Immune‐related factors associated with pneumonia in 127 children with coronavirus disease 2019 in Wuhan

Li, Yang; Deng, Wenyue; Xiong, Hao; Li, Hui; Chen, Zhi; Nie, Ying-Ming; Wang, Zhuo; Li, Kaili; Li, Jianxin

doi:10.1002/ppul.24907

Cited by 28 publications

(33 citation statements)

References 20 publications

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“…Of the included reports, 34 (56%) were peer-reviewed journal papers [ 3 , 8 – 40 ]. Two animal-based, basic science studies were included [ 30 , 41 ] but the overwhelming majority of reports were in humans, for which the most common designs were case-control (n = 26, 43%) [ 10 – 12 , 14 , 17 , 21 , 23 , 25 – 29 , 31 , 32 , 37 , 38 , 40 , 42 – 50 ] and cohort (n = 22, 36%) [ 8 , 13 , 15 , 16 , 20 , 22 , 34 , 36 , 39 , 51 – 62 ]. 50 studies (82%) considered participants sampled from hospital settings [ 8 , 9 , 11 – 29 , 31 – 40 , 42 , 43 , 45 , 46 , 48 – 50 , 53 , 54 , 56 – 65 ].…”

Section: Resultsmentioning

confidence: 99%

T cell response to SARS-CoV-2 infection in humans: A systematic review

et al. 2021

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Background Understanding the T cell response to SARS-CoV-2 is critical to vaccine development, epidemiological surveillance and disease control strategies. This systematic review critically evaluates and synthesises the relevant peer-reviewed and pre-print literature published from 01/01/2020-26/06/2020. Methods For this systematic review, keyword-structured literature searches were carried out in MEDLINE, Embase and COVID-19 Primer. Papers were independently screened by two researchers, with arbitration of disagreements by a third researcher. Data were independently extracted into a pre-designed Excel template and studies critically appraised using a modified version of the MetaQAT tool, with resolution of disagreements by consensus. Findings were narratively synthesised. Results 61 articles were included. 55 (90%) studies used observational designs, 50 (82%) involved hospitalised patients with higher acuity illness, and the majority had important limitations. Symptomatic adult COVID-19 cases consistently show peripheral T cell lymphopenia, which positively correlates with increased disease severity, duration of RNA positivity, and non-survival; while asymptomatic and paediatric cases display preserved counts. People with severe or critical disease generally develop more robust, virus-specific T cell responses. T cell memory and effector function has been demonstrated against multiple viral epitopes, and, cross-reactive T cell responses have been demonstrated in unexposed and uninfected adults, but the significance for protection and susceptibility, respectively, remains unclear. Conclusion A complex pattern of T cell response to SARS-CoV-2 infection has been demonstrated, but inferences regarding population level immunity are hampered by significant methodological limitations and heterogeneity between studies, as well as a striking lack of research in asymptomatic or pauci-symptomatic individuals. In contrast to antibody responses, population-level surveillance of the T cell response is unlikely to be feasible in the near term. Focused evaluation in specific sub-groups, including vaccine recipients, should be prioritised.

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Section: Resultsmentioning

confidence: 99%

T cell response to SARS-CoV-2 infection in humans: A systematic review

et al. 2021

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“…Children with pneumonia in the setting of COVID-19 have low levels of serum IgA and regulatory (CD4 + CD25 +) T cells, increased levels of high sensitivity (hs)-CRP, IL-10 and procalcitonin [32]. This may, therefore, suggest that dampened serum IgA and decreased circulating regulatory T cells contribute to the deranged immune response against SARS-CoV-2.…”

Section: Clinical Correlation Of Immune Response In Pediatric Covid-19mentioning

confidence: 99%

Severe COVID-19, multisystem inflammatory syndrome in children, and Kawasaki disease: immunological mechanisms, clinical manifestations and management

