Antiviral and immunomodulatory interferon-beta in high-risk COVID-19 patients: a structured summary of a study protocol for a randomised controlled trial

Objectives: The primary objective of the study is to demonstrate the efficacy of low-dose IFN-? in reducing the risk of SARS-CoV-2 recently infected elderly patients to progress towards severe COVID-19 versus control group within 28 days. Secondary objectives are:1)To assess the reduction in Intensive Care Unit (ICU) admission in patients treated with IFN-? versus control group within 28 days of randomization2)To assess the reduction in number of deaths in IFN- ? compared to control group (day 28)3)To evaluate the increase in proportion of participants returning to negative SARS-CoV-2 RT-PCR in IFN-? -treated versus control group at Day 14 and Day 284)To assess the increase in SARS-CoV-2-specific binding antibody titers in IFN-? compared to control group (day 28)5)To assess the safety of IFN-? -treated patients versus control group Trial design: Randomized, Open-Label, Controlled, Superiority Phase II Study. Patients, who satisfy all inclusion criteria and no exclusion criteria, will be randomly assigned to one of the two treatment groups in a ratio 2:1 (IFN-treated versus control patients). Randomization will be stratified by gender. Stratified randomization will balance the presence of male and female in both study arms. Participants: Male and female adults aged 65 years or older with newly diagnosed SARS-CoV-2 infection and mild COVID-19 symptoms are eligible for the study. The trial is being conducted in Rome. Participants will be either hospitalized or home isolated. A group of physicians belonging to the Special Unit for Regional Continued Care (USCAR), specifically trained for the study and under the supervision of the National Institute for Infectious Diseases "Lazzaro Spallanzani", will be responsible for the screening, enrolment, treatment and clinical monitoring of patients, thus acting as a bridge between clinical centers and territorial health management. Inclusion criteria are as follows:>= 65 years of age at time of enrolment;Laboratory-confirmed SARS-CoV-2 infection as determined by PCR, in any specimen < 72 hours prior to randomization;Subject (or legally authorized representative) provides written informed consent prior to initiation of any study procedures;Understands and agrees to comply with planned study procedures;Agrees to the collection of nasopharyngeal swabs and venous blood samples per protocol;Being symptomatic for less than 7 days before starting therapy;NEWS2 score <=2. Exclusion criteria are as follows:Hospitalized patients with illness of any duration, and at least one of the following:Clinical assessment (evidence of rales/crackles on exam) and SpO2 <= 94% on room air at rest or after walking test,ORAcute respiratory failure requiring mechanical ventilation and/or supplemental oxygen;Patients currently using IFN-? (e.g., multiple sclerosis patients);Patients undergoing chemotherapy or other immunosuppressive treatments;Patients with chronic kidney diseases;Known allergy or hypersensitivity to IFN (including asthma);Any autoimmune disease (resulting from patient anamnesis);Patients with signs of dementia or neurocognitive disorders;Patients with current severe depression and/or suicidal ideations;Being concurrently involved in another clinical trial;HIV infection (based on the anamnesis);Use of any antiretroviral medication;Impaired renal function (eGFR calculated by CKD-EPI Creatinine equation < 30 ml/min);Presence of other severe diseases impairing life expectancy (e.g. patients are not expected to survive 28 days given their pre-existing medical condition);Any physical or psychological impediment in a patient that could let the investigator to suspect his/her poor compliance;Lack or withdrawal of informed consent Intervention and comparator: Control arm: No specific antiviral treatment besides s