Clozapine treatment and risk of COVID-19 infection: retrospective cohort study

  1. Risha Govind
  2. Daniela Fonseca de Freitas
  3. Megan Pritchard
  4. Richard D. Hayes
  5. James H. MacCabe

Reviewed by

Read the full article See related articles

Listed in

Log in to save this article

Abstract

Clozapine, an antipsychotic with unique efficacy in treatment-resistant psychosis, is associated with increased susceptibility to infection, including pneumonia.

Aims

To investigate associations between clozapine treatment and increased risk of COVID-19 infection in patients with schizophrenia-spectrum disorders who are receiving antipsychotic medications in a geographically defined population in London, UK.

Method

Using information from South London and Maudsley NHS Foundation Trust (SLAM) clinical records, via the Clinical Record Interactive Search system, we identified 6309 individuals who had an ICD-10 diagnosis of schizophrenia-spectrum disorders and were taking antipsychotics at the time of the COVID-19 pandemic onset in the UK. People who were on clozapine treatment were compared with those on any other antipsychotic treatment for risk of contracting COVID-19 between 1 March and 18 May 2020. We tested associations between clozapine treatment and COVID-19 infection, adjusting for gender, age, ethnicity, body mass index (BMI), smoking status and SLAM service use.

Results

Of 6309 participants, 102 tested positive for COVID-19. Individuals who were on clozapine had increased risk of COVID-19 infection compared with those who were on other antipsychotic medication (unadjusted hazard ratio HR = 2 .62, 95% CI 1.73–3.96), which was attenuated after adjusting for potential confounders, including clinical contact (adjusted HR = 1.76, 95% CI 1.14–2.72).

Conclusions

These findings provide support for the hypothesis that clozapine treatment is associated with an increased risk of COVID-19 infection. Further research will be needed in other samples to confirm this association. Potential clinical implications are discussed.

Article activity feed

  1. Version published to 10.1192/bjp.2020.151
  2. ScreenIT

    SciScore for 10.1101/2020.06.17.20133595: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board StatementIRB: CRIS was approved as an anonymised data resource for secondary analysis by Oxfordshire Research Ethics Committee C (reference 18/SC/0372).
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Statistical analysis: The data were analysed using STATA for Windows version 15.1.
    STATA
    suggested: (Stata, RRID:SCR_012763)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    Limitations: We controlled for a number of potential confounders; however, there may still be residual confounding. There is a very large effect of inpatient status on the risk of COVID-19 infection. This is likely to arise partly from a higher risk of exposure to COVID-19 in hospital settings, and largely from the policy that inpatients showing any symptoms of COVID-19 were tested, while testing in the community was less comprehensive. Controlling for inpatient status on March 1, 2020, has not annulled the significant association between clozapine and COVID-19. However, we cannot rule out the possibility that clozapine-treated patients could be more likely to be tested for COVID-19, even after accounting for the differences in patient contact and inpatient status between the groups before March 1, 2020. During the study period, the Trust enacted a policy of attempting to discharge patients back into the community where possible, to free up inpatient capacity. We are making an assumption that the proportion of patients discharged did not differ between the clozapine treated group and the non-clozapine-treated group, and that the amount of care and monitoring before versus during the pandemic, remained proportional between groups. The most recent BMI of some patients in the study were from almost 15 years ago. While this is likely to give some indication of the BMI of the patients, it is important to note that BMI is more likely to have been recently measured in clozapine-trea...

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  3. Version published to 10.1101/2020.06.17.20133595v1 on medRxiv