Comparison of humoral immune response in heterologous and homologous COVID-19 booster vaccine groups using CoronaVac and mRNA-based BNT162b2 vaccines.

BACKGROUND: Heterologous COVID-19 booster vaccination is an alternative strategy to homologous vaccination, especially in developing countries, due to shortages, delays, or unequal distribution of COVID-19 vaccines. We compared cohorts vaccinated with different vaccine combinations to investigate whether a heterologous booster dose of mRNA-based BNT162b2 vaccine boosts the immune response in individuals primed with the CoronaVac vaccine. METHODS: Anti-RBD IgG is generally measured 4 weeks after primary immunization and 4 weeks after booster vaccination. Data on anti-receptor-binding domain (anti-RBD) IgG antibody titers and clinical characteristics were provided by infection control units. RESULTS: The highest median anti-RBD IgG antibody titers (14589 AU/mL) after primary immunization was observed in the group vaccinated with two doses of BNT162b2 vaccine. Antibody titers were lower 4 months or more after the second CoronaVac vaccine dose in CoronaVac recipients with or without previous COVID-19. In the homologous COVID-19 booster vaccine group (primed with two doses of CoronaVac 4 weeks apart and a single booster dose of CoronaVac) the median anti-RBD titers decreased from 1025 to 242 AU/mL before the booster dose. In the heterologous group (primed with two doses of CoronaVac 4 weeks apart and a single booster dose of BNT162b2), the median anti-RBD titer increased to 31624 AU/mL, a 132-fold increase, 16 days after the booster dose. CONCLUSIONS: After the second dose of CoronaVac, protective neutralizing antibody levels decrease over time, and a booster dose is required. Heterologous COVID-19 booster vaccination with BNT162b2 is effective at boosting neutralizing antibody levels.

Comparison of humoral immune response in heterologous and homologous COVID-19 booster vaccine groups using CoronaVac and mRNA-based BNT162b2 vaccines

ABSTRACT Background: Heterologous COVID-19 booster vaccination is an alternative strategy to homologous vaccination, especially in developing countries, due to shortages, delays, or unequal distribution of COVID-19 vaccines. We compared cohorts vaccinated with different vaccine combinations to investigate whether a heterologous booster dose of mRNA-based BNT162b2 vaccine boosts the immune response in individuals primed with the CoronaVac vaccine. Methods: Anti-RBD IgG is generally measured 4 weeks after primary immunization and 4 weeks after booster vaccination. Data on anti-receptor-binding domain (anti-RBD) IgG antibody titers and clinical characteristics were provided by infection control units. Results: The highest median anti-RBD IgG antibody titers (14589 AU/mL) after primary immunization was observed in the group vaccinated with two doses of BNT162b2 vaccine. Antibody titers were lower 4 months or more after the second CoronaVac vaccine dose in CoronaVac recipients with or without previous COVID-19. In the homologous COVID-19 booster vaccine group (primed with two doses of CoronaVac 4 weeks apart and a single booster dose of CoronaVac) the median anti-RBD titers decreased from 1025 to 242 AU/mL before the booster dose. In the heterologous group (primed with two doses of CoronaVac 4 weeks apart and a single booster dose of BNT162b2), the median anti-RBD titer increased to 31624 AU/mL, a 132-fold increase, 16 days after the booster dose. Conclusions: After the second dose of CoronaVac, protective neutralizing antibody levels decrease over time, and a booster dose is required. Heterologous COVID-19 booster vaccination with BNT162b2 is effective at boosting neutralizing antibody levels.

Response to "Letter to the Editor: Vaccine Failures in Pediatric Cases Caused by Streptococcus pneumoniae Serotype 19A".

We are happy to answer to the Letter from Ozkaya-Parlakay et al. to the Editor commenting on our recent paper, 1  investigated impact of the 13-valent pneumococcal conjugate vaccine (PCV13)  on the incidences of community-acquired pneumonia and pneumonia-related hospitalizations in children ≤5 years after its implementation into the national immunization program (NIP) of Turkey.   Ozkaya-Parlakay et al. draw attention to vaccine failure and importance of continuous  surveillance of relevant disease especially in the perspective of  Streptococcus pneumoniae  serotype 19A. They supported their opinion by their clinical observation of seven children who were vaccinated with PCV13 developed empyema and meningitidis caused by Streptococcus pneumoniae  serotype 19A 
 in Turkey.

