Outcomes of COVID-19 infection in patients treated with Clozapine

  1. Risha Govind
  2. Daniela Fonseca de Freitas
  3. Megan Pritchard
  4. Mizanur Khondoker
  5. James T Teo
  6. Robert Stewart
  7. Richard D. Hayes
  8. James H. MacCabe

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Abstract

Background

Clozapine, an antipsychotic, is associated with increased susceptibility to infection with COVID-19, compared to other antipsychotics.

Aims

To investigate associations between clozapine treatment and increased risk of adverse outcomes of COVID-19, namely COVID-related hospitalisation and intensive care treatment, and death, among patients taking antipsychotics with schizophrenia-spectrum disorders.

Method

Using data from South London and Maudsley NHS Foundation Trust (SLAM) clinical records, via the Clinical Record Interactive Search system, we identified 157 individuals who had an ICD-10 diagnosis of schizophrenia-spectrum disorders, were taking antipsychotics at the time of the COVID-19 pandemic in the UK, and had a laboratory-confirmed COVID-19 infection. The following health outcomes were measured: COVID-related hospitalisation, COVID-related intensive care treatment death. We tested associations between clozapine treatment and each outcome using logistic regression models, adjusting for gender, age, ethnicity, neighbourhood deprivation, obesity, smoking status, diabetes, asthma, bronchitis and hypertension using propensity scores.

Results

In the 157 individuals who developed COVID while on antipsychotics, there were 44 COVID-related hospitalisations, 13 COVID-related intensive care treatments and 13 deaths of any cause during the follow-up period. In the unadjusted analysis, there was no significant association between clozapine and any of the outcomes and there remained no associations following adjusting for the confounding variables.

Conclusions

In our sample of patients with COVID-19 and schizophrenia-spectrum disorders, we found no evidence that clozapine treatment puts patients at increased risk of hospitalisation, intensive care treatment or death, compared to any other antipsychotic treatment. However, further research should be considered in larger samples to confirm this.

Conflict of interest

RDH has received research funding from Roche, Pfizer, Janssen, and Lundbeck. DFF has received research funding from Janssen and Lundbeck. JHM has received research funding from Lundbeck. JTT has received research funding from Bristol-Meyers-Squibb. RS declares research support in the last 36 months from Janssen, GSK and Takeda.

Ethics statement

The research was conducted under ethical approval reference 18/SC/0372 from Oxfordshire Research Ethics Committee C.

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  1. ScreenIT

    SciScore for 10.1101/2021.04.13.21255384: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: CRIS was approved for use as a de-identified data resource for secondary analysis by Oxfordshire Research Ethics Committee C (reference 18/SC/0372).
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    STATA was also used to estimate power for the analysis.
    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:
    Strengths and limitations: As a strength of this study, SLAM is a near-monopoly service provider of all aspects of secondary mental health care to residents within a defined geographic catchment, allowing relatively comprehensive ascertainment of people with the disorders of interest receiving specialist care during the COVID-19 pandemic in the UK. The CRIS database provided the platform to ascertain the relevant sample and access information on a range of potential confounders. However, it is important to bear in mind that not all people with schizophrenia-spectrum disorders will have been receiving specialist mental healthcare at that time, so that generalisability is limited. Furthermore, not all COVID-19 infection episodes will have been ascertained, particularly during early stages of the pandemic when access to tests was very limited. Another important limitation of the analysis results from type II error. We acknowledge this analysis is underpowered, although the urgency of the situation led us to decide to present data available at this stage. The COVID-related hospitalisation and intensive care treatment data came from combining information provided by local general hospitals and supplementing that by reading clinical notes of each patients. For patients who did not receive COVID-related treatments at the local general hospitals, we have assumed their clinical notes would capture mentions of any COVID-related treatments they received. However, it cannot be ruled out ...

    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.

  2. Version published to 10.1101/2021.04.13.21255384v1 on medRxiv