Current evidence from the COVID-19 pandemic suggests that neonatal SARS-coronavirus-2 infections usually have a mild course. Data on how maternal infection during pregnancy affects fetal development are scarce. We present the unique case of a moderate preterm infant with intracranial bleeding and periventricular leukomalacia as a potential consequence of post-COVID-19 hyperinflammation during pregnancy.

Despite antibiotic therapy, infections with Neisseria meningitidis still demonstrate a high rate of morbidity and mortality even in developed countries. The fulminant septicaemic course, named Waterhouse-Friderichsen syndrome, with massive haemorrhage into the adrenal glands and widespread petechial bleeding suggest pathophysiological inhibition of platelet function. Our data show that N. meningitidis produces the important physiological platelet inhibitor and cardiovascular signalling molecule nitric oxide (NO), also known as endothelium-derived relaxing factor (EDRF). N. meningitidis -derived NO inhibited ADP-induced platelet aggregation through the activation of soluble guanylyl cyclase (sGC) followed by an increase in platelet cyclic nucleotide levels and subsequent activation of platelet cGMP- and cAMP- dependent protein kinases (PKG and PKA). Furthermore, direct measurement of horseradish peroxidase (HRP) passage through a vascular endothelial cell monolayer revealed that N. meningitidis significantly increased endothelial monolayer permeability. Immunfluorescence analysis demonstrated NO dependent disturbances in the structure of endothelial adherens junctions after co-incubation with N. meningitidis . In contrast to platelet inhibition, the NO effects on HBMEC were not mediated by cyclic nucleotides. Our study provides evidence that NO plays an essential role in the pathophysiology of septicaemic meningococcal infection.

Extremely immature preterm infants rarely present with a leukocytosis exceeding 30,000/microL. The pathogenetic sequence leading to leukemoid reactions in non-malignant diseases remains to be elucidated. Potential triggers for leukemoid reactions in premature infants include prenatal corticosteroids, chorioamnionitis and funisitis or systemic infection. In the two-year period from 2006 to 2007 all infants with a gestational age of less than 26 weeks were screened for leukocytosis. Among our cases, one preterm infant presented with a leukocyte count of 229,300/microL at the age of 48 hours, lasting throughout the first three weeks of life. Impairment of microcirculation and resulting organ dysfunction were not observed. Thus, invasive therapeutic procedures, which are routinely initiated in hyperleukocytosis in accompanying malignant diseases, may not have the same significance in extremely immature preterm infants and should be executed in these patients on an individual basis and with extreme caution.

Infection with group B streptococcus (GBS) is the most common cause of early onset neonatal sepsis in many countries, leading to neonatal morbidity and mortality. There is much evidence for a direct involvement of platelets in the pathogenesis of inflammation and sepsis. Several bacteria are known to directly interact with platelets leading to activation and aggregation, a phenomenon also observed with GBS. Here, we demonstrate that GBS rapidly bound to platelets; however, only strains isolated from septic patients bound fibrinogen on their surface and induced platelet thromboxane synthesis, platelet aggregation, and P-selectin (CD62P) expression. In contrast, GBS strains isolated from healthy newborns or healthy pregnant women induced only shape change, but not platelet thromboxane synthesis, platelet aggregation, or CD62P expression. All GBS strains investigated were able to activate FcgammaRIIA receptor signaling pathways including phospholipase C gamma2 (PLCgamma2), as well as calcium/calmodulin-dependent myosin kinase II (CaMKII) and phosphorylation of myosin light chain (MLC). In contrast, protein kinase C (PKC) was exclusively activated by GBS strains isolated from septic patients, and p38 mitogen activated protein kinase (p38 MAP kinase) was preferentially activated by septic GBS strains. Furthermore, stress signaling kinase SEK1/MKK4 and focal adhesion kinase (FAK) were activated by all tested GBS strains in a FcgammaRIIA-independent way. This study demonstrates that septic, but not colonizing, GBS strains bind fibrinogen on their surface, and that septic GBS strains influence platelet function not only via the FcgammaRIIA receptor, but also via pathways distinct from IgG-mediated signalling. These mechanisms lead to platelet aggregation and secretion, thereby possibly modulating the pathophysiologic course of GBS infections.

Summary. The fetal lung secretes significant quantities of surfactant during late gestation to prepare for initiation of respiration at birth. However, the mechanism by which this occurs has not been determined. Since Ca 2+ -phosphatidylserine (PS)-dependent protein kinase C has been implicated in surfactant secretion in adult lung, the present study was done to determine whether this enzyme is also involved in the initiation of surfactant release from fetal type II cells. Type II cells isolated from gestational day-24 fetal rabbits were used. Cells were prelabelled with [32 P] and [3 H]choline and exposed to 4␤ phorbol ester (10 −5 M) for 2 h. Secretion product and subcellular fractions were isolated by removing the culture medium, mixing with homogenate from adult rabbit lung, and subfractionating by centrifugation on a sucrose gradient. Samples of secretion product were also prepared for electron microscopy. Ca 2+ -PS-dependent protein kinase C was also assayed in some samples, and an add-back technique was used to determine whether enzyme activity in the intracellularly stored surfactant fraction was due to contamination.The results showed that material released by fetal type II cells after exposure to phorbol ester coprecipitated with adult rabbit lung lamellar bodies and microsomes. Morphologically, a range of forms, including lamellar-body-like structures, was detected. The released material originated largely from the lamellar body compartment of the fetal type II cells and displayed immunoreactivity with antibody to surfactant protein A (SP-A) at 35 and 70 kDa apparent molecular mass. Assay of protein kinase C in fetal type II cells showed that exposure to conditioned medium, which induces differentiation, increased activity. Incubation with phorbol ester induced translocation of activity to the microsomal fraction. Add-back assays suggested that protein kinase C activation by treatment with phorbol ester induced translocation of enzyme activity to the lamellar body fraction; none was detected prior to treatment.These results support a role for Ca 2+ -PS-dependent protein kinase C in initiation of surfactant release by interaction with the developing lamellar body compartment in fetal type II cells.