Deep immunophenotyping reveals biomarkers of multisystemic inflammatory syndrome in children in a Latin American cohort.

BACKGROUND: Multisystemic inflammatory syndrome in children (MIS-C) is a life-threatening disease that occurs 2-5 weeks after severe acute respiratory syndrome coronavirus 2 exposure and is characterized by severe multisystemic inflammation. Early recognition of MIS-C is key to prognosis; therefore, establishing clinical and laboratory biomarkers that predict complications is urgently needed. OBJECTIVE: We characterized the immune response and clinical features of patients with acute MIS-C and determined biomarkers of disease in a cohort of 42 Latin American patients. METHODS: Immune characterization was performed using flow cytometry from peripheral mononuclear cells and severe acute respiratory syndrome coronavirus 2-specific humoral and cellular response was performed using flow cytometry, enzyme-linked immunospot, enzyme-linked immunosorbent assay, and neutralizing antibody assays. RESULTS: MIS-C is characterized by robust T-cell activation and cytokine storm. We uncovered that while C-X-C motif chemokine ligand (CXCL) 9, IL-10, CXCL8, CXCL10, IL-6, and IL-18 are significantly elevated in patients with shock, while CCL5 was increased in milder disease. Monocyte dysregulation was specifically associated with KD-like MIS-C. Interestingly, MIS-C patients show a natural killer cell degranulation defect that is persistent after 6 months of disease presentation, suggesting it could underlie disease susceptibility. Most MIS-C had gastrointestinal involvement, and higher levels of neopterin were identified in their stools, potentially representing a biomarker of intestinal inflammation in MIS-C. Severe acute respiratory syndrome coronavirus 2-specific cellular response and neutralizing antibodies were identifiable in convalescent MIS-C patients, suggesting sustained immunity. CONCLUSION: Clinical characterization and comprehensive immunophenotyping of Chilean MIS-C cohort provide valuable insights in understanding immune dysregulation in MIS-C and identify relevant biomarkers of disease that could be used to predict severity and organ involvement.

[SARS-CoV-2 infection in people living with HIV. Topics on the global panorama and in Chile]. / Infección por SARS-CoV-2 en personas viviendo con VIH. Tópicos del panorama mundial y en Chile.

The COVID-19 disease is caused by the SARS-CoV-2 virus and was declared a pandemic by the WHO on March 11, 2020. To date, more than 500 million people have been infected and it has caused over 6 million deaths worldwide. People that belong to the most vulnerable risk groups, such as those at the extremes of life, patients with chronic comorbidities and those with severe immunosuppression, are especially susceptible to developing a severe form of COVID-19 infection and death. Subjects living with HIV, especially those in precarious immunological conditions or those in whom antiretroviral therapy is yet to be started, may be at risk of developing complications related to COVID-19, as observed with other infectious diseases. This review aims to determine the magnitude of the impact of the SARS-CoV-2 virus on people living with HIV in Chile.

Multicenter analysis of neutrophil extracellular trap dysregulation in adult and pediatric COVID-19.

Dysregulation in neutrophil extracellular trap (NET) formation and degradation may play a role in the pathogenesis and severity of COVID-19; however, its role in the pediatric manifestations of this disease, including multisystem inflammatory syndrome in children (MIS-C) and chilblain-like lesions (CLLs), otherwise known as "COVID toes," remains unclear. Studying multinational cohorts, we found that, in CLLs, NETs were significantly increased in serum and skin. There was geographic variability in the prevalence of increased NETs in MIS-C, in association with disease severity. MIS-C and CLL serum samples displayed decreased NET degradation ability, in association with C1q and G-actin or anti-NET antibodies, respectively, but not with genetic variants of DNases. In adult COVID-19, persistent elevations in NETs after disease diagnosis were detected but did not occur in asymptomatic infection. COVID-19-affected adults displayed significant prevalence of impaired NET degradation, in association with anti-DNase1L3, G-actin, and specific disease manifestations, but not with genetic variants of DNases. NETs were detected in many organs of adult patients who died from COVID-19 complications. Infection with the Omicron variant was associated with decreased NET levels when compared with other SARS-CoV-2 strains. These data support a role for NETs in the pathogenesis and severity of COVID-19 in pediatric and adult patients.

[Acute pancreatitis associated with SARS-CoV-2 infection in a pediatric patient]. / Pancreatitis aguda asociada a infección por SARS-CoV-2 en un paciente pediátrico.

