Potential protective role of the anti-PD-1 blockade against SARS-CoV-2 infection

Awadasseid, Annoor; Yin, Qiang; Wu, Yanling; Zhang, Wen

doi:10.1016/j.biopha.2021.111957

Cited by 15 publications

(12 citation statements)

References 88 publications

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“…In this study, we characterised the immunological profiles of patients with different severities of COVID-19, indicating that PD-1 and PD-L1 expression are related to disease severity and mortality. Based on these results, we conclude that both PD-1 and PD-L1 analysed in various lymphocyte T and B subsets may have applications as biomarkers of COVID-19 severity in addition to its roles in cancer therapy, as previously proposed [ 34 ], and may provide a basis for the use of exhaustion reversal agents to limit the progression of the COVID-19 in the severe stages.…”

Section: Discussionsupporting

confidence: 68%

Programmed Cell Death-1/Programmed Cell Death-1 Ligand as Prognostic Markers of Coronavirus Disease 2019 Severity

Niedźwiedzka-Rystwej

Majchrzak

Aksak‐Wąs

et al. 2022

Cells

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Current research proves that immune dysregulation is a common feature of coronavirus disease 2019 (COVID-19), and immune exhaustion is associated with increased disease mortality. Immune checkpoint molecules, including the programmed cell death-1 (PD-1)/PD-1 ligand (PD-L1) axis, may serve as markers of disease severity. Accordingly, in this study, we evaluated the expression of PD-1/PD-L1 in patients with COVID-19. Blood immunophenotypes of hospitalized patients with moderate (n = 17, requiring oxygen support) and severe (n = 35, requiring mechanical ventilation in the intensive care setting) COVID-19 were compared and associated with clinical, laboratory, and survival data. The associations between severity and lymphocyte profiles were analysed at baseline and after 7 and 14 days of in-hospital treatment. Forty patients without COVID-19 infection were used as controls. For PD-1-positive T and B lymphocyte subsets, notable increases were observed between controls and patients with moderate or severe COVID-19 for CD4+PD-1+ T cells, CD8+PD-1+ T and CD19+PD-1+ B cells. Similar trends were observed for PD-L1-positive lymphocytes, namely, CD4+PD-L1+ T cells, CD8+PD-L1+ T cells and CD19+PD-L1+ B cells. Importantly, all markers associated with PD-1 and PD-L1 were stable over time for the analysed time points in the moderate and severe COVID-19 groups. Increased abundances of PD-1+ and PD-L1+ lymphocytes were associated with disease severity and mortality and were stable over time in patients with moderate to severe COVID-19. These immune exhaustion parameters may be attractive biomarkers of COVID-19 severity.

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Section: Discussionsupporting

confidence: 68%

Programmed Cell Death-1/Programmed Cell Death-1 Ligand as Prognostic Markers of Coronavirus Disease 2019 Severity

Niedźwiedzka-Rystwej

Majchrzak

Aksak‐Wąs

et al. 2022

Cells

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“…These R&D efforts are yet to deliver convincing evidence of their effectiveness. However, anti-PD1/PDL1 and IL-7 therapeutics have shown signs of usefulness and efficacy during clinical trials [ 132 , 133 ]. Thus, similar strategies would be effective in treating SARS-CoV-2 infected patients.…”

Section: Immune-boosting Strategiesmentioning

confidence: 99%

Significance of Immune Status of SARS-CoV-2 Infected Patients in Determining the Efficacy of Therapeutic Interventions

Saratale

Shin

Shinde

et al. 2022

JPM

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Coronavirus disease 2019 (COVID-19) is now being investigated for its distinctive patterns in the course of disease development which can be indicated with miscellaneous immune responses in infected individuals. Besides this series of investigations on the pathophysiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), significant fundamental immunological and physiological processes are indispensable to address clinical markers of COVID-19 disease and essential to identify or design effective therapeutics. Recent developments in the literature suggest that deficiency of type I interferon (IFN) in serum samples can be used to represent a severe progression of COVID-19 disease and can be used as the basis to develop combined immunotherapeutic strategies. Precise control over inflammatory response is a significant aspect of targeting viral infections. This account presents a brief review of the pathophysiological characteristics of the SARS-CoV-2 virus and the understanding of the immune status of infected patients. We further discuss the immune system’s interaction with the SARS-CoV-2 virus and their subsequent involvement of dysfunctional immune responses during the progression of the disease. Finally, we highlight some of the implications of the different approaches applicable in developing promising therapeutic interventions that redirect immunoregulation and viral infection.