Impact of the 13-valent pneumococcal conjugate vaccine on the incidences of community-acquired pneumonia and pneumonia-related hospitalizations in children ≤5 years after its implementation into the national immunization program of Turkey.

The aim of the study was to investigate changes in the incidences of community-acquired pneumonia (CAP) and CAP-related hospitalizations following introduction of 13-valent pneumococcal conjugate vaccine (PCV13) in children ≤5 years of age into the national immunization programme (NIP) of Turkey. PCV7 was included in the NIP of Turkey in November 2008 and was replaced by PCV13 in late 2011. Changes in the incidences of CAP and CAP-related hospitalizations per 100,000 children admissions were investigated from 2011 to 2017. A total of 225,963 children visits were recorded; CAP was diagnosed in 4863 (2.15%) children and 1086 (22%) of them hospitalized between 2011 and 2017. The incidence of CAP declined from 5448 to 1144/100,000 from 2011 to 2017 (p = .001, r = -0.965). When the mean annual incidence of CAP between the transition period of PCV13 (2011/2012) was compared with a post-PCV13 period (2016/2017), CAP incidence was found to be 22% lower (p = .009). Also, the incidence of CAP-related hospitalization decreased significantly from 943 to 335/100,000 from 2011 to 2017 (p = .004 r = -0.91). Moreover, the mean incidence of CAP hospitalization declined 35% (p = .01) between the transition period of PCV13 and a post-PCV13 period. Thus, our study showed a significant reductions in the incidences of CAP and CAP-related hospitalization in children ≤5 years-old after the implementation of PCV13 into the NIP of Turkey.

Impact of the 13-valent pneumococcal conjugate vaccine on the incidences of acute otitis media, recurrent otitis media and tympanostomy tube insertion in children after its implementation into the national immunization program in Turkey.

The aim of this study was to investigate changes in the incidences of acute otitis media (AOM), recurrent AOM (rAOM) and tympanostomy tube (TT) insertion in children following the introduction of 13-valent pneumococcal conjugate vaccine (PCV13) into the national immunization program (NIP) of Turkey in April 2011. National coverage for the PCV7 was 97% in 2009, 93% in 2010, 96% in 2011 and for the PVC13 was 97% in 2012, 97% in 2013, 96% in 2014, 97% in 2015, 98% in 2016, and 96% in 2017 for Turkish children younger than 12 months of age. A total of 499932 pediatric visits were recorded, and AOM was diagnosed in 23005 (4.6%) children. The incidence of AOM in children ≤5 years of age decreased from 10700/100000 (2011) to 4712/100000 (2017), with a significant decreasing trend (p < .001, r = -0.965). When the mean annual incidences of AOM between the transition period of PCV13 (years 2011/2012) were compared with those of a post-PCV13 period (years 2016/2017) for children ≤5 years of age, the incidence of AOM was found to be decreased by 54% (p = 0.013). The mean incidence of TT insertion was found to be decreased by 65% (p = 0.003) between the transition period of PCV13 and a post-PCV13 period for children ≤5 years of age. On the other hand, rAOM incidence was found to be increased in whole pediatric age groups. Our study showed a significant decrease in the incidences of AOM and TT insertion in children ≤5 years old after implementation of PCV13 in the NIP in Turkey.

The Association between Serum 25-Hydroxy Vitamin D Level and Urine Cathelicidin in Children with a Urinary Tract Infection.

