ABSTRACT
Background: Smoking is the leading cause of cancer worldwide. Active smoking alters the inflammatory environment of the respiratory epithelium, increasing the production of potent pro-inflammatory cytokines that promote the recruitment of macrophages and neutrophils, leading to lung damage. We hypothesize that smoking-induced inflammation can impact on COVID-19 infection severity and mortality related to the proinflammatory cascade. Methods: Multicenter retrospective cohort of cancer patients (pts) with COVID-19 infection diagnosed by PCR/Ag detection (n=274) and CT-scan (N=13) in Mar-Apr/20r in 12 centers. Clinical and biological data were collected. Smoker was defined as active tobacco consumption and heavy smoker as >30 pack-year (PY). Primary endpoints were 30-day mortality rate and the rate of severe acute respiratory failure (SARF), defined by oxygen requirements >15 L/min. Results: A total of 287 pts were enrolled: 25 (9%) were active smokers, 127 (47%) were former and 116 (43%) never smoker. Among active smokers: 73% were heavy smokers, median age was 62y, 60% were male and median body mass index was 22. Regarding their comorbidities: 25% had hypertension, 8% cardiovascular disease, 28% chronic obstructive pulmonary disease and 24% diabetes. Thoracic tumors were the most common (52%), 72% had advanced disease and 56% were under systemic therapy. 92% of active smokers required hospitalization, 68% developed pneumonia and 58% required oxygen. Only 4% were escalated to the intensive care unit. Active smokers received treatment with hydroxychloroquine (91%), azithromycin (61%), antiviral therapy (33%) and steroids (29%). Only 4% received immunomodulatory drugs. SARF was the most common complication (25%) and no thromboembolic events were observed. A pro-inflammatory status was observed at COVID-19 diagnosis in active smokers, e.g. median of absolute neutrophil count was 6.35 (vs. 5.4), mean ferritin was 1269 (vs. 991) and D-Dimer was 2422 (vs. 1816);but with no significant differences. Overall mortality rate was 27%. Mortality rate was higher in active smokers (40% vs. 24% in non-smokers;p=0.08). Conclusions: Active smoking might be associated with severe COVID-19 infection and early death in cancer patients. Smoking induced-inflammation should be further explored. Legal entity responsible for the study: Aleix Prat. Funding: Has not received any funding. Disclosure: E. Auclin: Travel/Accommodation/Expenses: Mundifarma;Speaker Bureau/Expert testimony: Sanofi Genzime. S. Pilotto: Speaker Bureau/Expert testimony: Astra-Zeneca;Speaker Bureau/Expert testimony: Boehringer Ingelheim;Speaker Bureau/Expert testimony: Eli-Lilly;Speaker Bureau/Expert testimony: BMS. A. Prat: Honoraria (institution), Speaker Bureau/Expert testimony: Roche;Advisory/Consultancy, Speaker Bureau/Expert testimony: Pfizer;Honoraria (institution), Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis;Amgen;Speaker Bureau/Expert testimony: BMS;Honoraria (institution), Speaker Bureau/Expert testimony: Daiichi Sankyo;Nanostring;Advisory/Consultancy: Puma;Oncolytics Biotech;MSD;Honoraria (institution), Advisory/Consultancy: Lilly;Boehringer;Sysmex Europa GmbH;Medican Scientia inno. Research;Celgene;Astellas;Officer/Board of Directors: Breast International Group;Solti's Foundation;Actitud frente al cancer foundation. L. Mezquita: Speaker Bureau/Expert testimony, Research grant/Funding (self), Travel/Accommodation/Expenses: Bristol-Meyers Squibb;Speaker Bureau/Expert testimony: Tecnofarma;Honoraria (institution), Speaker Bureau/Expert testimony: Astrazeneca;Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche;Research grant/Funding (self): Boehringer Intelligence. All other authors have declared no conflicts of interest.