Adverse mental health consequences of COVID-19, including anxiety and depression, have been widely predicted but not yet accurately measured. There are a range of physical health risk factors for COVID-19, but it is not known if there are also psychiatric risk factors. In this electronic health record network cohort study using data from 69 million individuals, 62 354 of whom had a diagnosis of COVID-19, we assessed whether a diagnosis of COVID-19 (compared with other health events) was associated with increased rates of subsequent psychiatric diagnoses, and whether patients with a history of psychiatric illness are at a higher risk of being diagnosed with COVID-19.
We used the TriNetX Analytics Network, a global federated network that captures anonymised data from electronic health records in 54 health-care organisations in the USA, totalling 69·8 million patients. TriNetX included 62 354 patients diagnosed with COVID-19 between Jan 20, and Aug 1, 2020. We created cohorts of patients who had been diagnosed with COVID-19 or a range of other health events. We used propensity score matching to control for confounding by risk factors for COVID-19 and for severity of illness. We measured the incidence of and hazard ratios (HRs) for psychiatric disorders, dementia, and insomnia, during the first 14 to 90 days after a diagnosis of COVID-19.
In patients with no previous psychiatric history, a diagnosis of COVID-19 was associated with increased incidence of a first psychiatric diagnosis in the following 14 to 90 days compared with six other health events (HR 2·1, 95% CI 1·8–2·5 vs influenza; 1·7, 1·5–1·9 vs other respiratory tract infections; 1·6, 1·4–1·9 vs skin infection; 1·6, 1·3–1·9 vs cholelithiasis; 2·2, 1·9–2·6 vs urolithiasis, and 2·1, 1·9–2·5 vs fracture of a large bone; all p<0·0001). The HR was greatest for anxiety disorders, insomnia, and dementia. We observed similar findings, although with smaller HRs, when relapses and new diagnoses were measured. The incidence of any psychiatric diagnosis in the 14 to 90 days after COVID-19 diagnosis was 18·1% (95% CI 17·6–18·6), including 5·8% (5·2–6·4) that were a first diagnosis. The incidence of a first diagnosis of dementia in the 14 to 90 days after COVID-19 diagnosis was 1·6% (95% CI 1·2–2·1) in people older than 65 years. A psychiatric diagnosis in the previous year was associated with a higher incidence of COVID-19 diagnosis (relative risk 1·65, 95% CI 1·59–1·71; p<0·0001). This risk was independent of known physical health risk factors for COVID-19, but we cannot exclude possible residual confounding by socioeconomic factors.
Survivors of COVID-19 appear to be at increased risk of psychiatric sequelae, and a psychiatric diagnosis might be an independent risk factor for COVID-19. Although preliminary, our findings have implications for clinical services, and prospective cohort studies are warranted.
Using a large federated electronic health record network in the USA to create propensity score matched cohorts of patients, we found that COVID-19 survivors have a significantly higher rate of psychiatric disorders, dementia, and insomnia. We also showed that a previous psychiatric illness is independently associated with an increased risk of being diagnosed with COVID-19.
In the period between 14 and 90 days after COVID-19 diagnosis, 5·8% COVID-19 survivors had their first recorded diagnosis of psychiatric illness (F20–F48), compared with 2·5–3·4% of patients in the comparison cohorts. Thus, adults have an approximately doubled risk of being newly diagnosed with a psychiatric disorder after COVID-19 diagnosis. The comparable figures when recurrences of previous diagnoses are included are indicative of the rates of psychiatric disorder that might be anticipated in practice. These incidence figures are minimum estimates for three reasons. First, there will be patients who have not yet presented or received a diagnosis. Second, patients might seek health care from organisations not included in the network. Third, diagnostic rates overall in the network are about 30% lower for both psychiatric and physical disorders since the onset of COVID-19 (see appendix p 45), consistent with other evidence for reduced presentations in the USA.
