Keyword
Paroxysmal nocturnal hemoglobinuria; COVID-19; Omicron; complement inhibitor therapy; hemolysis;
Introduction
Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired and clonal disease characterized by hemolytic anemia, bone marrow failure, thrombophilia and multi-organ damage, which results from the mutation of the X -linked PIGA gene. The blockade of glycosylphosphatidylinositol (GPI) synthesis caused by mutation results in the absence of GPI-anchored protein (such as CD55 and CD59), and CD55-deficient and CD59-deficient blood cells are more susceptible to complement attack and lysis[1,2]. Coronavirus disease 2019 (COVID-2019) first emerged in Wuhan, Hubei, China, by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)[3]. SARS-CoV-2 was reported multiple variants, including Alpha, Beta, Gamma, Delta, Omicron, and Omicron shows a 13-fold increase in viral infectivity than Delta variant[4]. SARS-CoV-2 activate the complement system through the classical pathway, lectin pathway and the alternative pathway. Specific antibody directed against the receptor-binding domain of the spike protein initiates the classical pathway, the binding of mannose-binding lectin (MBL) with SARS-CoV-2 spike protein triggers the lectin pathway and SARS-CoV-2 spike protein may dysregulate the alternative pathway by binding heparan sulfate and competing with factor H, which is a negative regulator of complement activity[5,6]. After SARS-CoV-2 infection, patients with PNH more likely suffered the hemolysis[7–16], patients usually presented visible hemoglobinuria and a small number patients showed pancytopenia[17]. Terminal complement inhibitors (such as eculizumab) are promising in COVID-19 treatment by blocking the formation of membrane attack complex (MAC) and reducing pro-inflammatory and prothrombotic influence[5,6,18]. Due to the rarity of PNH, the clinical features of patients infected with SARS-CoV-2 were mostly case reports. China has been heavily affected by the SARS-CoV-2 Omicron outbreak with the peak in mid-December 2022. We collected clinical data from 20 PNH patients infected with SARS-CoV-2 Omicron and treated 5 patients with eculizumab.