Clinical characteristics and evolution of 71 neonates born to mothers with COVID-19 at a tertiary center in Brazil.

INTRODUCTION: Limited data are available on pregnant women with COVID-19 and their neonates. OBJECTIVE: This study aimed to describe clinical characteristics and evolution from birth to discharge of a retrospective cohort of 71 neonates, with one set of twins, born to women with COVID-19 diagnosed at the end of pregnancy. The authors included all newborns admitted into a neonatal unit of a tertiary hospital in Brazil, between March 2020 and March 2021, whose unvaccinated mothers had COVID-19 symptoms and RT-PCR (Real-Time Polymerase Chain Reaction) for SARS-CoV-2 positive within fourteen days prior to delivery. Newborns to mothers with COVID-19 symptoms and negative tests for SARS-CoV-2 were excluded. RESULTS: The main route of birth delivery was cesarean, corresponding to 60 pregnant women (84.5%). The foremost indications for cesarean were pregnant with critical disease (24.6%) and acute fetal distress (20.3%). The mean birth weight was 2452 g (865‒3870 g) and the mean gestational age was 345/7 weeks (25‒40 weeks). There were 45 premature newborns (63.3%), of which 21 newborns (29.5%) were less than 32 weeks of gestational age. RT-PCR for SARS-CoV-2 on oropharyngeal swabs was positive in 2 newborns (2.8%) and negative in the other 69 newborns (97.2%). Most newborns (51.4%) needed respiratory support. Therapeutic interventions during hospitalization were inotropic drugs (9.9%), antibiotics (22.8%), parenteral nutrition (26.8%), and phototherapy (46.5%). CONCLUSION: Maternal COVID-19 diagnosticated close to delivery has an impact on the first days of neonatal life.

Differences in children and adolescents with SARS-CoV-2 infection: a cohort study in a Brazilian tertiary referral hospital.

OBJECTIVES: To compare demographic/clinical/laboratory/treatments and outcomes among children and adolescents with laboratory-confirmed coronavirus disease 2019 (COVID-19). METHODS: This was a cross-sectional study that included patients diagnosed with pediatric COVID-19 (aged <18 years) between April 11, 2020 and April 22, 2021. During this period, 102/5,951 (1.7%) of all admissions occurred in neonates, children, and adolescents. Furthermore, 3,962 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection samples were processed in patients aged <18 years, and laboratory-confirmed COVID-19 occurred in 155 (4%) inpatients and outpatients. Six/155 pediatric patients were excluded from the study. Therefore, the final group included 149 children and adolescents (n=97 inpatients and 52 outpatients) with positive SARS-CoV-2 results. RESULTS: The frequencies of sore throat, anosmia, dysgeusia, headache, myalgia, nausea, lymphopenia, pre-existing chronic conditions, immunosuppressive conditions, and autoimmune diseases were significantly reduced in children and adolescents (p<0.05). Likewise, the frequencies of enoxaparin use (p=0.037), current immunosuppressant use (p=0.008), vasoactive agents (p=0.045), arterial hypotension (p<0.001), and shock (p=0.024) were significantly lower in children than in adolescents. Logistic regression analysis showed that adolescents with laboratory-confirmed COVID-19 had increased odds ratios (ORs) for sore throat (OR 13.054; 95% confidence interval [CI] 2.750-61.977; p=0.001), nausea (OR 8.875; 95% CI 1.660-47.446; p=0.011), and lymphopenia (OR 3.575; 95% CI 1.355-9.430; p=0.010), but also had less hospitalizations (OR 0.355; 95% CI 0.138-0.916; p=0.032). The additional logistic regression analysis on patients with preexisting chronic conditions (n=108) showed that death as an outcome was significantly associated with pediatric severe acute respiratory syndrome (SARS) (OR 22.300; 95% CI 2.341-212.421; p=0.007) and multisystem inflammatory syndrome in children (MIS-C) (OR 11.261; 95% CI 1.189-106. 581; p=0.035). CONCLUSIONS: Half of the laboratory-confirmed COVID-19 cases occurred in adolescents. Individuals belonging to this age group had an acute systemic involvement of SARS-CoV-2 infection. Pediatric SARS and MIS-C were the most important factors associated with the mortality rate in pediatric chronic conditions with COVID-19.

