Novel treatments and trials in COVID-19

Abstract Coronavirus disease 2019 (COVID-19), the disease arising from the beta coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has presented a major challenge to health-care systems and societies across the world. Although previous highly pathogenic coronaviruses have emerged, namely severe acute respiratory syndrome coronavirus 1 and Middle East respiratory syndrome coronavirus, neither had the spread nor the persistence to result in large clinical trials of drug therapy. Much of our therapeutic knowledge in these viruses was therefore informed by inference from observational, in vitro, and experimental model studies. As a result, when SARS-CoV-2 emerged with a noted high morbidity and mortality, initial therapeutic drug treatment was often empiric. There are currently over 4400 trials concerning COVID-19 registered on the World Health Organization international clinical trials registry, and while not all these are interventional therapeutic trials, this illustrates the desire of the international clinical-scientific community to develop systematic and evidence-based approaches for the management of this major threat. This chapter discusses the broad strategies of therapeutic pharmacological approaches suggested, namely antiviral therapy, antiinflammatories, and immunomodulatory. Nonpharmacological approaches are also to be discussed. Then, it reviews the approaches to trials and trial design, the development and use of core outcome sets, and regulation of trials in pandemic settings. It reviews the publication and preprint availability of completed trials before discussing the ethics of empiric treatment outside the context of trials.