Encephalopathy as neurological involvement of SARS-COV-2 infection

The most important characteristic symptom of patients with SARS-CoV-2 infection is respiratory distress. Additionally, some patients with COVID-19 disease presented neurologic signs, such as headache, nausea, and vomiting, too. Increasing evidence shows that coronaviruses are not only restrained to the lung but may also enter the central nervous system provoking neurological diseases. Mao and colleagues [1] describe the neurological manifestations of hospitalized patients with COVID-19 in Wuhan, China. Considering this retrospective case series study, 36.4% of patients had neurologic symptoms as acute cerebrovascular diseases, consciousness impairment, and skeletal muscle symptoms; however, the authors do not report any case of encephalitis.

We recently hospitalized a 56-year-old patient, previously healthy, referred to the emergency department for sudden onset of fever of > 38 °C fever, alteration of the state of consciousness, the difficulty of speech, and sleepy state challenging to awaken. The clinical picture started a week before with a cough treated with an empirical antibiotic drug (clarithromycin) with some initial benefit. Subsequently, he worsened, and the family doctor prescribed a second antibiotic drug (cefazolin). After the further deterioration of respiratory function, he was transported to hospital.

At the emergency department, the patient presented a generalized tonic–clonic crisis treated with diazepam. On presentation, he was febrile (body temperature 38.5 °C), tachycardic, and minimally arousable. He had extensor posturing of the upper extremities, nuchal rigor and withdrew both lower extremities to pain. He was not hypoxic throughout the clinical monitoring.

Extensive diagnostic studies were performed in peripheral blood documenting lymphocytopenia (total white cells 3430/mm³, lymphocytes 470/mm³) and C-reactive protein value of 21.3 mg/L. Toxicological testing was negative. Plasma procalcitonin had a normal value. Urine tests were regular. Results of serologic tests for L. pneumophila and the urinary antigen test for Legionella spp. were negative.

Chest x-ray showed no pathological signs, while the thoracic ultrasound documented an apparent mild interstitial involvement. The head computed tomography scan was normal. He started on empiric antibacterial and antiviral therapy.

The nasopharyngeal swab was positive for SARS-CoV-2. A lumbar puncture for liquor examination was also performed. Cerebrospinal fluid obtained 12 h after admission showed four cells/mm³ and elevated levels of glucose (82 mg/dL) and protein (115 mg/dL). The specific SARS-CoV-2 RNA was detected in a CSF, and culture for other viruses causing encephalitis was negative. Then the patient was treated experimentally with a monoclonal antibody against the IL-6 receptor (tocilizumab) with a rapid improvement of a general and neurological condition. In the following days, he reported anosmia.

This is another description of SARS-CoV-2 SNC involvement [2., 3., 4.]. The infection of SARS-CoV has been previously reported in the brains of both patients and experimental animals [5]. The exact way by which SARS-CoV can enter the central nervous system is not clearly demonstrated. Some evidence shows that coronavirus may first enter peripheral nerve terminals, and then they can enter the central nervous system via a synapse-connected pathway [6]. This trans-synaptic transfer has been well recognized for other coronaviruses, such as influenza [7]. Considering the similarity between SARS-CoV and SARS-CoV2, it is reasonable that SARS-CoV-2 also has similar potential. However, the description of this case provides evidence of invasion of the brain by the coronavirus also through the olfactory pathway rather than via peripheral nerves.