Effect of EIT-guided PEEP titration on prognosis of patients with moderate to severe ARDS: study protocol for a multicenter randomized controlled trial.

BACKGROUND: Acute respiratory syndrome distress (ARDS) is a clinical common syndrome with high mortality. Electrical impedance tomography (EIT)-guided positive end-expiratory pressure (PEEP) titration can achieve the compromise between lung overdistension and collapse which may minimize ventilator-induced lung injury in these patients. However, the effect of EIT-guided PEEP titration on the clinical outcomes remains unknown. The objective of this trial is to investigate the effects of EIT-guided PEEP titration on the clinical outcomes for moderate or severe ARDS, compared to the low fraction of inspired oxygen (FiO2)-PEEP table. METHODS: This is a prospective, multicenter, single-blind, parallel-group, adaptive designed, randomized controlled trial (RCT) with intention-to-treat analysis. Adult patients with moderate to severe ARDS less than 72 h after diagnosis will be included in this study. Participants in the intervention group will receive PEEP titrated by EIT with a stepwise decrease PEEP trial, whereas participants in the control group will select PEEP based on the low FiO2-PEEP table. Other ventilator parameters will be set according to the ARDSNet strategy. Participants will be followed up until 28 days after enrollment. Three hundred seventy-six participants will be recruited based on a 15% decrease of 28-day mortality in the intervention group, with an interim analysis for sample size re-estimation and futility assessment being undertaken once 188 participants have been recruited. The primary outcome is 28-day mortality. The secondary outcomes include ventilator-free days and shock-free days at day 28, length of ICU and hospital stay, the rate of successful weaning, proportion requiring rescue therapies, compilations, respiratory variables, and Sequential Organ Failure Assessment (SOFA). DISCUSSION: As a heterogeneous syndrome, ARDS has different responses to treatment and further results in different clinical outcomes. PEEP selection will depend on the properties of patients and can be individually achieved by EIT. This study will be the largest randomized trial to investigate thoroughly the effect of individual PEEP titrated by EIT in moderate to severe ARDS patients to date. TRIAL REGISTRATION: ClinicalTrial.gov NCT05207202. First published on January 26, 2022.

Pulmonary Surfactant: A Unique Biomaterial with Life-saving Therapeutic Applications.

Pulmonary surfactant is a complex lipoprotein mixture secreted into the alveolar lumen by type 2 pneumocytes, which is composed by tens of different lipids (approximately 90% of its entire mass) and surfactant proteins (approximately 10% of the mass). It is crucially involved in maintaining lung homeostasis by reducing the values of alveolar liquid surface tension close to zero at end-expiration, thereby avoiding the alveolar collapse, and assembling a chemical and physical barrier against inhaled pathogens. A deficient amount of surfactant or its functional inactivation is directly linked to a wide range of lung pathologies, including the neonatal respiratory distress syndrome. This paper reviews the main biophysical concepts of surfactant activity and its inactivation mechanisms, and describes the past, present and future roles of surfactant replacement therapy, focusing on the exogenous surfactant preparations marketed worldwide and new formulations under development. The closing section describes the pulmonary surfactant in the context of drug delivery. Thanks to its peculiar composition, biocompatibility, and alveolar spreading capability, the surfactant may work not only as a shuttle to the branched anatomy of the lung for other drugs but also as a modulator for their release, leading to innovative therapeutic avenues for the treatment of several respiratory diseases.

A recipe for a good clinical pulmonary surfactant.

The lives of thousands premature babies have been saved along the last thirty years thanks to the establishment and consolidation of pulmonary surfactant replacement therapies (SRT). It took some time to close the gap between the identification of the biophysical and molecular causes of the high mortality associated with respiratory distress syndrome in very premature babies and the development of a proper therapy. Closing the gap required the elucidation of some key questions defining the structure-function relationships in surfactant as well as the particular role of the different molecular components assembled into the surfactant system. On the other hand, the application of SRT as part of treatments targeting other devastating respiratory pathologies, in babies and adults, is depending on further extensive research still required before enough amounts of good humanized clinical surfactants will be available. This review summarizes our current concepts on the compositional and structural determinants defining pulmonary surfactant activity, the principles behind the development of efficient natural animal-derived or recombinant or synthetic therapeutic surfactants, as well as a the most promising lines of research that are already opening new perspectives in the application of tailored surfactant therapies to treat important yet unresolved respiratory pathologies.

