Immunocompromised individuals such as chronic lymphocytic leukemia (CLL) patients are at risk of impaired immune responses to vaccination. The objective of our study was to evaluate SARS-CoV-2-specific antibody responses in CLL patients, after the first, second and third doses of the BNT162b2 and mRNA-1273, and after a single dose for patients with confirmed prior COVID-19. Five hundred and thirty patients were included in the study. Patients received 2 doses at a 4-week interval, and a third dose if seronegative after the second dose. Response rate was 27% post-dose 1 and 52% post-dose 2. Post-dose 2 treatment-naïve patients had the highest response rate (72%) followed by patients previously treated by chemoimmunotherapy (60%). Among patients on therapy, patients on BTKi alone (22%) or in combination with anti-CD20 monoclonal antibodies or venetoclax (0%) had the poorer response rate whereas patients on venetoclax monotherapy achieved a significantly higher response rate (52%). A multivariate analysis identified as independent predictors of the absence of seroconversion: age >65 years, ongoing CLL treatment and gamma-globulins ≤6g/L. Post-dose 2 seronegative patients had a global post-dose 3 response rate of 35%. This study provides an argument for the use of a third dose and for prophylactic SARS-CoV-2 neutralizing monoclonal antibodies.

Background Reduced mortality at 28 days in patients treated with corticosteroids was demonstrated, but this result was not confirmed by certain large epidemiological studies. Our aim was to determine whether corticosteroids improve the outcomes of our patients hospitalized with COVID-19 pneumonia. Methods Our retrospective, single centre cohort study included consecutive patients hospitalized for moderate to severe COVID-19 pneumonia between March 15 and April 15 2020. An early short course of corticosteroids was given during the second phase of the study. The primary composite endpoint was the need for mechanical ventilation or mortality within 28 days of admission. A multivariate logistic regression model was used to estimate the propensity score, i.e. the probability of each patient receiving corticosteroid therapy based on the initial variables. Results About 120 consecutive patients were included, 39 in the “corticosteroids group”, 81 in the “no corticosteroids group”; their mean ages (±SD) were 66.4 ± 14.1 and 66.1 ± 15.2 years, respectively. Mechanical ventilation-free survival at 28 days was higher in the “corticosteroids group” than in the “no corticosteroids group” (71% and 29% of cases, respectively, p < .0001). The effect of corticosteroids was confirmed with HR .28 (95%CI .10–.79), p = .02. In older and comorbid patients who were not eligible for intensive care, the effect of corticosteroid therapy was also beneficial (HR .36 (95%CI .16–.80), p = .01). Conclusion A short course of corticosteroids reduced the risks of death or mechanical ventilation in patients with moderate to severe COVID-19 pneumonia in all patients and also in older and comorbid patients not eligible for intensive care.

HupB is an iron-regulated protein in Mycobacterium tuberculosis that functions as a positive regulator of mycobactin biosynthesis. It is essential for the growth and survival of the pathogen inside macrophages. Previously, using the full-length rHupB of M. tuberculosis, we demonstrated high levels of anti-HupB antibodies in the serum of pulmonary tuberculosis (TB) and, interestingly, extrapulmonary TB patients with negligible levels in household contacts and healthy controls. Here, we used three antigenic fragments of HupB, namely the recombinant HupB-F1 (aa 1-71), HupB-F2 (aa 63-161) and HupB-F3 (aa 164-214), as antigens in enzyme-linked immunosorbent assay (ELISA) to screen serum from TB patients. HupB-F2 showed enhanced immunoreactivity with serum from patients with pulmonary TB (three groups consisting of new cases, defaulters and recurrent cases) and extrapulmonary TB, with negligible levels in normal healthy controls. The negative correlation of the anti-(HupB-F2) antibodies with serum iron was maximal, with a Pearson's correlation coefficient value of -0.415. The study, in addition to strengthening the diagnostic potential of HupB, reflected the superior performance of HupB-F2 as an antigen in screening pulmonary and extrapulmonary TB.

Introduction: Studies have shown that the PD-1/PD-L1 immunomodulatory pathway slows down anti-tumor immunity in a number of cancers. The description of the expression of these molecules has never been performed in anal low-grade/ high grade squamous intra-epithelial lesions (LSIL/HSIL respectively). Materials and Methods: Patients followed in the AIN3 cohort were routinely sampled. For each selected sample, an immunohistochemical study was performed with anti-CD8, PD-1, PD-L1 antibodies. The presence and distribution of CD8+ lymphocytes, and the presence of PD-1+ lymphocytes and PD-L1+ epithelial cells were assessed. The comparison of these characteristics was performed between the HSIL and LSIL groups. Results: 33 patients were included and 78 samples selected (60 HSIL and 18 LSIL). CD8+ lymphocytes were observed more frequently in HSIL versus LSIL in the lamina propria or intra epithelial (respectively 90% vs. 60%, p = 0.01; and 62% vs. 33%, p = 0.04). PD-1+ lymphocytes were observed more frequently in HSIL versus LSIL (41% vs 11%, p = 0.03). There was no difference between HSIL and LSIL for PD-L1+ epithelial cells. Conclusions: Anal dysplastic lesions are accompanied by an inflammatory lymphocytic infiltrate expressing CD8 and PD-1, more frequent in high-grade lesions. These results highlight the involvement of the PD-1/PD-L1 pathway in the natural history of anal dysplasia.

Context Some women living with type 1 diabetes (T1D) complain of changes in glucose values according to the different phases of menstruation. Objective To evaluate this variability through continuous glucose monitoring (CGM) data in type 1 diabetes patients. Design Observational study Setting Ambulatory data, recruitment in two centers in Paris region Patients 24 women with type 1 diabetes having spontaneous menstrual cycles. Intervention Collection of CGM data for 62 spontaneous menstrual cycles, with evaluation of five three-day phases during each cycle: (i) early follicular (menstruations), (ii) mid-follicular, (iii) peri-ovulatory, (iv) mid-luteal, and (v) late luteal. Main outcome measure Time in range (TIR, pre-specified). Results TIR decreased for each consecutive phase (61±18%; 59±18%; 59±20%; 57±18% and 55±20%, p=0.02). The linear mixed model highlighted a decrease in TIR in the mid-luteal (p=0.03) and late luteal (p&lt;0.001) phases compared to the early follicular phase. Time above range was significantly higher during the late luteal phase than the early follicular phase (p=0.003). Time below range was significantly higher during the mid-follicular phase than in the early follicular phase. Conclusion In most of the study population, glucose levels rose linearly throughout the menstrual cycle, reaching a maximum in the late luteal phase. A sharp decrease was seen for most participants at the beginning of menstrual bleeding. This should be taken into consideration in daily care of type 1 diabetes patients to avoid hypoglycemia.