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The clinical outcome and disease severity in coronavirus disease 2019 (COVID-19) are heterogeneous, and the progression or fatality of the disease cannot be explained by a single factor like age or comorbidities. In this study, we used system-wide network-based system biology analysis using whole blood RNA sequencing, immunophenotyping by flow cytometry, plasma metabolomics, and single-cell-type metabolo-mics of monocytes to identify the potential determinants of COVID-19 severity at personalized and group levels. Digital cell quantification and immunophenotyping of the mononuclear phagocytes indicated a sub-stantial role in coordinating the immune cells that mediate COVID-19 severity. Stratum-specific and person-alized genome-scale metabolic modeling indicated monocarboxylate transporter family genes (e.g., SLC16A6), nucleoside transporter genes (e.g., SLC29A1), and metabolites such as a-ketoglutarate, succi-nate, malate, and butyrate could play a crucial role in COVID-19 severity. Metabolic perturbations targeting the central metabolic pathway (TCA cycle) can be an alternate treatment strategy in severe COVID-19.

Objectives The performance of blood cultures (BC) relies on optimal sampling. Sepsis guidelines do not specify which sampling protocol to use, but recommend two sets of BC bottles, each set containing one aerobic and one anaerobic bottle. For the single-site sampling (SSS) protocol, only one venipuncture is performed for all four bottles. The predominating multi-site sampling (MSS) protocol implies that BC bottles are collected from two separate venipuncture sites. The aim of this study was to compare SSS and MSS. Primary outcomes were number of BC sets collected, sample volume and diagnostic performance. Methods This was a retrospective clinical study comparing BC results in an emergency department before and after changing the sampling protocol to SSS from MSS. All BC samples were incubated in the BacT/ALERT BC system. Results The analysis included 5,248 patients before and 5,364 patients after the implementation of SSS. There was a significantly higher proportion of positive BCs sampled with SSS compared to MSS, 1,049/5,364 (19.56%) and 932/5,248 (17.76%) respectively (P=0.018). This difference was due to a higher proportion of solitary BC sets (two BC bottles) in MSS. Analyzing only patients with the recommended four BC bottles, there was no difference in positivity. SSS had a higher proportion of BC bottles with the recommended sample volumes of 8-12 ml than MSS (P<0.001). Conclusions Changing the sampling protocol to SSS from MSS resulted in higher positivity rates, higher sample volume and fewer solitary BC sets. These advantages of SSS should be considered in future sepsis guidelines., Correction for Ekwall-Larson et al., “Single-Site Sampling versus Multisite Sampling for Blood Cultures: a Retrospective Clinical Study”. Journal of Clinical Microbiology, vol. 60(9), e01180-22. DOI 10.1128/jcm.01180-22