New developments in neonatal respiratory management.

Respiratory distress syndrome (RDS) is the major cause of respiratory failure in preterm infants due to immature lung development and surfactant deficiency. Although the concepts and methods of managing respiratory problems in neonates have changed continuously, determining appropriate respiratory treatment with minimal ventilation-induced lung injury and complications is crucially important. This review summarizes neonatal respiratory therapy's advances and available strategies (i.e., exogenous surfactant therapy, noninvasive ventilation, and different ventilation modes), focusing on RDS management.

Management of severe neonatal respiratory distress due to vertical transmission of severe acute respiratory syndrome coronavirus 2: a case report.

BACKGROUND: Neonates with severe acute respiratory syndrome coronavirus 2 infection are usually asymptomatic or have mild to moderate symptoms. Acute respiratory distress syndrome due to severe acute respiratory syndrome coronavirus 2 with respiratory insufficiency is rare. Therefore, information about the best intensive care strategy for neonates requiring mechanical ventilation is lacking. We report a neonatal case of severe acute respiratory distress syndrome, probably due to vertical transmission of severe acute respiratory syndrome coronavirus 2, complicated by Staphylococcus aureus sepsis. We aim to inform pediatric providers on the clinical course and acute management considerations in coronavirus disease-related neonatal acute respiratory distress syndrome. CASE PRESENTATION: A late preterm (gestational age 36 0/7 weeks) Caucasian girl was born from a severe acute respiratory syndrome coronavirus 2-positive mother and tested positive for severe acute respiratory syndrome coronavirus 2 at 19 hours after birth. She developed acute respiratory distress syndrome requiring intensive care admission and mechanical ventilation. The clinical course was complicated by S. aureus pneumonia and bacteremia. Multimodal management included well-established interventions for respiratory distress syndrome such as surfactant therapy, high-frequency oscillatory ventilation, and inhaled nitric oxide, combined with therapies extrapolated from adult care for severe acute respiratory syndrome coronavirus 2 patients such as dexamethasone, coronavirus disease 2019-specific immunoglobins, and prophylactic low-molecular-weight heparin. The neonate was successfully weaned from the ventilator and improved clinically. CONCLUSION: This case shows a rare but serious neonatal severe acute respiratory syndrome coronavirus 2 infection, leading to severe acute respiratory distress syndrome. Because of limited therapy guidelines for neonates, we suggest multimodal management with awareness of the possibility of S. aureus coinfection, to treat this age group successful.

Adverse effects of prenatal dexamethasone exposure on fetal development.

Dexamethasone has been widely used in clinical practice to promote fetal lung maturity and reduce neonatal respiratory distress syndrome and perinatal mortality. Nevertheless, its administration is a double-edged sword, as a large number of studies have shown that there are obvious disadvantages in pregnant women and fetal development. In this review, we comprehensively retrospect the latest literature on the toxicological effects and mechanisms of dexamethasone on fetal development, in an attempt to provide a valuable basis for further studies and clinical trials in the future. Overall, prenatal dexamethasone exposure could lead to some adverse consequences on fetal organ systems through intrauterine programming based on the results of current animal and human researches. Potential sequelae include osteoarthritis, hypertension, fatty liver, glomerulosclerosis, depression, diabetes and infertility, some of which can pass on to the next generation. It must be noted that the evidence in humans is preliminary and limited by the small sample size. More studies in large-scale populations are needed to confirm if it raises the risk of sequelae in humans. In addition, we strongly support the application of dexamethasone as a pharmaceutical therapy in pregnant women with coronavirus disease 2019 before a better therapy is developed. However, the adverse side effects that may arise also cannot be ignored.

Ivermectin use associated with reduced duration of COVID-19 febrile illness in a community setting (preprint)

AIMS: SARS-CoV-2 infection (COVID-19) is a potentially lethal disease that may progress into severe respiratory distress syndrome requiring ventilatory support. While azithromycin (AZI) and hydroxychloroquine (HCQ) are considered similar to placebo in COVID-19, other drugs such as ivermectin (IVER), are being repurposed to treat this pandemic. This study was designed to assess the effects of ivermectin on duration of febrile illness and disease outcomes in mild-to-moderate COVID-19 infection in a community setting. METHODS: In this case-control study 95 suspected patients of mild-to-moderate COVID-19 were included. The controls (Group-A) received AZI+HCQ for seven days while the cases (Group-B) received IVER+AZI+HCQ for six days. RESULTS: A total of 41 patients were in Group-B, while 54 patients were in Group-A. Group-B had consistently and significantly shorter span of fever on days 5, 7, 10 and 14, where the logistic regression showed IVER as the major (Exp B 49•55; p<0•001) underlying factor. The Kaplan-Meier survival analysis showed that Group-A had a prolonged febrile illness (p<0•001). CONCLUSIONS: Ivermectin use is associated with reduced duration of febrile illness in COVID-19 in outpatient setting, thus potentially saving precious lives, reducing direct load on healthcare facilities and preventing high cost of management in a community setting.

