Pregnant women with coronavirus disease 2019 and intrauterine vertical transmission: a systematic review / Gestantes con enfermedad por coronavirus 2019 y transmisión vertical intrauterina: una revisión sistemática

Resumen Introducción . La enfermedad por coronavirus 2019 (COVID-19) es una enfermedad de las vías respiratorias potencialmente severa, producida por el coronavirus tipo 2 causante del síndrome respiratorio agudo grave (SARS-CoV-2). La transmisión intrauterina de la madre al feto es un motivo de debate. Objetivo. Identificar la evidencia disponible de transmisión vertical intrauterina en la gestante con COVID-19. Metodología. Revisión sistemática utilizando los términos: "Vertical transmission" AND "COVID-19" OR "SARS-CoV-2". Las bases de datos consultadas fueron MEDLINE/PubMed, Science Direct, Clinical Key, LILACS, SciELO, Google Scholar, medRxiv y SciELO Preprints. Resultados . Se identificaron 30 estudios que cumplieron los criterios de selección e incluían 476 gestantes. La infección se encontró en 9 neonatos (1,9%), el hisopado faríngeo en ellos se hizo dentro de las 48 horas del nacimiento. En 4 de ellos no se buscó la presencia del virus en otros tejidos y fluidos maternos, mientras que en los 5 casos restantes se identificó el ARN en la placenta de tres de ellos, en dos se encontró en el líquido amniótico y en uno en el canal vaginal. Los estudios fueron muy heterogéneos; así podemos mencionar la variedad de la población reportada, el número de muestras y momento de la toma en los neonatos, la falta de muestreo en los tejidos y fluidos maternos. Conclusiones . La transmisión vertical intrauterina del SARS-CoV-2 no ha sido demostrada de forma contundente debido a que la mayoría de las gestantes con la enfermedad ha tenido neonatos con la prueba molecular negativa (98,1%). Sin embargo, la heterogeneidad de los estudios tampoco permite descartar esta posibilidad.

ABSTRACT Introduction: Coronavirus disease 2019, also called COVID-19, is a potentially severe respiratory disease originated by the type 2 coronavirus that causes severe acute respiratory syndrome (SARS-CoV-2). Intrauterine transmission from mother to fetus is a matter of debate. Objective: To identify the available evidence of vertical intrauterine transmission in pregnant women with COVID-19. Methodology: A systematic review was performed using the terms: "Vertical transmission" AND "COVID-19" OR "SARSCoV-2" NOT "Review *". The databases consulted were MEDLINE/PubMed, Science Direct, Clinical Key, LILACS, SciELO, Google Scholar, medRxiv and SciELO Preprints. Results: Thirty primary studies met the selection criteria and included 476 pregnant women. Infection was found in 9 neonates (1.9%) in whom pharyngeal swabs were done within 48 hours of birth. In four of them the presence of the virus was not looked for in other maternal tissues and fluids; in the remaining 5 cases, the virus RNA was identified in the placenta of three of them, in two it was found in the amniotic fluid and in one in vaginal secretion. Studies were very heterogeneous, with great variety of the reported population, the number of samples and time of collection in neonates, the lack of sampling in maternal tissues and fluids. Conclusions: Vertical intrauterine transmission of SARS-CoV-2 has not been conclusively demonstrated in pregnant women with COVID-19 as the majority of patients with the disease had newborns with negative molecular test (98,1%). The heterogeneity of the studies does not allow to rule out this possibility either.

Fetal inflammatory response syndrome and postnatal multi-system inflammatory syndrome in COVID-19-positive neonates

Increasing incidences of COVID-19 in pregnant women, and lack of data regarding vertical transmission and extent of disease in newborns, has raised a concern towards it. The fetal inflammatory response syndrome (FIRS) and multisystem inflammatory syndrome in neonates (MIS-N) is also not a well-known entity till now. This case report of two newborns is an effort to describe the different clinical scenarios of COVID-19 and its response to the treatment. The first case suggests the possible in utero transmission which is a rare mode of infection as evident from previous data and the inflammatory response, getting treated by the use of immunotherapy and antivirals. The second case suggest the horizontal transmission acquired postnatally and the severity of multisystem inflammatory syndrome in neonate which could not be revived in spite all the efforts in treatment.

