Primary Omicron infection elicits weak antibody response but robust cellularimmunity in children

The Omicron variant of SARS-CoV-2 is now globally dominant but despite high prevalence little is known regarding the immune response in children. We determined the antibody and cellular immune response following Omicron infection in children aged 6-14 years and related this to prior SARS-CoV-2 infection and vaccination status. Primary Omicron infection elicited a weak antibody response and only 53% of children developed detectable neutralising antibodies. In contrast, children with secondary Omicron infection following prior infection with a pre-Omicron variant developed 24-fold higher antibody titres and neutralisation of Omicron. Vaccination elicited the highest levels of antibody response and was also strongly immunogenic following prior natural infection with Omicron. Cellular responses against Omicron were robust and broadly equivalent in all study groups. These data reveal that primary Omicron infection elicits a weak humoral immune response in children and may presage a clinical profile of recurrent infection as seen with antecedent seasonal coronaviruses. Vaccination may represent the most effective approach to control infection whilst cellular immunity should offer strong clinical protection.

Robust SARS-CoV-2-specific and heterologous immune responses after natural infection in elderly residents of Long-Term Care Facilities

Long term care facilities (LTCF) provide residential and/or nursing care support for frail and elderly people and many have suffered from a high prevalence of SARS-CoV-2 infection. Although mortality rates have been high in LTCF residents there is little information regarding the features of SARS-CoV-2-specific immunity after infection in this setting or how this may influence immunity to other infections. We studied humoral and cellular immunity against SARS-CoV-2 in 152 LTCF staff and 124 residents over a prospective 4-month period shortly after the first wave of infection and related viral serostatus to heterologous immunity to other respiratory viruses and systemic inflammatory markers. LTCF residents developed high levels of antibodies against spike protein and RBD domain which were stable over 4 months of follow up. Nucleocapsid-specific responses were also elevated in elderly donors but showed waning across all populations. Antibodies showed stable and equivalent levels of functional inhibition against spike-ACE2 binding in all age groups with comparable activity against viral variants of concern. SARS-CoV-2 seropositive donors showed high levels of antibodies to other beta-coronaviruses but serostatus did not impact humoral immunity to influenza or RSV. SARS-CoV-2-specific cellular responses were equivalent across the life course but virus-specific populations showed elevated levels of activation in older donors. LTCF residents who are survivors of SARS-CoV-2 infection thus show robust and stable immunity which does not impact responses to other seasonal viruses. These findings augur well for relative protection of LTCF residents to re-infection. Furthermore, they underlie the potent influence of previous infection on the immune response to Covid-19 vaccine which may prove to be an important determinant of future vaccine strategy. One sentence summeryCare home residents show waning of nucleocapsid specific antibodies and enhanced expression of activation markers on SARS-CoV-2 specific cells

Children develop strong and sustained cross-reactive immune responses against spike protein following SARS-CoV-2 infection

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 responses against spike and receptor binding domain (RBD) were high in children and seroconversion boosted antibody responses against seasonal Beta-coronaviruses through cross-recognition of the S2 domain. Seroneutralisation assays against alpha, beta and delta SARS-CoV-2 variants demonstrated comparable neutralising activity between children and adults. T cell responses against spike were >2-fold higher in children compared to adults and displayed a TH1 cytokine profile. SARS-CoV-2 spike-specific T cells were also detected in many seronegative children, revealing pre-existing responses that were cross-reactive with seasonal Alpha and Beta-coronaviruses. Importantly, all children retained high antibody titres and cellular responses at 6 months after infection whilst relative antibody waning was seen in adults. Spike-specific responses in children also remained broadly stable beyond 12 months. 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 novel features of SARS-CoV-2-specific immune responses in children and may provide insight into their relative clinical protection. Furthermore, this information will help to guide the introduction of vaccination regimens in the paediatric population.