ABSTRACT
The coronavirus disease 2019 (COVID-19) pandemic caused by infection with SARS-CoV-2 has led to more than 600 000 deaths worldwide. Patients with severe disease often experience acute respiratory distress characterized by upregulation of multiple cytokines. Immunomodulatory biological therapies are being evaluated in clinical trials for the management of the systemic inflammatory response and pulmonary complications in patients with advanced stages of COVID-19. In this review, we summarize the clinical pharmacology considerations in the development of immunomodulatory therapeutic proteins for mitigating the heightened inflammatory response identified in COVID-19.
Subject(s)
Coronavirus Infections/drug therapy , Immunologic Factors/administration & dosage , Pneumonia, Viral/drug therapy , Proteins/administration & dosage , Betacoronavirus/isolation & purification , COVID-19 , Coronavirus Infections/epidemiology , Coronavirus Infections/immunology , Drug Development , Humans , Immunologic Factors/pharmacology , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/immunology , Proteins/immunology , Proteins/pharmacology , SARS-CoV-2 , COVID-19 Drug TreatmentABSTRACT
Numerous drugs are being investigated for the treatment of COVID-19, including antivirals and therapies targeting complications related to COVID-19. The clinical presentation of COVID-19 varies from mild fever, cough, and dyspnea in the early stages of disease to severe complications such as acute respiratory distress syndrome, systemic hyperinflammation, and sepsis. A thorough understanding of the disease pathogenesis and the disease complications is essential to developing effective therapies to treat this potentially life-threatening disease. This review offers key clinical pharmacology considerations involved in the development of small molecules for the treatment of COVID-19. They are based on the major observed disease complications that impact drug absorption, distribution, metabolism, and elimination. We also address considerations regarding potential drug interactions, alternative routes and methods of administration, and dosing in patients on hemodialysis.
Subject(s)
Antiviral Agents/therapeutic use , COVID-19 Drug Treatment , Drug Development , Antiviral Agents/pharmacology , COVID-19/complications , COVID-19/virology , Drug Interactions , HumansABSTRACT
This literature review aims to provide a comprehensive current summary of the pathogenesis, clinical features, disease course, host immune responses, and current investigational antiviral and immunomodulatory pharmacotherapies to facilitate the development of future therapies and measures for prevention and control.