Impact of Sars-Cov-2 Infection in Hematopoietic Transplant Patients: Experience from the Madrid Group

Abstract

Peter Paschka and Hartmut Döhner contributed equally. Background. SARS-CoV-2 infection (COVID-19) has had a great impact worldwide and its mortality has been reported to be higher in patients with haematological malignancies. However, description of its effects and outcomes among recipient of hematopoietic stem cell transplantation (HSCT) is scarce. Objectives. To describe the characteristics, treatment and outcome of COVID-19 in recipients of HSCT reported to the Madrid registry of COVID-19 ("HEMATO-MADRID COVID-19 registry"). Results. Data of 842 patients from 23 hospitals with haematological malignancies and COVID-19 infection were reported in the Madrid registry between March and June 2020. Among those, 87 (10.3%) patients were HSCT recipients: 58 auto-HSCT and 29 allo-HSCT (7 of them from matched related donor (MRD), 12 matched unrelated donor (MUD) and 10 haplo-HSCT). Characteristics of the population are described in Table 1. Median age at COVID-19 infection was 61 years (IQR, 53-67) and 35 patients (40%) were female. Recipients of auto-HSCT with COVID-19 were older and showed a trend towards a higher incidence of arterial hypertension (28% vs 10%, p=0.067) without statistical differences in other comorbidities; active disease requiring treatment at COVID-19 diagnosis was more frequent in auto-HSCT recipients (65% vs. 21%, p<0.001). Median time from transplant to COVID19 infection was shorter in allo-HSCT patients (32 vs. 19 months, p=0.043). Nearly 40% of allo-recipients had active GVHD at COVID-19 debut, including pulmonary GVHD. A total of 63 (72%) patients required hospital admission and 13 patients (15%) received intensive care support. Allo-recipients showed a trend towards a higher need of hospital admission (79% vs. 68%, p=0.081). Most patients received anti-viral treatment with either hydroxichloroquine (47 patients, 54%), lopinavir/ritonavir (34 patients, 39%), remdesivir (5, 4%) and/or other treatments including azythromicin or interferon. 23 patients (26%) received anticytokine treatment with tocilizumab (15, 17%) and/or anakinra (8, 9%) and 27 patients (31%) received steroids. The overall response rate to treatment and supportive care was 80% in both groups. After a median follow-up of 50 days after the infection debut, overall-survival at day 50 was 84% for auto and 82% for allo-HSCT recipients (p=0.915). However, global mortality rate among the complete observation period was significantly higher in allo-recipients (24% vs. 17%, p <0.001). Conclusion. In our multicentric experience in a high COVID-19 impacted area, the median time of COVID-19 infection presentation was relatively late in transplanted patients, however shorter in allo-transplanted patients. COVID-19 related mortality was high in HSCT recipients, significantly higher in allo-transplanted patients. Factors associated to this higher mortality should be further investigated to promptly identify high-risk patients since the pandemic is still highly active worldwide. Disclosures Kwon: Gilead: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Jazz: Consultancy, Honoraria. Duarte:Incyte Corporation: Other: Has received speaker and advisor fees. Hernandez-Rivas:Rovi: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Celgene/BMS: Membership on an entity's Board of Directors or advisory committees. Jimenez Yuste:NovoNordisk: Consultancy, Honoraria, Research Funding; Roche: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; Grifols: Honoraria, Research Funding; Bayer: Honoraria; Sobi: Consultancy, Honoraria, Research Funding; CSL: Honoraria; Octapharma: Honoraria.

Reduction in incidence of non‐COVID‐19 respiratory virus infection amongst haematology inpatients following UK social distancing measures

“…9 Influenza, parainfluenza, and adenovirus can all cause severe disease in the immunocompromised, and SARS-CoV-2 has been shown to cause severe disease and excess mortality in those who have undergone HSCT and some haematological malignancies. 10,11 Regional surveillance networks have noted a significant reduction in influenza transmission in both southern 12 and northern hemispheres 13 (https://www.cdc.gov/flu/weekly/inde x.html) during their respective winter seasons in 2020-21. This has been attributed to non-pharmacological interventions and social distancing introduced to reduce SARS-CoV-2 transmission.Here, we describe the impact of UK social distancing measures on the incidence of non-SARS-CoV-2 respiratory viral infection in a cohort of haematology patients.…”

COVID‐19 outcomes in haematopoietic cell transplant recipients: A systematic review and meta‐analysis

“…Selected studies reported retrospective observational data from single‐centre experiences [4– 6 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 ], multicentre experiences [ 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 ] or registry data [ 7 , 8 , 42 , 43 , 44 , 45 ]. Seventeen studies [ 8 , 15 , 18 , 19 , 23 , 24 , 29 , 31 , 33 , 34 , 35 , 37 , 38 , 39 , 41 , 44 , 45 ] were from Europe (1153 patients), seven studies [ 4 , 6 , 17 , 20 , 22 ,…”

“…Seventeen studies [ 8 , 15 , 18 , 19 , 23 , 24 , 29 , 31 , 33 , 34 , 35 , 37 , 38 , 39 , 41 , 44 , 45 ] were from Europe (1153 patients), seven studies [ 4 , 6 , 17 , 20 , 22 , 25 , 36 ] were from North America (238 patients), seven studies [ 5 , 16 , 21 , 26 , 30 , 32 , 42 ] were from the Middle East (185 patients), two studies [ 28 , 40 ] were from South America (41 patients), one study [ 27 ] was from Asia (28 patients) and two studies [ 7 , 43 ] included patients from multiple regions (496 patients). Seventeen studies [ 7 , 8 , 16 , 21 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 35 , 38 , 39 , 40 , 41 , 45 ] included both adult and paediatric transplant recipients, 13 studies […”

“…Patient demographics and study characteristics are summarised in Table S1. Selected studies reported retrospective observational data from single‐centre experiences [4–6, 15–26], multicentre experiences [27–41] or registry data [7, 8, 42–45]. Seventeen studies [8, 15, 18, 19, 23, 24, 29, 31, 33–35, 37–39, 41, 44, 45] were from Europe (1153 patients), seven studies [4, 6, 17, 20, 22, 25, 36] were from North America (238 patients), seven studies [5, 16, 21, 26, 30, 32, 42] were from the Middle East (185 patients), two studies [28, 40] were from South America (41 patients), one study [27] was from Asia (28 patients) and two studies [7, 43] included patients from multiple regions (496 patients).…”

“…Selected studies reported retrospective observational data from single‐centre experiences [4–6, 15–26], multicentre experiences [27–41] or registry data [7, 8, 42–45]. Seventeen studies [8, 15, 18, 19, 23, 24, 29, 31, 33–35, 37–39, 41, 44, 45] were from Europe (1153 patients), seven studies [4, 6, 17, 20, 22, 25, 36] were from North America (238 patients), seven studies [5, 16, 21, 26, 30, 32, 42] were from the Middle East (185 patients), two studies [28, 40] were from South America (41 patients), one study [27] was from Asia (28 patients) and two studies [7, 43] included patients from multiple regions (496 patients). Seventeen studies [7, 8, 16, 21, 24–30, 35, 38–41, 45] included both adult and paediatric transplant recipients, 13 studies [4–6, 15, 18–20, 22, 23, 34, 36, 42, 43] only included adult patients ≥18 years old and five studies [17, 31–33, 37, 44] only included patients <18 years old.…”