Amendment 1 (Version 2) The Protocol Version 1 was amended to: • reflect inclusion of South Africa as a participating country, which also resulted in: o adjustment of sample volumes for cell subpopulations and cytokines, o removal of the Coordinating Investigator role, • provide clarification of: o inclusion of mildly symptomatic SARS-CoV-2 subjects, o inclusion, exclusion and discharge criteria, o procedures in the event of moderate or severe COVID-19 symptoms, o subject numbering procedures, o trial medication packaging, preparation and dosing, o cytokines / chemokines to be analyzed • use throat swabbing rather than throat wash for SARS-CoV-2 sampling at Screening, • add ECG and vital sign assessments on Day 1, 3, and 5 at 1h, 2h, and 4h post-dosing • address minor typos in the text.

Amendment 2 (Version 3) The Protocol Version 2 was amended to reflect the requests of the Paul-Ehrlich-Institut. These primarily required: • Description or clarification of: o Exclusion criteria (#11) o Stopping criteria o Withdrawal criteria o Endpoint descriptions o Eligibility of subjects with mild COVID-19 disease o Start of COVID-19 symptoms o Documentation of local tolerability AEs o Follow-up of unblinded subjects • Removal of: o Provision to replace early termination subjects • Addition of: o Further sentinel subjects o Extended follow-up of subjects with moderate/severe COVID-19

Amendment 3 (Version 4) The Protocol Version 3 was amended to reflect the requests of the Ethics Committee in addition to some administrative changes. These primarily required: • addition and clarification of timing and documentation of body temperature, respiratory rate, pulse rate, and SpO2 measures after subject discharge from the unit, • description of measures to be taken in the event of worsening COVID-19 symptoms after discharge from the unit, • clarification of the selection criteria relating to: o documentation of informed consent, o the use of oral contraceptives as a highly effective methods of contraception, o the exclusion of vulnerable subjects, • inclusion of FSH determination for potentially post-menopausal women, • clarification that IL-6 and IL-10 will be determined in both the general cytokine panel in the immediate safety analysis, • addition of subject training for taking readings, documentation of results and provision of equipment for use during out-patient follow up period (and subsequent collection at the End-of-Trial examination), • inclusion of a subject diary and diary review at appropriate timepoints, • clarification of withdrawal criteria, • use of PBMCs instead of monocytes for ex-vivo stimulation experiments.

Amendment 4 (Version 5) The Protocol Version 4 was amended to remove the exclusion of SARS-CoV-2 vaccinated subjects and to exclude the subjects with any vaccination in the 14-day period prior to the trial or planned for any time during the trial period. The sentinel treatment approach was extended to distinguish between vaccinated and non-vaccinated subjects. Subgroup analyses of efficacy and safety, based on vaccination status at Baseline, were therefore also included.

Amendment 5 (Version 6) The Protocol Version 5 was amended primarily to adjust the population selection criteria for: • All subjects by: o increasing the threshold for fever from ≥38°C to moderate or severe (≥38.5°C) o permitting mild cough, o fully SARS-CoV-2 vaccinated status is defined according to local requirements, o reduced minimum time since last smoking from 1 year to 3 months prior to enrollment, o Adjustment of exclusion criterion #11 for laboratory parameters. • Fully vaccinated subjects only by: o extending the permitted age range from 18 to 55 years up to 18 to 65 years, o removing the minimum viral genome copy number, o remove the maximum time period between first positive SARS-CoV-2 test by RT-PCR, qRT-PCR, or antigen test and enrollment (Day -1). In addition, stratification by SARS by qRT-PCR viral load titer was removed.