Neonatal Outcomes in Pregnant Women Infected with COVID-19 in Babol, North of Iran: A Retrospective Study with Short-Term Follow-Up.

During the coronavirus disease 2019 (COVID-19) pandemic, the number of pregnant women and neonates suffering from COVID-19 increased. However, there is a lack of evidence on clinical characteristics and neonatal outcomes in pregnant women with COVID-19. We evaluated short-term outcomes (4 weeks postdischarge) and symptoms in neonates born to mothers infected with COVID-19. In this retrospective cohort study, we included all neonates born to pregnant women with COVID-19 admitted to Ayatollah Rohani Hospital, Babol, Iran, from February 10 to May 20, 2020. Clinical features, treatments, and neonatal outcomes were measured. Eight neonates were included in the current study. The mean gestational age and birth weight of newborns were 37 ± 3.19 weeks (30₊6-40) and 3077.50 ± 697.64 gr (1720-3900), respectively. Apgar score of the first and fifth minutes in all neonates was ≥8 and ≥9 out of 10, respectively. The most clinical presentations in symptomatic neonates were respiratory distress, tachypnea, vomiting, and feeding intolerance. This manifestation and high levels of serum C-reactive protein (CRP) in three infants are common in neonatal sepsis. The blood culture in all of them was negative. They have been successfully treated with our standard treatment. Our pregnant women showed a pattern of clinical characteristics and laboratory results similar to those described for nonpregnant COVID-19 infection. This study found no evidence of intrauterine or peripartum transmission of COVID-19 from mother to her child. Furthermore, the long-term outcomes of neonates need more study.

Síndrome do desconforto respiratório agudo associada à COVID-19 tratada com DEXametasona (CoDEX): delineamento e justificativa de um estudo randomizado / COVID-19-associated ARDS treated with DEXamethasone (CoDEX): study design and rationale for a randomized trial

RESUMO Objetivo: A infecção causada pelo coronavírus da síndrome respiratória aguda grave 2 (SARS-CoV-2) disseminou-se por todo o mundo e foi categorizada como pandemia. As manifestações mais comuns da infecção pelo SARS-CoV-2 (doença pelo coronavírus 2019 - COVID-19) se referem a uma pneumonia viral com graus variáveis de comprometimento respiratório e até 40% dos pacientes hospitalizados, que podem desenvolver uma síndrome do desconforto respiratório agudo. Diferentes ensaios clínicos avaliaram o papel dos corticosteroides na síndrome do desconforto respiratório agudo não relacionada com COVID-19, obtendo resultados conflitantes. Delineamos o presente estudo para avaliar a eficácia da administração endovenosa precoce de dexametasona no número de dias vivo e sem ventilação mecânica nos 28 dias após a randomização, em pacientes adultos com quadro moderado ou grave de síndrome do desconforto respiratório agudo causada por COVID-19 provável ou confirmada. Métodos: Este é um ensaio pragmático, prospectivo, randomizado, estratificado, multicêntrico, aberto e controlado que incluirá 350 pacientes com quadro inicial (menos de 48 horas antes da randomização) de síndrome do desconforto respiratório agudo moderada ou grave, definida segundo os critérios de Berlim, causada por COVID-19. Os pacientes elegíveis serão alocados de forma aleatória para tratamento padrão mais dexametasona (Grupo Intervenção) ou tratamento padrão sem dexametasona (Grupo Controle). Os pacientes no Grupo Intervenção receberão dexametasona 20mg por via endovenosa uma vez ao dia, por 5 dias, e, a seguir, dexametasona por via endovenosa 10mg ao dia por mais 5 dias, ou até receber alta da unidade de terapia intensiva, o que ocorrer antes. O desfecho primário será o número de dias livres de ventilação mecânica nos 28 dias após a randomização, definido como o número de dias vivo e livres de ventilação mecânica invasiva. Os desfechos secundários serão a taxa de mortalidade por todas as causas no dia 28, a condição clínica no dia 15 avaliada com utilização de uma escala ordinal de seis níveis, a duração da ventilação mecânica desde a randomização até o dia 28, a avaliação com o Sequential Organ Failure Assessment Score após 48 horas, 72 horas e 7 dias, e o número de dias fora da unidade de terapia intensiva nos 28 dias após a randomização.

