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Primary cytomegalovirus infection during pregnancy has a high risk of vertical transmission, with severe fetal sequelae mainly associated with first-trimester infections. We conducted a retrospective analysis of 200 IU/kg cytomegalovirus-specific hyperimmune globulin (HIG), used in first-trimester maternal primary infections for congenital infection prevention. The primary outcome was vertical transmission, defined as neonatal viruria or positive amniocentesis if pregnancy was discontinued. HIG, initially administered monthly and since 2019 biweekly, was discontinued in negative amniocentesis cases. Women declining amniocentesis and positive amniocentesis cases with normal sonography were offered monthly HIG until delivery as a treatment strategy. The total transmission rate was 29.9% (32/107; 10 pregnancy terminations with positive amniocentesis, 18 completed pregnancies with positive amniocentesis and 4 declining amniocentesis). Maternal viremia was the only factor associated with fetal transmission (OR 4.62, 95% CI 1.55–13.74). The transmission rate was not significantly different whether HIG was started during the first or second trimester (28.2% vs. 33.3%; p = 0.58), or between monthly and biweekly subgroups (25.7% vs. 37.8%, p = 0.193). Pre-treatment maternal viremia could inform decisions as a predictor of congenital infection. [ABSTRACT FROM AUTHOR]

Introduction: Currently approved SARS-CoV-2 vaccines have been proven effective in protecting against severe COVID-19; however, they show variable efficacy against symptomatic infection and disease transmission. We studied the breakthrough COVID-19 infection (BTI) after booster vaccination against SARS-CoV-2 in people living with HIV (PWH). Methods: This was a retrospective, single-center, descriptive cohort study involving PWH, who were followed in the HIV Clinic of "Attikon" University Hospital in Athens, Greece. A BTI was defined as a case of laboratory-confirmed COVID-19 occurring at least 14 days after the third (booster) vaccine dose. Results: We studied 733 PWH [males: 89%, mean age: 45.2 ± 11.3 years, mean BMI: 26.1 ± 4.1, HIV stage at diagnosis (CDC classification): A/B/C = 80/9/11%, MSM: 72.6%] with well-controlled HIV infection. At least one comorbidity was recorded in 54% of cases. A history of ≥1 vaccination was reported by 90%, with 75% having been vaccinated with ≥3 vaccines. Four hundred and two (55%) PWH had a history of COVID-19 and 302 (41.2%) had a BTI, with only 15 (3.7%) needing hospitalization. Only one patient was admitted to the ICU, and no death was reported. Regarding BTI after booster dose, increased age (OR = 0.97, 95% CI: 0.96–0.99, per 1-year increase), and COVID-19 infection prior to booster dose (OR = 0.38, 95% CI: 0.21–0.68) were associated with a lower likelihood for BTI, whereas higher BMI (OR = 1.04, 95% CI: 1.01–1.08) and MSM as a mode of HIV transmission were associated with increased risk (OR = 2.59, 95% CI: 1.47–4.56). The incidence rate of total COVID-19 and BTI followed the epidemic curve of the general population, with the highest incidence recorded in June 2022. Conclusions: A significant proportion of PWH with well-controlled HIV infection experienced a BTI, with the majority of them having mild infection. These data, which include the period of Omicron variant predominance, confirm the importance of vaccination in the protection against severe COVID-19. [ABSTRACT FROM AUTHOR]

Background/Objectives: Glomerulopathy is a term used to describe a broad spectrum of renal diseases, characterized by dysfunction of glomerular filtration barrier, especially of podocytes. Several podocyte-associated proteins have been found and proved their usefulness as urine markers of podocyte dysfunction. Two of them are nephrin (NEP) and prodocalyxin (PDC). This study aims to evaluate the association of podocyte damage, as it is demonstrated via the concentrations of urinary proteins, with clinical and histological data from patients with several types of glomerulonephritis. Methods: We measured urine levels of two podocyte-specific markers, NEP and PDC (corrected for urine creatinine levels), in patients with a wide range of glomerulopathies. Serum and urine parameters as well as histological parameters from renal biopsy were recorded. Results: In total, data from 37 patients with glomerulonephritis and 5 healthy controls were analyzed. PDC and NEP concentrations correlated between them and with serum creatinine levels (p = 0.001 and p = 0.013 respectively), and with histological lesions associated with chronicity index of renal cortex, such as severe interstitial fibrosis, severe tubular atrophy and hyalinosis (for PDC/NEP, all p < 0.05). In addition, the PDC and NEP demonstrated statistically significant correlations with interstitial inflammation (p = 0.018/p = 0.028). Regarding electron microscopy evaluation, PDC levels were correlated with distinct characteristics, such as fibrils and global podocyte foot process fusion, whereas the NEP/CR ratio was uniquely significantly associated with podocyte fusion only in non-immune-complex-mediated glomerulonephritis (p = 0.02). Among the other clinical and histological parameters included in our study, a strong correlation between proteinuria >3 g/24 h and diffuse fusion of podocyte foot processes (p = 0.016) was identified. Conclusions: Podocalyxin and nephrin concentrations in urine are markers of podocyte dysfunction, and in our study, they were associated both with serum creatinine and histological chronicity indices. [ABSTRACT FROM AUTHOR]

Progressive multifocal leukoencephalopathy (PML) is a severe demyelinating disease of the central nervous system (CNS) caused by reactivation of the polyomavirus JC (JCV) typically in immunocompromised individuals. The risk of PML among rheumatic diseases may be higher for systemic lupus erythematosus (SLE), without, however, a clear association with the type and intensity of background therapy. We present the development and outcome of PML in a 32-year-old female lupus patient under mild immunosuppressive treatment, yet with marked B-cell lymphopenia in the peripheral blood and bone marrow (<1% of total lymphocytes). Despite treatment with the immune checkpoint inhibitor pembrolizumab, the patient showed progressive neurological and brain imaging deterioration and eventually died 15 months after PML diagnosis. To unveil possible underlying genetic liabilities, whole exome sequencing was performed which identified deleterious variants in GATA2 and CDH7 genes, which both have been linked to defective T- and/or B-lymphocyte production. These findings reiterate the possible role of disease-/patient-intrinsic factors, rather than that of drug-induced immunosuppression, in driving immune dysregulation and susceptibility to PML in certain patients with SLE. [ABSTRACT FROM AUTHOR]