Host-directed therapies for COVID-19.

PURPOSE OF REVIEW: Severe acute respiratory syndrome coronavirus-2-induced hyperinflammation is a major cause of death or end-organ dysfunction in COVID-19 patients. We review adjunct host-directed therapies (HDTs) for COVID-19 management. RECENT FINDINGS: The use of umbilical cord-derived mesenchymal stem cells as HDT for COVID-19 has been shown to be safe in phase 1 and 2 trials. Trials of anti-interleukin-6 receptor antibodies show promising mortality benefit in hospitalized COVID-19 patients. Repurposed drugs and monoclonal antibodies targeting specific cytokines acting on different aspects of the pro- and anti-inflammatory cascades are under evaluation. SUMMARY: A range of HDTs shows promise for reducing mortality and improving long term disability in patients with severe COVID-19, and require evaluation in randomized, controlled trials.

Immunometabolism: new insights and lessons from antigen-directed cellular immune responses.

Modulation of immune responses by nutrients is an important area of study in cellular biology and clinical sciences in the context of cancer therapies and anti-pathogen-directed immune responses in health and disease. We review metabolic pathways that influence immune cell function and cellular persistence in chronic infections. We also highlight the role of nutrients in altering the tissue microenvironment with lessons from the tumor microenvironment that shapes the quality and quantity of cellular immune responses. Multiple layers of biological networks, including the nature of nutritional supplements, the genetic background, previous exposures, and gut microbiota status have impact on cellular performance and immune competence against molecularly defined targets. We discuss how immune metabolism determines the differentiation pathway of antigen-specific immune cells and how these insights can be explored to devise better strategies to strengthen anti-pathogen-directed immune responses, while curbing unwanted, non-productive inflammation.