Successful Use of ECMO in the Treatment of Acute Respiratory Distress Syndrome Associated with SARS-CoV-2 in Children (preprint)

SARS-CoV-2 infection, in the vast majority, affect adult patients (1,2). The severity of COVID-19 and mortality are directly correlated with the increasing age of patients and the number of comorbidities (3). However, with the further development of the COVID-19 pandemic, severe cases of COVID-19 have been reported in children. About 0.8% -1% of sick children require hospitalization in an intensive care unit (4). The main syndromes that cause disease severity and mortality in children are acute respiratory distress syndrome, multisystem inflammation syndrome and multiple organ failure (5,6). The rapid development of severe respiratory failure and hypoxemia in respiratory distress syndrome leads to the use of various methods of respiratory therapy (7), and in case of their ineffectiveness to extracorporeal membrane oxygenation (8,9). In our report, we present two clinical cases of successful use of ECMO in children with COVID-19, who developed severe ARDS.

Comparison of early postnatal clinical outcomes of newborns born to pregnant women with COVID-19: a case-control study.

BACKGROUND: The ongoing COVID-19 pandemic has infected millions of people, including pregnant women and newborns and caused many deaths. Studies examining the effects of COVID-19 infection in pregnancy have mostly focused on maternal outcomes and there are limited data on neonatal outcomes. OBJECTIVES: This study aims to compare the early postnatal period clinical outcomes of newborns born to pregnant women with and without COVID-19. METHODS: A retrospective case-control study was used to compare the clinical characteristics of newborns born to pregnant women with and without COVID-19. This study was conducted between 11 March 2020 and 11 March 2021 at Denizli State Hospital, Turkey. This study included 202 newborns selected with a nonprobability method. The clinical records and laboratory results of 202 newborns were reviewed by applying a retrospective questionnaire. Neonatal outcomes were compared between the groups. RESULTS: There were 101 newborns born to pregnant women with COVID-19 in the case group and 101 without COVID-19 in the control group in the study. A considerably higher rate of newborns born to pregnant women with COVID-19 had cesarean delivery (79.2 versus 35.6%, p < .001), premature birth (28.7 versus 10.9%, p = .001), low birth weight (15.8 versus 6.9%, p = .046), neonatal respiratory distress syndrome (RDS) (37.6 versus 19.8%, p = .005), oxygen need (19.8 versus 37.6, p = .005), and neonatal intensive care unit admission (10.9 versus 37.6%, p = .001). Breastfeeding (1.0 versus 67.3%, p < .001) and nutrition with breast milk rates (33.7 versus 80.2%, p < .001) of newborns born to pregnant women with COVID-19 were significantly lower. The results of 101 newborns who received nasopharyngeal swab samples for COVID-19 were negative. CONCLUSION: Newborns born to pregnant women with COVID-19 were more likely to experience preterm birth, cesarean delivery, low birth weight, neonatal RDS, oxygen demand, need for intensive care, and breastfeeding problems. There was no vertical contamination according to the nasopharyngeal swab samples of the newborns.

Longitudinal Characterization of Circulating Neutrophils Uncovers Distinct Phenotypes Associated with Disease Severity in Hospitalized COVID-19 Patients (preprint)

