Summary: Infants hospitalized with a severe COVVI-19 ride an immune response which seems entirely different from that of adults or older children. The researchers found that the responses to interferon and inflammation were raised simultaneously – something never observed before in other viral infections.
The T and B cells in these infants were still naive but very activated, and some even produced their own responses of strong antibodies, surprising scientists given their age. These results suggest that infants’ immune systems operate on separate principles and may require specific age strategies for treatment and prevention.
Key facts:
- Double activation: Infants have shown an interferon and high – unusual inflammation in viral infections.
- Naive but active: Despite an infection never encountered, the T and B cells of infants have been strongly activated.
- Independent antibodies: Some infants have produced robust salting-cov-2 antibodies, despite their appearance on maternal immunity.
Source: St. Jude children’s research hospital
Infants hospitalized for the severe COVVI-19 have significantly different immune responses from those of adults or older children.
The result comes from scientists of the St. Jude children’s research hospital, the Jackson Laboratory for Genomic Medicine, Weill Cornell Medicine, Nationwide Children’s Hospital, Icahn School of Medicine of MT. Sinai and the University of Yale.
Researchers have established the unique characteristics of immune cells from infants hospitalized during light, moderate and severe covid-19. The study can help identify better ways to protect infants from the disease.
It was published today in Nature communications.
“This is one of the first studies to characterize the immune response in young infants hospitalized with a high-resolution severe COVVI-19,” said the self-coriller Octavio Ramilo, MD, president of the Department of Infectious Diseases by St. Jude.
“We have found that the response of the infant’s immune system at SARS-COV-2 is nothing like the immune response to any other age, emphasizing the need to study infants, in particular, if we want to prevent serious infections and understand the unique characteristics of the infant’s immune system.”
Employees have studied immune cells from infants ranging from a few weeks to 16 months that have been hospitalized with light, moderate or severe disease. They compared these cells to the immune cells of healthy infants and a published cohort of adults hospitalized with COVID-19.
The monocytes (one type of white blood cells) of hospitalized infants seemed to have characteristics similar to those of adults infected by the Sras-COV-2. However, two other types of major white blood cells, T and B, seemed very different from those in any other group. Hospitalized infants had more CD4 T cells.
In addition, the T and B cells were always activated although they are largely naive, having never encountered any infection. These T and B cells of infants also expressed the antiviral response to interferon, which led to a high expression of genes stimulated by interferon at a much higher level than in children or older adults.
Contradictory signals of the infant’s immune system
Almost all infant immune cells have expressed high levels of genes stimulated by interferon. At the same time, when the collaborators tested the blood of these infants, they found high levels of molecules causing inflammation (inflammatory cytokines), which differs from previous observations in light infected infants.
These results question the previous beliefs on the immune responses of the infant at SARS-COV-2.
“Normally, we believe that interferon and inflammation systems are in balance with each other,” said the Co-Prrimaire Author M. Asunción Mejías, MD, PHD, Department of Infectious Diseases by St. Jude.
“If one is regulated upwards, the other is downward regulated. But what we have found was different. In infants, the two systems have been regulated upwards in the same cells, monocytes, which we have never seen before in other respiratory viral infections.”
Scientists have identified the differences in the immune responses of these infants by sequencing unique RNA of white blood cells. RNA is a copy of DNA instructions which allows cells expressing the genes.
Looking at the RNA from individual cells, the researchers found the characteristics specific to infants and compared them by severity of the disease. They found a more serious illness associated with a higher gene expression of interferon and interferon stimulation. High levels of inflammatory cytokines were also correlated with a more serious disease.
“It is not clear if these high levels of interferon, genes stimulated by interferon and inflammatory cytokines protect those who suffer from a serious or contribute disease,” said Ramilo.
“But they clearly play an essential role, which will require other studies.”
Understanding the response to infant antibodies is an area to its infancy
B cells produce specialized molecules called antibodies that target particular parts of the viruses, bind them and stop infections. An infant is generally based on their mother’s antibodies up to the age of about 6 months.
