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Chronic bone loss is an under-recognized complication of malaria, the underlying mechanism of which remains incompletely understood. We have previously shown that persistent accumulation of Plasmodium products in the bone marrow leads to chronic inflammation in osteoblast (OB) and osteoclast (OC) precursors causing bone loss through MyD88, an adaptor molecule for diverse inflammatory signals. However, the specific contribution of MyD88 signaling in OB or OC precursors in malaria-induced bone loss remains elusive. To assess the direct cell-intrinsic role of MyD88 signaling in adult bone metabolism under physiological and infection conditions, we used the Lox-Cre system to specifically deplete MyD88 in the OB or OC lineages. Mice lacking MyD88 primarily in the maturing OBs showed a comparable decrease in trabecular bone density by microcomputed tomography to that of controls after Plasmodium yoelii non-lethal infection. In contrast, mice lacking MyD88 in OC precursors showed significantly less trabecular bone loss than controls, suggesting that malaria-mediated inflammatory mediators are primarily controlled by MyD88 in the OC lineage. Surprisingly, however, depletion of MyD88 in OB, but not in OC, precursors resulted in reduced bone mass with decreased bone formation rates in the trabecular areas of femurs under physiological conditions. Notably, insulin-like growth factor-1, a key molecule for OB differentiation, was significantly lower locally and systemically when MyD88 was depleted in OBs. Thus, our data demonstrate an indispensable intrinsic role for MyD88 signaling in OB differentiation and bone formation, while MyD88 signaling in OC lineages plays a partial role in controlling malaria-induced inflammatory mediators and following bone pathology. These findings may lead to the identification of novel targets for specific intervention of bone pathologies, particularly in malaria-endemic regions. [ABSTRACT FROM AUTHOR]

Invasive meningococcal disease (IMD) is caused by Neisseria meningitidis , with the main serogroups responsible for the disease being A, B, C, W, X, and Y. To date, several vaccines targeting N. meningitidis have been developed albeit with a short-lived protection. Given that MenW and MenB are the most common causes of IMD in Europe, Turkey, and the Middle East, we aimed to develop an outer membrane vesicle (OMV) based bivalent vaccine as the heterologous antigen source. Herein, we compared the immunogenicity, and breadth of serum bactericidal activity (SBA) assay-based protective coverage of OMV vaccine to the X serotype with existing commercial meningococcal conjugate and polysaccharide (PS) vaccines in a murine model. BALB/c mice were immunized with preclinical batches of the W + B OMV vaccine, either adjuvanted with Alum, CpG ODN, or their combinations, and compared with a MenACYW conjugate vaccine (NimenrixTM, Pfizer), and a MenB OMV-based vaccine (Bexsero®, GSK), The immune responses were assessed through enzyme-linked immunosorbent assay (ELISA) and SBA assay. Antibody responses and SBA titers were significantly higher in the W + B OMV vaccine when adjuvanted with Alum or CpG ODN, as compared to the control groups. Moreover, the SBA titers were not only significantly higher than those achieved with available conjugated ACYW vaccines but also on par with the 4CMenB vaccines. In conclusion, the W + B OMV vaccine demonstrated the capacity to elicit robust antibody responses, surpassing or matching the levels induced by licensed meningococcal vaccines. Consequently, the W + B OMV vaccine could potentially serve as a viable alternative or supplement to existing meningococcal vaccines. [ABSTRACT FROM AUTHOR]

Background: Influenza in children has been well described, whereas there has been a paucity of pediatric data regarding COVID‐19. It is crucial for clinicians to differentiate cases of COVID‐19 from cases of influenza because of the upcoming influenza season in the new pandemic era. Methods: This retrospective study included pediatric patients who were diagnosed with laboratory‐confirmed COVID‐19 between March and September 2020, or seasonal influenza between October 2019 and March 2020. Results: A total of 315 children were included in this study; 151 were diagnosed with influenza and 164 had confirmed COVID‐19. The median age of patients with COVID‐19 was 10 years (interquartile range [IQR]: 3–15 years), whereas the median age of patients with influenza was 4 years (IQR: 1–6 years) (p = 0.001). In the COVID‐19 group, 6.3% of patients had underlying diseases, the most frequent being neurological conditions (3%). In the influenza group, 20.9% of patients had an underlying disease, the most frequent being asthma (14.5%). Fever (odds ratio [OR]: 20.476; 95% confidence interval [CI]: 2.438–171.995; p = 0.005), dyspnea/tachypnea (OR 13.950; 95% CI: 2.607–74.634; p = 0.002), and increased C‐reactive protein (CRP) (OR: 7.650; 95% CI: 2.094–27.955; p = 0.002) were main predictors of influenza diagnosis in comparison to COVID‐19. Lymphopenia was detected in 43.2% of patients with influenza and 19.9% of patients with COVID‐19 (p = 0.001). Conclusions: The accurate differentiation between "influenza or COVID‐19" seems possible by evaluating a combination of factors including cough, fever, vomiting, leucopenia, lymphopenia, pneumonia, in pediatric patients with high CRP as well as age. [ABSTRACT FROM AUTHOR]

