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Summary: A subset of individuals with 'primary' or 'idiopathic' immune thrombocytopenia (ITP) who fail to respond to conventional first‐ and second‐line agents or who lose responsiveness are considered to have 'refractory' disease (rITP), placing them at increased risk of bleeding and complications of intensive treatment. However, the criteria used to define the refractory state vary among studies, which complicates research and clinical investigation. Moreover, it is unclear whether rITP is simply 'more severe' ITP, or if there are specific pathogenic pathways that are more likely to result in refractory disease, and whether the presence or development of rITP can be established or anticipated based on these differences. This paper reviews potential biological features that may be associated with rITP, including genetic and epigenetic risk factors, dysregulation of T cells and cytokine networks, antibody affinity and specificity, activation of complement, impaired platelet production and alterations in platelet viability and clearance. These findings indicate the need for longitudinal studies using novel clinically available methodologies to identify and monitor pathogenic T cells, platelet antibodies and other clues to the development of refractory disease. [ABSTRACT FROM AUTHOR]

Summary: Immune thrombocytopenia (ITP) is an acquired bleeding disorder mediated by pathogenic autoantibodies secreted by plasma cells (PCs) in many patients. In refractory ITP patients, the persistence of splenic and bone marrow autoreactive long‐lived PCs (LLPCs) may explain primary failure of rituximab and splenectomy respectively. The reactivation of autoreactive memory B cells generating new autoreactive PCs contributes to relapses after initial response to rituximab. Emerging strategies targeting B cells and PCs aim to prevent the settlement of splenic LLPCs with the combination of anti‐BAFF and rituximab, to deplete autoreactive PCs with anti‐CD38 antibodies, and to induce deeper B‐cell depletion in tissues with novel anti‐CD20 monoclonal antibodies and anti‐CD19 therapies. Alternative strategies, focused on controlling autoantibody mediated effects, have also been developed, including SYK and BTK inhibitors, complement inhibitors, FcRn blockers and inhibitors of platelet desialylation. [ABSTRACT FROM AUTHOR]

Summary: Patients with sickle cell disease (SCD) are considered to be immunocompromised, yet data on the antibody response to SARS‐CoV‐2 vaccination in SCD is limited. We investigated anti‐SARS‐CoV‐2 IgG titres and overall neutralizing activity in 201 adults with SCD and demographically matched non‐SCD controls. Unexpectedly, patients with SCD generate a more robust and durable COVID‐19 vaccine IgG response compared to matched controls, though the neutralizing activity remained similar across both cohorts. These findings suggest that patients with SCD achieve a similar antibody response following COVID‐19 vaccination compared to the general population, with implications for optimal vaccination strategies for patients with SCD. [ABSTRACT FROM AUTHOR]

Anti-spike antibody levels significantly increased by exposure number (i.e., vaccination and/or infection, I R i SP 2 sp = 0.34, I p i < 0.001), but anti-nucleocapsid antibody levels did not (Figure 1E,F). Anti-spike and anti-nucleocapsid antibody levels were quantified in 36 patients with sickle cell disease (SCD) and 22 control patients without SCD seen in the same haematology adult and paediatric clinics. All SCD participants and 95% of controls had detectable anti-spike protein antibodies; 21 (58.3%) and 11 (50.0%) had anti-nucleocapsid antibodies, respectively. Keywords: antibodies; coronavirus 2019 (COVID-19); severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); sickle cell disease; splenic function EN antibodies coronavirus 2019 (COVID-19) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sickle cell disease splenic function 680 683 4 08/10/22 20220815 NES 220815 Antibody response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and/or vaccination reduces infection risk.1 In the United States, people with sickle cell disease (SCD) have experienced considerable complications from SARS-CoV-2 infection.2,3 Functional hyposplenia, asplenia, or splenectomy in SCD can increase pathogen susceptibility and reduce vaccine responsiveness.4 We evaluated serum antibody levels for anti-nucleocapsid antibodies from past infection and anti-spike antibodies from vaccination and/or past infection in people with SCD. [Extracted from the article]

Summary: Patients with multiple myeloma (MM) have a suboptimal antibody response following vaccination against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and lower seroconversion rates following coronavirus disease 2019 (COVID‐19) compared with healthy individuals. In this context, we evaluated the development of neutralising antibodies (NAbs) against SARS‐CoV‐2 in non‐vaccinated patients with MM and COVID‐19 compared with patients after vaccination with two doses of the BNT162b2 vaccine. Serum was collected either four weeks post confirmed diagnosis or four weeks post a second dose of BNT162b2. NAbs were measured with a Food and Drug Administration‐approved enzyme‐linked immunosorbent assay methodology. Thirty‐five patients with COVID‐19 and MM along with 35 matched patients were included. The two groups did not differ in age, sex, body mass index, prior lines of therapy, disease status, lymphocyte count, immunoglobulin levels and comorbidities. Patients with MM and COVID‐19 showed a superior humoral response compared with vaccinated patients with MM. The median (interquartile range) NAb titre was 87·6% (71·6–94%) and 58·7% (21·4–91·8%) for COVID‐19‐positive and vaccinated patients, respectively (P = 0·01).Importantly, there was no difference in NAb production between COVID‐19‐positive and vaccinated patients who did not receive any treatment (median NAb 85·1% vs 91·7%, P = 0·14). In conclusion, our data indicate that vaccinated patients with MM on treatment without prior COVID‐19 should be considered for booster vaccine doses. [ABSTRACT FROM AUTHOR]