PB2226: THE ROLE OF COMPLEMENT IN THE IMMUNE RESPONSE OF SICKLE CELL DISEASE PATIENTS AFER COVID-19 VACCINATION

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Background: Healthcare systems around the world are still under considerable pressure from the constant threat of the coronavirus disease-19 (COVID-19) pandemic. Although adult sickle cell disease (SCD) patients were vaccinated as a high-risk group, due to their coexisting immunosuppression and possible development of acute thoracic syndrome, there are no data on the following immune response. Aims: We investigated the immune response of our SCD patients to COVID-19 vaccination. Methods: We prospectively studied adult SCD patients monitored at our Center who received at least one dose of COVID-19 vaccination until August 2021. We detected neutralizing antibodies (nAbs) against SARS-CoV-2 in patients’ sera (ELISA, cPass™ SARS-CoV-2 nAbs Detection Kit; GenScript, Piscataway, NJ, USA), 21 days after each vaccination dose. Levels ≥30% are considered as positive, while levels ≥50% are considered highly protective against severe disease. We investigated possible predictive factors, including age, usage of anticoagulants, pulmonary hypertension, previous episodes of vascular strokes, hydroxycarbamide administration, regular transfusions, renal damage and complement activation. Complement activation was detected in patient’s sera by measuring soluble C5b-9 with a commercially available enzyme-linked immunosorbent assay (ELISA) kit (Quidel, upper normal limit: 245 ng/ml), before vaccination and 21 days after the second dose. Results: Among 53 adult SCD patients monitored at our Center, 27 were studied after their first dose (24 received BNT162b2, 2 mRNA-1273, and 1 patient JNJ-78436735). Their median age was 40 years. Sixteen were female and 23 had the S/β genotype. NAbs ≥30% were detected in 14/27 patients, 11 of whom (84%) had already increased complement activation. On the contrary, among the 13 patients who did not develop nAbs after the first dose, only 5 (38.4%) were found with increased levels of soluble C5b-9 (p=0.042). The patient that received the single-shot JNJ vaccine did not develop adequate nAbs, despite increased C5b-9 baseline levels. Interestingly, 2/27 patients who had suffered from a vascular stroke in the past, also did not develop adequate nAbs (p=0.002). No other significant associations between nAbs and studied parameters were found. Clinically important SARS-CoV-2 inhibition and protection against severe disease indicated by nAbs ≥50% was detected only in 11/27 patients (40.7%) after the first dose. Twenty-one days after the second dose we were able to study 22 patients. NAbs significantly increased in all patients (p<0.001) at levels ≥50%, even though 12 patients had levels of <30% after the first dose. Similarly, a significant increase of C5b-9 levels was also detected after the second dose (p=0.009). This increase was above the upper normal limit in the majority of patients (16/22), although 13/22 had normal baseline levels. No complications of COVID-19 vaccinations were reported. Summary/Conclusion: Our study demonstrates a satisfactory immune response of adult SCD patients, primarily after the second vaccination dose. Complement activation seems to play an important role in the establishment of adequate immunogenic response. Patients suffering from serious complications, such as stroke, appear to develop clinically significant nAbs, only after the second dose. More data are needed regarding the duration and adequacy of immune responses in SCD patients in order to evaluate the necessity of additional doses.

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