Multiple studies have identified an association between neutrophils and COVID-19 disease severity; however, the mechanistic basis of this association remains incompletely understood. Here we collected 781 longitudinal blood samples from 306 hospitalized COVID-19 + patients, 78 COVID-19 - acute respiratory distress syndrome patients, and 8 healthy controls, and performed bulk RNA-sequencing of enriched neutrophils, plasma proteomics, cfDNA measurements and high throughput antibody profiling assays to investigate the relationship between neutrophil states and disease severity or death. We identified dynamic switches between six distinct neutrophil subtypes using non-negative matrix factorization (NMF) clustering. At days 3 and 7 post-hospitalization, patients with severe disease had an enrichment of a granulocytic myeloid derived suppressor cell-like state gene expression signature, while non-severe patients with resolved disease were enriched for a progenitor-like immature neutrophil state signature. Severe disease was associated with gene sets related to neutrophil degranulation, neutrophil extracellular trap (NET) signatures, distinct metabolic signatures, and enhanced neutrophil activation and generation of reactive oxygen species (ROS). We found that the majority of patients had a transient interferon-stimulated gene signature upon presentation to the emergency department (ED) defined here as Day 0, regardless of disease severity, which persisted only in patients who subsequently died. Humoral responses were identified as potential drivers of neutrophil effector functions, as enhanced antibody-dependent neutrophil phagocytosis and reduced NETosis was associated with elevated SARS-CoV-2-specific IgG1-to-IgA1 ratios in plasma of severe patients who survived. In vitro experiments confirmed that while patient-derived IgG antibodies mostly drove neutrophil phagocytosis and ROS production in healthy donor neutrophils, patient-derived IgA antibodies induced a predominant NETosis response. Overall, our study demonstrates neutrophil dysregulation in severe COVID-19 and a potential role for IgA-dominant responses in driving neutrophil effector functions in severe disease and mortality.Funding:We acknowledge support from the Ragon Institute of MGH, MIT and Harvard, the Massachusetts Consortium on Pathogen Readiness (MassCPR), the NIH (3R37AI080289-11S1, R01AI146785, U19AI42790-01, U19AI135995-02, U19AI42790-01, 1U01CA260476 – 01, CIVIC75N93019C00052, T32 GM007592), the American Lung Association, and the MGH Executive Committee on Research. A.-C.V. acknowledges funding support from the COVID-19 Clinical Trials Pilot grant from the Executive Committee on Research at MGH, a COVID-19 Chan Zuckerberg Initiative grant (2020-216954), and funds from the Manton Foundation and the Klarman Family Foundation.Declaration of Interests: M.S.F receives funding from Bristol-Myers Squibb. G.A. is a founder of Seromyx Systems Inc. N.H. holds equity in Biontech and holds equity in and advises Danger Bio. Ethics Approval Statement: The study was approved by the Mass General Brigham Institutional Review Board under protocol 2017P001681, with an approval for a waiver of informed consent in compliance with the 45CFR 46, 2018 Common rule.

Ibudilast, a Phosphodiesterase-4 Inhibitor, Ameliorates Acute Respiratory Distress Syndrome in Neonatal Mice by Alleviating Inflammation and Apoptosis.

BACKGROUND Acute respiratory distress syndrome (ARDS) is a sudden and serious disease with increasing morbidity and mortality rates. Phosphodiesterase 4 (PDE4) is a novel target for inflammatory disease, and ibudilast (IBU), a PDE4 inhibitor, inhibits inflammatory response. Our study investigated the effect of IBU on the pathogenesis of neonatal ARDS and the underlying mechanism related to it. MATERIAL AND METHODS Western blotting was performed to analyze the expression levels of PDE4, CXCR4, SDF-1, CXCR5, CXCL1, inflammatory cytokines, and proteins related to cell apoptosis. Hematoxylin-eosin staining was performed to observe the pathological morphology of lung tissue. Pulmonary edema score was used to assess the degree of lung water accumulation after pulmonary injury. Enzyme-linked immunosorbent assay (ELISA) was used to assess levels of inflammatory factors (TNF-alpha, IL-1ß, IL-6, and MCP-1) in serum. TUNEL assay was used to detect apoptotic cells. RESULTS Increased expression of PDE4 was observed in an LPS-induced neonatal ARDS mouse model, and IBU ameliorated LPS-induced pathological manifestations and pulmonary edema in lung tissue. In addition, IBU attenuated the secretion of inflammatory cytokines by inactivating the chemokine axis in the LPS-induced neonatal ARDS mouse model. Finally, IBU significantly reduced LPS-induced cell apoptosis in lung tissue. CONCLUSIONS IBU, a PDE4 inhibitor, protected against ARDS by interfering with pulmonary inflammation and apoptosis. Our findings provide a novel and promising strategy to regulate pulmonary inflammation in ARDS.

Face mask versus nasal prong or nasopharyngeal tube for neonatal resuscitation in the delivery room: a systematic review and meta-analysis.

