Why Does the Severity of COVID-19 Differ With Age?

Zimmermann, Petra; Curtis, Nigel

doi:10.1097/inf.0000000000003413

Cited by 70 publications

(49 citation statements)

References 204 publications

(501 reference statements)

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“…The Severe Acute Respiratory Syndrome COronaVirus 2 (SARS-CoV-2) has posed several challenges to the global population, in terms of morbidity and mortality, economic impact and social implications. The clinical impact on children has been overall milder compared with adults, in terms of disease severity and deaths [1], although also in the paediatric population hospitalizations, deaths and severe acute complications like the Multisystem Inflammatory Syndrome (MIS-C) have been recorded globally [2]. Later during the pandemic, patients and early follow-up data highlighted that a group of adults were still reporting a number of persisting symptoms (e.g.…”

Section: Introductionmentioning

confidence: 99%

Diagnosis and management of post-COVID (Long COVID) in children: a moving target

Morello

Martino

Buonsenso

2023

Current Opinion in Pediatrics

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Purpose of reviewThis review describes recent findings about post-COVID condition (PCC, or Long COVID) in children, including current knowledge about its epidemiology, clinical presentation, pathogenesis and care.Recent findingsThere is no internationally agreed definition of PCC, although now most researchers agree that it is a complex clinical symptomatology persisting for at least 3 months after COVID-19, without an alternative diagnosis. There are several uncertainties about paediatric PCC. So far, available literature suggest that 1–3% of recognized children with Severe Acute Respiratory Syndrome COronaVirus 2 (SARS-CoV-2) infection may develop PCC. Its pathogenesis is unknown, although there is increasing evidence about possible abnormalities in the immune responses, cellular metabolism and intestinal microbiota, along with chronic endothelitis.SummaryManagement of PCC in children is complex and require a multidisciplinary approach, with the goal of offering the best care possible to support diagnostics, research, mental health and access to research projects.

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Section: Introductionmentioning

confidence: 99%

Diagnosis and management of post-COVID (Long COVID) in children: a moving target

Morello

Martino

Buonsenso

2023

Current Opinion in Pediatrics

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“…recently proposed that the higher levels of SARS-CoV-2 antibodies observed in children as compared with adults result from the back-boosting of a higher preexisting immunity to beta HCoVs [ 19 , 20 ]. This model is not supported by our results showing that antibody levels to beta HCoVs follow an inverse relationship with age as compared with antibody levels to SARS-CoV-2, with higher levels in older as compared with younger children, most likely because of repeated exposures [ 14 ]. Our detailed analysis of the antibody response to individual domains of the S protein provides important insight into the role of cross-reactive immunity to HCoVs in the antibody response to SARS-CoV-2 infection in children.…”

Section: Discussionmentioning

confidence: 58%

“…The mechanism that could underlie the inverse association between child age and levels of SARS-CoV-2 antibodies is unclear. The robust innate immune response detected early during the course of SARS-CoV-2 infection in children is likely to play a role [ 5 , 13 , 14 , 16 ]. Trained immunity induced by common infections or vaccinations may contribute too [ 14 ].…”

Section: Discussionmentioning

confidence: 99%

“…The robust innate immune response detected early during the course of SARS-CoV-2 infection in children is likely to play a role [ 5 , 13 , 14 , 16 ]. Trained immunity induced by common infections or vaccinations may contribute too [ 14 ]. Our observation that avidity of RBD-specific IgG inversely correlated with age of children suggests that younger children have a unique capacity to develop effective germinal center reactions in response to SARS-CoV-2 infection.…”

Section: Discussionmentioning

confidence: 99%

“…Innate immunity involving type I interferons is essential for the control of SARS-CoV-2 replication during the early phase of the infection, whereas excessive innate immune responses play a pathogenic role later in the course of COVID-19 [ 12 ]. Children with mild COVID-19 develop robust innate immune responses that resolve faster than in adults, suggesting efficient control of inflammatory responses [ 5 , 13 , 14 ]. On the other hand, adaptive immune responses are essential to clear SARS-CoV-2 infection and provide immunity to re-infections with homologous SARS-CoV-2 or variants thereof [ 15 ].…”

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confidence: 99%

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Younger Children Develop Higher Effector Antibody Responses to SARS-CoV-2 Infection

Tomasi

Thiriard

Heyndríckx

et al. 2022

Open Forum Infectious Diseases

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Background The basis of the less severe clinical presentation of coronavirus disease 2019 (COVID-19) in children as compared with adults remains incompletely understood. Studies have suggested that a more potent boosting of immunity to endemic common cold coronaviruses (HCoVs) may protect children. Methods To test this hypothesis, we conducted a detailed analysis of antibodies induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children aged 2 months to 14 years. Results Younger children had higher titers of antibodies to SARS-CoV-2 receptor binding domain (RBD), S1 but not S2 domain, and total spike (S) protein, higher avidity RBD immunoglobulin G, and higher titers of neutralizing and complement-activating antibodies as compared with older children. In contrast, older children had higher titers of antibodies to HCoVs, which correlated with antibodies to the SARS-CoV-2 S2 domain but not with neutralizing or complement-activating antibodies. Conclusions These results reveal a unique capacity of young children to develop effector antibody responses to SARS-CoV-2 infection independently of their immunity to HCoVs.

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Humoral and cellular immune responses in vaccinated and unvaccinated children following SARS‐CoV‐2 Omicron infection

Toh,

Anderson,

Mazarakis

et al. 2024

Clin & Trans Imm

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ObjectivesThe immune response in children elicited by SARS‐CoV‐2 Omicron infection alone or in combination with COVID‐19 vaccination (hybrid immunity) is poorly understood. We examined the humoral and cellular immune response following SARS‐CoV‐2 Omicron infection in unvaccinated children and children who were previously vaccinated with COVID‐19 mRNA vaccine.MethodsParticipants were recruited as part of a household cohort study conducted during the Omicron predominant wave (Jan to July 2022) in Victoria, Australia. Blood samples were collected at 1, 3, 6 and 12 months following COVID‐19 diagnosis. Humoral immune responses to SARS‐CoV‐2 Spike proteins from Wuhan, Omicron BA.1, BA.4/5 and JN.1, as well as cellular immune responses to Wuhan and BA.1 were assessed.ResultsA total of 43 children and 113 samples were included in the analysis. Following Omicron infection, unvaccinated children generated low antibody responses but elicited Spike‐specific CD4 and CD8 T‐cell responses. In contrast, vaccinated children infected with the Omicron variant mounted robust humoral and cellular immune responses to both ancestral strain and Omicron subvariants. Hybrid immunity persisted for at least 6 months post infection, with cellular immune memory characterised by the generation of Spike‐specific polyfunctional CD8 T‐cell responses.ConclusionSARS‐CoV‐2 hybrid immunity in children is characterised by persisting SARS‐CoV‐2 antibodies and robust CD4 and CD8 T‐cell activation and polyfunctional responses. Our findings contribute to understanding hybrid immunity in children and may have implications regarding COVID‐19 vaccination and SARS‐CoV‐2 re‐infections.

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Why Does the Severity of COVID-19 Differ With Age?

Cited by 70 publications

References 204 publications

Diagnosis and management of post-COVID (Long COVID) in children: a moving target

Diagnosis and management of post-COVID (Long COVID) in children: a moving target

Younger Children Develop Higher Effector Antibody Responses to SARS-CoV-2 Infection

Humoral and cellular immune responses in vaccinated and unvaccinated children following SARS‐CoV‐2 Omicron infection

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