Altered somatic hypermutation patterns in COVID-19 patients classifies disease severity

IntroductionThe success of the human body in fighting SARS-CoV2 infection relies on lymphocytes and their antigen receptors. Identifying and characterizing clinically relevant receptors is of utmost importance.MethodsWe report here the application of a machine learning approach, utilizing B cell receptor repertoire sequencing data from severely and mildly infected individuals with SARS-CoV2 compared with uninfected controls.ResultsIn contrast to previous studies, our approach successfully stratifies non-infected from infected individuals, as well as disease level of severity. The features that drive this classification are based on somatic hypermutation patterns, and point to alterations in the somatic hypermutation process in COVID-19 patients.DiscussionThese features may be used to build and adapt therapeutic strategies to COVID-19, in particular to quantitatively assess potential diagnostic and therapeutic antibodies. These results constitute a proof of concept for future epidemiological challenges

Correlates of non-typhoidal Salmonella bacteraemia: A case–control study

Objective: Limited up-to-date evidence exists on host-related characteristics of non-typhoidal Salmonella (NTS) bacteraemia in high-income countries. Correlates of NTS bacteraemia in Israel were examined in this study. Methods: A case–control study was conducted using the medical records of patients hospitalized with NTS bacteraemia in Jerusalem during 1997–2016 (n = 106; 57 children, 49 adults). Two control groups were included: (1) randomly selected controls (n = 101), who were patients hospitalized due to bacteraemia with other pathogens; (2) patients with salmonellosis without bacteraemia (n = 112). Age-stratified logistic regression models were constructed. Results: In children, a recent emergency room visit was associated with an increased likelihood of NTS bacteraemia. In adults, the likelihood of NTS bacteraemia versus salmonellosis increased in relation to Charlson comorbidity score (adjusted odds ratio (aOR) 1.29, 95% confidence interval (CI) 1.00–1.66, for each 1-point increase in the score), while an inverse association was found with haemoglobin level (aOR 0.72, 95% CI 0.54–0.95). Steroid therapy increased the likelihood of NTS bacteraemia compared to patients with bacteraemia due to other pathogens (aOR 5.22, 95% CI 1.01–26.93). Conclusions: In children, NTS bacteraemia was probably present at their prior emergency room visit. A high comorbidity burden increased the likelihood of bacteraemia in adults with Salmonella infection, while haemoglobin level might be protective. Keywords: Non-typhoidal Salmonella, Bacteraemia, High-income country, Case–control, Hospitalizations, Immunosuppressio

Experimental and Compassionate Drug Use During the First Wave of the COVID-19 Pandemic: A Retrospective Single-Center Study

International audienc

Shared Medical and Environmental Risk Factors in Dry Eye Syndrome, Sjogren’s Syndrome, and B-Cell Non-Hodgkin Lymphoma: A Case-Control Study

Objectives. To assess whether there are shared exposures associated with Sjogren’s syndrome (SS), dry eye syndrome (DES), and B-cell non-Hodgkin lymphoma (B-NHL), in order to determine whether they are etiologically related. Methods. In a clinic-based case-control study, 702 participants (91 SS, 120 DES, 211 (age and sex frequency-matched) controls, and 280 B-NHL cases) were recruited and interviewed regarding exposures, medical history, and family history. Results. Female predominance was noted in SS (ratio 9.2 : 1). Eye dryness was severest in SS compared to DES and controls (P<0.001). Compared to controls, alcohol consumption was inversely associated with NHL, DES, and SS (odds ratio OR=0.47, 95% confidence interval (CI): 0.31-0.71; OR=0.54, 95% CI: 0.33-0.88; and OR=0.26, 95% CI: 0.14-0.49, respectively), while a previous history of infection requiring hospitalization was positively associated with all three conditions: NHL (OR=1.92; 95% CI: 1.23-2.99), DES (OR=3.29; 95% CI: 1.97-5.47), and SS (OR=4.74; 95% CI: 2.66-8.44). NHL patients were more likely to report first-degree relatives with hematologic cancer, while having first-degree relatives with an autoimmune disease (AID) was associated with SS (OR=5.25; 95% CI: 2.59-10.63) and DES (OR=3.55; 95% CI: 1.83-6.91) compared to controls. Conclusions. Some exposures are associated with all three conditions (such as an inverse association with alcohol consumption and a positive association with serious past infection), while a family history of AID appears to be shared by DES and SS, but not NHL subjects. Shared risk factors for all three conditions indicate possible mutual etiological pathways

Serological and hematological characteristics of Sjogren's syndrome and dry eye syndrome patients using a novel immune serology technique.

ObjectivesTo compare hematologic and serological parameters among patients with Sjogren's syndrome (SS), dry eye syndrome (DES) and controls, and validate a novel multiplex-serology method for identifying auto-antibodies in these populations.MethodsIn a clinic-based case-control study a total of 422 participants were recruited, including 91 with SS, 120 DES, and 211 controls (age and sex frequency-matched). We measured blood counts, anti-nuclear-antibodies (ANA), anti-SSA/SSB, anti-ribonucleoprotein (RNP), anti-double-stranded-DNA (DS-DNA), and rheumatoid factor (RF) using the "Immunodot" qualitative-ELISA assay. Immunoglobulins, C3 and C4 were measured by immune-fluorescence. Autoantibodies were also quantified with a newly-developed method using glutathione-S-transferase fusion proteins of SSA/Ro 52 and 60kD and SSB/La (multiplex-serology), measuring median fluorescence intensity (MFI).ResultsAmong DES patients, only 2% (95%CI: 0.36-6.3) had positive immune serology. SS patients had lower lymphocyte, hemoglobin and C3 levels but higher prevalence of RF, ANA, anti-SSA/B and higher IgG and MFI levels, compared to DES and controls (PConclusionsSerologic parameters distinguish SS from DES patients and controls. A newly-developed multiplex-serology technique may be useful to detect autoantibodies in large epidemiologic studies

SNP variations in IL10, TNFα and TNFAIP3 genes in patients with dry eye syndrome and Sjogren’s syndrome

Abstract Background Cytokines are known to be key players in dry eye syndrome (DES) and Sjogren’s syndrome (SS) pathogenesis. In this study we compared single nucleotide polymorphism (SNP) variations in genes encoding cytokine levels among SS and DES patients in Israel. Methods We recruited 180 subjects, 82 with SS and 98 with DES. Using a candidate gene approach and allele-specific PCR technique for genotyping, proportions of risk alleles in Tumor Necrosis Factor α (TNFα) (rs1800629), IinterLeukin-10 (IL-10) (rs1800896) and TNFAIP3 (rs2230926) SNPs were compared between study groups. Results Allelic distribution was found very similar to Caucasian (CEU – Utah residents with Northern and Western European roots) population distributions in these SNPs. While none of the SNPs’ variants were significantly associated with SS or DES in a recessive model, in an additive model the TNFα G risk allele was found higher among SS patients compared to DES (Homozygote-G: 84.2% vs. 70.8%; Heterozygote: 26.9% vs. 11.2%, respectively, p = 0.02). After adjustment for age, gender and ethnicity, these variants weren’t associated with SS. Genetic scoring reveals that SS patients are more likely to present variants of all three SNPs than DES subjects. Conclusions This is the first study evaluating these SNP variations among both patients with DES and patients with SS. We found the allelic distribution in each SNP to be very similar to that found in healthy Caucasian populations presented in the HapMap project. We found the TNFα allele significantly associated with DES for homozygotes, and associated with SS for heterozygotes in the additive model