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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.

SUBMITTER: Tembhare PR

PROVIDER: S-EPMC8652640 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:To determine if early CNS symptoms are associated with severe coronavirus disease 2019.DesignA retrospective, observational case series study design.SettingElectronic health records were reviewed for patients from five healthcare systems across the state of Florida, United States.PatientsA clinical sample (n = 36,615) of patients with confirmed diagnosis of coronavirus disease 2019 were included. Twelve percent (n = 4,417) of the sample developed severe coronavirus disease 2019, defined as requiring critical care, mechanical ventilation, or diagnosis of acute respiratory distress syndrome, sepsis, or severe inflammatory response syndrome.InterventionsNone.Measurement and main resultsWe reviewed the electronic health record for diagnosis of early CNS symptoms (encephalopathy, headache, ageusia, anosmia, dizziness, acute cerebrovascular disease) between 14 days before the diagnosis of coronavirus disease 2019 and 8 days after the diagnosis of coronavirus disease 2019, or before the date of severe coronavirus disease 2019 diagnosis, whichever came first. Hierarchal logistic regression models were used to examine the odds of developing severe coronavirus disease 2019 based on diagnosis of early CNS symptoms. Severe coronavirus disease 2019 patients were significantly more likely to have early CNS symptoms (32.8%) compared with nonsevere patients (6.11%; χ2[1] = 3,266.08, p < 0.0001, φ = 0.29). After adjusting for demographic variables and pertinent comorbidities, early CNS symptoms were significantly associated with severe coronavirus disease 2019 (odds ratio = 3.21). Diagnosis of encephalopathy (odds ratio = 14.38) was associated with greater odds of severe coronavirus disease 2019; whereas diagnosis of anosmia (odds ratio = 0.45), ageusia (odds ratio = 0.46), and headache (odds ratio = 0.63) were associated with reduced odds of severe coronavirus disease 2019.ConclusionsEarly CNS symptoms, and specifically encephalopathy, are differentially associated with risk of severe coronavirus disease 2019 and may serve as an early marker for differences in clinical disease course. Therapies for early coronavirus disease 2019 are scarce, and further identification of subgroups at risk may help to advance understanding of the severity trajectories and enable focused treatment.

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

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