Summary X‐linked lymphoproliferative disease (XLP) is an inherited immunodeficiency characterized by the clinical triad of increased susceptibility to primary Epstein–Barr virus (EBV) infection, dysgammaglobulinaemia and lymphoma. Most cases are caused by germline mutations in the SH2D1A gene, which encodes the adaptor molecule Signalling Lymphocytic Activation Molecule (SLAM)‐associated protein (SAP). Recently, a subset of patients with an XLP‐like phenotype was found to carry mutations in XIAP, the gene encoding the X‐linked inhibitor of apoptosis protein (XIAP). Studies of XLP patients and Sap−/− mice reveal that loss of SAP expression impairs immune cell activities, such as natural killer and CD8+ T cell cytotoxicity, T cell cytokine production, activation‐induced cell death, germinal centre formation and natural killer T cell development. Efforts to dissect the diverse roles of SAP and XIAP are enhancing our understanding of immune cell biology and defining how genetic defects in these molecules predispose to EBV‐specific as well as more general cellular and humoral immune dysfunction. These studies are also highlighting critical signalling pathways that might be amenable to pharmacological targeting to improve the treatment of XLP and other disorders associated with impaired antiviral and antitumour immunity.

Background Coronavirus disease‐2019 (COVID‐19) has been associated with an increased risk of acute cardiac events. However, the effect of COVID‐19 on repolarization heterogeneity is not yet established. In this study, we evaluated electrocardiogram (ECG) markers of repolarization heterogeneity in patients hospitalized with COVID‐19. In addition, we performed a systematic review and meta‐analysis of the published studies. Methods QT dispersion (QTd), the interval between T wave peak to T wave end (TpTe), TpTe/QT (with and without correction), QRS width, and the index of cardio‐electrophysiological balance (iCEB) were calculated in 101 hospitalized COVID‐19 patients and it was compared with 101 non‐COVID‐19 matched controls. A systematic review was performed in four databases and meta‐analysis was conducted using Stata software. Results Tp‐Te, TpTe/QT, QRS width, and iCEB were significantly increased in COVID‐19 patients compared with controls (TpTe = 82.89 vs. 75.33 ms (ms), p‐value = .005; TpTe/QT = 0.217 vs. 0.203 ms, p‐value = .026). After a meta‐analysis of 679 COVID‐19 cases and 526 controls from 9 studies, TpTe interval, TpTe/QT, and TpTe/QTc ratios were significantly increased in COVID‐19 patients. Meta‐regression analysis moderated by age, gender, diabetes mellitus, hypertension, and smoking reduced the heterogeneity. QTd showed no significant correlation with COVID‐19. Conclusion COVID‐19 adversely influences the ECG markers of transmural heterogeneity of repolarization. Studies evaluating the predictive value of these ECG markers are warranted to determine their clinical utility.