COVID-Vaccines in Pregnancy: Maternal and Neonatal Response over the First 9 Months after Delivery.

Vaccination against SARS-CoV-2 has been demonstrated to be safe during gestation. Nevertheless, there are no robust data investigating the entity of maternal antibodies' transmission through the placenta to the newborn and the persistence of the antibodies in babies' serum. The objective of this study is to assess the maternal antibody transmission and kinetics among newborns in the first months of life. Women having received one or two doses of anti-SARS-CoV-2 mRNA-vaccines during pregnancy at any gestational age, and their newborns, were recruited and followed-up over 9 months. Ninety-eight women and 103 babies were included. At birth, we observed a significant positive correlation between maternal and neonatal serum anti-SARS-CoV-2 antibody levels and a significant negative correlation between the time since last dose and antibody levels in mothers with two doses. Over the follow-up, the birth antibody level significantly decreased in time according to the received doses number at 3, 6, and 9 months. During the follow-up, we registered 34 dyad SARS-CoV-2 infection cases. The decreasing trend was slower in the SARS-CoV-2 infection group and among breastfed non-infected babies. Antibodies from maternal anti-SARS-CoV-2 vaccination are efficiently transferred via the placenta and potentially even through breast milk. Among newborns, antibodies show relevant durability in the first months of life.

CMV seroprevalence and coronary CMV-DNA detection in immunocompetent patients with heart diseases.

BACKGROUND: Acute coronary syndromes (ACS) are a major cause of morbidity and mortality. As cytomegalovirus (CMV) may contribute to cardio-vascular (CV) manifestations, we sought to provide a proof-of-concept for the involvement of coronary and/or systemic CMV-reactivation as a possible ACS trigger. METHODS: We prospectively enrolled consecutive patients undergoing a coronary angiography for ACS (acute-cases, N.=136), or non-ACS reasons (chronic-cases, N.=57). Matched coronary and peripheral blood-samples were processed for quantification of CMV-DNAemia (RT-PCR), CMV-IgG/IgM, and CMV-IgG avidity (ELISA). Peripheral-blood samples from 17 healthy subjects were included as controls. RESULTS: Out of the 193 cases included, 18.1% were aged ≤55 years, 92.5% were Central-European, and 100% immunocompetent. CMV-IgG seroprevalence was 91.7% (95%CI: 87.8-95.6), significantly higher than in healthy-controls (52.9% [95%CI: 29.2-76.5]; P<0.001), yet consistent across age-groups (P=0.602), male/females (P=0.765), and acute/chronic-cases (P=0.157). Median (IQR) IgG titers were 110 (84-163) AU/mL, with 0.62 (0.52-0.72) avidity, supporting a long history of infection. No acute CMV infections were found. In 22.6% (n/N.=40/177) of the IgG-positive cases low-level coronary and/or systemic CMV-DNAemia (always <40 copies/mL) was detected. While no differences in peripheral CMV-DNAemia prevalence were observed nor among cases nor controls, coronary CMV-DNAemia was more frequent in acute-cases without modifiable CV risk-factors (n/N.=4/10; 40.0%), than in chronic-cases (n/N.=6/55, 10.9%; P=0.029), or acute-cases with risk-factors (n/N.=16/112, 14.3%; P=0.058). CONCLUSIONS: CMV-IgG seroprevalence was high in patients with heart diseases. CMV-DNAemia can be found, although uncommonly, in coronary circulation during an ACS, with increased prevalence in older subjects and in absence of CV risk-factors, identifying possible areas for novel interventions.

The impact of valproic acid treatment on weight gain in pediatric patients with epilepsy.

BACKGROUND: Valproic acid (VPA) is an antiepileptic drug, used for focal and generalized seizure. VPA treatment resulted in significant weight gain but there are no systematic data about the prevalence of this side effect. The aim of the study was to evaluate the weight gain of a pediatric population with epilepsy. METHODS: We enrolled 38 patients, 17 females and 21 males with a mean age of 8.2±4.4 years. We evaluated data about height, weight and BMI at beginning of treatment and at 24, 36 and 48 months of follow-up. RESULTS: There is a statistically significant difference between the percentile value of weight and BMI at baseline and at 36 and 48 months of follow-up (P<0.01) but there is not statistically significant difference between the percentile value of height (P=0.22 and P=0.18). CONCLUSIONS: We believe that a nutritional support should be guaranteed to the pediatric patients with epilepsy that begin the VPA therapy.

