Blood Cancer Journal www.nature.com/bcj CORRESPONDENCE OPEN Breakthrough infections in MPN-COVID vaccinated patients © The Author(s) 2022 Blood Cancer Journal (2022)12:154 ; https://doi.org/ Vaccine doses (COVID-19 mRNA vaccine—Pfizer/BioNTech in 10.1038/s41408-022-00749-8 71%) were 1–2 and 3–4 in 77 and 23%, respectively. Only 3 patients (1%) received 4 vaccine shots. Adverse events (AE) attributed to vaccines (fever, headache) The first wave of COVID-19 in patients with myeloproliferative occurred in 8 patients (2.8%). No patient reported serious adverse neoplasms (MPN) including polycythemia vera (PV), essential events including thrombosis. thrombocythemia (ET), prefibrotic myelofibrosis (pre-PMF) and Overall, 18 reinfections were diagnosed; of these, 4 occurred overt myelofibrosis (MF), was characterized by severe illness, high during Delta and 14 during Omicron variants period (Table 1). hospitalization rate, and excess of mortality [1, 2]. Deaths Eight (6.1%) were recorded in unvaccinated and 10 (3.5%) in accounted for 28.5% of patients [1], an estimate 3-4-fold higher vaccinated patients (p = 0.22). Therefore, a statistically significant than in general population [3], and progressively decreased benefit of vaccination in individuals with prior COVID-19 was not thereafter [4]. This improvement was likely related to better critical apparent; however, these findings were based on a small number care management, less virulence of circulating variants of concern of reinfections and need confirmation by prolonging the follow-up 1234567890();,: (VOCs), younger patient’s age and vaccinations. The effectiveness in longitudinal studies to assess the durability of the protection in of vaccines to protect against disease severity, hospitalization and comparable groups [11]. death has been consistently demonstrated in the general Of note, among patients who developed reinfections, 9/10 population; [5] conversely, very limited information has been (90%) and 5/8 (63%) occurred during Omicron period in provided so far in rare diseases such as MPNs [6, 7] in which vaccinated and unvaccinated groups, respectively. The time vaccines elicit poor neutralizing antibody titers, particularly in MF interval between the first SARS-Cov-2 infection and the reinfection on ruxolitinib active treatment [8, 9]. was double in vaccinated than in unvaccinated patients (14.3 vs. We investigated 3 cohorts of COVID-MPN patients, observed since 7.5 months, respectively, p = 0.016), suggesting that booster or the beginning of the SARS-CoV2, from February 2020 to June 2022. repeat vaccination is important and the immunity wanes with In the European MPN-COVID registry, promoted by the LeukemiaNet time. Time from last vaccine shot to reinfection was 3.1 months. (ELN) (clinicaltrials.gov: NCT04385160), 863 MPN patients with Severity of reinfection was mild in the great majority of both COVID-19 have been enrolled, and in 649 of them, information on unvaccinated and vaccinated patients (88 and 67%, respectively, the vaccination status was provided. diagnosis of covid-19 required p = 0.72). a positive real-time reverse transcriptase polymerase chain reaction Overall, compared with the normal population, partial and fully from nasal swab and symptoms highly suggestive for sars-cov-2 hybrid vaccination in our MPN patient cohorts conferred a 10-fold infection. according to the most prevalent circulating vocs in europe lower protection (3.5%) than that reported in Italy (0.4%) [12] and at that time, 4 waves were identified: 