In patients with paroxysmal nocturnal hemoglobinuria (PNH), SARS-CoV-2 infection with the omicron variant can generate a severe hemolytic exacerbation, although eculizumab may be an effective treatment, according to findings from a study conducted in China and published in the journal Immunity, Inflammation and Disease.
Individuals with PNH, which is associated with a mutation in the X-linked PIGA gene, experience hemolytic anemia, thrombophilia, bone marrow failure, and multiorgan damage. The researchers of the current study obtained clinical and demographic data from 20 patients with PNH and COVID-19 omicron infection. All study participants, who were enrolled between December 2022 and February 2023, were outpatients from 1 of 4 centers.
High disease activity in patients with PNH and COVID-19 was defined as follows:
- Evidence of hemolysis (ie, elevated lactate dehydrogenase [LDH] of ≥1.5 times the upper limit of normal [ULN])
- History of 1 or more of these signs/symptoms: fatigue; hemoglobinuria, dyspnea; anemia (ie, hemoglobin <100 g/L); abdominal pain; major adverse vascular events, including thrombotic events; dysphagia; and/or erectile dysfunction
Read more about experimental therapies for patients with PNH
Of the 20 study participants, 14 were female and 6 were male. The median patient age was 37 years (range, 15-75 years). Overall, 55% (11 of 20) of the participants exhibited classic PNH and 45% (9 of 20) of them had PNH/aplastic anemia. The median time to occurrence of a hemolytic episode following a SARS-CoV-2 omicron infection was 3 days (range, 1-5 days).
In all, 10 of the 20 participants reported hemoglobinuria, whereas 10 others experienced cytopenia and worsening fatigue. No thrombotic events were reported in the study participants; however, D-dimer levels were elevated in 10 of the participants. These patients were treated with prophylactic low-molecular-weight heparin.
All participants had high disease activity, with their LDH levels higher than levels that had been reported since they were diagnosed with PNH. In 2 participants, mild pulmonary hypertension was observed. In addition, the glomerular filtration rate decreased in 5 individuals. In 1 of the patients, acute renal failure developed, which necessitated the use of hemodialysis.
Eculizumab was administered in 5 participants—4 females and 1 male. Of these 5 individuals, 3 had classic PNH and 2 had PNH/aplastic anemia. Following treatment with eculizumab, hemolysis was controlled (LDH, 13.53 × ULN vs 3.38 × ULN, respectively; P =.028). Eculizumab use also was associated with significantly improved red blood cell counts (P =.01) and hemoglobin levels (P =.005).
“Our study results preliminarily demonstrate SARS-CoV-2 infection could induce a hemolytic exacerbation in patients with PNH but eculizumab can effectively control acute hemolysis,” the researchers noted. “A large amount of long-term follow-up data are still needed to assess the impact of SARS-CoV-2 on patients with PNH, evaluate the dose and duration of eculizumab, and develop better prevention and control plans,” they concluded.
Reference
Yang H, Chai X, Gong Y, et al. Severe hemolytic exacerbations of Chinese PNH patients infected SARS‐CoV‐2 Omicron. Immun Inflamm Dis. Published online August 8, 2023. doi:10.1002/iid3.966
