Inflammatory and Immune Responses during SARS-CoV-2 Infection in Vaccinated and Non-Vaccinated Pregnant Women and Their Newborns.

BACKGROUND: Pregnant women are more susceptible to severe disease associated with SARS-CoV-2 infection. We performed a prospective study to analyze the inflammatory and immune profile after SARS-CoV-2 infection occurring in vaccinated or non-vaccinated pregnant women and their newborns. METHODS: Twenty-five pregnant women with SARS-CoV-2 infection were enrolled, and sixteen cord blood samples were obtained at delivery. RESULTS: We observed that IL-1ß, TNF-α, Eotaxin, MIB-1ß, VEGF, IL-15, IL-2, IL-5, IL-9, IL-10 and IL-1ra levels were significantly higher in vaccinated than non-vaccinated mothers. Furthermore, the newborns of the vaccinated mothers produced higher levels of IL-7, IL-5 and IL-12 compared to the newborns of non-vaccinated mothers. Anti-Spike (S) IgG levels were significantly higher in all vaccinated mothers and their newborns compared to the non-vaccinated group. We found that 87.5% of vaccinated women and 66.6% of non-vaccinated women mounted an S-specific T-cell response quantified by ELISpot assay. Moreover, 75.0% of vaccinated mothers and 38.4% of non-vaccinated mothers showed S-specific CD4+ T-cell proliferative response. The T-helper subset response was restricted to CD4+ Th1 in both vaccinated and non-vaccinated women. CONCLUSION: A higher level of cytokines, IgG antibodies and memory T cells was noted in the vaccinated women. Furthermore, the maternal IgG antibody trans-placental transfer occurred more frequently in vaccinated mothers and may protect the newborn.

Maternal pandemic-related stress during pregnancy associates with infants' socio-cognitive development at 12 months: A longitudinal multi-centric study.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Prenatal maternal stress during the COVID-19 pandemic and infant regulatory capacity at 3 months: A longitudinal study.

The COVID-19 pandemic is a global traumatic experience for citizens, especially during sensitive time windows of heightened plasticity such as pregnancy and neonatal life. Pandemic-related stress experienced by mothers during pregnancy may act as an early risk factor for infants' regulatory capacity development by altering maternal psychosocial well-being (e.g., increased anxiety, reduced social support) and caregiving environment (e.g., greater parenting stress, impaired mother-infant bonding). The aim of the present longitudinal study was to assess the consequences of pandemic-related prenatal stress on infants' regulatory capacity. A sample of 163 mother-infant dyads was enrolled at eight maternity units in northern Italy. They provided complete data about prenatal stress, perceived social support, postnatal anxiety symptoms, parenting stress, mother-infant bonding, and infants' regulatory capacity at 3 months of age. Women who experienced emotional stress and received partial social support during pregnancy reported higher anxious symptoms. Moreover, maternal postnatal anxiety was indirectly linked to the infants' regulatory capacity at 3 months, mediated by parenting stress and mother-infant bonding. Dedicated preventive interventions should be delivered to mothers and should be focused on protecting the mother-infant dyad from the detrimental effects of pandemic-related stress during the COVID-19 healthcare emergency.

Impact of SARS-CoV-2 infection during pregnancy and persistence of antibody response.

BACKGROUND: Pregnant women may be at an increased risk of developing severe or critical disease associated with the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection causing severities during pregnancy. We performed a prospective study to describe the impact of SARS-CoV-2 infection on pregnancy outcomes and on the newborn, depending on the severity of the disease. The antibody response and persistence of SARS-CoV-2 anti-Spike (S) IgG, IgA and anti-Nu- cleocapsid (NCP) IgG, was investigated. METHODS: A total of 48 pregnant women with SARS-CoV-2 infection were enrolled, and sequential serum samples from 30 of them were collected until one year after infection. Outcomes of pregnan- cy and newborn parameters were evaluated in comparison with 200 uninfected controls. RESULTS: Asymptomatic infection was observed in 31/48 women (64.5%), mild COVID-19 in 12/48 women (25.0%), while 5/48 women (10.5%) developed pneumonia. Women with pneumonia mount- ed significantly higher levels of anti-S IgG, IgA and anti-NCP IgG between 1 and 3 months after onset of infection compared to asymptomatic women. Anti-S IgG persisted in the majority of women from 6 months to at least one year after infection, especially in those with symptomatic infection and pneumonia, while anti-S IgA and anti-NCP IgG declined earlier. Pregnancy complications and new- born parameters were not significantly different from those observed in uninfected controls. CONCLUSION: Anti-SARS-CoV-2 antibody development and persistence was not impaired in pregnant women, while SARS-CoV-2 infection did not cause major pregnancy or newborn complications in asymptomatic or symptomatic women, nor in women with pneumonia receiving prompt clinical care.

