Analysis of adaptive immune cell populations and phenotypes in the patients infected by SARS-CoV-2

Yang, Xing; Dai, Tinglong; Zhou, Xiaofang; Qian, Hai; Guo, Rong; Le, Lei; X, Zhang; Zhang, D; Shi, Lei; Cheng, Yanxiang; Jian, Hu; Guo, Yuhong; Zhang, B

doi:10.1101/2020.03.23.20040675

Cited by 38 publications

(47 citation statements)

References 26 publications

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“…ICOS+CXCR3+ cTfh correlate with nAb responses upon viral infection or vaccination [46][47][48][49] . cTfh increase over the course of SARS-CoV-2 infection 8,15,16 . In our study the cTfh frequency was highest in the ICU patients, patients that also demonstrated the highest antibody titers, with indications of levels decreasing upon recovery.…”

Section: Discussionmentioning

confidence: 99%

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Divergent SARS-CoV-2-specific T and B cell responses in severe but not mild COVID-19

Oja

Saris

Ghandour

et al. 2020

Preprint

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the current coronavirus disease 2019 pandemic. Understanding both the immunological processes providing specific immunity and potential immunopathology underlying the pathogenesis of this disease may provide valuable insights for potential therapeutic interventions. Here, we quantified SARS-CoV-2 specific immune responses in patients with different clinical courses. Compared to individuals with a mild clinical presentation, CD4+ T cell responses were qualitatively impaired in critically ill patients.Strikingly, however, in these patients the specific IgG antibody response was remarkably strong. The observed disparate T and B cell responses could be indicative of a deregulated immune response in critically ill COVID-19 patients.The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a single-strand RNA virus that has been identified as the causative agent of coronavirus disease 2019 , mainly characterized by respiratory symptoms. This virus appears to be easily transmittable and highly virulent in a sizable fraction of the global population. Consequently, the WHO characterized COVID-19 as a pandemic by March 11 th , 2020. Despite socioeconomic lockdown in about a third of the world, the global number of confirmed SARS-CoV-2 infections surpassed 7 million 1,2 (https://covid19.who.int/). SARS-CoV-2 is primarily transmitted via respiratory droplets and aerosols. The virus infectsairway epithelial cells expressing the surface receptors ACE2 and TMPRSS2. The virus replicates and sheds virus particles, which cause the infected cell to undergo pyroptosis.During this process, damage-associated molecular patterns are released, activating a cascade of pro-inflammatory cytokines and chemokines that attract auxiliary immune cells to the site of infection promoting further inflammation 3 . In severely affected COVID-19 patients this pro-inflammatory cascade appears to be dysregulated, resulting in a life-threatening cytokine storm, which triggers acute respiratory distress syndrome (ARDS) and subsequently other organ dysfunction including, liver, heart, and kidney damage.Clinically, COVID-19 patients can be classified into mild, moderate, severe, and critical cases. Importantly, it has been proposed that the immune response against SARS-CoV-2 is linked to the severity of disease 2,4,5 . Although T cell responses against SARS-CoV-2 proteins have been characterized 6,7 , a comprehensive comparison of the quantity and quality of adaptive immune responses in patients with distinct clinical courses is yet to be performed.Among the cells recruited to the lungs are virus-specific T cells, that have been primed by dendritic cells in the lung draining lymph nodes, and set to kill virus-infected cells, thus preventing further spread and thereby limiting disease progression. Both SARS-CoV-2specific CD8 + and CD4 + T cells and T cells with an activated phenotype have been detected in the blood between 1 and 2 weeks after the onset of ...

