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Despite limited genomic diversity, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has shown a wide range of clinical manifestations in different patient populations. The mechanisms behind these host differences are still unclear. Here, we examined host response gene expression across infection status, viral load, age, and sex among shotgun RNA sequencing profiles of nasopharyngeal (NP) swabs from 430 individuals with PCRconfirmed SARS-CoV-2 and 54 negative controls. SARS-CoV-2 induced a strong antiviral response with up-regulation of antiviral factors such as OAS1-3 and IFIT1-3 and T helper type 1 (Th1) chemokines CXCL9/10/11, as well as a reduction in transcription of ribosomal proteins. SARS-CoV-2 culture in human airway epithelial (HAE) cultures replicated the in vivo antiviral host response 7 days post infection, with no induction of interferon-stimulated genes after 3 days. Patient-matched longitudinal specimens (mean elapsed time = 6.3 days) demonstrated reduction in interferon-induced transcription, recovery of transcription of ribosomal proteins, and initiation of wound healing and humoral immune responses. Expression of interferon-responsive genes, including ACE2, increased as a function of viral load, while transcripts for B cell-specific proteins and neutrophil chemokines were elevated in patients with lower viral load. Older individuals had reduced expression of the Th1 chemokines CXCL9/10/11 and their cognate receptor CXCR3, as well as CD8A and granzyme B, suggesting deficiencies in trafficking and/or function of cytotoxic T cells and natural killer (NK) cells. Relative to females, males had reduced B cell-specific and NK cell-specific transcripts and an increase in inhibitors of nuclear factor kappa-B (NF-κB) signaling, possibly

Following its emergence in Wuhan, China, in late November or early December 2019, the SARS-CoV-2 virus has rapidly spread globally. Genome sequencing of SARS-CoV-2 allows reconstruction of its transmission history, although this is contingent on sampling. We have analyzed 453 SARS-CoV-2 genomes collected between 20 February and 15 March 2020 from infected patients in Washington State, USA. We find that most SARS-CoV-2 infections sampled during this time derive from a single introduction in late January or early February 2020 which subsequently spread locally before active community surveillance was implemented.

SummaryLipid droplets, which store triglycerides and cholesterol esters, are a prominent feature of clear cell renal cell carcinoma (ccRCC). Although their presence in ccRCC is critical for sustained tumorigenesis, their contribution to lipid homeostasis and tumor cell viability is incompletely understood. Here we show that disrupting triglyceride synthesis compromises the growth of both ccRCC tumors and ccRCC cells exposed to tumor-like conditions. Functionally, hypoxia leads to increased fatty acid saturation through inhibition of the oxygen-dependent stearoyl-CoA desaturase (SCD) enzyme. Triglycerides counter a toxic buildup of saturated lipids, primarily by releasing the unsaturated fatty acid oleate (the principal product of SCD activity) from lipid droplets into phospholipid pools. Disrupting this process derails lipid homeostasis, causing overproduction of toxic saturated ceramides and acyl-carnitines as well as activation of the NF-κB transcription factor. Our work demonstrates that triglycerides promote homeostasis by “buffering” specific fatty acids.