Clozapine, neutropenia and Covid-19: should clinicians be concerned? 3 months report

Stefania Bonaccorso; Angelo Ricciardi; Sophie Ouabbou; Christos Theleritis; Arabella Ross-Michealides; Antonio Metastasio; Neil Stewart; Marwa Mohammed; Fabrizio Schifano

doi:10.1016/j.bbih.2021.100212

Clozapine, neutropenia and Covid-19: should clinicians be concerned? 3 months report

Stefania Bonaccorso, Angelo Ricciardi, Sophie Ouabbou, Christos Theleritis, Arabella Ross-Michealides, Antonio Metastasio, Neil Stewart, Marwa Mohammed, Fabrizio Schifano

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Abstract

Background: Clozapine is among the most effective antipsychotics used for treatment resistant schizophrenia. Adverse reactions to clozapine include neutropenia. In March 2020, at the start of the Coronavirus -19 pandemic, clinicians raised concerns regarding continuation of antipsychotic treatment, and specifically of clozapine, in patients with coronavirus disease. We aimed here at providing a short report focusing on the association between neutropenia and clozapine in a case series of psychiatric inpatients diagnosed with COVID-19.Patients & methods: We retrospectively inspected data of 10 patients on clozapine, admitted to Highgate Mental Health Centre, Camden & Islington NHS Foundation Trust, between March and July 2020; selection was based on their COVID-19 positive PCR test. We used a linear regression model to estimate whether there was a significant drop in the neutrophil count during SARS-CoV-2 infection.The analysis was done in R using a linear regression to the origin.Results: Data were collected on 10 patients, of which 7 were males. During COVID-19 infection, neutrophils' count (ANC) was 4.13 × 10 9/l (SD = 2.70) which constituted a significant drop from a baseline value of 5.2 × 10 9/l (SD = 2.24). The mean relative reduction in ANC was -0.2729 (SD = 0.1666). The beta value of 0.8377 obtained with the linear regression showed that ANC values during SARS-CoV-2 infection were 83.77% of the baseline ANC showing that within the two time points there was a decrease of 16.23%. The linear regression had a pvalue = 8.96 × 10 -8 and an adjusted R 2 of 95.94% which shows that the variability of the data is very well explained by the model. We also compared baseline ANC with ANC values approximately a month after resolution of the infection and results indicate that ANC values return to a 95% of baseline. Conclusions: Clinicians should bear in mind that a significant drop in neutrophils' count may occur in patients taking clozapine and affected from a SARS-CoV-2 infectionand that this drop is only transitory.

Original language	English
Article number	100212
Number of pages	4
Journal	Brain Behavior and Immunity
Volume	13
Early online date	28 Jan 2021
DOIs	https://doi.org/10.1016/j.bbih.2021.100212
Publication status	Published - May 2021

Keywords

Clozapine
Coronavirus
COVID-19
SARS-CoV-2
Psychosis
Schizophrenia
Lymphopenia
Agranulocytosis
Neutrophils
Neutropenia
Neutrophilia
absolute neutrophil count (ANC)

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10.1016/j.bbih.2021.100212Licence: CC BY-NC-ND

1-s20-S2666354621000156-main
© 2021 Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Final published version, 288 KBLicence: CC BY-NC-ND

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@article{aab3c9cb18b04f01948d3100c5806f58,

title = "Clozapine, neutropenia and Covid-19: should clinicians be concerned? 3 months report",

abstract = "Background: Clozapine is among the most effective antipsychotics used for treatment resistant schizophrenia. Adverse reactions to clozapine include neutropenia. In March 2020, at the start of the Coronavirus -19 pandemic, clinicians raised concerns regarding continuation of antipsychotic treatment, and specifically of clozapine, in patients with coronavirus disease. We aimed here at providing a short report focusing on the association between neutropenia and clozapine in a case series of psychiatric inpatients diagnosed with COVID-19.Patients & methods: We retrospectively inspected data of 10 patients on clozapine, admitted to Highgate Mental Health Centre, Camden & Islington NHS Foundation Trust, between March and July 2020; selection was based on their COVID-19 positive PCR test. We used a linear regression model to estimate whether there was a significant drop in the neutrophil count during SARS-CoV-2 infection.The analysis was done in R using a linear regression to the origin.Results: Data were collected on 10 patients, of which 7 were males. During COVID-19 infection, neutrophils' count (ANC) was 4.13 × 10 9/l (SD = 2.70) which constituted a significant drop from a baseline value of 5.2 × 10 9/l (SD = 2.24). The mean relative reduction in ANC was -0.2729 (SD = 0.1666). The beta value of 0.8377 obtained with the linear regression showed that ANC values during SARS-CoV-2 infection were 83.77% of the baseline ANC showing that within the two time points there was a decrease of 16.23%. The linear regression had a pvalue = 8.96 × 10 -8 and an adjusted R 2 of 95.94% which shows that the variability of the data is very well explained by the model. We also compared baseline ANC with ANC values approximately a month after resolution of the infection and results indicate that ANC values return to a 95% of baseline. Conclusions: Clinicians should bear in mind that a significant drop in neutrophils' count may occur in patients taking clozapine and affected from a SARS-CoV-2 infectionand that this drop is only transitory.",

keywords = "Clozapine, Coronavirus, COVID-19, SARS-CoV-2, Psychosis, Schizophrenia, Lymphopenia, Agranulocytosis, Neutrophils, Neutropenia, Neutrophilia, absolute neutrophil count (ANC)",

author = "Stefania Bonaccorso and Angelo Ricciardi and Sophie Ouabbou and Christos Theleritis and Arabella Ross-Michealides and Antonio Metastasio and Neil Stewart and Marwa Mohammed and Fabrizio Schifano",

note = "{\textcopyright} 2021 Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).",

year = "2021",

month = may,

doi = "10.1016/j.bbih.2021.100212",

language = "English",

volume = "13",

journal = "Brain Behavior and Immunity",

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T1 - Clozapine, neutropenia and Covid-19: should clinicians be concerned? 3 months report

