COVID-19 patients display distinct SARS-CoV-2 specific T-cell responses according to disease severity

AbstractBackgroundIn order to understand the role of dengue virus (DENV) specific T cell responses that associate with protection, we studied their frequency and phenotype in relation to clinical disease severity and resolution of viraemia in a large cohort of patients with varying severity of acute dengue infection.Methodology/Principal findingsUsing ex vivo IFNγ ELISpot assays we determined the frequency of dengue viral peptide (DENV)-NS3, NS1 and NS5 responsive T cells in 74 adult patients with acute dengue infection and examined the association of responsive T cell frequency with the extent of viraemia and clinical disease severity. We found that total DENV-specific and DENV-NS3-specific T cell responses, were higher in patients with dengue fever (DF), when compared to those with dengue haemorrhagic fever (DHF). In addition, early appearance of DENV-specific T cell responses was significantly associated with milder clinical disease (p=0.02). DENV peptide specific T cell responses inversely correlated with the degree of viraemia, which was most significant for DENV-NS3 specific T cell responses (Spearman’s r = −0.47, p=0.0003). The frequency of T cell responses to NS1, NS5 and pooled DENV peptides, correlated with the degree of thrombocytopenia but had no association with levels of liver transaminases. In contrast, DENV-IgG inversely correlated with the degree of thrombocytopenia and levels of liver transaminases.Conclusions/significanceEarly appearance of DENV-specific T cell IFNγ responses appears to associate with milder clinical disease and resolution of viraemia, suggesting a protective role in acute dengue infection.

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Differential regulation of T cell responses and disease severity by mycoplasma and its superantigen in autoimmune diabetic mice

Frontiers in Immunology ◽

10.3389/conf.fimmu.2013.02.00091 ◽

2013 ◽

Vol 4 ◽

Author(s):

Nourian Maziar ◽

Mu Hong

Keyword(s):

T Cell ◽

Disease Severity ◽

T Cell Responses ◽

Differential Regulation ◽

Diabetic Mice ◽

Cell Responses

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SARS-CoV-2 elicits robust adaptive immune responses regardless of disease severity

10.1101/2020.10.08.331645 ◽

2020 ◽

Author(s):

Stine SF Nielsen ◽

Line K Vibholm ◽

Ida Monrad ◽

Rikke Olesen ◽

Giacomo S Frattari ◽

...

Keyword(s):

Immune Response ◽

T Cell ◽

Immune Responses ◽

Disease Severity ◽

Adaptive Immune Response ◽

T Cell Responses ◽

Adaptive Immune Responses ◽

Cell Responses ◽

Adaptive Immune ◽

Robust Adaptive

AbstractThe SARS-CoV-2 pandemic currently prevails worldwide. To understand the immunological signature of SARS-CoV-2 infections and aid the search for treatments and vaccines, comprehensive characterization of adaptive immune responses towards SARS-CoV-2 is needed. We investigated the breadth and potency of antibody-, and T-cell immune responses, in 203 recovered SARS-CoV-2 infected patients who presented with asymptomatic to severe infections. We report very broad serological profiles with cross-reactivity to other human coronaviruses. Further, >99% had SARS-CoV-2 epitope specific antibodies, with SARS-CoV-2 neutralization and spike-ACE2 receptor interaction blocking observed in 95% of individuals. A significant positive correlation between spike-ACE2 blocking antibody titers and neutralization potency was observed. SARS-CoV-2 specific CD8+ T-cell responses were clear and quantifiable in 90% of HLA-A2+ individuals. The viral surface spike protein was identified as the dominant target for both neutralizing antibodies and CD8+ T cell responses. Overall, the majority of patients had robust adaptive immune responses, regardless of disease severity.Author summarySARS-CoV-2 can cause severe and deadly infections. However, the immunological understanding of this viral infection is limited. Currently, several vaccines are being developed to help limit transmission and prevent the current pandemic. However, basic understanding of the adaptive immune response developed during SARS-CoV-2 infections is needed to inform further vaccine development and to understand the protective properties of the developed immune response. We investigated, the adaptive immune response developed during SARS-CoV-2 infections in recovered patients experiencing a full spectrum of disease severity, from asymptomatic infections to severe cases requiring hospitalization. We used a novel multiplex serological platform, cell-based neutralization assays and dextramer flow cytometry assays to characterize a broad and robust humoral and cellular immune response towards SARS-CoV-2. We found that the vast majority of recovered individuals have clear detectable and functional SARS-CoV-2 spike specific adaptive immune responses, despite diverse disease severities. The detection of both a humoral and cellular functional spike specific immune response in the vast majority of the individuals, irrespective of asymptomatic manifestations, supports vaccine designs currently underway, and encourages further exploration of whether primary infections provide protection to reinfection.

