The persistent impact of SARS-CoV2 on the brain


On May 5, 2023, the World Health Organization (WHO) officially declared the end to the COVID-19 pandemic. While this announcement marked a significant milestone, it did not signal the cessation of concerns related to SARS-CoV2, particularly within the realm of neurological health. This article delves into the persistent neurological implications of the virus, emphasizing a groundbreaking study published in June 2023 by Thomasson et al. in Brain Communications (2).


The chronic phase of COVID-19 has brought forth a myriad of concerns, with emerging evidence pointing towards alterations in the limbic system. This chapter delves into the intricate interplay between SARS-CoV-2 infection and emotion recognition abilities, shedding light on the multifaceted connections within the limbic system. Beyond the well-documented olfactory and episodic memory disorders, reports have surfaced regarding diminished emotion recognition abilities in individuals who experienced moderate or severe symptoms during the acute phase of COVID-19.

Limbic System Alterations in the Chronic Phase

Neuroimaging studies employing methods such as fluorodeoxyglucose (18FDG) PET and MRI have unveiled hypometabolism or hypoconnectivity in cortical–subcortical brain regions, many of which are integral components of the limbic system. These alterations extend to the cerebellum, further emphasizing the widespread impact of SARS-CoV-2 on the neural architecture (1,3–5,13,15,16). Additionally, structural changes, including reduced grey-matter thickness in the orbitofrontal cortex and parahippocampal gyrus, have been observed, hinting at potential disruptions in limbic-related functions (17).

Behavioral and Neuroimaging Disconnect

While behavioral studies have explored emotion recognition abilities in the context of COVID-19, a significant gap remains in understanding the relationships between multimodal emotion recognition and structural and functional neuroimaging data. Current literature has largely focused on overall scores, neglecting individual emotions and their nuanced processing.

Secondary Neuropsychiatric Variables and Emotion Recognition

The intricate relationship between neuropsychiatric symptoms and emotion recognition abilities following SARS-CoV-2 infection remains unexplored. Conditions such as post-traumatic stress disorder (PTSD), anxiety, depressive symptoms, fatigue, and sleep disturbances have been documented post-infection, each known to influence emotional processing (19–24). However, no study to date has systematically assessed the impact of these variables on the recognition of individual multimodal emotions, considering the severity of respiratory symptoms in the acute phase.

Emotion Processing and the Limbic System

Understanding emotions involves a complex neural network, with the limbic circuits playing a pivotal role. Recent models suggest the existence of multiple differentiated limbic systems for emotional processes, encompassing anterior structures like the orbitofrontal cortex and amygdala for emotion processing and posterior structures, including the hippocampus, for memory functions (28). The intricate interplay between these limbic systems and the cerebellum adds another layer of complexity to the emotional processing landscape (29).

Study Objectives

This study aims to unravel the impact of the severity of respiratory symptoms during the acute phase of COVID-19 on emotion recognition abilities 6–9 months post-infection. It also seeks to explore the influence of secondary behavioral variables, such as olfaction, memory, and depressive symptoms, along with assessing the functional brain connectivity associated with emotion recognition.


The study includes 105 participants assessed 223.07 ± 41.69 days post-SARS-CoV-2 infection. A comprehensive battery of assessments, including neuropsychological functions, neuropsychiatric manifestations, olfactory performances, and multimodal emotion recognition tasks, were administered. Forty-five participants underwent functional MRI to explore associations between emotion recognition abilities and functional brain networks using partial least squares correlation (PLSC) analyses.

Neurotropic Nature of SARS-CoV2

SARS-CoV2, recognized as a neurotropic virus, is hypothesized to infiltrate neural tissue either hematogenously or through peripheral nerve endings, ultimately accessing the brain through retrograde transport (1). The long-term sequelae in COVID-19 survivors, especially within the neurology domain, have emerged as an area of heightened concern.

Limbic System Damage and Emotional Impairment

The study by Thomasson et al. sheds light on limbic system damage resulting from SARS-CoV2 infection. Published in June 2023, the research revealed that moderately and severely affected COVID-19 patients exhibited impaired emotion recognition, coupled with diminished memory and olfactory abilities. Additionally, alterations in functional connectivity patterns involving cortico-subcortical-cerebellar networks were identified at 6-9 months post-infection (2).