1st, February to June 2020 in 2 US cohorts in New York city (0.4%) [13] and California (0.3%) (wild-type original variant) 2nd, July 2020–June 2021 (alpha/beta/ [13]. Notably, this poor result was limited to myelofibrosis and to gamma); 3rd, July 2021–December 2021 (delta); and wave 4th, exposure to ruxolitinib in which the rate of reinfections was not January to June 2022 (Omicron). The severity of COVID-19 was different from that registered in severely immunocompromised categorized as asymptomatic, mild, moderate or severe/critical patients [14]. according to the NIH COVID-19 Treatment Guidelines [10]. BREAKTHROUGH INFECTIONS IN VACCINATED PATIENTS INFECTIONS IN VACCINATED PATIENTS WITH PREVIOUS WITHOUT PREVIOUS COVID-19 INFECTION COVID-19 (HYBRID VACCINATION) Breakthrough infections were reported in vaccinated patients Of 418 patients with prior COVID-19, 287 were vaccinated and 131, (ET = 89, PV = 75, MF = 54 and pre-PMF = 13) who had no at the moment of the present analysis, were not. Almost all previous history of COVID-19. Of these, 26 (11%) were hospitalized vaccinated cases (98%) had prior COVID-19 during the first and and their characteristics, compared with home-treated cases, are second pandemic wave. In unvaccinated cases, prior COVID-19 reported in Table 2. Hospitalized patients were more likely to be occurred frequently during the last 2 waves, including Delta and older (median age 76 years), males (69%), afflicted with MF (39%), Omicron VOCs (26%) (Table 1). Of note, unvaccinated cases and to have had prior exposure to ruxolitinib (42%: 7 MF and 4 experienced the first episode of COVID-19 less severe than PV). Of note, baseline values at COVID-19 diagnosis of C-reactive vaccinated ones (i.e., asymptomatic in 7.3% vs. 2.6%, respectively, protein (CRP) and neutrophil to lymphocyte ratio (NLR) were p = 0.003) and were younger (median age 59 years vs. 62 years, significantly higher in hospitalized than in home-managed cases respectively, p = 0.016). The proportion of PV, ET, pre-PMF was (CRP = 33.1 mg/dl vs. 2.0 and NLR = 5.9 vs. 3.3, p < 0.001). similar in the two groups while the proportion of MF patients was Although some infections occurred in the second wave, corre- lower in the vaccinated than unvaccinated group (19% vs 28%) sponding to Alpha/Beta/Gamma VOCs, the majority of break- (p = 0.024). No difference of driver mutations frequency and through episodes occurred during Delta and Omicron variant splenomegaly among the MPN phenotypes was found. periods (41% and 53%, respectively), and illness severity was mild Received: 19 October 2022 Revised: 2 November 2022 Accepted: 2 November 2022 Correspondence 2 Table 1. Characteristics of patients with previous COVID-19 infection according to vaccination status. Total pts with previous infection UNVACCINATED VACCINATED p N = 418 N = 131 N = 287 Male gender 189/418 (45.2%) 51/131 (38.9%) 138/287 (48.1%) 0.081 Age 61.3 (53.0–71.7) 59.3 (47.9–71.9) 61.8 (54.6–71.7) 0.016 > 70 124/417 (29.7%) 36/131 (27.5%) 88/286 (30.8%) 0.50 BMI 24.0 (21.3–26.5) 24.4 (21.7–26.1) 23.9 (21.3–26.5) 0.89 MPN diagnosis ET 156/418 (37.3%) 41/131 (31.3%) 115/287 (40.1%) 0.085 PV 133/418 (31.8%) 41/131 (31.3%) 92/287 (32.1%) 0.88 MF 90/418 (21.5%) 37/131 (28.2%) 53/287 (18.5%) 0.024 Early/pre-PMF 39/418 (9.3%) 12/131 (9.2%) 27/287 (9.4%) 0.94 Previous thrombosis 81/415 (19.5%) 24/129 (18.6%) 57/286 (19.9%) 0.75 Mutational status JAK2 V617F 303/408 (74.3%) 93/127 (73.2%) 210/281 (74.7%) 0.75 CALR 64/231 (27.7%) 19/89 (21.3%) 45/142 (31.7%) 0.087 