Reduction and Functional Exhaustion of T Cells in Patients With Coronavirus Disease 2019 (COVID-19)

Diao, Bo; Wang, Chenhui; Tan, Yingjun; Chen, Xiewan; Liu, Ying; Ning, Lifen; Chen, Li; Li, Min; Liu, Yueping; Wang, Gang; Yuan, Zilin; Feng, Zeqing; Zhang, Yi; Wu, Yuzhang; Chen, Yongwen

doi:10.3389/fimmu.2020.00827

Cited by 2,111 publications

(2,325 citation statements)

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“…T cell depletion in critically ill patients is in line with the clinically observed T cell lymphopenia, which was also negatively correlated with COVID-19 severity 67 . Recent research has demonstrated that SARS-CoV-2 dramatically reduces T cells, and up-regulates exhaustion markers PD-1, and Tim-3, especially in critically ill patients 67 The impaired IFN response in the critical could be responsible for the loss of viral replication control in these patients 67 . Moreover, highly accumulated PE lipids (Fig.…”

Section: Discussionsupporting

confidence: 76%

The Trans-omics Landscape of COVID-19

Chen

Ding

et al. 2020

Preprint

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The outbreak of coronavirus disease 2019 (COVID-19) has been causing a global health emergency. Although previous studies investigated COVID-19 at different omics levels, the molecular hallmarks of COVID-19, especially in those patients without comorbidities, have not been fully investigated. Here, we presented a trans-omics landscape for COVID-19 based on integrative analysis of genomic, transcriptomic, proteomic, metabolomic and lipidomic profiles from blood samples of 231 COVID-19 patients, ranging from asymptomatic to critically ill, importantly excluding those with any comorbidities. Notably, we found neutrophils heterogeneity existed between asymptomatic and critically ill patients. Expression discordance of inflammatory cytokines at mRNA and protein levels in asymptomatic patients could possibly be explained by post-transcriptional regulation by RNA binding proteins (RBPs) and microRNAs. Neutrophils over-activation, induced arginine depletion, and tryptophan metabolites accumulation contributed to T/NK cell dysfunction in critical patients. Anti-virus interferons were gradually suppressed along with disease severity. Overall, our study systematically revealed multi-omics characteristics of COVID-19, and the data we generated could hopefully help illuminate COVID-19 pathogenesis and provide valuable clues about potential therapeutic strategies for COVID-19.

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Section: Discussionsupporting

confidence: 76%

The Trans-omics Landscape of COVID-19

Chen

Ding

et al. 2020

Preprint

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“…Patients requiring ICU admission have signi cantly higher levels of IL-6, IL-10, and TNF-α. Further, the levels of IL-6, IL-10, and TNF-α inversely correlate with CD4 + and CD8 + T cell counts [24]. This fact is strengthened by our meta-analysis results.…”

Section: Discussionsupporting

confidence: 75%

Association of immunological features with COVID-19 severity: a systematic review and meta-analysis

