Emergency drug use in a pandemic: Harsh lessons from COVID-19

Abstract

The scientific and clinical communities have both experienced several harsh lessons on clinical care management and drug development during the COVID-19 pandemic. Here, we discuss several key lessons learned and describe a framework within which our two communities can work together and invest in to improve future pandemic responses. ll

Auxora vs. placebo for the treatment of patients with severe COVID-19 pneumonia: a randomized-controlled clinical trial

“…In patients with severe COVID-19 pneumonia, broad dysregulated immune responses have been identified with patients showing elevations in a range of proinflammatory cytokines [ 11 – 18 ]. These pathophysiologic events suggest that treatments with broad-based immunomodulatory effects may be more effective in treating COVID-19 pneumonia than those targeting specific immune pathways to prevent disease progression [ 11 – 19 ]. One such potential treatment is Auxora, a calcium release-activated calcium (CRAC) channel inhibitor.…”

What Should Be Learned From Repurposed Antivirals Against SARS-CoV-2?

“…Later studies showed that some patients infected with SARS-CoV-2 developed severe pneumonia and ARDS (Grant et al, 2021 ). Consequently, both antiviral and immunomodulatory drugs were contemplated and administered early in the pandemic (Martinez, 2020 ; Cross et al, 2021 ). Early studies (Tay et al, 2020 ) searched for parallelisms between SARS-CoV-2-related pneumonia and pneumonias connected to other human coronavirus diseases, such as severe acute respiratory syndrome (SARS-CoV) and Middle East respiratory syndrome (MERS-CoV).…”

“…However, the pathobiology of SARS-CoV-2-related pneumonia seems to be distinct from pneumonia caused by other respiratory viral and bacterial pathogens; the SARS-CoV-2-related pneumonia displays unusual clinical features and has a longer clinical course than severe pneumonia (Gattinoni et al, 2020 ; Grant et al, 2021 ). An accurate clinical characterization of SARS-CoV-2 infections, based on known clinical syndromes, is critical for the identification of effective therapies (Cross et al, 2021 ).…”

“…Remarkably, most of the repurposed drugs tested during this pandemic were administered off-label and outside of properly designed observational or clinical trials. However, unsuccessful approaches might reduce the public trust in evidence-based medicine (Cross et al, 2021 ). Therefore, clinical trials and methodologies for identifying effective drugs should be designed based on methodologies with the highest likelihood of success.…”

“…Consequently, repurposing immunomodulatory therapies might be more difficult than initially thought. Additionally, immunomodulatory therapies that might be useful for severe COVID-19 might be harmful in mild or moderate COVID-19, where the immune system can work effectively to control viral replication and disease (Cross et al, 2021 ).…”