Background The Clozapine Plus Working Group is frequently consulted for advice on measures in case of infection with SARSCoV-2 and on vaccination against COVID-19 in patients receiving clozapine.

Aim Inform about risks of infection with SARS-CoV-2 in patients with severe mental illness (SMI), patients with schizophrenia spectrum disorders (SSD), and patients treated with clozapine. Advise on monitoring of clozapine plasma levels and white blood cell count and differential in COVID-19 and after vaccination, as well as measures to be taken.

Method Literature research and case studies.

Results SMI patients and in particular SSD patients have an increased risk of infection with SARS-CoV-2 with more hospitalizations and higher mortality than non-psychiatric patients. Patients using clozapine may be at greater risk of infection. SARS-CoV-2 infection may cause a dangerous increase of clozapine plasma levels and generally mild and short-term granulocytopenia and lymphocytopenia, which are usually not a result of clozapine treatment.

Conclusion In case of COVID-19 extra alertness is required in patients with SMI and especially SSD. In clozapine users, in case of COVID-19, reduction in dose by half to three quarters of the original dose is recommended. When patients develop granulocytopenia, SARS-CoV-2 should be considered as the cause and not immediately clozapine. SMI patients and clozapine users in particular belong to a high risk group with a medical indication for early vaccination.