OBJECTIVE: Cathelicidin is an important antimicrobial peptide in the urinary tract. Cathelicidin expression is strongly stimulated by 1,25-dihydroxy vitamin D in epithelial cells, macrophages/monocytes, and neutrophils. Vitamin D and cathelicidin status in children with urinary tract infection (UTI) caused by Escherichia coli is unknown. To establish the relationship between serum vitamin D and urine cathelicidin levels in children with a UTI caused by Escherichia coli. METHODS: Serum 25-hydroxy vitamin D and urine cathelicidin levels were measured in 36 patients with UTI (mean age 6.8±3.6 years, range: 0.25-12.6 years) and 38 controls (mean age 6.3±2.8 years, range: 0.42-13 years). RESULTS: There were no significant differences in urine cathelicidin levels between the study and control groups (p>0.05). Eight (22.2%) patients in the study group and 21 (58.3%) children in the control group were found to have sufficient vitamin D (≥20 ng/mL). Patients with sufficient vitamin D had higher urine cathelicidin levels than the controls with sufficient vitamin D (respectively 262.5±41.1 vs. 168±31.6 ng/mL, p=0.001). There were no significant differences between the patients and controls with insufficient vitamin D (p>0.05). CONCLUSION: The children with vitamin D insufficiency may not be able to increase their urine cathelicidin level during UTI caused by Escherichia coli. There is a need of prospective studies in order to prove a beneficial effect of vitamin D supplementation for the restoration of cathelicidin stimulation and consequently for prevention of UTI recurrence.

The effect of the pre-pregnancy weight of the mother and the gestational weight gain on the bilirubin level of term newborn.

OBJECTIVE: Jaundice is a problem in newborns. There are many maternal and infant-related factors affecting neonatal jaundice. The maternal pre-pregnancy weight, maternal body mass index (BMI) and gestational weight gain may have an effect on the newborn bilirubin levels. We research the effect of the maternal pre-pregnancy weight and gestational weight gain on the bilirubin levels of the newborn infants in the first 2 weeks prospectively. METHODS: Term and healthy infants who were born between 38 and 42 weeks in our clinic were included in the study. Maternal pre-pregnancy BMIs were calculated. Babies were divided into three groups according to their mothers' advised amount of gestational weight gain. Total serum bilirubin (TSB) values of the newborns were measured in the 2nd, 5th and 15th postnatal days. RESULTS: In our study, the 5th and 15th day capillary bilirubin level of the babies with mothers who gained more weight than the advised amount during pregnancy were found statistically significant higher compared to the other two groups (p < 0.05). Similarly, the hematocrit level of the babies with mothers who gained more weight than the advised amount were found statistically significant higher compared to the other two groups (p < 0.05). CONCLUSIONS: We conclude that the babies with mothers who gained more weight than the advised amount were under risk for newborn jaundice. Therefore, these babies should be monitored more closely for neonatal jaundice and prolonged jaundice.

Effects of Inhaled Corticosteroids on the Growth Plates of Infant Rats.

The most significant adverse effect of inhaled steroid administration in children is suppression of hypothalamic-pituitary-adrenal axis responsiveness and suppression of growth. This study evaluates the effects of inhaled corticosteroids on the growth plates in infant rats. Rats aged 10 days were divided into five groups. Low and high doses of budesonide and fluticasone propionate (50-200-250 mcg/day) were applied with a modified spacer for 10 days. The rat's tibias were then removed and the effects of the steroids on the growth plates were compared. Growth cartilage chondrocyte proliferation and apoptosis rates; IGF-1 and glucocorticoid receptor levels; and resting, proliferative, hypertrophic, and total zone (TZ) measurements were compared using immunohistochemical-staining methods. With high doses of fluticasone, growth plates were affected much more than with high doses of budesonide (p = 0.01). Fluticasone, particularly at a dose of 250 mcg, inhibited the growth plate with an intensive negative impact on all parameters.

Cardiac troponin-I, brain natriuretic peptide and endothelin-1 levels in a rat model of doxorubicin-induced cardiac injury.

BACKGROUND: Cardiotoxicity, during or after therapy, is the most serious side effect of doxorubicin (DXR). The risk of developing cardiac impairment increases concomitantly with an increase in the cumulative dose of DXR. AIM: The aim was to evaluate the levels of cardiac troponin-I (cTnI), brain natriuretic peptide (BNP) and endothelin-1 (ET-1) in DXR induced cardiac injury. MATERIALS AND METHODS: Thirty-nine Wistar albino rats were divided into three groups; a control group and two-study groups that received low-dose DXR (LDD) and high-dose DXR (HDD) in a weekly schedule for reaching a cumulative dose. RESULTS: Serum cTnI level was significantly increased in both LDD and HDD-treated groups. Although serum BNP was not significantly increased either LDD or HDD-treated groups, ET-1 levels was significantly increased in only HDD-treated groups. Histopathologic injury was more evident in HDD-treated group. CONCLUSIONS: Serum cTnI was increased even in LDD and parallel to it low cardiac injury induced by DXR. In the low-dose group, BNP and ET-1 levels were not elevated significant as cTnI despite cardiac injury. Thus, cTnI may be a predictive marker in of DXR-induced cardiotoxicity.

