Comprehensive immune cell profiling depicts an early immune response associated with severe coronavirus disease 2019 in cancer patients

Abstract

Recent studies have highlighted multiple immune perturbations related to severe acute respiratory syndrome coronavirus 2 infection–associated respiratory disease [coronavirus disease 2019 (COVID‐19)]. Some of them were associated with immunopathogenesis of severe COVID‐19. However, reports on immunological indicators of severe COVID‐19 in the early phase of infection in patients with comorbidities such as cancer are scarce. We prospectively studied about 200 immune response parameters, including a comprehensive immune‐cell profile, inflammatory cytokines and other parameters, in 95 patients with COVID‐19 (37 cancer patients without active disease and intensive chemo/immunotherapy, 58 patients without cancer) and 21 healthy donors. Of 95 patients, 41 had severe disease, and the remaining 54 were categorized as having a nonsevere disease. We evaluated the association of immune response parameters with severe COVID‐19. By principal component analysis, three immune signatures defining characteristic immune responses in COVID‐19 patients were found. Immune cell perturbations, in particular, decreased levels of circulating dendritic cells (DCs) along with reduced levels of CD4 T‐cell subsets such as regulatory T cells (T regs ), type 1 T helper (Th1) and Th9; additionally, relative expansion of effector natural killer (NK) cells were significantly associated with severe COVID‐19. Compared with patients without cancer, the levels of terminal effector CD4 T cells, T regs , Th9, effector NK cells, B cells, intermediate‐type monocytes and myeloid DCs were significantly lower in cancer patients with mild and severe COVID‐19. We concluded that severely depleted circulating myeloid DCs and helper T subsets in the initial phase of infection were strongly associated with severe COVID‐19 independent of age, type of comorbidity and other parameters. Thus, our study describes the early immune response associated with severe COVID‐19 in cancer patients without intensive chemo/immunotherapy.

COVID-19 and lung cancer: update on the latest screening, diagnosis, management and challenges

“…Given that patients with lung cancer periodically undergo follow-up CT scans, a higher amount of COVID-19-suspicious imaging findings in asymptomatic patients is thus expected. 17 …”

“…Chronic immunosuppressive state in these patients limits their immune response, resulting in a reduced number of plasmacytoid dendritic cells that can respond to infection. 17 As a result of this compromised immune response, patients with cancer may experience prolonged viral clearance, leading to prolonged illness and worse outcomes.…”

“…Given that patients with lung cancer periodically undergo follow-up CT scans, a higher amount of COVID-19-suspicious imaging findings in asymptomatic patients is thus expected. 17 In patients with lung cancer receiving ICIs, the finding of pneumonitis constitutes a major challenge in identifying the correct diagnosis. Hence, a rapid and systematic differential diagnosis, focusing on druginduced pulmonary toxicity, tumor progression and SARS-CoV-2-induced pneumonitis is needed.…”

“…Chronic immunosuppressive state in these patients limits their immune response, resulting in a reduced number of plasmacytoid dendritic cells that can respond to infection. 17 As a result of this compromised immune response, patients with cancer may Data are generally conflicting regarding the use of ICIs during the pandemic, however, there is no proof to date of it being detrimental to patients. Therefore, whenever there is a survival benefit for patients, ICI treatments are better carried-out than withheld.…”

Immune-Guided Therapy of COVID-19

“…Moreover, cancer patients with COVID-19 showed significantly lower levels of terminal effector CD4 + T cells, Tregs, Th9, effector NK cells, B cells, intermediate-type monocytes, monocyte-derived DCs. These immune-cell perturbations were associated with both mild and severe COVID-19 (200).…”