Rapid Epidemiological Analysis of Comorbidities and Treatments as risk factors for COVID-19 in Scotland (REACT-SCOT): A population-based case-control study

Background The objectives of this study were to identify risk factors for severe coronavirus disease 2019 (COVID-19) and to lay the basis for risk stratification based on demographic data and health records. Methods and findings The design was a matched case-control study. Severe COVID-19 was defined as either a positive nucleic acid test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the national database followed by entry to a critical care unit or death within 28 days or a death certificate with COVID-19 as underlying cause. Up to 10 controls per case matched for sex, age, and primary care practice were selected from the national population register. For this analysis-based on ascertainment of positive test results up to 6 June 2020, entry to critical care up to 14 June 2020, and deaths registered up to 14 June 2020-there were 36,948 controls and 4,272 cases, of which 1,894 (44%) were care home residents. All diagnostic codes from the past 5 years of hospitalisation records and all drug codes from prescriptions dispensed during the past 240 days were extracted. Rate ratios for severe COVID-19 were estimated by conditional logistic regression. In a logistic regression using the age-sex distribution of the national population, the odds ratios for severe disease were 2.87 for a 10-year increase in age and 1.63 for male sex. In the case-control analysis, the strongest risk factor was residence in a care home, with rate ratio 21.4 (95% CI 19.1-23.9,p= 8 x 10(-644)). Univariate rate ratios for conditions listed by public health agencies as conferring high risk were 2.75 (95% CI 1.96-3.88,p= 6 x 10(-9)) for type 1 diabetes, 1.60 (95% CI 1.48-1.74,p= 8 x 10(-30)) for type 2 diabetes, 1.49 (95% CI 1.37-1.61,p= 3 x 10(-21)) for ischemic heart disease, 2.23 (95% CI 2.08-2.39,p= 4 x 10(-109)) for other heart disease, 1.96 (95% CI 1.83-2.10, p = 2 x 10(-78)) for chronic lower respiratory tract disease, 4.06 (95% CI 3.15-5.23,p= 3 x 10(-27)) for chronic kidney disease, 5.4 (95% CI 4.9-5.8,p= 1 x 10(-354)) for neurological disease, 3.61 (95% CI 2.60-5.00,p= 2 x 10(-14)) for chronic liver disease, and 2.66 (95% CI 1.86-3.79,p= 7 x 10(-8)) for immune deficiency or suppression. Seventy-eight percent of cases and 52% of controls had at least one listed condition (51% of cases and 11% of controls under age 40). Severe disease was associated with encashment of at least one prescription in the past 9 months and with at least one hospital admission in the past 5 years (rate ratios 3.10 [95% CI 2.59-3.71] and 2.75 [95% CI 2.53-2.99], respectively) even after adjusting for the listed conditions. In those without listed conditions, significant associations with severe disease were seen across many hospital diagnoses and drug categories. Age and sex provided 2.58 bits of information for discrimination. A model based on demographic variables, listed conditions, hospital diagnoses, and prescriptions provided an additional 1.07 bits (C-statistic 0.804). A limitation of this study is that records from primary care were not available. Conclusions We have shown that, along with older age and male sex, severe COVID-19 is strongly associated with past medical history across all age groups. Many comorbidities beyond the risk conditions designated by public health agencies contribute to this. A risk classifier that uses all the information available in health records, rather than only a limited set of conditions, will more accurately discriminate between low-risk and high-risk individuals who may require shielding until the epidemic is over. Author summaryWhy was this study done? Most people infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) do not become seriously ill: risk of severe or fatal disease is associated with older age, male sex, and conditions designated by public health agencies, including asthma, diabetes, and heart disease. Studies reported so far have focused on these listed conditions but have not examined medical records systematically to identify possible risk factors for severe coronavirus disease 2019 (COVID-19). The objectives of this study were to identify risk factors for severe COVID-19 and to lay the basis for risk stratification based on electronic health records. What did the researchers do and find? Using Scotland's capability for linking electronic health records, we report the first systematic study of the relationship of severe or fatal COVID-19 to preexisting health conditions and other risk factors. Residents in care homes were 21 times more likely to develop severe disease than people of the same age and sex not living in care homes. The conditions associated with increased risk include not only those already designated by public health agencies-asthma, diabetes, heart disease, disabling neurological disease, kidney disease-but other diagnoses that are associated with frailty and poor health such as strokes and a history of falls. In those without any listed conditions, use of prescribed drugs acting on the digestive system or nervous system is associated with increased risk of severe COVID-19. What do these findings mean? The risk to younger individuals without any recent history of hospital admission or use of prescription drugs is very low. This study lays a basis for calculating a risk score based on electronic health records for every individual in the population and using it to advise those at high risk of severe disease to shield themselves when there is a COVID-19 epidemic in their locality.