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Section: Discussionmentioning

confidence: 99%

“…It was recently shown that circulating follicular helper T cells (cTfh) are increased in Covid-19 patients and rise over the course of the infection 8,15,16 . However, possible differences in relation to disease severity were not assessed.…”

Section: T Cell Activation and Lymphopenia Are Associated With Diseasmentioning

confidence: 99%

Divergent SARS-CoV-2-specific T and B cell responses in severe but not mild COVID-19

Oja

Saris

Ghandour

et al. 2020

Preprint

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“…Indicative of in vivo activation, increased proportions of CD4 + and CD8 + T cells expressing CD69, CD38, CD44, or HLA-DR have been reported in COVID-19 patients ( 5 , 116 , 155 – 158 ) as has the presence of pathogenic GM-CSF + /IL-6 + and GM-CSF + /IFN + CD4 + T cells, with those experiencing severe disease presenting with significantly increased frequencies when compared to those with mild COVID-19 ( 116 ). Pointing toward a state of functional exhaustion or senescence, markedly higher percentages of CD4 + or CD8 + T cells expressing a variety of molecules such as NKG2A, PD-1, TIGIT, TIM-3 and CD57 have been detected in SARS-CoV-2-infected patients ( 116 , 134 , 154 , 159 ), with their presence coinciding with significantly reduced intracellular cytokine generation upon ex vivo stimulation ( 134 , 158 ).…”

Section: Pathogen Eliminationmentioning

confidence: 99%

“…Based on scRNA-seq data that has shown the presence of highly expanded and functionally-competent CD8 + T cells in the BALF of mild COVID-19 patients, it has been suggested that a robust adaptive immune response is critical to controlling SARS-CoV-2 infection ( 127 ). If correct, then combined with the aforementioned remodeled T cell pool of older adults and individuals with inflammatory co-morbidities, the SARS-CoV-2 driven induction of lymphocyte exhaustion ( 116 , 134 , 154 , 159 ) would hamper both the initiation and maintenance of such a response. Furthermore, due to the reduced vaccine efficacy that occurs as a consequence of both innate and adaptive immune dysfunction, alternative therapeutic strategies such as administration of the immunomodulatory drugs metformin and pioglitazone, have been proposed to protect these high risk groups against severe COVID-19 ( 174 ).…”

Section: Pathogen Eliminationmentioning

confidence: 99%

Immunesenescence: A Predisposing Risk Factor for the Development of COVID-19?

Hazeldine

Lord

2020

Front. Immunol.

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Bearing a strong resemblance to the phenotypic and functional remodeling of the immune system that occurs during aging (termed immunesenescence), the immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of Coronavirus disease 2019 (COVID-19), is characterized by an expansion of inflammatory monocytes, functional exhaustion of lymphocytes, dysregulated myeloid responses and the presence of highly activated senescent T cells. Alongside advanced age, male gender and pre-existing co-morbidities [e.g., obesity and type 2 diabetes (T2D)] are emerging as significant risk factors for COVID-19. Interestingly, immunesenescence is more profound in males when compared to females, whilst accelerated aging of the immune system, termed premature immunesenescence, has been described in obese subjects and T2D patients. Thus, as three distinct demographic groups with an increased susceptibility to COVID-19 share a common immune profile, could immunesenescence be a generic contributory factor in the development of severe COVID-19? Here, by focussing on three key aspects of an immune response, namely pathogen recognition, elimination and resolution, we address this question by discussing how immunesenescence may weaken or exacerbate the immune response to SARS-CoV-2. We also highlight how aspects of immunesenescence could render potential COVID-19 treatments less effective in older adults and draw attention to certain therapeutic options, which by reversing or circumventing certain features of immunesenescence may prove to be beneficial for the treatment of groups at high risk of severe COVID-19.

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“…Although SARS-CoV-2 reactive CD4 and CD8 T cells can be found in severe COVID-19 and can correlate with AB appearance and lower viral loads, CD4 T cells in severe disease are often dysfunctional or deregulated compared to mild COVID-19 (10,23,28,30,32,37,44,45). Conversely, recovering patients had increased virus specific and general CD4 T FH cells, and their SARS-CoV-2 reactive T cells expressed reduced inhibitory markers and elevated effector molecules (25,34,44,46,47).…”

Section: The Case For T Cellsmentioning

confidence: 99%