During the pandemic, the researchers examined if the immunity of a mother with non-school coronaviruses, who would cause colds, would help protect infants.
“We found that these infants had made a new response from solid and robust antibodies to Sars-Cov-2,” said Mejías.
“Their pre -existing maternal antibodies against endemic coronaviruses have not blocked infection at all.”
The observation was surprising; Some infants were as young as a few weeks and still created a response of antibodies to the virus. Infants are generally much older before starting to build such answers for other respiratory viruses.
The children of the study also lacked anti-interferon antibodies, which have been associated with a severe COVVI-19 in adults, stressing that adult immunity lessons may not result in infantile immune responses.
“We have shown that these hospitalized infants had responded to SARS-COV-2, but different from others,” said Ramilo. “As COVID-19 is now an endemic disease, we must better understand the unique characteristics of the infant’s immune system so that we can find ways to help these babies through such infections during their first months of life.”
Authors and financing
The other first author of the study is Djamel Nehar-Belaid of the Jackson Laboratory for Genomic Medicine. The other authors of co-corners of the study are Jacques Banchereau, the Jackson Laboratory for Genomic Medicine, and Virginia Pascual, Weill Cornell Medicine.
The other authors of the study are Zhaohui Xu, St. Jude; Radu Marches, Rushil Yerrabelli, Guo Chen and Duygu Ucar, the Jackson Laboratory for Genomic Medicine; Pablo Sánchez, Sara Mertz and Fang Ye, Nationwide Children’s Hospital; John Tsang, Yale University and Chan Zuckerberg Biohub and Teresa Aydillo, Lisa Miorin, Anastasija Cupic and Adolfo García-Sastre, Icahn School of Medicine at Mount Sinai.
Funding: The study was supported by subsidies from the National Institutes of Health (Jax Cancer Center P30CA0ca034196, U01AI131386, U19AI135972, U19AI142733 and U19AI168631), start -up funds of the Jackson laboratory, CRIPT for research on the influence pathogenesis and transmission) The influence of influence and pathogenesis diseases (center of excellence for the research and response contract in flu n ° 75N93021C00014) and Alsac, the organization of fundraising and awareness of St. Jude.
About this news of research of research-19
Author: Michael Sheffield
Source: St. Jude children’s research hospital
Contact: Michael Sheffield – Children’s Research Hospital St. Jude
Picture: The image is credited with Neuroscience News
Original search: Open access.
“The immune disturbances induced by the sras-cov2 in infants vary with the severity of the disease and differ from the responses of adults” by Octavio Ramilo et al. Nature communications
Abstract
Immune disturbances induced by sras-cov2 in infants vary with the severity of the disease and differ from adult responses
The differences in the immune profiles of children and adults with COVID-19 have been described above. However, no systematic study has been reported in infants hospitalized for serious illness.
We have applied a multidimensional approach to decipher the immune responses from infants infected with Sars-Cov-2 (n= 26; 10 subsequently, 11 moderate diseases and 5 serious; median age = 1.6 months) and paired controls (n= 14; median age = 2 months).
The unique cell profiling (SCRNA-SEQ) of PBMC has revealed substantial alterations of cell composition in infants infected by SAR-COV-2; With most types of cells, going to a gene stimulated by interferon (ISGHi) State, including: (i) CD14+ monocytes co-expressing the ISG and molecules linked to inflammasomas, (ii) ISGHi Naive cd4+ T, (III) ISG cellsHi CD8 proliferating cytotoxic+ T lymphocytes, and (iv) ISGHi naive and transient B cells.
We observe an increase in the serum concentrations of interfeons and inflammatory cytokines in infected infants.
The responses of antibodies at Sras-COV-2 are also systematically detected in the absence of anti-IFN autoantibodies. Compared to infected adults, infants have a similar ISG signature in monocytes but a significantly improved ISG signature in T and B cells.
These results provide an overview of separate immune responses to SARS-COV-2 during the first year of life and emphasize the importance of further defining the unique characteristics of early immunity.
