Congenital and Intrapartum SARS-CoV-2 Infection in Neonates: Hypotheses, Evidence and Perspectives.

INTRODUCTION: Both intrauterine and intrapartum mother-to-child transmission of SARS-CoV-2 have been reported. However, there is still disagreement as to the likelihood and frequency of such vertical transmission. OBJECTIVE: Summarize and analyze the published evidence on forms of SARS-CoV-2 vertical transmission (either intrauterine or intrapartum). EVIDENCE ACQUISITION: We carried out a review of literature published in English and Spanish from January 1, 2020 through October 30, 2020. Search engines included PubMed/MEDLINE, SciELO, LILACS, Cochrane, Google Scholar, ResearchGate and medRxiv. There were no restrictions concerning type of study. The review included 48 original research articles, 11 review articles, a meta-analysis, 2 pre-published articles, 15 systematic reviews, and 10 editorials or comments. DEVELOPMENT: Medical thinking on congenital or intrapartum maternal-fetal/neonatal transmission of SARS-CoV-2 has evolved from preliminary evidence that was divided as to whether these forms of vertical transmission were even possible to current evidence support ing both forms of transmission and hypothesizing as to the mechanisms that guide them. The presence of the SARS-CoV-2 virus in maternal, placental, fetal or neonatal tissues has been demonstrated by RT-PCR, specific immunoglobulin detection tests, immunostaining and in-situ hybridization. It is estimated that infections acquired either congenitally or intrapartum occur in 1.8%-8.0% of newborns born to women who test positive for COVID-19 at the end of their pregnancies. This review found 53 neonates who were diagnosed with COVID-19 in the first 48 hours of life by either RT-PCR or specific IgM tests. According to criteria outlined in this review, the timing of infection corresponded to congenital or intrapartum transmission in 39.6% (21/53) of COVID-19-positive newborns, to postpartum transmission in 15.1% (8/53) and remains unspecified in 45.3% (24/53). CONCLUSIONS: Congenital and intrapartum SARS-CoV-2 infection in the fetus/newborn is possible, but rare. International collaborative studies using common epidemiological surveillance instruments would allow for a more precise specification of the frequency of congenital and intrapartum SARS-CoV-2 infection at the population level.

Coronavirus and birth in Italy: results of a national population-based cohort study.

INTRODUCTION: The study was implemented to provide guidance to decision-makers and clinicians by describing hospital care offered to women who gave birth with confirmed SARS-CoV-2 infection. MATERIALS AND METHODS: National population-based prospective cohort study involving all women with confirmed SARS-CoV-2 infection who gave birth between February 25 and April 22, 2020 in any Italian hospital. RESULTS: The incidence rate of confirmed SARS-CoV-2 infection in women who gave birth was 2.1 per 1000 maternities at a national level and 6.9/1000 in the Lombardy Region. Overall one third of the women developed a pneumonia and 49.7% assumed at least one drug against SARS-CoV-2 infection. Caesarean rate was 32.9%, no mothers nor newborns died. Six percent of the infants tested positive for SARS-CoV-2 at birth. CONCLUSIONS: Clinical features and outcomes of COVID-19 in women who gave birth are similar to those described for the general population, most women developing mild to moderate illness.

Congenital and perinatal cytomegalovirus lung infection.

BACKGROUND: Cytomegalovirus (CMV) pneumonitis may be severe, even lethal, following congenital infection or in premature infants with perinatal infection. OBJECTIVE: To review the epidemiological, pathogenetic, clinical and therapeutic features of prenatal and perinatal CMV lung diseases. METHODS: Evaluation of all published papers listed on PubMed describing CMV pneumonitis in infants. RESULTS: CMV is frequent and severe in immunosuppressed infants but infrequent in full-term neonates and occurs more frequently after perinatal than after congenital infection, particularly in premature infants. In premature infants, CMV infection is often protracted and causes a diffuse interstitial pneumonitis leading to fibrosis and bronchopulmonary dysplasia (BPD). Congenital CMV infection should also be considered in newborns with severe acute respiratory distress syndrome and refractory respiratory failure with progression to early chronic lung disease. The association between breast milk-transmitted CMV and development of cystic lung disease and Wilson-Mikity syndrome has also been reported. Data on the efficacy of antiviral therapy for infants with respiratory CMV diseases are lacking and only anecdotal case reports are available. CONCLUSIONS: Persistent CMV infection appears to cause a diffuse necrotizing pneumonitis with fibrosis leading to BPD, in both immunocompromised or preterm infants and, less frequently in immunocompetent infants. The role of antiviral therapy remains to be elucidated.

A baby, a virus, and a rat.

The authors present a case initially thought to be a child abuse homicide that, after complete autopsy and thorough investigation, was determined to be caused by a viral infection and complicated by postmortem animal activity. Neonatal herpes simplex infection and postmortem skin defects are discussed.

Cytomegalovirus associated neonatal pneumonia and Wilson-Mikity syndrome: a causal relationship?

