Viral Dynamics of SARS-CoV-2 in Critically Ill Allogeneic Hematopoietic Stem Cell Transplant Recipients and Immunocompetent Patients with COVID-19.
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ABSTRACT:
SUBMITTER: Roedl K
PROVIDER: S-EPMC7874426 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The SARS-CoV-2 mRNA vaccine-induced humoral response and reactogenicity profile are described in allogeneic hematopoietic stem cell transplant (HSCT) recipients. 75.0% (by Simoa assay) or 80.0% (by Roche assay) of the HSCT cohort had a positive antibody response upon series completion, as compared to 100% in the healthy cohort.
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Project description:Allogeneic hematopoietic cell-transplant (alloHCT) recipients are at increased risk of complications from viral respiratory-tract infections (vRTIs). We measured cytokine concentrations in nasal washes (NWs) from pediatric alloHCT recipients to better understand their local response to vRTI. Forty-one immunologic analytes were measured in 70 NWs, collected during and after vRTI, from 15 alloHCT recipients (median age, 11 yr) with 19 episodes of vRTI. These were compared with NW cytokine concentrations from an independent group of otherwise healthy patients. AlloHCT recipients are able to produce a local response to vRTI and produce IFN-α2 and IL-12p40 in significant quantities above an uninfected baseline early in infection. Compared with otherwise healthy comparator-group patients, alloHCT recipients have higher NW concentrations of IL-4 when challenged with vRTI. Further study of these immunologic analytes as well as of type 1 versus type 2 balance in the respiratory mucosa in the context of vRTI during immune reconstitution may be of future research interest in this vulnerable patient population.
| S-EPMC7710331 | biostudies-literature
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| S-EPMC8616709 | biostudies-literature
Project description:BackgroundAllogeneic hematopoietic cell transplant recipients (allo-HCTRs) with positive cytomegalovirus (CMV) serology may have false-positive results due to blood product transfusion-associated passive immunity.MethodsThis single-center cohort study included allo-HCTRs with negative baseline (at malignancy diagnosis) CMV serology and indeterminate/low-positive (CMV IgG titer, ≥0.6-<50 U/mL) pretransplant CMV serology with negative pretransplant plasma CMV DNAemia. The CMV status of those patients was reclassified from R+ to R- (CMVR- reclassification group). We compared those patients to allo-HCTRs with negative (CMV IgG titer <0.6 U/mL) pretransplant CMV IgG (CMVR- group). We describe the number and type of patients whose pretransplant CMV status was reclassified from indeterminate/positive to negative. We reviewed all plasma CMV DNAemia tests performed during the first 6 months posttransplant in both groups to assess the safety of this approach.ResultsAmong 246 (84.5%) of 291 transplanted patients identified as CMVR+ pretransplant, 60 (24.4%) were reclassified from CMV serology indeterminate (N:10)/low-positive (N:50) to R-. Only 1 of 60 patients (1.67%) in the CMVR- reclassification group versus 3 of 44 (6.8%; P = .30) in the CMVR- group developed CMV DNAemia during the follow-up period. There were no significant differences in the number of CMV DNAemia tests performed, CMV DNAemia range, and time posttransplant between the 2 groups.ConclusionsOne of 4 allo-HCT CMVR+ may be falsely flagged as R+, with significant impact on donor selection and prophylaxis administration. A 2-step approach including CMV serology testing at hematologic malignancy diagnosis in allo-HCT candidates and careful review of pretransplant CMV IgG titers may help correctly classify CMV serology status.
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| S-EPMC7258645 | biostudies-literature
Project description:The safety and efficacy of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV2) emergency-use authorized (EUA) vaccines have been confirmed in the general population. However, there are no data on its safety and tolerability or efficacy in recipients of allogeneic hematopoietic stem cell transplant (HCT). We performed this study to identify the incidence of adverse events following SARS-CoV2 EUA vaccines, the incidence of new-onset graft-versus-host disease (GVHD) or worsening of existing GVHD after EUA vaccine administration, and the incidence SARS-CoV2 positivity in vaccinated HCT patients. We retrospectively reviewed 113 HCT patients who received at least one dose of EUA vaccine to describe the safety and tolerability, any impact on GVHD, and the incidence of SARS-CoV2 PCR positivity after vaccination. Patients received either Pfizer (BNT162b2) or Moderna (mRNA-1273) vaccines. Patients were included if they were 18 years or older and had received at least one dose of vaccine in the post-HCT setting. Most patients presented with myalgias/arthralgias (first dose, 7.7%; second dose, 14.6%), fatigue (first dose, 15.4%; second dose, 29.2%), and injection site pain (first dose, 40.4%; second dose, 43.8%). Other side-effects experienced by patients included nausea, vomiting, diarrhea, headache, and injection-site rash and swelling. Liver function abnormalities occurred in 18.6% of patients. Neutropenia, thrombocytopenia, and lymphopenia occurred in 13.3%, 11.5%, and 8.8% of patients, respectively. Forty percent of patients had active chronic GVHD at the time of vaccination, and worsening chronic GVHD occurred in 3.5% of the patients. New chronic GVHD developed in 9.7% of patients after vaccination. The SARS-CoV2 EUA vaccines were well tolerated in allogeneic HCT recipients.