Depression and Anxiety in Mothers Who Were Pregnant During the COVID-19 Outbreak in Northern Italy: The Role of Pandemic-Related Emotional Stress and Perceived Social Support.

The COVID-19 pandemic is a collective trauma that is threatening citizens' mental health resulting in increased emotional stress, reduced social support, and heightened risk for affective symptoms. The present study aimed to investigate the effects of antenatal pandemic-related emotional stress and perceived social support on the symptoms of depression and anxiety of mothers who were pregnant during the initial COVID-19 outbreak in northern Italy. A sample of 281 mothers was enrolled at eight maternity units in the first hotspot region of the COVID-19 outbreak in northern Italy. Participants filled out online questionnaires assessing the direct or indirect exposure to the SARS-CoV-2 virus, pandemic-related stress, perceived social support, as well as symptoms of depression and anxiety. Depressive and anxious symptomatology was above clinical concern, respectively, in 26 and 32% of the respondents. Mothers who reported no exposure to SARS-CoV-2 during pregnancy and those who reported at least one direct or indirect exposure did not differ in terms of affective symptoms. Continuous scores and risk for severe depression and anxiety were positively associated with prenatal pandemic-related emotional stress and negatively linked with perceived social support during pregnancy. Women who become mothers during the COVID-19 emergency may be at high risk for affective problems. Dedicated preventive programs are needed to provide adequate preventive support and care for maternal mental health during and after the COVID-19 pandemic.

Analysis of SARS-CoV-2 vertical transmission during pregnancy.

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.

SARS-CoV-2 infection testing at delivery: a clinical and epidemiological priority.

BACKGROUND: Universal testing has been suggested as a useful strategy for a safe exit from the total lockdown, without recurrence of COVID-19 epidemic, delivering women being considered a sentinel population. Further universal testing for pregnant women may be useful in order to define appropriate access to COVID19 areas, dedicated neonatal care, and personal protective equipment. METHODS: During the period 10-26 April, all consecutive women admitted for delivery at the Maternity Hospitals of the city of Milan and in six provinces of Lombardy: Brescia, Como, Lecco Monza, Pavia, and Sondrio. areas were tested with nasopharyngeal swabs.Results and conclusion: Out of 1566 women, 49 were tested positive for SARS-Cov-2 (3.1%, 95% Confidence Interval (CI) 2.3-4.0). This value is largely higher than Heath Authorities estimate. Of tested positive women, 22 (44.9%) had symptoms or reported close contacts with positive patients, that is were found at risk by the itemized questionnaire. In conclusion, routine estimate of frequency of positivity among delivering women can be consider a useful methods to monitor positivity at least in females in their fertile ages.

COVID-19 Obstetrics Task Force, Lombardy, Italy: Executive management summary and short report of outcome.

From February 24, 2020, a COVID-19 obstetric task force was structured to deliver management recommendations for obstetric care. From March 1, 2020, six COVID-19 hubs and their spokes were designated. An interim analysis of cases occurring in or transferred to these hubs was performed on March 20, 2020 and recommendations were released on March 24, 2020. The vision of this strict organization was to centralize patients in high-risk maternity centers in order to concentrate human resources and personal protective equipment (PPE), dedicate protected areas of these major hospitals, and centralize clinical multidisciplinary experience with this disease. All maternity hospitals were informed to provide a protected labor and delivery room for nontransferable patients in advanced labor. A pre-triage based on temperature and 14 other items was developed in order to screen suspected patients in all hospitals to be tested with nasopharyngeal swabs. Obstetric outpatient facilities were instructed to maintain scheduled pregnancy screening as per Italian guidelines, and to provide pre-triage screening and surgical masks for personnel and patients for pre-triage-negative patients. Forty-two cases were recorded in the first 20 days of hub and spoke organization. The clinical presentation was interstitial pneumonia in 20 women. Of these, seven required respiratory support and eventually recovered. Two premature labors occurred.