Lung injury caused by intrauterine inflammation has recently been strongly implicated in the pathogenesis of Wilson-Mikity syndrome (WMS). This article supports this theory by suggesting a causative role of intrauterine cytomegalovirus (CMV) infection for the development of WMS. A male premature infant, born at 33 weeks of gestational age, developed chronic lung disease compatible with WMS and diagnostic evaluation was positive for CMV infection. High-resolution computed tomography scan and lung histology revealed typical features of WMS in association with signs of interstitial pneumonia. CMV was found in urine, breastmilk, bronchoalveolar lavage material and lung tissue from open lung biopsy. Follow-up after treatment with ganciclovir and steroids showed resolving lung disease at the age of 6, 10 and 16 months, with lung function signs of mild obstruction. Assuming that a chance coexistence of cytomegalovirus pneumonia and Wilson-Mikity syndrome is rather unlikely, it is possible that intrauterine cytomegalovirus infection caused a pattern of lung injury consistent with Wilson-Mikity syndrome. Further cases of Wilson-Mikity syndrome should be investigated as to a possible role of congenital infection.

[Successful treatment of therapy refractory shock lung in a newborn infant with congenital varicella using extracorporeal membrane oxygenation]. / Erfolgreiche Behandlung einer therapierefraktären Schocklunge bei einem Neugeborenen mit connatalen Varicellen mittels Extracorporaler Membranoxygenierung.

A newborn with congenital varicella complicated by varicella pneumonia was transferred to our hospital on day 16 of life for the consideration of extracorporeal membrane oxygenation (ECMO). The newborn received varicella zoster immunoglobulin 13 hours after birth since the mother developed a varicella exanthema two days before delivery. On day 10 of life the newborn became clinically symptomatic with red macules and pustules. The chest roentgenogram revealed reticular pulmonary infiltrates in the right upper lobe. Antibacterial chemotherapy was initiated. In the following days the cutaneous lesions progressed, and respiratory symptoms like tachypnoea and oxygen dependence occurred. Chest roentgenograms revealed diffuse reticular and patchy pulmonary infiltrates. On day 14 of life antiviral chemotherapy with acyclovir was started. ECMO was initiated in the veno-arterial mode on day 17 due to severe respiratory failure despite maximal conventional assisted ventilation and carried out for 14 days. With the age of 10 weeks he was discharged from the hospital with mild chronic lung disease without oxygen requirements and without neurological handicap. ECMO might be considered as life saving support in newborns with severe congenital varicella, considered to have a high mortality risk.

[Perinatal herpes infection. Clinical aspects--therapy--follow-up]. / Die perinatale Herpesinfektion. Klinik--Therapie--Verlauf.

Herpes simplex virus may cause serious infections in neonates. In case of foetal infection in the first trimenon, abortions, stillbirth, prematurity, intrauterine growth retardation (not obligatory) and various malformations may result. Neonatal HSV infection is mostly the consequence of intrapartum virus acquisition during passage through the birth canal. The infection is mostly localised on the skin, at the eyes or the mouth or disseminated with or without HSV meningoencephalitis. It is difficult to establish the diagnosis, because neonatal herpes disease in the early stage is not easy to distinguish from other diseases in the newborn such as RDS, NEC or ICH. Antiviral therapy with aciclovir is the treatment of choice and seems to improve the outcome of neonatal herpes. Prognosis depends on early therapy. Treatment should be initiated in relation to clinical findings, because available diagnostic techniques do not always permit an early detection of the disease.

[Severe forms of herpes simplex in newborn infants]. / Tiazhelye formy gerpes-virusnoi infektsii u novorozhdennykh.

Generalized herpetic infection in the newborn runs its course in association with cerebral lesions as well as with injuries to the lungs, heart and liver. The infection diagnosis should take into account the mother's epidemiological anamnesis, the clinical manifestations in the child and the results of the simultaneous use of several methods (fluorescent antibody test, IEA, virological test). Of paramount importance is the simultaneous examination of the mother. Of no less importance is echoencephalography, namely the detection of cysts in white matter of the frontal lobes.

[Ultrastructural pathology of congenital infection provoked by respiratory viruses]. / Ul'trastrukturnaia patologiia vrozhdennoi infektsii, vyzvannoi respiratornymi virusami.

The ultrastructural study of fetal and newborn lungs in the intrauterine infection caused by respiratory viruses showed the virus reproduction to take place in type II alveolocytes with destructive changes in cell organelles. Each type of virus results in a certain picture of ultrastructural changes. Progressing cell organelles destruction with an intensive cytoplasm vacuolization and virion presence in the cytoplasmic matrix and on the endoplasmic network membranes is characteristic for influenza. Severe cytoplasm vacuolization with lipid formation, homogenization and condensation of membranous bodies, nuclear pyknosis are observed in parainfluenza. RS-infection is characterized by virion formation on the cytoplasmic cell membrane, numerous deformed membranous bodies, filling intercellular spaces and alveolar lumen with rough granular electron-dense material, massive release of organelles into the alveolar lumen. Edema and vacuolization of endothelium, edema and focal disappearance of basal membrane are observed in the capillary walls.