Traumatic Brain Injury in the Long-COVID Era

Abstract

Major determinants of the biological background or reserve, such as age, biological sex, comorbidities (diabetes, hypertension, obesity, etc.), and medications (e.g., anticoagulants), are known to affect outcome after traumatic brain injury (TBI). With the unparalleled data richness of coronavirus disease 2019 (COVID-19; ∼375,000 and counting!) as well as the chronic form, long-COVID, also called post-acute sequelae SARS-CoV-2 infection (PASC), publications (∼30,000 and counting) covering virtually every aspect of the diseases, pathomechanisms, biomarkers, disease phases, symptomatology, etc., have provided a unique opportunity to better understand and appreciate the holistic nature of diseases, interconnectivity between organ systems, and importance of biological background in modifying disease trajectories and affecting outcomes. Such a holistic approach is badly needed to better understand TBI-induced conditions in their totality. Here, I briefly review what is known about long-COVID/PASC, its underlying-suspected-pathologies, the pathobiological changes induced by TBI, in other words, the TBI endophenotypes, discuss the intersection of long-COVID/PASC and TBI-induced pathobiologies, and how by considering some of the known factors affecting the person's biological background and the inclusion of mechanistic molecular biomarkers can help to improve the clinical management of TBI patients.

Keywords: biological reserve; comorbidities; traumatic brain injury.

FIG. 1.

Onset and extent of major pathobiological changes during the various phases of severe COVID-19 and the hypothesized role of long-COVID/PASC affecting the outcome of TBI. The pathobiological changes identified or suspected during the acute, subacute, and chronic (long-COVID/PASC) phases of COVID-19 are listed. The dashed turquoise line indicates the relative intensity and relative timeline of pathobiologies of COVID-19. The solid turquoise line indicates the relative intensities of pathobiological changes associated with long-COVID/PASC. The solid yellow curve indicates the relative intensity and temporal changes of pathobiologies of TBI on a long-COVID/PASC background. Relevant references are in the text and listed in the references. DAMPs, damage-associated molecular patterns; PASC, post-acute sequelae SARS-CoV-2 infection; TBI, traumatic brain injury.