Protective humoral immunity in SARS-CoV-2 infected pediatric patients

Zhang, Yaguang; Xu, Jin; Jia, Rong; Yi, Chunyan; Gu, Wangpeng; Liu, Pengcheng; Dong, Xinran; Zhou, Hao; Shang, Bo; Cheng, Shipeng; Sun, Xiaoyu; Ye, Jing; Li, Xuezhen; Zhang, Jia; Ling, Zhiyang; Ma, Liyan; Wu, Bowen; Zeng, Mei; Zhou, Wenhao; Sun, Bing

doi:10.1038/s41423-020-0438-3

Cited by 49 publications

(54 citation statements)

References 9 publications

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“…We detected a robust and rapid plasmablast response encoding diverse anti-spike (19). Both peak plasmablast frequency and serologic titre for spike glycoprotein were higher in donor B, who presented with severe symptoms, than in donor C. Similar observations on the serologic titre and clinical severity have been reported by others (7,20).…”

Section: Plasmablast Responsessupporting

confidence: 86%

Breadth and function of antibody response to acute SARS-CoV-2 infection in humans

Huang

Tan

Chen

et al. 2020

Preprint

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Plasmablast responses and derived IgG monoclonal antibodies (MAbs) have been analysed in three COVID-19 patients. An average of 13.7% and 13.0% of plasmablast-derived IgG MAbs were reactive with virus spike glycoprotein or nucleocapsid, respectively. Of thirty-two antibodies specific for the spike glycoprotein, ten recognised the receptor-binding domain (RBD), thirteen were specific for non-RBD epitopes on the S1 subunit, and nine recognised the S2 subunit. A subset of anti-spike antibodies (10 of 32) cross-reacted with other betacoronaviruses tested, five targeted the non-RBD S1, and five targeted the S2 subunit. Of the plasmablast-derived MAbs reacting with nucleocapsid, over half of them (19 of 35) cross-reacted with other betacoronaviruses tested. The cross-reactive plasmablast-derived antibodies harboured extensive somatic mutations, indicative of an expansion of memory B cells upon SARS-CoV-2 infection. We identified 14 of 32 anti-spike MAbs that neutralised SARS-CoV-2 in independent assays at ≤ 133 nM (20 μg/ml) (five of 10 anti-RBD, three of 13 anti-non-RBD S1 subunit, six of nine anti-S2 subunit). Six of 10 anti-RBD MAbs showed evidence of blockade of ACE2 binding to RBD, and five of six of these were neutralising. Non-competing pairs of neutralising antibodies were identified, which offer potential templates for the development of prophylactic and therapeutic agents against SARS-CoV-2.

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Section: Plasmablast Responsessupporting

confidence: 86%

Breadth and function of antibody response to acute SARS-CoV-2 infection in humans

Huang

Tan

Chen

et al. 2020

Preprint

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“…This observation suggests that robust antibody response leads to disease severity while feeble response is associated with the elimination of virus (64). A case study on pediatric patients reports that 5 out of 6 children showed a protective humoral response, with neutralizing IgG and IgM antibodies targeting the N and S-RBD proteins of SARS-CoV-2 (65). These studies propose that IgM-based ELISA can be used for early diagnosis of patients along with qPCR techniques to improve the sensitivity and specificity of the technique.…”

