Extracorporeal Membrane Oxygenation for COVID-19-Associated Multisystem Inflammatory Syndrome in a 5-year-old

Severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2) is associated with multisystem inflammatory syndrome in children (MIS-C) that ranges from mild symptoms to cardiopulmonary collapse. A 5-year-old girl presented with shock and a rapid decline in left ventricular function requiring intubation. SARS-CoV-2 was diagnosed by viral Polymerase Chain Reaction (PCR), and she received remdesivir and COVID-19 convalescent plasma. Initial echocardiogram (ECHO) demonstrated low normal left ventricular function and mild left anterior descending coronary artery dilation. She remained hypotensive, despite high-dose epinephrine and norepinephrine infusions as well as stress-dose hydrocortisone. Admission SARS-CoV-2 IgG assay was positive, meeting the criteria for MIS-C. An ECHO 9 hours after admission demonstrated a severe decline in left ventricular function. Due to severe cardiogenic shock, she was cannulated for venoarterial extracorporeal support (ECMO). During her ECMO course, she was treated with remdesivir, intravenous methylprednisolone, intravenous immunoglobulin, and anakinra. She was decannulated on ECMO day 7, extubated the following day, and discharged home 2 weeks later without respiratory or cardiac support. The use of ECMO for cardiopulmonary support for pediatric patients with MIS-C is feasible and should be considered early as part of the treatment algorithm for patients with severe cardiopulmonary dysfunction

Systemic and Lower Respiratory Tract Immunity to SARS-CoV-2 Omicron and Variants in Pediatric Severe COVID-19 and Mis-C

Mucosal immunity plays an important role in the control of viral respiratory infections like SARS-CoV-2. While systemic immune responses against the SARS-2-CoV-2 have been studied in children, there is no information on mucosal antibody response, especially in the lower respiratory tract of children coronavirus disease 2019 (COVID-19) and post-infectious multisystem inflammatory syndrome in children (MIS-C) against emerging SARS-CoV-2 variants. Therefore, we evaluated neutralizing antibody responses in paired plasma and endotracheal aspirates of pediatric severe, acute COVID-19 or MIS-C patients against SARS-CoV-2 WA1/2020, as well as against variants of concern (VOCs). Neutralizing antibody responses against the SARS-CoV-2 WA1/2020 strain in pediatric plasma were 2-fold or 35-fold higher compared with the matched endotracheal aspirate in COVID-19 or MIS-C patients, respectively. In contrast to plasma, neutralizing antibody responses against the VOCs and variants of interest (VOIs) in endotracheal aspirates were lower, with only one endotracheal aspirate demonstrating neutralizing titers against the Iota, Kappa, Beta, Gamma, and Omicron variants. In conclusion, our findings suggest that children and adolescents with severe COVID-19 or MIS-C have weak mucosal neutralizing antibodies in the trachea against circulating SARS-CoV-2 Omicron and other VOCs, which may have implications for recovery and for re-infection with emerging SARS-CoV-2 variants

Fatal Pediatric COVID-19 Case With Seizures and Fulminant Cerebral Edema

The novel coronavirus, SARS-CoV-2, can present with a wide range of neurological manifestations, in both adult and pediatric populations. We describe here the case of a previously healthy 8-year-old girl who presented with seizures, encephalopathy, and rapidly progressive, diffuse, and ultimately fatal cerebral edema in the setting of acute COVID-19 infection. CSF analysis, microbiological testing, and neuropathology yielded no evidence of infection or acute inflammation within the central nervous system. Acute fulminant cerebral edema (AFCE) is an often fatal pediatric clinical entity consisting of fever, encephalopathy, and new-onset seizures followed by rapid, diffuse, and medically-refractory cerebral edema. AFCE occurs as a rare complication of a variety of common pediatric infections and a CNS pathogen is identified in only a minority of cases, suggesting a para-infectious mechanism of edema. This report suggests that COVID-19 infection can precipitate AFCE, and highlights the need for high suspicion and early recognition thereof

Effectiveness of Maternal mRNA COVID-19 Vaccination During Pregnancy Against COVID-19–Associated Hospitalizations in Infants Aged <6 Months During SARS-CoV-2 Omicron Predominance — 20 States, March 9, 2022–May 31, 2023

