Neuroinflammation in COVID‐19 and ADRD: Similarities, differences, and interactions

Abstract

Background:The severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) causes various neurological manifestations including neuroinflammation. Neuroinflammation is also present in Alzheimer's Disease and Related Dementias (ADRD).Despite the widespread and devastating impact of these conditions, the full causal mechanisms leading to neuroinflammation and its impact on outcomes remain elusive.Here we examine neuroinflammation in COVID-19 and ADRD in order to identify similarities, differences and interactions that could aid in addressing the biopsychosocial mechanisms and consequences in both conditions.Method: Using an expanded Adverse Outcome Pathway (AOP) approach we constructed a framework to compare the similarities and differences in key events leading to neuroinflammation. The framework is based on a meta-survey of the literature as well as existing AOPs. Key findings were assessed for similarities and differences regarding the clinical presentation, biological mechanisms, risk, protective factors, and treatment interventions. Additionally, we considered health disparities that may contribute to the worsening progression of both COVID-19 and ADRD. Result:The comparison and intersections of COVID-19 and ADRD show various overlapping factors across scales. An overlap of immune system and inflammatory processes exacerbate both conditions, potentially leading to increased mortality rates.Although there are major differences in the initiating events, timelines and molecular cascades, there are significant pathway commonalities across scales. Furthermore, commonalities in underlying conditions, such as obesity, Type 2 diabetes, cardiovascular disease, hypertension, and metabolic disorders, are major risk factors in both COVID-19 and ADRD, which worsen the outcomes. Additionally, lifestyle risk factors, such as poor nutrition, physical inactivity and cognitive status, may further exacerbate the deadly prognosis for both conditions. Conclusion:Given the crucial role of inflammation and immune system functioning in both these conditions, implementing preventative measures to strengthen the immune system and decrease comorbid conditions and lifestyle risk factors is imperative, especially for vulnerable populations. Mapping approaches such as AOPs can be particularly helpful in evaluating the weight of current evidence and knowledge gaps in a rapidly evolving scientific data landscape, such as the COVID-19 pandemic. These approaches can also serve as a foundation to further probe the complexities of multiscale interactions in diseases that may otherwise initially appear unrelated.

A Transformer-Based Model Trained on Large Scale Claims Data for Prediction of Severe COVID-19 Disease Progression

“…Our analysis shows significant effects of several prior diagnoses on the ARM onset, namely, type 2 diabetes, obesity, dementia, cardiovascular diseases, and respiratory diseases (see Table 3). These morbidities have previously been reported as risk factors for severe COVID-19 disease progression [33][34][35][36][37][38], and also the underlying molecular mechanisms have 10 been discussed [39,40]. Besides, we found significant effects between constipation, screening for malignant neoplasms, and infectious/parasitic diseases and the ARM onset.…”

The Adverse Outcome Pathway Framework Applied to Neurological Symptoms of COVID-19

“…In another gene, OAS1, was found to be linked to both AD and COVID-19 [ 146 ], yet further studies are needed to fully address the details of the interaction. However, various similarities, differences, and interactions between COVID-19 and ADRD have been proposed [ 147 , 148 ].…”