key: cord-0694292-839xdeb9 authors: Lee, L.; Starkey, T.; Cazier, J-B.; Kerr, R.; Middleton, G. title: COVID-19 mortality in hospitalized cancer patients is not significantly affected by chemotherapy or other anti-cancer treatments date: 2020-09-30 journal: Annals of Oncology DOI: 10.1016/j.annonc.2020.08.1742 sha: df8b29191b10659f41511df93f3cf5a00b120427 doc_id: 694292 cord_uid: 839xdeb9 nan We performed a large-scale integrated study of ACE2 and TMPRSS2 gene expression in 10,038 patients with cancer across and within organ systems, by normal versus tumor. We investigated its correlative pattern with clinical factors (age, gender, race, BMI and smoking history, etc.), HLA, immune signatures, and commensal microbiome. Results: Matched normal tissues generally display higher ACE2 and TMPRSS2 expression compared with tumor, with digestive organs expressing the highest levels. No consistent association was observed between clinical groups or HLA genotypes and ACE2/TMPRSS2 levels, after adjusting for tissue-specific expression. ACE2 expression showed a significant correlation with clinically relevant immune signatures including interferon-stimulated genes and the T cell-inflamed phenotype, and with macrophage cell subsets. Single-cell RNAseq analysis demonstrated little to no ACE2 or TMPRSS2 expression in lymphocytes or macrophages. ACE2 and TMPRSS2 showed a distinctive correlative pattern with 75 bacterial taxa in normal tissues particularly from colorectal cancers (gram-negative to positive ratio ¼ 2.6:1). LASSO regression models integrating multi-dimensional correlates revealed immune and microbiota are among the top-ranked features predicting ACE2 expression, while epithelial cell abundance is the dominant predictor for TMPRSS2. We investigated ACE2 and TMPRSS2 expression across clinical, genetic, immune, and microbiome domains. We identify novel associations with the microbiota and confirm host immunity associations with gene expression. We hope these data may better inform clinical considerations surrounding risk stratification and prevention approaches. Legal entity responsible for the study: The authors. We evaluated a screening strategy combining chest computed tomography (CT) and PCR for patients treated with radiotherapy (RT). Methods: A screening strategy was organized from March 18, in our RT department. An inspiratory breath hold chest acquisition was proposed during the CT simulation for RT. Images was reviewed by a radiologist according to the CO-RADS classification. A nasal swab with a polymerase chain reaction (PCR) assay was proposed by the radiation oncologist in case of evocative imaging or clinical context. For patients who were already undergoing RT at this time, a PCR was proposed in case of evocative symptoms and before concomitant chemotherapy. Background: The European SARS-CoV-2 pandemic had its first epicentre in Italy, particularly in the area of Bergamo. In spite of a significant mortality rate, in the majority of cases the spectrum of COVID-19 ranges from asymptomatic to mildly symptomatic infection. No information is available on the prevalence and clinical impact of asymptomatic or mildly symptomatic SARS-CoV-2 infection among actively treated cancer patients during pandemic. Methods: From April 1 st , 2020 to the end of the month, 560 consecutive and unselected patients, scheduled for anticancer treatment at our facility and without clinical suspicious of COVID-19, were evaluated and tested for SARS-CoV-2. We implemented a two-step diagnostics, including a rapid serological immunoassay for anti-SARS-CoV-2 IgG/IgM and a pharyngeal swab RT-PCR assay in case of IgM seropositivity. Results: In 560 patients, 172 (31%) resulted positive for SARS-CoV-2 IgM/IgG antibodies, regardless of type of cancer, stage and treatment. All IgM-seropositives were then tested with RT-PCR pharyngeal swabs and 55/146 (38%) proved to be SARS-CoV-2 carriers, with slightly difference b/w mildly symptomatic vs. asymptomatic patients (38 vs. 17). Therefore, the two-step procedure allowed the identification of 55 (10%) silent carriers in the whole study population and magnified the number needed to test (NNT) with the pharyngeal swab RT-PCR assay to detect a silent virus carrier (NNT: 2.6 vs. 10, with or without serological selection). At a very early follow up (8 wks) , in 114 SARS-CoV-2-seropostive/RT-PCR-negative patients, who continued their anticancer therapies, none but one developed a symptomatic COVID-19 illness. Conclusions: Among cancer patients, the two-step diagnostics strategy with serology followed by pharyngeal swab for asymptomatic or mildly symptomatic SARS-CoV-2 infection is feasible and effective and can help selecting cancer patients on treatment who might be silent carriers of the virus. The early safety outcome of patients previously exposed to SARS-CoV-2 supports the recommendation to continue active treatment, at least in the case of negative RT-PCR test. Legal entity responsible for the study: The authors. Funding: Has not received any funding. . This conjecture has considerable impact on the treatment