Zhang

Chen

et al. 2020

Preprint

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Abstract BackgroundWe aim to explore the association of immunological features with COVID-19 severity.MethodsWe conducted a meta-analysis to estimate mean difference (MD) of immune cells and cytokines levels with COVID-19 severity in PubMed and Web of Science.ResultsA total of 16 studies with 1689 COVID-19 patients were included. Compared with mild cases, severe cases showed significantly lower levels of immune cells, CD3+ T cell (× 106, MD, -413.87; 95%CI, -611.39 to -216.34), CD4+ T cell (× 106, MD, -225.89; 95%CI, -306.36 to -145.43), CD8+ T cell (× 106, MD, -138.59; 95%CI, -176.36 to -100.82), B cell (× 106/L; MD, -23.87; 95%CI, -43.97 to -3.78) and NK cell (× 106/L; MD, -57.12; 95%CI, -81.18 to -33.06), and significantly higher levels of cytokines, TNF-α (pg/ml; MD, 0.34; 95%CI, 0.09 to 0.59), IL-5 (pg/ml; MD, 14.2; 95%CI, 3.99 to 24.4), IL-6 (pg/ml; MD, 13.07; 95%CI, 9.80 to 16.35), and IL-10 (pg/ml; MD, 2.04; 95%CI, 1.32 to 2.75). However, no significant differences were found in other indicators, IFN-γ (pg/ml; MD, 0.26; 95%CI, -0.05 to 0.56), IL-2 (pg/ml; MD, 0.05; 95%CI, -0.49 to 0.60), IL-4 (pg/ml; MD, -0.03; 95%CI, -0.68 to 0.62), Treg cell (× 106, MD, -0.13; 95%CI, -1.40 to 1.14), and CD4+/CD8+ ratio (MD, 0.17; 95%CI, -0.14 to 0.49).ConclusionOur meta-analysis revealed significant lower levels in immune cells (CD3+ T, CD4+ T, CD8+ T, B and NK cells) and significant higher levels in cytokines (TNF-α, IL-5, IL-6 and IL-10) in severe cases compared with mild cases of COVID-19. Measurement of immunological features could help to assess disease severity for effective triage of COVID-19 patients.

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“…6 The recent data collected from patients with COVID-19 also confirmed that T-cell counts are negatively correlated with the changes in the production of IL-6, TNF-α, and other proinflammatory cytokines. 7 The cytokine release syndrome (CRS) or so-called cytokine storms are currently considered as the cause of critical illness and death. 8 Antibody-dependent enhancement (ADE), especially the suboptimal antibody-elated responds maybe the cause of the CRS.…”

Section: Introductionmentioning

confidence: 99%

Immunoregulation with mTOR inhibitors to prevent COVID‐19 severity: A novel intervention strategy beyond vaccines and specific antiviral medicines

Zheng¹,

Liu

2020

Journal of Medical Virology

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Coronavirus disease 2019 (COVID-19) has become a major global public health concern. The mortality rate for critically ill patients is up to 60%, and, thus, reducing the disease severity and case mortality is a top priority. Currently, cytokine storms are considered as the major cause of critical illness and death due to COVID-19.After a systematical review of the literature, we propose that cross-reactive antibodies associated with antibody-dependent enhancement (ADE) may actually be the cause of cytokine storms. It would be more difficult to develop vaccines for highly pathogenic human coronaviruses (CoVs) if ADE characteristics are taken into consideration. Therefore, it is urgent to find an effective way to prevent the occurrence of severe illness as severe acute respiratory syndrome CoV-2 specific drugs or vaccines are still in development. If the activation of memory B cells can be selectively inhibited in high-risk patients at an early stage of COVID-19 to reduce the production of cross-reactive antibodies against the virus, we speculate that ADE can be circumvented and severe symptoms can be prevented. The mammalian target of rapamycin (mTOR) inhibitors satisfy such needs and it is recommended to conduct clinical trials for mTOR inhibitors in preventing the severity of COVID-19. K E Y W O R D S ADE, antibody-dependent enhancement, coronavirus, cross-reactive antibody, cytokine storm, immunity, mTOR inhibitors, rapamycin How to cite this article: Zheng Y, Li R, Liu S. Immunoregulation with mTOR inhibitors to prevent COVID-19 severity: A novel intervention strategy beyond vaccines and specific antiviral medicines.

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Reduction and Functional Exhaustion of T Cells in Patients With Coronavirus Disease 2019 (COVID-19)

Cited by 2,111 publications

References 36 publications

The Trans-omics Landscape of COVID-19

The Trans-omics Landscape of COVID-19

Association of immunological features with COVID-19 severity: a systematic review and meta-analysis

Immunoregulation with mTOR inhibitors to prevent COVID‐19 severity: A novel intervention strategy beyond vaccines and specific antiviral medicines

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