Limbic System in Focus

Since the onset of the pandemic, the limbic system has been a focal point, given the loss of olfaction as a prominent symptom of SARS-CoV2 infection. Subsequent studies have showcased various alterations in metabolism, perfusion, structure, and connectivity within limbic structures following COVID-19 (3-6). Thomasson et al.’s study adds a crucial layer by highlighting the behavioral consequences of limbic system damage and associated functional connectivity changes at the 6-9 month post-infection mark.

Structural Changes in Limbic Sites

An intriguing aspect of the study was the exploration of potential structural changes in the limbic sites of the brain using volume-based morphometric (VBM) analyses. Notably, the authors reported no discernible structural differences in the anatomical images, yet the absence of a control group posed challenges in attributing changes to SARS-CoV2 infection. Previous studies have indicated limbic alterations even in mild, non-hospitalized patients, with reports of both atrophy and increased thickness of cortical areas at varying time points after infection (6,8,9).

Concerns About Neurodegeneration

The looming concern surrounding SARS-CoV2 involves secondary neurodegeneration, with cerebral cortical atrophy emerging as a noteworthy finding. While functional and network impairments may manifest without structural damage, the coexistence of atrophy could indicate a degenerative process requiring special consideration. The absence of certain brain parcels, such as the hippocampus and insula, in the authors’ VBM findings prompts a call for a detailed re-evaluation of these structures in comparison with an age-and sex-matched control group.

The Limbic System: The Emotional Center of the Brain

The limbic system, also known as the paleomammalian cortex, is a complex network of brain structures located deep within the temporal lobes, underneath the cerebral cortex. It plays a crucial role in regulating emotions, motivation, memory, and learning.

Key components of the limbic system:

  • Amygdala: This almond-shaped structure is responsible for processing emotions like fear, anger, and pleasure. It also plays a role in memory consolidation and emotional responses.
  • Hippocampus: This seahorse-shaped structure is crucial for learning and memory formation. It helps us store and retrieve information, and it plays a vital role in spatial navigation.
  • Hypothalamus: This tiny structure acts as the brain’s control center for various physiological functions, including hunger, thirst, sleep, and body temperature. It also regulates the release of hormones.
  • Cingulate cortex: This region is involved in processing emotions, attention, and decision-making. It also plays a role in self-awareness and consciousness.
  • Fornix: This bundle of nerve fibers connects the hippocampus to other parts of the limbic system, facilitating communication and information flow.
  • Mammillary bodies: These structures are involved in memory consolidation and spatial navigation. They also play a role in processing emotions.

Functions of the limbic system:

  • Emotional processing: The limbic system plays a central role in processing emotions, including fear, anger, joy, sadness, and love. It helps us interpret emotional cues in our environment and generate appropriate emotional responses.
  • Motivation and reward: The limbic system is involved in motivating us to engage in behaviors that are essential for survival and reproduction. It also helps us experience pleasure and reward, which reinforces our motivation to repeat behaviors that we find enjoyable.
  • Memory and learning: The limbic system plays a crucial role in various aspects of memory, including learning, consolidation, and retrieval. It helps us store and access information, and it allows us to remember experiences and emotions.
  • Regulation of physiological functions: The limbic system interacts with the hypothalamus to regulate various physiological functions such as sleep, hunger, thirst, and body temperature.
  • Social behavior: The limbic system is involved in processing social cues and regulating social behavior. It helps us understand the emotions of others and respond accordingly.

Damage to the limbic system can lead to various neurological and psychological disorders, such as:

  • Anxiety disorders
  • Depression
  • Post-traumatic stress disorder (PTSD)
  • Schizophrenia
  • Addiction
  • Alzheimer’s disease
  • Autism spectrum disorder


The limbic system is a vital part of the brain that plays a critical role in our emotional life, motivation, memory, and learning. Understanding how the limbic system works is essential for developing effective treatments for various neurological and psychological disorders.

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