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American Journal of Transplantation ; 22(Supplement 3):761-762, 2022.
Article in English | EMBASE | ID: covidwho-2063449


Purpose: The purpose of this study is to evaluate outcomes of readmission, rejection, graft dysfunction, graft failure, and death in SOT recipients (SOTR) after COVID-19 infection. Method(s): We conducted a retrospective cohort study of SOTR diagnosed with COVID-19 infection before 5/1/2021. COVID-19 disease severity was assigned retrospectively by NIH criteria and grouped into asymptomatic/mild and moderate/ severe/critical infection. Data collected included demographics, clinical features, treatment, and outcomes. Bivariate comparisons to evaluate characteristics associated with outcomes were performed with independent group t-tests for continuous variables and Fisher's exact tests for categorical variables. Result(s): 138 SOTR were diagnosed with COVID-19 at a median of 5 (IQR 3-8) years post-transplant with a mean age of 57+/-12 years at diagnosis. Most were kidney or liver recipients (Table 1);49 (36%) had asymptomatic or mild infection. 29 (21%) of SOTR had moderate, 26 (19%) severe, and 31 (22%) critical infection. Disease severity, treatment with steroids or remdesivir did not correlate with rejection. Most graft failures occurred in SOTR with critical (n=12) disease (Table 2). 102 (74%) SOTR were admitted to the hospital for COVID-19 infection, of which 27 (26%) were readmitted more than 2 months after their index hospitalization. Of the readmissions, 5 were for renal complications, 5 infectious, and 7 pulmonary. Among those hospitalized, 13 (13%) SOTR died during the index admission. Among the 27 SOTR who were readmitted, 3 (11%) SOTR died during readmission. The mean time from initial infection to death was 121+/-176 days. Conclusion(s): In this cohort, disease severity was associated with graft failure. Readmissions were frequent more than 2 months after the index admission. Mortality in those who were readmitted remained high. Rejection was relatively infrequent.

Open Forum Infectious Diseases ; 8(SUPPL 1):S555, 2021.
Article in English | EMBASE | ID: covidwho-1746350


Background. Solid organ transplant recipients (SOTR) have lower humoral responses following SARS-CoV-2 vaccination. Whether this equates to reduced vaccine effectiveness in SOTR or impacts disease severity is not yet known. We used the IDSA Emerging Infections Network (EIN) to identify SARS-CoV-2 cases in vaccinated SOTR. We describe their clinical characteristics and outcomes. Methods. On 4/7/21, we requested case reports via the EIN listserv of COVID-19 infection following SARS-CoV-2 vaccination in immunocompromised individuals. Case reports were collected until June 7th. Online data collection included patient demographics, dates of SARS-CoV-2 vaccine administration and clinical data related to COVID-19 infection. We performed a descriptive analysis of these patient factors and compared differences between early onset (< / = 21 days after completing vaccine series) and late onset infection ( > 21 days after completing vaccine series). Results. As of 6/7/21, 34 cases of COVID-19 infection after vaccination in SOTR were submitted. Most cases (79%) occurred in individuals who were fully vaccinated. Only 3 cases (8.5%) occurred in SOTR within their first year after transplantation. Clinical characteristics are listed in Table 1. The vaccine administration date was known for 26 SOTR among whom symptoms occurred a median of 26.5 days (IQR 21.75 days, range 5-79 days) after completing the COVID-19 vaccine series. Twenty-three SOTR (68%) required hospitalization of which 12 had critical illness. Outcome data was available for 29 individuals of whom 20 (69%) demonstrated improvement. When comparing SOTR with early versus late onset COVID-19 infection in relation to vaccination timing, there were no differences in disease severity (80% vs 75% with severe or critical disease, p=NS) or outcome (30% vs 31% died or deteriorating, p=NS). Table 1: Characteristics of Solid Organ Transplant Recipients with COVID-19 Infection Following SARS-CoV-2 Vaccination Conclusion. SARS-CoV-2 infections after vaccination are occurring in SOTR, including cases of critical illness, suggesting reduced vaccine effectiveness within this vulnerable population. We did not appreciate any correlation between time from vaccination and COVID-19 disease severity or outcome. Further studies evaluating the true incidence of and risk factors for breakthrough infections among vaccinated SOTR are needed.

