COVID-19 therapeutics for the pregnant patient.

SARS-CoV-2 infection can cause severe disease among pregnant persons. Pregnant persons were not included in initial studies of therapeutics for COVID-19, but cumulative experience demonstrates that most are safe for pregnant persons and the fetus, and effective for prevention or treatment of severe COVID-19.

Perinatal COVID-19: Implications for care of the newborn.

The maternal/newborn dyad presents special challenges to infection management. Early in the COVID-19 pandemic, lack of information regarding SARS-CoV-2 transmission and virulence made it difficult to develop appropriate care guidance when pregnant persons had COVID-19 at the time of presentation for childbirth. We will review the considerations for the parturient, newborn, and care team, and describe the evolution of perinatal COVID management guidance.

Neonatal and infant infection with SARS-CoV-2.

Despite the substantial body of investigative work describing the Coronavirus Disease 2019 (COVID-19) pandemic, its impact on neonates and infants remains less well characterized. Here, we review the data on epidemiology of COVID-19 in this population. Widespread use of universal testing for SARS-CoV-2 among pregnant persons presenting for delivery complicates interpretation of the risks of perinatal exposure. While many neonates and infants with COVID-19 are well-appearing or have only mild signs of illness, factors such as preterm birth, low birth weight, and medical comorbidities increase the risk of severe infection. We highlight potential protective maternal factors, summarize treatment options and discuss vaccine development. Higher quality data are needed to better inform our understanding of COVID-19 in neonates and infants.

Neonatal-perinatal collaboration during the COVID-19 pandemic.

The COVID-19 pandemic required perinatal clinicians to address the individual medical needs of the pregnant person and the fetus as well as the interdependent considerations of the maternal/newborn dyad. Regional, national and international collaborative groups utilized existing structures and in some cases, formed new partnerships to rapidly collect perinatal information. The urgent need to care for at-risk and infected pregnant persons required these groups to develop practical approaches to collect the data needed to safely inform practice. Here we will summarize the findings of five collaborative studies that leveraged differing methods to inform perinatal pandemic care.

Impact of SARS-CoV-2 infection during pregnancy on the placenta and fetus.

Pregnant people and their fetuses are vulnerable to adverse health outcomes from coronavirus 2019 disease (COVID-19) due to infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 has been associated with higher rates of maternal mortality, preterm birth, and stillbirth. While SARS-CoV-2 infection of the placenta and vertical transmission is rare, this may be due to the typically longer time interval between maternal infection and testing of the placenta and neonate. Placental injury is evident in cases of SARS-CoV-2-associated stillbirth with massive perivillous fibrin deposition, chronic histiocytic intervillositis, and trophoblast necrosis. Maternal COVID-19 can also polarize fetal immunity, which may have long-term effects on neurodevelopment. Although the COVID-19 pandemic continues to evolve, the impact of emerging SARS-CoV-2 variants on placental and perinatal injury/mortality remains concerning for maternal and perinatal health. Here, we highlight the impact of COVID-19 on the placenta and fetus and remaining knowledge gaps.

Prevention of mother-to-child transmission of HIV service interruptions amid COVID-19 pandemic.

BACKGROUND:  The coronavirus disease 2019 (COVID-19) caused global disruptions in healthcare service delivery. The prevention of mother-to-child transmission (PMTCT) of human immunodeficiency viruses (HIV) services were also interrupted, threatening the attainment of Sustainable Development Goal 3. This article describes the PMTCT service interruptions experienced during the COVID-19 pandemic in Tshwane healthcare facilities. METHODS:  A descriptive phenomenological design was used to explore and describe the experiences of healthcare providers offering PMTCT services during COVID-19 in the Tshwane district, Gauteng province. Purposive sampling was used to recruit participants. Data were collected through in-depth interviews with 16 participants, and Colaizzi's data analysis steps were followed in analysing the findings. RESULTS:  Participants reported interruptions in PMTCT service delivery during the pandemic. Non-adherence to scheduled visits resulted in patients defaulting or not adhering to treatment regimens, high viral loads and mother-infant pairs' loss to follow-up. Other features of service disruption included late antenatal bookings, low client flow and delays in conducting deoxyribonucleic acid-polymerase chain reaction (DNA-PCR) testing in HIV-exposed babies. In addition, staff shortages occurred because of re-assignments to COVID-19-related activities. Study participants were psychologically affected by the fear of contracting COVID-19 and worked in a frustrating and stressful environment. CONCLUSION:  Improved community-based follow-up services are critical to enhance PMTCT service outcomes and prevent infant HIV infections.Contribution: The findings may influence policymakers in developing strategies to curb HIV infections among mothers and children during pandemics.

