correction inclusion criteria to PaO2/FiO2 below 350

Section 6.1: Inclusion criteria 1 removed and changed to COVID-19 diagnosis confirmed by antigen detection test and/or PCR and/or positive serology, or any emerging and validated diagnostic laboratory test for COVID-19 within this period. Section 1.5, 6.1: Extra Inclusion criteria: In some patients, it may be impossible to get a confident laboratory confirmation of COVID-19 diagnosis after 24h of hospital admission because viral load is low and/or problems with diagnostic sensitivity. In those cases, in absence of an alternative diagnosis, and with highly suspect bilateral ground glass opacities on recent (<24h) chest-CT scan (confirmed by a radiologist and pulmonary physician as probable COVID-19), a patient can be enrolled as probable COVID-19 infected. In all cases, this needs confirmation by later seroconversion Section 10: redefining sampling.due to addition of extra study sites. Section 8.1.5: better definition of duration of treatment Section 13.6: Despite the known safety profile of the study medications and study design, a DSMB is foreseen. General: Better definition of progressive disease: Progression to ARDS requiring mechanical ventilation is removed and replaced by: progressive disease requiring mechanical ventilatory support. General: Safety follow-up period is 10-20 weeks. Section 1.6.1, 8.1.5: Nebulizing is preferably done in an isolation negative pressure chamber, and if not, personnel should use an FFP2 mask. Patient should self-administer the medication and where possible, the room should not be entered within one hour after administration. Section 9.4: arterial blood gas mandatory at D1, D6 and FU Section 9.2, 9.4: if arterial blood gas is taken within 24h before first dose administration, as described in point° the arterial blood gas of screening can be used as D1 value Section 7.1.2: If a patient decides to leave hospital before day 6 of the study, for example because of clinical improvement, the oxygenation parameters at da

addition site

Section 9.4: Schematic overview of the data collection & interventions: lay-out was updated to improve clarity. Section 9.4: Added to flowchart, as per standard of care during follow-up visit: - 6 minutes walk test (Section 4.2) - HRCT scan to assess HRCT fibrosis score Section 10: - Clarification on study blood sampling added: EDTA only to be collected in selected sites. - processing details of samples were updated from 1500RPM or 410g to 1770 g. General: Typo’s were corrected. General: “requiring invasive mechanical ventilatory support”: wording “invasive” changed to “non-invasive / invasive“. Section 9.2: “on page 36” added to “as described in point°”. Section 9.4: clinical assessments added to flowchart: Ordinal Scale Category, Clinical Sign Sore, NEWS2 Score, SOFA Score, HScore, CURB-65, APACHE II and Glasgow Coma Scale. Section 3.2, 4.2: Mean change of SOFA score between day 1 and day 6 or between day 1 and day 11: updated to day 10. Mean change NEWS2 score between day 1 and day 6 or between day 1 and day 11: updated to day 10.

PICF v 1.7 dd07-jul-2020NL PICF v1.2 dd07-jul-2020FR PICF v1.2 dd07-jul-2020ENG

extension of recruitment period until 30-dec-2020 extension of recruitment number from 80 to 82

extension of total study period until 30-jun-2021 extension of recruitment number from 82 to 88 (replacement of screenfailures)

General: Typo’s were corrected. Section 1.5 and 6.2 -patients on high dose systemic steroids (> 20 mg methylprednisolone or equivalent) Replaced by -patients on high dose systemic steroids (> 20 mg methylprednisolone or equivalent) for COVID-19 unrelated disorder AND - Patients with serum ferritin >2000 mcg/ml (which will exclude ongoing HLH) Replaced by - Patients with serum ferritin >2000 mcg/L (which will exclude ongoing HLH) Section 3.3 and Sections 4.1 and 4.2 Further clarification of Primary and Secondary endpoint measurements Section 4.3: Enumeration and description of planned pharmacodynamic measurements (biomarkers, flow cytometry, immunomonitoring) Section 9.3.6: Clarification on role of VIB-UGent Center for Inflammation Research Clarification of which pharmacodynamic parameters, biomarkers, immunomonitoring assays will be performed Definitions of follow-up visit were made consistent. Section 11: Shipment process of optional samples was updated. Section 11.3: Typo selected centres corrected to all centres Better description of sample handling and analysis by centers Secion 11.4 Clarification of sample storage and shipment, including role of VIB Section 12.3: correction statistical analysis team Further clarification on statistical analysis performed Section 13.4: Access to data and data ownership better defined Section 14.7: Period of first DSUR reporting modified to 1 year + 60 days