We analyzed qualitative data from 707 USA college students aged 18-22 in late April 2020 regarding if and how their relationships had changed at the start of the COVID-19 pandemic. Most (69%) participants experienced relationship changes, most of whom (77%) described negative changes: less overall contact, feeling disconnected, and increased tension, some of which was due to conflict over pandemic-related public health precautions. Physical distancing from social contacts also created emotional distancing: it was harder to maintain affective connections via online platforms and within the isolating context of shelter-in-place. Due to emerging adulthood being a sensitive window for social development, the COVID-19 pandemic-induced emotional distancing could have long-term ramifications for this cohort's relationships over the course of their lives.

Background

The mechanisms of aberrant circulating platelet behavior following injury remain unclear. Platelets retain megakaryocyte immature ribonucleic acid (RNA) splicing and protein synthesis machinery to alter their functions based on physiologic signals. We sought to identify fluctuating platelet-specific RNA transcripts in cell-free plasma (CFP) from traumatic brain injury (TBI) patients as proof-of-concept for using RNA sequencing to improve our understanding of postinjury platelet behavior. We hypothesized that we could identify differential expression of activated platelet-specific spliced RNA transcripts from CFP of patients with isolated severe fatal TBI (fTBI) compared with minimally injured trauma controls (t-controls), filtered by healthy control (h-control) data sets.

Methods

High-read depth RNA sequencing was applied to CFP from 10 patients with fTBI (Abbreviated Injury Scale [AIS] for head ≥3, AIS for all other categories <3, and expired) and five t-controls (Injury Severity Score ≤1, and survived). A publicly available CFP RNA sequencing data set from 23 h-controls was used to determine the relative steady state of splice-form RNA transcripts discoverable in CFP. Activated platelet-specific spliced RNA transcripts were derived from studies of ex vivo platelet activation and identified by splice junction presence greater than 1.5-fold or less than 0.67-fold ex vivo nonactivated platelet-specific RNA transcripts.

Results

Forty-two differentially spliced activated platelet-specific RNA transcripts in 34 genes were altered in CFP from fTBI patients (both upregulated and downregulated).

Conclusion

We have discovered differentially expressed activated platelet-specific spliced RNA transcripts present in CFP from isolated severe fTBI patients that are upregulated or downregulated compared with minimally injured trauma controls. This proof-of-concept suggests that a pool of immature platelet RNAs undergo splicing events after injury for presumed modulation of platelet protein products involved in platelet function. This validates our exploration of injury-induced platelet RNA transcript modulation as an upstream "liquid biopsy" to identify novel postinjury platelet biology and treatment targets for aberrant platelet behavior.

Level of evidence

Diagnostic tests, level V.