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Images in Neurology
May 29, 2020

Magnetic Resonance Imaging Alteration of the Brain in a Patient With Coronavirus Disease 2019 (COVID-19) and Anosmia

Author Affiliations
  • 1Department of Neuroradiology, IRCCS Istituto Clinico Humanitas and Humanitas University, Milan, Italy
  • 2Department of Radiology and Hematology & Oncology Division, Boston Children’s Hospital, Boston, Massachusetts
  • 3Department of Radiology and Advanced MRI Center, University of Massachusetts Medical School and Medical Center, Worcester, Massachusetts
  • 4UOC Malattie Neurodegenerative e Neurometaboliche Rare, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy
JAMA Neurol. Published online May 29, 2020. doi:10.1001/jamaneurol.2020.2125

The neurotropism of human coronaviruses has already been demonstrated in small animals, and in autoptic studies the severe acute respiratory syndrome coronavirus (SARS-CoV), which was responsible for the SARS outbreak during 2002 to 2003, was found in the brains of patients with infection.1 It has been proposed that the neuroinvasive potential of the novel SARS-CoV-2, responsible for coronavirus disease 2019 (COVID-19), may be at least partially responsible for the respiratory failure of patients with COVID-19.2 In this article, we share the magnetic resonance imaging (MRI) evidence of in vivo brain alteration presumably due to SARS-CoV-2 and demonstrate that anosmia can represent the predominant symptom in COVID-19.

A 25-year-old female radiographer with no significant medical history who had been working in a COVID-19 ward presented with a mild dry cough that lasted for 1 day, followed by persistent severe anosmia and dysgeusia. She did not have a fever. She had no trauma, seizure, or hypoglycemic event. Three days later, nasal fibroscopic evaluation results were unremarkable, and noncontrast chest and maxillofacial computed tomography results were negative. On the same day, a brain MRI was also performed. On 3-dimensional and 2-dimensional fluid-attenuated inversion recovery images, a cortical hyperintensity was evident in the right gyrus rectus (Figure 1) and a subtle hyperintensity was present in the olfactory bulbs (Figure 1). Because many patients in Italy are experiencing anosmia3 and the cortical signal alteration was suggestive of viral infection, a swab test was performed and reverse transcription–polymerase chain reaction analysis yielded positive results for SARS-CoV-2. During a follow-up MRI performed 28 days later, the signal alteration in the cortex completely disappeared and the olfactory bulbs were thinner and slightly less hyperintense (Figure 24). The patient recovered from anosmia. No brain abnormalities were seen in 2 other patients with COVID-19 presenting anosmia who underwent brain MRI 12 and 25 days from symptom onset.

Figure 1.  Brain Magnetic Resonance Imaging Alterations in a Patient With Coronavirus Disease 2019 (COVID-19) Presenting With Anosmia 4 Days From Symptom Onset
Brain Magnetic Resonance Imaging Alterations in a Patient With Coronavirus Disease 2019 (COVID-19) Presenting With Anosmia 4 Days From Symptom Onset

Coronal (A) and axial (B) reformatted 3-dimensional fluid-attenuated inversion recovery (FLAIR) images showing cortical hyperintensity in the right gyrus rectus (yellow arrowheads in A and B). In the inset in A, a coronal 2-dimensional FLAIR image shows subtle hyperintensity in the bilateral olfactory bulbs (white arrowheads). The cortical hyperintensity is present only in the posterior portion of the right gyrus rectus (B). Accordingly, the cortical hyperintensity of the right gyrus rectus is evident in the more posterior coronal image (A) and not in the anterior coronal one (inset).

Figure 2.  Follow-up Magnetic Resonance Imaging Study in the Same Patient 28 Days From Symptom Onset
Follow-up Magnetic Resonance Imaging Study in the Same Patient 28 Days From Symptom Onset

Coronal (A) and axial (B) reformatted 3-dimensional fluid-attenuated inversion recover (FLAIR) images showing complete resolution of the previously seen signal alteration within the cortex of the right gyrus rectus. In the inset, a coronal 2-dimensional FLAIR image shows a slight reduction of the hyperintensity and the thickness of the olfactory bulbs, suggesting a postinfection olfactory loss.4