Blood ; 138:1738, 2021.
Article in English | EMBASE | ID: covidwho-1736315


Introduction: Patients with hematologic malignancies are at an increased risk of morbidity and mortality from COVID-19 disease (Vijenthira, Blood 2020). This is likely a result of combination of immunodeficiency conferred by the disease and the therapeutics. The immunogenicity of the COVID-19 vaccines in patients with exposure to CD19 directed Chimeric Antigen Receptor (CAR)-T cell therapy is not established. CD19 CAR-T cell therapies cause B-cell aplasia, which in turn can affect humoral immune response against novel antigens. Herein, we present results from our prospectively conducted clinical study to evaluate immune responses against mRNA based COVID-19 vaccines in patients with lymphoma who have received CD19 directed CAR-T cell therapy. Methods: All patients and healthy controls were enrolled in a prospective clinical study evaluating immune responses against commercial COVID-19 RNA vaccines in patients with hematologic malignancies. Plasma samples were generated from heparinized peripheral blood of 4 heathy controls (HCs) receiving the same vaccines and 19 B cell lymphoma patients treated with CD19 CAR- T cells. Samples from ~4 weeks post second dose of the vaccine (d56) were available for 14 CAR-T patients, for 5 CAR-T patients samples were available from ~4 weeks after the first dose (d28). Plasma samples were analyzed in an enzyme-linked immunosorbent assay (ELISA) using different full-length recombinant SARS-CoV-2 proteins and control proteins. Neutralizing activity was measured using the cPass Neutralization Antibody Detection Kit (GenScript Biotech). Results: Results from 4 healthy controls and 19 patients (12 males and 7 females) with lymphoma are reported. Median age for the lymphoma patients is 65 years. Eleven patients had large B cell lymphoma, 5 had follicular lymphoma and 3 had mantle cell lymphoma as primary diagnoses. Seventeen patients had advance stage disease (III/IV stage) and had received a median of 3 prior lines of therapy. All patients received CD19 directed CAR-T cell therapy. Ten patients received Moderna vaccine and 9 received Pfizer vaccine. Median time between CAR-T infusion and first COVID-19 vaccine was 258 days. While the peripheral blood plasma from 3/4 HCs already showed substantial SARS-CoV-2 neutralizing activity at ~4 weeks after the first dose of COVID-19 mRNA vaccine, none of the 5 CD19 CAR-T patients analyzed evidenced any antibody-mediated neutralizing activity in their blood at the same point in time (Figure 1A). Around 4 weeks after receiving the second dose of the vaccine, all 4 HCs tested evidenced complete or almost complete neutralizing activity (Figure 1B). In marked contrast, only 1 out of 14 CAR-T patients analyzed evidenced any relevant antibody-mediated SARS-CoV-2 neutralizing activity in their blood (Figure 1B). Interestingly, when we asked whether a globally insufficient antibody-mediated immunity was the underlying cause of the lack of a response to the COVID-19 vaccine in our CAR-T patients, we found that that was clearly not the case since anti-Flu, -TT, and -EBV responses were equivalent to the ones observed in HCs (Figure 2A). However, while at ~4 weeks post second dose of the vaccine the HCs showed marked antibody titers against all the viral spike proteins including their “delta” variants (Figure 2B), that was not the case for our CAR-T patients. The vast majority of our CAR-T patients did not evidence IgG antibody responses against any of the SARS-CoV-2 proteins analyzed such as S1, S1 delta, RBD, RBD delta, or S2 (Figure 2B). Conclusion: In this prospectively conducted clinical study, 18 of 19 patients with lymphoma who have received CD19 CAR-T therapy had poor immunogenicity against mRNA based COVID-19 vaccines as measured by neutralization assays and antibody titers. The antibody titers against B.1.617.2 (delta variant, S1 and RBD protein) were also demonstrably poor. The antibody response to common pathogens (flu, EBV, TT) were preserved, suggesting impaired immune response against novel antigens. Long-term follow-up of this study is ongoin . APR and DJ contributed equally [Formula presented] Disclosures: Dahiya: Kite, a Gilead Company: Consultancy;Atara Biotherapeutics: Consultancy;BMS: Consultancy;Jazz Pharmaceuticals: Research Funding;Miltenyi Biotech: Research Funding. Hardy: American Gene Technologies, International: Membership on an entity's Board of Directors or advisory committees;InCyte: Membership on an entity's Board of Directors or advisory committees;Kite/Gilead: Membership on an entity's Board of Directors or advisory committees.