Section: Immune Response To Sars-cov-2mentioning

confidence: 99%

Overview of Immune Response During SARS-CoV-2 Infection: Lessons From the Past

et al. 2020

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After the 1918 flu pandemic, the world is again facing a similar situation. However, the advancement in medical science has made it possible to identify that the novel infectious agent is from the coronavirus family. Rapid genome sequencing by various groups helped in identifying the structure and function of the virus, its immunogenicity in diverse populations, and potential preventive measures. Coronavirus attacks the respiratory system, causing pneumonia and lymphopenia in infected individuals. Viral components like spike and nucleocapsid proteins trigger an immune response in the host to eliminate the virus. These viral antigens can be either recognized by the B cells or presented by MHC complexes to the T cells, resulting in antibody production, increased cytokine secretion, and cytolytic activity in the acute phase of infection. Genetic polymorphism in MHC enables it to present some of the T cell epitopes very well over the other MHC alleles. The association of MHC alleles and its downregulated expression has been correlated with disease severity against influenza and coronaviruses. Studies have reported that infected individuals can, after recovery, induce strong protective responses by generating a memory T-cell pool against SARS-CoV and MERS-CoV. These memory T cells were not persistent in the long term and, upon reactivation, caused local damage due to cross-reactivity. So far, the reports suggest that SARS-CoV-2, which is highly contagious, shows related symptoms in three different stages and develops an exhaustive T-cell pool at higher loads of viral infection. As there are no specific treatments available for this novel coronavirus, numerous small molecular drugs that are being used for the treatment of diseases like SARS, MERS, HIV, ebola, malaria, and tuberculosis are being given to COVID-19 patients, and clinical trials for many such drugs have already begun. A classical immunotherapy of convalescent plasma transfusion from recovered patients has also been initiated for the neutralization of viremia in terminally ill COVID-19 patients. Due to the limitations of plasma transfusion, researchers are now focusing on developing neutralizing antibodies against virus particles along with immuno-modulation of cytokines like IL-6, Type I interferons (IFNs), and TNF-α that could help in combating the infection. This review highlights the similarities of the coronaviruses that caused SARS and MERS to the novel SARS-CoV-2 in relation to their pathogenicity and immunogenicity and also focuses on various treatment strategies that could be employed for curing COVID-19.

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“…Although DCs are critical for the priming of both CD8 + and CD4 + T cells in all known viral infections 92 , 93 , in the late stages of infections, cross-reactive memory B cells that had been generated in response to previous infections enter infected mediastinal LNs via HEVs and also participate in antigen presentation to CD4 + T cells 39 . Although studies are still lacking, it is very likely that in primary SARS-CoV-2 infections this pathway is limited as SARS-CoV-2 cross-reactive memory B cells are rare in naive individuals 99 .…”

Section: Leukocytes Recruited To Infected Lungsmentioning

confidence: 99%

Leukocyte trafficking to the lungs and beyond: lessons from influenza for COVID-19

et al. 2020

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19). Understanding of the fundamental processes underlying the versatile clinical manifestations of COVID-19 is incomplete without comprehension of how different immune cells are recruited to various compartments of virus-infected lungs, and how this recruitment differs among individuals with different levels of disease severity. As in other respiratory infections, leukocyte recruitment to the respiratory system in people with COVID-19 is orchestrated by specific leukocyte trafficking molecules, and when uncontrolled and excessive it results in various pathological complications, both in the lungs and in other organs. In the absence of experimental data from physiologically relevant animal models, our knowledge of the trafficking signals displayed by distinct vascular beds and epithelial cell layers in response to infection by SARS-CoV-2 is still incomplete. However, SARS-CoV-2 and influenza virus elicit partially conserved inflammatory responses in the different respiratory epithelial cells encountered early in infection and may trigger partially overlapping combinations of trafficking signals in nearby blood vessels. Here, we review the molecular signals orchestrating leukocyte trafficking to airway and lung compartments during primary pneumotropic influenza virus infections and discuss potential similarities to distinct courses of primary SARS-CoV-2 infections. We also discuss how an imbalance in vascular activation by leukocytes outside the airways and lungs may contribute to extrapulmonary inflammatory complications in subsets of patients with COVID-19. These multiple molecular pathways are potential targets for therapeutic interventions in patients with severe COVID-19.

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Protective humoral immunity in SARS-CoV-2 infected pediatric patients

Cited by 49 publications

References 9 publications

Breadth and function of antibody response to acute SARS-CoV-2 infection in humans

Breadth and function of antibody response to acute SARS-CoV-2 infection in humans

Overview of Immune Response During SARS-CoV-2 Infection: Lessons From the Past

Leukocyte trafficking to the lungs and beyond: lessons from influenza for COVID-19

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