SARS-CoV-2 and the Brain: What Do We Know about the Causality of ‘Cognitive COVID?

Ali Awan, Hashir; Najmuddin Diwan, Mufaddal; Aamir, Alifiya; Ali, Muneeza; Di Giannantonio, Massimo; Ullah, Irfan; Shoib, Sheikh; De Berardis, Domenico

The second year of the COVID-19 (coronavirus disease) pandemic has seen the need to identify and assess the long-term consequences of a SARS-CoV-2 infection on an individual’s overall wellbeing, including adequate cognitive functioning. ‘Cognitive COVID’ is an informal term coined to interchangeably refer to acute changes in cognition during COVID-19 and/or cognitive sequelae with various deficits following the infection. These may manifest as altered levels of consciousness, encephalopathy-like symptoms, delirium, and loss of various memory domains. Dysexecutive syndrome is a peculiar manifestation of ‘Cognitive COVID’ as well. In the previous major outbreaks of viruses like SARS-CoV, MERS-CoV and Influenza. There have been attempts to understand the underlying mechanisms describing the causality of similar symptoms following SARS-CoV-2 infection. This review, therefore, is attempting to highlight the current understanding of the various direct and indirect mechanisms, focusing on the role of neurotropism of SARS-CoV-2, the general pro-inflammatory state, and the pandemic-associated psychosocial stressors in the causality of ‘Cognitive COVID.’ Neurotropism is associated with various mechanisms including retrograde neuronal transmission via olfactory pathway, a general hematogenous spread, and the virus using immune cells as vectors. The high amounts of inflammation caused by COVID-19, compounded with potential intubation, are associated with a deleterious effect on the cognition as well. Finally, the pandemic’s unique psychosocial impact has raised alarm due to its possible effect on cognition. Furthermore, with surfacing reports of post-COVID-vaccination cognitive impairments after vaccines containing mRNA encoding for spike glycoprotein of SARS-CoV-2, we hypothesize their causality and ways to mitigate the risk. The potential impact on the quality of life of an individual and the fact that even a minor proportion of COVID-19 cases developing cognitive impairment could be a significant burden on already overwhelmed healthcare systems across the world make it vital to gather further evidence regarding the prevalence, presentation, correlations, and causality of these events and reevaluate our approach to accommodate early identification, management, and rehabilitation of patients exhibiting cognitive symptoms.