Disseminated tuberculosis and hemophagocytic syndrome although TB prophylaxis in patients with inflammatory bowel disease treated with Infliximab

Purpose: We present de case of a 27-year-old woman admitted to ICU after scheduled splenectomy to study her short course of fever, leukopenia and splenic space-occupying lesions and splenomegaly. She has been previously treated with Infliximab due to indeterminate colitis and completed correct tuberculosis prophylaxis. Materials and methods: We reviewed our case in our regional Electronic Health DataBase IANUS and compared it with other case reports in literature, found in PubMed, with keywords tuberculosis, inflammatory disease and hemophagocytic lymphohistiocytosis. Results: After splenectomy, she needed intensive care due to acute respiratory failure, alveolar-interstitial pulmonary infiltrates, right pleural effusion and fever. Bone marrow aspirate resulted in hemophagocytic lymphohistiocytosis. Only multidisciplinary management in ICU and combined treatment with chemotherapy for hemophagocytic syndrome and tuberculostatics achieved her curation. Conclusion: Tuberculosis must always be considered in the differential diagnosis of hemophagocytic lymphohistiocytosis and acute respiratory failure despite correct prior prophylaxi

Predictors of in-hospital mortality in HIV-infected patients with COVID-19

Background Underlying immunodeficiency is associated with severe COVID-19, but the prognosis of persons with human immunodeficiency virus (HIV) (PWH) with COVID-19 is under debate. Aim: assessment of the mortality rate and major determinants of death in HIV-infected patients hospitalized with COVID-19 in Spain before vaccine availability. Design: Retrospective nationwide public database analysis. Methods Nationwide, retrospective, observational analysis of all hospitalizations with COVID-19 during year 2020 in Spain. Stratification was made according to HIV status. The National Registry of Hospital Discharges was used with the ICD-10 coding list. Results A total of 117 694 adults were hospitalized with COVID-19 during 2020. Only 234 (0.2%) were HIV-positives. More than 95% were on antiretroviral therapy. Compared to HIV-negatives, PWH were younger (mean age 53.2 vs. 66.5 years old; P<0.001) and more frequently male (74.8% vs. 56.6%; P<0.001). Most co-morbidities predisposing to severe COVID-19 (diabetes, hypertension, dementia and cardiovascular disease) were more frequent in HIV-negatives. In contrast, the rate of baseline liver disease was over 6-fold higher in PWH (27.4% vs. 4.4%; P<0.001). In-hospital mortality was lower in PWH (9.4% vs. 16%; P=0.004). In multivariate analysis, older age, dementia and especially advanced liver disease (relative risk (RR): 7.6) were the major determinants of death in PWH hospitalized with COVID-19. Conclusion HIV-infected patients hospitalized in Spain with COVID-19 during 2020 had better survival than HIV-negatives, most likely explained by younger age and lower rate of co-morbidities. However, advanced liver disease was a major predictor of death in PWH hospitalized with COVID-19

mtDNA Single-Nucleotide Variants Associated with Type 2 Diabetes

Type 2 diabetes (T2D) is a chronic systemic disease with a complex etiology, characterized by insulin resistance and mitochondrial dysfunction in various cell tissues. To explore this relationship, we conducted a secondary analysis of complete mtDNA sequences from 1261 T2D patients and 1105 control individuals. Our findings revealed significant associations between certain single-nucleotide polymorphisms (SNPs) and T2D. Notably, the variants m.1438A>G (rs2001030) (controls: 32 [27.6%], T2D: 84 [72.4%]; OR: 2.46; 95%CI: 1.64–3.78; p T (rs193302980) (controls: 498 [36.9%], T2D: 853 [63.1%]; OR: 2.57, 95%CI: 2.18–3.04, p C (rs3937033) (controls: 363 [43.4%], T2D: 474 [56.6%]; OR: 1.24, 95%CI: 1.05–1.47, p = 0.012) were significantly associated with the likelihood of developing diabetes. The variant m.16189T>C (rs28693675), which has been previously documented in several studies across diverse populations, showed no association with T2D in our analysis (controls: 148 [13.39] T2D: 171 [13.56%]; OR: 1.03; 95%CI: 0.815–1.31; p = 0.83). These results provide evidence suggesting a link between specific mtDNA polymorphisms and T2D, possibly related to association rules, topological patterns, and three-dimensional conformations associated with regions where changes occur, rather than specific point mutations in the sequence

Subcutaneous anti-COVID-19 hyperimmune immunoglobulin for prevention of disease in asymptomatic individuals with SARS-CoV-2 infection: a double-blind, placebo-controlled, randomised clinical trialResearch in context

Summary: Background: Anti-COVID-19 hyperimmune immunoglobulin (hIG) can provide standardized and controlled antibody content. Data from controlled clinical trials using hIG for the prevention or treatment of COVID-19 outpatients have not been reported. We assessed the safety and efficacy of subcutaneous anti-COVID-19 hyperimmune immunoglobulin 20% (C19-IG20%) compared to placebo in preventing development of symptomatic COVID-19 in asymptomatic individuals with SARS-CoV-2 infection. Methods: We did a multicentre, randomized, double-blind, placebo-controlled trial, in asymptomatic unvaccinated adults (≥18 years of age) with confirmed SARS-CoV-2 infection within 5 days between April 28 and December 27, 2021. Participants were randomly assigned (1:1:1) to receive a blinded subcutaneous infusion of 10 mL with 1 g or 2 g of C19-IG20%, or an equivalent volume of saline as placebo. The primary endpoint was the proportion of participants who remained asymptomatic through day 14 after infusion. Secondary endpoints included the proportion of individuals who required oxygen supplementation, any medically attended visit, hospitalisation, or ICU, and viral load reduction and viral clearance in nasopharyngeal swabs. Safety was assessed as the proportion of patients with adverse events. The trial was terminated early due to a lack of potential benefit in the target population in a planned interim analysis conducted in December 2021. ClinicalTrials.gov registry: NCT04847141. Findings: 461 individuals (mean age 39.6 years [SD 12.8]) were randomized and received the intervention within a mean of 3.1 (SD 1.27) days from a positive SARS-CoV-2 test. In the prespecified modified intention-to-treat analysis that included only participants who received a subcutaneous infusion, the primary outcome occurred in 59.9% (91/152) of participants receiving 1 g C19-IG20%, 64.7% (99/153) receiving 2 g, and 63.5% (99/156) receiving placebo (difference in proportions 1 g C19-IG20% vs. placebo, −3.6%; 95% CI -14.6% to 7.3%, p = 0.53; 2 g C19-IG20% vs placebo, 1.1%; −9.6% to 11.9%, p = 0.85). None of the secondary clinical efficacy endpoints or virological endpoints were significantly different between study groups. Adverse event rate was similar between groups, and no severe or life-threatening adverse events related to investigational product infusion were reported. Interpretation: Our findings suggested that administration of subcutaneous human hyperimmune immunoglobulin C19-IG20% to asymptomatic individuals with SARS-CoV-2 infection was safe but did not prevent development of symptomatic COVID-19. Funding: Grifols