Breakthrough haemolysis in paroxysmal nocturnal haemoglobinuria after COVID-19 infection and COVID vaccination: what is worse?

Abstract

INTRODUCTION
Over the last year, an increasing number of reports have highlighted the crucial role of complement activation in the pathogenesis and severity of COVID-19, the disease caused by the SARS-CoV-2 virus. The latter is part of the immunological hyper-response to the virus, and may contribute to endothelial damage, blood clotting, and cytopenia. Trials with complement inhibitors in severe COVID-19 are currently ongoing with promising results¹. Paroxysmal nocturnal haemoglobinuria (PNH) is a rare acquired haematopoietic stem cell disease caused by a somatic mutation of the PIGA gene resulting in an increased susceptibility of PNH cells to complement damage. Clinically, PNH is marked by intravascular haemolysis, increased thromboembolic risk, and bone marrow failure, and benefits from treatment with complement inhibitors. PNH patients have a higher risk of infection due to therapy with complement inhibitors and, in many cases, to the presence of concomitant bone marrow failure. Moreover, infections are well known triggers of haemolysis, together with drugs, trauma or surgical interventions. Breakthrough haemolysis (BTH) has been defined as a reactivation of haemolysis in patients treated with complement inhibitors. There is growing evidence to suggest that both COVID-19 and COVID vaccination may precipitate haemolysis in therapy-naïve PNH patients and may trigger BTH in those on anti-complement therapy. Here we describe the case of a PNH patient on therapy with the C5 inhibitor eculizumab, who developed BTH following both SARS-CoV-2 infection and COVID vaccination.