Relation of severe COVID-19 in Scotland to transmission-related factors and risk conditions eligible for shielding support: REACT-SCOT case-control study (preprint)

ABSTRACT

* Objectives - 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. * Design - Matched case-control study (REACT-SCOT). * Setting - Population of Scotland from 1 March 2020 to 28 January 2021. * Participants - All 160307 diagnosed cases of COVID-19 and 1564782 controls matched for age, sex and primary care practice, linked with all 204913 individuals identified as eligible for shielding by Public Health Scotland. * Main outcome measure - Severe COVID-19, defined as cases that entered critical care or were fatal. * Results - With those without risk conditions as reference category, the univariate rate ratio for severe COVID-19 was 5.3 (95% CI 5.0 to 5.7, p=4 x 10-527) in those with moderate risk conditions and 7.6 (95% CI 7.1 to 8.3, p=1 x 10-527) in those eligible for shielding. The highest rate was in solid organ transplant recipients rate ratio 13.6 (95% CI 9.6 to 19.2, p=8 x 10-50). In both the shielded and the general population, the 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 12.6 (95% CI 11.7 to 13.6, p=2 x 10-989) overall. In a case-crossover analysis 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 6.3 (95% CI 3.6 to 11.1, p=2 x 10-10). Among those eligible for shielding, the population attributable risk fraction (PARF) of severe cases for recent exposure to hospital was 36%. In the general population the PARF for recent exposure to hospital peaked at 46% in May 2020 and again at 64% in December 2020. * Conclusions - The 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.