Abstract Objective: The infection caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spreads worldwide and is considered a pandemic. The most common manifestation of SARS-CoV-2 infection (coronavirus disease 2019 - COVID-19) is viral pneumonia with varying degrees of respiratory compromise and up to 40% of hospitalized patients might develop acute respiratory distress syndrome. Several clinical trials evaluated the role of corticosteroids in non-COVID-19 acute respiratory distress syndrome with conflicting results. We designed a trial to evaluate the effectiveness of early intravenous dexamethasone administration on the number of days alive and free of mechanical ventilation within 28 days after randomization in adult patients with moderate or severe acute respiratory distress syndrome due to confirmed or probable COVID-19. Methods: This is a pragmatic, prospective, randomized, stratified, multicenter, open-label, controlled trial including 350 patients with early-onset (less than 48 hours before randomization) moderate or severe acute respiratory distress syndrome, defined by the Berlin criteria, due to COVID-19. Eligible patients will be randomly allocated to either standard treatment plus dexamethasone (Intervention Group) or standard treatment without dexamethasone (Control Group). Patients in the intervention group will receive dexamethasone 20mg intravenous once daily for 5 days, followed by dexamethasone 10mg IV once daily for additional 5 days or until intensive care unit discharge, whichever occurs first. The primary outcome is ventilator-free days within 28 days after randomization, defined as days alive and free from invasive mechanical ventilation. Secondary outcomes are all-cause mortality rates at day 28, evaluation of the clinical status at day 15 assessed with a 6-level ordinal scale, mechanical ventilation duration from randomization to day 28, Sequential Organ Failure Assessment Score evaluation at 48 hours, 72 hours and 7 days and intensive care unit -free days within 28.

[Congenital cytomegalovirus infection manifesting as neonatal respiratory distress in an HIV-exposed uninfected newborn]. / Pneumopathie congénitale à cytomégalovirus chez un nouveau-né à terme né de mère séropositive pour le VIH.

BACKGROUND: Cytomegalovirus (CMV) is one of the most common intrauterine infections, affecting approximately 1% of all live births. There are few reports on congenital CMV infections manifesting as isolated pneumonitis. CASE REPORT: We report a case of congenital CMV with neonatal respiratory distress affecting an HIV-exposed uninfected infant. This infant required noninvasive ventilation beginning within the first 15min of life. The initial chest X-ray showed diffuse bilateral ground-glass opacifications. Bacterial infection, meconium aspiration and hyaline membrane disease were excluded. Salivary quantitative CMV PCR was positive (2,342,261IU/mL) and serum viral load for CMV was low (476IU/mL). Bronchoalveolar lavage (BAL) performed on day 12 for quantitative CMV PCR was significantly positive (1,045,942IU/mL). Intravenous ganciclovir treatment was started on day 14 (7.5mg/kg/12h) for 2 weeks and oral valganciclovir (15mg/kg/12h) was given for 4 weeks afterwards. Ventilatory support was stopped on day 18. HIV serum viral load was negative on day 30. DISCUSSION: Congenital CMV infection can present as isolated pneumonitis with persistent neonatal respiratory symptoms, emphysematous lung disease, or persistent pulmonary hypertension. If this diagnosis is suspected, and even if CMV viremia remains low, BAL with quantitative CMV PCR must be performed to ascertain the diagnosis and indicate antiviral treatment. HIV-exposed uninfected infants have higher rates of congenital CMV infection when the mother's CD4 rate is<200/mm3. Most cases of CMV transmission in HIV-exposed uninfected infants have occurred by maternal endogenous reactivation or reinfection.

Importance of diagnostic work-up of Guillain-Barré syndrome in pregnancy.

