Russell Beth, Moss Charlotte, George Gincy, Santaolalla Aida, Cope Andrew, Papa Sophie, Van Hemelrijck Mieke
Translational Oncology and Urology Research, King's College London, London, UK.
All authors contributed equally.
Ecancermedicalscience. 2020 Mar 27;14:1022. doi: 10.3332/ecancer.2020.1022. eCollection 2020.
Cancer and transplant patients with COVID-19 have a higher risk of developing severe and even fatal respiratory diseases, especially as they may be treated with immune-suppressive or immune-stimulating drugs. This review focuses on the effects of these drugs on host immunity against COVID-19.
Using Ovid MEDLINE, we reviewed current evidence for immune-suppressing or -stimulating drugs: cytotoxic chemotherapy, low-dose steroids, tumour necrosis factorα (TNFα) blockers, interlukin-6 (IL-6) blockade, Janus kinase (JAK) inhibitors, IL-1 blockade, mycophenolate, tacrolimus, anti-CD20 and CTLA4-Ig.
89 studies were included. Cytotoxic chemotherapy has been shown to be a specific inhibitor for severe acute respiratory syndrome coronavirus in in vitro studies, but no specific studies exist as of yet for COVID-19. No conclusive evidence for or against the use of non-steroidal anti-inflammatory drugs (NSAIDs) in the treatment of COVID-19 patients is available, nor is there evidence indicating that TNFα blockade is harmful to patients in the context of COVID-19. COVID-19 has been observed to induce a pro-inflammatory cytokine generation and secretion of cytokines, such as IL-6, but there is no evidence of the beneficial impact of IL-6 inhibitors on the modulation of COVID-19. Although there are potential targets in the JAK-STAT pathway that can be manipulated in treatment for coronaviruses and it is evident that IL-1 is elevated in patients with a coronavirus, there is currently no evidence for a role of these drugs in treatment of COVID-19.
The COVID-19 pandemic has led to challenging decision-making about treatment of critically unwell patients. Low-dose prednisolone and tacrolimus may have beneficial impacts on COVID-19. The mycophenolate mofetil picture is less clear, with conflicting data from pre-clinical studies. There is no definitive evidence that specific cytotoxic drugs, low-dose methotrexate for auto-immune disease, NSAIDs, JAK kinase inhibitors or anti-TNFα agents are contraindicated. There is clear evidence that IL-6 peak levels are associated with severity of pulmonary complications.
癌症患者和接受移植的患者感染新型冠状病毒肺炎(COVID-19)后,发生严重甚至致命性呼吸系统疾病的风险更高,尤其是因为他们可能正在接受免疫抑制或免疫刺激药物治疗。本综述重点关注这些药物对宿主抗COVID-19免疫力的影响。
我们使用Ovid MEDLINE检索了免疫抑制或免疫刺激药物的现有证据:细胞毒性化疗、低剂量类固醇、肿瘤坏死因子α(TNFα)阻滞剂、白细胞介素-6(IL-6)阻断剂、Janus激酶(JAK)抑制剂、IL-1阻断剂、霉酚酸酯、他克莫司、抗CD20和CTLA4-Ig。
共纳入89项研究。体外研究表明细胞毒性化疗是严重急性呼吸综合征冠状病毒的特异性抑制剂,但目前尚无针对COVID-19的具体研究。对于非甾体抗炎药(NSAIDs)用于治疗COVID-19患者,尚无确凿的支持或反对证据,也没有证据表明在COVID-19背景下TNFα阻断对患者有害。已观察到COVID-19可诱导促炎细胞因子生成并分泌细胞因子,如IL-6,但没有证据表明IL-6抑制剂对调节COVID-19有有益影响。尽管JAK-STAT通路中有潜在靶点可用于冠状病毒治疗,且冠状病毒患者体内IL-1明显升高,但目前尚无证据表明这些药物在治疗COVID-19中起作用。
COVID-19大流行给病情严重患者的治疗决策带来了挑战。低剂量泼尼松龙和他克莫司可能对COVID-19有有益影响。霉酚酸酯的情况不太明确,临床前研究数据相互矛盾。没有确凿证据表明特定的细胞毒性药物、用于自身免疫性疾病的低剂量甲氨蝶呤、NSAIDs、JAK激酶抑制剂或抗TNFα药物是禁忌的。有明确证据表明IL-6峰值水平与肺部并发症的严重程度相关。