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the acute setting of COVID-19 compared with the doses approved for use in atypical hemolytic uremic syndrome.
Other treatments for COVID-19 (with unknown or unproven mechanisms of action) Acalabrutinib and ibrutinib Acalabrutinib and ibrutinib are bruton tyrosine kinase inhibitors, used for CLL and lymphoma treatment. Ex vivo analysis revealed significantly elevated BTK activity (BTK regulates macrophage signalling and activation), as evidenced by autophosphorylation, and increased IL-6 production in blood monocytes from patients with severe COVID-19 compared with blood monocytes from healthy volunteers. In a pilot study, 19 patients with severe COVID-19 received the BTK inhibitor acalabrutinib (Roschewski 2020). Within 10-14 days, oxygenation improved “in a majority of patients”, often within 1-3 days, and inflammation markers and lymphopenia normalized quickly in most patients. At the end of acalabrutinib treatment, 8/11 (72.7%) patients in the supplemental oxygen cohort had been discharged on room air. These results suggest that targeting excessive host inflammation with a BTK inhibitor can be a therapeutic strategy. A confirmatory RCT is underway. Some reports have speculated about a protective effect of ibrutinib, another BTK inhibitor (Thibaud 2020).
ASS/Aspirin Aspirin may help (a little bit). In a retrospective, observational cohort study of 412 adult patients admitted with COVID-19 to multiple US hospitals between March and July, 98 (24%) received aspirin within 24 hours of admission or 7 days prior to admission. Aspirin use had a crude association with less mechanical ventilation (36% vs. 48%, p = 0,03) and ICU admission (39% vs. 51%, p = 0,04), but no crude association with in-hospital mortality (26% vs. 23%, p = 0,51). After adjusting for 8 confounding variables, aspirin use was independently associated with decreased risk of mechanical ventilation (adjusted HR 0,56, 95% CI: 0,37-0,85, p = 0,007), ICU admission (adjusted HR 0,57, 95% CI: 0,38-0,85, p = 0,005), and in-hospital mortality (adjusted HR 0,53, 95% CI: 0,31-0,90, p = 0,02). According to the authors, a sufficiently powered randomized controlled trial is needed. The RECOVERY trial includes ASS as an option.
COVID Reference ENG 006.9
