SARS-CoV-2 in Pregnancy and Reproduction

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "SARS-CoV-2 and COVID-19".

Deadline for manuscript submissions: closed (15 August 2023) | Viewed by 15350

Special Issue Editors


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Guest Editor
Department of Health Sciences, University of Leicester, Leicester LE1 7RH, UK
Interests: infections in pregnancy and prenatal diagnosis
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
Department of Obstetrics and Gynaecology, Weill Cornell Medicine, Ar-Rayyan, Qatar
Interests: prenatal diagnosis and infections in pregnancy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The novel severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), following the first report in December 2019 of in Wuhan, China, and declared as a pandemic by the WHO on 11 March 2020 it has infected nearly 400 million people and killed over 5.7 million worldwide, according to the latest update from Johns Hopkins Coronavirus Resource Center. SARS-CoV-2, which causes the disease known as COVID-19 has spread rapidly to almost every country in the world. COVID-19 is associated with significant morbidity and mortality not only in the vulnerable but also in adults with co-morbidities. Pregnancy, a state of immunosuppression and one often complicated by co-morbidities, unsurprisingly, therefore, is associated with poorer outcomes when complicated by SARS-2-CoV infections. Furthermore, the severity of the infection on the mother has consequences on the fetus, which include prematurity and low birth weight. Since the outbreak in 2019, there continues to be multiple publications on reflecting our understanding of the virus and its consequences on the patient improves and its prevention and management.

In this series on COVID-19 and Pregnancy and Reproduction, we invite studies whose results will provide a better understanding and management of COVID-19 in pregnancy or review articles that would be authoritative both on the biology of the virus including mutagenesis, diagnostics, prevention (including immunisation) and management.

Prof. Dr. Justin C. Konje
Dr. Badreldeen Ahmed
Guest Editors

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Keywords

  • COVID-19
  • SARS-CoV-2
  • coronavirus
  • pregnancy
  • reproduction
  • vaccination
  • mutagenesis

Published Papers (8 papers)

