ABSTRACT
BackgroundClinically vulnerable individuals have been advised to shield themselves during the COVID-19 epidemic. The objectives of this study were to investigate: (1) the risk of severe COVID-19 in those eligible for shielding, and (2) the relation of severe COVID-19 to transmission-related factors in those in shielding and the general population. MethodsAll 178578 diagnosed cases of COVID-19 in Scotland from 1 March 2020 to 18 February 2021 were matched for age, sex and primary care practice to 1744283 controls from the general population. This dataset (REACT-SCOT) was linked to the list of 212702 individuals identified as eligible for shielding. Severe COVID-19 was defined as cases that entered critical care or were fatal. ResultsWith those without risk conditions as reference category, the univariate rate ratio for severe COVID-19 was 3.21 (95% CI 3.01 to 3.41) in those with moderate risk conditions and 6.3 (95% CI 5.8 to 6.8) in those eligible for shielding. The highest rate was in solid organ transplant recipients: rate ratio 13.4 (95% CI 9.6 to 18.8). Risk of severe COVID-19 increased with the number of adults but decreased with the number of school-age children in the household. Severe COVID-19 was strongly associated with recent exposure to hospital (defined as 5 to 14 days before presentation date): rate ratio 12.3 (95% CI 11.5 to 13.2) overall. To test for causality, a case-crossover analysis was undertaken; with less recent exposure only (15 to 24 days before first testing positive) as reference category, the rate ratio associated with recent exposure only was 5.9 (95% CI 3.6 to 9.7). The population attributable risk fraction for recent exposure to hospital peaked at 50% in May 2020 and again at 65% in December 2020. ConclusionsThe effectiveness of shielding vulnerable individuals was limited by the inability to control transmission in hospital and from other adults in the household. For solid organ transplant recipients, in whom the efficacy of vaccines is uncertain, these results support a policy of offering vaccination to household contacts. Mitigating the impact of the epidemic requires control of nosocomial transmission.
ABSTRACT
ObjectivesTo investigate the relation of severe COVID-19 to prior drug prescribing. DesignMatched 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. SettingScottish population. Main outcome measureSevere COVID-19, defined by entry to critical care or fatal outcome. ParticipantsAll 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. ResultsSevere 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. ConclusionsSevere 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. RegistrationENCEPP number EUPAS35558 What is already known on this topicTwo previous studies have examined the relationship of severe COVID-19 to drugs for the cardiovascular system. This is the first systematic study of the relationship of severe COVID-19 to prior drug prescribing. What this study addsSevere 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. These results support earlier warnings that these drug classes that these drugs might increase susceptibility to COVID-19, and reinforce existing guidance on reducing overprescribing of these drug classes.
