Introduction Respiratory viral infections are a major cause of morbidity and mortality among stem cell transplant recipients. While there is a substantial amount of information on prognostic factors and response to ribavirin therapy is available for RSV infections, this information is largely lacking for hMPV. Patients and methods In total, 71 patients were included in this study: 47 patients with RSV and 24 with hMPV. Forty‐one patients presented as an upper respiratory tract infection (URTI) and 30 as a primary lower respiratory tract infection (LRTI). Patients were stratified as per ISI criteria into low‐, moderate‐, and high‐risk groups. Twenty‐two patients in the URTI cohort received treatment with ribavirin (mainly oral), and 19 patients received no antiviral therapy. The decision for antiviral treatment was at the discretion of the attending physician. All 30 patients with primary LRTI and 10 patients with secondary LRTI were treated with ribavirin, 95% with the intravenous formulation. 45% of these patients received additional treatment with intravenous immunoglobulins. The viral load was assessed indirectly by using the CT value of the RT‐PCR. Results In the cohort, as whole 11.5% suffered a virus‐associated death, 5% in the URTI group, and 20% in the LRTI group. Sixty‐day mortality was significantly higher in the ISI high‐risk group (log‐rank P = .05). Mortality was independent of the type of virus (P = .817). Respiratory failure with an indication for mechanical ventilation developed in 11.5%, this risk was independent of the type of virus. Progression from URTI to LRTI was observed in 24% of cases with a significantly higher risk (75%) in the ISI high group (log‐rank P = .001). In the ISI high‐risk group, treatment with ribavirin significantly reduced the risk of progression (log‐rank P < .001). Neither the type of virus nor the viral load in the nasopharyngeal swab impacted the risk of progression (P = .529 and P = .141, respectively). The detection of co‐pathogens in the BAL fluid was borderline significant for mortality (P = .07). Conclusions We could detect no differences between RSV and hMPV with respect to progression to LRTI, risk of respiratory failure or need for mechanical ventilation and virus‐associated death. The ISI index is of predictive value in hMPV patients with a high ISI score and treatment with oral ribavirin has an equivalent protective effect in RSV and hMPV patients. Treatment of LRTI with intravenous ribavirin results in a similar outcome in RSV‐ and hMPV‐infected patients. We could not detect any benefit of adjunctive treatment with immunoglobulins in both primary and secondary LRTI. No role of viral load as an independent prognostic marker could be detected either for progression to LRTI or death.

IntroductionVaccination against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is approved and recommended for immunocompromised patients such as patients after allogeneic stem cell transplantation (allo-SCT). Since infections represent a relevant cause of transplant related mortality we analyzed the advent of immunization to SARS-CoV-2 vaccination in a bicentric population of allogeneic transplanted patients.MethodsWe retrospectively analyzed data of allo-SCT recipients in two German transplantation centers for safety and serologic response after two and three SARS-CoV-2 vaccinations. Patients received mRNA vaccines or vector-based vaccines. All patients were monitored for antibodies against SARS-CoV2-spike protein (anti-S-IgG) with an IgG ELISA assay or an EIA Assay after two and three doses of vaccination.ResultsA total of 243 allo-SCT patients underwent SARS-CoV-2 vaccination. The median age was 59 years (range 22-81). While 85% of patients received two doses of mRNA vaccines, 10% had vector-based vaccines and 5% received a mixed vaccination. The two vaccine doses were well tolerated with only 3% patients developing a reactivation of graft versus host disease (GvHD). Overall, 72% of patients showed a humoral response after two vaccinations. In the multivariate analysis age at time of allo-SCT (p=0.0065), ongoing immunosuppressive therapy (p= 0.029) and lack of immune reconstitution (CD4-T-cell counts &lt;200/μl, p&lt; 0.001) were associated with no response. Sex, intensity of conditioning and the use of ATG showed no influence on seroconversion. Finally, 44 out of 69 patients that did not respond after the second dose received a booster and 57% (25/44) showed a seroconversion.DiscussionWe showed in our bicentric allo-SCT patient cohort, that a humoral response could be achieve after the regular approved schedule, especially for those patients who underwent immune reconstitution and were free from immunosuppressive drugs. In over 50% of the initial non-responders after 2-dose vaccination, a seroconversion can be achieved by boostering with a third dose.

