Innate cell profiles during the acute and convalescent phase of SARS-CoV-2 infection in children

Neeland, Melanie R; Bannister, Samantha; Clifford, Vanessa; Dohle, Kate; Mulholland, Kim; Sutton, Philip; Curtis, Nigel; Steer, Andrew C.; Burgner, David; Crawford, Nigel; Tosif, Shidan; Saffery, Richard

doi:10.1038/s41467-021-21414-x

Cited by 82 publications

(92 citation statements)

References 20 publications

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“…NK cells are classically divided into cytokine producing CD56 bright NK cells and cytotoxic CD56 dim NK cells [ 4 ] and CD56 dim NK cells can be further stratified in less or more differentiated subsets based on surface expression of receptors such as NKG2A, CD57, CD62 L, and KIRs [ 11 , 12 ]. In acute SARS-CoV-2 infection, both the CD56 bright and CD56 dim NK cell subset drop in cell numbers in circulation [ 13 •• , 14 •• , 15 ] and this occurs even in mild infection [ 16 ]. This drop in numbers likely reflects active homing of NK cells from circulation to the lung since increased presence of NK cells in bronchioalveolar lavage (BAL) has been reported [ 17 , 18 ].…”

Section: Nk Cell and Unconventional T Cell Responses Against Sars-cov-2mentioning

confidence: 99%

Natural killer cells and unconventional T cells in COVID-19

Björkström

Ponzetta

2021

Current Opinion in Virology

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NK cells and diverse populations of unconventional T cells, such as MAIT cells, γδ T cells, invariant NKT cells, and DNT ɑβ cells are important early effector lymphocytes. While some of these cells, such as NK cell and MAIT cells, have well-established roles in antiviral defense, the function of other populations remains more elusive. Here, we summarize and discuss current knowledge on NK cell and unconventional T cell responses to SARS-CoV-2 infection. Also covered is the role of these cells in the pathogenesis of severe COVID-19. Understanding the early, both systemic and local (lung), effector lymphocyte response in this novel disease will likely aid ongoing efforts to combat the pandemic.

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Section: Nk Cell and Unconventional T Cell Responses Against Sars-cov-2mentioning

confidence: 99%

Natural killer cells and unconventional T cells in COVID-19

Björkström

Ponzetta

2021

Current Opinion in Virology

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“…Interestingly, an enrichment of “adaptive” NK cells was also observed [ 108 ]. A reduction in circulating NK cells has also been reported in children infected by SARS-CoV-2 prompting investigators to suggest that NK cells might have been recruited to sites of infection to provide protective immunity [ 111 ]. Overall, NK cells clearly mount a response to SARS-CoV-2 infection, but similar to hepatitis virus infections, they might become dysfunctional during severe disease, and their role in organs like the liver requires further investigation.…”

Section: Viral Infections Of the Livermentioning

confidence: 99%

The role of natural killer cells in liver inflammation

et al. 2021

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The liver is an important immunological site that can promote immune tolerance or activation. Natural killer (NK) cells are a major immune subset within the liver, and therefore understanding their role in liver homeostasis and inflammation is crucial. Due to their cytotoxic function, NK cells are important in the immune response against hepatotropic viral infections but are also involved in the inflammatory processes of autoimmune liver diseases and fatty liver disease. Whether NK cells primarily promote pro-inflammatory or tolerogenic responses is not known for many liver diseases. Understanding the involvement of NK cells in liver inflammation will be crucial in effective treatment and future immunotherapeutic targeting of NK cells in these disease settings. Here, we explore the role that NK cells play in inflammation of the liver in the context of viral infection, autoimmunity and fatty liver disease.

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“…Levels of virus within the upper airways at the time of primary infection are equivalent in children and adults (Madera, Crawford et al 2021), but relative changes over the course of infection are not known. Enhanced innate immune responses in children may play an important role in limiting systemic replication, which may explain the higher rates of asymptomatic and transient, mild illness in children exposed to the virus compared to adults (Neeland, Bannister et al 2021). One striking feature was that SARS-CoV-2 infection in children doubled the antibody titres against all four alpha and beta HCoV subtypes.…”

Section: Discussionmentioning

confidence: 99%

Children develop robust and sustained cross-reactive spike-specific immune responses following SARS-CoV-2 infection

Dowell

Butler

Jinks

et al. 2021

Preprint

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SARS-CoV-2 infection is generally mild or asymptomatic in children but the biological basis for this is unclear. We studied the profile of antibody and cellular immunity in children aged 3-11 years in comparison with adults. Antibody profiles in children were strong with high titres against spike protein and receptor binding domain (RBD). SARS-CoV-2 seroconversion in children strongly boosted antibody responses against seasonal beta-coronaviruses, partly through cross-recognition of the S2 domain, indicating a broad humoral response that was not seen in adults. T cell responses against spike were also >2-fold higher in children compared to adults and displayed a strong Th1 cytokine profile. SARS-CoV-2 spike-reactive cellular responses were present in more than half the seronegative children, indicating pre-existing cross-reactive responses or sensitization against SARS-CoV-2. Importantly, all children retained high antibody titres and cellular responses for more than 6 months after infection whilst relative antibody waning was seen in adults. Children thus distinctly generate robust, cross-reactive and sustained immune responses after SARS-CoV-2 infection with focussed specificity against spike protein. These observations demonstrate several novel features of SARS-CoV-2-specific immune responses in children and may provide insights into relative clinical protection in this group. Such information on the profile of natural infection will help to guide the introduction of vaccination regimens into the paediatric population.

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Innate cell profiles during the acute and convalescent phase of SARS-CoV-2 infection in children

Cited by 82 publications

References 20 publications

Natural killer cells and unconventional T cells in COVID-19

Natural killer cells and unconventional T cells in COVID-19

The role of natural killer cells in liver inflammation

Children develop robust and sustained cross-reactive spike-specific immune responses following SARS-CoV-2 infection

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