Clinical outcomes and immune responses to SARS‐CoV‐2 vaccination in severe aplastic anaemia

Abstract

Summary Patients with severe aplastic anaemia (SAA) are often not vaccinated against viruses due to concerns of ineffective protective antibody response and potential for pathogenic global immune system activation, leading to relapse. We evaluated the impact of COVID‐19 vaccination on haematological indices and disease status and characterized the humoural and cellular responses to vaccination in 50 SAA patients, who were previously treated with immunosuppressive therapy (IST). There was no significant difference in haemoglobin ( p = 0.52), platelet count ( p = 0.67), absolute lymphocyte ( p = 0.42) and neutrophil ( p = 0.98) counts prior to and after completion of vaccination series. Relapse after vaccination, defined as a progressive decline in counts requiring treatment, occurred in three patients (6%). Humoural response was detectable in 90% (28/31) of cases by reduction in an in‐vitro Angiotensin II Converting Enzyme (ACE2) binding and neutralization assay, even in patients receiving ciclosporin (10/11, 90.1%). Comparison of spike‐specific T‐cell responses in 27 SAA patients and 10 control subjects revealed qualitatively similar CD4 + Th1‐dominant responses to vaccination. There was no difference in CD4 + ( p = 0.77) or CD8 + ( p = 0.74) T‐cell responses between patients on or off ciclosporin therapy at the time of vaccination. Our data highlight appropriate humoural and cellular responses in SAA previously treated with IST and true relapse after vaccination is rare.

Variable Clinical Courses of Varicella Zoster Virus Infection–related or Vaccination-related Bone Marrow Failure

“…Acquired AA is an entity characterized by pancytopenia and bone marrow aplasia resulting from the immune-mediated destruction of hematopoietic stem cells 15 . Other viral infections such as hepatitis viruses, parvovirus, human immunodeficiency virus or vaccinations for influenza, pneumococcal, and SARS-CoV-2 are rarely associated with AA 16,17 . Here, we report 5 cases of severe BMF after varicella infection and summarize the cases reported in the literature.…”

“…15 Other viral infections such as hepatitis viruses, parvovirus, human immunodeficiency virus or vaccinations for influenza, pneumococcal, and SARS-CoV-2 are rarely associated with AA. 16,17 Here, we report 5 cases of severe BMF after varicella infection and summarize the cases reported in the literature.…”

SARS-CoV-2 vaccination in 361 non-transplanted patients with aplastic anemia and/or paroxysmal nocturnal hemoglobinuria

“…Six percent (3/50) patients relapsed post vaccination, although similar to our cohort, two of the three patients had discontinued AA treatment 2 and 30 days prior to vaccination, raising the question of whether this was vaccine-related relapse or due to withdrawal of immunosuppresion. 14 Potential considerations would be to suspend immunosuppression withdrawal during a vaccination program.…”

“…However, several groups have undertaken vaccine response studies in this patient cohort, demonstrating similar antibody response to healthy volunteers after the second SARS-CoV-2 vaccine irrespective of immunosuppression use. 8 , 14 In the current prospective study, some data points were missing, and a cohort of non-vaccinated patients would have been useful for comparison.…”

“…Six percent (3/50) patients relapsed post vaccination, although similar to our cohort, two of the three patients had discontinued AA treatment 2 and 30 days prior to vaccination, raising the question of whether this was vaccine-related relapse or due to withdrawal of immunosuppresion. 14 Potential considerations would be to suspend immunosuppression withdrawal during a vaccination program. PNH-related complications in those on complement inhibitors in our cohort were moderate, similar reports conclude up to a 14% breakthrough hemolysis risk in patients undergoing vaccination.…”