Autoantibodies Against Proteins Previously Associated With Autoimmunity in Adult and Pediatric Patients With COVID-19 and Children With MIS-C.

The antibody profile against autoantigens previously associated with autoimmune diseases and other human proteins in patients with COVID-19 or multisystem inflammatory syndrome in children (MIS-C) remains poorly defined. Here we show that 30% of adults with COVID-19 had autoantibodies against the lung antigen KCNRG, and 34% had antibodies to the SLE-associated Smith-D3 protein. Children with COVID-19 rarely had autoantibodies; one of 59 children had GAD65 autoantibodies associated with acute onset of insulin-dependent diabetes. While autoantibodies associated with SLE/Sjögren's syndrome (Ro52, Ro60, and La) and/or autoimmune gastritis (gastric ATPase) were detected in 74% (40/54) of MIS-C patients, further analysis of these patients and of children with Kawasaki disease (KD), showed that the administration of intravenous immunoglobulin (IVIG) was largely responsible for detection of these autoantibodies in both groups of patients. Monitoring in vivo decay of the autoantibodies in MIS-C children showed that the IVIG-derived Ro52, Ro60, and La autoantibodies declined to undetectable levels by 45-60 days, but gastric ATPase autoantibodies declined more slowly requiring >100 days until undetectable. Further testing of IgG and/or IgA antibodies against a subset of potential targets identified by published autoantigen array studies of MIS-C failed to detect autoantibodies against most (16/18) of these proteins in patients with MIS-C who had not received IVIG. However, Troponin C2 and KLHL12 autoantibodies were detected in 2 of 20 and 1 of 20 patients with MIS-C, respectively. Overall, these results suggest that IVIG therapy may be a confounding factor in autoantibody measurements in MIS-C and that antibodies against antigens associated with autoimmune diseases or other human proteins are uncommon in MIS-C.

Immunopathological signatures in multisystem inflammatory syndrome in children and pediatric COVID-19.

Pediatric Coronavirus Disease 2019 (pCOVID-19) is rarely severe; however, a minority of children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) might develop multisystem inflammatory syndrome in children (MIS-C), with substantial morbidity. In this longitudinal multi-institutional study, we applied multi-omics (analysis of soluble biomarkers, proteomics, single-cell gene expression and immune repertoire analysis) to profile children with COVID-19 (n = 110) and MIS-C (n = 76), along with pediatric healthy controls (pHCs; n = 76). pCOVID-19 was characterized by robust type I interferon (IFN) responses, whereas prominent type II IFN-dependent and NF-κB-dependent signatures, matrisome activation and increased levels of circulating spike protein were detected in MIS-C, with no correlation with SARS-CoV-2 PCR status around the time of admission. Transient expansion of TRBV11-2 T cell clonotypes in MIS-C was associated with signatures of inflammation and T cell activation. The association of MIS-C with the combination of HLA A*02, B*35 and C*04 alleles suggests genetic susceptibility. MIS-C B cells showed higher mutation load than pCOVID-19 and pHC. These results identify distinct immunopathological signatures in pCOVID-19 and MIS-C that might help better define the pathophysiology of these disorders and guide therapy.

Vaccine Oka Varicella Meningitis in Two Adolescents.

The live-attenuated varicella vaccine, a routine immunization in the United States since 1995, is both safe and effective. Like wild-type varicella-zoster virus, however, vaccine Oka (vOka) varicella can establish latency and reactivate as herpes zoster, rarely leading to serious disease, particularly among immunocompromised hosts. Previous cases of reactivated vOka resulting in meningitis have been described in young children who received a single dose of varicella vaccine; less is known about vOka reactivation in older children after the 2-dose vaccine series. We present 2 adolescents with reactivated vOka meningitis, 1 immunocompetent and 1 immunocompromised, both of whom received 2 doses of varicella vaccine many years before as children. Pediatricians should be aware of the potential of vOka varicella to reactivate and cause clinically significant central nervous system disease in vaccinated children and adolescents.

Fatal ehrlichial myocarditis in a healthy adolescent: a case report and review of the literature.

Ehrlichial myocarditis is an unusual finding in nonimmunosuppressed patients. A case of fatal ehrlichiosis with rapidly progressive myocarditis and multiorgan failure from Ehrlichia chaffeensis in a previously healthy adolescent is described.

Spontaneous drainage of neonatal cephalohematoma: a delayed complication of scalp abscess.

Neonatal cephalohematomas are known complications of traumatic deliveries, and the majority of cases resolve without intervention. Scalp abscesses are rare and often described as benign complications of fetal scalp monitoring. Spontaneous drainage of a neonatal cephalohematoma, with or without associated scalp abscess, has not yet been described. We present a case of a neonate with recurrent Escherichia coli bacteremia and spontaneous drainage of a large cephalohematoma through an overlying scalp abscess.

Evaluation of rotavirus vaccine effectiveness in a pediatric group practice.

Vaccines are traditionally tested under the optimal conditions of clinical trials (efficacy). However, their public health impact is better assessed under the real conditions of a clinical practice (effectiveness). The authors aimed to estimate the effectiveness of a rotavirus vaccine (rhesus rotavirus vaccine-tetravalent (RRV-TV)) to prevent rotavirus-related hospitalization among children

Pulmonary infections in children with HIV infection.

The epidemic of pediatric acquired immunodeficiency syndrome (AIDS) in the United States, which peaked during the mid-1980s and early 1990s, was characterized by a variety of opportunistic infections in children infected with human immunodeficiency virus (HIV), often as the presenting illness of their HIV infection. Pneumocystis carinii pneumonia (PCP) during infancy was responsible for significant morbidity and mortality, followed by many other opportunistic infections, including recurrent, serious bacterial infections; disseminated cytomegalovirus infection; and disseminated Mycobacterium avium complex (MAC) infection. Many of these infections involve the lower respiratory tract either as a primary site of infection or as one of the sites involved in disseminated disease. Since the mid- to late 1990s, the pediatric HIV epidemic in the United States has witnessed a dramatic decrease in the frequency of most opportunistic infections and other severe manifestations of HIV infection in children, primarily because of lower rates of mother-to-child HIV transmission, development and implementation of guidelines for PCP prophylaxis, and availability of highly active antiretroviral therapy. Far fewer children are at risk for clinical progression of HIV disease and for opportunistic infections. Despite these successful trends, pulmonary opportunistic infections and pulmonary disease remain common clinical manifestations of pediatric HIV disease.