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

Dowell, Alexander C.; Butler, Megan; Jinks, Elizabeth; Tut, Gokhan; Lancaster, Tara; Sylla, Panagiota; Begum, Jusnara; Bruton, Rachel; Pearce, Hayden; Verma, Kriti; Logan, Nicola; Tyson, Grace; Spalkova, Eliska; Margielewska-Davies, Sandra; Taylor, Graham S.; Syrimi, Eleni; Baawuah, Frances; Beckmann, Joanne; Okike, Ifeanyichukwu; Ahmad, Shazaad; Garstang, Joanna; Brent, Andrew; Brent, Bernadette; Ireland, Georgina; Aiano, Felicity; Amin-Chowdhury, Zahin; Jones, Samuel; Borrow, Ray; Linley, Ezra; Wright, John; Azad, Rafaq; Waiblinger, Dagmar; Davis, Chris; Thomson, Emma C.; Palmarini, Massimo; Willett, Brian J.; Barclay, William; Poh, John; Amirthalingam, Gayatri; Brown, Kevin E.; Ramsay, Mary; Zuo, Jianmin; Moss, Paul; Ladhani, Shamez

doi:10.1038/s41590-021-01089-8

Cited by 173 publications

(237 citation statements)

References 40 publications

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“…Under this scenario, since responses are short-lived, children are dependent on their primed innate immune system for continuing protection from reinfection. These data collectively contradict a recent study showing that children may actually generate more robust adaptive immune responses to SARS-CoV-2 than adults (Dowell et al, 2022). In a large cohort of convalescent primary school children and their teachers from England, it was shown that children make higher titres of cross-reactive antibodies and T cell memory responses than adults.…”

Section: Discussioncontrasting

confidence: 99%

Clonal dynamics of SARS-CoV-2-specific T cells in children and adults with COVID-19

Khoo

Jackson

Phetsouphanh

et al. 2022

Preprint

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Children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) develop less severe coronavirus disease 2019 (COVID-19) than adults. The mechanisms for the age-specific differences and the implications for infection-induced immunity are beginning to be uncovered. We show by longitudinal multimodal analysis that SARS-CoV-2 leaves a small footprint in the circulating T cell compartment in children with mild/asymptomatic COVID-19 compared to adult household contacts with the same disease severity who had more evidence of systemic T cell interferon activation, cytotoxicity and exhaustion. Children harbored diverse polyclonal SARS-CoV-2-specific naive T cells whereas adults harbored clonally expanded SARS-CoV-2-specific memory T cells. More naive interferon-activated CD4+ T cells were recruited into the memory compartment and recovery was associated with the development of robust CD4+ memory T cell responses in adults but not children. These data suggest that rapid clearance of SARS-CoV-2 in children may compromise their cellular immunity and ability to resist reinfection.

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Section: Discussioncontrasting

confidence: 99%

Clonal dynamics of SARS-CoV-2-specific T cells in children and adults with COVID-19

Khoo

Jackson

Phetsouphanh

et al. 2022

Preprint

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“…Reinfections were characterized by overall mild symptoms comparable to the initial infection and did lead to neither hospitalization nor death. It is, however, striking that mainly children and adolescents become reinfected, since children to a higher degree than adults develop a sustained cross-reactive immunity 16 . This may be explained by the very high incidences among children in the chosen study period, whereas adults and elderly had lower incidences.…”

Section: Discussionmentioning

confidence: 99%

Occurrence and significance of Omicron BA.1 infection followed by BA.2 reinfection

Stegger

Edslev

Sieber

et al. 2022

Preprint

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The newly found Omicron SARS-CoV-2 variant of concern has rapidly spread worldwide. Omicron carries numerous mutations in key regions and is associated with increased transmissibility and immune escape. The variant has recently been divided into four subvariants with substantial genomic differences, in particular between Omicron BA.1 and BA.2. With the surge of Omicron subvariants BA.1 and BA.2, a large number of reinfections from earlier cases has been observed, raising the question of whether BA.2 specifically can escape the natural immunity acquired shortly after a BA.1 infection. To investigate this, we selected a subset of samples from more than 1,8 million cases of infections in the period from November 22, 2021, until February 11, 2022. Here, individuals with two positive samples, more than 20 and less than 60 days apart, were selected. From a total of 187 reinfection cases, we identified 47 instances of BA.2 reinfections shortly after a BA.1 infection, mostly in young unvaccinated individuals with mild disease not resulting in hospitalization or death. In conclusion, we provide evidence that Omicron BA.2 reinfections do occur shortly after BA.1 infections but are rare.