We report a full-term neonate presenting with symptomatic congenital cytomegalovirus (CMV) infection with hepatosplenomegaly, 'blueberry muffin' rash, intracranial calcifications, thrombocytopenia and respiratory distress. Maternal history was relevant for Guillain-Barré syndrome (GBS) during the first trimester of pregnancy. CMV infection is an important cause of GBS; thus, women presenting GBS during pregnancy should be screened for CMV infection. If positive, they may benefit from specialised monitoring and treatment in the antenatal period, which may decrease the risk of major neurodevelopmental sequelae of congenital CMV in the neonate.

[Cytomegalovirus: congenital infection and clinical presentation in infants with respiratory distress syndrome]. / Citomegalovirus: infección congénita y presentacion clínica en recién nacidos con síndrome de dificultad respiratoria.

BACKGROUND: Respiratory distress syndrome (RDS) is a multifactorial and common disease that varies from 15 to 50 % in the newborn, causing 50 % of mortality. The RDS may be associated with bacterial and viral infections, and one of the most common viral agents is the cytomegalovirus (CMV). In the neonatal period the virus incidence goes from 0.4 to 2.5 % with a seroprevalence of 50 to 75 %; the incidence of infection in newborn with RDS is unknown. The objective was to determine the frequency of CMV infection in neonates with RDS and identify the risk factors associated with infection. METHODS: The CMV-DNA was identified in plasma by quantitative PCR; maternal and neonatal variables that defined the clinical findings were analyzed by logistic regression.The CMV-DNA was identified in plasma by quantitative PCR; maternal and neonatal variables that defined the clinical findings were analyzed by logistic regression. RESULTS: The frequency of CMV infection in 197 infants with RDS was 8.6 % (95 % CI, 4.7-12.5). The significant variables in newborn were: neutropenia (p = 0.012), thrombocytopenia (p = 0.021), mottled skin (p = 0.03), and the maternal significant variable was cervicovaginitis (p = 0.05). CONCLUSIONS: We reported for the first time the highest frecuency of CMV infection in newborns with RDS and the association of various risk factors with CMV infection.

Introducción: el síndrome de dificultad respiratoria (SDR) es una enfermedad común multifactorial que varía del 15 al 50 % en el recién nacido (RN), y la mortalidad es de 50 %. Puede estar asociado a infecciones bacterianas y virales, una de las más frecuentes: el citomegalovirus (CMV). En el periodo neonatal la incidencia de infección por CMV es de 0.4 a 2.5 % y la seroprevalencia de 50 a 75 %; se desconoce la incidencia de infección en los RN. El objetivo fue determinar la frecuencia de infección por CMV en recién nacidos con SDR e identificar factores de riesgo asociados a infección. Métodos: el DNA-CMV fue identificado en plasma por reacción en cadena de la polimerasa (PCR) cuantitativa, y las variables maternas y neonatales que definieron el cuadro clínico fueron analizadas por regresión logística. Resultados: la frecuencia de infección por CMV en 197 RN con SDR fue de 8.6 % (IC 95 % 4.7-12.5). Las variables significativas en los RN fueron: neutropenia (p = 0.012), trombocitopenia (p = 0.021), piel marmórea (p = 0.03) y la variable materna significativa fue cervicovaginitis (p = 0.05). Conclusiones: se reporta por primera vez la frecuencia más alta de infección por CMV en RN con SDR y la asociación de varios factores de riesgo con la infección por CMV.

[Neonatal parechovirus infection, fever, irritability and myositis]. / Infection à parechovirus du jeune nourrisson.