MPL 10/220 (4.5%) 5/88 (5.7%) 5/132 (3.8%) 0.53 JAK2 EXON12 1/126 (0.8%) 1/55 (1.8%) 0/71 (0.0%) 0.44 Spleen palpable No 270/386 (69.9%) 88/125 (70.4%) 182/261 (69.7%) Yes 111/386 (28.8%) 35/125 (28.0%) 76/261 (29.1%) 0.87 Previously splenectomized 5/386 (1.3%) 2/125 (1.6%) 3/261 (1.1%) Size below costal margin (cm) 4.0 (2.0–6.0) 4.5 (2.0–6.5) 3.0 (2.0–6.0) 0.30 MPN treatment post-COVID Phlebotomy 76/410 (18.5%) 24/130 (18.5%) 52/280 (18.6%) 0.98 Cytoreduction 289/418 (69.1%) 83/131 (63.4%) 206/287 (71.8%) 0.084 HU 196/412 (47.6%) 54/130 (41.5%) 142/282 (50.4%) 0.096 Anagrelide 13/412 (3.2%) 1/130 (0.8%) 12/282 (4.3%) 0.071 Interferon 12/412 (2.9%) 3/130 (2.3%) 9/282 (3.2%) 0.76 Ruxolitinib 63/412 (15.3%) 20/130 (15.4%) 43/282 (15.2%) 0.97 Antiplatelets post-COVID 250/410 (61.0%) 75/129 (58.1%) 175/281 (62.3%) 0.43 ASA 233/412 (56.6%) 73/130 (56.2%) 160/282 (56.7%) 0.91 Anticoagulants 95/409 (23.2%) 32/128 (25.0%) 63/281 (22.4%) 0.57 Characteristics of COVID-19 Wave 1 (Wild-type) 94/418 (22.5%) 14/131 (10.7%) 80/287 (27.9%) <0.001 2 (Alpha, Beta, Gamma) 284/418 (67.9%) 83/131 (63.4%) 201/287 (70.0%) 0.175 3 (Delta) 19/418 (4.5%) 17/131 (13.0%) 2/287 (0.7%) <0.001 4 (Omicron) 21/418 (5.0%) 17/131 (13.0%) 4/287 (1.4%) <0.001 COVID-19 severitya Asymptomatic infection 16/389 (4.1%) 9/123 (7.3%) 7/266 (2.6%) 0.003 Mild Illness 286/389 (73.5%) 84/123 (68.3%) 202/266 (75.9%) 0.11 Moderate Illness 25/389 (6.4%) 7/123 (5.7%) 18/266 (6.8%) 0.69 Severe/critical Illness 62/389 (15.9%) 23/123 (18.7%) 39/266 (14.7%) 0.31 Vaccine information Months since prior infection – – 5.9 (4.3–11.2) – No administered doses Only 1 dose – – 109/287 (38.0%) – 2 doses – – 112/287 (39.0%) – 3–4 doses – – 66/287 (23.0%) – Blood Cancer Journal (2022)12:154 Correspondence 3 Table 1. continued Total pts with previous infection UNVACCINATED VACCINATED p N = 418 N = 131 N = 287 Vaccine type Pfizer/BioNTech – – 204/287 (71.1%) – Moderna – – 53/287 (18.5%) – AstraZeneca – – 12/287 (4.2%) – Johnson&Johnson – – 3/287 (1.0%) – NA – – 15/287 (5.2%) – Reinfections 18 (4.3%) 8 (6.1%) 10 (3.5%) 0.22 Months to reinfection from prior COVID-19 13.1 (8.2–15.0) 7.5 (4.8–13.1) 14.3 (12.9–16.8) 0.016 Months to reinfection from last vaccine dose – – 3.1 (2.5–7.1) – Number of doses Only 1 dose – – 2/10 (20.0%) 2 doses – – 4/10 (40.0%) – 3–4 doses – – 4/10 (40.0%) Wave of reinfection 3 (Delta) 4/18 (22.2%) 3/8 (37.5%) 1/10 (10.0%) 0.27 4 (Omicron) 14/18 (77.8%) 5/8 (62.5%) 9/10 (90.0%) COVID-19 severitya Asymptomatic infection 2/17 (11.8%) 1/8 (12.5%) 1/9 (11.1%) 0.72 Mild Illness 13/17 (76.5%) 7/8 (87.5%) 6/9 (66.7%) Severe/critical Illness 2/17 (11.8%) 0/8 (0.0%) 2/9 (22.2%) Patient disposition Home-treated 16/18 (88.9%) 8/8 (100.0%) 8/10 (80.0%) 0.48 Hospitalized 2/18 (11.1%) 0/8 (0.0%) 2/10 (20.0%) Respiratory support 1/18 (5.6%) 0/8 (0.0%) 1/10 (10.0%) 1.00 ICU 1/18 (5.6%) 0/8 (0.0%) 1/10 (10.0%) 1.00 Symptoms Fever 5/18 (27.8%) 3/8 (37.5%) 2/10 (20.0%) 0.61 Cough 7/18 (38.9%) 1/8 (12.5%) 6/10 (60.0%) 0.066 Dyspnea 3/18 (16.7%) 0/8 (0.0%) 3/10 (30.0%) 0.22 Systemic 1/18 (5.6%) 0/8 (0.0%) 1/10 (10.0%) 1.00 Gastrointestinal 1/18 (5.6%) 0/8 (0.0%) 1/10 (10.0%) 1.00 Fatigue 6/18 (33.3%) 2/8 (25.0%) 4/10 (40.0%) 0.64 Outcome reinfections Deathb 1/18 (5.6%) 0/8 (0.0%) 1/10 (10.0%) 1.00 a According to the NIH COVID-19 Treatment Guidelines. b The dead patient was male with age > 70 years old, had a MF diagnosis treated with fedratinib (in a clinical trial) and had a severe breakthrough infection in the Omicron period (symptoms: