Increased Autonomic Reactivity and Mental Health Difficulties in COVID-19 Survivors: Implications for Medical Providers

Background Because there is a relationship between mental health (MH) and medical adversity and autonomic dysregulation, we hypothesized that individuals infected with COVID-19 would report greater current autonomic reactivity and more MH difficulties (emotional distress, mindfulness difficulties, and posttraumatic stress). We also hypothesized that individuals diagnosed with COVID-19 who are experiencing difficulties related to their prior adversity and those providing medical care to COVID-19 patients would be more negatively impacted due to their increased stress and infection rates. Method US participants (N = 1,638; 61% female; Age M = 46.80) completed online self-report measures of prior adversity, current autonomic reactivity and current MH difficulties, and COVID-19 diagnosis history. Participants diagnosed with COVID-19 (n = 98) were more likely to be younger and providing medical care to COVID-19 patients. Results Individuals diagnosed with COVID-19 reported increased current autonomic reactivity, being more negatively impacted by their prior MH/medical adversities, and currently experiencing more MH difficulties with an increased likelihood of clinically-significant PTSD and depression (p < 0.01 – p < 0.001). Current autonomic reactivity mediated 58.9% to 85.2% of the relationship between prior adversity and current MH difficulties; and COVID-19 diagnosis moderated and enhanced the effect of prior adversity on current autonomic reactivity (p < 0.01). Being a medical provider was associated with increased current autonomic reactivity (p < 0.01), while moderating and enhancing the relationship between current autonomic reactivity and emotional distress and posttraumatic stress symptoms (p < 0.05). Combining COVID-19 diagnosis with being a medical provider increased likelihood of clinically-significant PTSD and depression (p < 0.01). Conclusion Individuals diagnosed with COVID-19, particularly medical providers, have increased current autonomic reactivity that is associated with their prior adversities and current MH difficulties

DNA Specificity Determinants Associate with Distinct Transcription Factor Functions

To elucidate how genomic sequences build transcriptional control networks, we need to understand the connection between DNA sequence and transcription factor binding and function. Binding predictions based solely on consensus predictions are limited, because a single factor can use degenerate sequence motifs and because related transcription factors often prefer identical sequences. The ETS family transcription factor, ETS1, exemplifies these challenges. Unexpected, redundant occupancy of ETS1 and other ETS proteins is observed at promoters of housekeeping genes in T cells due to common sequence preferences and the presence of strong consensus motifs. However, ETS1 exhibits a specific function in T cell activation; thus, unique transcriptional targets are predicted. To uncover the sequence motifs that mediate specific functions of ETS1, a genome-wide approach, chromatin immunoprecipitation coupled with high-throughput sequencing (ChIP-seq), identified both promoter and enhancer binding events in Jurkat T cells. A comparison with DNase I sensitivity both validated the dataset and also improved accuracy. Redundant occupancy of ETS1 with the ETS protein GABPA occurred primarily in promoters of housekeeping genes, whereas ETS1 specific occupancy occurred in the enhancers of T cell–specific genes. Two routes to ETS1 specificity were identified: an intrinsic preference of ETS1 for a variant of the ETS family consensus sequence and the presence of a composite sequence that can support cooperative binding with a RUNX transcription factor. Genome-wide occupancy of RUNX factors corroborated the importance of this partnership. Furthermore, genome-wide occupancy of co-activator CBP indicated tight co-localization with ETS1 at specific enhancers, but not redundant promoters. The distinct sequences associated with redundant versus specific ETS1 occupancy were predictive of promoter or enhancer location and the ontology of nearby genes. These findings demonstrate that diversity of DNA binding motifs may enable variable transcription factor function at different genomic sites