key: cord-0280303-ffy0poxk authors: Velasquez Garcia, H. A.; Wilton, J.; Smolina, K.; Chong, M.; Rasali, D.; Otterstatter, M.; Rose, C.; Prystajecky, N.; David, S.; Galanis, E.; McKee, G.; Krajden, M.; Janjua, N. Z. title: Mental health and substance use associated with hospitalization among people with laboratory confirmed diagnosis of COVID-19 in British Columbia: a population-based cohort study date: 2021-08-28 journal: nan DOI: 10.1101/2021.08.26.21262697 sha: 9e71f2e4f36390c3c16649135e871758d4d302d2 doc_id: 280303 cord_uid: ffy0poxk Background: This study identified factors associated with hospital admission among people with laboratory-diagnosed COVID-19 cases in British Columbia. Methods: This study was performed using the BC COVID-19 Cohort, which integrates data on all COVID-19 cases, hospitalizations, medical visits, emergency room visits, prescription drugs, chronic conditions and deaths. The analysis included all laboratory-diagnosed COVID-19 cases in British Columbia as of January 15th, 2021. We evaluated factors associated with hospital admission using multivariable Poisson regression analysis with robust error variance. Findings: From 56,874 COVID-19 cases included in the analyses, 2,298 were hospitalized. Models showed significant association of the following factors with increased hospitalization risk: male sex (adjusted risk ratio (aRR)=1.27; 95%CI=1.17-1.37), older age (p-trend <0.0001 across age groups with a graded increase in hospitalization risk with increasing age [aRR 30-39 years=3.06; 95%CI=2.32-4.03, to aRR 80+years=43.68; 95%CI=33.41-57.10 compared to 20-29 years-old]), asthma (aRR=1.15; 95%CI=1.04-1.26), cancer (aRR=1.19; 95%CI=1.09-1.29), chronic kidney disease (aRR=1.32; 95%CI=1.19-1.47), diabetes (treated without insulin aRR=1.13; 95%CI=1.03-1.25, requiring insulin aRR=5.05; 95%CI=4.43-5.76), hypertension (aRR=1.19; 95%CI=1.08-1.31), injection drug use (aRR=2.51; 95%CI=2.14-2.95), intellectual and developmental disabilities (aRR=1.67; 95%CI=1.05-2.66), problematic alcohol use (aRR=1.63; 95%CI=1.43-1.85), immunosuppression (aRR=1.29; 95%CI=1.09-1.53), and schizophrenia and psychotic disorders (aRR=1.49; 95%CI=1.23-1.82). Among women of reproductive age, in addition to age and comorbidities, pregnancy (aRR=2.69; 95%CI=1.42-5.07) was associated with increased risk of hospital admission. Interpretation: Older age, male sex, substance use, intellectual and developmental disability, chronic comorbidities, and pregnancy increase the risk of COVID-19-related hospitalization. Funding: BC Centre for Disease Control, Canadian Institutes of Health Research. COVID-19 caused by SARS-CoV-2, affecting millions of people globally, resulted in a spectrum of health outcomes among those affected. Presentations range from asymptomatic and mild illnesses to severe disease that requires hospitalization with varying needs for more intensive levels of care. [1] [2] [3] Elevated levels of hospitalization and need for healthcare surge capacity, particularly intensive care unit (ICU), have been key drivers of pandemic response planning and contributed to societal disruption. 3 Studies have identified various demographic factors (e.g. being older in age, male) and chronic comorbidities (e.g. diabetes, cardiovascular disease (CVD), hypertension) as risk factors for hospitalization and other severe outcomes; 2 however, most studies were conducted on patients presenting at hospitals. There are very few population-based studies investigating risk factors in the entire population of COVID-19 diagnosed individuals in a jurisdiction. This can lead to potential selection bias when characterizing risk factors. Older age has been identified as the strongest risk factor for severe disease along with various comorbidities, 4 however, very few studies investigated relationship of substance use, intellectual disabilities and role of insulin dependent diabetes with the risk of severe outcomes. 5, 6 In addition, the clinical threshold to admit to hospital may vary across countries, especially early in the pandemic; hence, knowledge of factors associated with hospitalization in the Canadian context is important. Population-level hospitalization risk factor studies are also particularly essential for prioritization of interventions to reduce health system burden and maintain hospital capacity. In this study, we identified factors . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted August 28, 2021 Supplementary data (Appendix C). We described the baseline characteristics of participants including age, sex, and pregnancy status. We evaluated risk factors associated with hospital admission, calculating risk ratios through multivariable Poisson regression models with robust error variance. 