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Main Claim & Relevance:

This preprint brings forward several claims from different disciplines, all regarding potential long term effects of SARS-CoV-19 and their causes.

Firstly, MRI scans revealed that mild COVID patients had reduced cortical thickness as well as signs of vasogenic edema in all lobes of the brain. Neuropsychological evaluation of 61 participants an average of 59 days after diagnosis revealed fatigue in approximately 70% of individuals and daytime sleepiness in 36%. Nearly 28% of participants performed abnormally on the logical memory cognitive function tests. Infection with COVID was also associated with higher instances of anxiety and depression compared to asymptomatic COVID positive patients.

In brain tissue samples of 26 patients who died of COVID, a strong predominance of senile changes were found. Inflammatory processes were noted within the tissue, and in some cases areas of liquefactive necrosis were present. In all patients that showed degenerative changes in brain tissue, both SARS-CoV-2 genetic material and spike proteins were found within the tissue. The majority of cells infected with COVID were astrocytes.

Further experimentation revealed that astrocytes readily allow for viral replication, and the primary route of entry is through NRP1 receptors. Infection of stem cell derived astrocytes with COVID impacts their metabolism which reduces their ability to support neurons. The presence of COVID-infected astrocytes increased the rate of neuron apoptosis in vitro significantly.

Are the findings strong, reliable, potentially informative, not informative, or misleading?

The findings of this preprint range from reliable to potentially informative. While the MRI evaluation of patients was controlled against healthy patients, the psychological evaluation of the participants of this study was not compared to an age matched group of healthy participants. This calls into question the strength of this evidence. Similarly, the analysis of brain tissue was only performed on COVID-infected patients and no analysis was performed on a control group of healthy patients. Some of the claims such as senile changes may be explained by the demographics of the patient population rather than possible effects of COVID. In contrast, the investigation involving the role of NRP1 receptors, metabolic changes, and neuronal viability is well powered and both reliable and reproducible.

How might these ideas presented by the main claims further knowledge of the COVID-19 Pandemic?

The long term cognitive effects of SARS-CoV-2 have been well documented over the course of the pandemic, however their causes are still largely unknown. The ideas presented by the authors provide a potential insight into the causes and severity of "long COVID" cases. This not only helps to further our knowledge of the virus and how it functions, but it may also impact future medical care of patients.