Severe SARS-CoV-2 disease in the context of a NF-κB2 loss-of-function pathogenic variant.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus that emerged recently and has created a global pandemic. Symptomatic SARS-CoV-2 infection, termed coronavirus disease 2019 (COVID-19), has been associated with a host of symptoms affecting numerous organ systems, including the lungs, cardiovascular system, kidney, central nervous system, gastrointestinal tract, and skin, among others. OBJECTIVE: Although several risk factors have been identified as related to complications from and severity of COVID-19, much about the virus remains unknown. The host immune response appears to affect the outcome of disease. It is not surprising that patients with intrinsic or secondary immune compromise might be particularly susceptible to complications from SARS-CoV-2 infection. Pathogenic loss-of-function or gain-of-function heterozygous variants in nuclear factor-κB2 have been reported to be associated with either a combined immunodeficiency or common variable immunodeficiency phenotype. METHODS: We evaluated the functional consequence and immunologic phenotype of a novel NFKB2 loss of function variant in a 17-year-old male patient and describe the clinical management of SARS-CoV-2 infection in this context. RESULTS: This patient required a 2-week hospitalization for SARS-CoV-2 infection, including 7 days of mechanical ventilation. We used biologic therapies to avert potentially fatal acute respiratory distress syndrome and treat hyperinflammatory responses. The patient had an immunologic phenotype of B-cell dysregulation with decreased switched memory B cells. Despite the underlying immune dysfunction, he recovered from the infection with intense management. CONCLUSIONS: This clinical case exemplifies some of the practical challenges in management of patients with SARS-CoV-2 infection, especially in the context of underlying immune dysregulation.

Do lonely days invade the nights? Potential social modulation of sleep efficiency.

Loneliness predicts morbidity and mortality from broad-based causes, but the reasons for this effect remain unclear. Few differences in traditional health behaviors (e.g., smoking, exercise, nutrition) have been found to differentiate lonely and nonlonely individuals. We present evidence that a prototypic restorative behavior--sleep--does make such a differentiation, not through differences in time in bed or in sleep duration, but through differences in efficacy: In the study we report here, lonely individuals evinced poorer sleep efficiency and more time awake after sleep onset than nonlonely individuals. These results, which were observed in controlled laboratory conditions and were found to generalize to the home, suggest that lonely individuals may be less resilient than nonlonely individuals in part because they sleep more poorly. These results also raise the possibility that social factors such as loneliness not only may influence the selection of health behaviors but also may modulate the salubrity of restorative behaviors.