According to the results of a study published in Lancet Haematology, patients with paroxysmal nocturnal hemoglobinuria (PNH) and aplastic anemia had substantially reduced seroconversion rates and antibody responses following a first SARS-CoV-2 vaccination compared with those of volunteers without either condition. However, after a second vaccination, patients achieved seropositivity and antibody responses equivalent to those of volunteers without anemia.

“There is a concern that patients with [PNH and aplastic anemia] might be less able to mount an effective immune response due to their underlying disease or treatment-related immunosuppression, and might be at risk of more severe SARS-CoV-2 infections,” the researchers wrote in their report.

The researchers conducted a post-implementation, real-world, prospective, observational study to investigate antibody responses to SARS-CoV-2 vaccination in adult patients with PNH and aplastic anemia. Between January 1 and December 1, 2021, they recruited patients under the care of the UK PNH National Service in Leeds, UK, and volunteers without anemia from among the UK National Health Service and University of Leeds staff.

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Blood samples were collected from participants before vaccination and 4-6 weeks after the first and second vaccinations of ChAdOx1-S (Oxford-AstraZeneca) or BNT162b2 (Pfizer-BioNTech). The researchers tested serum spike-specific composite IgA, IgG, and IgM antibodies and compared responses of patients and volunteers without anemia. They also conducted post-hoc subgroup analyses to identify variables associated with response, including diagnosis (classic PNH, aplastic anemia-PNH overlap, and aplastic anemia), age, calcineurin inhibitor therapy, and vaccine type.

A total of 175 patients and 45 volunteers were enrolled in the study; those with concurrent immunosuppression for other indications were excluded from the final analysis (n=4). In evaluable participants (n=216; 55% female), the median age was 52 years (interquartile range [IQR], 40-67).

After a first vaccination, patients demonstrated a reduced seroconversion rate compared with that of the volunteers (63% vs 95%, respectively). The rate was similar across patient subgroups (63% in those with classic PNH, 68% in those with aplastic anemia-PNH, and 55% in those with aplastic anemia).

Patients also had a 2.4-fold lower antibody response than volunteers without anemia (median optical density [OD] ratio, 1.2 vs 2.9; P <.0001). All patient subgroups had significantly lower absolute antibody levels than those of the volunteers (median OD ratio, 1.2 for classic PNH; 1.4 for aplastic anemia-PNH; and 1.2 for aplastic anemia; P <.0001 for all).

After a second vaccination, patients achieved seropositivity and magnitude of antibody responses equivalent to those of the volunteers in the study. The seroconversion rate was 99% in patients and 98% in the volunteers, and the researchers observed no difference in antibody levels (median OD ratio, 3.3 in patients vs 4.0 in volunteers; P =.097).

Between the first and second vaccinations, the team observed an increase in the antibody response of 39% in volunteers (P =.0002), 175% in those with classic PNH (P =.0001), 184% in those with aplastic anemia-PNH (P =.0001), and 147% in those with aplastic anemia (P =.0034).

In multivariate analyses adjusted for other variables, factors significantly associated with reduced response to first vaccination were being a patient vs volunteer without anemia (odds ratio [OR], 9.10; 95% CI, 1.49-55.43]; P =.017), being female vs male (OR, 2.64; 95% CI, 1.24-5.59; P =.012), and receiving ChAdOx1-S vs BNT162b2 (OR, 2.52; 95% CI, 1.10-5.80; P =.030). The researchers found no significant associations between any variable and reduced response after the second vaccination.

“Our data highlight the importance of at least 2 vaccinations in patients with PNH or a history of aplastic anemia to achieve a good SARS-CoV-2 antibody response, and we expect that they will benefit from booster programs,” concluded the researchers. “Although we have found robust antibody levels after 2 vaccinations, further studies are needed to determine the longevity of response, degree of effective IgG responses, T-cell responses, and long-term infection outcomes.”


Pike A, McKinley C, Forrest B, et al. COVID-19 vaccination antibody responses in patients with aplastic anaemia and paroxysmal nocturnal haemoglobinuria. Published online June 30, 2022. Lancet Haematol. doi:10.1016/S2352-3026(22)00183-1