We thank Elizabeth Charlton and colleagues, Josef Finsterer, and Ella Burchill and colleagues for their comments on our Article in The Lancet Psychiatry.1Taquet M Geddes JR Husain M Luciano S Harrison PJ 6-month neurological and psychiatric outcomes in 236 379 survivors of COVID-19: a retrospective cohort study using electronic health records.Charlton and colleagues raise several interesting points. Regarding post-traumatic stress disorder (PTSD), we did not explore this specific diagnosis, although we did in an earlier Article.2Taquet M Luciano S Geddes JR Harrison PJ Bidirectional associations between COVID-19 and psychiatric disorder: retrospective cohort studies of 62 354 COVID-19 cases in the USA. We have now done so, extending the window for the index event to April 20, 2021. The risk of a first diagnosis of PTSD within 6 months of a COVID-19 diagnosis was 0·58% (95% CI 0·50–0·67). This risk was significantly higher than in the matched cohort of patients diagnosed with influenza (0·26% [0·23–0·31]; hazard ratio [HR] 2·12 [95% CI 1·74–2·59]; pvs 0·20% [0·12–0·35]; HR 4·55 [95% CI 2·59–7·98]; pUsing the same matched cohorts of patients with COVID-19 and with influenza diagnosed between Jan 20, 2020, and April 20, 2021, we also investigated the incidence and HRs for subtypes of dementia (table). The majority of diagnoses were of unspecified dementia but the relative increase was broadly similar across categories. We did not exclude people with a history of mild cognitive impairment or delirium, and therefore some patients diagnosed with dementia might have been in this high-risk or prodromal group, as we noted in the Discussion of our Article.1Taquet M Geddes JR Husain M Luciano S Harrison PJ 6-month neurological and psychiatric outcomes in 236 379 survivors of COVID-19: a retrospective cohort study using electronic health records.

TableIncidence and hazard ratio for dementia subtypes between matched cohorts of patients diagnosed with COVID-19 versus influenza

Data in parentheses are 95% CIs. Dementia subtypes are presented with their ICD-10 codes. The sum of incidences exceeds the total incidence of dementia because the same patient might be diagnosed with one subtype (eg, unspecified dementia) and then another (eg, Alzheimer's disease) within the follow-up period. No data can be shown for frontotemporal dementia and Lewy body dementia because they occurred in fewer than ten patients in each cohort (which is the minimum number to be returned by TriNetX to safeguard patients' anonymity).

We have no data as to which of the COVID-19 cases had been asymptomatic, but we assume that this group is substantially under-represented in our dataset because there is a bias towards symptomatic people presenting for testing (especially early in the pandemic), and because we used the U07.1 ICD-10 code to define cases, which refers to a confirmed diagnosis. Asymptomatic COVID-19 might well be associated with lower rates of subsequent psychiatric or neurological disorder, and our results should be interpreted with this important possibility in mind. We agree that asking about COVID-19 should become a routine item in medical history questionnaires. The idea of reverse redeployment will be attractive to mental health professionals but we suspect rather less so to our general medical colleagues.

Josef Finsterer commented on the overlap between the influenza and respiratory infections cohorts. We agree that we could have made them mutually exclusive; however, we chose not to do this to enable the respiratory infection cohort to be sufficiently large to enable all the COVID-19 cases to be included after propensity score matching. Our study was observational, and we did not attempt to list or explore all the potential mechanisms that might be involved. For instance, we did not investigate the list of putatively neurotoxic compounds that some patients might have received, since a comprehensive pharmacoepidemiological assessment was beyond the scope of the study. Similarly, we could have put various diagnostic combinations together, but we chose to present Guillain-Barré syndrome separately because of the previous suggestions of a specific association with COVID-19.3Fragiel M Miró Ò Llorens P et al.Incidence, clinical characteristics, risk factors and outcomes of Guillain-Barré syndrome in patients with COVID-19.We agree that undiagnosed COVID-19 in the control cohorts will have occurred, and we mention this and its implications in the Discussion of our Article.1Taquet M Geddes JR Husain M Luciano S Harrison PJ 6-month neurological and psychiatric outcomes in 236 379 survivors of COVID-19: a retrospective cohort study using electronic health records. To expect control cohorts in a real-world electronic health records study to be based on systematic negative PCR test data would be unrealistic. Finally, we acknowledge that we did not attempt to include every neurological syndrome. We have subsequently reported on cerebral venous thrombosis4Taquet M Husain M Geddes JR Luciano S Harrison PJ Cerebral venous thrombosis and portal vein thrombosis: a retrospective cohort study of 537,913 COVID-19 cases. and will be studying headache and some of the other diagnoses in future analyses.