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T cell responses in senior patients with community-acquired pneumonia related to disease severity

Experimental Cell Research ◽

10.1016/j.yexcr.2017.09.041 ◽

2017 ◽

Vol 361 (1) ◽

pp. 56-62 ◽

Cited By ~ 1

Author(s):

Lu-Qin Bian ◽

Ying Bi ◽

Shao-Wei Zhou ◽

Zi-Dan Chen ◽

Jun Wen ◽

...

Keyword(s):

T Cell ◽

Disease Severity ◽

T Cell Responses ◽

Community Acquired Pneumonia ◽

Cell Responses ◽

Senior Patients

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Heterogenous Cellular and Humoral Immune Trajectories after SARS-CoV-2 Infection: Compensatory Responses in a Population-Based Cohort

10.1101/2021.12.15.21267776 ◽

2021 ◽

Author(s):

Dominik Menges ◽

Kyra D Zens ◽

Tala Ballouz ◽

Nicole Caduff ◽

Daniel Llanas-Cornejo ◽

...

Keyword(s):

T Cell ◽

Immune Responses ◽

Disease Severity ◽

Cell Subset ◽

T Cell Responses ◽

Population Based ◽

Antibody Responses ◽

Igg Antibody ◽

Cell Responses ◽

Over Time

To better understand the development of immunity against SARS-CoV-2 over time, we evaluated humoral and cellular responses a population-based cohort of SARS-CoV-2-infected individuals covering the full spectrum of COVID-19 up to 217 days after diagnosis. We characterized anti-Spike (S)-IgA and -IgG antibody responses in 431 individuals and found that about 85% develop and maintain anti-S-IgG responses over time. In a subsample of 64 participants selected for a detailed characterization of immune responses, we additionally evaluated anti-Nucleocapsid (N)-IgG antibodies and T cell responses specific to viral Membrane (M), N, and S proteins. Most participants had detectable T cell responses to at least one of the four peptide pools analyzed, which were more frequent than antibody seropositivity. We found a moderate correlation between antibody and T cell responses, which declined over time and suggests important variability in response patterns between individuals. The heterogeneity of immune trajectories was further analyzed using cluster analyses taking into account joint antibody and T cell responses over time. We identified five distinct immune trajectory patterns, which were characterized by specific antibody, T cell and T cell subset patterns along with disease severity and demographic factors. Higher age, male sex, higher disease severity and being a non-smoker was significantly associated with stronger immune responses. Overall, the results highlight that there is a consistent and maintained antibody response among most SARS-CoV-2-infected individuals, while T cell responses appear to be more heterogenous but potentially compensatory among those with low antibody responses.

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Association of dengue virus‐specific polyfunctional T‐cell responses with clinical disease severity in acute dengue infection

Immunity Inflammation and Disease ◽

10.1002/iid3.271 ◽

2019 ◽

Vol 7 (4) ◽

pp. 276-285 ◽

Cited By ~ 4

Author(s):

Dulharie T. Wijeratne ◽

Samitha Fernando ◽

Laksiri Gomes ◽

Chandima Jeewandara ◽

Geethal Jayarathna ◽

...