10 For age, analyses were conducted as continuous as well as categorized into groups. To assess population differences across time, the cohort was stratified according to two waves or time periods: January 26 th to August 1 st , 2020, and August 2 nd , 2020 to January 15 th , 2021. Sensitivity analyses were performed by 1) stratifying the population by age group, and 2) by restricting the outcome to hospitalizations lasting more than two days to address severity. All statistical analyses were performed using R version 4.0.2. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted August 28, 2021. ; https://doi.org/10.1101/2021.08. 26.21262697 doi: medRxiv preprint The analysis included 56,874 COVID-19 cases diagnosed up to January 15 th , 2021; 2,298 (4.0%) of them were admitted to the hospital. A slightly higher proportion of people diagnosed as COVID-19 positive were male (51.2%), with much higher proportion among people requiring hospital admission (58.5% vs. 50.9) ( Table 1 ).The median age of COVID-19 cases was 35 years (IQR: , while that of people requiring hospital admission was nearly twice that (66 years; IQR:53-78). The proportion of hospitalized cases increased with each 10 year age-groups increment, from 0.2% in the youngest subpopulation (<20 years) to 34.2% in the eldest group (80+ years) (RR=66.96; 95%CI=52.35-85.65). Pregnant women were more likely to be hospitalized than women who were not (2.5% vs. 1.1%). Chronic comorbidities as risk factors: The proportion of comorbidities among hospitalized individuals was higher than in those who did not require hospitalization ( . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted August 28, 2021 In the analysis stratified by age (Table 4) , diabetes, and problematic alcohol use were associated with hospitalization across all age groups, with higher risk among younger groups that decreased with older age. Male sex, cancer and hypertension were associated with higher risk of hospital admission among those over 40 years of age. In the analysis restricted to hospitalizations lasting more than two days (Supplemental Table S4 ) did not show different findings compared with the overall analysis. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted August 28, 2021 In this large population-based analysis of all COVID-19 cases in BC, older age, male sex, pregnancy, and numerous chronic co-morbidities and other health-related conditions such as substance use were associated with increased hospitalization risk. Older age was the strongest predictor of hospital admission with risk increasing more than 40 fold for the oldest group compared to the 20-29 years. In addition to wellcharacterized co-morbidities, we found that injection drug use, 11 problematic alcohol use, schizophrenia, and psychotic disorders, 12 as well as intellectual and developmental disability, were independently associated with higher risk of hospitalization, highlighting syndemic of substance use, mental illness and COVID-19. Our findings have important implications for the vaccination program to prevent COVID-19 infection and severe outcomes and subsequently reduce hospital burden and mortality and were used to inform COVID-19 vaccination program in BC. 13 Our analysis confirms findings from other studies evaluating risk factors for severe COVID-19 outcomes, although ours is one of the few population-based analyses(i.e., includes all COVID-19 diagnoses in a jurisdiction). Most evaluations have also focused on in-hospital mortality, rather than morbidity. In addition to older age and male sex, a wide range of co-morbidities were associated with a higher risk of hospitalization, reflecting similar findings from other studies. 7, 14-19 These co-morbidities included asthma, chronic kidney disease, diabetes, cancer, immunosuppression and substance use. Associations between most co-morbidities and hospitalization were stronger at younger ages, highlighting the overall low risk of hospitalization among younger people without pre-existing co-morbidities, despite the findings that the hospitalization risk . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted August 28, 2021 infection and support our findings. [20] [21] [22] Pregnancy has been previously identified as a potential risk factor for ICU admission 23, 24 and severe disease, 25 but most studies have been limited to pregnant women who were already hospitalized (including for non-COVID-19 reasons such as childbirth). 23, 26 This finding could be in part the result of a lower clinical threshold for hospitalization of pregnant patients. Insulin-dependent diabetes, in particular in the stratum younger than 40 years, was associated with higher risk of hospitalization. To our knowledge this is the first report observing this phenomenon, though insulin use and increased risk of COVID-19-related death was described earlier. Further research is needed to better characterize this finding. Our analysis also highlights the intersection between the two ongoing public health emergencies in BC: the COVID-19 and the opioid overdose epidemics. The COVID-19 pandemic has exacerbated the pre-existing opioid epidemic, through mechanisms such as disruption of harm reduction services, 27 with BC experiencing a record high number of illicit drug toxicity deaths in 2020. 