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“…One possible explanation for high seroprevalence is potential cross-reactivity of antibodies against P. falciparum or common cold coronaviruses (CCC) In areas of Africa with a high incidence of malaria,[38,39] malaria cross-reactivity could follow two potential mechanisms: a) SARS-CoV-2 antibody tests falsely reacting in malaria hyperendemic areas, [40] or b) cross-protection through CD8+ t-cell activation from P. falciparum antigens [41] Broad anti-CCC antibodies have been identified following SARS-CoV-2 infection and vaccination. [42,43] The exact role of cross-reactivity on seroprevalence estimates warrant further investigation.…”

Section: Discussionmentioning

confidence: 99%

SARS-CoV-2 infection in Africa: A systematic review and meta-analysis of standardised seroprevalence studies, from January 2020 to December 2021

Lewis

Ware

Whelan

et al. 2022

Preprint

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IntroductionEstimating COVID-19 cumulative incidence in Africa remains problematic due to challenges in contact tracing, routine surveillance systems and laboratory testing capacities and strategies. We undertook a meta-analysis of population-based seroprevalence studies to estimate SARS-CoV-2 seroprevalence in Africa to inform evidence-based decision making on Public Health and Social Measures (PHSM) and vaccine strategy.MethodsWe searched for seroprevalence studies conducted in Africa published 01-01-2020 to 30-12-2021 in Medline, Embase, Web of Science, and Europe PMC (preprints), grey literature, media releases and early results from WHO Unity studies. All studies were screened, extracted, assessed for risk of bias and evaluated for alignment with the WHO Unity protocol for seroepidemiological investigations. We conducted descriptive analyses of seroprevalence and meta-analysed seroprevalence differences by demographic groups, place and time. We estimated the extent of undetected infections by comparing seroprevalence and cumulative incidence of confirmed cases reported to WHO. PROSPERO: CRD42020183634.ResultsWe identified 54 full texts or early results, reporting 151 distinct seroprevalence studies in Africa Of these, 95 (63%) were low/moderate risk of bias studies. SARS-CoV-2 seroprevalence rose from 3.0% [95% CI: 1.0-9.2%] in Q2 2020 to 65.1% [95% CI: 56.3-73.0%] in Q3 2021. The ratios of seroprevalence from infection to cumulative incidence of confirmed cases was large (overall: 97:1, ranging from 10:1 to 958:1) and steady over time. Seroprevalence was highly heterogeneous both within countries - urban vs. rural (lower seroprevalence for rural geographic areas), children vs. adults (children aged 0-9 years had the lowest seroprevalence) - and between countries and African sub-regions (Middle, Western and Eastern Africa associated with higher seroprevalence).ConclusionWe report high seroprevalence in Africa suggesting greater population exposure to SARS-CoV-2 and protection against COVID-19 disease than indicated by surveillance data. As seroprevalence was heterogeneous, targeted PHSM and vaccination strategies need to be tailored to local epidemiological situations.

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

Cited by 173 publications

References 40 publications

Clonal dynamics of SARS-CoV-2-specific T cells in children and adults with COVID-19

Clonal dynamics of SARS-CoV-2-specific T cells in children and adults with COVID-19

Occurrence and significance of Omicron BA.1 infection followed by BA.2 reinfection

SARS-CoV-2 infection in Africa: A systematic review and meta-analysis of standardised seroprevalence studies, from January 2020 to December 2021

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