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Background: Severe COVID-19 is linked to hyperactivation of the host immune response involving signaling through multiple spleen tyrosine kinase (SYK) pathways. Fostamatinib is an orally administered potent and selective inhibitor of SYK that has been approved in the US, Canada, Japan, and Europe for the treatment of chronic immune thrombocytopenia (ITP). Methods: We conducted a double-blind, randomized, placebo-controlled phase 3 trial of fostamatinib in adults hospitalized for COVID-19 who required oxygen supplementation (NCT04629703). Patients (pts) were randomly assigned 1:1 to receive fostamatinib (150 mg BID administered orally) or placebo for 14 days. All pts additionally received standard of care at their hospital. The primary endpoint was days on oxygen (days 1-29). Results: A total of 280 pts underwent randomization (with 141 assigned to fostamatinib and 139 to placebo). The primary endpoint was met; those who received fostamatinib had lower mean days on oxygen than those who received placebo (4.8 vs. 7.6 days, P=0.0136; Table 1). Fostamatinib showed significance or trend towards significance in all secondary endpoints of reducing mortality and morbidity compared to placebo. The mean change in the 8-point ordinal score from baseline to the average of Day 5 to 15 was significantly improved in pts who received fostamatinib vs. placebo (P=0.0092,Table 1). Furthermore, 6 pts were enrolled with a baseline ordinal score of 6 (3 in each group). All patients in the fostamatinib group survived, and all in the placebo group died by Day 30. A significantly higher proportion of pts who received fostamatinib were discharged from the hospital by Day 15 compared to placebo (P=0.0029,Table 1). Significantly more patients were alive and oxygen-free by Day 29 and Day 60 with fostamatinib treatment in comparison to placebo (P=0.0213 and P=0.0271, respectively, Table 1). Treatment-emergent adverse events were consistent with previous studies and were similar between the 2 groups. Conclusion: The addition of fostamatinib to standard of care treatment resulted in significantly fewer days on oxygen, an improved 8-point ordinal scale score, and significantly more patients alive and oxygen-free by Day 60 compared to placebo in pts with COVID-19 requiring hospitalization and supplemental oxygen. Disclosures: Deepa B. Gotur, MD, FCCP, FCCM, GSK: Advisor/Consultant|GSK: Speaker at ATS|Moderna: Advisor/Consultant Vadim Markovtsov, PhD, Rigel Pharmaceuticals, Inc.: Employee|Rigel Pharmaceuticals, Inc.: Stocks/Bonds Lucy Yan, MD, PhD, Rigel Pharmaceuticals, Inc.: Employee|Rigel Pharmaceuticals, Inc.: Stocks/Bonds Wolfgang Dummer, MD, PhD, Rigel Pharmaceuticals, Inc.: Stocks/Bonds.

The recent detection of a stochastic gravitational wave background (SGWB) at nanohertz frequencies by pulsar timing arrays (PTAs) has sparked a flurry of interest. Beyond the standard interpretation that the progenitor is a network of supermassive black hole binaries, many exotic models have also been proposed, some of which can potentially offer a better fit to the data. We explore how the various connections between gravitational waves and CMB spectral distortions can be leveraged to help determine whether a SGWB was generated primordially or astrophysically. To this end, we present updated $k$-space window functions which can be used for distortion parameter estimation on enhancements to the primordial scalar power spectrum. These same enhancements can also source gravitational waves (GWs) directly at second order in perturbation theory, so-called scalar-induced GWs (SIGWs), and indirectly through the formation of primordial black holes (PBHs). We perform a mapping of scalar power spectrum constraints into limits on the GW parameter space of SIGWs for $δ$-function features. We highlight that broader features in the scalar spectrum can explain the PTA results while simultaneously producing a spectral distortion (SD) within reach of future experiments. We additionally update PBH constraints from $μ$- and $y$-type spectral distortions. Refined treatments of the distortion window functions widen existing SD constraints, and we find that a future CMB spectrometer could play a pivotal role in unraveling the origin of GWs imprinted at or below CMB anisotropy scales.

Resilience in food supply chains (SCs) is critical to ensure food security, but it may come at a cost. Today, SCs face the challenge of balancing cost-effectiveness and resilience to remain competitive and viable. While reducing costs is critical to compete in the market, ensuring resilience is essential to withstand disruptions and guarantee food availability. This paper examines the relationship between resilience and cost at each sustainability pillar in food SCs. A critical literature review led to the development of a theoretical framework for evaluating the SC resilience and cost level, which can support operations management and decision-making processes.