Acquired aplastic anemia following SARS‐CoV‐2 vaccination

Abstract

COVID‐19 is a potential life‐threatening viral disease caused by SARS‐CoV‐2 and was declared a pandemic by the WHO in March 2020. mRNA‐based SARS‐CoV‐2 vaccines are routinely recommended in immune‐compromised patients, including patients with AA, as these patients are at increased risk of contracting COVID‐19 and developing a more severe course of disease. Between March 2021 and November 2021 relapse of AA occurred in four (age [median]: 53 years, range 30–84 years) out of 135 patients currently registered at our department and two de novo cases of AA in temporal context to vaccination against SARS‐CoV‐2, were documented. Median time after first COVID‐19 vaccination and relapse of AA was 77 days. All relapsed patients were vaccinated with the mRNA‐based vaccine Comirnaty®. Relapse in two out of the four patients was refractory to CsA/eltrombopag, favoring IST with hATG/CsA or BMT, respectively. Our observations should prompt clinicians to take vaccine‐induced relapse of AA or de novo AA after SARS‐CoV‐2 vaccination into account. Furthermore, careful clinical monitoring and vigilance for signs or symptoms that may indicate relapse of AA (e.g., bleeding complications) are indicated.

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

“…Three patients (6%) had a substantial decline in blood counts requiring reinitiation of IST with CSA: two after receiving one dose and one shortly after completing the two‐dose series. Comparable relapse rate and clinical outcomes were recently reported in four out of 135 AA individuals with outcomes ranging from transfusion independence after reinitiating IST to undergoing transplant 19 . Notably, in our study, all three subjects had blood counts categorized as weak PR with PLT below 50 × 10 9 /l and demonstrated instability prior to vaccine inoculation irrespective of time from initial SAA diagnosis and treatment.…”

“…This finding is contrary to a recent report suggesting CD8 + T‐cell‐dependent activation as a possible explanation for increased relapse risk in AA. 19 Cellular responses waned as time elapsed from completion of vaccination series. A similar finding was reported by evaluating the antibody and cellular response to COVID‐19 vaccination in patients receiving maintenance IST for immune‐mediated inflammatory diseases, 21 stressing the importance of booster doses to maintain cellular immunity after vaccination.…”

“…Our study revealed that, qualitatively, CD8 + responses to vaccination may be blunted in SAA patients. This finding is contrary to a recent report suggesting CD8 + T‐cell‐dependent activation as a possible explanation for increased relapse risk in AA 19 . Cellular responses waned as time elapsed from completion of vaccination series.…”

Pre-exposure to mRNA-LNP inhibits adaptive immune responses and alters innate immune fitness in an inheritable fashion

“…Severe aplastic anemia (affecting the hematopoietic stem cells and characterized by neutropenia and thrombocytopenia)-, cytopenia-and thrombocytopenia cases have all been reported with this platform in humans [43][44][45][46][47][48][49]. One small human study (56 volunteers) that monitored the immunological changes induced by this vaccine up to 21 days of the second shot reported a significant fluctuation in white blood cell numbers after the second injection of mRNA-LNP [11].…”

Aplastic anemia following the severe acute respiratory syndrome coronavirus‐2 vaccine

“…There have been several reports describing the possible relationship between the severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) vaccine and the development of hematological diseases, such as autoimmune hemolytic anemias, paroxysmal nocturnal hemoglobinuria or immune thrombocytopenic purpura [ 1 , 2 , 3 , 4 , 5 , 6 ]. Although a few reports have mentioned a potential relationship between the SARS‐CoV‐2 vaccine and the development of aplastic anemia (AA), data is still limited [ 7 , 8 , 9 , 10 ].…”