Cancer Management during COVID-19 Pandemic: Is Immune Checkpoint Inhibitors-Based Immunotherapy Harmful or Beneficial?

Abstract

The coronavirus disease 2019 (COVID-19) is currently representing a global health threat especially for fragile individuals, such as cancer patients. It was demonstrated that cancer patients have an increased risk of developing a worse symptomatology upon severe acute respiratory syndrome associated coronavirus-2 (SARS-CoV-2) infection, often leading to hospitalization and intensive care. The consequences of this pandemic for oncology are really heavy, as the entire healthcare system got reorganized. Both oncologists and cancer patients are experiencing rescheduling of treatments and disruptions of appointments with a concurrent surge of fear and stress. In this review all the up-to-date findings, concerning the association between COVID-19 and cancer, are reported. A remaining very debated question regards the use of an innovative class of anti-cancer molecules, the immune checkpoint inhibitors (ICIs), given their modulating effects on the immune system. For that reason, administration of ICIs to cancer patients represents a question mark during this pandemic, as its correlation with COVID-19-associated risks is still under investigation. Based on the mechanisms of action of ICIs and the current evidence, we suggest that ICIs not only can be safely administered to cancer patients, but they might even be beneficial in COVID-19-positive cancer patients, by exerting an immune-stimulating action.

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

“…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]. Nevertheless, a recent report by Di Cosimo et al stated that the occurrence of cytokine storm in COVID-19 patients was more likely to be driven by direct viral damage rather than immunemediated in ammation [40].…”

“…infection. ICI has exhibited immunity protection against several infectious agents [37], while also restoring cellular-mediated immunocompetence resulting in increased viral control [6,41]. In addition, ICI may enhance immune response to viral antigens without triggering adverse immune reactions [40], thus further suggesting the potential therapeutic utility of ICI.…”

“…In light of this, the question remains whether to postpone or continue active cancer treatment, including immune checkpoint inhibitor (ICI), which exerts immunomodulatory functions [5]. To the best of our knowledge, the current evidence on the effect of prior ICI treatment on cancer patients infected with COVID-19 remains equivocal [6][7][8]. Therefore, this meta-analysis aims to explore the association between ICI and COVID-19 outcomes in cancer patients, thus providing the best available evidence to guide real-time treatment decisions in such cases.…”

SARS-CoV-2 pathophysiology and its clinical implications: An integrative overview of the pharmacotherapeutic management of COVID-19

“…The consequence of COVID-19 infection in cancer patients is also dependent on the type of treatment to which they are subjected. The studies cited above refer only to a worse prognosis for COVID-19-positive cancer patients treated surgically or with chemotherapy [Lian W et al, 2020]; however little is known regarding the dual interaction existing between COVID-19 infection and the new immune checkpoint inhibitors (ICIs) in cancer patients ( Vivarelli et al, 2020 ). These ICIs, and in particular anti-PD-1/PD-L1 and anti-CTLA-4 antibodies, are currently used in a wide cohort of patients for the treatment of different advanced and metastatic tumors ( Christofi et al, 2019 ).…”

“…In this context, a growing body of evidence has elucidated some molecular mechanisms behing the interaction of ICIs, and in particular anti-PD-1/PD-L1, with SARS-CoV-2 and the immune cells responsible for the onset of cytokine storm in COVID-19 patients. Through the analysis of previous studies performed on mice and humans, a recent review of the literature proposed a possibile mechanism of action of anti-PD-1 treatement in contrasting viral infections ( Vivarelli et al, 2020 ). Indeed, the administration of anti-PD-1/PD-L1 agents (e.g.…”