On the use of immune checkpoint inhibitors in patients with viral infections including COVID-19

Gambichler, Thilo; Reuther, J; Scheel, Christina; Becker, Jürgen C.

doi:10.1136/jitc-2020-001145

Cited by 58 publications

(73 citation statements)

References 88 publications

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“…Most severe COVID-19 cases exhibit a cytokine storm syndrome, leading to a poor prognosis [177]. Although the immune response during COVID-19 progression has been extensively studied in the short time since SARS-CoV-2 was identified [178][179][180], the role of immune checkpoints in this process is still not clear [181]. Reports indicate that the absolute numbers of peripheral blood NK cells, B-cells, and CD4 + and CD8 + T lymphocytes were all lower in patients with acute respiratory distress syndrome due to SARS-CoV-2 infection compared with those in healthy controls.…”

Section: Immune Checkpoints In Covid-19mentioning

confidence: 99%

Immune Checkpoints in Viral Infections

Cai

Liu

Zhong

et al. 2020

Viruses

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As evidence has mounted that virus-infected cells, such as cancer cells, negatively regulate the function of T-cells via immune checkpoints, it has become increasingly clear that viral infections similarly exploit immune checkpoints as an immune system escape mechanism. Although immune checkpoint therapy has been successfully used in cancer treatment, numerous studies have suggested that such therapy may also be highly relevant for treating viral infection, especially chronic viral infections. However, it has not yet been applied in this manner. Here, we reviewed recent findings regarding immune checkpoints in viral infections, including COVID-19, and discussed the role of immune checkpoints in different viral infections, as well as the potential for applying immune checkpoint blockades as antiviral therapy.

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Section: Immune Checkpoints In Covid-19mentioning

confidence: 99%

Immune Checkpoints in Viral Infections

Cai

Liu

Zhong

et al. 2020

Viruses

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“…In addition, early hypotheses postulated that ICI may worsen COVID-19 outcomes due to potential immune hyperactivation [36][37][38], where they may upregulate pro-in ammatory cytokines [36,37] and over-activate CD8 T-cells [38]-resulting in the dysregulation and exhaustion of T-cells [36,39]. This hypothesis was supported by the fact that severe COVID-19 cases were associated with lymphopenia and immune hyperactivity [6,37]thus suggesting that ICI may synergistically exacerbate cytokine storm in COVID-19 infection [38].…”

Section: Discussionmentioning

confidence: 98%

Immune checkpoint inhibitor does not increase risks of poor outcomes in cancer patients with COVID-19 infection: A systematic review and meta-analysis

Lazarus

Budiman

Rinaldi

2020

Preprint

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Background The association between prior exposure to immune checkpoint inhibitor (ICI) and outcomes of cancer patients with coronavirus disease 2019 (COVID-19) infection has yet to be systematically evaluated. As the current evidence remains equivocal, this meta-analysis aims to investigate the effects of ICI treatment on COVID-19 prognosis, including mortality, severity, and hospitalization.Methods Eligible studies published up to 14 September 2020 were included and assessed for risk of bias using the Quality in Prognosis Studies tool. A random-effects meta-analysis was conducted to estimate the pooled effect size along with 95% confidence intervals (CIs). The quality of body evidence was evaluated using the modified Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework.Results Six studies involving a total of 1647 COVID-19-infected cancer patients were included in the systematic review. We discovered that prior ICI exposure was not associated with COVID-19 mortality (odds ratio [OR] 0.93 [95% CI: 0.37-2.36]; I2=30%), severity (OR 1.15 [95% CI: 0.40-3.28]; I2=0%), and hospitalization (OR 1.35 [95% CI: 0.64-2.87]; I2=51%). However, we discovered that prior exposure to chemoimmunotherapy predicted COVID-19 severity (OR 8.19 [95% CI: 2.67-25.08]; I2=0%), albeit with small sample size. GRADE assessments resulted in moderate-quality evidence for mortality, while the other outcomes yielded very low-to-low-quality evidenceConclusion Our findings indicated that ICI treatment should not be adjourned nor terminated during the current pandemic. Rather, COVID-19 vigilance should be increased, especially in patients receiving chemoimmunotherapy. Further studies with larger ICI cohorts are required to confirm our findingsTrial registration number: This project has been prospectively registered at PROSPERO (registration ID: CRD42020202142) on 4 August 2020.

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“…Noch nicht abschließend geklärt ist die Frage nach dem Infektionsrisiko unter Behandlung mit Immuncheckpointinhibitoren. Es existiert aus den vergangenen Jahren Evidenz zu verschiedenen viralen Infektionen und deren Verlauf unter Immuncheckpointinhibition (Anti-PD1, Anti-CTLA4) [5]. Derzeit dominiert die Einschätzung, dass virale Infektionen, auch die COVID-19-Pandemie, keine generelle Kontraindikation für die Therapie mit Immuncheckpointinhibitoren darstellen.…”

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