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Observational Study
. 2021 Jan 4;10(1):1854424.
doi: 10.1080/2162402X.2020.1854424.

Immunological alternation in COVID-19 patients with cancer and its implications on mortality

Guangyao Cai  1 , Yue Gao  1 , Shaoqing Zeng  1 , Yang Yu  1 , Xingyu Liu  1 , Dan Liu  1 , Ya Wang  1 , Ruidi Yu  1 , Aakash Desai  2 , Chunrui Li  3 , Qinglei Gao  1
Affiliations
Observational Study

Immunological alternation in COVID-19 patients with cancer and its implications on mortality

Guangyao Cai et al. Oncoimmunology. .

Abstract

Patients with malignancy were reportedly more susceptible and vulnerable to Coronavirus Disease 2019 (COVID-19), and witnessed a greater mortality risk in COVID-19 infection than noncancerous patients. But the role of immune dysregulation of malignant patients on poor prognosis of COVID-19 has remained insufficiently investigated. Here we conducted a retrospective cohort study that included 2,052 patients hospitalized with COVID-19 (Cancer, n = 93; Non-cancer, n = 1,959), and compared the immunological characteristics of both cohorts. We used stratification analysis, multivariate regressions, and propensity-score matching to evaluate the effect of immunological indices. In result, COVID-19 patients with cancer had ongoing and significantly elevated inflammatory factors and cytokines (high-sensitivity C-reactive protein, procalcitonin, interleukin (IL)-2 receptor, IL-6, IL-8), as well as decreased immune cells (CD8 + T cells, CD4 + T cells, B cells, NK cells, Th and Ts cells) than those without cancer. The mortality rate was significantly higher in cancer cohort (24.7%) than non-cancer cohort (10.8%). By stratification analysis, COVID-19 patients with immune dysregulation had poorer prognosis than those with the relatively normal immune system both in cancer and non-cancer cohort. By logistic regression, Cox regression, and propensity-score matching, we found that prior to adjustment for immunological indices, cancer history was associated with an increased mortality risk of COVID-19 (p < .05); after adjustment for immunological indices, cancer history was no longer an independent risk factor for poor prognosis of COVID-19 (p > .30). In conclusion, COVID-19 patients with cancer had more severely dysregulated immune responses than noncancerous patients, which might account for their poorer prognosis. Clinical Trial: This study has been registered on the Chinese Clinical Trial Registry (No. ChiCTR2000032161).

Keywords: COVID-19; SARS-CoV-2; cancer; immune response; mortality; prognosis.

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Figures

Figure 1.
Figure 1.
Flowchart of study design
Figure 2.
Figure 2.
Longitudinal changes in immunological indices in 6 weeks from COVID-19 onset. Grey dashed lines represent the limit of the normal range of every index. Time points with * indicated statistically significant differences between the cancer cohort and non-cancer cohort. hsCRP = high-sensitivity C-reactive protein. IL-2 R = interleukin-2 receptor. IL-6 = interleukin-6. IL-8 = interleukin-8. IL-10 = interleukin-10. TNF-α = tumor necrosis factor α. NK cells = natural killer cells
Figure 3.
Figure 3.
Comparison of immunological indices between groups stratified by history of cancer and survival outcome. Grey dashed lines represent the limit of the normal range of every immunological index. In all immunological indices, deceased patients had a significantly higher level of the immune disorder compared with discharged patients both in the cancer cohort and non-cancer cohort (Mann-Whitney U test, p < .05). hsCRP = high-sensitivity C-reactive protein. IL-2 R = interleukin-2 receptor. IL-6 = interleukin-6. IL-8 = interleukin-8. IL-10 = interleukin-10. TNF-α = tumor necrosis factor α. NK cells = natural killer cells
Figure 4.
Figure 4.
Kaplan-Meier survival plots according to different immunological indices stratified by the normal range. Log-rank test showed that stratification of immunological indices could distinguish the prognosis both in cancer and non-cancer cohort. hsCRP = high-sensitivity C-reactive protein. IL-2 R = interleukin-2 receptor. IL-6 = interleukin-6. IL-8 = interleukin-8. IL-10 = interleukin-10. TNF-α = tumor necrosis factor α. NK cells = natural killer cells
Figure 5.
Figure 5.
Kaplan-Meier survival plots for the whole included population (a), population after propensity-score matching 1 (b), and population after propensity-score matching 2 (c). Matching items of propensity-score matching 1 consisted of sex, age, symptoms, and comorbidities. Matching items of propensity-score matching 2 consisted of sex, age, symptoms, comorbidities, and immune indices including hsCRP, PCT, ferritin, TNF-α, IL-1β, IL-2 R, IL-6, IL-8, IL-10, lymphocytes. The prognosis was compared between cancer and non-cancer cohort with log-rank test
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Publication types

Grants and funding

The study was supported by the National Science and Technology Major Sub-Project [2018ZX10301402-002], the Technical Innovation Special Project of Hubei Province [2018ACA138], the National Natural Science Foundation of China [81772787, 81873452, and 81974405], and the Fundamental Research Funds for the Central Universities [2019kfyXMBZ024]. The sponsors of the study had no role in the study design, data collection, data analysis, data interpretation, or writing of the report. The corresponding author (Q-L G) had full access to all data in the study and final responsibility for the study.