The predictive power of insomnia symptoms on other aspects of mental health during the COVID-19 pandemic: a longitudinal study.

Symptoms of insomnia are an important risk factor for the development of mental disorders, especially during stressful life periods such as the coronavirus disease 2019 (COVID-19) pandemic. However, up to now, most studies have used cross-sectional data, and the prolonged impact of insomnia symptoms during the pandemic on later mental health remains unclear. Therefore, we investigated insomnia symptoms as a predictor of other aspects of mental health across 6 months, with altogether seven assessments (every 30 days, t0-t6), in a community sample (N = 166-267). Results showed no mean-level increase of insomnia symptoms and/or deterioration of mental health between baseline assessment (t0) and the 6- month follow-up (t6). As preregistered, higher insomnia symptoms (between persons) across all time points predicted reduced mental health at the 6-month follow-up. Interestingly, contrary to our hypothesis, higher insomnia symptoms at 1 month, within each person (i.e., compared to that person's symptoms at other time points), predicted improved rather than reduced aspects of mental health 1 month later. Hence, we replicated the predictive effect of averagely increased insomnia symptoms on impaired later mental health during the COVID-19 pandemic. However, we were surprised that increased insomnia symptoms at 1 month predicted aspects of improved mental health 1 month later. This unexpected effect might be specific for our study population and a consequence of our study design. Overall, increased insomnia symptoms may have served as a signal to engage in, and successfully implement, targeted countermeasures, which led to better short-term mental health in this healthy sample.

GM-CSF-activated human dendritic cells promote type 1 T follicular helper cell polarization in a CD40-dependent manner.

T follicular helper (Tfh) cells regulate humoral responses and present a marked phenotypic and functional diversity. Type 1 Tfh (Tfh1) cells were recently identified and associated with disease severity in infection and autoimmune diseases. The cellular and molecular requirements to induce human Tfh1 differentiation are not known. Here, using single-cell RNA sequencing (scRNAseq) and protein validation, we report that human blood CD1c+ dendritic cells (DCs) activated by GM-CSF (also known as CSF2) drive the differentiation of naive CD4+ T cells into Tfh1 cells. These Tfh1 cells displayed typical Tfh molecular features, including high levels of PD-1 (encoded by PDCD1), CXCR5 and ICOS. They co-expressed BCL6 and TBET (encoded by TBX21), and secreted large amounts of IL-21 and IFN-γ (encoded by IFNG). Mechanistically, GM-CSF triggered the emergence of two DC sub-populations defined by their expression of CD40 and ICOS ligand (ICOS-L), presenting distinct phenotypes, morphologies, transcriptomic signatures and functions. CD40High ICOS-LLow DCs efficiently induced Tfh1 differentiation in a CD40-dependent manner. In patients with mild COVID-19 or latent Mycobacterium tuberculosis infection, Tfh1 cells were positively correlated with a CD40High ICOS-LLow DC signature in scRNAseq of peripheral blood mononuclear cells or blood transcriptomics, respectively. Our study uncovered a novel CD40-dependent Tfh1 axis with potential physiopathological relevance to infection. This article has an associated First Person interview with the first author of the paper.