High serum 25-hydroxyvitamin D levels are associated with pediatric sepsis.

Despite major advances in intensive care, sepsis continues to be a major cause of morbidity and mortality. Vitamin D is involved in various physiologic functions, including cellular responses during infection and inflammation. The aim of this study was to evaluate diagnostic value of 25-hydroxyvitamin D in childhood sepsis because it can be fatal if diagnosis delayed. The study included 40 children with sepsis and 20 children without sepsis (control group). We included only the patients with high probable sepsis, judged by clinical and laboratory findings, including positive blood culture. Blood samples were collected from patients with sepsis before treatment (pre-treatment group) and 48-72 hours later (post-treatment group). Treatment varied from ampicillin-sulbactam to cephalosporin. Blood samples were collected from control group once on admission. Serum 25-hydroxyvitamin D levels were significantly higher in sepsis (pre-treatment group) than control group (74 ± 8 ng/ml vs. 28 ± 12 ng/ml, p = 0.01) and the serum 25-hydroxyvitamin D levels were decreased to 44 ± 5 ng/ml (p = 0.01) after treatment. Moreover, we found significant positive correlation between 25-hydroxyvitamin D and each of well-know sepsis markers, C-reactive protein, tumor necrosis factor-α and interleukin-6. A cut-off point of 20 ng/mL for serum 25-hydroxyvitamin D showed 84% sensitivity and 76% specificity for sepsis diagnosis. This is the first study evaluating the diagnostic role of vitamin D in pediatric sepsis, thereby suggesting that serum 25-hydroxyvitamin D level can be used as a diagnostic marker for sepsis with high sensitivity and specificity.

The utility of serial plasma sE-selectin measurements in the prediction of retinopathy of prematurity in premature infants.

BACKGROUND: sE-selectin has recently been suggested as a surrogate marker for prediction of ROP development. AIMS: The possible role of serial plasma sE-selectin measurements in early prediction and diagnosis of ROP was evaluated. STUDY DESIGN: Prospective observational study SUBJECTS: Forty six preterm infants aged <34weeks of gestation and weighing <1500 g were enrolled. Of these, 26 constituted the ROP group and 20 constituted the no-ROP group. sE-selectin levels were measured serially in blood samples on the 1st day and on 14th and 28th postnatal days. OUTCOME MEASURES: The primary outcome measure was to evaluate the role of sE-selectin concentrations in prediction of ROP. RESULTS: The mean gestational age and birth weight were significantly lower in the ROP group. The mean sE-selectin concentrations in ROP group were significantly greater than those in no-ROP group at each time point (1st, 14th and 28th days of postnatal life). A receiver operating characteristic (ROC) analysis showed that at a plasma concentration of ≥86ng/mL on the 1st postnatal day, sE-selectin had a sensitivity of 100% and a specificity of 94.1% with a positive predictive value of 96.3% and a negative predictive value of 100%. Plasma sE-selectin concentrations were significantly greater in infants who developed ROP in three different time points. CONCLUSIONS: This study shows for the first time that measurement of plasma sE-selectin concentrations as early as the first day of life might help identify preterm infants at risk of ROP.

Predictive value of soluble urokinase plasminogen activator receptor, soluble ST2, and IL-33 in bronchopulmonary dysplasia.