Vertical transmission of SARS-CoV2 during pregnancy: A high-risk cohort.

OBJECTIVE: Identify the potential for and risk factors of SARS-CoV-2 vertical transmission. METHODS: Symptomatic pregnant women with COVID-19 diagnosis in whom PCR for SARS-CoV-2 was performed at delivery using maternal serum and at least one of the biological samples: cord blood (CB), amniotic fluid (AF), colostrum and/or oropharyngeal swab (OPS) of the neonate. The association of parameters with maternal, AF and/or CB positivity and the influence of SARS-CoV-2 positivity in AF and/or CB on neonatal outcomes were investigated. RESULTS: Overall 73.4% (80/109) were admitted in hospital due to COVID-19, 22.9% needed intensive care and there were four maternal deaths. Positive RT-PCR for SARS-CoV-2 was observed in 14.7% of maternal blood, 13.9% of AF, 6.7% of CB, 2.1% of colostrum and 3.7% of OPS samples. The interval between COVID-19 symptoms and delivery was inversely associated with SARS-CoV-2 positivity in the maternal blood (p = 0.002) and in the AF and/or CB (p = 0.049). Maternal viremia was associated with positivity for SARS-CoV-2 in AF and/or CB (p = 0.001). SARS-CoV-2 positivity in the compartments was not associated with neonatal outcomes. CONCLUSION: Vertical transmission is possible in pregnant women with COVID-19 and a shorter interval between maternal symptoms and delivery is an influencing factor.

An autopsy study of the spectrum of severe COVID-19 in children: From SARS to different phenotypes of MIS-C.

BACKGROUND: COVID-19 in children is usually mild or asymptomatic, but severe and fatal paediatric cases have been described. The pathology of COVID-19 in children is not known; the proposed pathogenesis for severe cases includes immune-mediated mechanisms or the direct effect of SARS-CoV-2 on tissues. We describe the autopsy findings in five cases of paediatric COVID-19 and provide mechanistic insight into the mechanisms involved in the pathogenesis of the disease. METHODS: Children and adolescents who died with COVID-19 between March 18 and August 15, 2020 were autopsied with a minimally invasive method. Tissue samples from all vital organs were analysed by histology, electron microscopy (EM), reverse-transcription polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC). FINDINGS: Five patients were included, one male and four female, aged 7 months to 15 years. Two patients had severe diseases before SARS-CoV-2 infection: adrenal carcinoma and Edwards syndrome. Three patients were previously healthy and had multisystem inflammatory syndrome in children (MIS-C) with distinct clinical presentations: myocarditis, colitis, and acute encephalopathy with status epilepticus. Autopsy findings varied amongst patients and included mild to severe COVID-19 pneumonia, pulmonary microthrombosis, cerebral oedema with reactive gliosis, myocarditis, intestinal inflammation, and haemophagocytosis. SARS-CoV-2 was detected in all patients in lungs, heart and kidneys by at least one method (RT-PCR, IHC or EM), and in endothelial cells from heart and brain in two patients with MIS-C (IHC). In addition, we show for the first time the presence of SARS-CoV-2 in the brain tissue of a child with MIS-C with acute encephalopathy, and in the intestinal tissue of a child with acute colitis. Interpretation: SARS-CoV-2 can infect several cell and tissue types in paediatric patients, and the target organ for the clinical manifestation varies amongst individuals. Two major patterns of severe COVID-19 were observed: a primarily pulmonary disease, with severe acute respiratory disease and diffuse alveolar damage, or a multisystem inflammatory syndrome with the involvement of several organs. The presence of SARS-CoV-2 in several organs, associated with cellular ultrastructural changes, reinforces the hypothesis that a direct effect of SARS-CoV-2 on tissues is involved in the pathogenesis of MIS-C. FUNDING: Fundação de Amparo à Pesquisa do Estado de São Paulo, Conselho Nacional de Desenvolvimento Científico e Tecnológico, Bill and Melinda Gates Foundation.

