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1.
Ultrasound Obstet Gynecol ; 55(5): 586-592, 2020 05.
Article in English | MEDLINE | ID: covidwho-2273197

ABSTRACT

OBJECTIVES: There are limited case series reporting the impact on women affected by coronavirus during pregnancy. In women affected by severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), the case fatality rate appears higher in those affected in pregnancy compared with non-pregnant women. We conducted a rapid review to guide health policy and management of women affected by COVID-19 during pregnancy, which was used to develop the Royal College of Obstetricians and Gynaecologists' (RCOG) guidelines on COVID-19 infection in pregnancy. METHODS: Searches were conducted in PubMed and MedRxiv to identify primary case reports, case series, observational studies and randomized controlled trials describing women affected by coronavirus in pregnancy. Data were extracted from relevant papers. This review has been used to develop guidelines with representatives of the Royal College of Paediatrics and Child Health (RCPCH) and RCOG who provided expert consensus on areas in which data were lacking. RESULTS: From 9965 search results in PubMed and 600 in MedRxiv, 21 relevant studies, all of which were case reports or case series, were identified. From reports of 32 women to date affected by COVID-19 in pregnancy, delivering 30 babies (one set of twins, three ongoing pregnancies), seven (22%) were asymptomatic and two (6%) were admitted to the intensive care unit (ICU), one of whom remained on extracorporeal membrane oxygenation. No maternal deaths have been reported to date. Delivery was by Cesarean section in 27 cases and by vaginal delivery in two, and 15 (47%) delivered preterm. There was one stillbirth and one neonatal death. In 25 babies, no cases of vertical transmission were reported; 15 were reported as being tested with reverse transcription polymerase chain reaction after delivery. Case fatality rates for SARS and MERS were 15% and 27%, respectively. SARS was associated with miscarriage or intrauterine death in five cases, and fetal growth restriction was noted in two ongoing pregnancies affected by SARS in the third trimester. CONCLUSIONS: Serious morbidity occurred in 2/32 women with COVID-19, both of whom required ICU care. Compared with SARS and MERS, COVID-19 appears less lethal, acknowledging the limited number of cases reported to date and that one woman remains in a critical condition. Preterm delivery affected 47% of women hospitalized with COVID-19, which may put considerable pressure on neonatal services if the UK's reasonable worst-case scenario of 80% of the population being affected is realized. Based on this review, RCOG, in consultation with RCPCH, developed guidance for delivery and neonatal care in pregnancies affected by COVID-19, which recommends that delivery mode be determined primarily by obstetric indication and recommends against routine separation of affected mothers and their babies. We hope that this review will be helpful for maternity and neonatal services planning their response to COVID-19. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.


Subject(s)
Betacoronavirus , Coronavirus Infections/complications , Pneumonia, Viral/complications , Pregnancy Complications, Infectious , COVID-19 , Databases, Factual , Female , Fetal Development , Humans , Pandemics , Pregnancy , Pregnancy Outcome , Premature Birth , SARS-CoV-2
3.
Eur J Obstet Gynecol Reprod Biol ; 281: 63-67, 2023 Feb.
Article in English | MEDLINE | ID: covidwho-2158764

ABSTRACT

BACKGROUND: During pregnancy, certain viral infections are known to significantly affect fetal development. Data regarding the impact of COVID-19 viral infection in pregnancy, specifically in asymptomatic or mild cases, remains limited. This presents a challenge in providing prenatal counseling and antepartum surveillance in pregnancies complicated by COVID-19 infection. Placenta studies have demonstrated that vascular malperfusion patterns attributed to COVID-19 appear to depend on the timing of infection. Given these placental changes, we aim to evaluate the impact of COVID-19 on fetal growth in pregnant patients with asymptomatic or mild disease, stratified by trimester of infection. We hypothesize that COVID-19 infection, especially early in pregnancy, increases the risk of fetal growth restriction (FGR). STUDY DESIGN: This is a single institution, retrospective cohort study of patients ages 16-55 years old with a singleton delivery between December 10, 2020, and April 19, 2021 who had not received a COVID-19 vaccination prior to delivery. COVID-19 infection during pregnancy was defined as a positive SARS-CoV-2 RT-PCR test. FGR was defined as an estimated fetal weight less than the 10th percentile for gestational age or abdominal circumference less than the 10th percentile for gestational age. Maternal and fetal characteristics, including FGR, were compared between women with versus without COVID-19 infection during pregnancy. RESULTS: Among 1971 women with a singleton delivery, 208 (10.6 %) had a prior asymptomatic or mild COVID-19 infection during pregnancy. With the exception in the median prenatal BMI being significantly higher in the COVID-19 group (median, 27.5 vs 26.3, p = 0.04), there were no significant differences in demographics, baseline maternal comorbidities or gestational age between those with versus without COVID-19 infection during pregnancy, or in the proportion of their offspring with FGR (3.4 % (7/208) vs 4.8 % (84/1763), p = 0.36). When the 208 women were stratified by the timing of their COVID-19 infection, the proportion with an offspring with FGR was 8.7 % (2/23), 1.2 % (1/84), and 4.0 % (4/101), for those first diagnosed with COVID-19 during the 1st, 2nd, and 3rd trimesters, respectively (p = 0.72 Cochran-Armitage test for trend). CONCLUSION: Asymptomatic or mild COVID-19 infection in pregnancy, regardless of timing of infection, does not appear to be associated with FGR. Routine serial fetal growth assessment may not be warranted solely for history of COVID-19 infection.


Subject(s)
COVID-19 , Placenta , Pregnancy , Female , Humans , Adolescent , Young Adult , Adult , Middle Aged , Placenta/blood supply , Retrospective Studies , COVID-19 Vaccines , COVID-19/complications , COVID-19/diagnosis , SARS-CoV-2 , Fetal Development , Fetal Growth Retardation/etiology , Gestational Age
5.
Front Public Health ; 10: 986162, 2022.
Article in English | MEDLINE | ID: covidwho-2023009

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) - 2019 (COVID-19) has led to a worldwide public health concern. In addition to immediate impacts on human health and well-being, COVID-19 can result in unfortunate and long-term health consequences for future generations. In particular, pregnant women and developing fetuses in low-income settings could be prone to a higher risk of undernutrition, often due to an inadequate supply of food and nutrition during a pandemic outbreak like COVID-19. Such situations can subsequently lead to an increased risk of undesirable health consequences, such as non-communicable diseases, including obesity, metabolic syndrome, hypertension, and type 2 diabetes, in individuals born to exposed mothers via fetal programming. Moreover, COVID-19 infection or related stress during pregnancy can induce long-term programming outcomes on neuroendocrinological systems in offspring after birth. However, the long-lasting consequences of the transplacental transmission of COVID-19 in offspring are currently unknown. Here we hypothesize that a COVID-19 pandemic triggers intrauterine programming outcomes in offspring due to multiple maternal factors (e.g., nutrition deficiency, stress, infection, inflammation) during pregnancy. Thus, it is crucial to establish an integrated lifetime health information system for individuals born in or around the COVID-19 pandemic to identify those at risk of adverse pre-and postnatal nutritional programming. This approach will assist in designing specific dietary or other nutritional interventions to minimize the potential undesirable outcomes in those nutritionally programmed individuals.


Subject(s)
COVID-19 , Diabetes Mellitus, Type 2 , COVID-19/epidemiology , Female , Fetal Development , Humans , Pandemics , Pregnancy , SARS-CoV-2
6.
J Reprod Immunol ; 151: 103619, 2022 06.
Article in English | MEDLINE | ID: covidwho-1763859

ABSTRACT

Dexamethasone has been widely used in clinical practice to promote fetal lung maturity and reduce neonatal respiratory distress syndrome and perinatal mortality. Nevertheless, its administration is a double-edged sword, as a large number of studies have shown that there are obvious disadvantages in pregnant women and fetal development. In this review, we comprehensively retrospect the latest literature on the toxicological effects and mechanisms of dexamethasone on fetal development, in an attempt to provide a valuable basis for further studies and clinical trials in the future. Overall, prenatal dexamethasone exposure could lead to some adverse consequences on fetal organ systems through intrauterine programming based on the results of current animal and human researches. Potential sequelae include osteoarthritis, hypertension, fatty liver, glomerulosclerosis, depression, diabetes and infertility, some of which can pass on to the next generation. It must be noted that the evidence in humans is preliminary and limited by the small sample size. More studies in large-scale populations are needed to confirm if it raises the risk of sequelae in humans. In addition, we strongly support the application of dexamethasone as a pharmaceutical therapy in pregnant women with coronavirus disease 2019 before a better therapy is developed. However, the adverse side effects that may arise also cannot be ignored.


Subject(s)
COVID-19 Drug Treatment , Pregnancy Complications, Infectious , Respiratory Distress Syndrome, Newborn , Animals , Dexamethasone/adverse effects , Female , Fetal Development , Humans , Infant, Newborn , Pregnancy
7.
Reprod Toxicol ; 107: 69-80, 2022 01.
Article in English | MEDLINE | ID: covidwho-1531737

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection resulting in the coronavirus disease 2019 (COVID-19) has afflicted tens of millions of people in a worldwide pandemic. A recently developed recombinant Plant-Derived Virus-Like Particle Vaccine candidate for COVID-19 (CoVLP) formulated with AS03 has been shown to be well-tolerated and highly immunogenic in healthy adults. Since the target population for the vaccine includes women of childbearing potential, the objective of the study was to evaluate any untoward prenatal and postnatal effects of AS03-adjuvanted CoVLP administered intramuscularly to Sprague-Dawley female rats before cohabitation for mating (22 and 8 days prior) and during gestation (Gestation Days [GD] 6 and 19). The embryo-fetal development (EFD) cohort was subjected to cesarean on GD 21 and the pre/post-natal (PPN) cohort was allowed to naturally deliver. Effects of AS03-adjuvanted CoVLP was evaluated on pregnant rats, embryo-fetal development (EFD), during parturition, lactation and the development of the F1 offspring up to weaning Vaccination with AS03-adjuvanted CoVLP induced an antibody response in F0 females and anti-SARS-CoV-2 spike-specific maternal antibodies were detected in the offspring at the end of the gestation and lactation periods. Overall, there was no evidence of untoward effects of AS03-adjuvanted CoVLP on the fertility or reproductive performance of the vaccinated F0 females. There was no evidence of untoward effects on embryo-fetal development (including teratogenicity), or early (pre-weaning) development of the F1 offspring. These results support the acceptable safety profile of the AS03-adjuvanted CoVLP vaccine for administration to women of childbearing potential.


Subject(s)
COVID-19 Vaccines , COVID-19/prevention & control , Embryonic Development/drug effects , Fertility/drug effects , Fetal Development/drug effects , Polysorbates/administration & dosage , Squalene/administration & dosage , Vaccines, Virus-Like Particle/administration & dosage , alpha-Tocopherol/administration & dosage , Animals , Animals, Newborn , Antibodies, Viral/blood , Drug Combinations , Female , Immunoglobulin G/blood , Maternal-Fetal Exchange , Pregnancy , Rats, Sprague-Dawley , Recombinant Proteins/immunology , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology , Tobacco/genetics
8.
Eur Rev Med Pharmacol Sci ; 25(18): 5876-5884, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1451047

ABSTRACT

The risk stratification of young adults between subjects who will develop a mild form COVID-19 and subjects who will undergo a severe disease remains inaccurate. In this review, we propose that the Barker hypothesis might explain the increased susceptibility to severe forms of COVID-19 in subjects who underwent intrauterine growth restriction (IUGR). In this paper evidence indicating an association between a low birth weight and an adult phenotype which might favor a severe outcome of SARS-CoV-2 infection are presented: lower lung functional capacity; increased respiratory morbidity; changes in fibrinogen and Factor VII serum levels and dysregulation of the hemostasis and thrombosis system; acquisition of a pro-thrombotic phenotype; low nephron number, with decreased ability to sustain renal function and increased renal morbidity; heart remodeling, with a less efficient cardiac function; endothelial dysfunction, a risk factor for the insurgence of the multiple organ failure; remodeling of arteries, with changes in the elastic properties of the arterial wall, predisposing to the insurgence and progression of atherosclerosis; dysfunction of the innate immune system, a risk factor for immune diseases in adulthood. These data suggest that young and adult subjects born too small (IUGR) or too early (pre-terms) might represent a subgroup of "at risk subjects", more susceptible toward severe forms of COVID-19. Given that LBW may be considered a surrogate of IUGR, this phenotypic marker should be included among the indispensable clinical data collected in every patient presenting with SARS-COV-2 infection, irrespectively of his/her age.


Subject(s)
COVID-19/epidemiology , Disease Susceptibility/epidemiology , Fetal Development , Disease Susceptibility/virology , Fetal Growth Retardation , Humans , Infant, Low Birth Weight , Severity of Illness Index , Young Adult
9.
Reprod Toxicol ; 103: 28-35, 2021 08.
Article in English | MEDLINE | ID: covidwho-1246163

ABSTRACT

BNT162b2 is a vaccine developed to prevent coronavirus disease 2019 (COVID-19). BNT162b2 is a lipid nanoparticle formulated nucleoside-modified messenger RNA (mRNA) encoding the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein locked in its prefusion conformation. A developmental and reproductive toxicity study was conducted in rats according to international regulatory guidelines. The full human BNT162b2 dose of 30 µg mRNA/dose (>300 times the human dose on a mg/kg basis) was administered intramuscularly to 44 female rats 21 and 14 days prior to mating and on gestation days 9 and 20. Half of the rats were subject to cesarean section and full fetal examination at the end of gestation, and the other half were allowed to deliver and were monitored to the end of lactation. A robust neutralizing antibody response was confirmed prior to mating and at the end of gestation and lactation. The presence of neutralizing antibodies was also confirmed in fetuses and offspring. Nonadverse effects, related to the local injection site reaction, were noted in dams as expected from other animal studies and consistent with observations in humans. There were no effects of BNT162b2 on female mating performance, fertility, or any ovarian or uterine parameters nor on embryo-fetal or postnatal survival, growth, physical development or neurofunctional development in the offspring through the end of lactation. Together with the safety profile in nonpregnant people, this ICH-compliant nonclinical safety data supports study of BNT162b2 in women of childbearing potential and pregnant and lactating women.


Subject(s)
COVID-19 Vaccines/toxicity , Fertility , Fetal Development , Animals , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , BNT162 Vaccine , COVID-19 Vaccines/pharmacology , Cesarean Section , Female , Lactation , Pregnancy , Rats , Rats, Wistar
10.
Clin Nutr ESPEN ; 43: 1-8, 2021 06.
Article in English | MEDLINE | ID: covidwho-1240256

ABSTRACT

BACKGROUND & AIMS: Maternal gestational infection is a well-characterized risk factor for offsprings' development of mental disorders including schizophrenia, autism, and attention deficit disorder. The inflammatory response elicited by the infection is partly directed against the placenta and fetus and is the putative pathogenic mechanism for fetal brain developmental abnormalities. Fetal brain abnormalities are generally irreversible after birth and increase risk for later mental disorders. Maternal immune activation in animals models this pathophysiology. SARS-CoV-2 produces maternal inflammatory responses during pregnancy similar to previously studied common respiratory viruses. METHOD: Choline, folic acid, Vitamin D, and n-3 polyunsaturated fatty acids are among the nutrients that have been studied as possible mitigating factors for effects of maternal infection and inflammation on fetal development. Clinical and animal studies relevant to their use in pregnant women who have been infected are reviewed. RESULTS: Higher maternal choline levels have positive effects on the development of brain function for infants of mothers who experienced viral infections in early pregnancy. No other nutrient has been studied in the context of viral inflammation. Vitamin D reduces pro-inflammatory cytokines in some, but not all, studies. Active folic acid metabolites decrease anti-inflammatory cytokines. N-3 polyunsaturated fatty acids have no effect. CONCLUSIONS: Vitamin D and folic acid are already supplemented in food additives and in prenatal vitamins. Despite recommendations by several public health agencies and medical societies, choline intake is often inadequate in early gestation when the brain is forming. A public health initiative for choline supplements during the pandemic could be helpful for women planning or already pregnant who also become exposed or infected with SARS-CoV-2.


Subject(s)
Brain , COVID-19/complications , Choline/therapeutic use , Fetal Development , Mothers , Nutritional Status , Pregnancy Complications, Infectious/virology , Animals , Brain/drug effects , COVID-19/metabolism , COVID-19/virology , Child Development/drug effects , Choline/pharmacology , Developmental Disabilities/etiology , Developmental Disabilities/prevention & control , Dietary Supplements , Fatty Acids, Omega-3/pharmacology , Fatty Acids, Omega-3/therapeutic use , Female , Fetal Development/drug effects , Fetus/drug effects , Folic Acid/pharmacology , Folic Acid/therapeutic use , Humans , Infant , Inflammation/complications , Inflammation/metabolism , Nutritional Requirements , Pandemics , Placenta/metabolism , Pregnancy , Pregnancy Complications, Infectious/metabolism , SARS-CoV-2 , Vitamin D/pharmacology , Vitamin D/therapeutic use
11.
Environ Health ; 20(1): 34, 2021 03 26.
Article in English | MEDLINE | ID: covidwho-1154012

ABSTRACT

BACKGROUND: An unusual feature of SARS-Cov-2 infection and the COVID-19 pandemic is that children are less severely affected than adults. This is especially paradoxical given the epidemiological links between poor air quality and increased COVID-19 severity in adults and that children are generally more vulnerable than adults to the adverse consequences of air pollution. OBJECTIVES: To identify gaps in knowledge about the factors that protect children from severe SARS-Cov-2 infection even in the face of air pollution, and to develop a transdisciplinary research strategy to address these gaps. METHODS: An international group of researchers interested in children's environmental health was invited to identify knowledge gaps and to develop research questions to close these gaps. DISCUSSION: Key research questions identified include: what are the effects of SAR-Cov-2 infection during pregnancy on the developing fetus and child; what is the impact of age at infection and genetic susceptibility on disease severity; why do some children with COVID-19 infection develop toxic shock and Kawasaki-like symptoms; what are the impacts of toxic environmental exposures including poor air quality, chemical and metal exposures on innate immunity, especially in the respiratory epithelium; what is the possible role of a "dirty" environment in conveying protection - an example of the "hygiene hypothesis"; and what are the long term health effects of SARS-Cov-2 infection in early life. CONCLUSION: A concerted research effort by a multidisciplinary team of scientists is needed to understand the links between environmental exposures, especially air pollution and COVID-19. We call for specific research funding to encourage basic and clinical research to understand if/why exposure to environmental factors is associated with more severe disease, why children appear to be protected, and how innate immune responses may be involved. Lessons learned about SARS-Cov-2 infection in our children will help us to understand and reduce disease severity in adults, the opposite of the usual scenario.


Subject(s)
COVID-19/epidemiology , Child Health , Environmental Exposure/adverse effects , Environmental Health , Adult , Age Factors , Air Pollution/adverse effects , Air Pollution/prevention & control , COVID-19/immunology , COVID-19/pathology , COVID-19/prevention & control , Child , Disease Susceptibility/epidemiology , Disease Susceptibility/immunology , Disease Susceptibility/pathology , Environmental Exposure/prevention & control , Fetal Development , Humans , Hygiene Hypothesis , Immunity, Innate , Respiratory System/pathology , Respiratory System/virology , SARS-CoV-2
12.
Acta Obstet Gynecol Scand ; 100(6): 1034-1039, 2021 06.
Article in English | MEDLINE | ID: covidwho-1087948

ABSTRACT

INTRODUCTION: Our objective was to compare the fetal growth velocity and fetal hemodynamics in pregnancies complicated and in those not complicated by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. MATERIAL AND METHODS: Prospective case-control study of consecutive pregnancies complicated by SARS-CoV-2 infection during the second half of pregnancy matched with unaffected women. The z scores of head circumference, abdominal circumference, femur length, and estimated fetal weight were compared between the two groups. Fetal growth was assessed by analyzing the growth velocity of head circumference, abdominal circumference, femur length, and estimated fetal weight between the second- and third-trimester scans. Similarly, changes in the pulsatility index of uterine, umbilical, and middle cerebral arteries, and their ratios were compared between the two study groups. RESULTS: Forty-nine consecutive pregnancies complicated, and 98 not complicated, by SARS-CoV-2 infection were included. General baseline and pregnancy characteristics were similar between pregnant women with and those without SARS-CoV-2 infection. There was no difference in head circumference, abdominal circumference, femur length, and estimated fetal weight z scores between pregnancies complicated and those not complicated by SARS-CoV-2 infection at both the second- and third-trimester scans. Likewise, there was no difference in the growth velocity of all these body parameters between the two study groups. Finally, there was no difference in the pulsatility index of both maternal and fetal Doppler scans throughout gestation between the two groups. CONCLUSIONS: Pregnancies complicated by SARS-CoV-2 infection are not at higher risk of developing fetal growth restriction through impaired placental function. The findings from this study do not support a policy of increased fetal surveillance in these women.


Subject(s)
COVID-19/complications , Fetal Development , Hemodynamics , Pregnancy Complications, Infectious/virology , Pulsatile Flow , Adult , Biometry , Case-Control Studies , Female , Gestational Age , Humans , Pregnancy , Pregnancy Trimester, Second , Pregnancy Trimester, Third , Prospective Studies , SARS-CoV-2 , Ultrasonography, Doppler
13.
Early Hum Dev ; 155: 105322, 2021 04.
Article in English | MEDLINE | ID: covidwho-1053333

ABSTRACT

From the moment of the identification of SARS-CoV-2 as an etiological agent of the severe clinical pictures of pneumonia that were being slowly observed all over the world, numerous studies have been conducted to increase the knowledge about what was an unknown virus until then. The efforts were mainly aimed to acquire epidemiological, microbiological, pathogenetic, clinical, diagnostic, therapeutic and preventive information in order to increase the available weapons to fight an infection which was rapidly taking on the characteristics of the pandemic. Given the topicality of the problem, not everything has yet been fully understood and clarified, especially in the maternal-fetal­neonatal field, where we are beginning to question what could be the outcomes of newborn babies born to mothers who contracted SARS-CoV-2 infection during pregnancy. Thus, the aim of this review is to analyze the long-term outcomes of this infection that could affect the offspring, regardless of a possible maternal-fetal transmission, focusing on, above all, the role of maternal immune activation and the expression of the Angiotensin-converting enzyme 2 (ACE2) in particular at the placental level.


Subject(s)
COVID-19/complications , Infant, Newborn, Diseases/virology , Pregnancy Complications, Infectious/immunology , Pregnancy Complications, Infectious/virology , Adaptive Immunity , Angiotensin-Converting Enzyme 2/metabolism , COVID-19/immunology , COVID-19/therapy , COVID-19/transmission , Female , Fetal Development , Humans , Infant, Newborn , Infant, Newborn, Diseases/embryology , Infant, Newborn, Diseases/metabolism , Infectious Disease Transmission, Vertical , Placenta/immunology , Placenta/metabolism , Pregnancy , Time Factors
14.
Hum Reprod ; 36(1): 40-47, 2021 01 01.
Article in English | MEDLINE | ID: covidwho-906660

ABSTRACT

STUDY QUESTION: Does maternal infection with severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) in first trimester pregnancy have an impact on the fetal development as measured by nuchal translucency thickness and pregnancy loss? SUMMARY ANSWER: Nuchal translucency thickness at the first trimester scan was not significantly different in pregnant women with versus without SARS-CoV-2 infection in early pregnancy and there was no significantly increased risk of pregnancy loss in women with SARS-CoV-2 infection in the first trimester. WHAT IS KNOWN ALREADY: Pregnant women are more vulnerable to viral infections. Previous coronavirus epidemics have been associated with increased maternal morbidity, mortality and adverse obstetric outcomes. Currently, no evidence exists regarding possible effects of SARS-CoV-2 in first trimester pregnancies. STUDY DESIGN, SIZE, DURATION: Cohort study of 1019 women with a double test taken between 17 February and 23 April 2020, as a part of the combined first trimester risk assessment, and 36 women with a first trimester pregnancy loss between 14 April and 21 May 2020, prior to the double test. The study period was during the first SARS-CoV-2 epidemic wave in Denmark. PARTICIPANTS/MATERIALS, SETTING, METHODS: Cohort 1 included pregnant women with a double test taken within the study period. The excess serum from each double test was analyzed for SARS-CoV-2 antibodies. Results were correlated to the nuchal translucency thickness and the number of pregnancy losses before or at the time of the first trimester scan. Cohort 2 included women with a pregnancy loss before the gestational age for double test sample. Serum from a blood test taken the day the pregnancy loss was identified was analyzed for SARS-CoV-2 antibodies. The study was conducted at a public university hospital serving ∼12% of pregnant women and births in Denmark. All participants in the study provided written informed consent. MAIN RESULTS AND THE ROLE OF CHANCE: Eighteen (1.8%) women had SARS-CoV-2 antibodies in the serum from the double test suggestive of SARS-CoV-2 infection in early pregnancy. There was no significant difference in nuchal translucency thickness for women testing positive for previous SARS-CoV-2 infection (n = 16) versus negative (n = 966) (P = 0.62). There was no significantly increased risk of pregnancy loss for women with antibodies (n = 1) (OR 3.4, 0.08-24.3 95% CI, P = 0.27). None of the women had been hospitalized due to SARS-CoV-2 infection. None of the women with pregnancy loss prior to the double test (Cohort 2) had SARS-CoV-2 antibodies. LIMITATIONS, REASONS FOR CAUTION: These results may only apply to similar populations and to patients who do not require hospitalization due to SARS-CoV-2 infection. A limitation of the study is that only 1.8% of the study population had SARS-CoV-2 antibodies suggestive of previous infection. WIDER IMPLICATION OF THE FINDINGS: Maternal SARS-CoV-2 infection had no effect on the nuchal translucency thickness and there was no significantly increased risk of pregnancy loss for women with SARS-CoV-2 infection in first trimester pregnancy. Evidence concerning COVID-19 in pregnancy is still limited. These data indicate that infection with SARS-CoV-2 in not hospitalized women does not pose a significant threat in first trimester pregnancies. Follow-up studies are needed to establish any risk to a fetus exposed to maternal SARS-CoV-2 infection. STUDY FUNDING/COMPETING INTEREST(S): Prof. H.S.N. and colleagues received a grant from the Danish Ministry of Research and Education for research of COVID-19 among pregnant women. The Danish government was not involved in the study design, data collection, analysis, interpretation of data, writing of the report or decision to submit the paper for publication. A.I., J.O.-L., J.B.-R., D.M.S., J.E.-F. and E.R.H. received funding from a Novo Nordisk Foundation (NNF) Young Investigator Grant (NNF15OC0016662) and a Danish National Science Foundation Center Grant (6110-00344B). A.I. received a Novo Scholarship. J.O.-L. is funded by an NNF Pregraduate Fellowship (NNF19OC0058982). D.W. is funded by the NNF (NNF18SA0034956, NNF14CC0001, NNF17OC0027594). A.M.K. is funded by a grant from the Rigshospitalet's research fund. H.S.N. has received speaker's fees from Ferring Pharmaceuticals, Merck Denmark A/S and Ibsa Nordic (outside the submitted work). N.l.C.F. has received a grant from Gedeon Richter (outside the submitted work). A.M.K. has received speaker's fee from Merck (outside the submitted work). The other authors did not report any potential conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.


Subject(s)
Abortion, Spontaneous/epidemiology , COVID-19/complications , Fetal Development , Nuchal Translucency Measurement/statistics & numerical data , Pregnancy Complications, Infectious/virology , Abortion, Spontaneous/virology , Adult , Antibodies, Viral/blood , COVID-19/blood , COVID-19/diagnosis , COVID-19/virology , COVID-19 Serological Testing/statistics & numerical data , Cohort Studies , Denmark/epidemiology , Female , Humans , Pregnancy , Pregnancy Complications, Infectious/blood , Pregnancy Complications, Infectious/diagnosis , Pregnancy Trimester, First , SARS-CoV-2/immunology , SARS-CoV-2/isolation & purification
15.
BMC Med Res Methodol ; 20(1): 228, 2020 09 11.
Article in English | MEDLINE | ID: covidwho-751240

ABSTRACT

BACKGROUND: COVID-19, the disease caused by the highly infectious and transmissible coronavirus SARS-CoV-2, has quickly become a morbid global pandemic. Although the impact of SARS-CoV-2 infection in children is less clinically apparent, collecting high-quality biospecimens from infants, children, and adolescents in a standardized manner during the COVID-19 pandemic is essential to establish a biologic understanding of the disease in the pediatric population. This biorepository enables pediatric centers world-wide to collect samples uniformly to drive forward our understanding of COVID-19 by addressing specific pediatric and neonatal COVID-19-related questions. METHODS: A COVID-19 biospecimen collection study was implemented with strategic enrollment guidelines to include patients seen in urgent care clinics and hospital settings, neonates born to SARS-CoV-2 infected mothers, and asymptomatic children. The methodology described here, details the importance of establishing collaborations between the clinical and research teams to harmonize protocols for patient recruitment and sample collection, processing and storage. It also details modifications required for biobanking during a surge of the COVID-19 pandemic. RESULTS: Considerations and challenges facing enrollment of neonatal and pediatric cohorts are described. A roadmap is laid out for successful collection, processing, storage and database management of multiple pediatric samples such as blood, nasopharyngeal and oropharyngeal swabs, sputum, saliva, tracheal aspirates, stool, and urine. Using this methodology, we enrolled 327 participants, who provided a total of 972 biospecimens. CONCLUSIONS: Pediatric biospecimens will be key in answering questions relating to viral transmission by children, differences between pediatric and adult viral susceptibility and immune responses, the impact of maternal SARS-CoV-2 infection on fetal development, and factors driving the Multisystem Inflammatory Syndrome in Children. The specimens in this biorepository will allow necessary comparative studies between children and adults, help determine the accuracy of current pediatric viral testing techniques, in addition to, understanding neonatal exposure to SARS-CoV-2 infection and disease abnormalities. The successful establishment of a pediatric biorepository is critical to provide insight into disease pathogenesis, and subsequently, develop future treatment and vaccination strategies.


Subject(s)
Betacoronavirus , Coronavirus Infections/diagnosis , Pneumonia, Viral/diagnosis , Specimen Handling/methods , Adolescent , COVID-19 , Child , Child, Preschool , Coronavirus Infections/immunology , Coronavirus Infections/transmission , Female , Fetal Development , Hospitalization , Humans , Infant , Infant, Newborn , Male , Pandemics , Pneumonia, Viral/immunology , Pneumonia, Viral/transmission , SARS-CoV-2
17.
Front Immunol ; 11: 1672, 2020.
Article in English | MEDLINE | ID: covidwho-685034

ABSTRACT

Pregnancy comprises a unique immunological condition, to allow fetal development and to protect the host from pathogenic infections. Viral infections during pregnancy can disrupt immunological tolerance and may generate deleterious effects on the fetus. Despite these possible links between pregnancy and infection-induced morbidity, it is unclear how pregnancy interferes with maternal response to some viral pathogens. In this context, the novel coronavirus (SARS-CoV-2) can induce the coronavirus diseases-2019 (COVID-19) in pregnant women. The potential risk of vertical transmission is unclear, babies born from COVID-19-positive mothers seems to have no serious clinical symptoms, the possible mechanisms are discussed, which highlights that checking the children's outcome and more research is warranted. In this review, we investigate the reports concerning viral infections and COVID-19 during pregnancy, to establish a correlation and possible implications of COVID-19 during pregnancy and neonatal's health.


Subject(s)
Betacoronavirus , Coronavirus Infections/immunology , Coronavirus Infections/transmission , Pneumonia, Viral/immunology , Pneumonia, Viral/transmission , Pregnancy Complications, Infectious/immunology , Pregnancy Complications, Infectious/virology , COVID-19 , Child, Preschool , Coronavirus Infections/blood , Coronavirus Infections/virology , Cytokines/blood , Female , Fetal Development/immunology , Humans , Infant , Infant, Newborn , Infectious Disease Transmission, Vertical , Mothers , Pandemics , Pneumonia, Viral/blood , Pneumonia, Viral/virology , Pregnancy , Pregnancy Complications, Infectious/blood , SARS-CoV-2
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