INTRODUCTION: The recent discovery of SARS-CoV-2 and the disease COVID-19 which affects different organs and systems, mainly the respiratory one, representing a new challenge for physicians. Pancreatic affection is barely described, with only a few cases reported in the literature. OBJECTIVE: to communicate a case of acute pancreatitis associated with SARS-CoV-2 infection, to contribute to the knowledge of this new virus and its possible forms of presentation. CLINICAL CASE: An eleven-year-old male adolescent, with no history of contact with people confirmed or suspected of COVID-19, was admitted to the hospital with a 3-day history of periumbilical and epigastric abdominal pain, vomiting, and absence of stools, with no other symptoms. The laboratory tests showed increased pancreatic enzymes. Com puted tomography was compatible with acute edematous pancreatitis, without signs of biliary patho logy, diagnosing acute pancreatitis, at the same time that SARS-CoV-2 was isolated in the respiratory tract. Other possible differential diagnoses and history of epidemiological contact were ruled out. The patient was managed in the Critical Patient Unit with support measures. He evolved favorably, without respiratory symptoms. CONCLUSION: SARS-CoV-2 infection can be associated with atypical presentations, including acute pancreatitis. The physiopathological mechanism of pancreatic damage is not yet clear. Physicians should be aware of the COVID-19 involvement of other systems, beyond the respiratory one.

Severe Acute Respiratory Syndrome Coronavirus 2 Antibody Prevalence in Blood in a Large School Community Subject to a Coronavirus Disease 2019 Outbreak: A Cross-sectional Study.

BACKGROUND: A severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak affecting 52 people from a large school community in Santiago, Chile, was identified (12 March) 9 days after the first case in the country. We assessed the magnitude of the outbreak and the role students and staff played using self-administered antibody detection tests and a self-administered survey. METHODS: The school was closed on 13 March, and the entire community was placed under quarantine. We implemented a home-delivery, self-administered, immunoglobin (Ig) G/IgM antibody test and survey to a classroom-stratified sample of students and all staff from 4-19 May. We aimed to determine the overall seroprevalence rates by age group, reported symptoms, and contact exposure, and to explore the dynamics of transmission. RESULTS: The antibody positivity rates were 9.9% (95% confidence interval [CI], 8.2-11.8) for 1009 students and 16.6% (95% CI, 12.1-21.9) for 235 staff. Among students, positivity was associated with a younger age (P = .01), a lower grade level (P = .05), prior real-time polymerase chain reaction (RT-PCR) positivity (P = .03), and a history of contact with a confirmed case (P < .001). Among staff, positivity was higher in teachers (P = .01) and in those previously RT-PCR positive (P < .001). Excluding RT-PCR-positive individuals, antibody positivity was associated with fever in adults and children (P = .02 and P = .002, respectively), abdominal pain in children (P = .001), and chest pain in adults (P = .02). Within antibody-positive individuals, 40% of students and 18% of staff reported no symptoms (P = .01). CONCLUSIONS: Teachers were more affected during the outbreak and younger children were at a higher risk for infection, likely because index case(s) were teachers and/or parents from the preschool. Self-administered antibody testing, supervised remotely, proved to be a suitable and rapid tool. Our study provides useful information for school reopenings.

Neurologic Features Associated With SARS-CoV-2 Infection in Children: A Case Series Report.

INTRODUCTION: Although multiple neurologic manifestations associated with SARS-CoV-2 infection have been described in adults, there is little information about those presented in children. Here, we described neurologic manifestations associated with COVID-19 in the pediatric population. METHODS: Retrospective case series report. We included patients younger than 18 years, admitted with confirmed SARS-CoV-2 infection and neurologic manifestations at our hospital in Santiago, Chile. Demographics, clinical presentations, laboratory results, radiologic and neurophysiological studies, treatment, and outcome features were described. Cases were described based on whether they presented with predominantly central or peripheral neurologic involvement. RESULTS: Thirteen of 90 (14.4%) patients admitted with confirmed infection presented with new-onset neurologic symptoms and 4 patients showed epilepsy exacerbation. Neurologic manifestations ranged from mild (headache, muscle weakness, anosmia, ageusia), to severe (status epilepticus, Guillain-Barré syndrome, encephalopathy, demyelinating events). CONCLUSIONS: We found a wide range of neurologic manifestations in children with confirmed SARS-CoV-2 infection. In general, neurologic symptoms were resolved as the systemic presentation subsided. It is essential to recognize and report the main neurologic manifestations related to this new infectious disease in the pediatric population. More evidence is needed to establish the specific causality of nervous system involvement.