Results of the RENAISSANCE Study: REsponse to BNT162b2 COVID-19 vacciNe-short- And long-term Immune reSponSe evAluatioN in health Care workErs.

OBJECTIVE: To evaluate the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) anti-spike (S) IgG antibody production after vaccination with BNT162b2 and the protection from symptomatic breakthrough infections in health care workers. METHODS: This prospective observational study (RENAISSANCE) had as a primary end point the evaluation of serologic response to BNT162b2 14 days after a second dose. SARS-CoV-2 anti-S IgG antibodies were evaluated with LIAISON SARS-CoV-2 TrimericS IgG assay (DiaSorin S.p.A.), which is able to detect the presence of both binding and neutralizing antibodies for trimeric spike glycoprotein. Participants were recruited from February 1, 2021, to February 22, 2021. Occurrence of vaccine breakthrough infections was assessed by reverse transcription-polymerase chain reaction on symptomatic and contact cases up to June 6, 2021. RESULTS: Of 2569 staff evaluated, only 4 were nonresponders (0.16%; 95% CI, 0.04% to 0.41%). All 4 nonresponders were severely immunosuppressed and receiving treatment with mycophenolate mofetil or mycophenolic acid. At 14 days after the second dose, 67.5% (1733) of staff had anti-S IgG titers of 2000 BAU/mL or higher; 19.2% (494), between 1500 and 2000 BAU/mL; 9.8% (251), between 1000 and 1500 BAU/mL; and 3.4% (87), 1000 BAU/mL or lower. Women had a higher probability of having higher titers than men (64.5% [1044/1618] vs 58.3% [410/703]; P=.005). This was confirmed after adjustment for age group (odds ratio, 1.275; 95% CI, 1.062 to 1.531; P=.009). Four months after the end of the vaccination program, only 13 participants (0.26%) had experienced a breakthrough SARS-CoV-2 infection, including 1 nonresponder. This was the only participant requiring hospitalization for severe COVID-19. CONCLUSION: The vaccination campaign among health care workers at the ASST GOM Niguarda has resulted in a marked serologic response and reduction of incident COVID-19 cases. Yet, the lack of protection should not be overlooked in immunocompromised individuals.

Sex differences in electrolyte imbalances caused by SARS-CoV-2: A cross-sectional study.

BACKGROUND: Since SARS-CoV-2 spread, evidence regarding sex differences in progression and prognosis of COVID-19 have emerged. Besides this, studies on patients' clinical characteristics have described electrolyte imbalances as one of the recurrent features of COVID-19. METHODS: We performed a cross-sectional study on all patients admitted to the emergency department (ED) from 1 March to 31 May 2020 who had undergone a blood gas analysis and a nasopharyngeal swab test for SARS-CoV-2 by rtPCR. We defined positive patients as cases (n = 710) and negatives as controls (n = 619), for a total number of patients of 1.329. The study was approved by the local ethics committee Area 3 Milan. Data were automatically extracted from the hospital laboratory SQL-based repository in anonymised form. We considered as outcomes potassium (K+ ), sodium (Na+ ), chlorine (Cl- ) and calcium (Ca++ ) as continuous and as categorical variables, in their relation with age, sex and SARS-CoV-2 infection status. RESULTS: We observed a higher prevalence of hypokalaemia among patients positive for SARS-CoV-2 (13.7% vs 6% of negative subjects). Positive patients had a higher probability to be admitted to the ED with hypokalaemia (OR 2.75, 95% CI 1.8-4.1, P < .0001) and women were twice as likely to be affected than men (OR 2.43, 95% CI 1.67-3.54, P < .001). Odds ratios for positive patients to manifest with an alteration in serum Na+ was (OR 1.6, 95% CI 1.17-2.35, P < .001) and serum chlorine (OR 1.6, 95% CI 1.03-2.69, P < .001). Notably, OR for positive patients to be hypocalcaemic was 7.2 (95% CI 4.8-10.6, P < .0001) with a low probability for women to be hypocalcaemic (OR 0.63, 95% CI 0.4-0.8, P = .005). CONCLUSIONS: SARS-CoV-2 infection is associated with a higher prevalence of hypokalaemia, hypocalcaemia, hypochloraemia and sodium alterations. Hypokalaemia is more frequent among women and hypocalcaemia among men.

Frontline Screening for SARS-CoV-2 Infection at Emergency Department Admission by Third Generation Rapid Antigen Test: Can We Spare RT-qPCR?

