key: cord-323603-99d0wv1h
authors: Nunez Garcia, B.; Blanco Clemente, M.; Morito Aguilar, A.; Martinez Cutillas, M.; Traseira, C.; Garitaonaindia, Y.; Aguado Noya, R.; Alfaro Autor, C.; Visedo, G.; franco, F.; calvo de juan, V.; Provencio Pulla, M.
title: Real-world data: Cancer and SARS-CoV-2 infection
date: 2020-09-30
journal: Annals of Oncology
DOI: 10.1016/j.annonc.2020.08.1797
sha: 
doc_id: 323603
cord_uid: 99d0wv1h

nan

Methods: EGFR, KRAS, BRAF, BRCA1/2 mutation testing of advanced lung adenocarcinoma, metastatic colorectal, metastatic melanoma and ovarian cancer patients were performed by qPCR and NGS. NGS was also used for panel testing of hereditary breast cancer and cancers associated with Lynch syndrome. IORS's analytical output during the two-month long state of emergency was compared to the two-month period prior to the outbreak.

Results: A 57% reduction (188 vs. 81) in the total number of patients that were referred to IORS for targeted molecular testing was detected (EGFR -prior to initiation of TKI therapy 55 vs 26 patients, at progression 21 vs 4; KRAS 73 vs 34, BRAF 39 vs. 17). Due to the prolonged transport of the necessary consumables and the fact that two essential laboratory personnel were absent from the Institute (sensitive category and obligatory quarantine), somatic testing for BRCA1/2 mutations was not performed at all during the state of emergency. All new high-risk individuals with the referral for genetic counselling had to be postponed, so the lockdown was used to test the patients who were waiting for results. The number of NGS analyses for highrisk individuals increased by 50 % during the outbreak (36 vs. 72) and post-test genetic counselling was successfully performed by phone and/or web calls.

The SARS-CoV-2 pandemic had a profound negative effect on the overall diagnostic output of the centralized molecular diagnostics for cancer patients and high-risk individuals in Serbia. This effect will be further evaluated through the analysis of both the survival and quality of life of the cancer patients that were unable to receive targeted therapies in a timely efficient manner. The only positive effect of the pandemic was that the waiting lists for genetic testing of high-risk individuals were shortened.

Legal entity responsible for the study: The authors. Background: The COVID-19 pandemic has impacted significantly on health systems across the globe. It has been reported to have higher incidence and to be associated with worse outcomes in patients with cancer. Beaumont Hospital is a large Dublin-based teaching hospital which was at the centre of the Irish outbreak of COVID-19.

Methods: During the period 11 th March to 15 th May 2020, patients diagnosed with COVID-19 infection who were attending Beaumont Hospital for systemic anti-cancer therapy were included. Data were collected by chart review. Statistical analyses were performed using SPSS. Cancer-related prognosis was estimated using the Palliative Prognostic Score (PAP) with a score 11 associated with a 30-day survival of <30%.

Results: In total, 717 patients attended oncology services for cancer directed treatment during the study period. 27 of these patients were diagnosed with COVID-19 based on RT-PCR. A further 4 patients were diagnosed clinically due to characteristic symptoms and radiology. The median age was 60 (38-84). 12 (39%) were female. The most common cancer type was lung n¼9 (29%). 21 (67%) had metastatic disease; 4 (13%) locally advanced disease and 6 (19%) were being treated with curative intent. Of the 31 patients diagnosed with COVID-19, 25 (80%) were hospitalised and none were admitted to intensive care. In total, 12/31 (41%) died, of which 5 (41%) had lung cancer, 10 (83%) had an PS of 3 and 3 (25%) had received systemic anti-cancer treatment in the last 30 days of life. The median age was 66 (38-84). 4 (33%) were female. All had incurable, locally advanced or metastatic disease. The mean time from diagnosis to death was 9.5 days. Those with an ECOG performance status (PS) 3 were more likely to die than those with PS 2 (p<0.001).Compared to those who recovered, patients who died from COVID-19 had higher mean number of organs affected by cancer (3.7 vs. 1.8, p¼0.015) and higher mean PAP score (9.6 vs. 1.5, p<0.001).

Conclusions: Patients with cancer who contracted COVID-19 and died had more sites of metastatic disease, a poorer performance status, and a higher Palliative Prognostic Score. The presence of multi-organ involvement appears to predict for poorer outcomes in COVID-19 positive cancer patients.

Legal entity responsible for the study: The authors.

Funding: Has not received any funding. Conclusions: Patients with cancer, especially lung cancer, and SARS-CoV2 infection have a worse overall prognosis than the general population. Objective parameters such as LDH, CRP at admission, Brescia index or CURB-65 should alert us to a more serious evolution and suggest early an early intensive care unit (ICU) admission.