Human parechovirus (HPeV) is associated with central nervous system infection and sepsis-like illness in newborn infants. The most frequent signs are fever, seizures, irritability, rash, and encephalitis. We report 4 cases of full-term infants with HPeV infection. They were admitted from home to the pediatric emergency unit of our hospital in October 2012. The median age at onset of symptoms was 15 days. They all developed sepsis-like illness with predominantly gastrointestinal disease and irritability. Two patients developed respiratory problems and 2 a skin rash (concerning only the extremities for one). Two patients required hospitalization in an intensive care unit. There was normal or mild inflammatory syndrome, normal white blood cell or mild leukopenia, hepatitis. We describe for the first time elevation of muscular enzymes in 3 of these patients. The diagnosis of HPeV infection was made by positive HPeV real-time PCR in cerebrospinal fluid (including the patient without pleocytosis) and/or blood. HPeV may cause severe disease in the neonatal period and patients presenting with such signs should be evaluated for HPeV. It also should be considered in sudden infant death syndrome.

Swallowing and respiratory distress in hospitalized patients with bronchiolitis.

The aim of this study was to evaluate the risk of airway and/or pulmonary food or saliva aspiration in infants with moderate respiratory distress who are hospitalized with respiratory syncytial virus (RSV) bronchiolitis. This prospective, descriptive study was conducted during two epidemic RSV seasons at the Ricardo Gutiérrez Children's Hospital in Buenos Aires, Argentina. Included were otherwise healthy infants in their first wheezing episode with a modified Tal clinical score between 5 and 9. Swallowing was evaluated using a dynamic technetium-99 m colloid radionuclide salivagram using a gamma camera, followed by video fluoroscopy using nonionic and ionic contrast material. Fifteen patients (7 boys) were included. Age at evaluation (mean ± SD) was 4.3 ± 1.5 months; clinical score was 7.5 ± 1.4. Patients required (mean ± SD) supplemental oxygen and hospitalization 7.5 ± 3.7 and 8.8 ± 4.3 days, respectively. All technetium-99 m salivagram (10/10, as the gamma camera equipment was out of service during part of the study) and video fluoroscopy (15/15) studies were normal. No episodes of aspiration or laryngeal penetration were detected in any patient. Our study found that infants hospitalized with moderate respiratory distress due to RSV bronchiolitis did not show aspiration.

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.

Value of herpes simplex virus type-specific serology: a case report.

Genital herpes, usually caused by herpes simplex virus type 2 (HSV-2), is one of the most common sexually transmitted diseases in humans. By contrast, intrauterine HSV-2 infections have been described rarely in the literature. Our report describes a case of neonate who was delivered after 30+2 gestational weeks by cesarean section. He presented with a respiratory distress syndrome resulting in broncho-pulmonary dysplasia. At the age of 6 weeks, a chorioretinal scar was detected. During the 4th month of age, the infant developed recurrent HSV-2 infection with nasal lesions. The retrospective type-specific serologic diagnosis revealed previous HSV-2 infection of the mother resulting in prenatal HSV-2 infection of the infant. In conclusion, intrauterine HSV-2 infections may be underrepresented since they may not be associated with severe congenital malformations and the diagnosis requires the use of HSV type-specific serologic methods not widely applied in microbiological laboratories.

Respiratory syncytial virus potentiates ABCA3 mutation-induced loss of lung epithelial cell differentiation.

ATP-binding cassette transporter A3 (ABCA3) is a lipid transporter active in lung alveolar epithelial type II cells (ATII) and is essential for their function as surfactant-producing cells. ABCA3 mutational defects cause respiratory distress in newborns and interstitial lung disease (ILD) in children. The molecular pathomechanisms are largely unknown; however, viral infections may initiate or aggravate ILDs. Here, we investigated the impact of the clinically relevant ABCA3 mutations, p.Q215K and p.E292V, by stable transfection of A549 lung epithelial cells. ABCA3 mutations strongly impaired expression of the ATII differentiation marker SP-C and the key epithelial cell adhesion proteins E-cadherin and zonula occludens-1. Concurrently, cells expressing ABCA3 mutation acquired mesenchymal features as observed by increased expression of SNAI1, MMP-2 and TGF-ß1, and elevated phosphorylation of Src. Infection with respiratory syncytial virus (RSV), the most common viral respiratory pathogen in small children, potentiated the observed mutational effects on loss of epithelial and acquisition of mesenchymal characteristics. In addition, RSV infection of cells harboring ABCA3 mutations resulted in a morphologic shift to a mesenchymal phenotype. We conclude that ABCA3 mutations, potentiated by RSV infection, induce loss of epithelial cell differentiation in ATII. Loss of key epithelial features may disturb the integrity of the alveolar epithelium, thereby comprising its functionality. We suggest the impairment of epithelial function as a mechanism by which ABCA3 mutations cause ILD.