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“…8B). In fact, those two epitopes have their slopes S the closest to 0 among all epitopes (Supplemental (ii) a general lymphopenia (11)(12)(13)(14)(15)(16); and (iii) a broad (not SARS-CoV-2-specific T cell exhaustion and/or impaired function (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32). This was reported for immune cells both in the peripheral compartment (PBMCs) and in the lung and brain of symptomatic patients (13,69).…”

Section: Compared With Asymptomatic Covid-19 Patients Severely Ill Sy...mentioning

confidence: 73%

“…While the mechanisms that lead to severe COVID-19 remain to be fully elucidated, immune dysregulations are associated with the pathogenesis of COVID-19 including: (i) virus-specific adaptive immune responses that can trigger pathological processes characterized by localized or systemic inflammatory processes (7); (ii) increased levels of pro-inflammatory cytokines (8)(9)(10); and (iii) a broad lymphopenia (11)(12)(13)(14)(15)(16). Nevertheless, the role of CD4 + and CD8 + T cells in COVID-19 disease remains controversial (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32). CD4 + and CD8 + T cells specific to SARS-CoV-2 have been reported to be associated with less severe symptoms (33)(34)(35)(36)(37)(38)(39)(40)(41)(42).…”

Section: Introductionmentioning

confidence: 99%

High Frequencies of PD-1⁺TIM3⁺TIGIT⁺CTLA4⁺ Functionally Exhausted SARS-CoV-2-Specific CD4⁺ and CD8⁺ T Cells Associated with Severe Disease in Critically ill COVID-19 Patients

Coulon

Prakash

Dhanushkodi

et al. 2022

Preprint

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SARS-CoV-2-specific memory T cells that cross-react with common cold coronaviruses (CCCs) are present in both healthy donors and COVID-19 patients. However, whether these cross-reactive T cells play a role in COVID-19 pathogenesis versus protection remain to be fully elucidated. In this study, we characterized cross-reactive SARS-CoV-2-specific CD4+ and CD8+ T cells, targeting genome-wide conserved epitopes in a cohort of 147 non-vaccinated COVID-19 patients, divided into six groups based on the degrees of disease severity. We compared the frequency, phenotype, and function of these SARS-CoV-2-specific CD4+ and CD8+ T cells between severely ill and asymptomatic COVID-19 patients and correlated this with alpha-CCCs and beta-CCCs co-infection status. Compared with asymptomatic COVID-19 patients, the severely ill COVID-19 patients and patients with fatal outcomes: (i) Presented a broad leukocytosis and a broad CD4+ and CD8+ T cell lymphopenia; (ii) Developed low frequencies of functional IFN-gamma-producing CD134+CD138+CD4+ and CD134+CD138+CD8+ T cells directed toward conserved epitopes from structural, non-structural and regulatory SARS-CoV-2 proteins; (iii) Displayed high frequencies of SARS-CoV-2-specific functionally exhausted PD-1+TIM3+TIGIT+CTLA4+CD4+ and PD-1+TIM3+TIGIT+CTLA4+CD8+ T cells; and (iv) Displayed similar frequencies of co-infections with beta-CCCs strains but significantly fewer co-infections with alpha-CCCs strains. Interestingly, the cross-reactive SARS-CoV-2 epitopes that recalled the strongest CD4+ and CD8+ T cell responses in unexposed healthy donors (HD) were the most strongly associated with better disease outcome seen in asymptomatic COVID-19 patients. Our results demonstrate that, the critically ill COVID-19 patients displayed fewer co-infection with alpha-CCCs strain, presented broad T cell lymphopenia and higher frequencies of cross reactive exhausted SARS-CoV-2-specific CD4+ and CD8+ T cells. In contrast, the asymptomatic COVID-19 patients, appeared to present more co-infections with alpha-CCCs strains, associated with higher frequencies of functional cross-reactive SARS-CoV-2-specific CD4+ and CD8+ T cells. These findings support the development of broadly protective, T-cell-based, multi-antigen universal pan-Coronavirus vaccines.

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Potential protective role of the anti-PD-1 blockade against SARS-CoV-2 infection

Cited by 15 publications

References 88 publications

Programmed Cell Death-1/Programmed Cell Death-1 Ligand as Prognostic Markers of Coronavirus Disease 2019 Severity

Programmed Cell Death-1/Programmed Cell Death-1 Ligand as Prognostic Markers of Coronavirus Disease 2019 Severity

Significance of Immune Status of SARS-CoV-2 Infected Patients in Determining the Efficacy of Therapeutic Interventions

High Frequencies of PD-1⁺TIM3⁺TIGIT⁺CTLA4⁺ Functionally Exhausted SARS-CoV-2-Specific CD4⁺ and CD8⁺ T Cells Associated with Severe Disease in Critically ill COVID-19 Patients

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Potential protective role of the anti-PD-1 blockade against SARS-CoV-2 infection

Cited by 15 publications

References 88 publications

Programmed Cell Death-1/Programmed Cell Death-1 Ligand as Prognostic Markers of Coronavirus Disease 2019 Severity

Programmed Cell Death-1/Programmed Cell Death-1 Ligand as Prognostic Markers of Coronavirus Disease 2019 Severity

Significance of Immune Status of SARS-CoV-2 Infected Patients in Determining the Efficacy of Therapeutic Interventions

High Frequencies of PD-1+TIM3+TIGIT+CTLA4+ Functionally Exhausted SARS-CoV-2-Specific CD4+ and CD8+ T Cells Associated with Severe Disease in Critically ill COVID-19 Patients

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High Frequencies of PD-1⁺TIM3⁺TIGIT⁺CTLA4⁺ Functionally Exhausted SARS-CoV-2-Specific CD4⁺ and CD8⁺ T Cells Associated with Severe Disease in Critically ill COVID-19 Patients