Legal entity responsible for the study: The authors.

Funding: Has not received any funding. 

Background: The COVID-19 pandemic remains of pressing concern for patients with cancer. Mortality from COVID-19 is predicted by age and co-morbidities, but the relative contribution of cancer is poorly understood. As a tertiary academic hospital serving a large general and cancer population in a COVID-19 epicentre, we are uniquely placed to investigate this. We report data from our study, comparing cancer patients to an age-and sex-matched non-cancer cohort.

Methods: Patients with laboratory confirmed COVID-19 from 1 March to 31 May 2020 were included. Patients with a history of solid cancer were compared to an ageand sex-matched non-cancer cohort. Patients with haematological malignancies were excluded.

We identified 94 patients with cancer and 226 patients without cancer. In univariate analysis, age, South Asian ethnicity and co-morbidities predicted mortality (see table) . More in the cancer cohort had died compared to the non-cancer cohort (43.6% vs 34.1%). The higher mortality among cancer patients was statistically significant among those aged 70 years and above (OR 2.28, 1.14-4.50, p ¼ 0.02). After adjusting for age, ethnicity and co-morbidities, a history of cancer was an independent predictor of mortality following COVID-19 (HR 1.57, 95% CI:1.04-2.4, p ¼ 0.03). Patients with active malignancy also had similarly increased adjusted mortality (HR 1.64, 95% CI: 1.03 e 2.6, p ¼ 0.04). Increasing age (HR 1.49 every 10 years, 95% CI:1.25-1.8, p <0.001), South Asian ethnicity (HR 2.92, 95% CI:1.73-4.9, p <0.001) and cerebrovascular disease (HR 1.93, 95% CI:1.18-3.2, p ¼ 0.008) were also confirmed as independent predictors of mortality.

Conclusions: Along with known risk factors, cancer confers an independent risk for mortality in COVID-19. Taken together, our findings support the need to continue 'shielding' patients with cancer from exposure to COVID-19 infection. Increasing age and co-morbidity should take precedence when weighing up risk factors for severe COVID-19 infection in cancer patients.

Legal entity responsible for the study: University College London Hospitals NHS Foundation Trust. Background: SARS-CoV-2 infection is the cause of the respiratory illness COVID-19, which presents most frequently with respiratory symptoms. SARS-CoV-2 cell entry requires interactions with ACE2 and TMPRSS2 on the surface of the host cell. Cancer patients and, specifically, those with thoracic malignancies seem to experience poorer clinical outcomes.

Methods: We utilized bulk and single-cell transcriptional data from a combination of normal and malignant tissues and cells from aerodigestive and respiratory tracts to explore mechanisms governing the expression of ACE2 and TMPRSS2. Additionally, we determined the effect of EMT induction, ZEB1 modulation, and SARS-CoV-2 infection on ACE2 expression.

Results: Our bulk data suggests that aerodigestive and lung cancer models express a broad range of ACE2 and TMRPSS2, particularly in epithelial cells, and would serve as good models for studying SARS-CoV-2 infection. We assessed the relationship between ACE2 and epithelial differentiation in numerous datasets, and found consistent positive correlations with transcriptional and microRNA signifiers of epithelial differentiation. The miR-200 family e zinc finger E-box-binding homeobox 1 (ZEB1) pathway, which is an established regulator of EMT, also directly regulates ACE2 expression, likely via putative ZEB1 repressor sites located in the ACE2 promoter. Furthermore, SARS-CoV-2 infection reduces ACE2 expression and shifts cells to a more mesenchymal phenotype with loss of EPCAM and upregulation of ZEB1 and other EMT-associated genes.

Conclusions: ACE2-positive cells are almost exclusively epithelial and unexpectedly rare, considering the devastating impact of this infection. Following viral entry, SARS-CoV-2 infection induces molecular changes within the cells that are reminiscent of EMT, including increased ZEB1. ZEB1, in turn, appears to directly repress the expression of ACE2. This SARS-CoV-2-induced ACE2 deficiency, compounded by the downregulation of genes, including claudins, which play a critical role in restricting epithelial and endothelial permeability, exposes respiratory cells to increased risk of edema and acute respiratory distress syndrome (ARDS).

Legal entity responsible for the study: The authors. 

Patients with thoracic cancers affected by the coronavirus disease 2019 (COVID-19)

Mer) family receptor tyrosine kinase, is a known mediator of epithelial to mesenchymal transition (EMT) and therapeutic resistance in non-small cell lung cancer (NSCLC) and other cancers. Additionally, AXL plays a role in efficient Ebola and Zika viral entry and Table: 1734P Univariate analysis of risk factors for mortality

Elevated AXL expression following SARS-CoV-2 infection in nonsmall cell lung cancer