cough, dyspnea, fatigue) after 2 doses of vaccine and needed invasive respiratory support. in the great majority (86%), even though a moderate to severe likely excluding that hospitalization could be attributed to the infection accounted for more than half of hospitalized patients. waning of vaccine protection. This possibility is particularly Five deaths were registered: 3 and 2 in hospitalized and home relevant with Delta and Omicron variants which are able, at least managed cases, respectively (12% vs. 1%, p = 0.011). The number partially, to evade vaccine-induced immunity [11]. of vaccine doses was the same in the 2 groups, and patients fully In a multivariable logistic model fitted to predict hospitalization, vaccinated (3–4 shots) were 42% and 41%, respectively. Mild we found that this risk was age-related and substantially higher in adverse events (AE) attributed to vaccination were seen in only 3 males on ruxolitinib (Fig. 1S, panel A). Interestingly, these two patients (1.3%). factors were also related to a progressive increase of NLR Compared with the normal population of the 2 US cohorts of inflammatory biomarker (Fig. 1S, panel B), suggesting a connec- patients experiencing COVID-19 after vaccination [13], the tion between sex, aging and inflammation. proportion of hospitalization in our patients is markedly higher In conclusion, we have provided quantitative estimates of SARS- (11% vs 4.4% and 1.8%). This difference was not attributable to the CoV2 infections in vaccinated patients with MPN revealing a number of vaccine shots in home-managed and in hospitalized higher rate of severe disease than in the normal population. patients and the two groups did not differ regarding the time Compared to unvaccinated, a trend for a lower reinfection rate between the last shot of vaccination and the onset of infection, was found in patients with hybrid vaccination. In COVID-naïve Blood Cancer Journal (2022)12:154 Correspondence 4 Table 2. Characteristics of vaccine breakthrough infections according to the severity of Covid-19. Total pts without previous infection HOME-TREATED HOSPITALIZED p N = 231 N = 205 N = 26 Male gender 105/231 (45.5%) 87/205 (42.4%) 18/26 (69.2%) 0.010 Age at COVID diagnosis 60.4 (49.8–73.2) 57.4 (49.2–71.5) 75.5 (67.3–84.3) <0.001 >70 71/231 (30.7%) 55/205 (26.8%) 16/26 (61.5%) <0.001 MPN diagnosis ET 89/231 (38.5%) 80/205 (39.0%) 9/26 (34.6%) 0.66 PV 75/231 (32.5%) 68/205 (33.2%) 7/26 (26.9%) 0.52 MF 54/231 (23.4%) 44/205 (21.5%) 10/26 (38.5%) 0.054 Early/pre-PMF 13/231 (5.6%) 13/205 (6.3%) 0/26 (0.0%) 0.19 Previous thrombosis 36/231 (15.6%) 30/205 (14.6%) 6/26 (23.1%) 0.26 Mutational status JAK2 V617F 166/227 (73.1%) 147/203 (72.4%) 19/24 (79.2%) 0.48 CALR 34/136 (25.0%) 32/126 (25.4%) 2/10 (20.0%) 0.70 MPL 7/131 (5.3%) 6/123 (4.9%) 1/8 (12.5%) 0.36 JAK2 EXON12 0/70 (0.0%) 0/65 (0.0%) 0/5 (0.0%) Spleen palpable No 152/218 (69.7%) 136/193 (70.5%) 16/25 (64.0%) Yes 64/218 (29.4%) 55/193 (28.5%) 9/25 (36.0%) 0.60 Previously splenectomized 2/218 (0.9%) 2/193 (1.0%) 0/25 (0.0%) Size below costal margin (cm) 5.0 (2.0–7.0) 4.5 (2.0–7.0) 6.0 (4.0–20.0) 0.11 MPN-treatment before COVID Phlebotomy 38/230 (16.5%) 36/204 (17.6%) 2/26 (7.7%) 0.20 Cytoreduction pre-COVID 167/230 (72.6%) 144/204 (70.6%) 23/26 (88.5%) 0.054 Type: HU 93/231 (40.3%) 83/205 (40.5%) 10/26 (38.5%) 0.84 Anagrelide 19/231 (8.2%) 19/205 (9.3%) 0/26 (0.0%) 0.11 Interferon 5/231 (2.2%) 5/205 (2.4%) 0/26 (0.0%) 0.42 Ruxolitinib 40/231 (17.3%) 29/205 (14.1%) 11/26 (42.3%) <0.001 Other 11/231 (4.8%) 9/205 (4.4%) 2/26 (7.7%) 0.36 Characteristics of Covid-19 Wave 2 (Alpha, Beta, Gamma) 14/231 (6.1%) 11/205 (5.4%) 3/26 (11.5%) 0.20 3 (Delta) 94/231 (40.7%) 79/205 (38.5%) 15/26 (57.7%) 0.061 4 (Omicron) 123/231 (53.2%) 115/205 (56.1%) 8/26 (30.8%) 0.015 COVID-19 severitya Asymptomatic infection 11/220 (5.0%) 11/197 (5.6%) 0/23 (0.0%) 0.61 Mild Illness 190/220 (86.4%) 180/197 (91.4%) 10/23 (43.5%) <0.001 Moderate Illness 6/220 (2.7%) 4/197 (2.0%) 2/23 (8.7%) 0.12 Severe/critical Illness 13/220 (5.9%) 2/197 (1.0%) 11/23 (47.8%) <0.001 Respiratory support 19/231 (8.2%) 3/205 (1.5%) 16/26 (61.5%) <0.001 ICU 5/230 (2.2%) 1/204 (0.5%) 4/26 (15.4%) <0.001 Saturation 98.0 (96.0–99.0) 98.0 (97.0–99.0) 92.0 (88.0–94.0) <0.001 Lab values at COVID diagnosis Hb 12.9 (11.3–14.0) 13.0 (11.5–14.1) 11.5 (9.0–13.1) 0.002 HCT 40.0 (36.0–44.0) 40.5 (36.7–44.5) 37.5 (27.3–40.1) 0.004 RDW 16.5 (14.3–18.7) 16.0 (13.9–18.1) 18.3 (15.4–18.9) 0.093 WBC 7.5 (5.5–10.5) 7.5 (5.7–10.2) 8.1 (4.8–11.5) 0.93 Neutrophils 68.9 (56.9–76.0) 67.1 (56.3–75.0) 75.3 (63.0–82.8) 0.028 Lymphocytes 18.2 (10.9–26.8) 19.8 (12.0–28.2) 13.1 (7.4–18.5) 0.005 Neutrophils/lymphocytes ratio 3.6 (2.1–6.0) 3.3 (2.0–5.3) 5.9 (3.6–10.2) <0.001 PLT 401.0 (226.0–608.5) 430.0 (274.0–622.0) 199.0 (119.0–294.0) <0.001 LDH 243.0 (200.0–470.0) 236.5 (191.0–447.0) 415.0 (269.0–573.0) 0.022 CRP 8.9 (1.4–32.9) 2.0 (0.9–16.0) 33.1 (17.0–123.0) <0.001 Fibrin 402.0 (339.0–579.0) 339.0 (309.0–480.0) 432.0 (360.0–726.0) 0.12 D-dimer 510.0 (270.0–759.0) 331.5 (185.0–568.5) 650.0 (440.0–910.0) 0.015 Blood Cancer Journal (2022)12:154 Correspondence 5 Table 2. continued Total pts without previous infection HOME-TREATED HOSPITALIZED p N = 231 N = 205 N = 26 Vaccine information Months from last vaccine dose to infection 4.0 (1.4–6.6) 4.0 (1.5–6.7) 2.6 (1.2–6.0) 0.37 N° administered doses Only 1 dose 22/231 (9.5%) 19/205 (9.3%) 3/26 (11.5%) 0.90 2 doses 115/231 (49.8%) 103/205 (50.2%) 12/26 (46.2%) 3–4 doses 94/231 (40.7%) 83/205 (40.5%) 11/26 (42.3%) Vaccine type Pfizer/BioNTech 179/231 (77.5%) 164/205 (80.0%) 15/26 (57.7%) 0.010 Moderna 28/231 (12.1%) 22/205 (10.7%) 6/26 (23.1%) 0.069 AstraZeneca 18/231 (7.8%) 14/205 (6.8%) 4/26 (15.4%) 0.13 Johnson&Johnson 5/231 (2.2%) 4/205 (2.0%) 1/26 (3.8%) 0.45 UNK 1/231 (0.4%) 1/205 (0.5%) 0/26 (0.0%) – Outcome Death 5/231 (2.2%) 2/205 (1.0%) 3/26 (11.5%) 0.011 a According to the NIH COVID-19 Treatment Guidelines. MPN patients, current original vaccine shots have shown a limited Spain. 10Center Research and Innovation of Myeloproliferative protection against delta and omicron VOCs. While waiting for the Neoplasms (CRIMM), Department of Experimental and Clinical results of the new boosters targeting the newest strains of the Medicine, Azienda Ospedaliera Universitaria Careggi, University of omicron variants, we suggest a prompt identification of the MPN Florence, Florence, Italy. 11Department of Medicine, University of subgroup at high risk of hospitalization, in which early treatment Verona, Azienda Ospedaliera Universitaria Integrata, Verona, Italy. 12 with the recent monoclonal antibodies against the spike protein AOU SS.Antonio e Biagio e C.Arrigo, Alessandria, Italy. 13Hospital of the SARS-CoV-2 virus, anti-inflammatory and antiviral drugs can Clinic de Barcelona, Barcelona, Spain. 14Department of Hematology, be suggested. Vall d’Hebron Institute of Oncology (VHIO), Vall d’Hebron Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus, C/Natzaret, ✉ 115-117, 08035 Barcelona, Spain. 