Effect of Early pregnancy associated protein-1 on Spike protein and ACE2 interactions: Implications in SARS Cov-2 vertical transmission.

INTRODUCTION: Several factors influence transmission of 2019-nCoV from mother to fetus during pregnancy, thus the dynamics of vertical transmission is unclear. The role of cellular protective factors, namely a 90 KDa glycoprotein, Early pregnancy-associated protein (Epap-1), expressed by placental endothelial cells in women during early pregnancy would provide an insight into role of placental factors in virus transmission. Since viral spike protein binding to the ACE2 receptors of the host cells promotes virus invasion in placental tissue, an analysis of effects of Epap-1 on the Spike-ACE2 protein binding was studied. METHODS: Epap-1 was isolated from MTP placental tissue. Molecular interaction of Epap-1 and variants of the spike was analyzed in silco. The interaction of Epap-1 with Spike and RBD were analyzed using ELISA and immunofluorescence studies. RESULTS: The results in silico showed an interaction of Epap-1 with S-protein at RBD region involving K417, Y449, Y453, Y456, Y473, Q474, F486, Q498, N501 residues of spike with Y61, F287, I302, N303, N305, S334, N465, G467, N468 residues of Epap-1 leading to interference of S-protein and ACE2 interaction [1]. Further, the interaction is conserved among the variants. The studies in vitro confirm that Epap-1 affects S protein-ACE2 and RBD- ACE2 binding, thus suggesting that during early pregnancy, SARS CoV-2 infection may be protected by Epap-1 protein present in placental tissue. The results were further confirmed by pseudovirus expressing Spike and RBD in an infection assay. DISCUSSION: Epap-1 interferes with Spike and RBD interaction with ACE2, suggesting a possible mechanism of the antiviral environment during pregnancy.

Newborns at risk of COVID-19, the story continues.

After more than 4 years of the SARS-CoV-2 pandemic, a great deal of knowledge on how this virus affects pregnant women, the fetus and the newborn has accumulated. Guidelines for mode of delivery, cord clamping, skin to skin, breastfeeding, and rooming-in have become uniform across the world. Vaccination has considerably improved outcomes, but hesitancy amongst pregnant patients and the emergence of variants remain challenged and SARS-CoV-2 positivity during pregnancy continues to be associated with an increased risk of maternal complications, premature delivery and higher neonatal mortality and morbidity. An emerging body of data now exists on the effect of SARS-CoV-2 in pregnancy on early neonatal outcomes, medical education in obstetrics and pediatrics, and longer-term developmental outcomes. In this article, we review the development in this field since our last review.

Vertical transmission of SARS-CoV-2 delta-variant in a preterm infant.

BACKGROUND: As SARS-CoV-2 continues to be relevant and cause illnesses, the effect of emerging virus variants on perinatal health remains to be elucidated. It was demonstrated that vertical transmission of SARS-CoV-2 is a relatively rare event in the original SARS-CoV-2 strain. However, very few reports describe vertical transmission related to the delta-variant. CASE PRESENTATION: We report a case of a preterm male neonate born to a mother with positive SARS-CoV-2 and mild respiratory complications. The neonate was born by cesarean section due to fetal distress. The rupture of the amniotic membrane was at delivery. The neonate had expected prematurity-related complications. His nasopharyngeal swabs for RT-PCR were positive from birth till three weeks of age. RT-ddPCR of the Placenta showed a high load of the SARS-CoV-2 virus with subgenomic viral RNA. RNAscope technique demonstrated both the positive strand of the S gene and the orf1ab negative strand. Detection of subgenomic RNA and the orf1ab negative strand indicats active viral replication in the placenta. CONCLUSIONS: Our report demonstrates active viral replication of the SARS-CoV-2 delta-variant in the placenta associated with vertical transmission in a preterm infant.

