Improved outcomes over time and higher mortality in CMV seropositive allogeneic stem cell transplantation patients with COVID-19; An infectious disease working party study from the European Society for Blood and Marrow Transplantation registry

Abstract

IntroductionCOVID-19 has been associated with high morbidity and mortality in allogeneic hematopoietic stem cell transplant (allo-HCT) recipients.MethodsThis study reports on 986 patients reported to the EBMT registry during the first 29 months of the pandemic.ResultsThe median age was 50.3 years (min – max; 1.0 – 80.7). The median time from most recent HCT to diagnosis of COVID-19 was 20 months (min – max; 0.0 – 383.9). The median time was 19.3 (0.0 - 287.6) months during 2020, 21.2 (0.1 - 324.5) months during 2021, and 19.7 (0.1 – 383.9) months during 2022 (p = NS). 145/986 (14.7%) patients died; 124 (12.6%) due to COVID-19 and 21 of other causes. Only 2/204 (1%) fully vaccinated patients died from COVID-19. There was a successive improvement in overall survival over time. In multivariate analysis, increasing age (p<.0001), worse performance status (p<.0001), contracting COVID-19 within the first 30 days (p<.0001) or 30 – 100 days after HCT (p=.003), ongoing immunosuppression (p=.004), pre-existing lung disease (p=.003), and recipient CMV seropositivity (p=.004) had negative impact on overall survival while patients contracting COVID-19 in 2020 (p<.0001) or 2021 (p=.027) had worse overall survival than patients with COVID-19 diagnosed in 2022.DiscussionAlthough the outcome of COVID-19 has improved, patients having risk factors were still at risk for severe COVID-19 including death.

Respiratory virus infections after allogeneic stem cell transplantation: Current understanding, knowledge gaps, and recent advances

“…We therefore focused on the evidence available in fully vaccinated HSCT recipients. Although vaccination did not eliminate breakthrough SARS‐CoV‐2 infections in fully vaccinated HSCT recipients (incidence of 15% at 1 year after full vaccination), 99 its severity was clearly reduced in terms of higher asymptomatic cases (>45%), lower rate of LRTD (<15%) and lower mortality (<5%), especially in those with higher antibody titers after vaccination 99,100,183,184 . In allo‐HCT recipients, older age, lymphopenia <1 × 10E9/mL, active GvHD, corticosteroids use, ongoing immunosuppressant drugs and vaccination within the first year of transplant were associated with lower amount of antibodies 179,185 .…”

Impact of tixagevimab/cilgavimab prophylaxis in patients undergoing allogeneic hematopoietic stem cell transplants and CAR T-cell therapy: A single center experience

“…Although we observed prolonged viral shedding, especially in the CAR T cell therapy group, it is worth highlighting that, despite being highly immunocompromised, no patients developed severe Covid-19 and only one had moderate infection with radiological signs of low-tract respiratory involvement. A recent EBMT registry study confirmed a better outcome of Covid-19 in HSCT-recipients contracting the infection during Omicron waves as compared to cases diagnosed in 2020 [18] . Despite this might be partially explained by the introduction of new therapeutic and vaccination strategies, recent SARS-CoV-2 strains seem to be associated with less severe manifestations.…”

Targeting CMV Reactivation to Optimize Care for Critically Ill COVID-19 Patients: A Review on the Therapeutic Potential of Antiviral Treatment

“…In addition, a pre-print study utilizing machine learning to predict the risk of COVID-19 infection and severity in 4510 adults found that CMV-specific antibodies were the strongest predictors of infection risk [ 34 ]. Moreover, CMV seropositivity has been shown to independently affect overall survival in allogeneic hematopoietic cell transplantation (allo-HCT) patients with COVID-19 [ 35 ]. The negative impact of CMV seropositivity on survival after hematopoietic cell transplantation is mediated by the patient’s serostatus, irrespective of the donor’s serostatus.…”