AU - Bonaccorso, Stefania

AU - Ricciardi, Angelo

AU - Ouabbou, Sophie

AU - Theleritis, Christos

AU - Ross-Michealides, Arabella

AU - Metastasio, Antonio

AU - Stewart, Neil

AU - Mohammed, Marwa

AU - Schifano, Fabrizio

PY - 2021/5

Y1 - 2021/5

N2 - Background: Clozapine is among the most effective antipsychotics used for treatment resistant schizophrenia. Adverse reactions to clozapine include neutropenia. In March 2020, at the start of the Coronavirus -19 pandemic, clinicians raised concerns regarding continuation of antipsychotic treatment, and specifically of clozapine, in patients with coronavirus disease. We aimed here at providing a short report focusing on the association between neutropenia and clozapine in a case series of psychiatric inpatients diagnosed with COVID-19.Patients & methods: We retrospectively inspected data of 10 patients on clozapine, admitted to Highgate Mental Health Centre, Camden & Islington NHS Foundation Trust, between March and July 2020; selection was based on their COVID-19 positive PCR test. We used a linear regression model to estimate whether there was a significant drop in the neutrophil count during SARS-CoV-2 infection.The analysis was done in R using a linear regression to the origin.Results: Data were collected on 10 patients, of which 7 were males. During COVID-19 infection, neutrophils' count (ANC) was 4.13 × 10 9/l (SD = 2.70) which constituted a significant drop from a baseline value of 5.2 × 10 9/l (SD = 2.24). The mean relative reduction in ANC was -0.2729 (SD = 0.1666). The beta value of 0.8377 obtained with the linear regression showed that ANC values during SARS-CoV-2 infection were 83.77% of the baseline ANC showing that within the two time points there was a decrease of 16.23%. The linear regression had a pvalue = 8.96 × 10 -8 and an adjusted R 2 of 95.94% which shows that the variability of the data is very well explained by the model. We also compared baseline ANC with ANC values approximately a month after resolution of the infection and results indicate that ANC values return to a 95% of baseline. Conclusions: Clinicians should bear in mind that a significant drop in neutrophils' count may occur in patients taking clozapine and affected from a SARS-CoV-2 infectionand that this drop is only transitory.

AB - Background: Clozapine is among the most effective antipsychotics used for treatment resistant schizophrenia. Adverse reactions to clozapine include neutropenia. In March 2020, at the start of the Coronavirus -19 pandemic, clinicians raised concerns regarding continuation of antipsychotic treatment, and specifically of clozapine, in patients with coronavirus disease. We aimed here at providing a short report focusing on the association between neutropenia and clozapine in a case series of psychiatric inpatients diagnosed with COVID-19.Patients & methods: We retrospectively inspected data of 10 patients on clozapine, admitted to Highgate Mental Health Centre, Camden & Islington NHS Foundation Trust, between March and July 2020; selection was based on their COVID-19 positive PCR test. We used a linear regression model to estimate whether there was a significant drop in the neutrophil count during SARS-CoV-2 infection.The analysis was done in R using a linear regression to the origin.Results: Data were collected on 10 patients, of which 7 were males. During COVID-19 infection, neutrophils' count (ANC) was 4.13 × 10 9/l (SD = 2.70) which constituted a significant drop from a baseline value of 5.2 × 10 9/l (SD = 2.24). The mean relative reduction in ANC was -0.2729 (SD = 0.1666). The beta value of 0.8377 obtained with the linear regression showed that ANC values during SARS-CoV-2 infection were 83.77% of the baseline ANC showing that within the two time points there was a decrease of 16.23%. The linear regression had a pvalue = 8.96 × 10 -8 and an adjusted R 2 of 95.94% which shows that the variability of the data is very well explained by the model. We also compared baseline ANC with ANC values approximately a month after resolution of the infection and results indicate that ANC values return to a 95% of baseline. Conclusions: Clinicians should bear in mind that a significant drop in neutrophils' count may occur in patients taking clozapine and affected from a SARS-CoV-2 infectionand that this drop is only transitory.

KW - Clozapine

KW - Coronavirus

KW - COVID-19

KW - SARS-CoV-2

KW - Psychosis

KW - Schizophrenia

KW - Lymphopenia

KW - Agranulocytosis

KW - Neutrophils

KW - Neutropenia

KW - Neutrophilia

KW - absolute neutrophil count (ANC)

U2 - 10.1016/j.bbih.2021.100212

DO - 10.1016/j.bbih.2021.100212

M3 - Article

C2 - 33527097

SN - 0889-1591

VL - 13

JO - Brain Behavior and Immunity

JF - Brain Behavior and Immunity

M1 - 100212

ER -

Clozapine, neutropenia and Covid-19: should clinicians be concerned? 3 months report

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Keywords

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