Even as the COVID-19 pandemic was sweeping across the world, new symptoms and clinical presentations appeared, often confusing the picture. A case report from Italy, published in the journal JAMA Neurology in May 2020, shows that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may be a neurotropic virus, and may cause infection to present primarily with anosmia.
Human Coronavirus Infection
Human coronaviruses have already been shown to infect the nervous system in small animals. Autopsies of humans who suffered from SARS (severe acute respiratory syndrome) in 2002 to 2003 showed the presence of the SARS-CoV virus in the brain. Similarly, the SARS-CoV-2 may invade nervous tissue, and this may, partly at least, result in respiratory failure.
Coronaviruses (CoVs) are members of the largest group of viruses that are responsible for respiratory and gastrointestinal infections. Members of this group have caused three pandemics in the last two decades: first, the SARS outbreak in 2002, and the Middle East respiratory syndrome (MERS) pandemic in 2012. The current COVID-19 pandemic is thus the third outbreak caused by a coronavirus.
The symptoms of COVID-19 infection include fever, a dry cough, tiredness, anosmia, loss of taste, a sore throat, gut symptoms like diarrhea, headache, and leg pain. However, the majority of patients with COVID-19 do not know it, being completely asymptomatic, or develop only a mild bout of symptoms like sneezing or coughing.
In about 20% of cases, the infection progresses to cause severe pneumonia, acute respiratory distress syndrome (ARDS), multi-organ failure, and sometimes death, in a significant minority of cases. Despite the severe impact on the lungs, more evidence is coming in that the virus can also affect other organs and body systems, which could imply that the pandemic could leave behind acute and chronic sequelae.
The Brain and COVID-19
This could include neurological conditions. Patients with a history of stroke are among those at higher risk for COVID-19-induced ARDS, as has been shown by numerous case series. Conversely, over a third of COVID-19 patients in a Chinese study, had neurological signs such as acute stroke or loss of consciousness.
This is supported by the presence of agitation, confusion, signs of motor neuron involvement, and brain disorder in the majority of patients with this infection in a French study. In fact, the MERS-CoV outbreak was also associated with severe manifestations related to the nervous system.
The Case Report
The case study describes a female radiographer aged 25 years, with no underlying medical illness, who was working in a COVID-19 ward. She had a mild dry cough, which vanished after a day, to subsequently develop persistent and almost complete loss of smell and a weakened sense of taste. There was no fever, then or ever.
She had no history of any trauma, seizure, or hypoglycemic episode at any time. On the third day of anosmia, she underwent a fibroscopic evaluation of the nasal cavity, which failed to show any positive findings. A chest CT and CT of the maxillofacial cavities also did not show any particular findings. An MRI of the brain was also carried out, which included both 3D and 2D fluid-attenuated inversion recovery images.
The Imaging Findings
These images showed a hyperintense area in the cortex of the right gyrus rectus, as well as a less obvious hyperintense region in the olfactory bulbs. The occurrence of anosmia in many patients with COVID-19, in Italy, and because the altered cortical image suggested a viral infection of the area, the patient had a swab taken for reverse transcription-polymerase chain (RT-PCR) testing, to detect SARS-CoV-2.
The test was positive. A follow-up MRI which was taken after 28 days showed complete resolution of the hyperintensity in the right gyrus rectus cortex, while the olfactory bulbs had become less hyperintense and appeared slimmer.
The patient’s anosmia eventually resolved. Interestingly, two other COVID-19 patients who also had anosmia did not show any signal alterations in MRIs of the brain at 12 and 25 days from the earliest symptom.
The Importance of This Case Report
The investigators say this is the first time that the human brain has been shown to be involved in a living patient with COVID-19, in the form of an alteration in the brain cortical signal that suggests viral invasion of the brain in a part that is linked to olfaction. The differential diagnoses in this patient could have been conditions like status epilepticus, changes like those seen in posterior reversible encephalopathy syndrome, other viral infections, and anti NMDA encephalitis, but none of these were probable in the clinical circumstances.
The subtle changes in the olfactory bulb, in addition to the other MRI findings, led the scientists to wonder if the virus could be invading the olfactory bulb and through this pathway, the brain, causing sensorineural dysfunction of the olfactory sense. However, this can be proved only if the evidence is compiled by the study of cerebrospinal fluid (CSF) and pathologic studies of the brain tissue.
A possible issue raised here is the absence of brain changes on MRI in two other COVID-19 patients who also had anosmia, as well as the disappearance of the MRI changes at the 28-day follow-up examination of this patient. This could indicate the extreme transience of these findings, which might occur only at the earliest stage of infection, or that they do not occur in all patients.
Another important finding from this case study is that some COVID-19 patients present only with anosmia, and it is necessary to evaluate this finding in the current situation to avoid missing the diagnosis in these otherwise asymptomatic patients and thus facilitating continued disease transmission from such individuals.
- Politi, L. S. et al. (2020). Magnetic Resonance Imaging Alteration of the Brain in a Patient with Coronavirus Disease 2019 (COVID-19) and Anosmia. JAMA Neurology doi:10.1001/jamaneurol.2020.2125.