Evaluation of presepsin as a diagnostic tool in newborns with risk of early-onset neonatal sepsis.

Objectives: To evaluate the efficacy of presepsin (P-SEP) as a potential biomarker of early-onset neonatal sepsis (EOS) and compare it to other routinely used markers of inflammation. To establish the cut-off values of P-SEP for EOS. Study design: 184 newborns were prospectively recruited between January 2018 to December 2020. Newborns >34th gestational week with suspected infection were included up to 72 h after delivery, and divided into three categories (i.e., unlikely, possible, and probable infection) based on risk factors, clinical symptoms and laboratory results. Values of plasma P-SEP were sequentially analyzed. Results: Median values of P-SEP in newborns with probable infection were significantly higher compared to healthy newborns (p = 0.0000013) and unlikely infection group (p = 0.0000025). The AUC for discriminating the probable infection group from the unlikely infection group was 0.845 (95% Cl: 0.708-0.921). The diagnostic efficacy of P-SEP was highest when used in combination with IL-6 and CRP (0.97; 95% CI: 0.911-0.990). The optimal cut-off value of P-SEP was determined to be 695 ng/L. Conclusion: P-SEP, when combined with IL-6 and CRP, may be utilized as a negative predictive marker of EOS (NPV 97.2%, 95% CI: 93.3-101), especially in newborns at low to medium risk of infection.

Searching for COVID-19 Antibodies in Czech Children-A Needle in the Haystack.

During the COVID-19 pandemics of 2020, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), both adults and children were shown to mount a specific antibody response to the virus. As infected children often exhibit mild symptoms or even remain asymptomatic, they are likely to be under tested for the direct presence of the virus. Mapping the SARS-CoV-2 antibodies frequency informs more accurately on the disease prevalence and helps guide the protective and therapeutic strategies. To date, only few seroprevalence studies included children. In the Czech Republic, in April 2020, the overall SARS-CoV-2 seroprevalence was estimated not to exceed 1.3%. In July and August, 2020, we screened 200 children (0-18 years of age), who attended the pediatric department of a large hospital in Prague for various COVID-19-unrelated reasons, for the presence of SARS-CoV-2 antibodies. Zero seropositive subjects were found. Therefore, we hereby report a low (<0.5%) seroprevalence amongst children in Prague, as of August, 2020.

Anti-IL6 Autoantibodies in an Infant With CRP-Less Septic Shock.

Background: Interleukin-6 (IL-6) is a pleiotropic cytokine with a multitude of pro-inflammatory effects. Serum C-reactive protein (CRP) is an acute phase protein induced mainly by IL-6 in response to inflammatory conditions, particularly infection. The biological functions of CRP include opsonisation, induction of phagocytosis, complement activation, or chemotaxis enhancement. Factors interfering with IL-6-mediated recruitment of innate immune responses, such as the presence of anti-IL6 antibodies, may therefore compromise the host resistance to microbial pathogens. This has major implications for the use of IL-6-targeting biologics, such as tocilizumab or sarilumab in rheumatologic, immune dysregulation diseases, and cancer. Case presentation: 20-month-old Czech female developed severe septic shock with clinical and laboratory signs of systemic inflammation but no increase of CRP or IL-6. The offending pathogen was most likely Staphylococcus aureus, detected in a throat swab; the response to antibiotic treatment was prompt. A defect in the integrity of IL-6/CRP axis was suspected and verified by the detection of neutralizing IL-6 antibodies in the serum of the child. Conclusion: We report a first case of systemic bacterial infection in a patient with anti-IL6 autoantibodies. Disturbed IL-6 signaling, whether iatrogenic by targeted IL-6 blockade or endogenous due to the presence of autoantibodies against IL-6, represents a risk factor for increased infectious susceptibility. Patients with severe bacterial infection without elevation of CRP should be examined for the presence of anti-IL6 autoantibodies.