Abstract
The complex pathophysiologic interplay between SARS-CoV-2 infection and complement activation is the subject of active investigation. It is clinically mirrored by the occurrence of exacerbations of complement mediated diseases during COVID-19 infection. These include complement-mediated hemolytic anemias such as paroxysmal nocturnal hemoglobinuria (PNH), autoimmune hemolytic anemia (AIHA), particularly cold agglutinin disease (CAD), and hemolytic uremic syndrome (HUS). All these conditions may benefit from complement inhibitors that are also under study for COVID-19 disease. Hemolytic exacerbations in these conditions may occur upon several triggers including infections and vaccines and may require transfusions, treatment with complement inhibitors and/or immunosuppressors (i.e., steroids and rituximab for AIHA), and result in thrombotic complications. In this manuscript we describe four patients (2 with PNH and 2 with CAD) who experienced hemolytic flares after either COVID-19 infection or SARS-Cov2 vaccine and provide a review of the most recent literature. We report that most episodes occurred within the first 10 days after COVID-19 infection/vaccination and suggest laboratory monitoring (Hb and LDH levels) in that period. Moreover, in our experience and in the literature, hemolytic exacerbations occurring during COVID-19 infection were more severe, required greater therapeutic intervention, and carried more complications including fatalities, as compared to those developing after SARS-CoV-2 vaccine, suggesting the importance of vaccinating this patient population. Patient education remains pivotal to promptly recognize signs/symptoms of hemolytic flares and to refer to medical attention. Treatment choice should be based on the severity of the hemolytic exacerbation as well as of that of COVID-19 infection. Therapies include transfusions, complement inhibitor initiation/additional dose in the case of PNH, steroids/rituximab in patients with CAD and warm type AIHA, plasma exchange, hemodialysis and complement inhibitor in the case of atypical HUS. Finally, anti-thrombotic prophylaxis should be always considered in these settings, provided safe platelet counts.
Highlights
There is an increasing interest in the relationship between COVID-19 infection and complement activation
Case Description A 27-year-old man was diagnosed with paroxysmal nocturnal hemoglobinuria (PNH) in 2010 associated with transfusion dependent anemia (Hb 6.8 g/dL, LDH 7.5 x upper limit of normality, ULN, PLT 121x109/L, neutrophils 1.8 x109/L, reticulocytes 121x109/L) and symptoms of hemolysis with abdominal pain
A CT scan revealed bilateral interstitial pneumonia and he was admitted to hospital and treated with antibiotics, dexamethasone, and low molecular weight heparin (LMWH), as well as an earlier dose of eculizumab (10 days after the previous one)
Summary
There is an increasing interest in the relationship between COVID-19 infection and complement activation. CAD is an autoimmune hemolytic anemia caused by cold reactive antierythrocyte autoantibodies usually of the IgM class that are intrinsically able to fix complement with consequent positivity of the direct antiglobulin test (DAT) for C3d (5). This may result in both IVH and EVH due to either terminal activation of complement and membrane attack complex (MAC) formation, or C3b deposition on erythrocytes and reticulo-endothelial phagocytosis. The atypical form may be secondary to bacteria, medication, or immune processes capable of endothelial damage, or to congenital or acquired conditions inducing widespread complement activation, such as atypical familial HUS In the latter cases C5 inhibitors are employed with clinical benefit (8). In this manuscript we describe four patients who experienced PNH BTH and CAD exacerbation after either COVID infection or SARS-Cov vaccine and we review the most recent literature
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