To complement RT-qPCR testing for diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, many countries have introduced the use of rapid antigen tests. As they generally display lower real-life performances than expected, their correct positioning as frontline screening is still controversial. Despite the lack of data from daily clinical use, third generation microfluidic assays (such as the LumiraDx SARS-CoV-2 Ag test) have recently been suggested to have similar performances to RT-qPCR and have been proposed as alternative diagnostic tools. By analyzing 960 nasopharyngeal swabs from 960 subjects at the emergency department admissions of a tertiary COVID-19 hospital, LumiraDx assay demonstrated a specificity of 97% (95% CI: 96-98), and a sensitivity of 85% (95% CI: 82-89) in comparison with RT-qPCR, which increases to 91% (95% CI: 86-95) for samples with a cycle threshold ≤ 29. Fifty false-negative LumiraDx-results were confirmed by direct quantification of genomic SARS-CoV-2 RNA through droplet-digital PCR (median (IQR) load = 5880 (1657-41,440) copies/mL). Subgenomic N and E RNAs were detected in 52% (n = 26) and 56% (n = 28) of them, respectively, supporting the presence of active viral replication. Overall, the LumiraDx test complies with the minimum performance requirements of the WHO. Yet, the risk of a misrecognition of patients with active COVID-19 persists, and the need for confirmatory RT-qPCR should not be amended.

Length-weight growth analysis up to 12 months of age in three groups according to the dietary pattern followed from pregnant mothers and children during the first year of life.

BACKGROUND: The aim of the present study is to analyse the length-weight growth up to 12 months of age in three groups considering the respective dietary pattern followed from the pregnant mothers and from the infants during the first year of the life. Moreover, the cultural inference of vegetarianism has been studied. METHODS: Between September 2017 and May 2018, more than 100 mothers have been proposed to participate in this study. As a result of preliminary evaluation, which ensures the presence of inclusion criteria and the absence of exclusion criteria, 55 mothers and their 63 children have been enrolled and assessed with a questionnaire previously created for the study. RESULTS: A statistically significant difference has emerged between the omnivorous and the vegan group from the comparison for the weight of children at birth, 6 months and 12 months, both when expressed in grams and when expressed in growth percentiles. Furthermore, between the two children groups just mentioned, a significant difference has emerged from the comparison for the length expressed in growth percentiles at 12 months and for the body mass index at 6 months. No statistically significant differences have emerged between the omnivorous group and the lacto-ovo/lactovegetarian group and between the latter and the vegan one. CONCLUSIONS: Although differences between the three groups of children have emerged with regard to some anthropometric parameters, their length-weight growth during the first year of life has been harmonic and physiological regardless of the type of planned diet.

Effectiveness of infection-containment measures on SARS-CoV-2 seroprevalence and circulation from May to July 2020, in Milan, Italy.

OBJECTIVE: Through a hospital-based SARS-CoV-2 molecular and serological screening, we evaluated the effectiveness of two months of lockdown and two of surveillance, in Milan, Lombardy, the first to be overwhelmed by COVID-19 pandemics during March-April 2020. METHODS: All subjects presenting at the major hospital of Milan from May-11 to July-5, 2020, underwent a serological screening by chemiluminescent assays. Those admitted were further tested by RT-PCR. RESULTS: The cumulative anti-N IgG seroprevalence in the 2753 subjects analyzed was of 5.1% (95%CI = 4.3%-6.0%), with a peak of 8.4% (6.1%-11.4%) 60-63 days since the peak of diagnoses (March-20). 31/106 (29.2%) anti-N reactive subjects had anti-S1/S2 titers >80 AU/mL. Being tested from May-18 to June-5, or residing in the provinces with higher SARS-CoV-2 circulation, were positively and independently associated with anti-N IgG reactivity (OR [95%CI]: 2.179[1.455-3.264] and 3.127[1.18-8.29], respectively). In the 18 RT-PCR positive, symptomatic subjects, anti-N seroprevalence was 33.3% (95% CI: 14.8%-56.3%). CONCLUSION: SARS-CoV-2 seroprevalence in Milan is low, and in a downward trend after only 60-63 days since the peak of diagnoses. Italian confinement measures were effective, but the risk of contagion remains concrete. In hospital-settings, the performance of molecular and serological screenings upon admission remains highly advisable.

Detection and quantification of SARS-CoV-2 by droplet digital PCR in real-time PCR negative nasopharyngeal swabs from suspected COVID-19 patients.

Since SARS-CoV-2-based disease (COVID-19) spreads as a pandemic, the necessity of a highly sensitive molecular diagnosis that can drastically reduce false negatives reverse transcription PCR (rtPCR) results, raises as a major clinical need. Here we evaluated the performance of a ddPCR-based assay to quantify SARS-CoV-2 titer in 55 suspected COVID-19 cases with negative rtPCR results thanks to in-house ddPCR assay (targeting RdRp and host RNaseP). Samples were collected at ASST-GOM Niguarda between February and May 2020 at hospital admission. Clinical and imaging data were obtained for clinical staging and definition of disease severity. Patients were mainly female (45.5%) with a median age of 73 (57-84) years. ddPCR-based assay detected SARS-CoV-2 genome in nasopharyngeal samples of 19 (34.5%) patients (median viral-load: 128 copies/mL, IQR: 72-345). In 15 of them (78.9%), chest CT showed a classical COVID-19 bilateral interstitial pneumonia; 14 patients (73.7%) showed severe COVID-19 manifestations. ddPCR did not identify any trace of SARS-CoV-2 genome in the respiratory samples of the remaining 36 patients. The serological assay performed in a subgroup of 34 patients at the later stage of illness (from 3 days to 90 days after) confirmed the presence of SARS-CoV-2 antibodies in all patients tested positive for SARS-CoV-2 in ddPCR (100%). Contrariwise, negative tests were observed in 95.0% ddPCR negative patients (P<0.001). Thanks to a ddPCR-based assay, we achieved a rapid and accurate SARS-CoV-2 diagnosis in rtPCR-negative respiratory samples of individuals with COVID-19 suspect, allowing the rapid taking care and correct management of these patients.

The impact of lacto-ovo-/lacto-vegetarian and vegan diets during pregnancy on the birth anthropometric parameters of the newborn.

Introduction: The data in the literature on the appropriateness of vegetarian diets during pregnancy and the impact on the birth anthropometric parameters of the newborn are divergent and conflicting. The aim of the present study is to compare the birth anthropometric parameters of three groups of children distinguished according to the dietary pattern followed by their mothers during pregnancy. Moreover, the second aim is to study the cultural inference of vegetarianism.Materials and methods: Between September 2017 and May 2018, from the Pediatric Service of the Campus Bio-Medico University Hospital of Rome and vegetarian-oriented societies, detailed information have been provided to all mothers who showed interest in participating in the study. More than 100 mothers gave their consent, but in consideration of the criteria of inclusion and exclusion only 55 with the respective children (for a total of 63 kids) have been enlisted in the study. Based on the dietary pattern followed by women during pregnancy, the participants have been divided into three groups: vegan group, lacto-ovo-/lacto-vegetarian group, and omnivorous group. The data necessary for the study have been collected through a questionnaire previously created and sent electronically to 55 enrolled mothers.Results: From our statistical analysis, it has emerged that birth weight, both when expressed in grams and when expressed in growth percentiles, of the vegan mothers' children is lower than that of the omnivorous mothers' children. No significant difference has emerged from the comparison for the length, cranial circumference and BMI at birth between the three groups.Conclusion: Although from our study statistically significant differences in birth weight between the vegan group and the omnivorous one has emerged, the values of this anthropometric parameter were all included within the physiological range decided by the experts in the field. From this, it emerges that the planning of any type of diet with experts in the field is indispensable to ensure a physiological development of the fetus, but given the limited number of participants we cannot draw unequivocal and certain conclusions on this subject.

Innocent heart murmurs and enuresis: Examining a possible link.

OBJECTIVE: The aim of this study was to evaluate the prevalence of innocent heart murmurs in children affected by nocturnal enuresis (NE). RESULTS: The prevalence of innocent heart murmurs in G2 was 6.34%. This condition was significantly more frequent in children who suffered from NE. Indeed, in G1, the prevalence of innocent heart murmurs was 21.45%, although there were few differences between the children with monosymptomatic NE and non-monosymptomatic NE; moreover, this prevalence was higher in males. MATERIAL AND METHODS: We enrolled a total of 401 children (G1), 300 males and 101 females, aged 5-15 years, affected by NE and referred to the Service of Pediatrics, "Campus Bio-Medico" University Hospital of Rome, from September 2013 to September 2018, into the study. The control group was composed of 394 children without NE (G2). The study was carried out in compliance with the Helsinki Declaration. CONCLUSION: These findings made us aware of the presence of possible underlying mechanisms, which explain the association between a higher prevalence of innocent heart murmurs and enuresis, and further studies are required to explore this issue.