Risks of mental health outcomes in people with covid-19: cohort study

Abstract

Objective: To estimate the risks of incident mental health disorders in survivors of the acute phase of covid-19.

Design: Cohort study.

Setting: US Department of Veterans Affairs.

Participants: Cohort comprising 153 848 people who survived the first 30 days of SARS-CoV-2 infection, and two control groups: a contemporary group (n=5 637 840) with no evidence of SARS-CoV-2, and a historical control group (n=5 859 251) that predated the covid-19 pandemic.

Main outcomes measures: Risks of prespecified incident mental health outcomes, calculated as hazard ratio and absolute risk difference per 1000 people at one year, with corresponding 95% confidence intervals. Predefined covariates and algorithmically selected high dimensional covariates were used to balance the covid-19 and control groups through inverse weighting.

Results: The covid-19 group showed an increased risk of incident anxiety disorders (hazard ratio 1.35 (95% confidence interval 1.30 to 1.39); risk difference 11.06 (95% confidence interval 9.64 to 12.53) per 1000 people at one year), depressive disorders (1.39 (1.34 to 1.43); 15.12 (13.38 to 16.91) per 1000 people at one year), stress and adjustment disorders (1.38 (1.34 to 1.43); 13.29 (11.71 to 14.92) per 1000 people at one year), and use of antidepressants (1.55 (1.50 to 1.60); 21.59 (19.63 to 23.60) per 1000 people at one year) and benzodiazepines (1.65 (1.58 to 1.72); 10.46 (9.37 to 11.61) per 1000 people at one year). The risk of incident opioid prescriptions also increased (1.76 (1.71 to 1.81); 35.90 (33.61 to 38.25) per 1000 people at one year), opioid use disorders (1.34 (1.21 to 1.48); 0.96 (0.59 to 1.37) per 1000 people at one year), and other (non-opioid) substance use disorders (1.20 (1.15 to 1.26); 4.34 (3.22 to 5.51) per 1000 people at one year). The covid-19 group also showed an increased risk of incident neurocognitive decline (1.80 (1.72 to 1.89); 10.75 (9.65 to 11.91) per 1000 people at one year) and sleep disorders (1.41 (1.38 to 1.45); 23.80 (21.65 to 26.00) per 1000 people at one year). The risk of any incident mental health diagnosis or prescription was increased (1.60 (1.55 to 1.66); 64.38 (58.90 to 70.01) per 1000 people at one year). The risks of examined outcomes were increased even among people who were not admitted to hospital and were highest among those who were admitted to hospital during the acute phase of covid-19. Results were consistent with those in the historical control group. The risk of incident mental health disorders was consistently higher in the covid-19 group in comparisons of people with covid-19 not admitted to hospital versus those not admitted to hospital for seasonal influenza, admitted to hospital with covid-19 versus admitted to hospital with seasonal influenza, and admitted to hospital with covid-19 versus admitted to hospital for any other cause.

Conclusions: The findings suggest that people who survive the acute phase of covid-19 are at increased risk of an array of incident mental health disorders. Tackling mental health disorders among survivors of covid-19 should be a priority.

Fig 1

Flowchart showing selection of cohort. VHA=Veterans Health Administration

Fig 2

Risks of incident mental health outcomes in covid-19 group during the post-acute phase compared with contemporary control group. Outcomes were ascertained 30 days after the initial SARS-CoV-2 positive test result until the end of follow-up. Hazard ratios are estimated through the follow-up and adjusted for age, race, sex, area deprivation index, body mass index, smoking status, number of outpatient encounters, history of hospital admission, use of long term care, cancer, chronic kidney disease, chronic lung disease, dementia, diabetes mellitus, dysautonomia, hyperlipidemia, hypertension, estimated glomerular filtration rate, systolic and diastolic blood pressure, and algorithmically selected high dimensional covariates. Risk differences are estimated at one year. MDD=major depressive disorder; PTSD=post-traumatic stress disorder; SSRI=selective serotonin reuptake inhibitor; SNRI=serotonin-noradrenaline (norepinephrine) reuptake inhibitor

Fig 3

Risks of incident composite mental health outcomes in covid-19 group compared with contemporary control group. Composite outcomes consisted of any mental health related drug prescription, any mental health diagnosis, and any mental health diagnosis or prescription. Outcomes were ascertained 30 days after the initial SARS-CoV-2 positive test result until end of follow-up. Hazard ratios are estimated through the follow-up and adjusted for age, race, sex, area deprivation index, body mass index, smoking status, number of outpatient encounters, history of hospital admission, use of long term care, cancer, chronic kidney disease, chronic lung disease, dementia, diabetes mellitus, dysautonomia, hyperlipidemia, hypertension, estimated glomerular filtration rate, systolic and diastolic blood pressure, and algorithmically selected high dimensional covariates. Risk differences are estimated at one year

Fig 4

Survival probability of incident composite mental health outcomes in covid-19 group compared with contemporary control group. Outcomes were ascertained 30 days after the initial SARS-CoV-2 positive test result until end of follow-up. Shaded areas are 95% confidence intervals. Numbers of participants at risk across groups are also presented

Fig 5

Risks of incident mental health outcomes in covid-19 group compared with contemporary control group by care setting. Outcomes were ascertained 30 days after the initial SARS-CoV-2 positive test result until end of follow-up. Hazard ratios are estimated through the follow-up and adjusted for age, race, sex, area deprivation index, body mass index, smoking status, number of outpatient encounters, history of hospital admission, use of long term care, cancer, chronic kidney disease, chronic lung disease, dementia, diabetes mellitus, dysautonomia, hyperlipidemia, hypertension, estimated glomerular filtration rate, systolic and diastolic blood pressure, and algorithmically selected high dimensional covariates. Risk differences are estimated at one year. MDD=major depressive disorder; PTSD=post-traumatic stress disorder; SSRI=selective serotonin reuptake inhibitor; SNRI=serotonin and noradrenaline (norepinephrine) reuptake inhibitor

Fig 6

Risks of incident composite mental health outcomes in covid-19 group compared with contemporary control group by care setting. Outcomes were ascertained 30 days after the initial SARS-CoV-2 positive test result until end of follow-up. Hazard ratios are estimated through the follow-up and adjusted for age, race, sex, area deprivation index, body mass index, smoking status, number of outpatient encounters, history of hospital admission, use of long term care, cancer, chronic kidney disease, chronic lung disease, dementia, diabetes mellitus, dysautonomia, hyperlipidemia, hypertension, estimated glomerular filtration rate, systolic and diastolic blood pressure, and algorithmically selected high dimensional covariates. Risk differences are estimated at one year

Fig 7

Survival probability of incident composite mental health outcomes in covid-19 group compared with contemporary control group by care setting. Outcomes were ascertained 30 days after the initial SARS-CoV-2 positive test result until end of follow-up. Shaded areas are 95% confidence intervals. Numbers of participants at risk across groups are also presented

Fig 8

Risks of incident composite mental health outcomes in people by covid-19 and seasonal influenza status and care setting. Outcomes were ascertained 30 days after enrollment of the cohort until end of follow-up. Hazard ratios adjusted for age, race, sex, area deprivation index, body mass index, smoking status, number of outpatient encounters, history of hospital admission, use of long term care, cancer, chronic kidney disease, chronic lung disease, dementia, diabetes mellitus, dysautonomia, hyperlipidemia, hypertension, estimated glomerular filtration rate, systolic and diastolic blood pressure, and algorithmically selected high dimensional covariates