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Research

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11 pages, 1062 KiB  
Article
Maternal COVID-19 Serological Changes—Comparison between Seroconversion Rate in First and Third Trimesters of Pregnancy and Subsequent Obstetric Complications: A Cohort Study
by Maria N. Rayo, Adriana Aquise, Irene Fernandez-Buhigas, Lorena Gonzalez-Gea, Coral Garcia-Gonzalez, Mirian Sanchez-Tudela, Miguel Rodriguez-Fernandez, Diego Tuñon-Le Poultel, Belen Santacruz and Maria M. Gil
Viruses 2023, 15(12), 2386; https://doi.org/10.3390/v15122386 - 05 Dec 2023
Viewed by 862
Abstract
Pregnant women are especially vulnerable to respiratory diseases. We aimed to study seroconversion rates during pregnancy in a cohort of consecutive pregnancies tested in the first and third trimesters and to compare the maternal and obstetric complications in the women who seroconverted in [...] Read more.
Pregnant women are especially vulnerable to respiratory diseases. We aimed to study seroconversion rates during pregnancy in a cohort of consecutive pregnancies tested in the first and third trimesters and to compare the maternal and obstetric complications in the women who seroconverted in the first trimester and those who did so in the third. This was an observational cohort study carried out at the Hospital Universitario de Torrejón, in Madrid, Spain, during the first peak of the COVID-19 pandemic. All consecutive singleton pregnancies with a viable fetus attending their 11–13-week scan between 1 January and 15 May 2020 were included and seropositive women for SARS-CoV2 were monthly follow up until delivery. Antibodies against SARS-CoV-2 (IgA and IgG) were analyzed on stored serum samples obtained from first- and third-trimester routine antenatal bloods in 470 pregnant women. Antibodies against SARS-CoV-2 were detected in 31 (6.6%) women in the first trimester and in 66 (14.0%) in the third trimester, including 48 (10.2%) that were negative in the first trimester (seroconversion during pregnancy). Although the rate of infection was significantly higher in the third versus the first trimester (p = 0.003), no significant differences in maternal or obstetric complications were observed in women testing positive in the first versus the third trimester. Full article
(This article belongs to the Special Issue SARS-CoV-2 in Pregnancy and Reproduction)
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12 pages, 571 KiB  
Article
Placental Infection Associated with SARS-CoV-2 Wildtype Variant and Variants of Concern
by Ana Medel-Martinez, Cristina Paules, María Peran, Pilar Calvo, Sara Ruiz-Martinez, María Ormazabal Cundin, Alberto Cebollada-Solanas, Mark Strunk, Jon Schoorlemmer, Daniel Oros and Marta Fabre
Viruses 2023, 15(9), 1918; https://doi.org/10.3390/v15091918 - 13 Sep 2023
Viewed by 878
Abstract
The original SARS-CoV-2 lineages have been replaced by successive variants of concern (VOCs) over time. The aim of this study was to perform an assessment of the placental infection by SARS-CoV-2 according to the predominant variant at the moment of COVID-19 diagnosis. This [...] Read more.
The original SARS-CoV-2 lineages have been replaced by successive variants of concern (VOCs) over time. The aim of this study was to perform an assessment of the placental infection by SARS-CoV-2 according to the predominant variant at the moment of COVID-19 diagnosis. This was a prospective study of SARS-CoV-2-positive pregnant women between March 2020 and March 2022. The population was divided into pregnancies affected by COVID-19 disease during 2020 (Pre-VOC group) and pregnancies affected after December 2020 by SARS-CoV-2 variants of concern (VOC group). The presence of virus was assessed by RT-PCR, and the viral variant was determined by whole genome sequencing. A total of 104 placentas were examined, among which 54 cases belonged to the Pre-VOC group and 50 cases belonged to the VOC group. Sixteen positive placental RT-PCR tests for SARS-CoV-2 were reported. The NGS analysis confirmed the SARS-CoV-2 lineage in placenta tissue. All samples corresponded to the Pre-VOC group, whereas no placental presence of SARS-CoV-2 was detected in the VOC group (16, 29.6% vs. 0, 0.0% p = 0.000). Preterm birth (9, 16.7% vs. 2, 4%; p = 0.036) and hypertensive disorders of pregnancy (14, 25.9% vs. 3, 6%; p = 0.003) were more frequent in the Pre-VOC group than in the VOC group. Finally, the VOC group was composed of 23 unvaccinated and 27 vaccinated pregnant women; no differences were observed in the sub-analysis focused on vaccination status. In summary, SARS-CoV-2-positive placentas were observed only in pregnancies infected by SARS-CoV-2 wildtype. Thus, placental SARS-CoV-2 presence could be influenced by SARS-CoV-2 variants, infection timing, or vaccination status. According to our data, the current risk of SARS-CoV-2 placental infection after maternal COVID disease during pregnancy should be updated. Full article
(This article belongs to the Special Issue SARS-CoV-2 in Pregnancy and Reproduction)
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12 pages, 280 KiB  
Article
Four Waves of the COVID-19 Pandemic: Comparison of Clinical and Pregnancy Outcomes
by Sladjana Mihajlovic, Dejan Nikolic, Milena Santric-Milicevic, Biljana Milicic, Marija Rovcanin, Andjela Acimovic and Milan Lackovic
Viruses 2022, 14(12), 2648; https://doi.org/10.3390/v14122648 - 27 Nov 2022
Cited by 8 | Viewed by 1529
Abstract
During the last two and a half years, clinical manifestations, disease severity, and pregnancy outcomes have differed among pregnant patients with SARS-CoV-2 infection. These changes were preceded by the presence of new variants of SARS-CoV-2, known in the literature as variants of concern. [...] Read more.
During the last two and a half years, clinical manifestations, disease severity, and pregnancy outcomes have differed among pregnant patients with SARS-CoV-2 infection. These changes were preceded by the presence of new variants of SARS-CoV-2, known in the literature as variants of concern. The aim of this study is to describe the differences between maternal clinical characteristics and perinatal outcomes among pregnant women with COVID-19 during four waves of the COVID-19 epidemic in Serbia. This retrospective study included a series of 192 pregnant patients who were hospitalized due to the severity of their clinical status of SARS-CoV-2 infection. During four outbreaks of COVID-19 infection in Serbia, we compared and analyzed three sets of variables, including signs, symptoms, and characteristics of COVID-19 infection, clinical endpoints, and maternal and newborn parameters. During the dominance of the Delta variant, the duration of hospitalization was the longest (10.67 ± 1.42 days), the frequency of stillbirths was the highest (17.4%), as well as the frequency of progression of COVID infection (28.9%) and the requirement for non-invasive oxygen support (37%). The dominance of the Delta variant was associated with the highest number of prescribed antibiotics (2.35 ± 0.28), the most common presence of nosocomial infections (21.7%), and the highest frequency of corticosteroid therapy use (34.8%). The observed differences during the dominance of four variants of concern are potential pathways for risk stratification and the establishment of timely and proper treatments for pregnant patients. Early identification of the Delta variant, and possibly some new variants with similar features in the future, should be a priority and, perhaps, even an opportunity to introduce more accurate and predictive clinical algorithms for pregnant patients. Full article
(This article belongs to the Special Issue SARS-CoV-2 in Pregnancy and Reproduction)
11 pages, 278 KiB  
Article
Imbalanced Angiogenesis in Pregnancies Complicated by SARS-CoV-2 Infection
by Valentina Giardini, Sara Ornaghi, Carlo Gambacorti-Passerini, Marco Casati, Andrea Carrer, Eleonora Acampora, Maria Viola Vasarri, Francesca Arienti and Patrizia Vergani
Viruses 2022, 14(10), 2207; https://doi.org/10.3390/v14102207 - 07 Oct 2022
Cited by 9 | Viewed by 1765
Abstract
COVID-19 and preeclampsia (preE) share the ANG-II mediated endothelial dysfunction, resulting from a significant dysregulation of RAS and an imbalanced proportion of anti-angiogenic and pro-angiogenic soluble plasmatic factors. Of note, an increased incidence of preE has been reported among COVID-19-infected mothers compared to [...] Read more.
COVID-19 and preeclampsia (preE) share the ANG-II mediated endothelial dysfunction, resulting from a significant dysregulation of RAS and an imbalanced proportion of anti-angiogenic and pro-angiogenic soluble plasmatic factors. Of note, an increased incidence of preE has been reported among COVID-19-infected mothers compared to the general pregnant population. The two most promising angiogenic markers are the soluble fms-like tyrosine kinase receptor-1 (sFlt-1), the major antiangiogenic factor, and the placental growth factor (PlGF), a powerful angiogenic factor. Since these markers have proven useful in the prediction, diagnosis, and severity of preE, this study aimed to evaluate their maternal serum levels in pregnancies complicated by SARS-CoV-2 infection and to assess their potential use to guide the management of these women. A retrospective analysis of SARS-CoV-2-positive pregnant women was performed. The serum levels of sFlt-1 and PlGF were collected at the diagnosis of SARS-CoV-2 infection at the hospital, before the beginning of steroid/hydroxychloroquine and/or antithrombotic therapy. The sFlt-1/PlGF ratio was stratified using cut-off values clinically utilized in the diagnosis and prediction of preE (low < 38, intermediate 38–85/110* and high >85/110*, * if before or after the 34th week of gestation). A total of 57 women were included, of whom 20 (35%) had signs and symptoms of COVID-19 at hospital presentation and 37 (65%) were asymptomatic. None were vaccinated. The mean gestational age at diagnosis of SARS-CoV-2 infection was 32 weeks in symptomatic patients and 37 weeks and 5 days in asymptomatic ones (p = 0.089). sFlt-1 serum levels were higher in SARS-CoV-2 positive asymptomatic patients compared to women with COVID-19 related symptoms (4899 ± 4357 pg/mL vs. 3187 ± 2426 pg/mL, p = 0.005). sFlt-1/PlGF at admission was <38 in 18 of the 20 symptomatic women (90%) compared to 22 (59%) of the asymptomatic patients (p = 0.018). Of note, two of the three women admitted to the intensive care unit had a very low ratio (<2). In turn, rates of patients with sFlt-1/PlGF at admission > 85/110 were not significantly different between the two groups: 11% in asymptomatic patients (4/37) vs. none of the symptomatic patients (p = 0.286), and all of them presented a placental dysfunction, like preE (n = 1) and FGR (n = 3). Of note, there were no stillbirths or maternal or neonatal deaths among symptomatic patients; also, no cases of preE, FGR, or small for gestational age neonates were diagnosed. In conclusion, our data suggest that SARS-CoV-2 infection during pregnancy could influence the angiogenic balance. A significant pathological alteration of the sFlt-1/PlGF ratio cannot be identified during the symptomatic phase; however, if left untreated, SARS-CoV-2 infection could potentially trigger placental dysfunction. Full article
(This article belongs to the Special Issue SARS-CoV-2 in Pregnancy and Reproduction)

Review

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21 pages, 346 KiB  
Review
Immunisation against COVID-19 in Pregnancy and of Women Planning Pregnancy
by Justin C. Konje, Mariam Al Beloushi and Badreldeen Ahmed
Viruses 2023, 15(3), 621; https://doi.org/10.3390/v15030621 - 24 Feb 2023
Cited by 3 | Viewed by 1658
Abstract
Following reports of the first human SARS-CoV2 infection in December 2019 from Wuhan Province, China, there was such rapid spread that by March 2021, the World Health Organization (WHO) had declared a pandemic. Over 6.5 million people have died from this infection worldwide, [...] Read more.
Following reports of the first human SARS-CoV2 infection in December 2019 from Wuhan Province, China, there was such rapid spread that by March 2021, the World Health Organization (WHO) had declared a pandemic. Over 6.5 million people have died from this infection worldwide, although this is most likely an underestimate. Until vaccines became available, mortality and severe morbidity were costly in terms of life lost as well as the cost of supporting the severely and acutely ill. Vaccination changed the landscape, and following worldwide adoption, life has gradually been returning to normal. The speed of production of the vaccines was unprecedented and undoubtedly ushered in a new era in the science of fighting infections. The developed vaccines were on the already known platforms for vaccine delivery: inactivated virus, virus vector, virus-like particles (VLP) subunit, DNA and mRNA. The mRNA platform was used for the first time to deliver vaccines to humans. An understanding of these platforms and the pros and cons of each are important for clinicians who are often challenged by the recipients on the advantages and risks of these vaccines. These vaccines have so far and reassuringly been shown to be safe in reproduction (with no effect on gametes) and pregnancy (not associated with congenital malformations). However, safety remains paramount and continuing vigilance is critical, especially against rare fatal complications such as vaccine-induced thrombocytopenia and myocarditis. Finally, the waning immunity months after vaccination means repeated immunisation is likely to be ongoing, but just how often and how many such revaccinations should be recommended remains uncertain. Research into other vaccines and alternate delivery methods should continue as this infection is likely to be around for a long time. Full article
(This article belongs to the Special Issue SARS-CoV-2 in Pregnancy and Reproduction)

Other

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15 pages, 3127 KiB  
Case Report
Congenital SARS-CoV-2 Infection in Two Neonates with Confirmation by Viral Culture of the Placenta in One Case
by Joseph V. Vayalumkal, Amuchou S. Soraisham, Ayman Abou Mehrem, Anirban Ghosh, Jessica K. E. Dunn, Kevin Fonseca, Hong Zhou, Byron M. Berenger, Elaine S. Chan, Marie-Anne Brundler, Yi-Chan Lin, David H. Evans, Sharon Rousso, Verena Kuret and John M. Conly
Viruses 2023, 15(6), 1310; https://doi.org/10.3390/v15061310 - 31 May 2023
Cited by 1 | Viewed by 2243
Abstract
Congenital infections with SARS-CoV-2 are uncommon. We describe two confirmed congenital SARS-CoV-2 infections using descriptive, epidemiologic and standard laboratory methods and in one case, viral culture. Clinical data were obtained from health records. Nasopharyngeal (NP) specimens, cord blood and placentas when available were [...] Read more.
Congenital infections with SARS-CoV-2 are uncommon. We describe two confirmed congenital SARS-CoV-2 infections using descriptive, epidemiologic and standard laboratory methods and in one case, viral culture. Clinical data were obtained from health records. Nasopharyngeal (NP) specimens, cord blood and placentas when available were tested by reverse transcriptase real-time PCR (RT-PCR). Electron microscopy and histopathological examination with immunostaining for SARS-CoV-2 was conducted on the placentas. For Case 1, placenta, umbilical cord, and cord blood were cultured for SARS-CoV-2 on Vero cells. This neonate was born at 30 weeks, 2 days gestation by vaginal delivery. RT-PCR tests were positive for SARS-CoV-2 from NP swabs and cord blood; NP swab from the mother and placental tissue were positive for SARS-CoV-2. Placental tissue yielded viral plaques with typical morphology for SARS-CoV-2 at 2.8 × 102 pfu/mL confirmed by anti-spike protein immunostaining. Placental examination revealed chronic histiocytic intervillositis with trophoblast necrosis and perivillous fibrin deposition in a subchorionic distribution. Case 2 was born at 36 weeks, 4 days gestation. RT-PCR tests from the mother and infant were all positive for SARS-CoV-2, but placental pathology was normal. Case 1 may be the first described congenital case with SARS-CoV-2 cultivated directly from placental tissue. Full article
(This article belongs to the Special Issue SARS-CoV-2 in Pregnancy and Reproduction)
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14 pages, 2341 KiB  
Case Report
SARS-CoV-2 Is Persistent in Placenta and Causes Macroscopic, Histopathological, and Ultrastructural Changes
by André Luiz N. Parcial, Natália Gedeão Salomão, Elyzabeth Avvad Portari, Laíza Vianna Arruda, Jorge José de Carvalho, Herbert Leonel de Matos Guedes, Thayana Camara Conde, Maria Elizabeth Moreira, Marcelo Meuser Batista, Marciano Viana Paes, Kíssila Rabelo and Adriano Gomes-Silva
Viruses 2022, 14(9), 1885; https://doi.org/10.3390/v14091885 - 26 Aug 2022
Cited by 4 | Viewed by 3971
Abstract
SARS-CoV-2 is a virus that belongs to the Betacoronavirus genus of the Coronaviridae family. Other coronaviruses, such as SARS-CoV and MERS-CoV, were associated with complications in pregnant women. Therefore, this study aimed to report the clinical history of five pregnant women infected with [...] Read more.
SARS-CoV-2 is a virus that belongs to the Betacoronavirus genus of the Coronaviridae family. Other coronaviruses, such as SARS-CoV and MERS-CoV, were associated with complications in pregnant women. Therefore, this study aimed to report the clinical history of five pregnant women infected with SARS-CoV-2 (four symptomatic and one asymptomatic who gave birth to a stillborn child) during the COVID-19 pandemic. They gave birth between August 2020 to January 2021, a period in which there was still no vaccination for COVID-19 in Brazil. In addition, their placental alterations were later investigated, focusing on macroscopic, histopathological, and ultrastructural aspects compared to a prepandemic sample. Three of five placentas presented SARS-CoV-2 RNA detected by RT-PCRq at least two to twenty weeks after primary pregnancy infection symptoms, and SARS-CoV-2 spike protein was detected in all placentas by immunoperoxidase assay. The macroscopic evaluation of the placentas presented congested vascular trunks, massive deposition of fibrin, areas of infarctions, and calcifications. Histopathological analysis showed fibrin deposition, inflammatory infiltrate, necrosis, and blood vessel thrombosis. Ultrastructural aspects of the infected placentas showed a similar pattern of alterations between the samples, with predominant characteristics of apoptosis and detection of virus-like particles. These findings contribute to a better understanding of the consequences of SARS-CoV-2 infection in placental tissue, vertical transmission. Full article
(This article belongs to the Special Issue SARS-CoV-2 in Pregnancy and Reproduction)
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5 pages, 205 KiB  
Case Report
Evidence of Maternal Antibodies Elicited by COVID-19 Vaccination in Amniotic Fluid: Report of Two Cases in Italy
by Francesca Colavita, Alessandra Oliva, Aurora Bettini, Andrea Antinori, Enrico Girardi, Concetta Castilletti, Francesco Vaia and Giuseppina Liuzzi
Viruses 2022, 14(7), 1592; https://doi.org/10.3390/v14071592 - 21 Jul 2022
Cited by 3 | Viewed by 1498
Abstract
With SARS-CoV-2 infection, pregnant women may be at a high risk of severe disease and adverse perinatal outcomes. A COVID-19 vaccination campaign represents the key strategy to combat the pandemic; however, public acceptance of maternal immunization has to be improved, which may be [...] Read more.
With SARS-CoV-2 infection, pregnant women may be at a high risk of severe disease and adverse perinatal outcomes. A COVID-19 vaccination campaign represents the key strategy to combat the pandemic; however, public acceptance of maternal immunization has to be improved, which may be achieved by highlighting the promising mechanism of passive immunity as a strategy for protecting newborns against SARS-CoV-2 infection. We tested the anti-SARS-CoV-2 antibody response following COVID-19 full-dose vaccination in the serum and amniotic fluid of two pregnant women who presented between April and June 2021, at the Center for the Treatment and Prevention of Infections in Pregnancy of the National Institute for Infectious Diseases “L. Spallanzani”, for antenatal consultancy. Anti-SARS-CoV-2 IgG was found in residual samples of amniotic fluid collected from both women at the 18th week of gestation (63 and 131 days after the second dose’s administration). Titers in amniotic fluid mirrored the levels detected in serum and were inversely linked to the time from vaccination. Our results suggest that antibodies elicited by COVID-19 vaccination can cross the placenta and reach the fetus; therefore, they may offer passive immunity at birth. It is critical to fully understand the kinetics of the maternal response to vaccination, the efficiency of IgG transfer, and the persistence of antibodies in infants to optimize maternal immunization regimens. Full article
(This article belongs to the Special Issue SARS-CoV-2 in Pregnancy and Reproduction)
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