Transmission of COVID-19 From an Asymptomatic Mother to Fetus Leading to Death of Neonate From Pneumonia.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) responsible for the coronavirus disease 2019 (COVID-19) pandemic has rarely impacted neonates. When infection does occur, it is typically asymptomatic. We describe a case of a neonate born to a 25-year-old mother who was COVID-19 positive but asymptomatic. An emergent cesarean section was performed during week 30 of gestation due to category three fetal heart tracings. The neonate, unfortunately, died on the day of life 12 from respiratory distress secondary to severe COVID-19 pneumonia. This is an important case that illustrates the deleterious impact COVID-19 infection can have on neonates. It is a unique case of the compassionate use of remdesivir for a neonate. The patient's respiratory decline soon after birth, lends support that the virus responsible for COVID-19 can be transmitted vertically.

Immediate Pre-Partum SARS-CoV-2 Status and Immune Profiling of Breastmilk: A Case-Control Study.

Objetive: To address the prevalence of SARS-CoV-2 and the evolutionary profile of immune compounds in breastmilk of positive mothers according to time and disease state. Methods: Forty-five women with term pregnancies with confirmed non-severe SARS-CoV-2 infection (case group), and 96 SARS-CoV-2 negative women in identical conditions (control group) were approached, using consecutive sample. Weekly (1st to 5th week postpartum) reverse transcription polymerase chain reaction (RT-PCR) in nasopharyngeal swabs (cases) and breastmilk (cases and controls) were obtained. Concentration of cytokines, chemokines, and growth factors in breastmilk (cases and controls) were determined at 1st and 5th week post-partum. Results: Thirty-seven (study group) and 45 (control group) women were enrolled. Symptomatic infection occurred in 56.8% of women in the study group (48% fever, 48% anosmia, 43% cough). SARS-CoV-2 RNA was not found in breastmilk samples. Concentrations of cytokines (IFN-γ, IL-1ra, IL-4, IL-6, IL-9, IL-13, and TNF-α) chemokines (eotaxin, IP-10, MIP-1α, and RANTES) and growth factors (FGF, GM-CSF, IL7, and PDGF-BB) were higher in breastmilk of the study compared with the control group at 1st week postpartum. Immune compounds concentrations decreased on time, particularly in the control group milk samples. Time of nasopharyngeal swab to become negative influenced the immune compound concentration pattern. Severity of disease (symptomatic or asymptomatic infection) did not affect the immunological profile in breast milk. Conclusions: This study confirms no viral RNA and a distinct immunological profile in breastmilk according to mother's SARS-CoV-2 status. Additional studies should address whether these findings indicate efficient reaction against SARS-CoV-2 infection, which might be suitable to protect the recipient child.

Possible Vertical Transmission From an Unsuspected SARS-CoV-2-Infected Mother to Her Newborn.

Although the Coronavirus Disease 2019 (COVID-19) has been found to have multiple routes of transmission, limited data exist on whether the vertical transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can occur from asymptomatic infected mothers to their newborns during pregnancy. We report a full-term newborn girl who was found to be positive for COVID-19 at 24 hours of life and subsequently symptomatic with fever, tachycardia, tachypnea, elevated lactate dehydrogenase, and elevated total bilirubin. The newborn was delivered by a mother who was not suspected of having COVID-19 before giving birth, but who developed fever and dyspnea five hours after delivery and was found to be positive for COVID-19. Upon further history collection, the mother reported recent mild nasal congestion in the days prior to delivery. This case highlights that the vertical transmission of COVID-19 to a newborn may occur late during the third trimester from a mother who was not suspected of having the infection. All pregnant women may need to be screened for COVID-19 symptoms, including non-specific symptoms, prior to admission for labor and delivery floors in order to perform diagnostic tests and recommended safety precautions to keep newborns and hospital personnel safe.

Coronavirus Disease 2019 (COVID-19): A Pediatric Perspective.

Coronavirus disease 2019, the new public health emergency that originated in China, is spreading rapidly across the globe with limited tools to confine this growing pandemic. The virus, severe acute respiratory syndrome coronavirus 2, is transmitted by droplet infection from person to person. Our current understanding of the disease spectrum is limited. The proportion of infected children is significantly less compared to adults with the majority of them showing mild symptoms. More than half of symptomatic children present with fever and cough. However, the extent of asymptomatic infection in children and the role they play in community transmission is still undetermined. Although there are case reports of neonates infected with severe acute respiratory syndrome coronavirus 2, vertical transmission from infected mother to new-born is yet to be proven. The disease is confirmed by demonstration of the virus by real-time reverse transcriptase-polymerase chain reaction in respiratory secretions. Due to the lack of specific antiviral agents, we rely on infection-control measures to prevent disease spread and on supportive care for infected ones. This article has summarized the clinical characteristics of children with coronavirus disease 2019 based on published case reports.