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

Abstract

ObjectivesTo 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.DesignMatched case-control study (REACT-SCOT).SettingPopulation of Scotland from 1 March 2020 to 28 January 2021.ParticipantsAll 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 measureSevere COVID-19, 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 5.3 (95% CI 5.0 to 5.7, p=4 × 10−527) in those with moderate risk conditions and 7.6 (95% CI 7.1 to 8.3, p=1 × 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 × 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 × 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 × 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.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.SummaryWhat is already known on this topic?Individuals designated as “clinically extremely vulnerable” – about 3% of the population – have been advised to shield themselves during the COVID-19 epidemicThe effectiveness of this shielding programme has not been evaluated.What this study addsHospital-acquired infection has made a substantial contribution to the burden of COVID-19 in the population, accounting for more than half of severe cases in early December 2020.For vulnerable individuals to be shielded, the risk of hospital-acquired infection must be reduced and support must be provided for other adults in the household to co-isolate with the vulnerable individual.Solid organ transplant recipients are at the highest risk; vaccination of household contacts should be considered for this group.

WasR< 1 before the English lockdowns? On modelling mechanistic detail, causality and inference about Covid-19

“…For example, in addition to the mismatches expected from not modelling hospital acquired infections (e.g. McKeigue et al, 2021), it seems likely that there was some on the ground variability in the severity of disease sufficient for hospitalization, and in rates of discharge, particularly early in the epidemic and when loads were high. For the hospital deaths we set κ = 2000, which gives a likelihood very close to Poisson.…”

“…Another difficulty is the problem of nosocomial infection (e.g. McKeigue et al, 2021), which became significant over the period of the apparent improvements, but is likely to reduce the apparent IFR, since patients infected in hospital, while vulnerable, are obviously likely to have lower mortality rates than patients admitted to hospital because their Covid infection had resulted in serious illness.…”

“…6. Within hospital transmission is not modelled, although hospital-acquired infections have been reported to account for a quarter of hospitalized cases at times in both waves (Discombe, 2020), reports which are corroborated by public NHS data (NHS, 2021), and there is good evidence that the actual figure was higher (McKeigue et al, 2021). This will compromise the hospital data fit.…”

Efficacy of two doses of COVID-19 vaccine against severe COVID-19 in those with risk conditions and residual risk to the clinically extremely vulnerable: the REACT-SCOT case-control study

“…As previously (1), to minimise ascertainment bias we pre-specified the primary outcome measure as severe COVID-19, defined as diagnosed cases with entry to critical care within 28 days of presentation or fatal outcome (any death within 28 days of a positive test or any death for which COVID-19 was coded as underlying cause). Cases and controls were classified into three broad risk categories: no risk condition; at least one of the moderate risk conditions designated by public health agencies (1); or eligible for shielding (3). For further analyses, the shielding category was subdivided as described previously into six categories: solid organ transplant, specific cancers, severe respiratory conditions, other rare conditions, on immunosuppressants, and additional conditions (3).…”

“…The REACT-SCOT matched case-control study was established by Public Health Scotland at the beginning of the epidemic to investigate risk factors for severe COVID-19 (1). Using this framework, we have reported on the relation of severe COVID-19 to risk conditions including those designated as clinically extremely vulnerable (CEV) and therefore eligible for the shielding programme in Scotland (1)(2)(3). We have previously reported a comparison of the efficacy of vaccination against severe COVID-19 between CEV people and those with moderate risk conditions or no risk conditions, based on data up to 16 March 2021 (4).…”