4. Results
4.1 Status of hemolytic episodes with SARS-CoV-2 Omicron infection
A total of 20 PNH patients diagnosed with SARS-CoV-2 Omicron infection were enrolled in this study. 6 (30%, 6/20) were male, 14 (70%, 14/20) were female and the median age was 37 years (range 15–75years). Eleven patients (55%, 11/20) presented classical PNH and nine patients (45%, 9/20) were diagnosed with PNH/AA. They accepted glucocorticoid maintenance and transfusion in the past. None of them were treated with complement inhibitors. The median time to episode occurred is three days after SARS-CoV-2 Omicron infection (1-5 days).
10 patients (50%, 10/20) complained of hemoglobinuria. Other 10 patients (50%, 10/ 20) presented with worsen fatigue and cytopenia. Although no thrombotic event happened, D-dimer (median 2.55mg/L, range 0.57– 4.47mg/L) was elevated in 10 patients, and all of them received prophylactic low molecular weight heparin.
Mild pulmonary hypertension was found in two patients (32mmHg and 35mmHg, respectively). The glomerular filtration rate in five patients (25%, 5/20) was lower than 60ml/min/1.73m2. One patient underwent hemodialysis due to acute renal failure.
The level of LDH (2555U/L vs 1542U/L, 9.43×ULN vs 5.62×ULN, p=0.011), total bilirubin (TBIL) (49.56μmol/L vs 28.92 μmol/L, p=0.031) and indirect bilirubin (IBIL) (29.31 μmol/L vs 17.8μmol/L, p=0.017) were higher than the most severe hemolysis previously recorded. Anemia became worsened compared to the previous period — RBC (2.17×1012/L vs 2.42×1012/L, p=0.356), Hb (66 g/L vs 71 g/L, p=0.459) (Table 1). The decrease in GFR was nearly statistically significant(113.65 ml/min/1.73m2 vs 118.3 ml/min/1.73m2, p=0.055).
4.2 Efficacy of eculizumab
5 patients were administrated with eculizumab. After eculizumab treatment, hemolysis was controlled (LDH 13.53×ULN vs 3.38×ULN, p=0.028), and RBC count (1.96×1012/L vs 2.45×1012/L, p=0.01), and level of hemoglobin (64 g/L vs 83 g/L, p=0.005) were also improved significantly (Table 2) (Figure 1). The improvement in IBIL was nearly statistically significant (31.7 1μmol/L vs 20.69 μmol/L, p=0.057). The elevated D-dimers in two patients also decreased significantly after treatment— 4.04 mg/L vs 1.47 mg/L, 2.15 mg/L vs 1.37 mg/L, respectively. During hemolysis, one patient had a high IL-6 serum concentration, 31.29 times higher than the upper limit of the normal —165.83 pg/mL while after eculizumab treatment IL-6 drops to 4.98 pg/mL. Because of emergency use, the patients treated by eculizumab could not be vaccinated against Neisseria meningitidis and Streptococcus pneumoniae in advance, but infection did not occur with the whole course of penicillin prophylaxis.
4.3 Outcomes of COVID-19 and PNH
In our study, 12 of 20 (60%) were hospitalized. 2 (2/20, 10%) patients developed severe COVID-19—one with severe viral pneumonia but recovered after two doses of eculizumab with oxygen support and the other with acute renal failure but recovered after hemodialysis.
Of the 5 patients using eculizumab, 2 were not in HDA status. But 13 of the other 15 patients remained in HDA status during the second week after infection with SARS-CoV-2 Omicron.