In-depth virological assessment of kidney transplant recipients with COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread widely, causing coronavirus disease 2019 (COVID-19) and significant mortality. However, data on viral loads and antibody kinetics in immunocompromised populations are lacking. We aimed to determine nasopharyngeal and plasma viral loads via reverse transcription-polymerase chain reaction and SARS-CoV-2 serology via enzyme-linked immunosorbent assay and study their association with severe forms of COVID-19 and death in kidney transplant recipients. In this study, we examined hospitalized kidney transplant recipients with nonsevere (n = 21) and severe (n = 19) COVID-19. SARS-CoV-2 nasopharyngeal and plasma viral load and serological response were evaluated based on outcomes and disease severity. Ten recipients (25%) displayed persistent viral shedding 30 days after symptom onset. The SARS-CoV-2 viral load of the upper respiratory tract was not associated with severe COVID-19, whereas the plasma viral load was associated with COVID-19 severity (P = .010) and mortality (P = .010). All patients harbored antibodies during the second week after symptom onset that persisted for 2 months. We conclude that plasma viral load is associated with COVID-19 morbidity and mortality, whereas nasopharyngeal viral load is not. SARS-CoV-2 shedding is prolonged in kidney transplant recipients and the humoral response to SARS-CoV-2 does not show significant impairment in this series of transplant recipients.

[Acute myeloid leukemia with mutated RUNX1 at the university hospitals of Strasbourg]. / Étude rétrospective des leucémies aiguës myéloïdes mutées RUNX1 aux hôpitaux ­universitaires de Strasbourg.

RUNX1 is essential during human hematopoiesis. Numerous RUNX1 deregulations have been described, including translocations and germline or somatic mutations. Recurrent de novo RUNX1 mutations in acute myeloid leukemias (AML) prompted the creation of a provisional entity of AML with mutated RUNX1 in the 2016 WHO. In addition, recent genomic studies underlined rare AML patients with plasmacytoid dendritic cell (pDC) expansion and high RUNX1 mutations frequency. To better characterized AML with RUNX1 mutations, we retrospectively investigated a cohort of 32 patients diagnosed at Strasbourg University Hospital. Detailed clinical and biological features were aggregated. The presence of a pDC contingent was assessed by cytology and flow cytometry. In our cohort, no common features were identified either in term of cytology, stage of leukemia arrest or mutational features. Based on our observations, mutated RUNX1 AMLs do not appear to be a distinct AML entity. The new 2022 WHO classification includes AML with mutated RUNX1 within AML myelodysplasia-related category. We also identified within our cohort a patient whose AML fulfilled AML-pDC criteria, a rare and newly included entity in the last WHO classification.

Evolution of antibody responses up to 13 months after SARS-CoV-2 infection and risk of reinfection.

BACKGROUND: Assessment of the kinetics of SARS-CoV-2 antibodies is essential in predicting risk of reinfection and durability of vaccine protection. METHODS: This is a prospective, monocentric, longitudinal, cohort clinical study. Healthcare workers (HCW) from Strasbourg University Hospital were enrolled between April 6th and May 7th, 2020 and followed up to 422 days. Serial serum samples were tested for antibodies against the Receptor Binding Domain (RBD) of the spike protein and nucleocapsid protein (N) to characterize the kinetics of SARS-CoV-2 antibodies and the incidence of reinfection. Live-neutralization assays were performed for a subset of samples before and after vaccination to analyze sensitivity to SARS-CoV-2 variants. FINDINGS: A total of 4290 samples from 393 convalescent COVID-19 and 916 COVID-19 negative individuals were analyzed. In convalescent individuals, SARS-CoV-2 antibodies followed a triphasic kinetic model with half-lives at month (M) 11-13 of 283 days (95% CI 231-349) for anti-N and 725 days (95% CI 623-921) for anti-RBD IgG, which stabilized at a median of 1.54 log BAU/mL (95% CI 1.42-1.67). The incidence of SARS-CoV-2 infections was 12.22 and 0.40 per 100 person-years in COVID-19-negative and COVID-19-positive HCW, respectively, indicating a relative reduction in the incidence of SARS-CoV-2 reinfection of 96.7%. Live-virus neutralization assay revealed that after one year, variants D614G and B.1.1.7, but less so B.1.351, were sensitive to anti-RBD antibodies at 1.4 log BAU/mL, while IgG ≥ 2.0 log BAU/mL strongly neutralized all three variants. These latter anti-RBD IgG titers were reached by all vaccinated HCW regardless of pre-vaccination IgG levels and type of vaccine. INTERPRETATION: Our study demonstrates a long-term persistence of anti-RBD antibodies that may reduce risk of reinfection. By significantly increasing cross-neutralizing antibody titers, a single-dose vaccination strengthens protection against variants. FUN1DING: None.