[Clinical course and outcomes of influenza A (H1N1) 2009 in pregnant women].

AIM: Study of course of pregnancy, delivery, postpartum period and perinatal outcomes in pregnant women with influenza A (H1N1) 2009. MATERIALS AND METHODS: Course of pregnancy and outcomes in 16 women, who had influenza A (H1N1) 2009, were analyzed. Influenza A (H1N1) 2009 virus was detected by PCR. RESULTS: Influenza A (H1N1) 2009 had a severe course and high rates of complications: pneumonia (100%), respiratory distress syndrome (25%), placental deficiency (100%). Most of the neonates (87%) from mothers, who had influenza A (H1N1) 2009, had neonatal period disorders: congenital pneumonia--2 (12.5%), cerebral ischemia--10 (62.5%), hyperbilirubinemia--2 (12.5%), vegeto-visceral syndrome--4 (25%), hemorrhagic, convulsive and respiratory distress syndrome--1 (6.7%) each. Alteration in placenta was detected--influenza placentitis. Transplacental route of virus transmission was not detected. CONCLUSION: Pregnant women are a high risk group for influenza and serious complications caused by the virus. Influenza A (H1N1) 2009 has a more severe course and a higher rate of complications in both mothers and neonates.

Acute respiratory distress syndrome by cytomegalovirus infection in an immunocompetent infant.

A 2-month-old female infant was admitted with progressive respiratory distress, fever, and diagnosed with acute respiratory distress syndrome (ARDS). The primary pulmonary pathogen was proven to be cytomegalovirus (CMV) from bronchoalveolar lavage fluid, urine, and blood specimens. Other immunologic findings were normal. CMV-induced ARDS has not been reported previously in immunocompetent infants.

VATS management of an enlarging multicystic pneumatocele.

A multicystic pneumatocele progressively enlarged when the patient required positive pressure ventilation for an intercurrent respiratory syncytial virus infection. Video Assisted Thoracoscopic Surgery was used to visualize the pneumatocele for cannulation. One chamber of the pneumatocele was cannulated with a pigtail catheter and another large chamber ruptured, without cannulation. The multicystic pneumatocele resolved with this therapy.

Coxsackie virus infection of the placenta associated with neurodevelopmental delays in the newborn.

OBJECTIVE: To determine if viral infection of the placenta was associated with long-term neurodevelopmental delays in the newborn. METHODS: Placental tissue from seven newborn infants with severe respiratory failure and subsequent neurodevelopmental abnormalities as well as ten normal controls and five cases of known placental infection (cytomegalovirus, herpes simplex virus, and parvovirus) were tested by in situ hybridization or reverse transcriptase in situ polymerase chain reaction (PCR) for adenovirus, coxsackie virus, cytomegalovirus, Epstein Barr virus, herpes simplex virus, influenza A virus, picornavirus, polyoma virus, parvovirus, respiratory syncytial virus, rotavirus, and varicella zoster virus. RESULTS: Coxsackie virus RNA was detected in six of the seven cases, and in none of the ten normal controls or five cases with known viral infection. Viral RNA localized primarily to the Hofbauer cells and trophoblasts of the terminal villi. Immunohistochemical analysis for the coxsackie virus antigen VP1 yielded equivalent results. CONCLUSIONS: In utero coxsackie virus of the placenta is associated with the development of severe respiratory failure and central nervous system sequelae in the newborn. This underscores the importance of detailed pathologic and viral examination of the placenta in cases of systemic illness in the newborn.