The COVID-19 Pandemic Period, SARS-CoV-2 Infection, and Perinatal Health.

This cohort study assesses population-level associations of COVID-19 with birth parent and infant health, distinguishing the COVID-19 pandemic period from individual SARS-CoV-2 infection.

Covid-19 infection in pregnant women: Auditory evaluation in infants.

 Recent studies showed that COVID-19 infection can affect cochleo-vestibular system. The possibility of a vertical transmission is controversial. Some studies suggested that it is possible but unlikely, others find no evidence of vertical transmission. The objective of this study was to investigate whether exposure to COVID-19 during pregnancy or at birth has an impact on the hearing of the offspring. As part of the national hearing screening program, we performed in all newborns between January 2022 and February 2023, TEOAEs (Transient Evoked Otoacoustic Emissions) at birth and at 3 months. For those "REFER" at the third month test, we performed aABR (Automatic Auditory Brainstem Response) at 6 months. We analysed separately result between infants born to COVID-positive mothers during pregnancy and those born to COVID-negative mothers. To statistical verify differences we performed "Chi-square test". We enrolled a total of 157 infants, of whom 16 were born to mothers who had a molecular PCR test positive for COVID-19. In the latter we tested a total of 32 ears and only 1 ear (3,1%) resulted "REFER". On the other hand, in the control group we tested a total of 282 ears and 22 (7,8%) were found to be "REFER". Our study showed no significant differences in audiological assessment between newborns exposed to COVID-19 infection during pregnancy or at birth compared to the unexposed group. However, further studies with a larger patient's sample will be necessary for a more comprehensive evaluation.

Seroprevalence and placental transfer of SARS-CoV-2 antibodies in unvaccinated pregnant women.

PURPOSE: Pregnant women are at risk of severe SARS-CoV-2 infection, potentially leading to obstetric and neonatal complications. Placental transfer of antibodies directed to SARS-CoV-2 may be protective against neonatal COVID-19, but this remains to be studied. We aimed to determine the seroprevalence of SARS-CoV-2 antibodies in a population of unvaccinated pregnant women and to determine the placental transfer of these antibodies. METHODOLOGY: A total of 1197 unvaccinated women with mostly unknown pre-study SARS-CoV-2 infection status, were tested at delivery for SARS-CoV-2 spike protein IgG antibodies during the first year of the pandemic. Umbilical cord samples were collected and assessed for seropositivity if the mother was seropositive. Maternal characteristics, pregnancy and neonatal outcomes and data on SARS-CoV-2 infection were extracted from medical records. RESULTS: Specific IgG were detected in 258 women (21.6%). A significant placental transfer to the newborn was observed in 81.3% of cases. The earlier in the 2nd and 3rd trimesters that the mother had contracted the disease and the more symptomatic she was, the greater the likelihood of transplacental transfer of IgG to her newborn. CONCLUSION: Approximately one in five women had detectable anti-SARS-CoV-2 spike protein IgG antibodies at delivery during the first year of the pandemic, and these antibodies were significantly transferred to their fetuses. This research provides further evidence to better understand the dynamics of the placental transfer of SARS-CoV-2 IgG antibodies from mothers to their newborns, which is necessary to improve vaccination strategies.

Challenges of breastfeeding during COVID-19 and baby friendly protocols adopted at a maternity health center in the northern Emirates of UAE: a comprehensive review.

