key: cord-0957757-5ydwc1ig authors: Cui, Haoran; Liu, Jiaxin; Zhang, Leiliang title: The high expression of key components of inflammasome and pyroptosis might lead to severe COVID-19 infection in cancer patients date: 2022-02-03 journal: J Infect DOI: 10.1016/j.jinf.2022.01.043 sha: 09b04c29f1f468e07ef245519b04f9f0b43b746b doc_id: 957757 cord_uid: 5ydwc1ig nan  The expression levels of ASC were up-regulated in all cancer type we examined  All five NLRP3-inflammasome/pyroptosis components were up-regulated in LAML and PAAD Dear editor, Previous studies found that both the incidence of corona virus disease 2019 infection and the severe rate were high in cancer patients (1, 2) . Recent papers showed that the high expression level of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) host factors including the receptor and entry factors in cancer tissues could partially explain the COVID-19 susceptibility of cancer patients (3, 4) . However, why patients with cancer infected by SARS-CoV-2 more likely develop severe symptoms is not clear. PAAD and UCEC were significantly higher than that in normal tissues (Fig. 1D) . Interestingly, no cancer tissue contains lower expression level of ASC compared with normal tissues within the scope of current study. Cleaved gasdermin D (GSDMD) forms pores at the plasma membrane which allows for the release of IL-18, IL-1β and the influx of ions leading to pyroptosis (9) . GSDMD was up-regulated in CHOL, DLBC, GBM, head and neck squamous cell carcinoma (HNSC), LAML, PAAD, skin cutaneous melanoma (SKCM) and THYM, while GSDMD was down-regulated in ACC, KICH, LUSC, ovarian serous cystadenocarcinoma (OV), pheochromocytoma and paraganglioma (PCPG) and PRAD (Fig. 1E) . The symptoms of COVID-19 infection could be asymptomatic, mild, or severe. Studies have shown that cytokine storm induced by NLRP3-inflammasome caused more severe disease in COVID-19 patients. We found that ASC was up-regulated in all cancer types in current study, which could partially explain the severe symptoms in cancer patients. Interestingly, all five key components of NLRP3-inflammasome and pyroptosis we examined in this study were up-regulated in LAML and PAAD ( Fig. 2A and 2B), indicating the high severe COVID-19 rate in those two types of cancer patients infected with SARS-CoV-2. Previous studies explained the high infection rate of cancer patients through SARS-CoV-2 host factors. Here, we linked the COVID-19 severe symptoms to the up-regulation of key components of NLRP3-inflammasome and pyroptosis. Our results advanced the understanding on the link between COVID-19 and cancer, which will further alert the public to pay more careful attention to the patients with COVID-19. Fatality rate of COVID-19 in patients with malignancies: a sytematic review and meta-analysis Clinical characteristics and prognosis in cancer patients with COVID-19: A single center's retrospective study The COVID-19 susceptibility of cancer patients might due to the high expression of SARS-CoV-2 required host factors The high expression of SARS-CoV-2 cell receptors might lead to higher COVID-19 infection rates in cancer patients Inflammasome activation at the crux of severe COVID-19 GEPIA2021: integrating multiple deconvolution-based analysis into GEPIA A Genome-wide CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) Screen Identifies NEK7 as an Essential Component of NLRP3 Inflammasome Activation The PYRIN-CARD protein ASC is an activating adaptor for caspase-1 Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death ASC (D) and GSDMD (E) in cancer patients. ns 001. Fig. 2. All five key components of NLRP3-inflammasome and pyroptosis we examined were up-regulated in LAML (A) and PAAD (B) patients This work was supported by grants from Shandong Provincial Natural Science The authors declare that there are no conflicts of interest.