Changes of sleep patterns in primary care workers during the first wave of the COVID-19 pandemic in 2022 in Shanghai (preprint)

Background The COVID-19 pandemic has had a significant influence on the sleep health of healthcare workers (HCWs); however, there are no studies on this aspect in primary HCWs. The purpose of this cross-sectional, web-based study was to explore the prevalence and factors associated with sleep disorders among primary care providers during the first COVID-19 outbreak in 2022 in Shanghai. Methods: From July 12 to August 15, 2022, primary HCWs were invited to participate in a survey of their sociodemographic and work-related characteristics, various sleep dimensions (regularity, quality, daytime sleepiness, timing, efficiency, and duration), and exposure to COVID-19 patients and a screening for common mental disorders (depression, burnout, and stress). Results: A total of 313 primary HCWs participated the survey, representing 11 distinct healthcare roles. 84% of respondents showed a deterioration in at least one sleep dimension compared to those at pre-pandemic levels; sleep quality (decline of 66%) and daytime sleepiness (increase of 56%) were the most strongly affected domains. After excluding 145 primary HCWs with pre-pandemic “poor sleep,” positive depression screening (odds ratio [OR], 3.08; 95% confidence interval [CI], 1.59–5.98), weekly burnout symptoms (OR, 2.57; 95% CI, 1.32–5.03), and high psychological stress (OR, 4.51; 95% CI, 2.09–9.72) were associated with poor sleep patterns during the pandemic. After adjusting for significant differences between groups, for every 1-point increase in the perceived stress scale score, there was an associated 12% increased risk of poor sleep (adjusted OR, 1.12; 95% CI, 1.05–1.21; P=0.002). Conclusion: A majority of the primary HCWs showed a significant worsening of sleep quality, with an increase in daytime sleepiness, during the first wave of the COVID‑19 pandemic in 2022 in Shanghai. HCWs with high stress were at a greater risk of sleep disorders.

Large-scale single-cell analysis reveals critical immune characteristics of COVID-19 patients (preprint)

Dysfunctional immune response in the COVID-19 patients is a recurrent theme impacting symptoms and mortality, yet the detailed understanding of pertinent immune cells is not complete. We applied single-cell RNA sequencing to 284 samples from 205 COVID-19 patients and controls to create a comprehensive immune landscape. Lymphopenia and active T and B cell responses were found to coexist and associated with age, sex and their interactions with COVID-19. Diverse epithelial and immune cell types were observed to be virus-positive and showed dramatic transcriptomic changes. Elevation of ANXA1 and S100A9 in virus-positive squamous epithelial cells may enable the initiation of neutrophil and macrophage responses via the ANXA1-FPR1 and S100A8/9-TLR4 axes. Systemic up-regulation of S100A8/A9, mainly by megakaryocytes and monocytes in the peripheral blood, may contribute to the cytokine storms frequently observed in severe patients. Our data provide a rich resource for understanding the pathogenesis and designing effective therapeutic strategies for COVID-19.

Modeling the Opening SARS-CoV-2 Spike: an Investigation of its Dynamic Electro-Geometric Properties (preprint)

The recent COVID-19 pandemic has brought about a surge of crowd-sourced initiatives aimed at simulating the proteins of the SARS-CoV-2 virus. A bottleneck currently exists in translating these simulations into tangible predictions that can be leveraged for pharmacological studies. Here we report on extensive electrostatic calculations done on an exascale simulation of the opening of the SARS-CoV-2 spike protein, performed by the Folding@home initiative. We compute the electric potential as the solution of the non-linear Poisson-Boltzmann equation using a parallel sharp numerical solver. The inherent multiple length scales present in the geometry and solution are reproduced using highly adaptive Octree grids. We analyze our results focusing on the electro-geometric properties of the receptor-binding domain and its vicinity. This work paves the way for a new class of hybrid computational and data-enabled approaches, where molecular dynamics simulations are combined with continuum modeling to produce high-fidelity computational measurements serving as a basis for protein bio-mechanism investigations.

Clinical and molecular characteristics of COVID-19 patients with persistent SARS-CoV-2 infection (preprint)

The clinical features, molecular characteristics, and immune responses of COVID-19 patients with persistent SARS-CoV-2 infection are not yet well described. In this study, we investigated the differences in clinical parameters, laboratory indexes, plasma cytokines, and peripheral blood mononuclear cell responses, which were assessed using single-cell RNA-sequencing in patients with non-critical COVID-19 with long durations (LDs) and short durations (SDs) of viral shedding. Our results revealed that clinical parameters and laboratory indexes, such as c-reactive protein (CRP) and D-dimer, were comparable between SDs and LDs. Most inflammatory cytokines/chemokines, such as IL-2, IL2R, TNFα/β, IL1β, and CCL5 were present at low levels in LDs. Our single-cell RNA-sequencing revealed a reconfiguration of the peripheral immune cell phenotype in LDs, including decreases in natural killer (NK) cells and CD14+ monocytes and an increase in regulatory T cells (Tregs). Furthermore, most cell subsets in LDs consistently exhibited reduced expression of ribosomal protein (RP) genes, indicating dysfunctions in cytokine/chemokine synthesis, folding, modification, and assembly. Accordingly, the negative correlation between the RP levels and viral shedding duration was validated in an independent cohort of bulk-RNA-sequencing data from 103 non-critical patients, which may help guide clinical management and resource allocation. Moreover, peripheral T and NK cells and memory B cells in LDs likely failed to activate, which contributed to the persistence of viral shedding.