IMPORTANCE: The current neonatal resuscitation guidelines recommend positive pressure ventilation via face mask or nasal prongs at birth. Using a nasal interface may have the potential to improve outcomes for newborn infants. OBJECTIVE: To determine whether nasal prong/nasopharyngeal tube versus face mask during positive pressure ventilation of infants born <37 weeks' gestation in the delivery room reduces in-hospital mortality and morbidity. DATA SOURCES: MEDLINE (through PubMed), Google Scholar and EMBASE, Clinical Trials.gov and the Cochrane Central Register of Controlled Trials through August 2019. STUDY SELECTION: Randomised controlled trials comparing nasal prong/nasopharyngeal tube versus face mask during positive pressure ventilation of infants born <37 weeks' gestation in the delivery room. DATA ANALYSIS: Risk of bias was assessed using the Covidence Collaboration Tool, results were pooled into a meta-analysis using a random effects model. MAIN OUTCOME: In-hospital mortality. RESULTS: Five RCTs enrolling 873 infants were combined into a meta-analysis. There was no statistical difference in in-hospital mortality (risk ratio (RR 0.98, 95% CI 0.63 to 1.52, p=0.92, I2=11%), rate of chest compressions in the delivery room (RR 0.37, 95% CI 0.10 to 1.33, p=0.13, I2=28%), rate of intraventricular haemorrhage (RR 1.54, 95% CI 0.88 to 2.70, p=0.13, I2=0%) or delivery room intubations in infants ventilated with a nasal prong/tube (RR 0.63, 95% CI 0.39,1.02, p=0.06, I2=52%). CONCLUSION: In infants born <37 weeks' gestation, in-hospital mortality and morbidity were similar following positive pressure ventilation during initial stabilisation with a nasal prong/tube or a face mask.

Exogenous pulmonary surfactant in COVID-19 ARDS. The similarities to neonatal RDS suggest a new scenario for an 'old' strategy.

Acute respiratory distress syndrome (ARDS) related to SARS-CoV-2 infection has some unusual characteristics that differentiate it from the pathophysiology described in the more 'typical' ARDS. Among multiple hypotheses, a close similarity has been suggested between COVID-19 ARDS and neonatal respiratory distress syndrome (RDS). With this opinion paper, we investigated the pathophysiological similarities between infant respiratory diseases (RDS and direct neonatal ARDS (NARDS)) and COVID-19 in adults. We also analysed, for the first time, similarities in the response to exogenous surfactant administration in terms of improved static compliance in RDS and direct NARDS, and adult COVID-19 ARDS. In conclusion, we believe that if the pathological processes are similar both from the pathophysiological point of view and from the response in respiratory mechanics to a recruitment treatment such as surfactant, perhaps the latter could be considered a plausible option and lead to recruitment in clinical trials currently ongoing on patients with COVID-19.

Advanced ventilatory support and mortality in hospitalized patients with COVID-19 caused by Gamma (P.1) variant of concern compared to other lineages: cohort study at a reference center in Brazil (preprint)

Background: The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variant of concern (VOC) Gamma (P.1) has increased transmissibility and resulted in elevated hospitalization, intensive care unit occupancy and mortality rates in Brazil. It is not known whether this VOC is also associated with more severe clinical course of disease. Methods This was a retrospective cohort study with non-elderly patients hospitalized for COVID-19 from June to December/2020 (first period) and February to May/2021 (second period) at a reference hospital in Brazil. Two cohorts were performed: the main cohort, composed by patients with SARS-CoV-2 lineages confirmed by whole genome sequencing; and the sensitivity cohort, composed by all eligible patients admitted before and after the emergence of Gamma. The primary outcome was the incidence rate of need of advanced ventilatory support. Results In the main cohort a total of 86 (43 Gamma and 43 non-Gamma) patients were included. Baseline characteristics were similar, except that Gamma patients had lower median Charlson’s comorbidity score. The crude and adjusted incidence rates of advanced respiratory support (adjusted Hazard Ratio [aHR], 1.78; 95% Confidence Interval [CI], 1.05–3.03), invasive respiratory support (aHR, 2.64; 95% CI, 1.34–5.19) and 28-day mortality from onset of symptoms (aHR, 4.73; 95% CI, 1.15–19.41) and adjusted 28-day mortality from hospital admission (aHR, 3.72; 95% CI, 1.19–11.65) were significantly higher in patients infected by Gamma. These patients had significantly lower days alive and free of supplemental oxygen support. The sensitivity cohort included 433 patients: 259 from the first and 174 from the second period (before and after the emergence of Gamma, respectively). Baseline characteristics were similar, except for a higher incidence of severe distress respiratory syndrome in patients from second group at admission. Patients from the second period had significantly higher incidence rates of advanced respiratory support (aHR, 2.04; 95% CI, 1.60–2.59), invasive ventilatory support (aHR, 2.72; 95%CI, 2.05–3.62), and 28-day mortality from the onset of symptoms (aHR, 2.62; 95%CI, 1.46–4.72). Conclusions Our study suggests that in non-elderly hospitalized patients, COVID-19 caused by Gamma VOC may present a more severe clinical course, with increased need of advanced respiratory support and higher 28-day mortality.

