SARS-CoV-2 immune repertoire in MIS-C and pediatric COVID-19

Supriya Ravichandran1, Juanjie Tang1, Gabrielle Grubbs1

  • 1Division of Viral Products, Center for Biologics Evaluation and Research, FDA, Silver Spring, MD, USA.

Nature Immunology
|October 6, 2021
PubMed

Insights

Researchers identified unique severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody signatures in children. These viral fingerprints correlate with disease severity and offer targets for diagnostics and vaccines.

Area of Science:

  • Virology
  • Immunology
  • Pediatrics

Background:

  • Understanding the antibody response to SARS-CoV-2 in children is limited.
  • Pediatric COVID-19 presents with diverse clinical manifestations, including multisystem inflammatory syndrome in children (MIS-C).

Purpose of the Study:

  • To characterize the viral antibody fingerprint in children following SARS-CoV-2 infection.
  • To identify antibody signatures associated with disease severity and potential serodiagnostic targets.

Main Methods:

  • Proteome-wide immunoprofiling of children with varying COVID-19 severity, MIS-C, and controls.
  • Analysis of IgM, IgG, and IgA epitope diversity, antibody binding, and avidity.
  • Assessment of antibody-binding kinetics and neutralization capacity.

Main Results:

  • Antibodies recognized epitopes beyond spike and nucleocapsid proteins, including nonstructural proteins (NSPs) and open reading frames (ORFs).
  • Specific antibody parameters distinguished between mild/moderate COVID-19, severe COVID-19, and MIS-C.
  • Antibody avidity to the prefusion spike protein correlated with decreased illness severity.

Conclusions:

  • SARS-CoV-2 infection induces distinct antibody signatures in children, varying with disease severity.
  • Identified epitopes in NSP12, ORF3a, and ORF8 show potential for serodiagnosis.
  • Antibody responses, particularly neutralization, highlight targets for vaccine and therapeutic development in pediatric populations.

Related Concept Videos

Rous Sarcoma Virus (RSV) and Cancer01:03

Rous Sarcoma Virus (RSV) and Cancer

Rous Sarcoma virus or RSV was discovered by F. Peyton Rous in the year 1911 as a filterable transmissible agent that could cause tumors in chickens. He won a Nobel Prize for this discovery in 1966. His experiments clearly demonstrated that some cancers could be caused by infectious agents and led to the discovery of many more cancer-causing viruses in animals as well as humans.
RSV is a retrovirus that contains two copies of a plus-strand  RNA genome. Its genome consists of four main open...
5.6K
Immunodeficiency Diseases01:25

Immunodeficiency Diseases

Immunodeficiency disorders are conditions in which the immune system's ability to fight infectious disease and cancer is compromised or entirely absent. The immune system comprises a complex network of cells, tissues, and organs that work together to protect the body from potentially harmful invaders. When this system is deficient or not functioning properly, it leaves the body susceptible to infections, diseases, or other complications.
There are three main causes of immunodeficiency...
1.3K
Single Nucleotide Polymorphisms-SNPs01:05

Single Nucleotide Polymorphisms-SNPs

A single nucleotide polymorphism or SNP is a single nucleotide variation at a specific genomic position in a large population. It is the most prevalent type of sequence variation found in the human genome. Point mutations that occur in more than 1% of the population qualify as SNPs. These are present once every 1000 nucleotides on an average in the human genome. Replacement of a purine with another purine (A/G) or a pyrimidine with another pyrimidine (C/T) is known as a transition. In contrast,...
16.8K
Immune Response Against Viral Pathogens01:29

Immune Response Against Viral Pathogens

The immune system's response to viral infections is a complex and coordinated process involving natural killer (NK) cells, T cell-mediated responses, and antibody-mediated responses.
NK Cells
NK cells are a crucial part of our innate immune system, acting as the first line of defense against viral infections. These cells can recognize and kill infected cells without prior exposure to the virus, effectively slowing down the spread of infection. Additionally, NK cells produce proinflammatory...
1.1K
Development of Immunocompetence01:22

Development of Immunocompetence

The initiation of cell-mediated immunity can be observed as early as the third month of fetal growth, with active antibody-mediated immunity following approximately one month later.
The initial cells that migrate from the fetal thymus settle within the skin and epithelial tissues lining the mouth, digestive tract, and in females, the uterus and vagina. These cells, including skin-based dendritic cells, serve as antigen-presenting cells, playing a key role in T cell activation.
Subsequent T...
516