  We consider the recent surge of information on the potential benefits of
acid-suppression drugs in the context of COVID-19, with an eye on the
variability (and confusion) across the reported findings--at least as regards
the popular antacid famotidine. The inconsistencies reflect contradictory
conclusions from independent clinical-based studies that took roughly similar
approaches, in terms of experimental design (retrospective, cohort-based, etc.)
and statistical analyses (propensity-score matching and stratification, etc.).
The confusion has significant ramifications in choosing therapeutic
interventions: e.g., do potential benefits of famotidine indicate its use in a
particular COVID-19 case? Beyond this pressing therapeutic issue, conflicting
information on famotidine must be resolved before its integration in
ontological and knowledge graph-based frameworks, which in turn are useful in
drug repurposing efforts. To begin systematically structuring the rapidly
accumulating information, in the hopes of clarifying and reconciling the
discrepancies, we consider the contradictory information along three proposed
'axes': (1) a context-of-disease axis, (2) a degree-of-[therapeutic]-benefit
axis, and (3) a mechanism-of-action axis. We suspect that incongruencies in how
these axes have been (implicitly) treated in past studies has led to the
contradictory indications for famotidine and COVID-19. We also trace the
evolution of information on acid-suppression agents as regards the
transmission, severity, and mortality of COVID-19, given the many literature
reports that have accumulated. By grouping the studies conceptually and
thematically, we identify three eras in the progression of our understanding of
famotidine and COVID-19. Harmonizing these findings is a key goal for both
clinical standards-of-care (COVID and beyond) as well as ontological and
knowledge graph-based approaches.
