COVID-19 is Observed in Older Children During the Omicron Wave in New York City.

BACKGROUND: The Omicron variant of SARS-CoV-2 has a predilection for the upper airways, causing symptoms such as sore throat, hoarse voice, and stridor. OBJECTIVE: We describe a series of children with COVID-19-associated croup in an urban multicenter hospital system. METHODS: We conducted a cross-sectional study of children ≤18 years of age presenting to the emergency department during the COVID-19 pandemic. Data were extracted from an institutional data repository comprised of all patients who were tested for SARS-CoV-2. We included patients with a croup diagnosis by International Classification of Diseases, 10th revision code and a positive SARS-CoV-2 test within 3 days of presentation. We compared demographics, clinical characteristics, and outcomes for patients presenting during a pre-Omicron period (March 1, 2020-December 1, 2021) to the Omicron wave (December 2, 2021-February 15, 2022). RESULTS: We identified 67 children with croup, 10 (15%) pre-Omicron and 57 (85%) during the Omicron wave. The prevalence of croup among SARS-CoV-2-positive children increased by a factor of 5.8 (95% confidence interval 3.0-11.4) during the Omicron wave compared to prior. More patients were ≥6 years of age in the Omicron wave than prior (19% vs. 0%). The majority were not hospitalized (77%). More patients ≥6 years of age received epinephrine therapy for croup during the Omicron wave (73% vs. 35%). Most patients ≥6 years of age had no croup history (64%) and only 45% were vaccinated against SARS-CoV-2. CONCLUSION: Croup was prevalent during the Omicron wave, atypically affecting patients ≥6 years of age. COVID-19-associated croup should be added to the differential diagnosis of children with stridor, regardless of age. © 2022 Elsevier Inc.

Urine-based multi-omic comparative analysis of COVID-19 and bacterial sepsis-induced ARDS.

BACKGROUND: Acute respiratory distress syndrome (ARDS), a life-threatening condition during critical illness, is a common complication of COVID-19. It can originate from various disease etiologies, including severe infections, major injury, or inhalation of irritants. ARDS poses substantial clinical challenges due to a lack of etiology-specific therapies, multisystem involvement, and heterogeneous, poor patient outcomes. A molecular comparison of ARDS groups holds the potential to reveal common and distinct mechanisms underlying ARDS pathogenesis. METHODS: We performed a comparative analysis of urine-based metabolomics and proteomics profiles from COVID-19 ARDS patients (n = 42) and bacterial sepsis-induced ARDS patients (n = 17). To this end, we used two different approaches, first we compared the molecular omics profiles between ARDS groups, and second, we correlated clinical manifestations within each group with the omics profiles. RESULTS: The comparison of the two ARDS etiologies identified 150 metabolites and 70 proteins that were differentially abundant between the two groups. Based on these findings, we interrogated the interplay of cell adhesion/extracellular matrix molecules, inflammation, and mitochondrial dysfunction in ARDS pathogenesis through a multi-omic network approach. Moreover, we identified a proteomic signature associated with mortality in COVID-19 ARDS patients, which contained several proteins that had previously been implicated in clinical manifestations frequently linked with ARDS pathogenesis. CONCLUSION: In summary, our results provide evidence for significant molecular differences in ARDS patients from different etiologies and a potential synergy of extracellular matrix molecules, inflammation, and mitochondrial dysfunction in ARDS pathogenesis. The proteomic mortality signature should be further investigated in future studies to develop prediction models for COVID-19 patient outcomes.

Multi-omic comparative analysis of COVID-19 and bacterial sepsis-induced ARDS.

BACKGROUND: Acute respiratory distress syndrome (ARDS), a life-threatening condition characterized by hypoxemia and poor lung compliance, is associated with high mortality. ARDS induced by COVID-19 has similar clinical presentations and pathological manifestations as non-COVID-19 ARDS. However, COVID-19 ARDS is associated with a more protracted inflammatory respiratory failure compared to traditional ARDS. Therefore, a comprehensive molecular comparison of ARDS of different etiologies groups may pave the way for more specific clinical interventions. METHODS AND FINDINGS: In this study, we compared COVID-19 ARDS (n = 43) and bacterial sepsis-induced (non-COVID-19) ARDS (n = 24) using multi-omic plasma profiles covering 663 metabolites, 1,051 lipids, and 266 proteins. To address both between- and within- ARDS group variabilities we followed two approaches. First, we identified 706 molecules differently abundant between the two ARDS etiologies, revealing more than 40 biological processes differently regulated between the two groups. From these processes, we assembled a cascade of therapeutically relevant pathways downstream of sphingosine metabolism. The analysis suggests a possible overactivation of arginine metabolism involved in long-term sequelae of ARDS and highlights the potential of JAK inhibitors to improve outcomes in bacterial sepsis-induced ARDS. The second part of our study involved the comparison of the two ARDS groups with respect to clinical manifestations. Using a data-driven multi-omic network, we identified signatures of acute kidney injury (AKI) and thrombocytosis within each ARDS group. The AKI-associated network implicated mitochondrial dysregulation which might lead to post-ARDS renal-sequalae. The thrombocytosis-associated network hinted at a synergy between prothrombotic processes, namely IL-17, MAPK, TNF signaling pathways, and cell adhesion molecules. Thus, we speculate that combination therapy targeting two or more of these processes may ameliorate thrombocytosis-mediated hypercoagulation. CONCLUSION: We present a first comprehensive molecular characterization of differences between two ARDS etiologies-COVID-19 and bacterial sepsis. Further investigation into the identified pathways will lead to a better understanding of the pathophysiological processes, potentially enabling novel therapeutic interventions.

