COVID-19 Infection in Patients with Paroxysmal Nocturnal Hemoglobinuria in Italy
Authors: Barcellini Wilma , Fattizzo Bruno , Quattrocchi Luisa , Giannotta Juri Alessandro , Aydin Semra , Barone Federica , Carbone Cecilia , Beggiato Eloise , Bianchi Paola , Di Bona Eros , Notaro Rosario , Iori Anna Paola 
Published: February 2021

COVID-19 pandemic has raised several concerns regarding patients with hematologic and immune-mediated diseases. It can be assumed that Paroxysmal nocturnal hemoglobinuria (PNH), both classic hemolytic and associated with aplastic anemia, particularly on treatment with complement inhibitors, may be more susceptible and have higher morbidity and mortality rates from COVID-19 than the general population. Italy has been heavily affected from the COVID-19 outbreak with the peak of contagions at the end of March 2020. As of July, 23 2020 the cumulative incidence of COVID-19 in Italy was 0.4% (1 case every 246 residents) (ranging from 0.06% - 1/1621- in Calabria to 0.9% - 1/106 - in Lombardy). We conducted a survey on 126 patients with PNH (77 females/49 males, median age 48 years, range 19-86) among 7 reference Italian centers in order to evaluate the occurrence and clinical characteristics of COVID-19 infection from the outbreak until the time of writing. According to International PNH Interest Group (IPIG) classification, 95 patients suffered from classic hemolytic PNH, 24 had associated bone marrow failures (aplastic anemia or myelodysplastic syndrome), and 7 had subclinical PNH (clone size &lt;10%). Sixty-nine cases were on complement fraction 5 (C5) inhibition (72 eculizumab and 19 ravulizumab). Comorbidities were present in 33 patients, including arterial hypertension (N=14), ischemic cardiomyopathy (N=3), atrial fibrillation (N=2), diabetes mellitus (N=2), breast cancer (N=3), colon cancer (N=1), prostate cancer (N=1), Crohn disease (N=1), and Hashimoto thyroiditis (N=1). During the observation period, only one patient (55 years female), from Milan, Lombardy, not on C5-inhibitor was diagnosed with COVID-19 infection (positive swab, ageusia, and mild fever for few days). No hemolytic flare occurred, nor hospital admission was required. She received azithromycin and low molecular heparin. Other 6 patients, all on C5-inhibitors, experienced fever (N=5) and cough (N=2), and/or dysgeusia (N=1), of whom 2 experienced breakthrough hemolysis (BTH), but swabs and CT scans (N=2) were negative. At variance, 6 patients (4 on eculizumab and 2 on ravulizumab) experienced BTH without COVID-19 symptoms. Interestingly, a young male patient on eculizumab, working as medical doctor in a COVID-19 ward, did not contract the infection. In conclusion, this survey suggests that PNH subjects, either on complement inhibition or not, are not at significantly higher risk of COVID-19 infection as compared with the general population. As a matter of fact, the basic protective measures against COVID-19 have always been advised to PNH patients particularly during treatment and were presumably carefully followed during the pandemic. On the other hand, immune activation and inflammation are thought to play an important role in the clinical severity of COVID-19 pneumonia. Complement inhibition, which is under investigation in COVID-19 disease, seems at least not disadvantageous in PNH.

Disclosures
Barcellini: Agios: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Alexion: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: invited speaker , Research Funding; Novartis: Honoraria, Other: invited speaker , Research Funding; Bioverativ: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees. Bianchi:Agios Pharmaceuticals: Other: Scientific Advisor. Notaro:Biocryst: Membership on an entity's Board of Directors or advisory committees; Alexion Pharmaceuticals: Honoraria.