15ASST Papa Giovanni XXIII, Tiziano Barbui 1 , Alessandra Carobbio 1, Arianna Ghirardi1, Alessandra Iurlo 2, Valerio De Stefano 3, Marta Anna Sobas4, Bergamo, Italy. 16ASST-Spedali Civili, Brescia, Italy. 17AOU Città della Elisa Rumi5, Elena Maria Elli6, Francesca Lunghi7, Salute e della Scienza di Torino, Torino, Italy. 18Hospital Universitario Mercedes Gasior Kabat8, Beatriz Cuevas 9, 12 de Octubre, Madrid, Spain. 19AOU Maggiore della Carità, Novara, Paola Guglielmelli 10, Massimiliano Bonifacio 11, Italy. 20University Hospital Halle, Department of Hematology/ Monia Marchetti12, Alberto Alvarez-Larran13, Laura Fox14, Oncology, 06112 Halle (Saale), Germany. 21Hospital del Mar, Marta Bellini15, Rosa Daffini16, Giulia Benevolo17, Barcelona, Spain. 22IRCCS Azienda Ospedaliero-Universitaria di Gonzalo Carreno-Tarragona 18, Andrea Patriarca 19, Bologna, Bologna, Italy. 23Guy’s and St. Thomas’ NHS Foundation Haifa Kathrin Al-Ali20, Maria Marcio Miguel Andrade-Campos21, Trust, London, United Kingdom. 24Hospital Universitario Infanta Francesca Palandri 22, Claire Harrison23, Leonor, Madrid, Spain. 25Hospital Gregorio Maranon, Madrid, Spain. 26 Maria Angeles Foncillas24, Santiago Osorio25, Department of Hematology, Oncology, Hemostaseology, and Stem Steffen Koschmieder 26, Elena Magro Mazo27, Cell Transplantation, Faculty of Medicine, RWTH Aachen University, Jean-Jacques Kiladjian28, Estefanía Bolaños Calderón29, Aachen, Germany. 27Hospital Universitario Principe de Asturias, Florian H. Heidel30, Keina Quiroz Cervantes 31, Alcalà de Henares, Madrid, Spain. 28Hospital Saint-Louis, Paris, Martin Griesshammer32, Valentin Garcia-Gutierrez 33, France. 29Hospital Clinico San Carlos, Madrid, Spain. 30University Alberto Marin Sanchez34, Juan Carlos Hernandez-Boluda 35, Medicine Greifswald - Hematology, Oncology, Stem Cell Emma Lopez Abadia36, Giuseppe Carli37, Miguel Sagues Serrano38, Transplantation and Palliative Care Sauerbruchstraße, 17475 Rajko Kusec39, Blanca Xicoy Cirici40, Margarita Guenova41, Greifswald, Germany. 31Hospital Universitario de Mostoles, Madrid, Begona Navas Elorza42, Anna Angona43, Edyta Cichocka44, Spain. 32University Clinic for Hematology, Oncology, Hemostaseology Anna Kulikowska de Nałęcz45, Daniele Cattaneo 2,46, and Palliative Care, Johannes Wesling Medical Center, Minden, Cristina Bucelli2, Silvia Betti3, Oscar Borsani 5, Fabrizio Cavalca6, Germany. 33Hospital Ramon y Cajal, IRYCIS, Madrid, Spain. 34Hospital Sara Carbonell13, Natalia Curto-Garcia23, Lina Benajiba28, General Universitario de Albacete, Albacete, Spain. 35Hospital Clinico Alessandro Rambaldi 15,46 and Alessandro Maria Vannucchi10 Universitario, INCLIVA, Valencia, Spain. 36Hospital General de Elche, 1 FROM Research Foundation, Papa Giovanni XXIII Hospital, Bergamo, Elche (Alicante), Spain. 37Ospedale San Bortolo, Vicenza, Italy. 38ICO Italy. 2Hematology Division, Foundation IRCCS Ca’ Granda Ospedale L’Hospitalet-Hospital Moises Broggi, Sant Joan Despì, Barcelona, Maggiore Policlinico, Milan, Italy. 3Dipartimento di Scienze Spain. 39University Hospital Dubrava-School of Medicine University of Radiologiche ed Ematologiche, Sezione di Ematologia, Università Zagreb, Department of haematology, Clinic of internal medicine, Cattolica del Sacro Cuore – Policlinico Universitario Agostino Gemelli Zagreb, Croatia. 40ICO Hospital Germans Trias i Pujol, Badalona IRCCS, Rome, Italy. 4Department of Hematology, Blood Neoplasms (Barcelona), Josep Carreras Leukemia Research Institute, Universitat and Bone Marrow Transplantation, Wroclaw Medical University, Autònoma de Barcelona, Barcelona, Spain. 