COVID-19 infection and subsequent psychiatric morbidity, sleep problems and fatigue: analysis of an English primary care cohort of 226,521 positive patients

Objectives The primary hypothesis was that the risk of incident or repeat psychiatric illness, fatigue and sleep problems increased following COVID-19 infection. The analysis plan was pre-registered (https://osf.io/n2k34/). Design Matched cohorts were assembled using a UK primary care registry (the CPRD-Aurum database). Patients were followed-up for up to 10 months, from 1st February 2020 to 9th December 2020. Setting Primary care database of 11,923,499 adults (>16 years). Participants From 232,780 adults with a positive COVID-19 test (after excluding those with <2 years historical data or <1 week follow-up), 86,922 without prior mental illness, 19,020 with anxiety or depression, 1,036 with psychosis, 4,152 with fatigue and 4,539 with sleep problems were matched to up to four controls based on gender, general practice and year of birth. A negative control used patients who tested negative for COVID-19 and patients negative for COVID with an influenza diagnosis. Main Outcomes and Measures Cox proportional hazard models estimated the association between a COVID-19 positive test and subsequent psychiatric morbidity (depression, anxiety, psychosis, or self-harm), sleep problems, fatigue or psychotropic prescribing. Models adjusted for comorbidities, ethnicity, smoking and BMI. Results After adjusting for observed confounders, there was an association between testing positive for COVID-19 and almost all markers of psychiatric morbidity, fatigue and sleep problems. The adjusted hazard ratio (aHR) for incident psychiatric morbidity was 1.75 (95% CI 1.56-1.96). However, there was a similar risk of incident psychiatric morbidity for those with a negative COVID-19 test (aHR 1.57, 95% CI 1.51-1.63) and a larger increase associated with influenza (aHR 2.97, 95% CI 1.36-6.48). Conclusions There is consistent evidence that COVID-19 infection elevates risk of fatigue and sleep problems, however the results from the negative control analysis suggests that residual confounding may be responsible for at least some of the association between COVID-19 and psychiatric morbidity.