Efficacy of Anti-Sars-Cov-2 mRNA Vaccines in Adults with Severe Acquired Aplastic Anemia with or without Allograft

Introduction: Vaccines against SARS-CoV-2 have shown remarkable efficacy and thus constitute an important preventive option against COVID-19 infections, especially in immunocompromised hosts. Several studies have now demonstrated a good response to SARS-CoV-2 mRNA vaccines in allogeneic hematopoietic stem cell transplant (Allo-HSCT) recipients. In the specific context of acquired severe aplastic anemia (ASAA), some data exist on post-vaccination results after treatment by horse antithymocyte globulin (hATG) and cyclosporin (CsA) while a few cases of SAA have been related to COVID-19 infection. However, as yet, no specific results are available for ASAA patients (pts) who received an Allo-HSCT.

Methods: This real life monocentric observational study aimed at describing the incidence and severity of COVID 19 infections and humoral responses after anti- SARS-Cov-2 mRNA vaccines in a cohort of 27 ASAA pts who received either an allo-HSCT (n=13) or hATG+CsA (n=14) between 2012 and 2022 in our Hematology Department. Data were collected in personal file records, during routine follow-up visits or using phone contact. COVID 19 infection severity was defined by the need for hospitalization and/or subsequent related death. Antibody responses to the SARS-CoV-2 spike protein receptor-binding domain were also considered (all tests using Elecsys®, Roche, Rotkreuz, Switzerland), the highest value being >2500 BAU/mL. Based on a threshold of 250 BAU/mL, responses were classified as "weak" or "good, higher levels having been shown to correlate with the rate of neutralizing antibodies.

Results: Pts characteristics are given in Table 1. None of the pts had presented a symptomatic or asymptomatic COVID-19 infection before V1. Afterwards, almost half of the pts (n=13, 48%) were documented with COVID 19 infection, mostly as a non-severe form (n=12, 92%, asymptomatic n=3 and mild n=9). Only one severe COVID 19 infection occurred and required hospitalization in intensive care unit for one month. This severe form occurred in the only pt who had not been vaccinated. This pt had been treated with hATG+CsA 18 months earlier and was still receiving CsA.

The incidence of infection was similar between allo-HSCT (8/13) and ATG+CsA (5/14) pts (p=0.26), as well as in pts with idiopathic ASAA (8/12) or paroxysmal nocturnal hemoglobinuria (5/15; p=0.13). No difference either was seen between pts still under immunosuppressive therapy (CsA; 3/8) or not (10/19; p=0.76) or between pts vaccinated before (5/6) or after (8/20) Allo/hATG+CsA (p=0.16). All 3 patients who received only V1 and V2 vaccines contracted the infection and the incidence of COVID-19 infection was significantly lower in patients with 4 vaccines (11%) vs those with 3 (57%; p=0.05).

After a median time of 36 days (range: 20 - 232) after V2, 75% (n=12/16) of the pts showed a good antibody response, 11 reaching the highest IgG titer, and this proportion increased after V3 and V4. Indeed, at a median time of 70 days (range: 17 - 221) after V3, 95% (n=19/20) showed a good antibody response, 17 pts reaching the highest IgG titer. At a median time of 60 days (range: 2-195) after V4, 100% (n=7/7) of the pts showed a good antibody response, 4 reaching the highest IgG titer.

Conclusion: In this cohort, almost half of adults with ASAA presented with COVID-19 infection with no difference between patients previously allotransplanted and those who had received only hATG+CsA. Moreover, prolonged exposure to CsA did not appear to affect this incidence. Remarkably, none of the vaccinated patients presented a severe form of COVID-19 infection, indicating a very good efficiency of the vaccines. This protection increased with the number of shots as the incidence of COVID-19 was lower and the number of pts reaching good humoral response higher after a second booster. As the latter seems to be more protective, it should be proposed to all ASAA adult patients for whom systemic immune responses appear to be efficient.

Chevallier:Abbvie: Honoraria; Jazz Pharmaceuticals: Honoraria; Takeda: Honoraria; Incyte: Research Funding; Pfizer: Research Funding.