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.