BACKGROUND: Bronchopulmonary dysplasia (BPD) remains an important complication of preterm births. The soluble form of ST2 (sST2), interleukin-33 (IL-33), and soluble form of the urokinase plasminogen activator receptor (suPAR) have attracted increasing attention as biomarkers for different diseases. The aim of the current study was to assess the predictive value of plasma sST2, IL-33, and suPAR levels in patients with risk of BPD development. METHODS: A total of 38 babies were studied prospectively on delivery to the neonatal intensive care unit. Serum levels of IL-33, sST2, and suPAR were measured using enzyme-linked immunosorbent assay. Serum samples were collected from umbilical cord (at the time of delivery, termed CB) and peripheral blood (on day 14, termed PB). RESULTS: Levels of suPAR (PB-suPAR) and sST2 (PB-sST2) in the peripheral blood of the BPD group were significantly higher than the corresponding levels in the non-BPD group (P < 0.001, P = 0.028, respectively. There was a statistically significant correlation between PB-suPAR levels and the severity of BPD (P < 0.001)) when the suPAR results were analyzed using the receiver operating characteristic curve. CONCLUSION: PB-suPAR and PB-sST2 levels are sensitive and specific independent predictive biomarkers in preterm babies with BPD.

The relationship between the first episode of wheezing and matrix metalloproteinases-9 and MMP-2 and tissue inhibitors of MMP-1 levels in preterm infants.

AIMS: Matrix metalloproteinases (MMP) have been associated with neonatal lung morbidity and MMP dysregulation contributes to the pathology of chronic and acute lung disorders. Most of the previous studies were performed in the 1(st) weeks of life of the preterm newborns. There are no data on the serum levels of MMP-2, MMP-9 or tissue inhibitors of matrix metalloproteinases (TIMP-1) from preterm infants recovering from lung morbidities. We aimed to compare MMP-2, MMP-9 and TIMP-1 levels in preterm and term infants hospitalized with their first episode of wheezing. METHODS: We prospectively evaluated 18 preterm infants with a history of chronic lung disease, respiratory distress syndrome or oxygen therapy and 14 age- and sex-matched term infants who were admitted for a first episode of wheezing. We quantified total serum concentrations of MMP-2, MMP-9 and TIMP-1 to assess whether these serum markers levels were associated with the first episode of wheezing in infants with a history of oxygen therapy during the neonatal period. RESULTS: Upon hospitalization, MMP-2 and TIMP-1 levels were higher in preterm infants than in term infants. In contrast, there was no significant relationship between MMP-9 levels or the MMP-9/TIMP-1 ratio between preterm and term infants. The area under the receiver operating characteristic curve for MMP-2 was 0.70 (95% confidence interval [CI] 0.51-0.89). The area under the curve for TIMP-1 was 0.78 (95% CI 0.61-0.94). MMP-9, MMP-2 and TIMP-1 levels did not correlate with gestational age, gender or severity of wheezing. CONCLUSION: The negative proportion of MMP-9 to TIMP-1 that we detected in term infants was not present in preterm infants. The balance of MMP-9 to TIMP-1 may have been disrupted by lung damage in the premature infants. Overproduction of MMP-2 and TIMP-1 in the serum may be associated with the pathogenesis of wheezing in preterm infants.

Nanoduct sweat conductivity measurements in 2664 patients: relationship to age, arterial blood gas, serum electrolyte profiles and clinical diagnosis.

BACKGROUND: The Nanoduct(®) device has acceptable diagnostic accuracy, but there is not enough systematic data supporting its usage in the diagnosis of cystic fibrosis (CF). METHODS: A retrospective review of patients with an indication for the sweat test was conducted. The conductivity test was repeated in patients who had values higher than 60 mmol/L, and they were referred for sweat chloride measurements. Associations between sweat conductivity measurements and age, gender, (pH, HCO(3), pCO(2), Na, K, Cl), family history, consanguinity, indications for the test and number of hospitalization were studied. RESULTS: Among 2,664 patients, 16 children had sweat conductivity values higher than 80. The median age of patients diagnosed with CF was 4 months old. Age, pH, HCO(3), Na, Cl, K and the sweat conductivity test were statistically related (P < 0.001). The ROC curve showed very high agreement between the 2nd conductivity test and the sweat test. CONCLUSIONS: Patients suspected to have CF can be screened using the Nanoduct(®) conductivity device in non-qualified centers.

Toll-like receptor levels and caffeine responsiveness in rat pups during perinatal period.

