In the context of suspected neonatal sepsis, early diagnosis and stratification of patients according to clinical severity is not yet effectively achieved. In this diagnostic trial, we aimed to assess the accuracy of presepsin (PSEP) for the diagnosis and early stratification of supposedly septic neonates. PSEP, C-reactive protein (CRP), and procalcitonin (PCT) were assessed at the onset of sepsis suspicion (T0), every 12–24 h for the first 48 h (T1–T4), and at the end of antibiotic therapy (T5). Enrolled neonates were stratified into three groups (infection, sepsis, septic shock) according to Wynn and Wong’s definitions. Sensitivity, specificity, and area under the ROC curve (AUC) according to the severity of clinical conditions were assessed. We enrolled 58 neonates with infection, 77 with sepsis, and 24 with septic shock. PSEP levels were higher in neonates with septic shock (median 1557.5 pg/mL) and sepsis (median 1361 pg/mL) compared to those with infection (median 977.5 pg/mL) at T0 (p < 0.01). Neither CRP nor PCT could distinguish the three groups at T0. PSEP’s AUC was 0.90 (95% CI: 0.854–0.943) for sepsis and 0.94 (95% CI: 0.885–0.988) for septic shock. Maximum Youden index was 1013 pg/mL (84.4% sensitivity, 88% specificity) for sepsis, and 971.5 pg/mL for septic shock (92% sensitivity, 86% specificity). However, differences in PSEP between neonates with positive and negative blood culture were limited. Thus, PSEP was an early biomarker of neonatal sepsis severity, but did not support the early identification of neonates with positive blood culture.

After 18 months of the COVID‐19 pandemic, data concerning SARS‐CoV‐2 infection in pregnant women and their neonates are progressively taking the place of complete uncertainty. Here, we summarize updated evidence regarding several critical aspects of perinatal SARS‐CoV‐2 infection, including 1) vertical transmission of the virus in utero, which is possible but seems rare according to current epidemiological data; 2) how COVID‐19 during pregnancy can shape maternal and neonatal outcomes, either directly or indirectly; 3) how recommendations regarding the management of infected dyads have been progressively modified in light of new scientific evidence; and 4) how maternal infection or vaccination can induce the passive protection of fetuses and neonates against the infection, through the transfer of specific antibodies before and after birth.

Background: An unclassified primary antibody deficiency (unPAD) is a widely heterogeneous clinical entity, recently identified within the spectrum of Inborn Errors of Immunity (IEIs). Since unPAD has been traditionally considered as a mild condition, it has incorrectly received little attention, resulting in the paucity of extensive and comparable studies describing its natural history. To address the gaps in characterizing, understanding, and managing pediatric unPAD patients, the Italian Primary Immunodeficiency Network (IPINet) Ped-unPAD study has recently been launched. Methods: Seventeen IPINeT Centers have expressed interest to participate, and data collection is still on-going. Hereby, we anticipate preliminary key issues emerging from the first 110 enrolled patients, attending three IPINet Centers. Results: A proportion of unPAD patients have experienced a severe infectious phenotype, which required hospitalization in a quarter of patients and antibiotic prophylaxis or Immunoglobulin Replacement Therapy in approximately 10% of patients. In this partial cohort, a mean follow-up (FU) of 5 years confirmed unPAD diagnosis in fifty percent of cases, with the remaining being reclassified as the Transient Hypogammaglobulinemia of Infancy (25%) and other IEIs (25%), such as a Common Variable Immunodeficiency, Selective IgA deficiency, Selective IgM deficiency, and IgG3 subclass deficiency. Conclusions: Despite a phenotype overlap at diagnosis, clinicians should be aware that unPAD is a mutable condition that deserves comprehensive evaluation and long-term monitoring to dissect the final diagnosis for optimal treatment.