ACUTE KIDNEY INJURY AND SARS-COV-19 IN CHILDREN: DATA FROM THE NATIONAL COVID COHORT COLLABORATIVE

B Introduction: b Acute Kidney Injury (AKI) occurs frequently in adult patients with SARS-CoV-19 and confers a higher risk of mortality. Harmonized, multi-institution datasets such as the National COVID Cohort Collaborative (N3C), a repository of over 6.3 million patients from 56 sites, offer a unique opportunity to assess AKI and clinical outcomes. AKI was associated with disease severity ( SP 2 sp , p< 0.001), with 457/602 (76%) of severe patients, but only 9,817/75,209 (13%) of mild patients, meeting AKI criteria. [Extracted from the article] Copyright of Critical Care Medicine is the property of Lippincott Williams & Wilkins and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Acute kidney injury in critically Ill children and young adults with suspected SARS-CoV2 infection.

BACKGROUND: We aimed to study the association of suspected versus confirmed infection with the novel SARS-CoV2 virus with the prevalence of acute kidney injury (AKI) in critically ill children. METHODS: Sequential point-prevalence study of children and young adults aged 7 days to 25 years admitted to intensive care units under investigation for SARS-CoV2 infection. AKI was staged in the first 14 days of enrollment using KDIGO creatinine-based staging. SARS-CoV2 positive (CONFIRMED) were compared to SUSPECTED (negative or unknown). Outcome data was censored at 28-days. RESULTS: In 331 patients of both sexes, 179 (54.1%) were CONFIRMED, 4.2% (14) died. AKI occurred in 124 (37.5%) and severe AKI occurred in 63 (19.0%). Incidence of AKI in CONFIRMED was 74/179 (41.3%) versus 50/152 (32.9%) for SUSPECTED; severe AKI occurred in 35 (19.6%) of CONFIRMED and 28 (18.4%) of SUSPECTED. Mortality was 6.2% (n = 11) in CONFIRMED, but 9.5% (n = 7) in those CONFIRMED with AKI. On multivariable analysis, only Hispanic ethnicity (relative risk 0.5, 95% CI 0.3-0.9) was associated with less AKI development among those CONFIRMED. CONCLUSIONS: AKI and severe AKI occur commonly in critically ill children with SARS-CoV2 infection, more than double the historical standard. Further investigation is needed during this continuing pandemic to describe and refine the understanding of pediatric AKI epidemiology and outcomes. TRIAL REGISTRATION: NCT01987921. IMPACT: What is the key message of the article? AKI occurs in children exposed to the novel SARS-CoV2 virus at high prevalence (~40% with some form of AKI and 20% with severe AKI). What does it add to the existing literature? Acute kidney injury (AKI) occurs commonly in adult patients with SARS-CoV2 (COVID), very little data describes the epidemiology of AKI in children exposed to the virus. What is the impact? A pediatric vaccine is not available; thus, the pandemic is not over for children. Pediatricians will need to manage significant end-organ ramifications of the novel SARS-CoV2 virus including AKI.

Secretory phospholipase A2 in SARS-CoV-2 infection and multisystem inflammatory syndrome in children (MIS-C).

Secretory phospholipase 2 (sPLA2) acts as a mediator between proximal and distal events of the inflammatory cascade. Its role in SARS-CoV-2 infection is unknown, but could contribute to COVID-19 inflammasome activation and cellular damage. We present the first report of plasma sPLA2 levels in adults and children with COVID-19 compared with controls. Currently asymptomatic adults with a history of recent COVID-19 infection (≥4 weeks before) identified by SARS-CoV-2 IgG antibodies had sPLA2 levels similar to those who were seronegative (9 ± 6 vs.17 ± 28 ng/mL, P = 0.26). In contrast, children hospitalized with severe COVID-19 had significantly elevated sPLA2 compared with those with mild or asymptomatic SARS-CoV-2 infection (269 ± 137 vs. 2 ± 3 ng/mL, P = 0.01). Among children hospitalized with multisystem inflammatory syndrome in children (MIS-C), all had severe disease requiring pediatric intensive care unit (PICU) admission. sPLA2 levels were significantly higher in those with acute illness <10 days versus convalescent disease ≥10 days (540 ± 510 vs. 2 ± 1, P = 0.04). Thus, sPLA2 levels correlated with COVID-19 severity and acute MIS-C in children, implicating a role in inflammasome activation and disease pathogenesis. sPLA2 may be a useful biomarker to stratify risk and guide patient management for children with acute COVID-19 and MIS-C. Therapeutic compounds targeting sPLA2 and inflammasome activation warrant consideration.

Altered amino acid profile in patients with SARS-CoV-2 infection.

