Neurological Sequelae of COVID-19: A Scoping Review of Routine Brain MRI Findings in Post-COVID Condition


While COVID-19 is slowly fading from the headlines, a growing number of people report persistent symptoms of the condition that has become internationally recognized as long COVID or post-COVID condition (PCC).

This condition is associated with over 60 heterogeneous physical and psychological symptoms affecting multiple organ systems. The heterogeneity of long COVID symptoms has generated sometimes controversial and confusing findings, leading to debates and conflicting reports in medical research.

This article delves into the realm of neurological sequelae of COVID-19, specifically focusing on the findings of routine brain MRI in adult patients who have recovered from the symptoms of acute COVID-19.

The Complex Landscape of Long COVID

Long COVID, or PCC, presents a complex and multifaceted clinical picture. This condition can manifest as a wide range of symptoms affecting various organ systems. These symptoms include but are not limited to fatigue, fever, headache, runny nose, sore throat, poor well-being, and a myriad of neurological issues. Such heterogeneity in symptoms has posed challenges for both diagnosis and treatment [5,6].

Additionally, there have been controversies surrounding the attribution of these symptoms solely to COVID-19, as some COVID-negative patients have reported similar or even higher rates of symptoms typically associated with PCC [7,8].

The complexity of long COVID extends to medical imaging research, where studies have reported conflicting findings regarding the effects of SARS-CoV-2 infection on brain structure and function [9,10].

Challenges in Neuroimaging Research for Long COVID

One of the areas where controversy and complexity arise is in neuroimaging research related to long COVID. Studies have used advanced neuroimaging techniques, such as diffusion tensor imaging, to investigate changes in brain structure and function. However, these techniques are not part of routine clinical practice and are more time-consuming and resource-intensive [11].

This presents challenges in incorporating these advanced MRI findings into existing diagnostic pathways, which prioritize cost-effectiveness and efficiency [12,13]. Furthermore, the computational post-processing required for advanced imaging techniques prolongs the decision-making process regarding their widespread use in clinical practice [14].

Healthcare resource utilization and cost-effectiveness are crucial considerations when evaluating the potential implementation of advanced MRI techniques for long COVID diagnosis [15]. Therefore, it is essential to assess the capabilities of routine brain MRI in providing insights into the neurological sequelae of COVID-19.

The Need for a Scoping Review

Given the conflicting, confusing, and heterogeneous nature of existing knowledge on the neurological sequelae of COVID-19, as well as the limitations associated with advanced neuroimaging techniques, a scoping review is crucial. This review aims to map the research conducted in this area and identify gaps in our understanding. The primary research question guiding this scoping review is: What is known from the published literature about the changes in the brain observed on routine MRI in adult patients who have recovered from the symptoms of acute COVID-19?

Review Findings and Discussion

In this scoping review, we identified seven studies published until April 2023 that addressed biomarkers of PCC detectable on routine brain MRI.

The key finding of this review is that the neurophysiological manifestations following COVID-19 infection are not associated with visually detectable brain MRI lesions in the majority of cases.

While one study reported a statistically significant relation between abnormal MRI findings (white matter lesions) and neurophysiological malfunctioning, this result is inconclusive due to small sample size and the absence of control for confounding factors [25].

One notable area of contradiction in the studies was the association between cerebral microbleeds and the severity of COVID-19. Some studies found microbleeds in both ICU and non-ICU patients, while others identified them primarily in ICU patients. However, it is essential to consider that microvascular pathology is common in ICU patients, regardless of COVID-19 [30,31].

Moreover, there was no clear evidence that microbleeds contributed to long COVID symptoms or cognitive dysfunction [32,33].

The findings reported in the included studies are heterogeneous, inconsistent, and not always clearly defined. For instance, perivascular spaces were identified as the most common brain MRI abnormality in one study but were not consistently reported in others. Perivascular spaces are typically considered a normal finding and may not be clinically significant [37]. However, the enlargement of perivascular spaces was explored in one study as a potential marker of dysfunction, although it did not show significant associations with clinical outcomes [37].


This scoping review highlights the ambiguity of using routine brain MRI for the diagnosis and management of long COVID. Despite the heterogeneity of findings in the included studies, none of the reported brain MRI abnormalities showed significant correlations with long COVID symptoms. As a result, the use of routine brain MRI for long COVID patients should be reserved for cases where potentially life-threatening conditions are suspected, and clinical judgment should guide its utilization.

Limitations of this scoping review include its reliance on a single database, exclusion of preprints, and the omission of grey literature, potentially leading to missed relevant results. Additionally, the heterogeneity of brain MRI abnormalities prevented the conduct of a meta-analysis. However, the consistent absence of clinical significance in these abnormalities across studies suggests a need for further research to better understand the neurological sequelae of COVID-19 and their implications for diagnosis and management.

In conclusion, while long COVID remains a complex and challenging condition, routine brain MRI does not appear to be a reliable tool for identifying specific neurological biomarkers associated with its symptoms. Future research should focus on a comprehensive and multidisciplinary approach to better understand and address the diverse and persistent symptoms of long COVID.

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