of cancer patients and large, multi-centre data to support this assumption is lacking due to the contingencies of the pandemic. Results: An analysis of the first 800 cancer patients with symptomatic COVID-19 disease entered into the UKCCMP registry has been performed. Approximately half of these patients have a mild COVID-19 disease course (52%). Mortality was observed in 226 patients (28%) and risk of death was significantly associated with advancing patient age, sex (M>F) and the presence of other co-morbidities. Approximately one third had received cytotoxic chemotherapy within 4 weeks prior to testing positive for COVID-19. After adjusting for age, sex and comorbidities, recent receipt of chemotherapy had no significant effect on mortality from COVID-19 disease, when compared to cancer patients who had not received recent chemotherapy. No significant effect on mortality was also observed for patients with recent immunotherapy, hormonal therapy, targeted therapy or radiotherapy use. Conclusions: Mortality from COVID-19 in cancer patients appears to be principally driven by age, sex and co-morbidities. We are not able to identify evidence that cancer patients on cytotoxic chemotherapy or other anti-cancer treatment are at significantly increased risk of mortality from COVID-19 disease compared to those not on active treatment. Legal entity responsible for the study: Gary Middleton. Funding: University of Birmingham. Disclosure: All authors have declared no conflicts of interest. https://doi.org/10.1016/j.annonc.2020.08.1742 Determinants of mortality from SARS-CoV-2 infection in European cancer patients Azienda Ospedaliera Universitaria Maggiore della Carità Hospital Clínic de Barcelona University of Piemonte Orientale and Maggiore della Carita' Hospital In total, 36 patients (19%) patients were escalated to high-dependency or intensive care. At time of analysis, 59 patients had died (29%), 53 were discharged from hospital (26%) and 92 (45%) were in-hospital survivors. Mortality was higher in patients aged >/¼ 65 (36% versus 16%), in those with >/¼ 2 comorbidities (40% versus 18%) and developing >/¼ 1 complication from COVID-19 (38% versus 4%, p¼0.004). Multi-variable analyses confirmed age >/¼ 65 and >/¼ 2 co-morbidities to predict for patient mortality independent of tumor stage, active malignancy or anti-cancer therapy. Conclusions: In the early outbreak of SARS-CoV-2 infection in Europe co-morbid burden and advancing age Speaker Bureau/Expert testimony Expert testimony, received lecture fees : Bayer Healthcare; Travel/Accommodation/ Expenses: BMS; Advisory/Consultancy: Mina Therapeutics; EISAI Research grant/Funding (institution): MSD; BMS. A. Patriarca: Advisory/Consultancy: Takeda; Sanofi. G. Gaidano: Advisory/Consultancy, Speaker Bureau/Expert testimony: Janssen; Abbvie; Advisory/Consultancy Advisory/Consultancy: MSD Advisory/Consultancy: Array Biopharma; Astra Zeneca; Bayer; Beigene Inflection Biosciences Limited; Ipsen; Kura; Lilly; MSD Merck Serono; Merrimack; Merus; Molecular Partners; Novartis; Peptomics Advisory/Consultancy: Pfeizer; Honoraria (self), Advisory/ Consultancy, Research grant/Funding (self): Novartis Honoraria (self): MSD Oncology Travel/Accommodation/Expenses: Daiichi Sankyo; Advisory/Consultancy: BMS Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): Roche Advisory/Consultancy: Pierre Fabre; MSD Expert testimony: Daiichi Sankyo; Speaker Bureau/ Expert testimony: Teva; Gentili; Pfizer; AstraZeneca All other authors have declared no conflicts of interest 1680P SARS-CoV-2 infections in outpatients with cancer: Most infected patients are asymptomatic carriers without impact on chemotherapy Haemotology Oncology It is still unclear whether oncological patients harbor a higher risk for an infection with the SARS-CoV-2 and for developing severe forms of COVID-19 Furthermore, it is unclear whether an infection affects essential therapy treatment and if a therapy increases the risk for an infection Methods: We tested every patient (n¼1286) in 7 different oncology outpatient clinics from 04/15/2020 and 04/26/2020 for COVID-19 infection regardless of whether symptoms were present or not. Virus RNA was extracted using the MGIEasy extraction kit in combination with SP-960 robots and a RT qPCR was performed Noteworthy is the fact that 22 (55%) of the positively tested patients were undergoing systemic therapy of which 10 (45.5%) patients received chemotherapy and 4 (18.2%) patients received immunomodulating antibodies. Conclusions: A consequent testing for COVID-19 in cancer patients is obligate to identify asymptomatric positive carrier to separate this potential vector group from COVID negative patients since the majority (37/40) of positive patients was asymptomatic virus-carriers (92,5 %). The data we collected contrasts strongly the hypothesis that cancer patients are suspected to be highly vulnerable for SARS-CoV-2 infections. Only a minority (3/40) of positively tested tumor patients showed symptoms. An asymptomatic COVID-19 infection seems to have no impact on the further course of a chemotherapy