A Randomized Single Blind Controlled Trial of Combination Therapy (Spironolactone and Sitagliptin) in Hospitalized Adult Patients with Covid-19 (preprint)

Background: COVID-19 may cause respiratory distress syndrome, ICU admission and death. Treatment of COVID-19 to prevent hospitalization, respiratory distress syndrome and death remains a priority. Our investigation sought to determine whether combination of spironolactone and Sitagliptin could reduce hospitalization for outpatient and death for inpatient with SARS-CoV-2 infection.Methods: This single blind, 4-arms, prospective randomized clinical trial was conducted at Shiraz University of Medical Sciences and Bushehr University of Medical Sciences hospitals during the second wave of the COVID-19 pandemic between December 2020 and April 2021. We randomized hospitalized adult patients with COVID-19 pneumonia into four groups: control (standard therapy), combination (Sitagliptin, spironolactone and standard therapy), Sitagliptin (Sitagliptin and standard therapy) or spironolactone (spironolactone and standard therapy). The primary outcome was the clinical improvement of the patients in the hospital as measured on an eight-point numerical scale ranging from no limitation of activities (score 1) to death (score 8). The secondary outcomes included intubation, ICU admission, end organ damages, CT findings and paraclinical information. We also treated 60 outpatients with SARS-CoV-2 infection to assess hospitalization rate.Results: 263 admitted patients were randomly assigned to control group (87 patients), combination group (60 patients), Sitagliptin group (66 patients) and Spironolactone group (50 patients). There were no significant differences in baseline characteristics, except for higher age in control group. The intervention groups, especially combination therapy, had better clinical outcomes. However, the mortality rate was lower in spironolactone receivers. Our intervention reduced lung infiltration but not the area of involvement in lung. The combination (Sitagliptin, spironolactone) therapy for outpatients with SARS-CoV-2 infection could reduce hospitalization rate to less than 2 percent.Conclusion: Sitagliptin and spironolactone can potentially improve clinical outcomes of hospitalized COVID-19 patients. Furthermore, early prescription of this combination can reduce hospitalization rate.Clinical Trial Registration Details: IRCT registration number: IRCT20201003048904N2, Registration date: December 10, 2020. Funding Information: This project is supported by Shiraz University of Medical Sciences, Bushehr University Medical Sciences, Faghihi Hospital and Shohadaye_Khalije_Fars Hospital. Declaration of Interests: The author has declared that no conflict of interest exists.Ethics Approval Statement: The ethics committee of Shiraz University of Medical Sciences (IR.SUMS.MED.REC.1399.550) and Bushehr University of Medical Sciences (IR.BPUMS.REC.1399.140) approved the study. We followed the declaration of Helsinki and Iranian national guidelines for ethics in research to design the study. The research physicians had routinely collected a written formal informed consent at the time of admission.

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.

Association of Maternal SARS-CoV-2 Infection in Pregnancy With Neonatal Outcomes.