The psychiatric effects of COVID-19 were broad but not uniform. The HR was greater for anxiety disorders than for mood disorders. The impact of COVID-19 on anxiety is in line with expectations and highlights the need for effective and accessible interventions. Our data show increased diagnoses in all major anxiety disorder categories, and it remains unclear whether post-COVID-19 anxiety will have a particular post-traumatic stress disorder-like picture. Rates of insomnia diagnosis were also markedly elevated, in agreement with predictions that circadian disturbances will follow COVID-19 infection. By contrast, we did not find a clear signal for newly diagnosed psychotic disorders, despite case reports suggesting that this might occur.The two to three times increased risk of dementia after COVID-19 infection extends findings from previous case series and is concerning. Some of the excess might reflect misdiagnosed cases of delirium, or transient cognitive impairments due to reversible cerebral events. However, our exclusion of the first 14 days after COVID-19 diagnosis reduces this likelihood, and the incidence of dementia was not higher among inpatients (who are more prone to having delirium) than outpatients (appendix p 45), further suggesting that delirium misdiagnosis does not explain this finding. Detailed follow-up and investigation of this group should be a research priority, as should evaluation of other severe neuropsychiatric phenotypes that become apparent.
The HRs from COVID-19 were higher compared with all other cohorts, indicating that COVID-19 has an impact on psychiatric health above and beyond that which occurs after other acute health events. Since our severity and contextual factors hypotheses cannot explain most of the associations, it is necessary to explore the cause of the particular effect of COVID-19 on the risk of psychiatric disorder. Despite various speculations, the underlying mechanisms are unknown and require urgent investigation. The relationship between the severity of illness (as proxied by inpatient admission) and psychiatric outcomes, albeit modest, might represent a dose–response relationship, suggesting that the association might at least partly be mediated by biological factors directly related to COVID-19 (eg, viral load, breathlessness, or the nature of the immune response).We did not anticipate that psychiatric history would be an independent risk factor for COVID-19. This finding appears robust, being observed in all age strata and in both sexes, and was substantial—a 1·65 times excess. This result was not related to any specific psychiatric diagnostic category, and was similar regardless of whether the diagnosis was made within 1 or 3 years, and whether or not the known physical risk factors for COVID-19 were present. The risk persisted when problems related to housing and economic circumstances were controlled for. This result is consistent with a recent case-control study using a different US electronic health record network, although the previous study found much higher relative risks.
Nevertheless, we interpret this finding cautiously, as a Korean study found no association between psychiatric diagnosis and COVID-19 diagnosis, albeit in a much smaller sample and with less matching.15 Possible explanations for the association include behavioural factors (eg, less adherence to social distancing recommendations) and residual socioeconomic and lifestyle factors (eg, smoking) that are not sufficiently captured by the available data in any of the studies. It could also be that vulnerability to COVID-19 is increased by the pro-inflammatory state postulated to occur in some forms of psychiatric disorder or be related to psychotropic medication.
The strengths of this study are the sample size, the amount of data available, the use of propensity score matching, the range of sensitivity analyses, and the real-world nature of the data. The study also has limitations. First, despite the matching and use of various comparison cohorts, there might well be residual confounding, particularly related to social and economic factors, which are not captured in the network and which could influence outcomes. Second, we do not know whether diagnoses were made in primary or secondary care, nor by whom. It is possible that some health-care centres were closed as a result of lockdowns and this might influence where and how patients were diagnosed. The study can provide no information about undiagnosed patients with COVID-19. Third, clinicians might be more likely to diagnose a psychiatric illness after a COVID-19 diagnosis than after the comparison events because of a difference in the nature or extent of assessments; this could also lead to improved detection of conditions (eg, dementia), which had been present but undiagnosed before COVID-19 diagnosis. Fourth, some patients might receive additional care, especially for mental health, at locations not included in the network; this would reduce the absolute incidence figures but is unlikely to confound the relative risks associated with COVID-19. Fifth, propensity score matching raises some statistical issues, but these should not affect the results to any extent. Moreover, similar results were seen in the unmatched analyses. Sixth, we did not control statistically for multiple comparisons, although most results were significant at the p<0·0001 level or lower. Finally, our results cannot necessarily be generalised to other populations or health-care settings.
In conclusion, our findings are of sufficient robustness and magnitude to have some immediate implications. The figures provide minimum estimates of the excess in psychiatric morbidity to be anticipated in survivors of COVID-19 and for which services need to plan.
As COVID-19 sample sizes and survival times increase, it will be possible to refine these findings and to identify rarer and delayed psychiatric presentations. Prospective cohort studies and inclusive case registers will be valuable to complement electronic health record analyses. It will also be important to explore additional risk factors for contracting COVID-19, and for developing psychiatric disorders thereafter, as some elements might prove to be modifiable.
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