Encephalitic syndrome and anosmia in COVID‐19: Do these clinical presentations really reflect SARS‐CoV‐2 neurotropism? A theory based on the review of 25 COVID‐19 cases

Abstract

Since the discovery of coronavirus disease 2019 (COVID‐19), a disease caused by the new coronavirus severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), the pathology showed different faces. There is an increasing number of cases described as (meningo)encephalitis although evidence often lacks. Anosmia, another atypical form of COVID‐19, has been considered as testimony of the potential of neuroinvasiveness of SARS‐CoV‐2, though this hypothesis remains highly speculative. We did a review of the cases reported as brain injury caused by SARS‐CoV‐2. Over 98 papers found, 21 were analyzed. Only four publications provided evidence of the presence of SARS‐CoV‐2 within the central nervous system (CNS). When facing acute neurological abnormalities during an infectious episode it is often difficult to disentangle neurological symptoms induced by the brain infection and those due to the impact of host immune response on the CNS. Cytokines release can disturb neural cells functioning and can have in the most severe cases vascular and cytotoxic effects. An inappropriate immune response can lead to the production of auto‐antibodies directed toward CNS components. In the case of proven SARS‐CoV‐2 brain invasion, the main hypothesis found in the literature focus on a neural pathway, especially the direct route via the nasal cavity, although the virus is likely to reach the CNS using other routes. Our ability to come up with hypotheses about the mechanisms by which the virus might interact with the CNS may help to keep in mind that all neurological symptoms observed during COVID‐19 do not always rely on CNS viral invasion.

Highlights

• Review of 25 COVID‐19 cases with neurological symptoms.

• Evidence of the SARS‐CoV‐2 presence in the brain is often lacking.

• Brain magnetic resonance imagery is the most accurate exam to explore brain damages.

• SARS‐CoV‐2 can cause anosmia and neurological symptoms without invading the brain.

• The routes used by SARS‐CoV‐2 to invade the brain may lead to different symptoms.