41National Specialised Wrocław, Poland. 5Department of molecular medicine, University of Hospital for Active Treatment of Hematological Diseases, Sofia, Pavia, Pavia, Italy. 6Hematology Division and Bone Marrow Bulgaria. 42Hospital Moncloa, Madrid, Spain. 43ICO Girona Hospital Transplant Unit, San Gerardo Hospital, ASST Monza, Monza, Italy. Josep Trueta, Girona, Spain. 44Department of Hematology and Bone 7 IRCCS Ospedale San Raffaele, Milano, Italy. 8Hospital Universitario Marrow Transplantation, Nicolaus Copernicus Hospital, Torun, La Paz, Madrid, Spain. 9Hospital Universitario de Burgos, Burgos, Poland. 45Department of Hematology and Internal Diseases, State Blood Cancer Journal (2022)12:154 Correspondence 6 46 Hospital, Opole, Poland. Università degli Studi di Milano, Milano, ACKNOWLEDGEMENTS Italy. ✉email: tbarbui@fondazionefrom.it The study was supported by a research grant by the COVID “3 × 1 project”, BREMBO S.p.A., Bergamo, Italy (T.B.) and by AIRC 5 × 1000 call “Metastatic disease: the key unmet need in oncology” to MYNERVA project, #21267 (MYeloid NEoplasms Research Venture AIRC). A detailed description of the MYNERVA project is available at https:// DATA AVAILABILITY progettomynerva.it (A.M.V., P.G.). The study was also supported by HARMONY PLUS, Aggregated data available by request. Patient-level data will not be shared. which is funded through the Innovative Medicines Initiative (IMI), Europe’s largest public–private initiative aiming to speed up the development of better and safer medicines for patients. The HARMONY Alliance has received funding from IMI 2 Joint REFERENCES Undertaking and is listed under grant agreement No. 945406. This Joint Undertaking 1. Barbui T, Vannucchi AM, Alvarez-Larran A, Iurlo A, Masciulli A, Carobbio A, et al. receives support from the European Union’s Horizon 2020 Research and Innovation High mortality rate in COVID-19 patients with myeloproliferative neoplasms after Programme and the European Federation of Pharmaceutical Industries and abrupt withdrawal of ruxolitinib. Leukemia. 2021;35:485–93. Associations (EFPIA). IMI supports collaborative research projects and builds networks 2. Barbui T, Carobbio A, Ghirardi A, Iurlo A, Sobas MA, Elli EM, et al. Determinants of of industrial and academic experts in order to boost pharmaceutical innovation in early triage for hospitalization in MPN patients with COVID-19. Am J Hematol Europe. 2022. https://doi.org/10.1002/ajh.26732. 3. Nachtigall I, Lenga P, Jóźwiak K, Thürmann P, Meier-Hellmann A, Kuhlen R, et al. Clinical course and factors associated with outcomes among 1904 patients hospitalized with COVID-19 in Germany: an observational study. Clin Microbiol AUTHOR CONTRIBUTIONS TB conceived and designed the study, supervised the analysis and wrote the paper. Infect. 2020;26:1663–9. AMV, SK revised the study and contributed to manuscript writing. AC and AG 4. Barbui T, Iurlo A, Masciulli A, Carobbio A, Ghirardi A, Carioli G, et al. Second versus performed statistical analysis. VDS, MAS, ER, EME, FL, MGK, BC, PG, MB, MM, AAL, LF, first wave of COVID-19 in patients with MPN. Leukemia. 2022;36:897–900. MB, RD, GB, GCT, AP, HKAA, MMMAC, FP, CH, MAF, SO, SK, EMM, JJK, EBC, FHH, KQC, 5. Nordström P, Ballin M, Nordström A. Risk of infection, hospitalisation, and death MG, VGG, AMS, JCHB, ELA, GC, MSS, RK, BXC, MG, BNE, AA, EC, AKDN, DC, CB, SB, OB, up to 9 months after a second dose of COVID-19 vaccine: a retrospective, total FC, SC, NCG, LB, AR collected data. All authors revised and approved the final version population cohort study in Sweden. Lancet. 