Shared inflammatory pathways and therapeutic strategies in COVID-19 and cancer immunotherapy

Abstract

COVID-19, the syndrome caused by the infection with SARS-CoV-2 coronavirus, is characterized, in its severe form, by interstitial diffuse pneumonitis and acute respiratory distress syndrome (ARDS). ARDS and systemic manifestations of COVID-19 are mainly due to an exaggerated immune response triggered by the viral infection. Cytokine release syndrome (CRS), an inflammatory syndrome characterized by elevated levels of circulating cytokines, and endothelial dysfunction are systemic manifestations of COVID-19. CRS is also an adverse event of immunotherapy (IMTX), the treatment of diseases using drugs, cells, and antibodies to stimulate or suppress the immune system. Graft-versus-host disease complications after an allogeneic stem cell transplant, toxicity after the infusion of chimeric antigen receptor-T cell therapy and monoclonal antibodies can all lead to CRS. It is hypothesized that anti-inflammatory drugs used for treatment of CRS in IMTX may be useful in reducing the mortality in COVID-19, whereas IMTX itself may help in ameliorating effects of SARS-CoV-2 infection. In this paper, we focused on the potential shared mechanisms and differences between COVID-19 and IMTX-related toxicities. We performed a systematic review of the clinical trials testing anti-inflammatory therapies and of the data published from prospective trials. Preliminary evidence suggests there might be a benefit in targeting the cytokines involved in the pathogenesis of COVID-19, especially by inhibiting the interleukin-6 pathway. Many other approaches based on novel drugs and cell therapies are currently under investigation and may lead to a reduction in hospitalization and mortality due to COVID-19.

Lower response to BNT162b2 vaccine in patients with myelofibrosis compared to polycythemia vera and essential thrombocythemia

“…Intriguingly, NK-cell dysfunction and T-cell exhaustion were reported in MPN patients even in the absence of treatment, potentially resulting in an impaired response to SARS-CoV-2 infection, whereas suppressive effects by ruxolitinib in NK-cells and T-cells, which were reported too, resulted in its use in several COVID-19 clinical trials [ 5 ]. Two systematic reviews and one meta-analysis confirmed the protective role of JAK inhibitors in reducing the risk of mortality in hospitalized patients with COVID-19 [ 6 , 7 ]. So far, and with results opposite to ours, there is only one published study on 21 patients with myeloproliferative neoplasms which has demonstrated polyfunctional T-cell responses with no detrimental effect exerted by ruxolitinib, and significant higher post-vaccine anti-S IgG and neutralizing antibody titers in myelofibrosis compared to patients with other MPN subsets, after a single dose of BNT162b2 mRNA vaccine [ 8 ].…”

Immune-Mediated Mechanisms in Patients Testing Positive for SARS-CoV-2: Protocol for a Multianalysis Study

“…Only genetic depletion of the IFNα/β receptor protected mice from death. In addition, other cytokines released by inflammatory monocytes, such as IL1β, IL-6 (also confirmed in COVID-19 patients recently [ 18 ]), and inducible nitric oxide synthase, appeared important.…”

Drug-Target Network Study Reveals the Core Target-Protein Interactions of Various COVID-19 Treatments

“…This drug showed clinical status improvement, although it was not statistically significant, in a phase 3 trial in patients with cardiometabolic risk factors [ 63 ]. Finally, (3) ruxolitinib is a JAK inhibitor with a similar mechanism to baricitinib [ 64 ].…”