To our knowledge, this is the first report of in vivo human brain involvement in a patient with COVID-19 showing a signal alteration compatible with viral brain invasion in a cortical region (ie, posterior gyrus rectus) that is associated with olfaction. Alternative diagnoses (eg, status epilepticus, posterior reversible encephalopathy syndrome–like alterations, other viral infections, and anti–N-methyl-d-aspartate receptor encephalitis) are unlikely given the clinical context. Based on the MRI findings, including the slight olfactory bulb changes, we can speculate that SARS-CoV-2 might invade the brain through the olfactory pathway and cause an olfactory dysfunction of sensorineural origin; cerebrospinal fluid and pathology studies are required to confirm this hypothesis. Ours and others’ observations of normal brain imaging in other patients with COVID-19–associated olfactory dysfunctions4 and the disappearance of the cortical MRI abnormalities in the follow-up study of this patient suggest that imaging changes are not always present in COVID-19 or might be limited to the very early phase of the infection. Further, anosmia can be the predominant COVID-19 manifestation, and this should be considered for the identification and isolation of patients with infection to avoid disease spread.

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Article Information

Corresponding Author: Letterio S. Politi, MD, IRCCS Istituto Clinico Humanitas, via Alessandro Manzoni 56, Rozzano 20089, Italy (letterio.politi@hunimed.eu).

Published Online: May 29, 2020. doi:10.1001/jamaneurol.2020.2125

Conflict of Interest Disclosures: None reported.

Additional Contributions: We thank Simona Superbi and Cristiana Lucarini (Department of Neuroradiology, IRCCS Istituto Clinico Humanitas) for technical support and the patient for granting permission to publish this information. No compensation was provided.

References
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Gu  J, Gong  E, Zhang  B,  et al.  Multiple organ infection and the pathogenesis of SARS.   J Exp Med. 2005;202(3):415-424. doi:10.1084/jem.20050828PubMedGoogle ScholarCrossref
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Li  YC, Bai  WZ, Hashikawa  T.  The neuroinvasive potential of SARS-CoV2 may play a role in the respiratory failure of COVID-19 patients.   J Med Virol. 2020. doi:10.1002/jmv.25824PubMedGoogle Scholar
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Giacomelli  A, Pezzati  L, Conti  F,  et al.  Self-reported olfactory and taste disorders in SARS-CoV-2 patients: a cross-sectional study.   Clin Infect Dis. 2020;ciaa330. doi:10.1093/cid/ciaa330PubMedGoogle Scholar
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Eliezer  M, Hautefort  C, Hamel  AL,  et al.  Sudden and complete olfactory loss function as a possible symptom of COVID-19.   JAMA Otolaryngol Head Neck Surg. 2020. doi:10.1001/jamaoto.2020.0832PubMedGoogle Scholar
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    1 Comment for this article
    EXPAND ALL
    UFPs Could Be a Carrier for SARS-CoV-2 to Brain Structures via the Olfactory Pathway
    Giovanni Ghirga, Pediatrician, Italy |
    Ultrafine particles (<100 nm, UFPs) comprise more than 90% of the total concentration of submicron particles in urban areas, and 70%–80% in suburban areas (1). Nose-to-brain transport of airborne ultrafine particles (UFPs) via the olfactory pathway has been verified as a possible route for particle translocation into the brain (2). Particulate matter represents an effective carrier for virus transport (3). UFPs could be a carrier for SARS-CoV-2 to the brain structures via the olfactory pathway, and pathologic studies of the olfactory pathway aimed to observe or exclude the role of UFPs as a carrier for SARS-CoV-2 transportation from the nose to the brain are needed.

    REFERENCES

    1) Manigrasso M, Protano C, Martellucci S, Mattei V, Vitali M, Avino P. International Journal of Environmental Research and Public Health. Evaluation of the Submicron Particles Distribution Between Mountain and Urban Site: Contribution of the Transportation for Defining Environmental and Human Health Issues. Int. J. Environ. Res. Public Health 2019, 16, 1339.
    2) Tian L, Shang Y, Chen R, Bai R, Chen C, et al. Correlation of regional deposition dosage for inhaled nanoparticles in human and rat olfactory. Particle and Fibre Toxicology (2019) 16:6. https://doi.org/10.1186/s12989-019-0290-8
    3) SIMA, University of Bologna, and University of Bari, Italy. Evaluation of the potential relationship between Particulate Matter (PM) pollution and COVID-19 infection spread in Italy. Position Paper. http://www.simaonlus.it/wpsima/wp-content/uploads/2020/03/COVID_19_position-paper_ENG.pdf. Accessed 29 May 2020.
    CONFLICT OF INTEREST: None Reported
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