The bradykinin-2 receptor antagonist, icatibant, improves lung function in patients with SARS-CoV2 associated ARDS - First results of a prospective off-label use patient-related observational study. Contact: Johannes Tebbe University Hospital OWL – Campus Lippe Klinikum Lippe Röntgenstrasse 18 34560 Detmold Germany E-Mail: johannes-josef.tebbe@klinikum-lippe.de Co-Authors: Nidhi-Su-Ann Kulamadayil-Heidenreich Holger Heidenreich Torsten Hansen Stephan Gielen Date of data Collection: 03/2020/ - 05/2021 Geographic location: The data were collected in the district of Lippe in Germany Keywords: COVID19-ARDS, Icatibant Data and file overview: The Icatibant source data file contains all the data for the patients we included in the analysis. The table shows the contents in German in the headings of the individual columns. Here, the normal ranges of laboratory values and dimensions are indicated for the laboratory values. Each row in the table represents the data for one patient. Column A: Age of the patient Column B: Gender Column C: Date of admission to the clinic Column D to V: Laboratory values of each patient with progression determinations. Column W: blood group Column Y & Z: values of the SARC-CoV2 smear with ct-value Column AA: Imaging data (chest X-ray). Column AB: previous diseases Column AD: course of ventilation therapy and oxygen application Column AE-AH: respiratory rates in the course Column AI-AL: data for calculation of the Horowitz ratio during the course of therapy The data table titled "Horowitz table" contains the calculated Horowitz ratio values of the individual patients. The basis for the calculation is the source data from the columns AI-AL of the "Icatibant-source-Table". The other data are self-explanatory. Methodilogical information: In an open-label observational study SARS-CoV2-positive COVID19 patients with moderate to severe ARDS received icatibant as off label use following informed consent. The study protocol was approved by the local ethics committee of the Medical Association of Westphalia-Lippe, Münster, Germany and conducted in accordance with the ethical principles of the Helsinki Declaration (DRKS00025792). All treated patients evaluated SARS-CoV2 positive (via rt-PCR) on admission to the hospital and had continuous documentation of all known COVID19 associated prognostic parameters as well as documentation of lung function via clinically measurable oxygenation (O2 substitution requirement, respiratory rate). At the time of icatibant substitution, symptom onset was at least 6 days but a maximum of 12 days ago. All patients presented with moderate to severe COVID19 disease with lung involvement in terms of COVID19-ARDS at the start of treatment. The manifestation of ARDS was confirmed according to the applicable Berlin criteria for ARDS. The Horowitz ratio was used to define the severity of the ARDS present: Horowitz-ratio = paO2/(FiO2) mmHg [Horowitz ratio associated with a) mild ARDS: 300 -201 mmHg; b) moderate ARDS: 200 – 101 mmHg; c) severe ARDS: <100 mmHg] The Horowitz ratio was calculated for each individual COVID19-ARDS patient at inclusion in the study and 24 hours after Icatibant substitution. Typical pneumonic infiltrates were documented in the lung X-ray of all patients. Icatibant (Firazyr, Shire Pharmaceuticals Ireland) was administered subcutaneously at a total dose of 60mg (2 x 30mg) twice, 6 hours apart. All COVID19-associated parameters were subsequently further documented until endpoints were reached. O2 substitution requirements to achieve a peripheral oxygen saturation of >90 mmHg and respiratory rate were evaluated in the observation immediately before and 24 hours after completion of icatibant substitution. Endpoints defined were discharge from hospital and the need for mechanical invasive ventilation. Patients whose hypertension was treated with an ACE inhibitor were not included in the study. Statistical analysis of the data was automated (Sigma Stat, Jandel Corporation). The calculation of the necessary number of cases and the test power was done automatically (G-Power Version 3.1.9.6; 1992-2020; University Kiel, Mannheim & Düsseldorf – Germany). The data of all studies were analyzed by One Way ANOVA of ranks (*) and differences between groups were evaluated by an all pairwise multiple comparison procedure (Dunn´s method; #). P < 0.05 was considered significant. In the statistical analysis, the values of individual patients were tested in pairs (baseline vs. icatibant). In addition, the statistical comparison was made between the three different ARDS groups (pre-icatibant vs. post-icatibant).