Severe clinical spectrum with high mortality in pediatric patients with COVID-19 and multisystem inflammatory syndrome

OBJECTIVES: To assess the outcomes of pediatric patients with laboratory-confirmed coronavirus disease (COVID-19) with or without multisystem inflammatory syndrome in children (MIS-C). METHODS: This cross-sectional study included 471 samples collected from 371 patients (age&lt;18 years) suspected of having severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The study group comprised 66/371 (18%) laboratory-confirmed pediatric COVID-19 patients: 61 (92.5%) patients tested positive on real-time reverse transcription-polymerase chain reaction tests for SARS-CoV-2, and 5 (7.5%) patients tested positive on serological tests. MIS-C was diagnosed according to the criteria of the Center for Disease Control. RESULTS: MIS-C was diagnosed in 6/66 (9%) patients. The frequencies of diarrhea, vomiting, and/or abdominal pain (67% vs. 22%, p=0.034);pediatric SARS (67% vs. 13%, p=0.008);hypoxemia (83% vs. 23%, p=0.006);and arterial hypotension (50% vs. 3%, p=0.004) were significantly higher in patients with MIS-C than in those without MIS-C. The frequencies of C-reactive protein levels &gt;50 mg/L (83% vs. 25%, p=0.008) and D-dimer levels &gt;1000 ng/mL (100% vs. 40%, p=0.007) and the median D-dimer, troponin T, and ferritin levels (p&lt;0.05) were significantly higher in patients with MIS-C. The frequencies of pediatric intensive care unit admission (100% vs. 60%, p=0.003), mechanical ventilation (83% vs. 7%, p&lt;0.001), vasoactive agent use (83% vs. 3%, p&lt;0.001), shock (83% vs. 5%, p&lt;0.001), cardiac abnormalities (100% vs. 2%, p&lt;0.001), and death (67% vs. 3%, p&lt;0.001) were also significantly higher in patients with MIS-C. Similarly, the frequencies of oxygen therapy (100% vs. 33%, p=0.003), intravenous immunoglobulin therapy (67% vs. 2%, p&lt;0.001), aspirin therapy (50% vs. 0%, p&lt;0.001), and current acute renal replacement therapy (50% vs. 2%, p=0.002) were also significantly higher in patients with MIS-C. Logistic regression analysis showed that the presence of MIS-C was significantly associated with gastrointestinal manifestations [odds ratio (OR)=10.98;95%CI (95% confidence interval)=1.20-100.86;p=0.034] and hypoxemia [OR=16.85;95%CI=1.34-211.80;p=0.029]. Further univariate analysis showed a positive association between MIS-C and death [OR=58.00;95%CI=6.39-526.79;p&lt;0.0001]. CONCLUSIONS: Pediatric patients with laboratory-confirmed COVID-19 with MIS-C had a severe clinical spectrum with a high mortality rate. Our study emphasizes the importance of investigating MIS-C in pediatric patients with COVID-19 presenting with gastrointestinal involvement and hypoxemia.

Use of lung ultrasound in neonates during the COVID-19 pandemic

In the current pandemic, caused by infection with severe acute respiratory syndrome coronavirus 2, ultrasound has played a fundamental role in patients who develop the resulting disease, designated coronavirus disease 2019 (COVID-19). In this study we present ultrasound images of the lungs of neonates with a suspected or confirmed diagnosis of COVID-19, distinguishing between the changes related to COVID-19 and those unrelated to the disease. Ultrasound examinations were performed by a pediatric sonographer. A total of 27 neonates were evaluated. Among those who presented no respiratory symptoms, some tested negative for COVID-19 and others tested positive. All of those who were pulmonary symptomatic, negative for COVID-19 presented transient tachypnea of the newborn and respiratory distress syndrome. Lung ultrasound images obtained in COVID-19-negative neonates showed, in some cases, a normal pattern (with A lines, few B lines, a thin, linear pleural line, and no pleural effusion), whereas in others showed coalescent B lines and areas of opacity. In two of the COVID-19-positive neonates, lung ultrasound examination showed several coalescent B lines, pleural thickening, and areas of opacity. Lung ultrasound in the neonatal period appears to be applicable within the context of the current pandemic, allowing efficient evaluation of COVID-19-related changes in neonates, as well as of pathologies inherent to the neonatal period. Resumo Na pandemia atual causada pelo SARS-CoV-19, a ultrassonografia (US) tem apresentado papel fundamental nos pacientes com COVID-19. Neste trabalho são mostradas imagens ultrassonográficas de recém-nascidos (RNs) suspeitos ou positivos para COVID-19 e alterações pulmonares não relacionadas a essa doença. As imagens ultrassonográficas foram obtidas por médico especialista em US pediátrica. Foram avaliados 27 RNs, sendo incluídos RNs assintomáticos da parte respiratória, COVID negativos e positivos, e RNs sintomáticos para a parte respiratória, COVID-negativos, observados na taquipneia transitória do recém-nascido ou na síndrome do desconforto respiratório. As imagens ultrassonográficas dos RNs negativos para COVID-19 mostraram tanto o padrão normal (presença de linhas A, poucas linhas B, linha pleural fina e linear, ausência de efusão pleural) quanto a presença de linhas B coalescentes e áreas de condensação pulmonar. Destaca-se a presença de dois RNs COVID-19 positivos apresentando múltiplas linhas B coalescentes, espessamento pleural e com áreas de condensação. Com este trabalho, os autores procuram demonstrar a aplicabilidade da US pulmonar dentro do contexto da pandemia da COVID-19, incluindo as doenças inerentes ao período neonatal.

