Quality of Life, Fatigue, and Physical Symptoms Post-COVID-19 Condition: A Cross-Sectional Comparative Study.

The magnitude of post-COVID-19 syndrome was not thoroughly investigated. This study evaluated the quality of life and persistence of fatigue and physical symptoms of individuals post-COVID-19 compared with noninfected controls. The study included 965 participants; 400 had previous COVID-19 disease and 565 controls without COVID-19. The questionnaire collected data on comorbidities, COVID-19 vaccination, general health questions, and physical symptoms, in addition to validated measures of quality of life (SF-36 scale), fatigue (fatigue severity scale, FSS), and dyspnea grade. COVID-19 participants complained more frequently of weakness, muscle pain, respiratory symptoms, voice disorders, imbalance, taste and smell loss, and menstrual problems compared to the controls. Joint symptoms, tingling, numbness, hypo/hypertension, sexual dysfunction, headache, bowel, urinary, cardiac, and visual symptoms did not differ between groups. Dyspnea grade II-IV did not differ significantly between groups (p = 0.116). COVID-19 patients scored lower on the SF-36 domains of role physical (p = 0.045), vitality (p < 0.001), reported health changes (p < 0.001), and mental-components summary (p = 0.014). FSS scores were significantly higher in COVID-19 participants (3 (1.8-4.3) vs. 2.6 (1.4-4); p < 0.001). COVID-19 effects could persist beyond the acute infection phase. These effects include changes in quality of life, fatigue, and persistence of physical symptoms.

Clinical, genetic, and functional characterization of the glycine receptor ß-subunit A455P variant in a family affected by hyperekplexia syndrome.

Hyperekplexia is a rare neurological disorder characterized by exaggerated startle responses affecting newborns with the hallmark characteristics of hypertonia, apnea, and noise or touch-induced nonepileptic seizures. The genetic causes of the disease can vary, and several associated genes and mutations have been reported to affect glycine receptors (GlyRs); however, the mechanistic links between GlyRs and hyperekplexia are not yet understood. Here, we describe a patient with hyperekplexia from a consanguineous family. Extensive genetic screening using exome sequencing coupled with autozygome analysis and iterative filtering supplemented by in silico prediction identified that the patient carries the homozygous missense mutation A455P in GLRB, which encodes the GlyR ß-subunit. To unravel the physiological and molecular effects of A455P on GlyRs, we used electrophysiology in a heterologous system as well as immunocytochemistry, confocal microscopy, and cellular biochemistry. We found a reduction in glycine-evoked currents in N2A cells expressing the mutation compared to WT cells. Western blot analysis also revealed a reduced amount of GlyR ß protein both in cell lysates and isolated membrane fractions. In line with the above observations, coimmunoprecipitation assays suggested that the GlyR α1-subunit retained coassembly with ßA455P to form membrane-bound heteromeric receptors. Finally, structural modeling showed that the A455P mutation affected the interaction between the GlyR ß-subunit transmembrane domain 4 and the other helices of the subunit. Taken together, our study identifies and validates a novel loss-of-function mutation in GlyRs whose pathogenicity is likely to cause hyperekplexia in the affected individual.