Severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2), emerged at the end of 2019 and caused an infection named COVID‐19 (Guan, Ni et al. 2020). Patients with compromised immune systems are at increased risk of complications but this risk is not precisely defined (Liang, Guan et al. 2020). Although age, gender, comorbidities and ethnicity are risk factors for adverse outcomes (Huang, Wang et al. 2020), various pre‐existing conditions, including haematological cancers, have also been reported to correlate with poor outcomes (Aries, Davies et al. 2020, He, Chen et al. 2020, Malard, Genthon et al. 2020, Martin‐Moro, Marquet et al. 2020, medRxiv 2020)

Emerging evidence suggests that activation of the complement system is critical in the pathogenesis of the novel coronavirus, SARS‐CoV‐2, the causative agent of COVID‐19 related lung injury. Inhibition of the terminal complement pathway by targeting complement protein 5 (C5) may be an effective therapeutic intervention in CoV‐mediated disease.¹ Paroxysmal nocturnal haemoglobinuria (PNH) is a rare, acquired hematopoietic stem cell (HSC) disease characterized by intravascular haemolysis, increased thromboembolic risk and bone marrow failure.²

Background: Clozapine remains underused despite its unparalleled efficacy in treatment-refractory schizophrenia. One of the reasons for its underuse is the fear of severe neutropenia and its consequences. Aims: To scrutinise the association between severe neutropenia and clozapine in a cohort of patients clinically diagnosed with clozapine-induced severe neutropenia. Method: We used data from the South London and Maudsley National Health Service Foundation Trust’s anonymised case register, known as the Clinical Record Interactive Search. We extracted details of cases where clozapine use was associated with two consecutive neutrophil counts below 1.5 × 10⁹/L. A panel of clinicians independently assessed each case. Agreement was reached on which cases clozapine was the likely or definite cause of the severe neutropenia, the risk to life and whether or not rechallenge with clozapine could be attempted. Results: There were 96 cases where two consecutive neutrophil counts below 1.5 × 10⁹/L were registered. The panel judged that 9 (9.4%) were definitely caused by clozapine and a further 11 (11.5%) were probably caused by clozapine. Overall, 18 (18.8%) patients should be precluded from ever receiving clozapine again according to the panel (all from the 20 cases where clozapine was the definite or probable cause). Of the remaining 76 cases of severe neutropenia the cause could not be determined in 60 cases, but in 11 cases the cause was benign ethnic neutropenia, in 2 others the cause was cancer chemotherapy, in 2 it was infections and in 1 it was laboratory error. In almost 80% of cases, clozapine was not the clear cause of the neutropenia observed. Conclusions: The large majority of severe neutropenia episodes mandating cessation of clozapine may not be caused by clozapine. Threshold-based monitoring systems cause unnecessary stopping of clozapine because they lack the necessary specificity for clozapine-related blood disorders.

Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by hemolysis and thrombosis and is associated with significant morbidity and mortality. Although complement inhibitors have significantly changed the outcomes in PNH patients, breakthrough hemolysis (BTH) may still occur as a response to stress factors such as pregnancy, surgery, and infections. Despite the well-described association between bacterial infections and hemolysis in PNH patients, little is known about the effect of respiratory viruses on triggering hemolytic episodes. This is the first study, to our knowledge, addressing this question. We retrospectively analyzed 34 patients with PNH disease between 2016 and 2018, who were on eculizumab treatment and who presented with respiratory symptoms and were subsequently tested for 10 respiratory viruses (influenza A, influenza B, parainfluenza, respiratory syncytial virus, adenovirus, rhinovirus, and human metapneumovirus). NTS+ patients had higher inflammatory markers, with the majority requiring antibiotics. Acute hemolysis, along with a significant drop in hemoglobin, was noted in the NTS+ group, with three of them requiring a top-up transfusion and two requiring an extra dose of eculizumab. Furthermore, the time from the last eculizumab dose was longer in the NTS+ patients who had BTH, than those who did not. Our data indicate that respiratory virus infections pose a significant risk for BTH in PNH patients on complement inhibitor treatment, underlining the need for regular screening and close monitoring of patients with respiratory symptoms. Furthermore, it implies a higher risk for patients who are not established on complement inhibitors, suggesting the necessity for greater vigilance in these patients.