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A complete response to the challenge of COVID-19 requires diagnosis, prevention, and treatment strategies. Until recently, the treatment arm has included largely ineffective, often unproven medications with minimal impact on disease outcomes. The earlier experimental therapies are now giving way to approved antiviral drugs with a demonstrated capacity for SARS-CoV-2 suppression, and more are on the way. New oral antiviral drugs will expand treatment options for persons with COVID-19 and, if used early, become the first line of defense for reducing hospitalization, mortality, and virus spread. Several oral medications have been approved for treating COVID-19 on an emergency use basis in the United States (US), European Union (EU), United Kingdom (UK), China, Russia, and India, with other countries now facilitating regulatory reviews and approvals. Here, we compare the risk/benefit profiles of three leading oral antiviral drugs: Favipiravir, Molnupiravir, and Paxlovid. These compounds have distinct features supporting their targeted use by persons with COVID-19 disease.

Objectives. COVID-19 is a contagious multisystem inflammatory disease caused by a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We have studied the efficacy of Aprotinin (nonspecific serine proteases inhibitor) and Avifavir or Hydroxychloroquine (HCQ) combinations for the therapy of COVID-19. Methods. Three prospective single-center (cohorts 1 – 3) studies included participants with moderate COVID-19-related pneumonia, laboratory-confirmed SARS-CoV-2 and admitted to the hospitals. Patients received combinations of intravenous (IV) Aprotinin (1,000,000 KIU daily, 3 days) and HCQ (cohort 1), inhalation (inh) treatment with Aprotinin (625 KIU 4 times per day, 5 days) and HCQ (cohort 2) or IV Aprotinin (1,000,000 KIU daily for 5 days) and Avifavir (cohort 3). Results. In the cohorts 1 – 3, the combination therapy showed 100% efficacy in preventing the transfer of patients (n = 30) to the intensive care unit (ICU). The effect of combination therapy in the cohort 3 was the most prominent and the median time to SARS-CoV-2 elimination was 3.5 days (IQR 3.0 – 4.0), normalization of CRP concentration was 3.5 days (IQR 3 – 5), of D-dimer concentration - 5 days (IQR 4 – 5); body temperature - 1 day (IQR 1 – 3), improvement in clinical status or discharge from the hospital - 5 days (IQR 5 – 5), and improvement in lung lesions of patients on 14 day - 100%. Conclusions. The administration of Aprotinin combinations prevented the transfer of moderate COVID-19 patients to the ICU for mechanical ventilation (ALV) or non-invasive ventilation (NIV) and by shortening of their hospital stay.