Importance: The outcomes of newborn infants of women testing positive for SARS-CoV-2 in pregnancy is unclear. Objective: To evaluate neonatal outcomes in relation to maternal SARS-CoV-2 test positivity in pregnancy. Design, Setting, and Participants: Nationwide, prospective cohort study based on linkage of the Swedish Pregnancy Register, the Neonatal Quality Register, and the Register for Communicable Diseases. Ninety-two percent of all live births in Sweden between March 11, 2020, and January 31, 2021, were investigated for neonatal outcomes by March 8, 2021. Infants with malformations were excluded. Infants of women who tested positive for SARS-CoV-2 were matched, directly and using propensity scores, on maternal characteristics with up to 4 comparator infants. Exposures: Maternal test positivity for SARS-CoV-2 in pregnancy. Main Outcomes and Measures: In-hospital mortality; neonatal resuscitation; admission for neonatal care; respiratory, circulatory, neurologic, infectious, gastrointestinal, metabolic, and hematologic disorders and their treatments; length of hospital stay; breastfeeding; and infant test positivity for SARS-CoV-2. Results: Of 88 159 infants (49.0% girls), 2323 (1.6%) were delivered by mothers who tested positive for SARS-CoV-2. The mean gestational age of infants of SARS-CoV-2-positive mothers was 39.2 (SD, 2.2) weeks vs 39.6 (SD, 1.8) weeks for comparator infants, and the proportions of preterm infants (gestational age <37 weeks) were 205/2323 (8.8%) among infants of SARS-CoV-2-positive mothers and 4719/85 836 (5.5%) among comparator infants. After matching on maternal characteristics, maternal SARS-CoV-2 test positivity was significantly associated with admission for neonatal care (11.7% vs 8.4%; odds ratio [OR], 1.47; 95% CI, 1.26-1.70) and with neonatal morbidities such as respiratory distress syndrome (1.2% vs 0.5%; OR, 2.40; 95% CI, 1.50-3.84), any neonatal respiratory disorder (2.8% vs 2.0%; OR, 1.42; 95% CI, 1.07-1.90), and hyperbilirubinemia (3.6% vs 2.5%; OR, 1.47; 95% CI, 1.13-1.90). Mortality (0.30% vs 0.12%; OR, 2.55; 95% CI, 0.99-6.57), breastfeeding rates at discharge (94.4% vs 95.1%; OR, 0.84; 95% CI, 0.67-1.05), and length of stay in neonatal care (median, 6 days in both groups; difference, 0 days; 95% CI, -2 to 7 days) did not differ significantly between the groups. Twenty-one infants (0.90%) of SARS-CoV-2-positive mothers tested positive for SARS-CoV-2 in the neonatal period; 12 did not have neonatal morbidity, 9 had diagnoses with unclear relation to SARS-CoV-2, and none had congenital pneumonia. Conclusions and Relevance: In a nationwide cohort of infants in Sweden, maternal SARS-CoV-2 infection in pregnancy was significantly associated with small increases in some neonatal morbidities. Given the small numbers of events for many of the outcomes and the large number of statistical comparisons, the findings should be interpreted as exploratory.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection in Febrile Infants Without Respiratory Distress.

We report 2 cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (COVID-19) in infants presenting with fever in the absence of respiratory distress who required hospitalization for evaluation of possible invasive bacterial infections. The diagnoses resulted from routine isolation and real-time reverse-transcription polymerase chain reaction-based testing for SARS-CoV-2 for febrile infants in an outbreak setting.

Trends in the Utilization of the Pediatric Emergency Department during the COVID-19 Outbreak (preprint)

Background: Despite numerous prior interventions to reduce unnecessary visits to the emergency department (ED), overutilization and overreliance on EDs continue to negatively impact quality of care and cost. Objective: Motivated by finding solutions to ED overuse, we evaluated the effect of COVID19 on pediatric ED utilization, specifically focusing on patients with pulmonary diagnoses. Methods: A retrospective study was conducted to review visits to the pediatric ED at Phoenix Children’s Hospital. The baseline pre-COVID19 period ranged from 01/01/2016 to 03/14/2019. Post-COVID19 data were collected from 03/15/2020 to 07/31/2020. Study subjects included all patients between 0-18 years of age. Data was collected biweekly for the number of ED visits, admission to hospital from ED, presenting diagnosis and pulmonary consults. Results: The average number of biweekly ED visits decreased significantly from 3437 during baseline to 2061 post-COVID19, while the percent of hospital admissions increased from 0.14% to 0.18% (p< 0.01). A significant decrease was also observed in the biweekly average number of pulmonology consults (527 to 250), and the percent of pulmonology consults (0.15% to 0.11%), presenting diagnosis of asthma (130 to 59), tracheostomy (7 to 6), cystic fibrosis (7 to 5), cough/wheeze (66 to 41) and bronchiolitis/upper and lower respiratory tract infections (300 to 126). No changes were detected in chronic respiratory failure, respiratory distress or hypoxemia. Conclusion: Many factors including telehealth, improved infection control measures, social responsibility, and fear of getting sick may have played a role in the reduction in our ED visits during the COVID pandemic.