Immune responses to SARS-CoV-2 in three children of parents with symptomatic COVID-19

Tosif, Shidan; Neeland, Melanie R; Sutton, Philip; Licciardi, Paul V.; Sarkar, Sohinee; Selva, Kevin J.; Ha, Lien Anh; Donato, Celeste; Toh, Zheng Quan; Higgins, Rachel A; Sandt, Carolien E. van de; Lemke, Melissa M.; Lee, Christina Y.; Shoffner, Suzanne K.; Flanagan, Katie L.; Arnold, Kelly B.; Mordant, Francesca L; Mulholland, Kim; Bines, Julie E; Dohle, Kate; Pellicci, Daniel G.; Curtis, Nigel; McNab, Sarah; Steer, Andrew C.; Saffery, Richard; Subbarao, Kanta; Chung, Amy W.; Kedzierska, Katherine; Burgner, David; Crawford, Nigel

doi:10.1038/s41467-020-19545-8

Cited by 100 publications

(118 citation statements)

References 36 publications

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“…However, data on the cellular immune response in non-hospitalised children with mild infection, the most common clinical course of children with COVID-19, are limited. A previous study of two parents with PCR-confirmed symptomatic SARS-CoV-2 infection and their three SARS-CoV-2 PCR-negative children showed that all exposed children mounted a cellular immune response characterised by striking changes in the frequency of innate immune cells over time 7 , suggesting that household exposure to SARS-CoV-2 induces a change in the immune response even in the absence of virological confirmation of infection.…”

Section: Introductionmentioning

confidence: 89%

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

et al. 2021

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Children have mild severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) confirmed disease (COVID-19) compared to adults and the immunological mechanisms underlying this difference remain unclear. Here, we report acute and convalescent innate immune responses in 48 children and 70 adults infected with, or exposed to, SARS-CoV-2. We find clinically mild SARS-CoV-2 infection in children is characterised by reduced circulating subsets of monocytes (classical, intermediate, non-classical), dendritic cells and natural killer cells during the acute phase. In contrast, SARS-CoV-2-infected adults show reduced proportions of non-classical monocytes only. We also observe increased proportions of CD63+ activated neutrophils during the acute phase to SARS-CoV-2 in infected children. Children and adults exposed to SARS-CoV-2 but negative on PCR testing display increased proportions of low-density neutrophils that we observe up to 7 weeks post exposure. This study characterises the innate immune response during SARS-CoV-2 infection and household exposure in children.

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Section: Introductionmentioning

confidence: 89%

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

et al. 2021

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“…We have previously demonstrated that antibodies that are directed against non-structural proteins of the virus, namely ORF3b and ORF8, can be used for accurate diagnosis of SARS-CoV-2 infection 14 . Whilst the cellular immune profile of children appears comparable to adults in a small case study 6 , there are no reports on the humoral antibody landscape and kinetics in pediatric cases. There is a lack of information on the SARS-CoV-2 antibody responses in adults or children to the virus accessory proteins, for instance ORF3b, ORF6 and ORF7a, which have been reported to be potent interferon antagonists that may play a role in immune evasion [15][16][17] .…”

Section: Introductionmentioning

confidence: 96%

The SARS-CoV-2 antibody landscape is lower in magnitude for structural proteins, diversified for accessory proteins and stable long-term in children