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Project description:Recent data suggest human rhinovirus (HRV) is associated with lower respiratory tract infection and mortality in hematopoietic cell transplant (HCT) recipients. Examining risk factors for prolonged viral shedding may provide critical insight for the development of novel therapeutics and help inform infection prevention practices. Our objective was to identify risk factors for prolonged shedding of HRV post-HCT. We prospectively collected weekly nasal samples from allogeneic HCT recipients from day 0 to day 100 post-transplant, and performed real-time reverse transcriptase PCR (December 2005 to February 2010). Subjects with symptomatic HRV infection and a negative test within 2 weeks of the last positive were included. Duration of shedding was defined as time between the first positive and first negative samples. Cycle threshold (Ct) values were used as a proxy for viral load. HRV species were identified by sequencing the 5' noncoding region. Logistic regression analyses were performed to evaluate factors associated with prolonged shedding (≥21 days). We identified 38 HCT recipients with HRV infection fulfilling study criteria (32 adults, 6 children). Median duration of shedding was 9.5 days (range, 2 to 89 days); 18 patients had prolonged shedding. Among 26 samples sequenced, 69% were species A, and species B and C accounted for 15% each; the median shedding duration of HRV did not differ among species (P = .17). Bivariable logistic regression analyses suggest that initial high viral load (low Ct value) is associated with prolonged shedding. HCT recipients with initial high viral loads are at risk for prolonged HRV viral shedding.
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Project description:The protective capacity and duration of humoral immunity after SARS-CoV-2 infection are not yet understood in solid organ transplant recipients. A prospective multicenter study was performed to evaluate the persistence of anti-nucleocapsid IgG antibodies in liver transplant recipients 6 months after coronavirus disease 2019 (COVID-19) resolution. A total of 71 liver transplant recipients were matched with 71 immunocompetent controls by a propensity score including variables with a well-known prognostic impact in COVID-19. Paired case-control serological data were also available in 62 liver transplant patients and 62 controls at month 3 after COVID-19. Liver transplant recipients showed a lower incidence of anti-nucleocapsid IgG antibodies at 3 months (77.4% vs. 100%, p < .001) and at 6 months (63.4% vs. 90.1%, p < .001). Lower levels of antibodies were also observed in liver transplant patients at 3 (p = .001) and 6 months (p < .001) after COVID-19. In transplant patients, female gender (OR = 13.49, 95% CI: 2.17-83.8), a longer interval since transplantation (OR = 1.19, 95% CI: 1.03-1.36), and therapy with renin-angiotensin-aldosterone system inhibitors (OR = 7.11, 95% CI: 1.47-34.50) were independently associated with persistence of antibodies beyond 6 months after COVID-19. Therefore, as compared with immunocompetent patients, liver transplant recipients show a lower prevalence of anti-SARS-CoV-2 antibodies and more pronounced antibody levels decline.
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Project description:Human cytomegalovirus (HCMV) reactivation is a major infectious cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). HCMV is a ubiquitous beta-herpesvirus which asymptomatically infects immunocompetent individuals but establishes lifelong latency, with the potential to reactivate to a life-threatening productive infection when the host immune system is suppressed or compromised. Opportunistic HCMV reactivation is the most common viral complication following engraftment after HSCT and is associated with a marked increase in non-relapse mortality, which appears to be linked to complex effects on post-transplant immune recovery. This minireview explores the cellular sites of HCMV latency and reactivation in HSCT recipients and provides an overview of the risk factors for HCMV reactivation post-HSCT. The impact of HCMV in shaping post-transplant immune reconstitution and its relationship with patient outcomes such as relapse and graft-versus-host disease will be discussed. Finally, we survey current and emerging strategies to prevent and control HCMV reactivation in HSCT recipients, with recent developments including adoptive T cell therapies to accelerate HCMV-specific T cell reconstitution and new anti-HCMV drug therapy for HCMV reactivation after HSCT.
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