Protection Against Breakthrough Delta/Omicron Variants in Vaccinated Patients with Myeloproliferative Neoplasms (MPN)

Abstract

Background Information on breakthrough SARS-CoV-2 infections in MPN vaccinated patients (pts) is very limited. In these diseases, effectiveness of coronavirus disease 2019 (Covid-19) vaccines may be influenced not only by the MPN phenotype and the intrinsic reduced immunological competence, but also by the prior Covid-19 infection that can elicit a natural immunity against reinfections. Patients In the European LeukemiaNet (ELN) observational registry, 863 MPN pts with Covid-19 have been enrolled since February 2020 and in 649 of them, information on the vaccination status is now available. To ensure that well characterized reinfections were considered, diagnosis of breakthrough Covid-19 included a positive naso-pharyngeal swab and symptoms highly suggestive for SARS CoV-2 infection. ResultsBreakthrough infections in vaccinated patients with previous Covid-19 infection The effectiveness of previous Covid-19 infection in preventing reinfections was tested in a group of 131 and 287 unvaccinated and vaccinated MPN pts, respectively. Prior Covid-19 occurred during the first and second wave in 74% and 98% pts, respectively and the interval between Covid-19 and the breakthrough infection in unvaccinated and in vaccinated was similar (8.5 months). Administered vaccine doses (Pfizer in 71%) were 1-2 and 3-4 in 77% and 23% of vaccinated cases, respectively. The proportion of PV, ET, pre-PMF was similar in the two groups while the number of MF pts was lower (19%) than in the unvaccinated group (28%) (p=0.024). Reinfections occurred during delta (n=4) or omicron variants period (n=14) in 8 (6.1%) and 10 (3.5%) unvaccinated and vaccinated pts (p=ns) and hospitalization was required in 0 and 2 pts, respectively. Severity of the acute infection was variable and 1 death was registered.Breakthrough infections in vaccinated patients without previous Covid-19 infection Breakthrough infections were reported in 231 vaccinated cases (ET=89, PV=75, MF=54 and pre-PMF=13) without prior Covid-19. In 51% of pts the administered vaccine doses were 1-2 and 3-4 in 49%. No relevant vaccine related side effects were registered. Time interval from vaccination to Covid-19 was 8.1 months. Twenty-six pts (11%) required hospitalization and 205 (89%) were managed at home. Hospitalized pts were older (median age 76), males (69%) with MF (39%), and prior exposure to ruxolitinib (42%, 7 MF and 4 PV). Of note, values of C-reactive protein (CRP) and neutrophil/lymphocyte ratio (NLR) were significantly more elevated in hospitalized cases (CRP=33.1 vs. 2.0 and NLR=5.9 vs. 3.3, p<0.001). Although some infections occurred in the second wave, corresponding to alpha/beta/gamma coronavirus infection (6%), the majority of breakthrough episodes occurred in delta and omicron variant periods (41% and 53%). Three deaths were registered in hospitalized pts. We explored the risk of hospitalization and evaluated the marginal effect of gender, age and ruxolitinib exposure in a logistic model fitted to predict this event. We found that the risk of hospitalization was substantially higher only in males on ruxolitinib and increased with age (Figure). We also found that the inflammatory status measured with NLR could explain these results (data not shown). Conclusion The effectiveness of previous Covid-19 in preventing reinfection occurring during the delta and omicron variants of SARS-CoV-2 was robust (94% and 97% in unvaccinated and vaccinated pts, respectively). This is good news for MPN patients who recovered from Covid-19 and the hope is that this effectiveness can work against any future SARS-CoV-2 variant. In the cohort of vaccinated pts without prior Covid-19, we identified a subgroup of patients with more severe delta and omicron disease, at high risk of hospitalization, consisting of males who were on ruxolitinib and had elevated inflammatory biomarkers. Subsequent studies are needed to interpret these latest results. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal