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"Spinillo Arsenio"
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Analysis of SARS-CoV-2 vertical transmission during pregnancy
2020
The impact of SARS-CoV-2 infection during gestation remains unclear. Here, we analyse the viral genome on maternal and newborns nasopharyngeal swabs, vaginal swabs, maternal and umbilical cord plasma, placenta and umbilical cord biopsies, amniotic fluids and milk from 31 mothers with SARS-CoV-2 infection. In addition, we also test specific anti-SARS-CoV-2 antibodies and expression of genes involved in inflammatory responses in placentas, and in maternal and umbilical cord plasma. We detect SARS-CoV-2 genome in one umbilical cord blood and in two at-term placentas, in one vaginal mucosa and in one milk specimen. Furthermore, we report the presence of specific anti-SARS-CoV-2 IgM and IgG antibodies in one umbilical cord blood and in one milk specimen. Finally, in the three documented cases of vertical transmission, SARS-CoV-2 infection was accompanied by a strong inflammatory response. Together, these data support the hypothesis that in utero SARS-CoV-2 vertical transmission, while low, is possible. These results might help defining proper obstetric management of COVID-19 pregnant women, or putative indications for mode and timing of delivery.
The impact of SARS-CoV-2 infection in pregnancy remains underexplored. Here, the authors provide a comprehensive characterization of virus and immunological parameters in 31 SARS-CoV-2-infected pregnant women, finding evidence of vertical transmission in two of the mother-child pairs.
Journal Article
The role of multiple high‐risk human papillomavirus infection on the persistence recurrence of high‐grade cervical lesions after standard treatment: A systematic review and a meta‐analysis
by
Pasquali, Marianna Francesca
,
Dominoni, Mattia
,
Spinillo, Arsenio
in
Bias
,
Conization - methods
,
Female
2024
Introduction The role of multiple high‐risk human papillomavirus (HR‐HPV) infections on the occurrence of persistence/recurrence of high‐grade squamous intraepithelial lesion (HSIL) after conization/surgery for cervical intraepithelial neoplasia was evaluated. Material and methods A systematic search of Pubmed/Medine, Scopus, Cochrane databases from inception to June 30, 2023 was performed. Three reviewers independently screened the s of the selected studies and extracted data from full‐text articles. The data were subsequently tabulated and compared for consistency. The bias associated with each included study was evaluated according to the OSQE method. PROSPERO registration number CRD42023433022. Results Out of 1606 records screened, 22 full text articles met the inclusion criteria. A total of 8321 subjects treated (loop electrosurgical excision, laser or surgery) because of HSIL were followed‐up and included in the meta‐analysis. The pooled prevalence of overall persistence and/or recurrence was 17.6 (95% CI: 12.3–23.5) in multiple and 14.3 (95% CI: 10.1–19.2) in single HR‐HPV infections detected shortly before or at surgery. The pooled rate of multiple HR‐HPV infections was 25% (95% CI: 20.4–30). The odds ratio of histologically confirmed HSIL persistence and/or recurrence was significantly higher (OR: 1.38, 95% CI:1.08–1.75, p = 0.01, heterogeneity = 39%) among multiple than single HR‐HPV infections. Increased risk of HSIL persistence/recurrence was more marked among studies with multiple HR‐HPVs prevalence ≥25% (12 studies, N = 3476) (OR: 1.47, 95% CI: 1.18–1.84, heterogeneity = 0%) and in those evaluating true histologically confirmed recurrence after at least 6 months of negative follow‐up (9 studies, N = 5073) (OR: 1.67, 95% CI: 1.17–2.37, heterogeneity = 37%). Multiple HR‐HPVs infection detected during follow‐up visits had no effect on the risk of recurrence although the number of included studies was small (4 studies, N = 1248) (OR: 0.98, 95% CI: 0.68–1.39, heterogeneity = 0%). The risk of bias was rated as high in 10 and low‐moderate in 12 studies, respectively. In subgroup analysis, the risk of bias of the included studies (low/moderate vs. high), had a small, although not significant effect on the odds ratios of persistence/recurrence of HSIL (OR: 1.57, 95% CI: 1.23–2 for low‐moderate risk of bias and OR: 1.06, 95% CI: 0.65–1.75 for high risk of bias; p‐value for subgroup differences = 0.17). Conclusions Multiple HR‐HPVs infections at the time of standard treatment of HSIL entail a small but significant increased risk of persistence/recurrence of HSIL and should be taken into account in the follow‐up plan. Multiple HR‐HPVs infection among women treated for HSIL is common, involving 25% of the subjects, and is associated with a small but significantly increased risk of persistence/recurrence of high‐grade cervical lesions. In the future multiple HR‐HPV infections should be considered into the follow‐up strategy of women treated for HSIL.
Journal Article
A Randomized Trial of Hyperimmune Globulin to Prevent Congenital Cytomegalovirus
2014
Congenital infection with cytomegalovirus is a major cause of morbidity in neonates. In this phase 2, placebo-controlled trial, hyperimmune globulin given to mothers with primary CMV infection at 5 to 26 weeks of gestation did not significantly alter the course of infection.
Every year, approximately 0.6% of all newborns in the United States and the European Union are congenitally infected with human cytomegalovirus (CMV).
1
,
2
Approximately 20% of these infected newborns are symptomatic at birth or will have sequelae such as sensorineural hearing loss, cognitive defects, and motor defects.
3
Primary CMV infection that develops in a woman during pregnancy confers the highest risk of congenital infection and disease.
4
Identification of pregnant women with primary CMV infection is feasible by means of detection of virus-specific IgM and low IgG avidity. However, the unavailability of a therapeutic intervention of proven efficacy in the case . . .
Journal Article
Neurodevelopmental outcome of preterm very low birth weight infants admitted to an Italian tertiary center over an 11-year period
by
La Piana, Roberta
,
Caporali, Camilla
,
Orcesi, Simona
in
692/308/3187
,
692/700/1720/3185
,
692/700/1720/3186
2021
Preterm very low birth weight infants (VLBWi) are known to be at greater risk of adverse neurodevelopmental outcome. Identifying early factors associated with outcome is essential in order to refer patients for early intervention. Few studies have investigated neurodevelopmental outcome in Italian VLBWi. The aim of our longitudinal study is to describe neurodevelopmental outcome at 24 months of corrected age in an eleven-year cohort of 502 Italian preterm VLBWi and to identify associations with outcome. At 24 months, Griffiths’ Mental Developmental Scales were administered. Neurodevelopmental outcome was classified as: normal, minor sequelae (minor neurological signs, General Quotient between 76 and 87), major sequelae (cerebral palsy; General Quotient ≤ 75; severe sensory impairment). 75.3% showed a normal outcome, 13.9% minor sequelae and 10.8% major sequelae (3.8% cerebral palsy). Male gender, bronchopulmonary dysplasia, abnormal neonatal neurological assessment and severe brain ultrasound abnormalities were independently associated with poor outcome on multivariate ordered logistic regression. Rates of major sequelae are in line with international studies, as is the prevalence of developmental delay over cerebral palsy. Analysis of perinatal complications and the combination of close cUS monitoring and neurological assessment are still essential for early identification of infants with adverse outcome.
Journal Article
Maternal pandemic-related stress during pregnancy associates with infants’ socio-cognitive development at 12 months: A longitudinal multi-centric study
by
Capelli, Elena
,
Roberti, Elisa
,
Grumi, Serena
in
Auditory stimuli
,
Babies
,
Biology and Life Sciences
2023
Prenatal maternal stress is a key risk factor for infants' development. Previous research has highlighted consequences for infants' socio-emotional and cognitive outcomes, but less is known for what regards socio-cognitive development. In this study, we report on the effects of maternal prenatal stress related to the COVID-19 pandemic on 12-month-old infants' behavioral markers of socio-cognitive development.
Ninety infants and their mothers provided complete longitudinal data from birth to 12 months. At birth, mothers reported on pandemic-related stress during pregnancy. At infants' 12-month-age, a remote mother-infant interaction was videotaped: after an initial 2-min face-to-face episode, the experimenter remotely played a series of four auditory stimuli (2 human and 2 non-human sounds). The auditory stimuli sequence was counterbalanced among participants and each sound was repeated three times every 10 seconds (Exposure, 30 seconds) while mothers were instructed not to interact with their infants and to display a neutral still-face expression. Infants' orienting, communication, and pointing toward the auditory source was coded micro-analytically and a socio-cognitive score (SCS) was obtained by means of a principal component analysis.
Infants equally oriented to human and non-human auditory stimuli. All infants oriented toward the sound during the Exposure episode, 80% exhibited any communication directed to the auditory source, and 48% showed at least one pointing toward the sound. Mothers who reported greater prenatal pandemic-related stress had infants with higher probability of showing no communication, t = 2.14 (p = .035), or pointing, t = 1.93 (p = .057). A significant and negative linear association was found between maternal prenatal pandemic-related stress and infants' SCS at 12 months, R2 = .07 (p = .010), while adjusting for potential confounders.
This study suggests that prenatal maternal stress during the COVID-19 pandemic might have increased the risk of an altered socio-cognitive development in infants as assessed through an observational paradigm at 12 months. Special preventive attention should be devoted to infants born during the pandemic.
Journal Article
Respiratory Syncytial Virus in Pregnancy: An Obstetrics View
by
Dominoni, Mattia
,
Spinillo, Arsenio
,
Gardella, Barbara
in
Babies
,
Congenital diseases
,
Disease
2024
Respiratory syncytial virus (RSV) represents one of the most prevalent causes of lower respiratory tract infection in newborns and children by the time they are two years old, with a peak rate of hospitalization in those between two and three months of age and a high risk of morbidity and mortality, especially under the age of six months of life [...]
Journal Article
Conditioned Medium From Human Amniotic Mesenchymal Stromal Cells Limits Infarct Size and Enhances Angiogenesis
by
Ciuffreda, Maria Chiara
,
Malpasso, Giuseppe
,
Pisano, Federica
in
Amniotic Fluid - cytology
,
Amniotic Fluid - metabolism
,
Amniotic membrane
2015
The paracrine properties of human amniotic membrane‐derived mesenchymal stromal cells (hAMCs) have not been fully elucidated. The goal of the present study was to elucidate whether hAMCs can exert beneficial paracrine effects on infarcted rat hearts, in particular through cardioprotection and angiogenesis. Moreover, we aimed to identify the putative active paracrine mediators. hAMCs were isolated, expanded, and characterized. In vitro, conditioned medium from hAMC (hAMC‐CM) exhibited cytoprotective and proangiogenic properties. In vivo, injection of hAMC‐CM into infarcted rat hearts limited the infarct size, reduced cardiomyocyte apoptosis and ventricular remodeling, and strongly promoted capillary formation at the infarct border zone. Gene array analysis led to the identification of 32 genes encoding for the secreted factors overexpressed by hAMCs. Among these, midkine and secreted protein acidic and rich in cysteine were also upregulated at the protein level. Furthermore, high amounts of several proangiogenic factors were detected in hAMC‐CM by cytokine array. Our results strongly support the concept that the administration of hAMC‐CM favors the repair process after acute myocardial infarction. The goal of this study was to elucidate whether human amniotic membrane‐derived mesenchymal stromal cells (hAMCs) can exert beneficial paracrine effects on infarcted rat hearts. In particular, the administration of hAMC‐conditioned medium repaired ischemic damage through cardioprotection and angiogenesis. Finally, several putative active paracrine mediators that might account for the effects observed were identified by gene and protein arrays.
Journal Article
Phenotype and specificity of T cells in primary human cytomegalovirus infection during pregnancy: IL-7Rpos long-term memory phenotype is associated with protection from vertical transmission
by
Jarrossay, David
,
Lanzavecchia, Antonio
,
Gerna, Giuseppe
in
Antigens
,
Biology and Life Sciences
,
Birth defects
2017
Congenital human cytomegalovirus (HCMV) infection is the major cause of birth defects and a precise definition of the HCMV-specific T-cell response in primary infection may help define reliable correlates of immune protection during pregnancy. In this study, a high throughput method was used to define the frequency of CD4+ and CD8+ T cells specific for four HCMV proteins in the naïve compartment of seronegative subjects and the effector/memory compartments of subjects with primary/remote HCMV infection. The naïve repertoire displayed comparable frequencies of T cells that were reactive with HCMV structural (pp65, gB and the pentamer gHgLpUL128L) and non-structural (IE-1) proteins. Whereas, following natural infection, the majority of effector/memory CD4+ and CD8+ T cells recognized either gB or IE-1, respectively, and pp65. The pattern of T cell reactivity was comparable at early and late stages of infection and in pregnant women with primary HCMV infection transmitting or not transmitting the virus to the fetus. At an early stage of primary infection, about 50% of HCMV-reactive CD4+ T cells were long-term IL-7Rpos memory cells, while 6-12 months later, the frequency of these cells increased to 70%, approaching 100% in remote infections. In contrast, only 10-20% of HCMV-specific CD8+ T cells were long-term memory cells up to 12 months after infection onset, thereafter increasing to 70% in remote infections. Interestingly, a significantly higher frequency of HCMV-specific CD4+ T cells with a long-term IL-7Rpos memory phenotype was observed in non-transmitting compared to transmitting women. These findings indicate that immunodominance in HCMV infection is not predetermined in the naïve compartment, but is the result of virus-host interactions and suggest that prompt control of HCMV infection in pregnancy is associated with the rapid development of long-term IL-7Rpos memory HCMV-specific CD4+ T cells and a low risk of virus transmission to the fetus.
Journal Article
Multiple human papillomavirus infection and high-grade cervical squamous intraepithelial lesions among women with human immunodeficiency virus: a systematic review and a meta-analysis
by
Pasquali, Marianna Francesca
,
Dominoni, Mattia
,
Spinillo, Arsenio
in
Cellular biology
,
Cervical cancer
,
Cohort analysis
2024
This study aimed to evaluate the prevalence of multiple high-risk (HR) human papillomavirus (HPV) infections in women with human immunodeficiency virus (HIV) compared to negative controls. This study also aimed to assess the impact of multiple HR-HPVs on the risk of high-grade squamous cervical lesions (HSILs) among women with HIV.
We performed a systematic search of PubMed/Medline, Scopus, Cochrane databases, and ClinicalTrials.gov from 1 January 2004 to 30 June 2023, including screenings and clinical studies evaluating the rates and role of multiple HPV infections in squamous intraepithelial lesions (SILs). Three reviewers independently screened the abstracts of the selected studies and extracted data from full-text articles. The data were subsequently tabulated and compared for consistency. The bias associated with each included study was evaluated according to the OSQE method.
Forty-seven studies meet definitive inclusion criteria. The quality of the observations was considered low in 26 of the included studies and moderate in 21 of the included studies. In comparative screening studies, the pooled prevalence of multiple HR-HPV was 39.1% (95% CI = 33.7-44.7) among women with (
= 1734) and 21.6% (95% CI = 17.3-26.1) in those without HIV infection (
= 912) (OR = 2.33, 95% CI = 1.83-2.97,
= 2.8%). The pooled ORs of HR-HPV multiple infections were similar in African (OR = 2.72, 95% CI = 1.89-3.9) and non-African countries (OR = 2.1, 95% CI = 1.46-3,
for difference = 0.96). Among women with HIV, the risk of HSIL diagnosed either by cytology or histology was higher among those with overall (OR = 2.62, 95% CI = 1.62-4.23) and HR multiple infections than those with single HPV infection (OR = 1.93, 95% CI = 1.51-2.46). Among women with HIV, the excess rates of multiple HPV infections and the excess risk of associated HSIL were consistent across studies including both HIV-naïve subjects and those on antiretroviral therapy, as well as in studies with different rates of immunocompromised women. When study quality (low vs. moderate) was used as a moderator, the results were unchanged.
Multiple HR-HPV infections are common among women living with HIV and are associated with an increased prevalence of HSIL. These associations were also confirmed in studies with high rates of antiretroviral therapy and low rates of immunocompromise.
: PROSPERO [registration number: CRD42023433022].
Journal Article
Minimal prevalence of HPV vaccination and common occurrence of high-risk HPV types in pregnant women with HIV: data from a national study in Italy
by
Dalzero Serena
,
Guaraldi Giovanni
,
Floridia Marco
in
Abnormalities
,
Cytology
,
Human immunodeficiency virus
2022
Among 733 pregnant women with HIV followed between 2013 and 2021, only 8 (1.1%) had prior HPV vaccination. One had low-grade squamous intraepithelial lesions [LSIL], and none had HPV type information. Among the 725 non-vaccinated women, 578 (79.7%) had information on cervical cytology. Rate of cytologic abnormalities in this group was 20.6% (0.2% atypical glandular cells of undetermined significance [AGC], 1.7% atypical squamous cells of undetermined significance [ASC-US], 11.1% LSIL, and 7.6% high-grade squamous intraepithelial lesions [HSIL]). Among 56 women with HPV type information, 75.0% carried high risk types, with similar occurrence in women with and without cytologic abnormalities, 30.4% had multiple high-risk types, and 75.9% carried at least one of the types included in the currently recommended 9-valent vaccine.
Journal Article