Dysregulated immune responses contribute to the excessive and uncontrolled inflammation observed in severe COVID-19. However, how immunity to SARS-CoV-2 is induced and regulated remains unclear. Here, we uncover the role of the complement system in the induction of innate and adaptive immunity to SARS-CoV-2. Complement rapidly opsonizes SARS-CoV-2 particles via the lectin pathway. Complement-opsonized SARS-CoV-2 efficiently induces type-I interferon and pro-inflammatory cytokine responses via activation of dendritic cells, which are inhibited by antibodies against the complement receptors (CR) 3 and 4. Serum from COVID-19 patients, or monoclonal antibodies against SARS-CoV-2, attenuate innate and adaptive immunity induced by complement-opsonized SARS-CoV-2. Blocking of CD32, the FcγRII antibody receptor of dendritic cells, restores complement-induced immunity. These results suggest that opsonization of SARS-CoV-2 by complement is involved in the induction of innate and adaptive immunity to SARS-CoV-2 in the acute phase of infection. Subsequent antibody responses limit inflammation and restore immune homeostasis. These findings suggest that dysregulation of the complement system and FcγRII signaling may contribute to severe COVID-19.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10987522 | PMC |
| http://dx.doi.org/10.1038/s44318-024-00061-0 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Learning the language of antibody hypervariability.
Proc Natl Acad Sci U S A
January 2025
Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA 02139.
Protein language models (PLMs) have demonstrated impressive success in modeling proteins. However, general-purpose "foundational" PLMs have limited performance in modeling antibodies due to the latter's hypervariable regions, which do not conform to the evolutionary conservation principles that such models rely on. In this study, we propose a transfer learning framework called Antibody Mutagenesis-Augmented Processing (AbMAP), which fine-tunes foundational models for antibody-sequence inputs by supervising on antibody structure and binding specificity examples.
View Article and Find Full Text PDFSafety and Immunogenicity of SARS-CoV-2 Spike Receptor-Binding Domain andN-Terminal Domain mRNA Vaccine.
J Infect Dis
January 2025
Moderna, Inc., Cambridge, MA 02142, USA.
Background: mRNA-1283 is an investigational COVID-19 mRNA vaccine encoding the receptor-binding and N-terminal domains of the SARS-CoV-2 spike protein in contrast to the original mRNA-1273, which encodes the full-length spike protein.
Methods: A phase 2a, dose-ranging, observer-blind, randomized study (NCT05137236) conducted in adults (≥18 years) previously vaccinated with mRNA-1273 evaluated the safety and immunogenicity of a single dose of mRNA-1283 (2.5, 5, and 10 µg) and its bivalent formulation, mRNA-1283.
Analytical review of facial nerve palsy following SARS-CoV-2 vaccination: comprehensive assessment.
Eur Arch Otorhinolaryngol
January 2025
Department of Otolaryngology-Head and Neck Surgery, Temerty Faculty of Medicine, University of Toronto, 6 Queen's Park Crescent West, Suite 120, Toronto, ON, M5S 3H2, Canada.
Purpose: The SARS-CoV-2 vaccination has reduced COVID-19 infection, though facial nerve palsy (FNP) has emerged as a notable side effect of the vaccine. We evaluated the current literature on the clinical presentation and outcomes of FNP related to COVID-19 vaccination.
Methods: A comprehensive search of seven databases was conducted for studies up to January 2023.
Long-term mitochondrial and metabolic impairment in lymphocytes of subjects who recovered after severe COVID-19.
Cell Biol Toxicol
January 2025
Lab. Genetics and Molecular Bases of Complex Diseases, Health Research Institute of Hospital Clínico San Carlos (IdISSC), 28040, Madrid, Spain.
The underlying mechanisms explaining the differential course of SARS-CoV-2 infection and the potential clinical consequences after COVID-19 resolution have not been fully elucidated. As a dysregulated mitochondrial activity could impair the immune response, we explored long-lasting changes in mitochondrial functionality, circulating cytokine levels, and metabolomic profiles of infected individuals after symptoms resolution, to evaluate whether a complete recovery could be achieved. Results of this pilot study evidenced that different parameters of aerobic respiration in lymphocytes of individuals recuperated from a severe course lagged behind those shown upon mild COVID-19 recovery, in basal conditions and after simulated reinfection, and they also showed altered glycolytic capacity.
View Article and Find Full Text PDFThe Family Doctor in the "COVID-19 Era".
Healthcare (Basel)
December 2024
Internal Medicine I-Discipline of Medical Semiology I, Department V, Center of Advanced Research in Cardiology and Hemostasology, "Victor Babeș" University of Medicine and Pharmacy, Eftimie Murgu Sq. No. 2, 300041 Timisoara, Romania.
The SARS-CoV-2 virus infection, the most severe pandemic in recent human history, found healthcare systems around the world more or less unprepared. Adjusting to this challenge involved changes in the daily routines of healthcare systems, as well as the patients, once again highlighting the importance of primary care (family physician or general practitioner). In the context of the COVID-19 pandemic, the family doctor in Romania played a crucial role in patient management, rapidly adapting to the changes and challenges imposed by the state of emergency.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!