Disease severity dictates SARS-CoV-2-specific neutralizing antibody responses in COVID-19

Chen, Xiangyu; Pan, Zhiwei; Yue, Shuai; Yu, Fei; Zhang, Junsong; Yang, Yang; Ren, Li; Liu, Bingfeng; Yang, Xiaofan; Gao, Leiqiong; Li, Zhirong; Huang, Qizhao; Xu, Lifan; Tang, Jianfang; Hu, Li; Zhao, Jing; Liu, Pinghuang; Zhang, Guozhong; Chen, Yaokai; Deng, Kai; Ye, Lilin

doi:10.1101/2020.07.29.20164285

Cited by 39 publications

(61 citation statements)

References 31 publications

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“…Furthermore, Gene Set Variation Analysis (GSVA) with public gene sets revealed that gene sets related to B cell response and T cell response were predominantly enriched in the aged group (G3) at 2 dpi, compared to the juvenile (G1) or the young adult (G2) ferrets (Fig. 4D), which is in agreement with a recent clinical study that showed stronger antibody and T cell responses in severe COVID-19 patients than mild patients 21,22 . Moreover, other immune-related gene sets, including IFN response, macrophage activation, and NK cell activation, were also highly enriched in the aged group at 2 dpi (Fig.…”

Section: Transcriptional Pro Le Of Immune-related Genes In Lung Tissusupporting

confidence: 90%

Age-dependent pathogenic characteristics of SARS-CoV-2 infection in ferrets

Kim

Koh

et al. 2021

Preprint

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The sero-prevalence of SARS-CoV-2 in healthy people is not significantly different among age groups, but persons age 65 years or older had strikingly higher COVID-19 mortality compared to younger individuals. To understand COVID-19 manifestations in patients of different ages, ferrets in three age groups were infected with SARS-CoV-2. Although SARS-CoV-2 was isolated from all ferrets regardless of age, aged ferrets (≥3 years old) showed higher viral load, longer nasal virus shedding, and more severe lung inflammatory cell infiltration and clinical symptom compared to ≤6 months juvenile and 1-2 years young adult groups. Transcriptome analysis of aged ferret lungs revealed strong enrichment of gene sets related to type I interferon, activated T cell, and M1 macrophage responses, mimicking the gene expression profile of severe COVID-19 patients. Thus, SARS-CoV-2-infected aged ferrets highly recapitulate COVID-19 patients with severe symptoms and are useful for understanding an age-associated infection, transmission, and pathogenesis of SARS-CoV-2.

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Section: Transcriptional Pro Le Of Immune-related Genes In Lung Tissusupporting

confidence: 90%

Age-dependent pathogenic characteristics of SARS-CoV-2 infection in ferrets

Kim

Koh

et al. 2021

Preprint

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“…perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in The copyright holder for this this version posted February 16, 2021. ; https://doi.org/10.1101/2021.02.12.21251298 doi: medRxiv preprint equivocally related to COVID-19 disease severity (34,35), we investigated their possible prognostic accuracy for overall-mortality at 28 days in ICU patients. ROC curve analyses using continuous biomarker values indicated that the only significant predictor was IgG against the Spike/TLR2 mimic peptide, but only modestly so, with an area under the curve of 0.64.…”

Section: Baseline Serologies and Icu Patients Prognosismentioning

confidence: 99%

SARS-CoV2- infection as a trigger of humoral response against apolipoprotein A-1

Pagano¹,

Yerly²,

Meyer

et al. 2021

Preprint

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Aims: Unravelling autoimmune targets triggered by SARS-CoV-2 infection may provide crucial insights in the physiopathology of the disease and foster the development of potential therapeutic candidate targets and prognostic tools. We want to determine whether SARS-CoV-2 exposure could trigger a humoral response against apolipoprotein A-1 (anti-apoA-1 IgG) through molecular mimicry and assess its relationship to patient prognosis. Methods and Results: Anti-Spike domain 1 (SD1) IgGs, anti-apoA-1 IgGs and against mimic peptides, as well as cytokines were assessed by immunoassays on a case-control (n=101), an intensive care unit (ICU; n=126) with a 28-days follow-up, and a general population cohort (n=663) with available samples in the pre and post-pandemic period. Linear sequence homologies and antibodies cross-reactivity between apoA-1, TLR2, and Spike epitopes were identified. Overall, anti-apoA-1 IgG levels were higher in COVID-19 patients or anti-SARS-CoV-2 seropositive individuals than in healthy donors or anti-SARS-CoV-2 seronegative individuals (p<0.0001). Significant and similar associations were noted between anti-apoA-1, anti-SARS-CoV-2 IgG, cytokines, and lipid profile. In ICU patients, anti-SARS-CoV-2 and anti-apoA-1 seroconversion rates displayed similar 7-days kinetics, reaching 82% for anti-apoA-1 seropositivity. C-statistics (CS) indicated that anti-Spike/TLR2 mimic-peptide IgGs displayed a significant prognostic accuracy for overall mortality at 28 days (CS: 0.64; p=0.02). In the general population, SARS-CoV-2 exposure increased baseline anti-apoA-1 IgG levels. Conclusions: COVID-19 induces a marked humoral response against the major protein of high-density lipoproteins. As a correlate of poorer prognosis in other clinical settings, such autoimmunity signatures may relate to long-term COVID-19 prognosis assessment and warrant further scrutiny in the current COVID-19 pandemic.

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“…However, many essential aspects of virus-host interactions during SARS-CoV-2 infection remain unclear, including the production and longevity of virus-specific antibodies in infected persons, and their implications on protection from re-infection. At present, there are conflicting data on the incidence of virus-neutralizing antibodies in asymptomatic and non-severe cases of COVID-19 [8,9]. Given the range of disease severity in humans, it is important to elucidate the similarities and differences between symptomatic and asymptomatic infections of SARS-CoV-2 and their implications for long-term protection, potential re-infections, herd immunity, and treatment options.…”

Section: Introductionmentioning

confidence: 99%

Titers of Neutralizing Antibodies against SARS-CoV-2 Are Independent of Symptoms of Non-Severe COVID-19 in Young Adults

Jónsdóttir

Bielecki

Siegrist

et al. 2021

Viruses

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Neutralizing antibodies are an important part of the humoral immune response to SARS-CoV-2. It is currently unclear to what extent such antibodies are produced after non-severe disease or asymptomatic infection. We studied a cluster of SARS-CoV-2 infections among a homogeneous population of 332 predominantly male Swiss soldiers and determined the neutralizing antibody response with a serum neutralization assay using a recombinant SARS-CoV-2-GFP. All patients with non-severe COVID-19 showed a swift humoral response within two weeks after the onset of symptoms, which remained stable for the duration of the study. One month after the outbreak, titers in COVID-19 convalescents did not differ from the titers of asymptomatically infected individuals. Furthermore, symptoms of COVID-19 did not correlate with neutralizing antibody titers. Therefore, we conclude that asymptomatic infection can induce the same humoral immunity as non-severe COVID-19 in young adults.

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Disease severity dictates SARS-CoV-2-specific neutralizing antibody responses in COVID-19

Cited by 39 publications

References 31 publications

Age-dependent pathogenic characteristics of SARS-CoV-2 infection in ferrets

Age-dependent pathogenic characteristics of SARS-CoV-2 infection in ferrets

SARS-CoV2- infection as a trigger of humoral response against apolipoprotein A-1

Titers of Neutralizing Antibodies against SARS-CoV-2 Are Independent of Symptoms of Non-Severe COVID-19 in Young Adults

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