2022;399:814–23. of the manuscript. 6. Ali EAH, Khamees I, Alshurafa A, Qasim H, Abu-Tineh MA, Ahmed K, et al. Severe acute respiratory syndrome coronavirus 2 omicron variant in patients with philadelphia-negative myeloproliferative neoplasm: a single center experience. Oncology. 2022;100:460–6. COMPETING INTERESTS 7. Cattaneo D, Bucelli C, Cavallaro F, Consonni D, Iurlo A. Impact of diagnosis and The authors declare no competing interests. treatment on response to COVID-19 vaccine in patients with BCR-ABL1-negative myeloproliferative neoplasms. A single-center experience. Blood Cancer J. 2021;11:185. ADDITIONAL INFORMATION 8. Fiorino F, Sicuranza A, Ciabattini A, Santoni A, Pastore G, Simoncelli M, et al. The Supplementary information The online version contains supplementary material slower antibody response in myelofibrosis patients after two doses of mRNA available at https://doi.org/10.1038/s41408-022-00749-8. SARS-CoV-2 vaccine calls for a third dose. Biomedicines. 2021;9:1480. 9. Pimpinelli F, Marchesi F, Piaggio G, Giannarelli D, Papa E, Falcucci P, et al. Lower Correspondence and requests for materials should be addressed to Tiziano Barbui. response to BNT162b2 vaccine in patients with myelofibrosis compared to polycythemia vera and essential thrombocythemia. J Hematol Oncol. Reprints and permission information is available at http://www.nature.com/ 2021;14:119. reprints 10. National Institutes of Health Treatment Guidelines Panel. Coronavirus Diseases 2022 (COVID-19). COVID-19 Treatment Guidelines. [2022 August]. Available from: Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims https://www.covid19treatmentguidelines.nih.gov/. in published maps and institutional affiliations. 11. Tada T, Zhou H, Dcosta BM, Samanovic MI, Mulligan MJ, Landau NR. Partial resistance of SARS-CoV-2 delta variants to vaccine-elicited antibodies and con- valescent sera. iScience. 2021;24:103341. 12. Flacco ME, Soldato G, Acuti Martellucci C, Di Martino G, Carota R, Caponetti A, et al. Risk of SARS-CoV-2 reinfection 18 months after primary infection: Open Access This article is licensed under a Creative Commons population-level observational study. Front Public Health. 2022;10:884121. Attribution 4.0 International License, which permits use, sharing, 13. León TM, Dorabawila V, Nelson L, Lutterloh E, Bauer UE, Backenson B, et al. adaptation, distribution and reproduction in any medium or format, as long as you give COVID-19 cases and hospitalizations by COVID-19 vaccination status and pre- appropriate credit to the original author(s) and the source, provide a link to the Creative vious COVID-19 diagnosis—California and New York, May-November 2021. Commons license, and indicate if changes were made. The images or other third party MMWR Morb Mortal Wkly Rep. 2022;71:125–31. material in this article are included in the article’s Creative Commons license, unless 14. Basic-Jukic N, Arnol M, Maksimovic B, Aleckovic-Halilovic M, Racki S, Barbic J, et al. indicated otherwise in a credit line to the material. If material is not included in the Clinical characteristics and outcomes of kidney transplant recipients with SARS- article’s Creative Commons license and your intended use is not permitted by statutory CoV-2 reinfections. Transplantation 2022;106:e501–2. regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http:// creativecommons.org/licenses/by/4.0/. © The Author(s) 2022 Blood Cancer Journal (2022)12:154