Use of Sotrovimab in a cohort of pregnant women with a high risk of COVID 19 progression: a single-center experience.

Neutralizing monoclonal antibodies (mAbs) have been shown to reduce disease progression in patients with underlying predisposing conditions. Unfortunately, there is no evidence on the use of Sotrovimab in pregnant women. Herein we present a case series of pregnant women who received mAbs with Sotrovimab following the Italian Drug Agency (AIFA) indications. Since February 1, 2022 all pregnant women - regardless of gestational age - admitted to Obstetrics & Gynaecology of Policlinico University of Bari, with positive nasopharyngeal NAAT for SARS-CoV-2 were screened according to the AIFA indications for Sotrovimab and, if eligible, were proposed for treatment. Data on COVID-19, pregnancy, delivery, newborn outcomes, and adverse events were collected. From February 1 to May 15, 2022, 58 pregnant women were screened. Fifty (86%) patients were eligible, 19 of them (32.7%) denied their consent, in 18 cases (31%), the drug was temporarily unavailable, and the remaining 13 (22%) were treated with Sotrovimab. Out of these 13 patients, 6 (46%) were in the 3rd and 7 (54%) in the 2nd trimester of pregnancy. None of the 13 patients experienced adverse reactions due to Sotrovimab and all had a good clinical outcome. Furthermore, evaluating pre- and post-infusion clinical status and hematochemical profile, a reduction in D-dimers and an increase in SARS-CoV-2 antibodies (p < 0.01) during the 72 h following the infusion were observed. Our data, the first on the use of Sotrovimab in pregnant women, showed the safety and efficacy drug profile and its potential crucial role in preventing COVID-19 disease progression.

"GONE WITH THE WIND": The Transitory Effects of COVID-19 on the Gynecological System.

The coronavirus disease no longer seems to represent an insurmountable global problem. This is thanks to the advent of coronavirus vaccines, which have alleviated the most serious symptoms associated with this disease. On the other hand, there are still many extrapulmonary symptoms of COVID-19, and among these also those of a gynecological nature. At the moment, there are several questions in this field, one above all concerns the causal link between COVID-19, vaccines and gynecological alterations. Furthermore, another important aspect is represented by the clinical impact of post-COVID-19 gynecological alterations on the female population which, to date, would seem to be mainly due to their duration, even if the extent of these symptoms is still poorly understood. Furthermore, it is not possible to foresee eventual long-term aggravations, or more serious symptoms caused by other viral variants that may arrive in the future. In this review, we focus on this theme and attempt to reorganize the different pieces of a puzzle which, to date, does not seem to have shown us its complete picture.

Adverse Maternal Outcomes in Pregnant Women Affected by Severe-Critical COVID-19 Illness: Correlation with Vaccination Status in the Time of Different Viral Strains' Dominancy.

This is a monocentric and cross-sectional study conducted at the COVID-19 Division of the Obstetrical and Gynecological Unit and Intensive Care Units (ICUs) of Policlinico di Bari, in Bari, Italy, between September 2020 and April 2022. This study aimed to identify the prevalence of severe-critical COVID-19 illness requiring access to the Intensive Care Unit (ICU) among 287 pregnant patients, and possible correlations between the SARS-CoV-2 variants, the specific pandemic wave (dominated by wild, Alpha, Delta, and Omicron strains), and severe-critical adverse maternal outcomes. The prevalence of severe-critical COVID-19 illness was 2.8% (8/287), reaching 4.9% (8/163) excluding the 4th wave (Omicron dominant). The Delta variant determined the highest risk ratio and odds for access to the ICU due to severe-critical COVID-19-related symptoms compared to the other variants (wild, Alpha, Omicron). During the third wave (Delta), the ICU cases underwent a higher rate of hyperimmune plasma infusion (75%), antibiotic therapy (75%), and remdesivir (33%); all of the patients were intubated. During the Omicron wave, the patients were asymptomatic or with few symptoms: most of them (70%) were vaccinated with a median of two doses. The maternal outcome worsened in the case of Alpha and, especially, Delta variants for severe-critical COVID-19-related symptoms and ICU access.

SARS-CoV-2 Vaccines and Adverse Effects in Gynecology and Obstetrics: The First Italian Retrospective Study.

The most common effects reported by the Italian Medicine Agency following administration of SARS-CoV-2 vaccine are myalgia, soreness to the arm of inoculation, fever, and asthenia. To date, there are no specific and official reports registered by the Italian Medicine Agency on possible alterations of the menstrual cycle, or of the female reproductive system, following the vaccine. Actually, clinical experience showed a spread of transient adverse drug reactions of the menstrual cycle, following the administration of all COVID-19 vaccine types, both mRNA and Adenovirus vectored ones. In this work, we conducted the first retrospective study on Italian patients vaccinated for SARS-CoV-2 in the period between April 2021 and April 2022, to report the onset of menstrual changes after the vaccine in order to understand: etiology, duration of possible adverse effects, and the extent of the phenomenon. We recruited 100 women aged 18-45, vaccinated for SARS-CoV-2, who were asked to complete a questionnaire consisting of 12 multiple choice questions about the effects of the vaccine on the reproductive system. Thirty-seven of them received three doses of the vaccine, while the remaining 63 received two doses. Symptoms such as delayed menstruation and abnormal uterine bleeding (metrorrhagia, menometrorrhagia, and menorrhagia) were generally reported within the first three weeks of vaccination, especially after the second dose, with a percentage of 23% and 77%, respectively. These preliminary data suggest that this problem may be broader and deserving of further investigation in the future.

Obstetric outcomes in pregnant COVID-19 women: the imbalance of von Willebrand factor and ADAMTS13 axis.