Ella Burchill and colleagues rightly draw attention to the salient finding regarding myoneural junction and muscle disorders. They are correct that most diagnoses in this category were to G72.8 rather than to myasthenia gravis or other specific diagnoses, and we agree that critical illness-associated neuropathy and myopathy are indeed plausible explanations. We also agree that neuromuscular complications of COVID-19 merit attention both for research and rehabilitation.

SL is an employee of TriNetX. All other authors declare no competing interests.

References1.Taquet M Geddes JR Husain M Luciano S Harrison PJ

6-month neurological and psychiatric outcomes in 236 379 survivors of COVID-19: a retrospective cohort study using electronic health records.

Lancet Psychiatry. 8: 416-4272.Taquet M Luciano S Geddes JR Harrison PJ

Bidirectional associations between COVID-19 and psychiatric disorder: retrospective cohort studies of 62 354 COVID-19 cases in the USA.

Lancet Psychiatry. 8: 130-1403.Fragiel M Miró Ò Llorens P et al.

Incidence, clinical characteristics, risk factors and outcomes of Guillain-Barré syndrome in patients with COVID-19.

Ann Neurol. 89: 598-6034.Taquet M Husain M Geddes JR Luciano S Harrison PJ

Cerebral venous thrombosis and portal vein thrombosis: a retrospective cohort study of 537,913 COVID-19 cases.

medRxiv. ()Article InfoPublication HistoryIdentification

DOI: https://doi.org/10.1016/S2215-0366(21)00202-9

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ScienceDirectAccess this article on ScienceDirect Linked Articles6-month neurological and psychiatric outcomes in 236 379 survivors of COVID-19: a retrospective cohort study using electronic health records

Our study provides evidence for substantial neurological and psychiatric morbidity in the 6 months after COVID-19 infection. Risks were greatest in, but not limited to, patients who had severe COVID-19. This information could help in service planning and identification of research priorities. Complementary study designs, including prospective cohorts, are needed to corroborate and explain these findings.

Full-Text PDF Open AccessNeuropsychiatric disorders and COVID-19

Maxime Taquet and colleagues reported an increased incidence of neurological and psychiatric disorders in patients diagnosed with COVID-19 (ie, group 1) compared with two matched control cohorts: patients diagnosed with influenza (ie, group 2) and patients diagnosed with any respiratory tract infection, including influenza (ie, group 3).1 In my opinion, having two control groups containing patients with influenza is a shortcoming of the study, and patients with influenza in group 3 should have been transferred to group 2.

Full-Text PDF Neuropsychiatric disorders and COVID-19

We read with interest the Article by Maxime Taquet and colleagues that reports on the incidence rates of anxiety disorders after a COVID-19 diagnosis,1 and we noted from the appendix that this outcome includes codes F40–F48 of the ICD-10. Given the known occurrence of developing post-traumatic stress disorder after admission to an intensive therapy unit,2 we wondered if the authors had considered re-analysing their data to assess the incidence of post-traumatic stress disorder in survivors of COVID-19, including both those treated in intensive therapy units and those treated elsewhere?

Full-Text PDF Neuropsychiatric disorders and COVID-19

We read with interest the Article by Maxime Taquet and colleagues1 in The Lancet Psychiatry that evaluated a large population (n=236 379) for neurological and psychiatric complications of COVID-19 via analysis of diagnostic codes associated with electronic health notes.1 The highest hazard ratios (HRs) reported were for myoneural junction or muscle disease (ICD-10 codes G70–73), with HR 5·28 (95% CI 3·71–7·53) after COVID-19 versus after influenza and 4·52 (3·65–5·59) after COVID-19 versus after other respiratory tract infection.

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