Associations of severe COVID-19 with polypharmacy in the REACT-SCOT case-control study

McKeigue, P. M.; Kennedy, S.; Weir, A.; Bishop, J.; McGurnaghan, S. J.; McAllister, D.; Robertson, C.; Wood, R.; Lone, N.; Murray, J.; Caparrotta, T. M.; Smith-Palmer, A.; Goldberg, D.; McMenamin, J.; Ramsay, C.; Guthrie, B.; Hutchinson, S.; Colhoun, H. M.

Objectives -- To investigate the relation of severe COVID-19 to prior drug prescribing. Design -- Matched case-control study (REACT-SCOT) based on record linkage to hospital discharges since June 2015 and dispensed prescriptions issued in primary care during the last 240 days. Setting -- Scottish population. Main outcome measure -- Severe COVID-19, defined by entry to critical care or fatal outcome. Participants -- All 4272 cases of severe COVID-19 in Scotland since the start of the epidemic, with 36948 controls matched for age, sex and primary care practice. Results -- Severe COVID-19 was strongly associated with the number of non-cardiovascular drug classes dispensed. This association was strongest in those not resident in care homes, in whom the rate ratio (95% CI) associated with dispensing of 12 or more drug classes versus none was 10.8 (8.7, 13.2), and was not accounted for by treatment of conditions designated as conferring increased risk. Of 17 drug classes postulated at the start of the epidemic to be "medications compromising COVID", all were associated with increased risk of severe COVID-19. The largest effect was for antipsychotic agents: rate ratio 4.14 (3.39, 5.07). Other drug classes with large effects included proton pump inhibitors (rate rato 2.19 (1.70, 2.80) for >= 2 defined daily doses/day), opioids (3.62 (2.65, 4.94) for >= 50 mg morphine equivalent/day) and gabapentinoids. These associations persisted after adjusting for covariates, and were stronger with recent than with non-recent exposure. Conclusions -- Severe COVID-19 is associated with polypharmacy and with drugs that cause sedation, respiratory depression or dyskinesia, have anticholinergic effects or affect the gastrointestinal system. These associations are not easily explained by co-morbidity. Although the evidence for causality is not conclusive, these results support existing guidance on reducing overprescribing of these drug classes and limiting inappropriate polypharmacy as a potential means of reducing COVID-19 risk. Registration -- ENCEPP number EUPAS35558