Solid organ transplant patients are vulnerable to suffering neurologic complications from a wide array of viral infections and can be sentinels in the population who are first to get serious complications from emerging infections like the recent waves of arboviruses, including West Nile virus, Chikungunya virus, Zika virus, and Dengue virus. The diverse and rapidly changing landscape of possible causes of viral encephalitis poses great challenges for traditional candidate‐based infectious disease diagnostics that already fail to identify a causative pathogen in approximately 50% of encephalitis cases. We present the case of a 14‐year‐old girl on immunosuppression for a renal transplant who presented with acute meningoencephalitis. Traditional diagnostics failed to identify an etiology. RNA extracted from her cerebrospinal fluid was subjected to unbiased metagenomic deep sequencing, enhanced with the use of a Cas9‐based technique for host depletion. This analysis identified West Nile virus (WNV). Convalescent serum serologies subsequently confirmed WNV seroconversion. These results support a clear clinical role for metagenomic deep sequencing in the setting of suspected viral encephalitis, especially in the context of the high‐risk transplant patient population.

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While pregnancy increases the risk for severe COVID19, the clinical and immunological implications of COVID19 on maternal-fetal health remain unknown. Here, we present the clinical and immunological landscapes of 93 COVID19 mothers and 45 of their SARS-CoV-2-exposed infants through comprehensive serum proteomics profiling for >1400 cytokines of their peripheral and cord blood specimens. Prenatal SARS-CoV-2 infection triggers NF-κB-dependent proinflammatory immune activation. Pregnant women with severe COVID19 show increased inflammation and unique IFNλ antiviral signaling, with elevated levels of IFNL1 and IFNLR1. Furthermore, SARS-CoV-2 infection re-shapes maternal immunity at delivery altering the expression of pregnancy complication-associated cytokines, inducing MMP7, MDK, ESM1, and reducing BGN and CD209. Finally, COVID19-exposed infants exhibit induction of T cell-associated cytokines (IL33, NFATC3 and CCL21), while some undergo IL-1β/IL-18/CASP1 axis-driven neonatal respiratory distress despite birth at term. Our findings demonstrate COVID19-induced immune rewiring in both mothers and neonates, warranting long-term clinical follow-up to mitigate potential health risks.

Summary Kawasaki disease (KD) is the leading cause of acquired heart disease in children. In addition to coronary artery abnormalities, aneurysms and myocarditis, acute KD is also associated with echocardiogram (ECG) abnormalities in 40–80% of patients. Here, we show that these ECG changes are recapitulated in the Lactobacillus casei cell wall extract (LCWE)‐induced KD vasculitis mouse model. LCWE‐injected mice developed elevated heart rate and decreased R wave amplitude, with significant differences in prolonged ventricular repolarization. LCWE‐injected mice developed cardiac ganglion inflammation, that may affect the impulse‐conducting system in the myocardium. Furthermore, serum nerve growth factor (NGF) was significantly elevated in LCWE‐injected mice, similar to children with KD vasculitis, associated with increased neural remodeling of the myocardium. ECG abnormalities were prevented by blocking interleukin (IL)‐1 signaling with anakinra, and the increase in serum NGF and cardiac neural remodeling were similarly blocked in Il1r1−/− mice and in wild‐type mice treated with anakinra. Thus, similar to clinical KD, the LCWE‐induced KD vasculitis mouse model also exhibits electrophysiological abnormalities and cardiac neuronal remodeling, and these changes can be prevented by blocking IL‐1 signaling. These data support the acceleration of anti‐IL‐1 therapy trials to benefit KD patients.

Background As COVID‐19‐positive donors are becoming more common, there is an increasing need for the transplant community to evaluate the safety and efficacy of organ transplant from a SARS‐CoV‐2‐infected donor. Methods Here we describe outcomes of two pediatric kidney transplant recipients who were vaccinated against COVID‐19 and received their allograft from a SARS‐CoV‐2‐positive donor. Results Both donors did not die from a COVID‐19‐related illness; the first donor had 1 week of COVID‐19 symptoms 4 weeks prior to donation and the second was asymptomatic. Donor 1 had a Ct of 33.4 at 3 days and Donor 2 with a Ct of 37.2 at 16 days prior to donation. The first recipient was positive for SARS‐CoV‐2 anti‐spike IgG on the day of transplant, but the second patient was negative and both patients received IVIg perioperatively. There was no evidence of SARS‐CoV‐2 transmission or compromised renal function at 86‐ and 80‐day post‐transplant, respectively. Conclusions This case series suggests favorable short‐term outcomes with accepting SARS‐CoV‐2‐positive donors for pediatric renal transplantation, after thorough evaluation of the donor's risk for transmission, assessing the recipient's serologic status to SARS‐CoV‐2, and considering pre‐emptive measures to mitigate the risk for severe COVID‐19 should the recipient acquire donor‐derived SARS‐CoV‐2.