Background: This study aimed to evaluate the effectiveness and optimal use of corticosteroids in children with severe coronavirus disease 2019 (COVID‐19) pneumonia, for which effective treatment is still lacking with respect to this population. Methods: We conducted a retrospective study and included patients (aged < 18 years) with severe COVID‐19 pneumonia and/or acute respiratory distress syndrome (ARDS) who received standard doses (2–4 mg/kg/day) and high doses (>250 mg/day) of methylprednisolone (MPZ). We adjusted for patients on steroid treatments with a propensity score and compared the side effects of different MPZ doses and patient survival. Results: Fifty‐nine patients were included: 61% were male, the median age was 8, interquartile range (IQR) 2–15) years. The overall survival was 84.4% in patients treated with standard‐dose MPZ (n = 45, 76.3%) and 92.2% in patients treated with high‐dose MPZ (n = 14, 23.7%; p = 0.67). The demographic, clinical, and laboratory data did not differ significantly after propensity score matching, apart from bradycardia, which was a prominent feature of the high‐dose group. The clinical and radiological response rates on day 7 were higher and the need for invasive mechanical ventilation (IMV) was lower in the high‐dose group. Conclusion: The patients with high‐dose MPZ had better clinical and radiological responses than those with standard‐dose MPZ, although the mortality rate did not differ between standard and high‐dose regimens of MPZ. [ABSTRACT FROM AUTHOR]

Objective: The COVID-19 outbreak that has spread all around the world is still a threat for humankind. Epidemiological, clinical, laboratory, and radiological features of the disease are enlightened day by day. It was aimed to evaluate the characteristics of children and their parents with COVID-19 to aid in diagnosis and treatment. Material and Methods: A retrospective review of the medical records of pediatric patients and their parents who were confirmed as COVID-19 positive, between April 23, and May 28, 2020, was conducted. Results: A total of 93 children and 81 adults were evaluated in the present study. Asymptomatic and mild cases accounted for 63.5% of the children and 50% of the parents. Of the children, 3.2% had moderate illness, whereas this was 9.8% for the parents There was a statistically significant difference in terms of the severity of illness between the children and their parents (p =0.01). Although it had a milder clinical course in children, one child died. Increased levels of C-reactive protein (CRP) were observed in 8.6% of the children and 48.1% of the patients, and there was statistically significant difference in terms of CRP levels between the children and their parents (p =0.001). Conclusion: The clinical, laboratory, and radiological features of COVID-19 showed differences in the children and their parents. It should be kept in mind that COVID-19 can be fatal in children, although the course of the disease appears to be milder in children than in their parents [ABSTRACT FROM AUTHOR]

The disease course of children with coronavirus disease 2019 (COVID‐19) seems milder as compared with adults, however, actual reason of the pathogenesis still remains unclear. There is a growing interest on possible relationship between pathogenicity or disease severity and biomarkers including cytokines or chemokines. We wondered whether these biomarkers could be used for the prediction of the prognosis of COVID‐19 and improving our understanding on the variations between pediatric and adult cases with COVID‐19. The acute phase serum levels of 25 cytokines and chemokines in the serum samples from 60 COVID‐19 pediatric (n = 30) and adult cases (n = 30) including 20 severe or critically ill, 25 moderate and 15 mild patients and 30 healthy pediatric (n = 15) and adult (n = 15) volunteers were measured using commercially available fluorescent bead immunoassay and analyzed in combination with clinical data. Interferon gamma‐induced protein 10 (IP‐10) and macrophage inflammatory protein (MIP)−3β levels were significantly higher in patient cohort including pediatric and adult cases with COVID‐19 when compared with all healthy volunteers (p ≤.001 in each) and whereas IP‐10 levels were significantly higher in both pediatric and adult cases with severe disease course, MIP‐3β were significantly lower in healthy controls. Additionally, IP‐10 is an independent predictor for disease severity, particularly in children and interleukin‐6 seems a relatively good predictor for disease severity in adults. IP‐10 and MIP‐3β seem good research candidates to understand severity of COVID‐19 in both pediatric and adult population and to investigate possible pathophysiological mechanism of COVID‐19. [ABSTRACT FROM AUTHOR]

Introduction: Limited data are available for pediatric patients with coronavirus disease 2019 (COVID-19), especially with regard to disease management strategies. Objective: To assess the children with COVID-19. Method: We conducted a retrospective review of the medical records of pediatric patients on March 11 and May 23, 2020. Results: We evaluated 77 COVID-19 pediatric patients, of whom 45.5% were male, with a median age of 8 years (interquartile range [IQR] = 2-13), and 6.4% had underlying diseases. Patients were classified according to severity, with the percentages of asymptomatic, mild, moderate, and critical/severe cases determined to be 24.7%, 41.6%, 29.9%, and 3.9%, respectively. Extracorporeal membrane oxygenation and mechanic ventilation were only required for 1 patient. Targeted therapies were used in 3 patients. Conclusion: The disease course of COVID-19 appears to be milder in children than in adults, and the treatment course primarily consists of supportive care. [ABSTRACT FROM AUTHOR]