Expert recommendations for the care of newborns of mothers with COVID-19

This article presents expert recommendations for assisting newborn children of mothers with suspected or diagnosed coronavirus disease 2019 &lt;/mac_aq&gt;(COVID-19). The consensus was developed by five experts with an average of 20 years of experience in neonatal intensive care working at a reference university hospital in Brazil for the care of pregnant women and newborns with suspected or confirmed COVID-19. Despite the lack of scientific evidence regarding the potential for viral transmission to their fetus in pregnant mothers diagnosed with or suspected of COVID-19, it is important to elaborate the lines of care by specialists from hospitals caring for suspected and confirmed COVID-19 cases to guide multidisciplinary teams and families diagnosed with the disease or involved in the care of pregnant women and newborns in this context. Multidisciplinary teams must be attentive to the signs and symptoms of COVID-19 so that decision-making is oriented and assertive for the management of the mother and newborn in both the hospital setting and at hospital discharge.

Use of lung ultrasound in neonates during the COVID-19 pandemic.

In the current pandemic, caused by infection with severe acute respiratory syndrome coronavirus 2, ultrasound has played a fundamental role in patients who develop the resulting disease, designated coronavirus disease 2019 (COVID-19). In this study we present ultrasound images of the lungs of neonates with a suspected or confirmed diagnosis of COVID-19, distinguishing between the changes related to COVID-19 and those unrelated to the disease. Ultrasound examinations were performed by a pediatric sonographer. A total of 27 neonates were evaluated. Among those who presented no respiratory symptoms, some tested negative for COVID-19 and others tested positive. All of those who were pulmonary symptomatic, negative for COVID-19 presented transient tachypnea of the newborn and respiratory distress syndrome. Lung ultrasound images obtained in COVID-19-negative neonates showed, in some cases, a normal pattern (with A lines, few B lines, a thin, linear pleural line, and no pleural effusion), whereas in others showed coalescent B lines and areas of opacity. In two of the COVID-19-positive neonates, lung ultrasound examination showed several coalescent B lines, pleural thickening, and areas of opacity. Lung ultrasound in the neonatal period appears to be applicable within the context of the current pandemic, allowing efficient evaluation of COVID-19-related changes in neonates, as well as of pathologies inherent to the neonatal period.

Na pandemia atual causada pelo SARS-CoV-19, a ultrassonografia (US) tem apresentado papel fundamental nos pacientes com COVID-19. Neste trabalho são mostradas imagens ultrassonográficas de recém-nascidos (RNs) suspeitos ou positivos para COVID-19 e alterações pulmonares não relacionadas a essa doença. As imagens ultrassonográficas foram obtidas por médico especialista em US pediátrica. Foram avaliados 27 RNs, sendo incluídos RNs assintomáticos da parte respiratória, COVID negativos e positivos, e RNs sintomáticos para a parte respiratória, COVID-negativos, observados na taquipneia transitória do recém-nascido ou na síndrome do desconforto respiratório. As imagens ultrassonográficas dos RNs negativos para COVID-19 mostraram tanto o padrão normal (presença de linhas A, poucas linhas B, linha pleural fina e linear, ausência de efusão pleural) quanto a presença de linhas B coalescentes e áreas de condensação pulmonar. Destaca-se a presença de dois RNs COVID-19 positivos apresentando múltiplas linhas B coalescentes, espessamento pleural e com áreas de condensação. Com este trabalho, os autores procuram demonstrar a aplicabilidade da US pulmonar dentro do contexto da pandemia da COVID-19, incluindo as doenças inerentes ao período neonatal.