Indications for Hospitalization in Children with SARS-CoV-2 Infection during the Omicron Wave in New York City.

The emergence of the Omicron variant was accompanied by an acute increase in COVID-19 cases and hospitalizations in New York City. An increased incidence of COVID-19-associated croup in children during the Omicron wave has been recognized, suggesting that there may be other changes in clinical symptoms and severity. To better understand clinical outcomes and health care utilization in children infected with SARS-CoV-2 during the Omicron wave, we performed a cross-sectional study in pediatric patients aged ≤18 years who were tested for SARS-CoV-2 in pediatric emergency departments within a large medical system in New York City from 2 December 2021 to 23 January 2022. We described the clinical characteristics and outcomes of pediatric patients who presented to the pediatric emergency department and were hospitalized with SARS-CoV-2 infection during the Omicron wave in New York City. There were 2515 children tested in the ED for SARS-CoV-2 of whom 794 (31.6%) tested positive. Fifty-eight children were hospitalized for a COVID-19-related indication, representing 7.3% of all COVID-19-positive children and 72% of hospitalized COVID-19-positive children. Most (64%) children hospitalized for a COVID-19-related indication were less than 5 years old. Indications for hospitalization included respiratory symptoms, clinical monitoring of patients with comorbid conditions, and exacerbations of underlying disease. Eleven (19%) hospitalized children were admitted to the ICU and six (10%) required mechanical ventilation. Children infected with COVID-19 during the Omicron wave, particularly those less than 5 years old, were at risk for hospitalization. A majority of hospitalizations were directly related to COVID-19 infection although clinical indications varied with less than a half being admitted for respiratory diseases including croup. Our findings underscore the need for an effective COVID-19 vaccine in those less than 5 years old, continued monitoring for changes in clinical outcomes and health care utilization in children as more SARS-CoV-2 variants emerge, and understanding that children are often admitted for non-respiratory diseases with COVID-19.

Integrative metabolomic and proteomic signatures define clinical outcomes in severe COVID-19.

The coronavirus disease-19 (COVID-19) pandemic has ravaged global healthcare with previously unseen levels of morbidity and mortality. In this study, we performed large-scale integrative multi-omics analyses of serum obtained from COVID-19 patients with the goal of uncovering novel pathogenic complexities of this disease and identifying molecular signatures that predict clinical outcomes. We assembled a network of protein-metabolite interactions through targeted metabolomic and proteomic profiling in 330 COVID-19 patients compared to 97 non-COVID, hospitalized controls. Our network identified distinct protein-metabolite cross talk related to immune modulation, energy and nucleotide metabolism, vascular homeostasis, and collagen catabolism. Additionally, our data linked multiple proteins and metabolites to clinical indices associated with long-term mortality and morbidity. Finally, we developed a novel composite outcome measure for COVID-19 disease severity based on metabolomics data. The model predicts severe disease with a concordance index of around 0.69, and shows high predictive power of 0.83-0.93 in two independent datasets.

Baseline haemoglobin A1c and the risk of COVID-19 hospitalization among patients with diabetes in the INSIGHT Clinical Research Network.

AIMS: To examine the association between baseline glucose control and risk of COVID-19 hospitalization and in-hospital death among patients with diabetes. METHODS: We performed a retrospective cohort study of adult patients in the INSIGHT Clinical Research Network with a diabetes diagnosis and haemoglobin A1c (HbA1c) measurement in the year prior to an index date of March 15, 2020. Patients were divided into four exposure groups based on their most recent HbA1c measurement (in mmol/mol): 39-46 (5.7%-6.4%), 48-57 (6.5%-7.4%), 58-85 (7.5%-9.9%), and ≥86 (10%). Time to COVID-19 hospitalization was compared in the four groups in a propensity score-weighted Cox proportional hazards model adjusting for potential confounders. Patients were followed until June 15, 2020. In-hospital death was examined as a secondary outcome. RESULTS: Of 168,803 patients who met inclusion criteria; 50,016 patients had baseline HbA1c 39-46 (5.7%-6.4%); 54,729 had HbA1c 48-57 (6.5-7.4%); 47,640 had HbA1c 58-85 (7.5^%-9.9%) and 16,418 had HbA1c ≥86 (10%). Compared with patients with HbA1c 48-57 (6.5%-7.4%), the risk of hospitalization was incrementally greater for those with HbA1c 58-85 (7.5%-9.9%) (adjusted hazard ratio [aHR] 1.19, 95% confidence interval [CI] 1.06-1.34) and HbA1c ≥86 (10%) (aHR 1.40, 95% CI 1.19-1.64). The risk of COVID-19 in-hospital death was increased only in patients with HbA1c 58-85 (7.5%-9.9%) (aHR 1.29, 95% CI 1.06, 1.61). CONCLUSIONS: Diabetes patients with high baseline HbA1c had a greater risk of COVID-19 hospitalization, although association between HbA1c and in-hospital death was less consistent. Preventive efforts for COVID-19 should be focused on diabetes patients with poor glucose control.