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Tumor necrosis factor (TNF) is a key regulator of inflammatory responses and has been implicated in many pathological conditions. We used structure-based design to engineer variant TNF proteins that rapidly form heterotrimers with native TNF to give complexes that neither bind to nor stimulate signaling through TNF receptors. Thus, TNF is inactivated by sequestration. Dominant-negative TNFs represent a possible approach to anti-inflammatory biotherapeutics, and experiments in animal models show that the strategy can attenuate TNF-mediated pathology. Similar rational design could be used to engineer inhibitors of additional TNF superfamily cytokines as well as other multimeric ligands.

The statements and opinions expressed in COVID-19 Curbside Consults are based on experience and the available literature as of the date posted. While we try to regularly update this content, any offered recommendations cannot be substituted for the clinical judgment of clinicians caring for individual patients. ABSTRACT Cleveland Clinic recognized the importance of mitigating community transmission of COVID-19 by keeping people at home. Patient-care activities quickly pivoted to remote touches, preserving continuity through a variety of digital and telephonic modalities. As the number of confi rmed cases grew, standardizing home-based care became critical to managing high-risk patients, moderating the risk of exposure for healthcare workers, and reducing the amount of community spread through appropriate education on home-based care for exposed or infected individuals. This novel, team-based approach to caring for patients with COVID-19 incorporates a self-monitoring app for patient engagement, monitors symptoms for early intervention, and promotes a holistic view of care.