BACKGROUND: Thrombotic microangiopathy has been invoked as one of the most important mechanisms of damage in COVID-19 patients. Protease ADAMTS13 is a marker of microangiopathy responsible for controlling von Willebrand multimers size. Von Willebrand factor/ADAMTS13 ratio has been found impaired in COVID-19 patients outside pregnancy. METHODS: We prospectively investigated 90 pregnant women admitted to two tertiary academic hospitals in Italy with a laboratory-confirmed diagnosis of SARS-CoV-2 infection. Demographic, clinical information and routine laboratory data were collected at the hospital admission and until discharge. We investigated whether vonWillebrand /ADAMTS13 axis imbalance is a predictor of adverse outcomes. Logistic regression analysis, which controlled for potential confounders, was performed to evaluate the association between laboratory parameters and clinical outcomes. RESULTS: Most women (55.6%) were parae, with median gestational age at admission of 39 weeks. At hospital admission, 63.3% were asymptomatic for COVID-19 and 24.4% showed more than one sign or symptom of infection. Nulliparae with group O showed Willebrand / ADA MTS-13 ratios significantly lower than non-O, whereas in multiparae this difference was not observed. Logistic regression showed that ratio von Willebrand to ADAMTS13 was significantly and independently associated with preterm delivery (OR 1.9, 95%CI 1.1-3.5). CONCLUSION: This study shows an imbalance of vonWillebrand /ADAMTS13 axis in pregnant women with COVID-19, leading to a significantly higher and independent risk of preterm delivery. Monitoring these biomarkers might support decision making process to manage and follow-up pregnancies in this setting.

COVID-19 Infection in Pregnancy: Obstetrical Risk Factors and Neonatal Outcomes-A Monocentric, Single-Cohort Study.

The effects of coronavirus disease 2019 caused by severe acute respiratory syndrome coronavirus 2 on pregnant women and neonates are mainly unknown, since limited data are available in the literature. We conducted a monocentric and cross-sectional study enrolling 122 un-vaccinated pregnant women with COVID-19 infection tested by RT-PCR nasopharyngeal swab. Only 4.1% of the patients had severe COVID-19 symptoms together with major respiratory symptoms and intensive care unit admission, whereas 35.25% of women had comorbidities and two-thirds of them were overweight or obese. COVID-19 was detected mainly in the third trimester (98.36%) and multiparous women (59.02%). The mode of delivery was influenced by mild-severe COVID-19 symptoms, with a higher number of urgent or emergent cesarean sections than spontaneous or operative vaginal births. Preterm births were associated with high BMI, mode of delivery (higher among cesarean sections), nulliparity, and severe COVID-19 symptoms. In cases of severe COVID-19 symptoms, there was a higher rate of respiratory distress syndrome among newborns. In the end, only the presence of a severe COVID-19 infection worsened the obstetrical and neonatal outcomes, with higher rates of urgent or emergent cesarean section, preterm births, and neonatal respiratory distress syndrome.

Updates on Children with Allergic Rhinitis and Asthma during the COVID-19 Outbreak.

BACKGROUND: During the lockdown period caused by the SARS-CoV-2 pandemic, we monitored via online survey the trend of allergic symptoms and the therapeutic compliance in patients followed at our center. MATERIAL AND METHODS: In June 2020, we selected children followed at the Allergy and Immunology Service of Umberto I Hospital, aged between 6 and 16 years old, diagnosed with asthma and/or rhinitis and sensitized to grass pollen or dust mite. We sent an email with 12 multiple-choice questions investigating several areas: type of disease and sensitization, recurrence of symptoms, medication use during lockdown compared to the same period of the previous year. RESULTS: The results of 82 questionnaires showed that 17.8% of patients suffered from asthma, 24.4% from rhinitis, and 57.8% from both. Within the group of asthmatic children, most of them presented an improvement of their symptoms. Likewise, with regard to allergic rhinitis, most of them reported better clinical conditions. Regarding treatment, we observed a global decrease in the use of on-demand therapies (salbutamol, nasal corticosteroid, and antihistamine) for both pathologies. In addition, there was a reduction in the use of basal therapy for asthma and rhinitis from 2019 (23.3%) to 2020 (15.5%). CONCLUSIONS: Our data show a general trend of clinical improvement and a reduction in the use of on-demand and basal therapy in allergic children during the lockdown.

SARS-CoV-2 and Placenta: New Insights and Perspectives.

The study of SARS-CoV-2 positive pregnant women is of some importance for gynecologists, obstetricians, neonatologists and women themselves. In recent months, new works have tried to clarify what happens at the fetal-placental level in women positive for the virus, and different pathogenesis mechanisms have been proposed. Here, we present the results of a large series of placentas of Coronavirus disease (COVID) positive women, in a reference center for COVID-positive pregnancies, on which we conducted histological, immunohistochemical and electron microscopy investigations. A case-control study was conducted in order to highlight any histopathological alterations attributable to SARS-CoV-2. The prevalence of maternal vascular malperfusion was not significantly different between cases and controls (54.3% vs. 43.7% p = 0.19), whereas the differences with regard to fetal vascular malperfusion (21.1% vs. 4.2% p < 0.001) were significant. More frequent in cases with respect to controls were decidual arteriopathy (40.9% vs. 1.4% p < 0.0001), decidual inflammation (32.4% vs. 0.7% p < 0.0001), perivillous fibrin deposition (36.6% vs. 3.5% p < 0.0001) and fetal vessel thrombi (22.5% vs. 0.7% p < 0.0001). No significant differences in the percentage of terminal villous hyperplasia and chorioamnionitis were observed between the two groups. As the pandemic continues, these studies will become more urgent in order to clarify the possible mechanism of maternal-fetal transmission of the virus.