Expansion of SARS-CoV-2–Specific Antibody-Secreting Cells and Generation of Neutralizing Antibodies in Hospitalized COVID-19 Patients

Varnaitė, Renata; García, Marina; Glans, Hedvig; Maleki, Kimia T.; Sandberg, J; Tynell, Janne; Christ, Wanda; Lagerqvist, Nina; Ásgeirsson, Hilmir; Ljunggren, Hans‐Gustaf; Ahlén, Gustaf; Frelin, Lars; Sällberg, Matti; Blom, Kim; Klingström, Jonas; Gredmark‐Russ, Sara

doi:10.4049/jimmunol.2000717

Cited by 77 publications

(52 citation statements)

References 26 publications

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“…Moreover, our findings are not in accordance with previous ones [ 21 ] that showed IgM and IgG antibodies positive as early as the fourth day after illness onset and IgM and IgG seroconversion that increased from the ninth and eleventh day, respectively. Our findings agree with those of Varnaitė et al [ 22 ], who found that in COVID-19 patients, an expansion of antibody-secreting plasma cells against SARS-CoV-2 occurred 19 days after COVID-19 symptom debut with a production of IgM and IgG, consistent with Lee et al [ 23 ], who highlighted that in acute respiratory syncytial virus infection, antibody-secreting plasma cell expansion could be detected 22–45 days after the onset of symptoms due to the longer acute respiratory syncytial virus shedding time in the respiratory tract, indicating that the kinetics of the ASC response might be due to pathogen persistence. In our opinion, these three patients were paradigmatic of the true pathogenetic aim of SARS-CoV2 that tries to contaminate, remain, and spread as long as possible.…”

Section: Discussionsupporting

confidence: 94%

Immune Response Failure in Paucisymptomatic Long-Standing SARS-CoV-2 Spreaders

Corrao

Gervasi²,

Bernardo³

et al. 2021

Clinics and Practice

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The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly spread throughout the world. This disease has a spectrum of different clinical pictures with different outcomes. Herein, we report all the data from three paucisymptomatic patients during a hospital stay that might represent a paradigmatic example of the method by which SARS-CoV-2 is shed. We demonstrated the lack of an adequate qualitative and quantitative immune response by multiparametric flow cytometry analysis. Our data can provide a new perspective about the method by which SARS-CoV-2 is shed and the clinical weight of viral persistence. In all three cases, the long persistence of the virus and the consistent reduction in both innate and adaptative immune cells are not associated with greater disease severity. These patients might represent at least part of the population. In particular, one patient oscillated between positive and negative swab tests several times without presenting any immune response. In all three cases, the immune response failure was not associated with a clinically significant involvement, indicating that it is not the virus’s ability to impair the immune system, as well as its presence and persistence the fundamental mechanism that might causally lead to death. Finally, this kind of immune response in paucisymptomatic patients could pose a considerable danger to public health that questions the quarantine period. It is urgent to quantify the phenomenon with a large sample study.

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Section: Discussionsupporting

confidence: 94%

Immune Response Failure in Paucisymptomatic Long-Standing SARS-CoV-2 Spreaders

Corrao

Gervasi²,

Bernardo³

et al. 2021

Clinics and Practice

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“…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 ]. Most studies originated from China (n = 32, 52%) [ 11 – 13 , 15 – 21 , 23 – 29 , 31 – 39 ,…”

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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“…Micro-neutralization assay for measurement of neutralizing antibody titers was performed as previously described 30 33 , and ggplot2 (v.3.3.2) 34 . Data was normalized in R using the scale argument within the PCA function.…”

Section: Clinical Parameters and Serologymentioning

confidence: 99%

Innate lymphoid cell composition associates with COVID-19 disease severity

García

Kokkinou

García

et al. 2020

Preprint

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Objectives: The role of innate lymphoid cells (ILCs) in coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is unknown. Understanding the immune response in COVID-19 could contribute to unravel the pathogenesis and identification of treatment targets. To describe the phenotypic landscape of circulating ILCs in COVID-19 patients and to identify ILC phenotypes correlated to serum biomarkers, clinical markers, and laboratory parameters relevant in COVID-19. Methods: Blood samples collected from moderately (n=11) and severely ill (n=12) COVID-19 patients as well as healthy control donors (n=16), were analyzed with 18-parameter flow cytometry. Using supervised and unsupervised approaches, we examined the ILC activation status and homing profile. Clinical and laboratory parameters were obtained from all COVID-19 patients and serum biomarkers were analyzed with multiplex immunoassays. Results: ILCs were largely depleted from the circulation of COVID-19 patients compared with healthy controls. Remaining circulating ILCs from patients revealed increased frequencies of ILC2 in moderate COVID-19, with a concomitant decrease of ILC precursors (ILCp), as compared with controls. ILC2 and ILCp showed an activated phenotype with increased CD69 expression, whereas expression levels of the chemokine receptors CXCR3 and CCR4 were significantly altered in ILC2 and ILCp, and ILC1, respectively. The activated ILC profile of COVID-19 patients was associated with soluble inflammatory markers, while frequencies of ILC subsets were correlated with laboratory parameters that reflect the disease severity. Conclusion: This study provides insights into the potential role of ILCs in immune responses against SARS-CoV-2, particularly linked to the severity of COVID-19.

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Expansion of SARS-CoV-2–Specific Antibody-Secreting Cells and Generation of Neutralizing Antibodies in Hospitalized COVID-19 Patients

Cited by 77 publications

References 26 publications

Immune Response Failure in Paucisymptomatic Long-Standing SARS-CoV-2 Spreaders

Immune Response Failure in Paucisymptomatic Long-Standing SARS-CoV-2 Spreaders

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

Innate lymphoid cell composition associates with COVID-19 disease severity

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