Severe clinical spectrum with high mortality in pediatric patients with COVID-19 and multisystem inflammatory syndrome.

OBJECTIVES: To assess the outcomes of pediatric patients with laboratory-confirmed coronavirus disease (COVID-19) with or without multisystem inflammatory syndrome in children (MIS-C). METHODS: This cross-sectional study included 471 samples collected from 371 patients (age<18 years) suspected of having severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The study group comprised 66/371 (18%) laboratory-confirmed pediatric COVID-19 patients: 61 (92.5%) patients tested positive on real-time reverse transcription-polymerase chain reaction tests for SARS-CoV-2, and 5 (7.5%) patients tested positive on serological tests. MIS-C was diagnosed according to the criteria of the Center for Disease Control. RESULTS: MIS-C was diagnosed in 6/66 (9%) patients. The frequencies of diarrhea, vomiting, and/or abdominal pain (67% vs. 22%, p=0.034); pediatric SARS (67% vs. 13%, p=0.008); hypoxemia (83% vs. 23%, p=0.006); and arterial hypotension (50% vs. 3%, p=0.004) were significantly higher in patients with MIS-C than in those without MIS-C. The frequencies of C-reactive protein levels >50 mg/L (83% vs. 25%, p=0.008) and D-dimer levels >1000 ng/mL (100% vs. 40%, p=0.007) and the median D-dimer, troponin T, and ferritin levels (p<0.05) were significantly higher in patients with MIS-C. The frequencies of pediatric intensive care unit admission (100% vs. 60%, p=0.003), mechanical ventilation (83% vs. 7%, p<0.001), vasoactive agent use (83% vs. 3%, p<0.001), shock (83% vs. 5%, p<0.001), cardiac abnormalities (100% vs. 2%, p<0.001), and death (67% vs. 3%, p<0.001) were also significantly higher in patients with MIS-C. Similarly, the frequencies of oxygen therapy (100% vs. 33%, p=0.003), intravenous immunoglobulin therapy (67% vs. 2%, p<0.001), aspirin therapy (50% vs. 0%, p<0.001), and current acute renal replacement therapy (50% vs. 2%, p=0.002) were also significantly higher in patients with MIS-C. Logistic regression analysis showed that the presence of MIS-C was significantly associated with gastrointestinal manifestations [odds ratio (OR)=10.98; 95%CI (95% confidence interval)=1.20-100.86; p=0.034] and hypoxemia [OR=16.85; 95%CI=1.34-211.80; p=0.029]. Further univariate analysis showed a positive association between MIS-C and death [OR=58.00; 95%CI=6.39-526.79; p<0.0001]. CONCLUSIONS: Pediatric patients with laboratory-confirmed COVID-19 with MIS-C had a severe clinical spectrum with a high mortality rate. Our study emphasizes the importance of investigating MIS-C in pediatric patients with COVID-19 presenting with gastrointestinal involvement and hypoxemia.

Role of a Neonatal Intensive Care Unit during the COVID-19 Pandemia: recommendations from the neonatology discipline.

On 11th March 2020, the World Health Organization (WHO) declared the COVID-19 a pandemic. The Obstetrics and Neonatology disciplines needed to be revised to suit the institutional need to expand intensive care beds to care for confirmed or suspected patients with COVID-19 in the state of São Paulo, following the recommendations of the Institutional Crisis Committee. Three different actions were needed: the structuring of teams and advanced medical post to attend COVID-19-free patients and those with suspect or confirmed COVID-19; elaborating the protocols from the delivery room throughout hospitalization. Some special considerations about breastfeeding and rooming-in were needed. The third action was the drafting of a protocol to admit infants from other hospitals with confirmed COVID-19 as the unit never admitted outpatients before.