Introduction

Since late 2019, the novel coronavirus disease 2019 (COVID-19), which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has emerged as a global pandemic¹. It is highly contagious, still ongoing and is confirmed to have infected 200 million and killed 5 million people worldwide². While many COVID-19 patients recover without any notable lasting symptoms, a significant proportion of COVID-19 patients continue to have persistent neurological sequelae³ including stroke, visual defects, anosmia/dysgeusia, brain fog4, among others. To date, these manifestations are not well understood. Long-haul COVID-19 syndrome⁴ is expected to become a serious healthcare burden in the next several years⁵. Here, we report our preliminary neuroradiological findings from ultrahigh field MRI at 7T in patients with post-COVID neurological symptoms.

Methods

In this study, 8 patients (age: 54 ± 10, 4 female), who had recovered from COVID-19 and presented with post-COVID neurological symptoms, were enrolled. All patients underwent whole brain MRI on a Siemens Magnetom 7T scanner (Siemens Healthineers, Erlangen, Germany) using a 1Tx/32Rx head coil (Nova Medical, Wilmington, MA). The MRI protocol was specifically developed for this COVID-19 study and included axial T1-weighted MP2RAGE, FLAIR, T2-weighted TSE, susceptibility weighted imaging (SWI), as well as coronal-oblique T2-weighted TSE (imaging plane oriented perpendicular to olfactory bulbs) and a T2*-weighted multiecho spoiled-gradient-echo sequence to capture the brainstem perpendicular to the imaging plane (Siemens MEDIC sequence, shimmed across brainstem). (The protocol also included DTI, ASL and rs-fMRI). Images were evaluated by 3 fellowship-trained neuroradiologists for T2/FLAIR hyperintensities (based on the Fazekas scale), infarcts, chronic microhemorrhages and macrohemorrhages, encephalopathy features, brain volume loss (qualitative), olfactory bulb abnormalities and brainstem abnormalities. Findings that differed among the readers were reviewed and adjudicated in consensus.

Results

The post-COVID neurological symptoms of each patient are listed in Table 1. The neuroradiological findings from 7T MRI are also listed in Table 1. The neuroradiological findings were heterogeneous across the patients. No infarcts and no encephalopathy features were observed in any patient. Bilateral olfactory bulb thinning (Figure 1) was observed in Patient 4, who presented neurological symptoms of dysgeusia and COVID long haul syndrome. Brainstem abnormalities were observed in two patients: microhemorrhage in the left dorsal pons Patient 2 and hyperintensity in the lower medulla tracts in Patient 4. Figure 2 shows three images of the brainstem in Patient 4 acquired with the multiecho spoiled-gradient-echo sequence (Siemens MEDIC).

Chronic microhemorrhage was observed in Patient 3 in the left frontal subinsular region (Figure 3A). Chronic macrohemorrhage was observed in Patient 2 in the right frontal cortex (Figure 3B). Both Patients 2 and 3 presented with the neurological symptom of encephalopathy. Moderate FLAIR/T2 hyperintensities (Fazekas scale 2) were observed in Patient 6 (Figure 4). Patient 6 presented with several neurological symptoms including COVID long haul syndrome, numbness, headache and blurry vision, as listed in Table 1. Mild hyperintensities (Fazekas scale 1) were observed in 6 patients.

The following incidental findings, which are likely unrelated to COVID-19, were observed: arachnoid cysts in two patients and prominent arachnoid granulations in four patients.

The time between COVID-19 diagnosis and 7T MRI was 12 ± 5 months.

Finally, it should be noted that Patients 2, 3 and 4 were hospitalized at the time of COVID-19 infection and underwent brain MRI at 1.5T as part of their clinical care. These acute-stage 1.5T MRI exams did not reveal any abnormalities.

Discussion

In this ongoing study, we report our preliminary neuroradiological findings from brain MRI at 7T in 8 patients with post-COVID neurological symptoms. The neuroradiological findings are very heterogeneous. It is interesting that these findings persist even after 12 months post COVID infection. In particular, three of the patients in this study underwent brain MRI at 1.5T as part of their clinical care during COVID-related hospitalization, and those patients did not present any findings from the 1.5T MRI exams at the acute phase, even though they presented findings from 7T MRI. The reason for this is unknown: it is possible that this is due to the lack of high resolution and SNR in the clinical exams, or that these findings are chronic in nature. It is also interesting that 4 of 8 patients presented the incidental finding of prominent arachnoid granulations. This may indicate lymphatic involvement in the neurotropism of SARS-CoV-2 virus.

It should be noted that thinning of the olfactory bulbs was observed in one patient. However, this patient presented dysgeusia as a neurological finding, and not anosmia. Anosmia is more likely to be related to thinning of the olfactory bulbs. It is possible that the patient did have anosmia but failed to report it (both anosmia and dysgeusia are often concurrent in COVID-19).

Because of the small sample size of this study, it was not possible to derive any associations between the neurological symptoms and the 7T neuroradiological findings. We would like to note that this study is ongoing and in the early stages, and we expect to have a larger sample size of both post-COVID patients and age and sex-matched healthy controls very soon. We expect to find meaningful links between 7T neuroradiological findings and neurological symptoms in a larger cohort of post-COVID patients.