Comprehensive immune cell profiling depicts an early immune response associated with severe COVID-19 disease in cancer patients

Tembhare, Prashant R; Sriram, Harshini N; Chatterjee, Gaurav; Khanka, Twinkle; Gokarn, Anant; Mirgh, Sumeet; Rajendra, Akhil; Chaturvedi, Anumeha; Ghogale, Sitaram G; Deshpande, Nilesh; Girase, Karishma; Dalvi, Kajal; Rajpal, Sweta; Patkar, Nikhil; Trivedi, Bhakti; Joshi, Amit; Murthy, Vedang; Shetty, Nitin; Nair, Sudhir; More, Ashwini; Kamtalwar, Sujeet; Chavan, Preeti; Bhat, Vivek; Bhat, Prashant; Subramanian, Papagudi G; Gupta, Sudeep; Khattry, Navin

Recent studies have highlighted multiple immune perturbations related to SARS-CoV-2 infection-associated respiratory disease (COVID-19). Some of them were associated with immunopathogenesis of the severe COVID-19. However, the reports on immunological indicators of severe COVID-19 in the early phase of infection in patients with comorbidities like cancer are scarce. We prospectively studied ~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 into non-severe disease. We evaluated the association of immune response parameters with severe COVID-19. By principal component analysis, three immune signatures defining characteristic immune response in COVID-19 patients were found. Immune cell perturbations, in particular, decreased levels of circulating dendritic cells (DC) along with reduced levels of CD4 T-cell subsets such as regulatory T cells (Tregs), Th1, Th9 and relative expansion of effector NK cells were significantly associated with severe-COVID-19. Compared to patients without cancer, the levels of terminal effector-CD4 T, Tregs, Th9, effector NK cells, B cells, intermediate-type monocytes, and myeloid-DC 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 the 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 disease in cancer patients without intensive chemo/immunotherapy.