Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive degeneration of upper and lower motor neurons. The heterogeneous nature of ALS at the clinical, genetic, and pathological levels makes it challenging to develop diagnostic and prognostic tools that fit all disease phenotypes. Limitations associated with the functional scales and the qualitative nature of mainstay electrophysiological testing prompt the investigation of more objective quantitative assessment. Biofluid biomarkers have the potential to fill that gap by providing evidence of a disease process potentially early in the disease, its progression, and its response to therapy. In contrast to other neurodegenerative diseases, no biomarker has yet been validated in clinical use for ALS. Several fluid biomarkers have been investigated in clinical studies in ALS. Biofluid biomarkers reflect the different pathophysiological processes, from protein aggregation to muscle denervation. This review takes a pathophysiologic approach to summarizing the findings of clinical studies utilizing quantitative biofluid biomarkers in ALS, discusses the utility and shortcomings of each biomarker, and highlights the superiority of neurofilaments as biomarkers of neurodegeneration over other candidate biomarkers.

The ongoing pandemic has stimulated study of the Renin Angiotensin Aldosterone System (RAAS), and how it can be manipulated to treat COVID-19. Studies are examining whether drugs that act on the RAAS system might be useful to treat COVID-19. COVID-19 and the RAAS are closely linked both in infection and in possible post-infection inflammatory cascades. We detail the Physiology and Pharmacology of the RAAS including the effects of aldosterone and atrial natriuretic peptide. It is appropriate that the theoretical benefits of modulation of the RAAS should be considered based on available knowledge of the complexity of the system. In this short review we have tried to explain the actions of the angiotensin family of peptides and produce a relatively simple model and diagrammatic summary of the RAAS and the possible sites of intervention.