Infants aged <6 months are not eligible for COVID-19 vaccination. Vaccination during pregnancy has been associated with protection against infant COVID-19–related hospitalization. The Overcoming COVID-19 Network conducted a case-control study during March 9, 2022–May 31, 2023, to evaluate the effectiveness of maternal receipt of a COVID-19 vaccine dose (vaccine effectiveness [VE]) during pregnancy against COVID-19–related hospitalization in infants aged <6 months and a subset of infants aged <3 months. VE was calculated as (1 – adjusted odds ratio) x 100% among all infants aged <6 months and <3 months. Case-patients (infants hospitalized for COVID-19 outside of birth hospitalization and who had a positive SARS-CoV-2 test result) and control patients (infants hospitalized for COVID-19–like illness with a negative SARS-CoV-2 test result) were compared. Odds ratios were determined using multivariable logistic regression, comparing the odds of receipt of a maternal COVID-19 vaccine dose (completion of a 2-dose vaccination series or a third or higher dose) during pregnancy with maternal nonvaccination between case- and control patients. VE of maternal vaccination during pregnancy against COVID-19–related hospitalization was 35% (95% CI = 15%–51%) among infants aged <6 months and 54% (95% CI = 32%–68%) among infants aged <3 months. Intensive care unit admissions occurred in 23% of all case-patients, and invasive mechanical ventilation was more common among infants of unvaccinated (9%) compared with vaccinated mothers (1%) (p = 0.02). Maternal vaccination during pregnancy provides some protection against COVID-19–related hospitalizations among infants, particularly those aged <3 months. Expectant mothers should remain current with COVID-19 vaccination to protect themselves and their infants from hospitalization and severe outcomes associated with COVID-19

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Characteristics and Outcomes of US Children and Adolescents With Multisystem Inflammatory Syndrome in Children (MIS-C) Compared With Severe Acute COVID-19

Importance Refinement of criteria for multisystem inflammatory syndrome in children (MIS-C) may inform efforts to improve health outcomes. Objective To compare clinical characteristics and outcomes of children and adolescents with MIS-C vs those with severe coronavirus disease 2019 (COVID-19). Setting, Design, and Participants Case series of 1116 patients aged younger than 21 years hospitalized between March 15 and October 31, 2020, at 66 US hospitals in 31 states. Final date of follow-up was January 5, 2021. Patients with MIS-C had fever, inflammation, multisystem involvement, and positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcriptase–polymerase chain reaction (RT-PCR) or antibody test results or recent exposure with no alternate diagnosis. Patients with COVID-19 had positive RT-PCR test results and severe organ system involvement. Exposure SARS-CoV-2. Main Outcomes and Measures Presenting symptoms, organ system complications, laboratory biomarkers, interventions, and clinical outcomes. Multivariable regression was used to compute adjusted risk ratios (aRRs) of factors associated with MIS-C vs COVID-19. Results Of 1116 patients (median age, 9.7 years; 45% female), 539 (48%) were diagnosed with MIS-C and 577 (52%) with COVID-19. Compared with patients with COVID-19, patients with MIS-C were more likely to be 6 to 12 years old (40.8% vs 19.4%; absolute risk difference [RD], 21.4% [95% CI, 16.1%-26.7%]; aRR, 1.51 [95% CI, 1.33-1.72] vs 0-5 years) and non-Hispanic Black (32.3% vs 21.5%; RD, 10.8% [95% CI, 5.6%-16.0%]; aRR, 1.43 [95% CI, 1.17-1.76] vs White). Compared with patients with COVID-19, patients with MIS-C were more likely to have cardiorespiratory involvement (56.0% vs 8.8%; RD, 47.2% [95% CI, 42.4%-52.0%]; aRR, 2.99 [95% CI, 2.55-3.50] vs respiratory involvement), cardiovascular without respiratory involvement (10.6% vs 2.9%; RD, 7.7% [95% CI, 4.7%-10.6%]; aRR, 2.49 [95% CI, 2.05-3.02] vs respiratory involvement), and mucocutaneous without cardiorespiratory involvement (7.1% vs 2.3%; RD, 4.8% [95% CI, 2.3%-7.3%]; aRR, 2.29 [95% CI, 1.84-2.85] vs respiratory involvement). Patients with MIS-C had higher neutrophil to lymphocyte ratio (median, 6.4 vs 2.7, P < .001), higher C-reactive protein level (median, 152 mg/L vs 33 mg/L; P < .001), and lower platelet count (<150 ×103 cells/μL [212/523 {41%} vs 84/486 {17%}, P < .001]). A total of 398 patients (73.8%) with MIS-C and 253 (43.8%) with COVID-19 were admitted to the intensive care unit, and 10 (1.9%) with MIS-C and 8 (1.4%) with COVID-19 died during hospitalization. Among patients with MIS-C with reduced left ventricular systolic function (172/503, 34.2%) and coronary artery aneurysm (57/424, 13.4%), an estimated 91.0% (95% CI, 86.0%-94.7%) and 79.1% (95% CI, 67.1%-89.1%), respectively, normalized within 30 days. Conclusions and Relevance This case series of patients with MIS-C and with COVID-19 identified patterns of clinical presentation and organ system involvement. These patterns may help differentiate between MIS-C and COVID-19

Neurologic Involvement in Children and Adolescents Hospitalized in the United States for COVID-19 or Multisystem Inflammatory Syndrome