Keyword(s):

T Cell ◽

Dengue Virus ◽

Disease Severity ◽

Dengue Infection ◽

T Cell Responses ◽

Clinical Disease ◽

Cell Responses

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The dichotomous and incomplete adaptive immunity in COVID-19 patients with different disease severity

Signal Transduction and Targeted Therapy ◽

10.1038/s41392-021-00525-3 ◽

2021 ◽

Vol 6 (1) ◽

Author(s):

Leiqiong Gao ◽

Jing Zhou ◽

Sen Yang ◽

Lisha Wang ◽

Xiangyu Chen ◽

...

Keyword(s):

T Cell ◽

B Cell ◽

Adaptive Immunity ◽

Disease Severity ◽

Protective Immunity ◽

Rational Design ◽

T Cell Responses ◽

Cell Responses ◽

Asymptomatic Patients ◽

B Cell Responses

AbstractThe adaptive immunity that protects patients from coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is not well characterized. In particular, the asymptomatic patients have been found to induce weak and transient SARS-CoV-2 antibody responses, but the underlying mechanisms remain unknown; meanwhile, the protective immunity that guide the recovery of these asymptomatic patients is elusive. Here, we characterized SARS-CoV-2-specific B-cell and T-cell responses in 10 asymptomatic patients and 64 patients with other disease severity (mild, n = 10, moderate, n = 32, severe, n = 12) and found that asymptomatic or mild symptomatic patients failed to mount virus-specific germinal center (GC) B cell responses that result in robust and prolonged humoral immunity, assessed by GC response indicators including follicular helper T (TFH) cell and memory B cell responses as well as serum CXCL13 levels. Alternatively, these patients mounted potent virus-specific TH1 and CD8+ T cell responses. In sharp contrast, patients of moderate or severe disease induced vigorous virus-specific GC B cell responses and associated TFH responses; however, the virus-specific TH1 and CD8+ T cells were minimally induced in these patients. These results, therefore, uncovered the protective immunity in asymptomatic patients and also revealed the strikingly dichotomous and incomplete humoral and cellular immune responses in COVID-19 patients with different disease severity, providing important insights into rational design of effective COVID-19 vaccines.

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The dichotomous and incomplete adaptive immunity in COVID-19

10.1101/2020.09.05.20187435 ◽

2020 ◽

Cited By ~ 1

Author(s):

Leiqiong Gao ◽

Jing Zhou ◽

Sen Yang ◽

Xiangyu Chen ◽

Yang Yang ◽

...

Keyword(s):

T Cell ◽

B Cell ◽

Adaptive Immunity ◽

Disease Severity ◽

Protective Immunity ◽

Rational Design ◽

T Cell Responses ◽

Cell Responses ◽

Asymptomatic Patients ◽

B Cell Responses

The adaptive immunity that protects patients from coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is not well characterized. In particular, the asymptomatic patients have been found to induce weak and transient SARS-CoV-2 antibody responses, but the underlying mechanisms remain unknown; meanwhile, the protective immunity that guide the recovery of these asymptomatic patients is also not well studied. Here, we characterized SARS-CoV-2-specific B-cell and T-cell responses in 10 asymptomatic patients and 49 patients with other disease severity (mild, n=10, moderate, n=32, severe, n=7) and found that asymptomatic or mild symptomatic patients failed to mount virus-specific germinal center (GC) B cell responses that result in robust and long-term humoral immunity, assessed by GC response indicators including follicular helper T (TFH) cell and memory B cell responses as well as serum CXCL13 levels. Alternatively, these patients mounted potent virus-specific TH1 and CD8+ T cell responses. In sharp contrast, patients of moderate or severe disease induced vigorous virus-specific GC B cell responses and associated TFH responses; however, the virus-specific TH1 and CD8+ T cells were minimally induced in these patients. These results therefore uncovered the protective immunity in asymptomatic patients and revealed the strikingly dichotomous and unbalanced humoral and cellular immune responses in COVID-19 patients with different disease severity, providing important insights into rational design of COVID-19 vaccines.

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