Hachim

Kavian

et al. 2021

Preprint

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BackgroundChildren are less clinically affected by SARS-CoV-2 infection than adults with the majority of cases being mild or asymptomatic and the differences in infection outcomes are poorly understood. The kinetics, magnitude and landscape of the antibody response may impact the clinical severity and serological diagnosis of COVID-19. Thus, a comprehensive investigation of the antibody landscape in children and adults is needed.MethodsWe tested 254 plasma from 122 children with symptomatic and asymptomatic SARS-CoV-2 infections in Hong Kong up to 206 days post symptom onset, including 146 longitudinal samples from 58 children. Adult COVID-19 patients and pre-pandemic controls were included for comparison. We assessed antibodies to a 14-wide panel of SARS-CoV-2 structural and accessory proteins by Luciferase Immunoprecipitation System (LIPS).FindingsChildren have lower levels of Spike and Nucleocapsid antibodies than adults, and their cumulative humoral response is more expanded to accessory proteins (NSP1 and Open Reading Frames (ORFs)). Sensitive serology using the three N, ORF3b, ORF8 antibodies can discriminate COVID-19 in children. Principal component analysis revealed distinct serological signatures in children and the highest contribution to variance were responses to non-structural proteins ORF3b, NSP1, ORF7a and ORF8. Longitudinal sampling revealed maintenance or increase of antibodies for at least 6 months, except for ORF7b antibodies which showed decline. It was interesting to note that children have higher antibody responses towards known IFN antagonists: ORF3b, ORF6 and ORF7a. The diversified SARS-CoV-2 antibody response in children may be an important factor in driving control of SARS-CoV-2 infection.

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“…For the base-case, susceptibility to infection was constant across ages, but as a sensitivity analysis, we reduced susceptibility by half for children under 10 years of age. [27][28][29] In our model, all symptomatic cases were identified and isolated within 24 hours following symptom onset. For isolation of silent infections, we varied the proportion identified and the time from infection to identification in the range 2 to 5 days, reflecting observed delays in testing and contact tracing.…”

Section: Methodsmentioning

confidence: 99%

Simulated identification of silent COVID-19 infections among children and estimated future infection rates with vaccination

Moghadas

Fitzpatrick

Shoukat

et al. 2021

Preprint

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ImportanceA significant proportion of COVID-19 transmission occurs silently during the pre-symptomatic and asymptomatic stages of infection. Children, while being important drivers of silent transmission, are not included in COVID-19 vaccination campaigns given their exclusion from clinical trials thus far.ObjectiveTo investigate the impact of a targeted approach to identifying silent infections among children as a proxy for their vaccination.DesignThis study used an age-structured disease transmission model to simulate the synergistic impact of interventions in reducing attack rates over the course of one year.SettingA synthetic population representative of the demographics of the United States (US).ParticipantsSix age groups of 0-4, 5-10, 11-18, 19-49, 50-64, 65+ years old, stratified for their population size based on US census data.ExposuresVaccination of adults, self-isolation of all symptomatic cases within 24 hours of symptom onset, and detection of silent infections.Main Outcomes and MeasuresVaccination of adults was implemented to reach a 40% coverage over the course of one year with a vaccine efficacy of 95% against symptomatic and severe COVID-19. Without vaccination of children, we determined the proportion and speed that would be required for identifying silent infections among this age group to suppress future attack rates below 5%.ResultsA targeted approach that identifies 20.6% and 28.6% of silent infections among children within 2 or 3 days post-infection, respectively, would be required to bring attack rates under 5% with vaccination of adults. If silent infections among children remained undetected, achieving the same attack rates would require an unrealistically high vaccination coverage (at least 82%) of this age group, in addition to the base-case 40% vaccination coverage of adults. The results were robust in sensitivity analyses with respect to vaccine efficacy against infection and reduced susceptibility of children to infection.Conclusions and RelevanceIn the absence of vaccine availability for children, a targeted approach to rapid identification of silent COVID-19 infections in this age group can significantly mitigate disease burden. Without measures to interrupt transmission chains from silent infections, vaccination of adults is unlikely to contain the outbreaks in the near term.Key PointsQuestionWhat is the impact of a targeted strategy for identification of silent COVID-19 infections among children in the absence of their vaccination?FindingsIn this modelling study, we found that identifying 20-30% of silent infections among children within three days post-infection would bring attack rates below 5% if only adults were vaccinated. If silent infections among children remained undetected, achieving the same attack rate would require an unrealistically high vaccination coverage (at least 82%) of this age group, in addition to vaccination of adults.MeaningRapid identification of silent infections among children can replicate effects of their vaccination.

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Immune responses to SARS-CoV-2 in three children of parents with symptomatic COVID-19

Cited by 100 publications

References 36 publications

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

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

The SARS-CoV-2 antibody landscape is lower in magnitude for structural proteins, diversified for accessory proteins and stable long-term in children

Simulated identification of silent COVID-19 infections among children and estimated future infection rates with vaccination

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