This article is made available for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.Importance Coronavirus disease 2019 (COVID-19) affects the nervous system in adult patients. The spectrum of neurologic involvement in children and adolescents is unclear. Objective To understand the range and severity of neurologic involvement among children and adolescents associated with COVID-19. Setting, Design, and Participants Case series of patients (age <21 years) hospitalized between March 15, 2020, and December 15, 2020, with positive severe acute respiratory syndrome coronavirus 2 test result (reverse transcriptase-polymerase chain reaction and/or antibody) at 61 US hospitals in the Overcoming COVID-19 public health registry, including 616 (36%) meeting criteria for multisystem inflammatory syndrome in children. Patients with neurologic involvement had acute neurologic signs, symptoms, or diseases on presentation or during hospitalization. Life-threatening involvement was adjudicated by experts based on clinical and/or neuroradiologic features. Exposures Severe acute respiratory syndrome coronavirus 2. Main Outcomes and Measures Type and severity of neurologic involvement, laboratory and imaging data, and outcomes (death or survival with new neurologic deficits) at hospital discharge. Results Of 1695 patients (909 [54%] male; median [interquartile range] age, 9.1 [2.4-15.3] years), 365 (22%) from 52 sites had documented neurologic involvement. Patients with neurologic involvement were more likely to have underlying neurologic disorders (81 of 365 [22%]) compared with those without (113 of 1330 [8%]), but a similar number were previously healthy (195 [53%] vs 723 [54%]) and met criteria for multisystem inflammatory syndrome in children (126 [35%] vs 490 [37%]). Among those with neurologic involvement, 322 (88%) had transient symptoms and survived, and 43 (12%) developed life-threatening conditions clinically adjudicated to be associated with COVID-19, including severe encephalopathy (n = 15; 5 with splenial lesions), stroke (n = 12), central nervous system infection/demyelination (n = 8), Guillain-Barré syndrome/variants (n = 4), and acute fulminant cerebral edema (n = 4). Compared with those without life-threatening conditions (n = 322), those with life-threatening neurologic conditions had higher neutrophil-to-lymphocyte ratios (median, 12.2 vs 4.4) and higher reported frequency of D-dimer greater than 3 μg/mL fibrinogen equivalent units (21 [49%] vs 72 [22%]). Of 43 patients who developed COVID-19–related life-threatening neurologic involvement, 17 survivors (40%) had new neurologic deficits at hospital discharge, and 11 patients (26%) died. Conclusions and Relevance In this study, many children and adolescents hospitalized for COVID-19 or multisystem inflammatory syndrome in children had neurologic involvement, mostly transient symptoms. A range of life-threatening and fatal neurologic conditions associated with COVID-19 infrequently occurred. Effects on long-term neurodevelopmental outcomes are unknown

Supporting Mental Health Recovery for Māori Whaiora: The Success Stories of Māori Whaiora and Non-Māori Clinicians

Māori people experiencing mental health issues have been historically under-served by mental health services. In the last three decades the development of Kaupapa Māori health services has provided a culturally responsive option for Māori. However, many Māori are still using mainstream mental health services and there is a need to develop a greater understanding of effective cross-cultural practice within the broader service system. This research, Supporting mental health recovery for Māori whaiora: The success stories of Māori whaiora and non-Māori clinicians, sought stories of positive cross-cultural engagement in a mainstream service lacking in Māori cultural resources. The hermeneutic methodology was informed by appreciative inquiry and brought a Māori interpretive lens. The stories of 13 people (7 whaiora and 6 clinicians) who felt something good had happened in their cross-cultural work were analysed to uncover the phenomenon of the relationship. Aspects of Māori and non-Māori experience were drawn from the stories and further illuminated by Māori cultural notions, relevant literature, and nuanced by the personal pre (and ever growing) understandings of the researcher. Exploring positive stories provided an opportunity to shed light on the cross-cultural practices, marked first by difference, misunderstanding and tension which, the participants revealed, lead to trust, respect and collaborative working. Tension and success appeared to be two sides of the same coin within the cross-cultural exchanges. Maintaining distance, giving time, acknowledging gaps in knowledge, respectful listening and giving power to the other were shown to be important steps. The willingness to share and blend points of view lead to new ways of creating recovery pathways and upheld the mana (status) and expertise of the other. Recommendations for practice and teaching include the importance of reflecting on one’s own history and prejudices, learning to dwell with uncertainty and the discomfort caused by difference. Clinicians are encouraged to see and hear, beyond ethnicity, the human they are working with. Future researchers are challenged to resist fault-finding and problem-solving and instead pursue an understanding of positive encounters. Cross-cultural research can extend knowledge and enhance already existing positive cross-cultural health care engagements to benefit Māori and other cultures in Aotearoa/New Zealand