Highlights d Acute SARS-CoV-2 infection is associated with shifts in the nasal microbiome d Abundance of Pseudomonas aeruginosa increases with SARS-CoV-2 viral RNA load d Healthcare providers and infected patients share some nasal microbiome features d The nasal transcriptome of infected patients reveals inflammation and neuron damage

Much of the research conducted on SARS-CoV-2 and COVID-19 has focused on the systemic host response, especially that generated by severely ill patients. Very few studies have investigated the impact of acute SARS-CoV-2 within the nasopharynx, the site of initial infection and viral replication. In this study we profiled changes in the nasal microbial communities as well as in host transcriptional profile during acute SARS-CoV-2 infection using 16S amplicon sequencing and RNA sequencing. These analyses were coupled to viral genome sequencing. Our microbiome analysis revealed that the nasal microbiome of COVID patients was unique and was marked by an expansion of bacterial pathogens. Some of these microbes (i.e. Acinetobacter) were shared with COVID negative health care providers from the same medical center but absent in COVID negative outpatients seeking care at the same institutions suggesting acquisition of nosocomial respiratory pathogens. Specifically, we report a distinct increase in the prevalence and abundance of the pathogen Pseudomonas aeruginosa in COVID patients that correlated with viral RNA load. These data suggest that the inflammatory environment caused by SARS-CoV-2 infection and potentially exposure to the hospital environment leads to an expansion of bacterial pathogens in the nasal cavity that could contribute to increased incidence of secondary bacterial infections. Additionally, we observed a robust host transcriptional response in the nasal epithelia of COVID patients, indicative of an antiviral innate immune repones and neuronal damage. Finally, analysis of viral genomes did not reveal an association between viral loads and viral sequences.

Atherosclerosis is a chronic inflammatory disease characterized by the development of plaque in arteries. Interactions between monocytes, endothelial cells and lipoproteins play a major role in the disease pathogenesis. C1q is traditionally known for activation of the complement cascade, leading to inflammation and clearance of foreign targets. However, we previously showed that C1q bound to modified lipoproteins (e.g. oxLDL) plays a protective role by polarizing monocytes and macrophages towards an anti-inflammatory state during engulfment and increases survival and efferocytic function of macrophage foam cells. Additionally, C1q modulates macrophage chemokine production in in vitro and in in vitro models of atherosclerosis. Here we investigate C1q modulation of both endothelial cell chemokine production, and functions affecting monocyte migration. Human aortic endothelial cells (HAEC) were incubated with oxLDL +/− C1q. RNA and supernatants were collected for chemokine gene regulation and protein analysis, respectively. Monocyte adhesion and transendothelial migration were also measured. The data show that C1q modulates chemokine gene and protein expression, increases monocyte adhesion and transendothelial migration and enhances HAEC monolayer permeability. Thus, C1q interactions with HAEC in hyperlipidemic conditions may result in increased availability of phagocytes for clearance in the early atherosclerotic lesion. However in later stages infiltrating cells may contribute to disease progression through an increased proinflammatory environment and complement activation. Understanding timing and molecular mechanisms in atherosclerosis will be vital for the development of novel treatments.