恶性实体肿瘤使用和未使用免疫检查点抑制剂治疗患者新型冠状病毒感染后临床特征的对比分析

Comparative Analysis of Clinical Characteristics of Patients with Malignant Solid Tumors Treated with and without Immunocheckpoint Inhibitors after COIVD-19 Infection

摘要: 背景：随着医学科学的不断发展，免疫检查点抑制剂(immune checkpoint inhibiter, ICIs)在恶性实体肿瘤中的应用越来越广泛。而新型冠状病毒肺炎(coronavirus disease 2019, COVID-19)作为一种可能引发肺炎的呼吸道疾病，在使用和未使用ICIs治疗的恶性实体肿瘤患者中临床表现是否存在差异是临床关注问题之一。虽然COVID-19不会暴发流行，但临床中仍时常可见，一旦患者合并感染，是否影响临床治疗决策，仍然是需要关注的问题，故本研究纳入感染后患者进行相关分析，以期为临床选择提供指导。目的：分析ICIs治疗组和非ICIs治疗组的恶性实体肿瘤患者感染新型冠状病毒后的临床表现，探索两组之间临床表现差异以及可能的原因。方法：回顾性收集2022-12至2023-02期间就诊于陕西省肿瘤医院内一科的实体肿瘤患者，按照是否接受免疫检查点抑制剂分为ICIs治疗组和非ICIs治疗组，使用卡方检验分析两组新冠感染发生率是否存在差别。同时，在阳性患者中，使用卡方检验分析两组发热症状、咳嗽咳痰症状及肺炎发生率之间是否存在差异，使用两独立样本t检验分析两组患者阳性持续时间。结果：最终纳入191例住院实体肿瘤患者，其中，ICIs治疗组68例，非ICIs治疗组123例，两组中阳性感染分别为57例和98例，COVID-19感染在两组中的发生率不具有统计学意义(p = 0.48)。其中，阳性患者共计155人，ICIs治疗组57人，非ICIs治疗组98人，两组发热发生率无统计学差异(p = 0.67)；阳性持续天数两组间无统计学差异(p = 0.79)；咳嗽咳痰症状两组间无统计学差异(p = 0.99)；复查胸部CT共计142例，ICIs治疗组中，肺炎发生率较非ICIs组升高，差异具有统计学意义(p = 0.03)；咳嗽咳痰症状与肺炎之间不存在相关性(p = 0.82)。结论：ICIs经治的实体肿瘤患者中COIVD-19感染后肺炎的发生率明显增加，可能与ICIs激活机体免疫使肺内免疫稳态失衡，增加淋巴结细胞肺内浸润，而COIVD-19感染后启动机体炎性因子释放，同样导致机体免疫功能失衡，两者相互作用相关。

Abstract: Background: With the continuous development of medical science, the application of immune checkpoint inhibitors (ICIs) in malignant solid tumors is becoming increasingly widespread. However, as a respiratory disease that may cause pneumonia, whether the clinical manifestations of novel coronavirus disease 2019 (COVID-19) in patients with malignant solid tumors treated with and without ICIs are different is one of the clinical concerns. Although COVID-19 does not have an outbreak, it is still commonly seen in clinical practice. Once a patient is co infected, whether it affects clinical treatment decisions remains a concern. Therefore, this study included post infection patients for relevant analysis in order to provide guidance for clinical selection. Objective: Therefore, the purpose of this study is to analyze the clinical manifestations of patients with malignant solid tumors infected with COIVD-19 in the ICIs treatment group and the non-ICIs treatment group, and explore the differences in clinical manifestations between the two groups and the possible reasons. Methods: Retrospectively collect the solid tumor patients who visited the First Department of Shaanxi Cancer Hospital from December 2022 to February 2023, and divide them into the ICIs treatment group and the non-ICIs treatment group according to whether they accept the inhibitors of the immune checkpoint, and use chi-square test to analyze whether there is a difference in the incidence of COVID-19 infection between the two groups. At the same time, among positive patients, we use chi-square test to analyze whether there are differences between the two groups in fever symptoms, cough and phlegm symptoms, and pneumonia incidence, and use the two-independent sample t test to analyze the positive duration. Results: Finally, 191 hospitalized solid tumor patients were included, including 68 in the ICIs treatment group and 123 in the non-ICIs treatment group. There were 57 and 98 positive infections in both groups, respectively. The incidence of COVID-19 infection in both groups was not statistically significant (p = 0.48). Among them, there were a total of 155 positive patients, including 57 in the ICIs treatment group and 98 in the non-ICIs treatment group. There was no statistically significant difference in the incidence of fever between the two groups (p = 0.67); There was no statistically significant difference in the duration of positivity between the two groups (p = 0.79); There was no statistically significant difference in cough and phlegm symptoms between the two groups (p = 0.99); A total of 142 chest CT cases were rechecked. Among the ICIs treatment group, the incidence of pneumonia was higher than that of the non-ICIs group, with a statistically significant difference (p = 0.03); There is no correlation between cough and sputum symptoms and pneumonia (p = 0.82). Conclusion: The incidence of pneumonia after COIVD-19 infection in solid tumor patients treated with ICIs is significantly increased, which may be due to the activation of the body’s immune system by ICIs, which leads to imbalance of immune homeostasis in the lungs and increases infiltration of lymph node cells in the lungs. However, COIVD-19 infection triggers the release of inflammatory factors in the body, which also leads to imbalance of immune function in the body. The interaction leads to a significant increase in the incidence of pneumonia.