Re-Framing Long COVID as Central Nervous System Dysfunction

Four years after the emergence of long COVID, science is little closer to understanding its cause, pathogenesis, prevention or treatment than it was at its outset. This is due in part to the lack of an explanatory hypothesis that fits the scattergram of data emerging from basic, clinical and epidemiological research. We propose a unifying hypothesis that connects a triggering viral infection to the pathogenesis and the plethora of 200 symptoms: that long COVID is a central nervous system disorder of biologic origin, provisionally named “Post-COVID CNS dysfunction (PCCD)”. As neuroscience develops, it has become increasingly evident that much of mental illness and cognitive impairment has its basis in brain structure, chemistry and function. Applying this to long COVID, we propose that its symptoms are mediated through virus-induced biological mechanisms acting on or within the CNS. Both past and future research should be combined to test the PCCD hypothesis. This can open the pathway to significant progress in prevention, care and therapeutics. A multi-sector collaborative platform—with the leadership of the federal government’s Office of Long COVID Research and Practice—could, for example, assist in testing, improving, and implementing this hypothesis.