et al. 2020

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Multisystem inflammatory syndrome (MIS-C) is a pediatric hyperinflammation disorder caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). It has now been reported from several countries the world over. Some of the clinical manifestations of MIS-C mimic Kawasaki disease (KD) shock syndrome. MIS-C develops 4-6 weeks following SARS-CoV-2 infection, and is presumably initiated by adaptive immune response. Though it has multisystem involvement, it is the cardiovascular manifestations that are most prominent. High titres of anti-SARS-CoV-2 antibodies are seen in these patients. As this is a new disease entity, its immunopathogenesis is not fully elucidated. Whether it has some overlap with KD is still unclear. Current treatment guidelines recommend use of intravenous immunoglobulin and high-dose corticosteroids as first-line treatment. Mortality rates of MIS-C are lower compared to adult forms of severe COVID-19 disease. Keywords Multisystem inflammatory syndrome (MIS-C) • Kawasaki disease (KD) • Hyperinflammation • Coronavirus disease 2019 • Kawasaki-like disease Background Kawasaki disease (KD) is a medium vessel vasculitis of undetermined etiology usually affecting children below 5 years [1-3]. Rowley et al. had hypothesized as far back as 2004 that an unidentified respiratory infectious agent with tropism to vascular tissue, likely a virus, could be linked to the etiology of KD [4]. This putative RNA virus, presumably a ubiquitous one, resulted in persistent infection in bronchial epithelium and macrophages and was associated with intracytoplasmic inclusions [5, 6]. Rheumatology INTERNATIONAL Jayakanthan Kabeerdoss and Rakesh Kumar Pilania are the joint first authors and they contributed equally. Disclaimer We hereby state that this manuscript is original and no part of the manuscript has either been published before, or is under consideration of publication elsewhere. The definition of scientific term alluded to, in the manuscript have been duly cited.

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“…• Two studies found children generally developed a detectable antibody response to SARS-CoV-2 infection [99,100]. • Two studies found children with pneumonia generally mounted lower IgG [101] and IgA responses [102]. • One study found no significant difference between the levels of antibody in children and adults [98].…”

Section: Childrenmentioning

confidence: 99%

Antibody response to SARS-CoV-2 infection in humans: A systematic review

et al. 2020

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Background Progress in characterising the humoral immune response to Severe Acute Respiratory Syndrome 2 (SARS-CoV-2) has been rapid but areas of uncertainty persist. Assessment of the full range of evidence generated to date to understand the characteristics of the antibody response, its dynamics over time, its determinants and the immunity it confers will have a range of clinical and policy implications for this novel pathogen. This review comprehensively evaluated evidence describing the antibody response to SARS-CoV-2 published from 01/01/2020-26/06/2020. Methods Systematic review. Keyword-structured searches were carried out in MEDLINE, Embase and COVID-19 Primer. Articles were independently screened on title, abstract and full text by two researchers, with arbitration of disagreements. Data were double-extracted into a pre-designed template, and studies critically appraised using a modified version of the Public Health Ontario Meta-tool for Quality Appraisal of Public Health Evidence (MetaQAT) tool, with resolution of disagreements by consensus. Findings were narratively synthesised. Results 150 papers were included. Most studies (113 or 75%) were observational in design, were based wholly or primarily on data from hospitalised patients (108, 72%) and had important methodological limitations. Few considered mild or asymptomatic infection. Antibody dynamics were well described in the acute phase, up to around three months from disease onset, but the picture regarding correlates of the antibody response was inconsistent. IgM was consistently detected before IgG in included studies, peaking at weeks two to five and declining over a further three to five weeks post-symptom onset depending on the patient group; IgG peaked around weeks three to seven post-symptom onset then plateaued, generally persisting for at least eight weeks. Neutralising antibodies were detectable within seven to 15 days following disease onset, with levels increasing until days 14–22 before levelling and then decreasing, but titres were lower in those with asymptomatic or clinically mild disease. Specific and potent neutralising antibodies have been isolated from convalescent plasma. Cross-reactivity but limited cross-neutralisation with other human coronaviridae was reported. Evidence for protective immunity in vivo was limited to small, short-term animal studies, showing promising initial results in the immediate recovery phase. Conclusions Literature on antibody responses to SARS-CoV-2 is of variable quality with considerable heterogeneity of methods, study participants, outcomes measured and assays used. Although acute phase antibody dynamics are well described, longer-term patterns are much less well evidenced. Comprehensive assessment of the role of demographic characteristics and disease severity on antibody responses is needed. Initial findings of low neutralising antibody titres and possible waning of titres over time may have implications for sero-surveillance and disease control policy, although further evidence is needed. The detection of potent neutralising antibodies in convalescent plasma is important in the context of development of therapeutics and vaccines. Due to limitations with the existing evidence base, large, cross-national cohort studies using appropriate statistical analysis and standardised serological assays and clinical classifications should be prioritised.

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Immune‐related factors associated with pneumonia in 127 children with coronavirus disease 2019 in Wuhan

Cited by 28 publications

References 20 publications

T cell response to SARS-CoV-2 infection in humans: A systematic review

T cell response to SARS-CoV-2 infection in humans: A systematic review

Severe COVID-19, multisystem inflammatory syndrome in children, and Kawasaki disease: immunological mechanisms, clinical manifestations and management

Antibody response to SARS-CoV-2 infection in humans: A systematic review

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