28 Our findings indicate that individuals at high risk of overdose, as indicated by IDU, are also at higher risk of COVID-19 hospitalization. This is the first study investigating impact of COVID-19 on people who inject drugs. IDU was the second co-morbidity most strongly associated with hospitalization in our analysis. Similarly problematic alcohol use, and schizophrenia and psychotic disorders were also associated with higher risk of hospitalization. The higher risk of COVID-19-related . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted August 28, 2021 hospitalization highlights the syndemic of substance use, mental illness and COVID-19. Many underlying social conditions such as unstable housing, lower socioeconomic status and many co-occurring co-morbidities may have exacerbated the effect of COVID-19 infection among these individuals. Prioritization of vaccination for this population group could reduce disparities and increased risk of hospitalization. Our analysis had several limitations. We relied on administrative data to identify patient characteristics and co-morbidities; this may have led to some level of misclassification. Similarly, for the same reason, it is not possible to evaluate clinical severity of the event leading to hospital admission. Further, we did not have information on socioeconomic status, race/ethnicity, and obesity. Also, given that the evaluation of the COVID-19 status depends on the BC diagnostic testing guidelines (varying over time to focus on symptom-based assessment since April 21st, 2020), 29 selective ascertainment of symptomatic cases is expected, resulting in exclusion of asymptomatic cases. 30 In conclusion, older age, male sex, pregnancy, and various comorbidities and healthconditions including substance use were associated with higher risk of hospital admission in this population-based analysis. These findings have informed the COVID-19 vaccination program rollout in BC and will be useful for informing the prioritization of vaccination in other jurisdictions to prevent infection and severe outcomes. 13 In addition, these findings will also inform monitoring of individual patients by their healthcare providers at higher risk of severe outcomes. Finally there is a need for further characterizing syndemics of substance use, mental illness and COVID-19. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted August 28, 2021 HAVG and NZJ contributed to study conception, design, and analyzed data. NZJ, NP and MK were involved in funding acquisition. NJ, SD, EG, JW, MC, and MK were involved in data acquisition. All authors contributed to data interpretation. HAVG was responsible for the first draft of the manuscript. All authors contributed to critical revision of the manuscript. All authors had access to and verified all the data and accept responsibility for the decision to submit for publication. The database for the study has been accessed and verified by HAVG and NZJ. All authors had full access to all the data and had final responsibility for the decision to submit for publication. The study is based on data contained in various provincial registries and databases. Access to data could be requested through the BC Centre for Disease Control Institutional Data Access for researchers who meet the criteria for access to confidential data. Requests for the data may be sent to datarequest@bccdc.ca. MK has received grant funding via his institution from Roche Molecular Systems, Boehringer Ingelheim, Merck, Siemens Healthcare Diagnostics and Hologic Inc. All other authors have no potential conflicts of interest to declare. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted August 28, 2021. The funders of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. All inferences, opinions, and conclusions drawn in this report are those of the authors, and do not reflect the opinions or policies of the Data Steward(s). We acknowledge the assistance of the Provincial Health Services Authority, BC Centre for Disease Control, BC Ministry of Health and Regional Health Authority staff involved in data access, procurement, and management. We gratefully acknowledge the residents of British Columbia whose data are integrated in the British Columbia COVID-19 Cohort (BCC19C). . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted August 28, 2021. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted August 28, 2021. ; . It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted August 28, 2021. . It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted August 28, 2021. . It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted August 28, 2021. T a b l e 2 -F a c t o r s a s s o c i a t e d w i t h h o s p i t a l i z a t i o n s t a t u s i n m u l t i v a r i a b l e P o i s s o n r e g r e s s i o n a n a l y s i s w i t h r o b u s t e r r o r v a r i a n c e a m o n g c o n f i r m e d c a s e s , B C C O V I D -1 9 C o h o r t V a r i a b l e C a t e g o r y 2 0 2 l y m p h o m a " , " m e t a s t a t i c c a n c e r " , a n d " s o l i d t u m o r w i t h o u t m e t a s t a s i s " I C D -9 / I C D -1 0 c o d e s f r o m g r o u p s 1 8 , 1 9 & 2 0 o f E l i x h a u s e r C o m o r b i d i t y S c o r e , i n D A D , M S P & N A C R S r e c o r d s . 2 A s s e s s e d v i a " r e n a l d i s e a s e " I C D -9 / I C D -1 0 c o d e s f r o m g r o u p 1 4 o f E l i x h a u s e r C o m o r b i d i t y S c o r e , i n D A D , M S P & N A C R S r e c o r d s . 3 A n y t y p e ; i n c l u d e s c o n c o m i t a n t t r e a t m e n t w i t h a n t i h y p e r g l y c e m i c a g e n t s . 4 S u n d a r a m M E , C a l z a v a r a A , M i s h r a S , K u s t r a R , C h a n A K , H a m i l t o n M A , e t a l . I n d i v i d u a l a n d s o c i a l d e t e r m i n a n t s . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted August 28, 2021 T a b l e 3 -F a c t o r s a s s o c i a t e d w i t h h o s p i t a l i z a t i o n s t a t u s i n m u l t i v a r i a b l e P o i s s o n r e g r e s s i o n a n a l y s i s w i t h r o b u s t e r r o r v a r i a n c e a m o n g w o m e n o f r e p r o d u c t i v e a g e ( 1 5 -4 9 y e a r s -o l d ) , . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted August 28, 2021 m e d c a s e s , B C C O V I D -1 9 C o h o r t , s t r a t i f i e d b y a g e g r o u p . V a r i a b l e A g e g r o u p A l l a g e g r o u p s ⁰ ( N = 5 . It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted August 28, 2021. Intensive care management of coronavirus disease 2019 (COVID-19): challenges and recommendations Risk factors for COVID-19-related mortality in people with type 1 and type 2 diabetes in England: a population-based cohort study Hospital surge capacity in a tertiary emergency referral centre during the COVID-19 outbreak in Italy COVID-19 and risk factors for hospital admission, severe disease and death 3rd update. Norwegian Institute of Public Health COVID-19 risk and outcomes in patients with substance use disorders: analyses from electronic health records in the United States The impact of substance use disorder on COVID-19 outcomes Risk Factors for Coronavirus Disease 2019 (COVID-19)-Associated Hospitalization: COVID-19-Associated Hospitalization Surveillance Network and Behavioral Risk Factor Surveillance System Characteristics of Adults aged 18-49 Years without Underlying Conditions Hospitalized with Laboratory-Confirmed COVID-19 in the United States SARS-CoV-2 Delta VOC in Scotland: demographics, risk of hospital admission, and vaccine effectiveness A Modified Poisson Regression Approach to Prospective Studies with Binary Data COVID-19 risk and outcomes in patients with substance use disorders: analyses from electronic health records in the United States Mental disorders and risk of COVID-19-related mortality, hospitalisation, and intensive care unit admission: a systematic review and meta-analysis. The Lancet Psychiatry Government of British Columbia. COVID-19 Immunization Plan Preexisting Comorbidities Predicting COVID-19 and Mortality in the UK Biobank Community Cohort Systematic Review and Meta-Analysis of Sex-Specific COVID-19 Clinical Outcomes Incidence, clinical features, and outcomes of COVID-19 in Canada: impact of sex and age Factors associated with hospital admission and critical illness among 5279 people with coronavirus disease Risk factors and outcomes of COVID-19 in New York City; a retrospective cohort study Population risk factors for severe disease and mortality in COVID-19: A global systematic review and metaanalysis COVID-19 and Sex Differences: Mechanisms and Biomarkers Sex differences in immune responses that underlie COVID-19 disease outcomes Sex, age, and hospitalization drive antibody responses in a COVID-19 convalescent plasma donor population Update: Characteristics of Symptomatic Women of Reproductive Age with Laboratory-Confirmed SARS-CoV-2 Infection by Pregnancy Status -United States Are clinical outcomes worse for pregnant women at ≥ 20 weeks' gestation infected with coronavirus disease 2019? A multicenter case-control study with propensity score matching Pregnancy as a risk factor for severe coronavirus 2019 (COVID-19) disease using standardized clinical criteria Clinical manifestations, risk factors, and maternal and perinatal outcomes of coronavirus disease 2019 in pregnancy: Living systematic review and meta-analysis Overdose Response Indicators British Columbia Coroner's Service. Illicit drug toxicity deaths in BC BC Centre for Disease Control. Phases of COVID-19 testing in BC Proportion of asymptomatic infection among COVID-19 positive persons and their transmission potential: A systematic review and meta-analysis International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity