Protocol for a prospective, hospital-based registry of pregnant women with SARS-CoV-2 infection in India: PregCovid Registry study

IntroductionPregnant women are at increased risk of contracting coronavirus disease 2019 (COVID-19) due to several factors and therefore require special attention. However, the consequences of the COVID-19 pandemic on pregnant women and their newborns remain uncharted. The PregCovid registry aims to document the impact of SARS-CoV-2 infection on pregnant, post-partum women and their newborns. The aim of the registry is also to determine mother-to-child transmission of SARS-CoV-2 infection in India. Methods and analysisPregCovid is a hospital-based registry for capturing information of pregnant, post-partum women with COVID-19 and their newborns in India. Medical case records of pregnant and post-partum women with laboratory-confirmed diagnoses of COVID-19 will be captured in real-time using an online electronic patient record (EPR) software. The frequency of each symptom will be calculated. The laboratory data will be analyzed for calculating the frequency of laboratory parameters consistently higher in women with COVID- The adverse pregnancy and neonatal outcomes will be analyzed and their frequency will be calculated. Response to treatment will be analyzed for frequency calculation (number of women treated with different treatment regimens). The mother-to-child transmission data will be analyzed from the RT-PCR and/ antibody data of neonatal and maternal samples tested wherever the information is available. The registry data will be crucial for developing strategies for reducing the adverse impact of COVID-19 on pregnant women and their new-born. Ethics and disseminationThe study is approved by the Institutional Ethics Committee of ICMR-National Institute for Research in Reproductive Health (#55/2020), BYL Nair Hospital, Mumbai, India (# 63/2020); and all the 18 participating study sites under Medical Education and Drugs Department of Government of Maharashtra. The Institutional Ethics Committees granted a waiver of consent as the data is collected from the medical case records. Trial registration numberCTRI/2020/05/025423 Article summaryO_ST_ABSStrengths and limitations of this studyC_ST_ABSO_LIThe PregCovid registry is a hospital-based registry at dedicated COVID-19 hospitals in India. The registry will help to identify new epidemiological, clinical characteristics, obstetrics outcomes associated with pregnant women and/post-partum women with COVID-19 in India. The study will also generate information on clinical presentations and outcomes of neonatal born to mothers with COVID-19 in India. C_LIO_LIPregCovid registry will provide evidence of mother to child transmission of SARS-CoV-2 infection in Indian women C_LIO_LIThe evidence on unusual presentations of COVID-19 in pregnant and post-partum women will be generated. C_LIO_LIThe follow-up of participants is only till the discharge from the hospital. Long-term follow-up is not included in the study. C_LI

Survival upon Staphylococcus aureus mediated wound infection in Caenorhabditis elegans and the mechanism entailed.

Infection following injury is one of the major threats which causes huge economic burden in wound care management all over the world. Injury often results with poor healing when coupled by following infection. In contrast to this, we observed enhanced survival of wound infected worms compared to wounded worms in Caenorhabditis elegans wound model while infecting with Staphylococcus aureus. Hence, the study was intended to identify the mechanism for the enhanced survival of wound infected worms through LCMS/MS based high throughput proteomic analysis. Bioinformatics analyses of the identified protein players indicated differential enrichment of several pathways including MAPK signaling, oxidative phosphorylation and phosphatidylinositol signaling. Inhibition of oxidative phosphorylation and phosphatidylinositol signaling through chemical treatment showed complete reversal of the enhanced survival during wound infection nevertheless mutant of MAPK pathway did not reverse the same. Consequently, it was delineated that oxidative phosphorylation and phosphatidylinositol signaling are crucial for the survival. In this regard, elevated calcium signals and ROS including O- and H2O2 were observed in wounded and wound infected worms. Consequently, it was insinuated that presence of pathogen stress could have incited survival in wound infected worms with the aid of elevated ROS and calcium signals.

Persistence of SARS-CoV-2 in the first trimester placenta leading to vertical transmission and fetal demise from an asymptomatic mother

Coronaviruses infect the respiratory tract and are known to survive in these tissues during the clinical course of infection. However, how long can SARS-CoV-2 survive in the tissues is hitherto unknown. Herein, we report a case where the virus is detected in the first trimester placental cytotrophoblast and syncytiotrophoblasts five weeks after the asymptomatic mother cleared the virus from the respiratory tract. This first trimester placental infection was vertically transmitted as the virus was detected in the amniotic fluid and fetal membranes. This congenitally acquired SARS-CoV-2 infection was associated with hydrops and fetal demise. This is the first study providing concrete evidences towards persistent tissue infection of SARS-CoV-2, its congenital transmission in early pregnancy leading to intrauterine fetal death.

Pregnancy outcomes, Newborn complications and Maternal-Fetal Transmission of SARS-CoV-2 in women with COVID-19: A systematic review

ObjectiveThe aim of this systematic review was to examine the maternal and fetal outcomes in pregnant women with COVID-19 and also assess the incidence of maternal-fetal transmission of SARS CO-V-2 infection. Data sourcesWe searched PUMBED. Medline, Embase, MedRxiv and bioRxiv databases upto 3rd May 2020 utilizing combinations of word variants for "coronavirus" or "COVID-19" or "severe acute respiratory syndrome" or "SARS-COV-2" and "pregnancy". We also included data from preprint articles. Study eligibility criteriaOriginal case reports and case series on pregnant women with diagnosis of SARS-CoV-2 infection. Study appraisal and synthesis methodsWe included 50 studies reporting the information on 441 pregnant women and 391 neonates. The primary outcome measures were maternal health characteristics and adverse pregnancy outcomes, neonatal outcomes and SARS-CoV-2 infection in neonates was extracted. Treatments given to pregnant women with COVID-19 were also recorded. ResultsOut of 441 women affected by COVID-19 in pregnancy, 387 women have delivered. There are nine maternal deaths reported. In pregnant women with COVID-19, the most common symptoms were fever (56%), cough (43%), myalgia (19%), dyspnea (18%) and diarrhea (6%). Pneumonia was diagnosed by CT scan imaging in 96 % of COVID-19 pregnant women. Pregnancy complications included delivery by cesarean section (80%), preterm labor (26%), fetal distress (8%) and premature rupture of membranes (9%). Six still births (2%) are reported. The most common co-morbidities associated with pregnant women with COVID-19 were hypertensive disorders (10%), diabetes (9%), placental disorders (2%), co-infections (3%), scarred uterus (3%) and hypothyroidism (3%). Amongst the neonates of COVID-19 mothers, preterm birth (25%), respiratory distress syndrome (8%), pneumonia (8%) were reported. There were four neonatal deaths reported. Vertical transmission rate of SARS-CoV-2 is estimated to be 8%. ConclusionIn pregnant women with COVID-19, hypertensive disorders and diabetes are common comorbidities and there is a risk of preterm delivery and maternal death. Amongst the neonates born to mothers with COVID-19, respiratory distress syndrome and pneumonia are common occurrence. There are reports of still births and neonatal deaths. There is an evidence of vertical transmission of SARS-CoV-2 infection in women with COVID-19.