Infants born prematurely are prone to bronchopulmonary dysplasia which is a devastating form of chronic lung disease that develops in very low birth weight infants. Toll-like receptors (TLRs) are pattern recognition receptors that initiate innate immune responses. We tested TLR2, 4, and 9 levels in the lungs of rat pups given caffeine at the first days of postnatal life. Twenty-four rat pups equally divided into three groups. The study group received caffeine immediately after birth for ten days. The levels of TLR9 were found significantly higher in study group than control groups. We conclude that the beneficial and anti-inflammatory effects of caffeine in the lungs of newborn rats may be due to increased TLR9 levels.

Effect of breastfeeding on serum zinc levels and growth in healthy infants.

BACKGROUND: This study investigated the association among breastfeeding, serum zinc levels, and nutritional status of children. SUBJECTS AND METHODS: One hundred healthy infants were included in the study. Anthropometric measurements of the children were taken, and their plasma zinc levels were determined. The mothers were interviewed about the duration of breastfeeding and nutrition pattern of the children at the time of zinc measurement. RESULTS: Low zinc levels were associated with lower weight measurements (r=0.49, p<0.001), but the association between height and zinc level was not statistically significant (r=0.18, p>0.05). There was a negative correlation between breastfeeding duration and weight-for-age percentile (r=-0.2, p<0.05), height-for-age percentile (r=-0.3, p<0.05), and serum zinc level (r=-0.3, p=0.002). The pattern of nutrition correlated only with the weight of the infant (r=0.2, p<0.05) and not with either height or serum zinc levels (p>0.05). CONCLUSIONS: Exclusive breastfeeding beyond 6 months of age has negative effects on serum zinc levels and can be associated with low weight gain, which will be especially important in developing countries.

Factor v deficiency associated with congenital cardiac disorder and intracranial hemorrage.

Factor V deficiency is an inherited disorder, in which the clotting factor V is low. The disorder is very rare, occurring in only one in one million people. It is inherited as an autosomal recessive disorder. The results of coagulation studies include a prolonged prothrombin time and partial thromboplastin time associated with reduced plasma factor V content. Patients with factor V deficiency have a hemophiliac like hemorrhagic disorder. Epistaxis, bruising, and menorrhagia are some of the common features. If treatment is needed, fresh frozen plasma is typically given. In this report we present a 12 year old girl who was admitted to our clinic with recurrent nosebleeds and intracranial hemorrage after head trauma. After examination, factor V deficiency was diagnosed. She also had congenital cardiac disorder (VSD), probably a co-incidental finding.

Correlation between cord blood apelin and IGF-1 levels in retinopathy of prematurity.

AIM: We hypothesized that circulating apelin concentrations in preterm babies might be linked with retinopathy of prematurity (ROP), similar to IGF-1 levels. PATIENTS & METHODS: A total of 97 infants born with a gestational age before 32 weeks in 2007-2009 were screened for ROP at the Gata Haydarpasa Hospital (Turkey). Fourteen of them with classified ROP stage 3-5 comprised our study group. RESULTS: The non-ROP group had higher apelin and IGF-1 levels than ROP neonates at birth. After 4-6 weeks, postnatal ROP subjects had lower apelin and IGF-1 levels than non-ROP controls. At the end of the study, the change in apelin levels was positively correlated with the change in IGF-1 levels (r = 0.852; p = 0.01). CONCLUSION: We suggested that the pathogenesis of ROP, which is regarded as a neovascular retinal disorder, includes variations in the levels of apelin and IGF-1.

Effects of maternal smoking on fetal organs.

BACKGROUND: Unfavorable effects of in-utero smoke exposure have been shown in several studies. OBJECTIVES: In this experimental study, the authors aimed at showing detrimental effects of cigarette smoke on fetal tissues by assessing apoptosis that is detected by performing TUNEL staining. MATERIAL AND METHODS: Designed groups were smoke exposed rats before and during pregnancy and control groups. Rat offsprings were sacrificed when they were 12 days old. RESULTS: Lung, kidney, adrenal and gonad tissues were harvested for histopathologic analysis and assessed by TUNEL (Terminal dUTP Nick End Labeling) staining. CONCLUSIONS: Smoke exposure caused increased apoptotic activity in lung parenchyma of study groups.