Low plasma arginine bioavailability has been implicated in endothelial dysfunction and immune dysregulation. The role of arginine in COVID-19 is unknown, but could contribute to cellular damage if low. Our objective was to determine arginine bioavailability in adults and children with COVID-19 vs. healthy controls. We hypothesized that arginine bioavailability would be low in patients with COVID-19 and multisystem inflammatory syndrome in children (MIS-C). We conducted a prospective observational study of three patient cohorts; arginine bioavailability was determined in asymptomatic healthy controls, adults hospitalized with COVID-19, and hospitalized children/adolescents <21 y old with COVID-19, MIS-C, or asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection identified on admission screen. Mean patient plasma amino acids were compared to controls using the Student's t test. Arginine-to-ornithine ratio, a biomarker of arginase activity, and global arginine bioavailability ratio (GABR, arginine/[ornithine+citrulline]) were assessed in all three groups. A total of 80 patients were included (28 controls, 32 adults with COVID-19, and 20 pediatric patients with COVID-19/MIS-C). Mean plasma arginine and arginine bioavailability ratios were lower among adult and pediatric patients with COVID-19/MIS-C compared to controls. There was no difference between arginine bioavailability in children with COVID-19 vs. MIS-C. Adults and children with COVID-19 and MIS-C in our cohort had low arginine bioavailability compared to healthy adult controls. This may contribute to immune dysregulation and endothelial dysfunction in COVID-19. Low arginine-to-ornithine ratio in patients with COVID-19 or MIS-C suggests an elevation of arginase activity. Further study is merited to explore the role of arginine dysregulation in COVID-19.

Severe acute respiratory syndrome coronavirus 2 infection and critically ill children.

PURPOSE OF REVIEW: Amidst an ongoing pandemic, the delineation of the pediatric consequence of infection from the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) virus is emerging. This review summarizes available pediatric data and covers the aspects of epidemiology, critical illness with acute infection [coronavirus disease 2019 (COVID-19)], the discovered multi-inflammatory syndrome in children (MIS-C), and management options. RECENT FINDINGS: The available data from the source of the initial viral transmission and then through Europe, Africa, and the Western Hemisphere identifies important aspects of the SARS-CoV2 pandemic: 1) Pediatric infection occurs commonly, is likely underestimated, and transmission patterns remain incompletely described, 2) Pediatric patients suffer multiple end-organ injuries but COVID-19 is not the same prevalence in terms of severity as in adults, 3) MIS-C is a novel and life-threatening manifestation of exposure to the virus, 4) Management using a combination of supportive care, standard practice intensive care management, and anti-inflammatory agents is associated with recovery, 5) Long-term sequelae of viral exposure is unknown at this time. SUMMARY: Emerging evidence suggests pediatric patients are at risk for severe and life-threatening effects of exposure to SARS-CoV2. As the pandemic continues, further research is warranted - particularly as a vaccine is not yet available for use in children.

Quantitative SARS-CoV-2 Serology in Children With Multisystem Inflammatory Syndrome (MIS-C).

OBJECTIVES: We aimed to measure severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serological responses in children hospitalized with multisystem inflammatory syndrome in children (MIS-C) compared with those with coronavirus disease 2019 (COVID-19), those with Kawasaki disease (KD), and hospitalized pediatric controls. METHODS: From March 17, 2020, to May 26, 2020, we prospectively identified hospitalized children with MIS-C (n = 10), symptomatic COVID-19 (n = 10), and KD (n = 5) and hospitalized controls (n = 4) at Children's Healthcare of Atlanta. With institutional review board approval, we obtained prospective and residual blood samples from these children and measured SARS-CoV-2 spike receptor-binding domain (RBD) immunoglobulin M and immunoglobulin G (IgG), full-length spike IgG, and nucleocapsid protein antibodies using quantitative enzyme-linked immunosorbent assays and SARS-CoV-2 neutralizing antibodies using live-virus focus-reduction neutralization assays. We statistically compared the log-transformed antibody titers among groups and performed linear regression analyses. RESULTS: All children with MIS-C had high titers of SARS-CoV-2 RBD IgG antibodies, which correlated with full-length spike IgG antibodies (R 2 = 0.956; P < .001), nucleocapsid protein antibodies (R 2 = 0.846; P < .001), and neutralizing antibodies (R 2 = 0.667; P < .001). Children with MIS-C had significantly higher SARS-CoV-2 RBD IgG antibody titers (geometric mean titer 6800; 95% confidence interval 3495-13 231) than children with COVID-19 (geometric mean titer 626; 95% confidence interval 251-1563; P < .001), children with KD (geometric mean titer 124; 95% confidence interval 91-170; P < .001), and hospitalized controls (geometric mean titer 85; P < .001). All children with MIS-C also had detectable RBD immunoglobulin M antibodies, indicating recent SARS-CoV-2 infection. RBD IgG titers correlated with the erythrocyte sedimentation rate (R 2 = 0.512; P < .046) and with hospital (R 2 = 0.548; P = .014) and ICU lengths of stay (R 2 = 0.590; P = .010). CONCLUSIONS: Quantitative SARS-CoV-2 serology may have a role in establishing the diagnosis of MIS-C, distinguishing it from similar clinical entities, and stratifying risk for adverse outcomes.