Safety perspectives on presently considered drugs for the treatment of COVID‐19

Abstract

Intense efforts are underway to evaluate potential therapeutic agents for the treatment of COVID‐19. In order to respond quickly to the crisis, the repurposing of existing drugs is the primary pharmacological strategy. Despite the urgent clinical need for these therapies, it is imperative to consider potential safety issues. This is important due to the harm–benefit ratios that may be encountered when treating COVID‐19, which can depend on the stage of the disease, when therapy is administered and underlying clinical factors in individual patients. Treatments are currently being trialled for a range of scenarios from prophylaxis (where benefit must greatly exceed risk) to severe life‐threatening disease (where a degree of potential risk may be tolerated if it is exceeded by the potential benefit). In this perspective, we have reviewed some of the most widely researched repurposed agents in order to identify potential safety considerations using existing information in the context of COVID‐19.

Patient and Citizen Participation in the Identification of Ethical Considerations Aiming to Address Uncertainty in the Evaluation of Promising Interventions in a Pandemic Context

“…Assessing the benefit-risk balance of promising interventions is a necessary step in decision-making regarding their access by the population ( 33 ). This assessment is distinct from the evaluation carried out by research ethics boards when approving the conduct of projects.…”

“…The perceived advantage of testing pre-existing interventions is that they have already been shown to be safe in a clinical research setting. However, it is still important to assess all the safety parameters of interventions in the particular setting of the current pandemic, including specific responses to the infectious agent and interactions with any concomitant intervention ( 33 ). Penman et al stressed the importance of assessing the benefit-risk balance of a given intervention before considering its use for COVID-19, especially if it is an intervention for preventing infections.…”

“…The assessment of what constitutes an acceptable benefit-risk balance varies from one individual to another and according to the context in which the person finds herself (e.g., life stage, the presence of comorbidities, and a predisposition to risks) ( 33 ). Papadimos et al argue that this assessment is value-laden and should, at the individual level, respect the patient's own values and priorities.…”

“…The characteristics that define such a profile include, among others, the form of the disease (mild, moderate or severe), the individual's overall health status (presence of comorbidities, stage of the disease, predisposition to complications), the care trajectory (pre-hospitalization, hospitalization, use of mechanical ventilation), and the intent of the promising intervention (a reduction in symptoms, in hospitalization, in the use of mechanical ventilation, or of mortality). In this regard, Penman et al propose that it might be acceptable to expose patients with severe late-stage COVID-19 disease to a given intervention, whereas this would not be acceptable at all to patients with a mild or moderate form of the disease ( 33 ). The benefit-risk balance of access to promising interventions could thus vary according to the patient's profile.…”

SARS-COV-2 Mpro conformational changes induced by covalently bound ligands

“…Currently, patients with COVID-19 are treated with repurposed drugs, which effects are often controversial due to the adverse events or the lack of fully proven clinical verification of their therapeutic effects. Therefore, there is still a need for novel treatments and the investigation of potential drug targets remains the cornerstone when designing novel, safe and effective antiviral drugs (Penman et al, 2020 ).…”