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Introduction Different vaccines have been recently approved by FDA and EMA for the prevention of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, demonstrating a protection rate ranging from 60% to almost 95% in phase II/III trials. Immunocompromised patients, including those undergoing allogeneic stem cell transplantation (allo-SCT), were excluded from vaccine trials. While EBMT recommended the vaccination for transplanted patients, data concerning efficacy and safety in this particular setting are scarce. Since infections represent a relevant cause of transplant-related mortality and the treatment and management of SARS-CoV-2 infection in allo-SCT patients proved to be challenging and complex, we prospectively evaluated the safety and the development of protective response against SARS-CoV-2 vaccines in our allogeneic transplanted patients. Materials and Methods Starting in March 2021, allogeneic stem cell transplanted patients with different hematological diseases underwent COVID-19 vaccination. Taking into account the EBMT recommendations, we considered patients suitable for vaccination when (1) they were at least 3-6 months after allo-SCT, (2) didn't have any graft versus host (GvHD) activity, and (3) received less than 0,5 mg/kg steroids as part of the immunosuppressive treatment. There was no recommendation for a specific type of vaccine, with the only exception for life-attenuated vaccines, which are mostly contraindicated in the post allo-SCT setting. Vaccinated patients were regularly monitored for the potential development of adverse events. The anti-SARS-CoV-2 Spike protein antibodies were measured in blood samples to assess the humoral response. In case of no response with undetectable anti-Spike antibodies 2 week after the second dose of vaccine, we repeated the measurements at regular intervals until week + 6-8 after the completion of vaccination. Patients with no measurable antibodies 8 weeks after completion of the vaccination were considered as no responders. Results Between 03/2021 and 06/2021 a total of 83 patients underwent COVID-19 vaccination (including first and second dose) during the post allo-SCT follow-up. Patients' characteristics are listed in Table 1. Most patients (77%) received BNT162b2, while only a small subgroup (8%) underwent a mixed vaccination after a first dose of ChAdOx1-S. We considered the mixed vaccination mostly to maximize the response. Overall, the two vaccine doses were well tolerated, with only 5% of patients developing a reactivation of GvHD. No relevant grade 3 or 4 organ toxicities were observed. Overall, 66% of patients in our cohort showed a humoral response. The incidence of positive serology was lower in patients who underwent the vaccination within the first 18 months after allo-SCT (29% vs 83% for patients &gt;18 months after allo-SCT, p&lt; 0.001). In multivariate analysis other risk factors that were associated with poor or no response were lack of immune reconstitution (p&lt; 0.001) and ongoing immunosuppressive therapy (p= 0.009). The age of patients at the time of vaccination, sex, intensity of conditioning regimen and the use of ATG did not prove to have an influence for a humoral response during the post-transplant follow up. Discussion The achievement of a protective immunity against SARS-CoV-2 represents a crucial event for a frail population, like allogeneic stem cell transplanted patients. So far and to our knowledge little is known about the safety and efficacy of the COVID-19 vaccination in this particular setting. Here, we report one of the first series of patients undergoing COVID-19 vaccination after allo-SCT. We demonstrated that a humoral response can be achieved, especially for those patients who are in the long-term follow-up, underwent immune reconstitution and are free from immunosuppressive drugs. For the other patients, who represent the frailer subgroup, in the absence of a documented immune response after 2 doses of vaccine, the option of a third dose in order to increase the probability of response should be evaluated in prospective clinical trials. Figure 1 Figure 1. Disclosures Viardot: Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; F. Hoffmann-La Roche Ltd: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; University Hospital of Ulm: Current Employment; Amgen: Membership on an entity's Board of Directors or advisory committees; Kite/Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees. Döhner: Roche: Consultancy, Honoraria; Agios: Consultancy, Honoraria, Research Funding; Astellas: Consultancy, Honoraria, Research Funding; Jazz: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Ulm University Hospital: Current Employment; Abbvie: Consultancy, Honoraria, Research Funding; Oxford Biomedicals: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Astex: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Research Funding; AstraZeneca: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy, Honoraria, Research Funding; Helsinn: Consultancy, Honoraria; Pfizer: Research Funding; Berlin-Chemie: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; GEMoaB: Consultancy, Honoraria. Sala: Novartis: Consultancy, Honoraria; Celgene/BMS: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Jazz: Consultancy, Honoraria.