Gastrointestinal Manifestations in Hospitalized Children With Acute SARS-CoV-2 Infection and Multisystem Inflammatory Condition: An Analysis of the VIRUS COVID-19 Registry

BACKGROUND: Describe the incidence and associated outcomes of gastrointestinal (GI) manifestations of acute coronavirus disease 2019 (COVID-19) and multisystem inflammatory syndrome in hospitalized children (MIS-C). METHODS: Retrospective review of the Viral Infection and Respiratory Illness Universal Study registry, a prospective observational, multicenter international cohort study of hospitalized children with acute COVID-19 or MIS-C from March 2020 to November 2020. The primary outcome measure was critical COVID-19 illness. Multivariable models were performed to assess for associations of GI involvement with the primary composite outcome in the entire cohort and a subpopulation of patients with MIS-C. Secondary outcomes included prolonged hospital length of stay defined as being >75th percentile and mortality. RESULTS: Of the 789 patients, GI involvement was present in 500 (63.3%). Critical illness occurred in 392 (49.6%), and 18 (2.3%) died. Those with GI involvement were older (median age of 8 yr), and 18.2% had an underlying GI comorbidity. GI symptoms and liver derangements were more common among patients with MIS-C. In the adjusted multivariable models, acute COVID-19 was no associated with the primary or secondary outcomes. Similarly, despite the preponderance of GI involvement in patients with MIS-C, it was also not associated with the primary or secondary outcomes. CONCLUSIONS: GI involvement is common in hospitalized children with acute COVID-19 and MIS-C. GI involvement is not associated with critical illness, hospital length of stay or mortality in acute COVID-19 or MIS-C.

Variation in use of anti-viral and anti-inflammatory medications in patients hospitalized with COVID-19: Results from the international viral infection and respiratory illness universal study (virus)

RATIONALE: In the absence of effective therapies at the start of the Coronavirus disease of 2019 (COVID-19) pandemic, anti-viral and antiinflammatory medications were used for management of COVID-19 without robust evidence of their benefit. The patterns of use, implementation, and de-implementation of these medications is unclear. METHODS: We performed a retrospective, observational study on an international cohort of adult patients hospitalized from March 2020 to November 2020 with laboratory confirmed COVID-19 infection, receiving supplemental oxygen, and enrolled in the Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study (VIRUS) Registry. The primary outcome of interest was to describe the hospital-level variation in the most commonly used medications repurposed for empiric management of patients hospitalized with COVID-19 (hydroxychloroquine, remdesivir, corticosteroids, and anti-IL-6 therapies). Secondary outcomes included geographic and temporal variation in medication use. RESULTS: Among 6,621 patients with COVID-19 across 86 hospitals (predominantly USbased [88%]), 1,373 (20.7%, hospital usage rates range 0%-96.4%) received corticosteroids, 1,302 (19.7%, range 0%-100%) received hydroxychloroquine, 602 (9.1%, range: 0%-65.7%) received remdesivir, and 405 (6.1%, range 0%-87.5%) received an anti-IL6 medication. USbased hospitals vs non-US hospitals showed differences in medication use with 9.9% vs. 0.8% use of remdesivir, 19.5% vs 33.2% use of corticosteroids, 18.7% vs 29.6% use of hydroxychloroquine and 6.3% vs. 3.9% use of anti-IL6 medications. Comparing use prior to July 2020 with use after July 2020, prescription of remdesivir increased from 6.5% to 20.5%, corticosteroid use increased from 17.5% to 35.0%, hydroxychloroquine use decreased from 23.9% to 1.1% and anti-IL6 use decreased from 7.0% to 2.4%. CONCLUSIONS: Hospital-level variation and geographic variation in use of repurposed anti-viral and anti-inflammatory medications for the management of COVID-19 infection was large. Coinciding with accrual of scientific evidence, the use of remdesivir and corticosteroids increased over time, while the use of hydroxychloroquine and anti-IL6 medications decreased over time. Further studies are needed to evaluate the drivers of hospital variation and impact on clinical outcomes.

Variation in high-flow nasal cannula and non-invasive ventilation practice patterns during the COVID-19 pandemic: Results from the international viral infection and respiratory illness universal study (virus)

RATIONALE: Critical care guidelines have supported use of non-invasive respiratory support modalities in patients with acute respiratory failure from COVID-19 since the beginning of the pandemic. However, concerns surrounding viral particle aerosolization, nosocomial spread, and patient self-induced lung injury have likely influenced choice of respiratory support strategies. To date, high flow nasal cannula (HFNC) and non-invasive positive pressure ventilation (NIPPV) practice patterns have not been characterized for patients with COVID-19. METHODS: We enrolled hospitalized patients aged 18 years or older with laboratory confirmed COVID-19 infection who received supplemental oxygen, using the Society of Critical Care Medicine Discovery VIRUS Registry. The primary outcome was hospital-level variation in use of HFNC and NIPPV, summarized using the intraclass correlation coefficient and median odds ratio. Hierarchical random effects models were used to estimate patient and hospital factors associated with HFNC and NIPPV use. Risk-adjusted estimation of the association between hospital HFNC/NIPPV use and patient risk of receiving invasive mechanical ventilation (IMV) was assessed as a secondary outcome. RESULTS: Among 8,532 patients with COVID-19 receiving oxygen support across 73 hospitals, the majority were treated in the US (92.3%) and were older (median age 63 years, IQR 52-74), white (49.1%), men (56.8%) with median SOFA score of 4 (IQR 1-6) and admission PaO2:FiO2 below 300 (49.4%). Of these, 5,298 (62.1%) received low flow oxygen (nasal cannula or face mask), while 1,768 (20.7%) received HFNC, 773 (9.1%) received NIPPV and 693 (8.1%) received both HFNC/NIPPV. Patient SOFA score (OR 0.92, 95% CI 0.90, 0.95), treatment for COVID-19 after July versus March-June (OR 1.3, 95% CI 1.0, 1.6) and ICU versus floor admission (OR 10.3, 95% CI 8.2, 12.8) were associated with HFNC/NIPPV use. After adjusting for patient and hospital characteristics, the hospital of admission contributed to 27% of the variation in use of HFNC and/or NIPPV. Odds of receiving either modality at a randomly selected high vs. low HFNC/NIPPV utilization hospital was 2.9. Hospital rates of HFNC/NIPPV use were not associated with patient receipt of IMV (OR 0.87, 95% CI 0.7, 1.1). CONCLUSION: Throughout the course of the COVID-19 pandemic, use of HFNC and NIPPV varied widely across hospitals, though use of non-invasive respiratory support modalities was not associated with patient risk for invasive mechanical ventilation. Further evaluation of HFNC and NIPPV exposure, progression to IMV and subsequent mortality within these subgroups may provide additional insights regarding optimal oxygenation and ventilation strategies of patients with COVID-19.

