Immune Control in Repeated Babesia microti Infection in a Patient With B-Cell Deficiency.

The immunology of human babesiosis is poorly investigated. We present a comprehensive investigation of a 75-year-old man with B-cell deficiency who experienced 3 episodes of babesiosis over a 6-year period. Slowly evolving clinical immunity was observed, as evidenced by milder clinical symptoms and lower peak parasite burden after each subsequent babesiosis episode. The patient exhibited several striking immunologic findings. First, the patient had exceptionally high Babesia microti-specific antibodies despite very few circulating B cells, which predominantly coexpressed CD27 (memory marker) and CD95 (death receptor). Second, we demonstrated the presence of long-lasting NK cells and expansion of T memory stem cells. Third, levels of the IP-10 cytokine directly correlated with parasite burden. These results raise fundamental questions on the priming, maintenance, and location of a B-cell population that produces high antibody levels in the face of severe B-cell deficiency. Our results should invoke interest among researchers to study the immunology and pathogenesis of human babesiosis.

SARS-CoV-2 viral clearance and evolution varies by type and severity of immunodeficiency.

Despite vaccination and antiviral therapies, immunocompromised individuals are at risk for prolonged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but the immune defects that predispose an individual to persistent coronavirus disease 2019 (COVID-19) remain incompletely understood. In this study, we performed detailed viro-immunologic analyses of a prospective cohort of participants with COVID-19. The median times to nasal viral RNA and culture clearance in individuals with severe immunosuppression due to hematologic malignancy or transplant (S-HT) were 72 and 40 days, respectively, both of which were significantly longer than clearance rates in individuals with severe immunosuppression due to autoimmunity or B cell deficiency (S-A), individuals with nonsevere immunodeficiency, and nonimmunocompromised groups (P < 0.01). Participants who were severely immunocompromised had greater SARS-CoV-2 evolution and a higher risk of developing resistance against therapeutic monoclonal antibodies. Both S-HT and S-A participants had diminished SARS-CoV-2-specific humoral responses, whereas only the S-HT group had reduced T cell-mediated responses. This highlights the varied risk of persistent COVID-19 across distinct immunosuppressive conditions and suggests that suppression of both B and T cell responses results in the highest contributing risk of persistent infection.

SARS-CoV-2 Viral Clearance and Evolution Varies by Extent of Immunodeficiency.

Despite vaccination and antiviral therapies, immunocompromised individuals are at risk for prolonged SARS-CoV-2 infection, but the immune defects that predispose to persistent COVID-19 remain incompletely understood. In this study, we performed detailed viro-immunologic analyses of a prospective cohort of participants with COVID-19. The median time to nasal viral RNA and culture clearance in the severe hematologic malignancy/transplant group (S-HT) were 72 and 40 days, respectively, which were significantly longer than clearance rates in the severe autoimmune/B-cell deficient (S-A), non-severe, and non-immunocompromised groups (P<0.001). Participants who were severely immunocompromised had greater SARS-CoV-2 evolution and a higher risk of developing antiviral treatment resistance. Both S-HT and S-A participants had diminished SARS-CoV-2-specific humoral, while only the S-HT group had reduced T cell-mediated responses. This highlights the varied risk of persistent COVID-19 across immunosuppressive conditions and suggests that suppression of both B and T cell responses results in the highest contributing risk of persistent infection.

Factors Affecting Paramedic Response Readiness to CBRN Threats in Ontario, Canada.

OBJECTIVE: To determine factors associated with increased response readiness to CBRN threats of paramedics in Ontario, Canada. METHODS: An internet-based survey was distributed via email and delivered at the start of each shift presentation during October, 2019. The target population was active-duty paramedics in the Ontario region of Canada. The survey was comprised of 6 sections pertaining to demographics, attitudinal components of risk perception, self-efficacy, deployment concerns, and resilience. Survey mean, univariate, and multivariate regression analyses were used to find the individual effect of each variable. RESULTS: The univariate analysis indicated that higher response readiness was associated with additional training, education, CBRN, and family concerns, and incident experience. However, some variables were non-significant in the multivariate analysis. Increased response readiness was associated with CBRN concerns and training. CONCLUSION: CBRN concerns and focused training regarding terrorism were both associated with increased response readiness. The information from the study can be used to build upon existing knowledge and support paramedics though training and preparation for CBRN specific disasters. The findings may also be used to improve current competency-based frameworks focused on response readiness.

Longitudinal SARS-CoV-2 Nucleocapsid Antibody Kinetics, Seroreversion, and Implications for Seroepidemiologic Studies.

Given widespread use of spike antibody in generating coronavirus disease vaccines, SARS-CoV-2 nucleocapsid antibodies are increasingly used to indicate previous infection in serologic surveys. However, longitudinal kinetics and seroreversion are poorly defined. We found substantial seroreversion of nucleocapsid total immunoglobulin, underscoring the need to account for seroreversion in seroepidemiologic studies.

Circulating Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Vaccine Antigen Detected in the Plasma of mRNA-1273 Vaccine Recipients.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) proteins were measured in longitudinal plasma samples collected from 13 participants who received two doses of mRNA-1273 vaccine. Eleven of 13 participants showed detectable levels of SARS-CoV-2 protein as early as day 1 after first vaccine injection. Clearance of detectable SARS-CoV-2 protein correlated with production of immunoglobulin G (IgG) and immunoglobulin A (IgA).

MicroRNA-17 Modulates Regulatory T Cell Function by Targeting Co-regulators of the Foxp3 Transcription Factor.

Regulatory T (Treg) cells are important in maintaining self-tolerance and immune homeostasis. The Treg cell transcription factor Foxp3 works in concert with other co-regulatory molecules, including Eos, to determine the transcriptional signature and characteristic suppressive phenotype of Treg cells. Here, we report that the inflammatory cytokine interleukin-6 (IL-6) actively repressed Eos expression through microRNA-17 (miR-17). miR-17 expression increased in Treg cells in the presence of IL-6, and its expression negatively correlated with that of Eos. Treg cell suppressive activity was diminished upon overexpression of miR-17 in vitro and in vivo, which was mitigated upon co-expression of an Eos mutant lacking miR-17 target sites. Also, RNAi of miR-17 resulted in enhanced suppressive activity. Ectopic expression of miR-17 imparted effector-T-cell-like characteristics to Treg cells via the de-repression of genes encoding effector cytokines. Thus, miR-17 provides a potent layer of Treg cell control through targeting Eos and additional Foxp3 co-regulators.