[Rapid diagnosis of principal respiratory viruses in the city of Havana, 1995-97]. / Diagnóstico rápido de los principales virus respiratorios en Ciudad de la Habana, 1995-97.

Acute respiratory diseases (ARD) are the most common infections in humans and difficult to prevent. Viruses have been recognized as predominant ethiological agents. In Cuba, ARD constitute a major problem of health and are the first cause of morbidity and important cause of mortality. In this paper, rapid diagnosis was performed to 516 clinical samples which arrived to the Reference Respiratory Viruses Laboratory of the Pedro Kourí Institute of Tropical Medicine (IPK) from different parts of Havana City during 1995, 1996 and 1997. The results obtained have shown 218 positive samples (Influenza A, 89; respiratory syncytial virus 52; Influenza B, 45; Adenovirus, 13; human parainfluenza virus(HPIV)-1, 6; HPIV-2, 3 and HPIV-3, 10). Influenza A was the virus most frequently found in adults, whereas in closed population of teen-agers and adults, Influenza B was frequently found. Furthermore, respiratory syncytial virus was the most important pathogen in children's under 1 year of age.

Diagnóstico rápido de los principales virus respiratorios en Ciudad de la Habana, 1995-97 / Rapid diagnosis of principal respiratory viruses in the city of Havana, 1995-97

Acute respiratory diseases (ARD) are the most common infections in humans and difficult to prevent. Viruses have been recognized as predominant ethiological agents. In Cuba, ARD constitute a major problem of health and are the first cause of morbidity and important cause of mortality. In this paper, rapid diagnosis was performed to 516 clinical samples which arrived to the Reference Respiratory Viruses Laboratory of the Pedro KourY Institute of Tropical Medicine (IPK) from different parts of Havana City during 1995, 1996 and 1997. The results obtained have shown 218 positive samples (Influenza A, 89; respiratory syncytial virus 52; Influenza B, 45; Adenovirus, 13; human parainfluenza virus(HPIV)-1, 6; HPIV-2, 3 and HPIV-3, 10). Influenza A was the virus most frequently found in adults, whereas in closed population of teen-agers and adults, Influenza B was frequently found. Furthermore, respiratory syncytial virus was the most important pathogen in childrens under 1 year of age.(AU)

Fetal brain infection with human parvovirus B19.

Intrauterine parvovirus B19 infection is known to be one of the causes of hydrops fetalis. However, there are few reports of the pathologic changes in the central nervous system. Postmortem examination of a fetus revealed multinucleated giant cells of macrophage/microglia lineage and many small calcifications around the vessels, predominantly in the cerebral white matter. Parvovirus B19 genome DNA was detected in the nucleus of the multinucleated giant cells and solitary endothelial cells by polymerase chain reaction amplification and in situ polymerase chain reaction methods. Capsid antigen was also demonstrated in the cytoplasm of the endothelial cells by immunofluorescent assay. Thus, intrauterine B19 parvovirus infection could be associated with marked neuropathologic changes in the fetal brain at the midembryonal period. Neurologic follow-up of complications may be necessary for children who survive the intrauterine infection.

Surfactant replacement therapy in RSV-induced acute respiratory distress syndrome (ARDS).

Acute respiratory distress syndrome (ARDS) associated with severe respiratory syncytial virus infection is rare. We report a 5-month-old Indian girl who was admitted to our intensive care ward with severe respiratory failure who fulfilled the criteria for ARDS using both Murray's Lung Injury Score of > 2.5 and the American-European Consensus Conference definition for ARDS. She developed diffuse bilateral alveolar infiltrates, severe hypoxaemia (PaO2/FiO2 < 100) and required high PEEP (> 15 cm H2O) 24 hours after admission. RSV was isolated from her nasopharyngeal secretion. She also had clinical features suggestive of a primary immunodeficiency and had laboratory evidence of combined T and B cell defect. There was unsustained clinical improvement with a dose of surfactant administered at 36 hours of PICU stay, and she continued to deteriorate and succumbed after 19 days in the PICU.