Pediatric COVID-19: A report from viral infection and respiratory illness universal study (VIRUS)

INTRODUCTION: Coronavirus disease (COVID-19) has affected all age groups across the world. There is limited multi-center data on characteristics and outcomes of COVID-19 in hospitalized children. Using Society of Critical Care Medicine (SCCM) Viral Infection and Respiratory Illness Universal Study (VIRUS) registry - a large, multicenter, international database, we sought to describe the characteristics, pre-existing conditions, need for pediatric intensive care unit (PICU) admission and outcomes in children hospitalized with COVID-19. METHODS: We conducted a retrospective review of data submitted to SCCM VIRUS database and included COVID-19 positive children hospitalized between February 2020 to July 2020. We collected data on demographics, symptoms and signs, pre-existing conditions, occurrence of MIS-C (multi-system inflammatory syndrome in children), need for PICU admission, hospital mortality and length of stay (LOS) among children hospitalized with COVID-19. We reported findings using descriptive analysis with median and interquartile range (IQR). RESULTS: A total 419 children (<18 years) were admitted to 49 participating hospitals due to COVID-19. The median age was 7 (1-15) years (N=413) and male: female ratio was 1.2:1. A majority were White (48%), followed by African American (23%) and other race (22%) (out of N=412). The ethnic distribution consisted of 52% Non-Hispanic, 39% Hispanic and 9% unknown (out of N=410). The median (IQR) weight was 27 (9-64.5) kgs (out of N=407) and height was 120 (67-161) cm (out of N=377). A majority of children presented with fever (61%), followed by nausea/vomiting (29%), dry cough (24%) and abdominal pain (19%). Half (51%) of children had pre-existing conditions (out of N=336), 28% children had CDC criteria of MIS-C (out of N=365) and 45% children needed PICU care (out of N=402). The hospital mortality was 3.5% (out of N=313) and LOS [median (IQR)] was 4 (1.8-8.1) days (N=313) with majority (93%) children discharged to home without assistance (out of N=296). CONCLUSIONS: This report describes the characteristics and outcomes of children hospitalized with COVID-19 from one of the largest COVID-19 global database. Though a good proportion of children hospitalized with COVID-19 had pre-existing conditions and needed PICU care, overall hospital mortality was low.

Risk factors for severe COVID-19 illness in children: Analysis of the virus: COVID-19 registry

INTRODUCTION: A very small proportion of children who get infected with the novel coronavirus (COVID-19) have a severe disease requiring ICU care. Little is known about what risk factors are associated with severe disease in children. The purpose of this study was to compare characteristics of children with ?severe? disease defined as those requiring ICU admission vs. ?moderate? disease (hospital but not ICU admission) using the VIRUS: COVID 19 registry. METHODS: Retrospective analysis of the Society of Critical Care Medicine VIRUS: COVID-19 registry encompassing children hospitalized at 49 participating sites between 02/20 to 07/20. Patient demographics and clinical presentations were compared among patients who required ICU admission vs. those who did not. Univariate and Multivariate logistic regression was performed using JMP. RESULTS: Data was available for 398 children, of which 181 (45.4%) were admitted to ICU. Children who required ICU admission were older (10 years vs. 3.67 years, p<0.01) and were more likely to be African American (28.8% versus 17.8%, p= 0.02). A higher proportion of patients who required ICU admission have pre-existing conditions (58.2% vs. 44.3%, p= 0.01). Asthma was the most common pre-existing condition;but, a higher proportion of ICU admits had a diagnosis of asthma (14.2% vs. 7.52%, p= 0.01). The most common presenting symptom was fever;however, this did not differ between groups. Nausea/vomiting (38.4% vs. 22.1%, p<0.01), dyspnea (31.8% vs 17.7%, p<0.01) and abdominal pain (25.2% vs. 14.1%, p<0.01) were more common in patients requiring ICU admission. A significantly higher proportion of patients who required ICU had multisystem inflammatory syndrome of childhood [MIS-C (45.9% vs. 6.8%, p<0.01)] and acute kidney injury (9.34% vs. 1.7%, p<0.01). Race (AA vs white, odds ratio 1.9, p = 0.02) and age (p <0.01) were associated with the risk of ICU admission on multi variate logistic regression. Presence of preexisting conditions was not significant after accounting for age and race (p=0.07). CONCLUSIONS: Preliminary data suggest that children requiring ICU admissions for severe COVID-19 infections are more likely to be older and from African American race. Asthma is the most common preexisting condition. Gastrointestinal complains are more likely in severe COVID infections.