Integrative systems immunology uncovers molecular networks of the cell cycle that stratify COVID-19 severity.

Several perturbations in the number of peripheral blood leukocytes, such as neutrophilia and lymphopenia associated with Coronavirus disease 2019 (COVID-19) severity, point to systemic molecular cell cycle alterations during severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. However, the landscape of cell cycle alterations in COVID-19 remains primarily unexplored. Here, we performed an integrative systems immunology analysis of publicly available proteome and transcriptome data to characterize global changes in the cell cycle signature of COVID-19 patients. We found significantly enriched cell cycle-associated gene co-expression modules and an interconnected network of cell cycle-associated differentially expressed proteins (DEPs) and genes (DEGs) by integrating the molecular data of 1469 individuals (981 SARS-CoV-2 infected patients and 488 controls [either healthy controls or individuals with other respiratory illnesses]). Among these DEPs and DEGs are several cyclins, cell division cycles, cyclin-dependent kinases, and mini-chromosome maintenance proteins. COVID-19 patients partially shared the expression pattern of some cell cycle-associated genes with other respiratory illnesses but exhibited some specific differential features. Notably, the cell cycle signature predominated in the patients' blood leukocytes (B, T, and natural killer cells) and was associated with COVID-19 severity and disease trajectories. These results provide a unique global understanding of distinct alterations in cell cycle-associated molecules in COVID-19 patients, suggesting new putative pathways for therapeutic intervention.

Previous vitamin D status and total cholesterol are associated with SARS-CoV-2 infection.

BACKGROUND: The relationship of vitamin D status and other biochemical parameters with the risk of SARS-CoV-2 infection remains inconclusive, especially in regions with high solar incidence. Therefore, we aimed to associate the 25-hydroxyvitamin D (25(OH)D) concentrations and lipid profile prior to the SARS-CoV-2 tests in a population from a sunny region in Brazil (5 degrees S, 35 degrees W). METHODS: This retrospective cohort study enrolled 1634 patients tested for SARS-CoV-2 of a private medical laboratory with 25(OH)D concentration and lipid profile measured ≥ 7 days before the date of the first SARS-CoV-2 RT-PCR test and were categorized according to 25(OH)D sufficiency (≥30 ng/mL) or insufficiency (<30 ng/mL). Multiple logistic regression analyses were performed to assess risk factors associated with positive tests for SARS-CoV-2. RESULTS: Average serum 25(OH)D was 33.6 ng/mL. Vitamin D deficiency (<20 ng/mL) was only found in 2.6% of the participants. Multivariate analysis demonstrated that patients > 49 y with insufficient 25(OH)D (<30 ng/mL) presented increased odds to test positive for SARS-CoV-2 (OR: 2.02, 95 %CI: 1.15 to 3.55, P = 0.015). The same is observed among those with total cholesterol > 190 mg/dL (OR: 1.90, 95 %CI: 1.10 to 3.28, P = 0.020). CONCLUSIONS: Previous insufficient 25(OH)D (<30 ng/mL) concentration and high total cholesterol were associated with SARS-CoV-2 infection among adults > 48 y in the study population. Further studies should be conducted to confirm whether measurement of 25(OH)D and lipid profile could be useful to identify patients who are more susceptible to COVID-19.