 2026Article
- Hyperinflammation by Human Macrophages Induced by SARS-CoV-2 Anti-Spike IgG Is Dependent on Glucose and Fatty Acid Metabolism.European journal of immunology · 2025Article
- Anti-SARS-CoV-2 antibodies from severe COVID-19 individuals or S2 immunizations do not worsen disease in hamsters.Communications biology · 2025Article
- N-Glycosylation of Antibodies: Biological Effects During Infections and Therapeutic Applications.Antibodies (Basel, Switzerland) · 2025Review
93 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
36 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Patients diagnosed with coronavirus disease 2019 (COVID-19) become critically ill primarily around the time of activation of the adaptive immune response. Here, we provide evidence that antibodies play a role in the worsening of disease at the time of seroconversion. We show that early-phase severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2) spike protein-specific immunoglobulin G (IgG) in serum of critically ill COVID-19 patients induces excessive inflammatory responses by human alveolar macrophages. We identified that this excessive inflammatory response is dependent on two antibody features that are specific for patients with severe COVID-19. First, inflammation is driven by high titers of anti-spike IgG, a hallmark of severe disease. Second, we found that anti-spike IgG from patients with severe COVID-19 is intrinsically more proinflammatory because of different glycosylation, particularly low fucosylation, of the antibody Fc tail. Low fucosylation of anti-spike IgG was normalized in a few weeks after initial infection with SARS-CoV-2, indicating that the increased antibody-dependent inflammation mainly occurs at the time of seroconversion. We identified Fcγ receptor (FcγR) IIa and FcγRIII as the two primary IgG receptors that are responsible for the induction of key COVID-19-associated cytokines such as interleukin-6 and tumor necrosis factor. In addition, we show that anti-spike IgG-activated human macrophages can subsequently break pulmonary endothelial barrier integrity and induce microvascular thrombosis in vitro. Last, we demonstrate that the inflammatory response induced by anti-spike IgG can be specifically counteracted by fostamatinib, an FDA- and EMA-approved therapeutic small-molecule inhibitor of Syk kinase.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.