BACKGROUND: The outbreak of Coronavirus disease (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS CoV-2) has caused worldwide panic in the global population taking people's lives, creating fear, and affecting mother-child relationships. Many questions were raised on the dangers of being infected with COVID-19 for newborns and safety concerns during feeding by COVID-19-positive mothers. Moreover, questions and doubts about the safety of the administration of vaccinations for nursing mothers are still open. This review attempts to fill the existing literature gap by exploring concepts concerning COVID-19 and breastfeeding mothers, the safety of vaccinations, the beneficial effects of breastfeeding on both mother and child, important hygiene recommendations for SARS-CoV-2 infected mothers, and possible solutions to optimize breastfeeding and safety precautions amidst the fear of emergence of novel variants. METHODS: All relevant publications from Google Scholar, PubMed, Web of Science, and Scopus search engines from December 2019 to October 2022 related to SARS-CoV-2, breastfeeding, COVID-19, lactating guidelines, and vaccination were included using 'Breastfeeding AND vaccine AND SARS-CoV-2' as MESH TERMS. Apart from the literature review, existing maternity protocols followed in Northern UAE were gathered from lactation consultants practicing in the UAE. RESULTS: Out of 19,391 records generated, only 24 studies were analyzed and summarized in this exhaustive review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow chart. Previous studies suggest that breastmilk is predominantly the primary source of nutrition for neonates. Breast milk is a rich source of antibodies that help the baby to fight against infections including other benefits. Hygiene recommendations for suspected or confirmed COVID-19-infected mothers are required along with psychological and emotional support. CONCLUSIONS: The administration of vaccinations should be advised and encouraged to protect the mothers with antibodies and the neonates by the passive transmission of antibodies through breast milk. This is a significant reason for not stopping breastfeeding even in case of COVID-19 infection. With adherence to proper hygiene methods, breastfeeding is recommended to be continued as the benefits greatly outweigh the risks.

SARS-CoV-2 Infection Among Newborn Infants: A Scoping Review.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection of mothers may increase the risk of complications and adverse birth outcomes among newborn infants born more than 37 weeks' gestation. PURPOSE: The aim of this scoping review is to identify the research gaps in the literature on SARS-CoV-2 positive newborn infants born at more than 37 weeks' gestation in United States (U.S.). DATA SOURCES: A search for relevant articles was conducted using multiple resources including three databases CINAHL, Ovid MEDLINE, and Web of Science. This scoping review included case reports, case series, cohort, and retrospective studies focusing on newborn infants born more than 37 weeks of gestation with SARS-CoV-2 infection. STUDY SELECTION: A total of 4262 citations were screened, and 12 articles met the eligibility criteria. DATA EXTRACTION: Two authors independently screened the articles using a multi-step approach. RESULTS: This review identified the gaps in literature on newborn infants up to one month of age. Few studies have focused on SARS-CoV-2 positive newborn infants born more than 37 gestational weeks. This review demonstrates a higher prevalence of community-acquired SARS-CoV-2 infections among infants following discharge. IMPLICATIONS OF PRACTICE AND RESEARCH: Few U.S. based studies have focused on newborn infants born more than 37 weeks' gestation with SARS-CoV-2 infection. Future follow-up studies are essential on these infants especially during the first 30 days of life. Discharge teaching on SARS-CoV-2 infection is vital in reducing community transmission, admissions, and emergency department visits.

HIV prevalence among children admitted with severe acute malnutrition and associated factors with mother-to-child HIV transmission at Mulago Hospital, Uganda: A mixed methods study.

BACKGROUND: Despite global efforts to eliminate mother-to-child-transmission of HIV (MTCT), many children continue to become infected. We determined the prevalence of HIV among children with severe acute malnutrition (SAM) and that of their mothers, at admission to Mwanamugimu Nutrition Unit, Mulago Hospital, Uganda. We also assessed child factors associated with HIV-infection, and explored factors leading to HIV-infection among a subset of the mother-child dyads that tested positive. METHODOLOGY: We conducted a cross-sectional evaluation within the REDMOTHIV (Reduce mortality in HIV) clinical trial that investigated strategies to reduce mortality among HIV-infected and HIV-exposed children admitted with SAM at the Nutrition Unit. From June 2021 to December 2022, we consecutively tested children aged 1 month to 5 years with SAM for HIV, and the mothers who were available, using rapid antibody testing upon admission to the unit. HIV-antibody positive children under 18 months of age had a confirmatory HIV-DNA PCR test done. In-depth interviews (IDIs) were conducted with mothers of HIV positive dyads, to explore the individual, relationship, social and structural factors associated with MTCT, until data saturation. Quantitative data was analyzed using descriptive statistics and logistic regression in STATAv14, while a content thematic approach was used to analyze qualitative data. RESULTS: Of 797 children tested, 463(58.1%) were male and 630(79.1%) were ≤18months of age; 76 (9.5%) tested positive. Of 709 mothers, median (IQR) age 26 (22, 30) years, 188(26.5%) were HIV positive. Sixty six of the 188 mother-infant pairs with HIV exposure tested positive for HIV, an MTCT rate of 35.1% (66/188). Child age >18 months was marginally associated with HIV-infection (crude OR = 1.87,95% CI: 1.11-3.12, p-value = 0.02; adjusted OR = 1.72, 95% CI: 0.96, 3.09, p-value = 0.068). The IDIs from 16 mothers revealed associated factors with HIV transmission at multiple levels. Individual level factors: inadequate information regarding prevention of MTCT(PMTCT), limited perception of HIV risk, and fear of antiretroviral drugs (ARVs). Relationship level factors: lack of family support and unfaithfulness (infidelity) among sexual partners. Health facility level factors: negative attitude of health workers and missed opportunities for HIV testing. Community level factors: poverty and health service disruptions due to the COVID-19 pandemic. CONCLUSION: In this era of universal antiretroviral therapy for PMTCT, a 10% HIV prevalence among severely malnourished children is substantially high. To eliminate vertical HIV transmission, more efforts are needed to address challenges mothers living with HIV face intrinsically and within their families, communities and at health facilities.

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Objective: To construct a deep learning-based target detection method to help radiologists perform rapid diagnosis of lesions in the CT images of patients with novel coronavirus pneumonia (NCP) by restoring detailed information and mining local information. Methods: We present a deep learning approach that integrates detail upsampling and attention guidance. A linear upsampling algorithm based on bicubic interpolation algorithm was adopted to improve the restoration of detailed information within feature maps during the upsampling phase. Additionally, a visual attention mechanism based on vertical and horizontal spatial dimensions embedded in the feature extraction module to enhance the capability of the object detection algorithm to represent key information related to NCP lesions. Results: Experimental results on the NCP dataset showed that the detection method based on the detail upsampling algorithm improved the recall rate by 1.07% compared with the baseline model, with the AP50 reaching 85.14%. After embedding the attention mechanism in the feature extraction module, 86.13% AP50, 73.92% recall, and 90.37% accuracy were achieved, which were better than those of the popular object detection models. Conclusion: The feature information mining of CT images based on deep learning can further improve the lesion detection ability. The proposed approach helps radiologists rapidly identify NCP lesions on CT images and provides an important clinical basis for early intervention and high-intensity monitoring of NCP patients.

Retrospective Cohort Study on the Impact of the COVID-19 Pandemic on Pregnancy Outcomes for Women Living With HIV in British Columbia.

BACKGROUND: For pregnant women living with HIV (WLWH), engagement in care is crucial to maternal health and reducing the risk of perinatal transmission. To date, there have been no studies in Canada examining the impact of the COVID-19 pandemic on pregnant WLWH. METHODS: This was a retrospective cohort study assessing the impact of the pandemic on perinatal outcomes for pregnant WLWH using data from the Perinatal HIV Surveillance Program in British Columbia, Canada. We compared maternal characteristics, pregnancy outcomes, and clinical indicators related to engagement with care between a prepandemic (January 2017-March 2020) and pandemic cohort (March 2020-December 2022). We investigated preterm birth rates with explanatory variables using logistic regression analysis. RESULTS: The prepandemic cohort (n = 87) had a significantly (P < 0.05) lower gestational age at the first antenatal encounter (9.0 vs 11.8) and lower rates of preterm births compared with the pandemic cohort (n = 56; 15% vs 37%). Adjusted odds of preterm birth increased with the presence of substance use in pregnancy (aOR = 10.45, 95% confidence interval: 2.19 to 49.94) in WLWH. There were 2 cases of perinatal transmission of HIV in the pandemic cohort, whereas the prepandemic cohort had none. CONCLUSIONS: The pandemic had pronounced effects on pregnant WLWH and their infants in British Columbia including higher rates of preterm birth and higher gestational age at the first antenatal encounter. The nonstatistically significant increase in perinatal transmission rates is of high clinical importance.

Maternal and neonatal outcomes of French prospective multicenter cohort study COVIPREG during the first two COVID-19 waves.

BACKGROUND: SARS-CoV-2 infection on pregnant women was the subject of many questions since the COVID-19 pandemic. METHODS: We aim to assess maternal and neonatal outcomes of SARS-CoV-2 infection contracted during 2nd and 3rd trimesters of pregnancy during the first two COVID-19 waves across a prospective French multicenter cohort study. Patients were included between April 2020 and January 2021 in 10 maternity hospitals in Paris area with two groups (i) pregnant women with a positive SARS-CoV-2 nasopharyngeal RT-PCR between [14WG; 37WG[(symptomatic infection), (ii) pregnant women with a negative serology (or equivocal) at delivery and without a positive SARS-CoV-2 nasopharyngeal RT-PCR at any time during pregnancy (G2 group) MAIN FINDINGS: 2410 pregnant women were included, of whom 310 had a positive SARS-CoV-2 nasopharyngeal RT-PCR and 217 between [14WG; 37WG[. Most infections occurred between 28 and 37 weeks of gestation (56 %). Most patients could be managed as outpatients, while 23 % had to be hospitalized. Among women with a positive RT-PCR, multiparous women were over-represented (OR = 2.45[1.52;3.87]); were more likely to deliver before 37 weeks of gestation (OR = 2.19[1.44;3.24]) and overall cesarean deliveries were significantly increased (OR = 1.53[1.09;2.13]). CONCLUSIONS: This study highlights the maternal, obstetrical, and neonatal burden associated with SARS-CoV-2 infections during the first two pandemic waves before availability of vaccines. TRIAL REGISTRATION: NCT04355234 (registration date: 21/04/2020).

Global Transcriptomic Analysis of Placentas from Women with Gestational SARS-CoV-2 Infection during the Third Trimester of Pregnancy.

The COVID-19 pandemic has had a significant and enduring influence on global health, including maternal and fetal well-being. Evidence suggests that placental dysfunction is a potential consequence of SARS-CoV-2 infection during pregnancy, which may result in adverse outcomes such as preeclampsia and preterm birth. However, the molecular mechanisms underlying this association remain unclear, and it is uncertain whether a mature placenta can protect the fetus from SARS-CoV-2 infection. To address the above gap, we conducted a transcriptome-based study of the placenta in both maternal and fetal compartments. We collected placental samples from 16 women immediately after term delivery, seven of which had SARS-CoV-2 infection confirmed by PCR before parturition. Notably, we did not detect any viral load in either the maternal or fetal compartments of the placenta, regardless of symptomatic status. We separately extracted total RNA from placental tissues from maternal and fetal compartments, constructed cDNA libraries, and sequenced them to assess mRNA. Our analysis revealed 635 differentially expressed genes when a false discovery rate (FDR ≤ 0.05) was applied in the maternal placental tissue, with 518 upregulated and 117 downregulated genes in the SARS-CoV-2-positive women (n = 6) compared with the healthy SARS-CoV-2-negative women (n = 8). In contrast, the fetal compartment did not exhibit any significant changes in gene expression with SARS-CoV-2 infection. We observed a significant downregulation of nine genes belonging to the pregnancy-specific glycoprotein related to the immunoglobulin superfamily in the maternal compartment with active SARS-CoV-2 infection (fold change range from -13.70 to -5.28; FDR ≤ 0.01). Additionally, comparing symptomatic women with healthy women, we identified 1788 DEGs. Furthermore, a signaling pathway enrichment analysis revealed that pathways related to oxidative phosphorylation, insulin secretion, cortisol synthesis, estrogen signaling, oxytocin signaling, antigen processing, and presentation were altered significantly in symptomatic women. Overall, our study sheds light on the molecular mechanisms underlying the reported clinical risks of preeclampsia and preterm delivery in women with SARS-CoV-2 infection. Nonetheless, studies with larger sample sizes are warranted to further deepen our understanding of the molecular mechanisms of the placenta's anti-viral effects in maternal SARS-CoV-2 infection.