Research press release


Nature Neuroscience

Neuroscience: SARS-CoV-2 may enter the brain via the nose

重症急性呼吸器症候群コロナウイルス2(SARS-CoV-2)は、ヒトの鼻の中を通って脳に入り込む可能性のあることを示唆する剖検結果について報告する論文が、Nature Neuroscience に掲載される。この知見は、新型コロナウイルス感染症(COVID-19)患者に観察された神経症状の一部を説明する上で役立つ可能性があり、診断や感染予防対策に役立つ可能性もある。


今回、Frank Heppnerたちの研究グループは、COVID-19で死亡した33人の患者(男性22人、女性11人)を対象として、ウイルス感染とウイルスの複製が起こる最初の部位である可能性の高い鼻咽頭(鼻腔につながる喉の上部)と脳を調べた。これらの患者の死亡時の年齢は71.6歳(中央値)で、COVID-19の症状が発現してから死亡するまでの期間は31日(中央値)だった。脳と鼻咽頭にはSARS-CoV-2のRNAとタンパク質が存在しており、鼻咽頭からは無傷のウイルス粒子も検出された。SARS-CoV-2のRNAのレベルが最も高かったのは嗅粘膜だった。Heppnerたちは、罹病期間が、検出可能なSARS-CoV-2のRNA量と逆相関していたことを指摘しており、このことは、罹病期間の短い症例ではSARS-CoV-2のRNAレベルが高いことを示している。



SARS-CoV-2 may enter the brain of people through the nose, suggests an autopsy study published in Nature Neuroscience. These findings may help explain some of the neurological symptoms observed in COVID-19 patients and may inform diagnosis and measures to prevent infection.

SARS-CoV-2 not only affects the respiratory tract but also impacts the central nervous system (CNS), resulting in neurological symptoms such as loss of smell, taste, headache, fatigue and nausea. Although recent research has described the presence of viral RNA in the brain and cerebrospinal fluid, it remains unclear where the virus enters and how it is distributed within the brain.

Frank Heppner and colleagues examined the nasopharnyx (the upper part of the throat that connects to the nasal cavity), a likely first site of viral infection and replication, and the brains of 33 patients (22 males and 11 females) who died with COVID-19. The median age at the time of death was 71.6 years, and the time from onset of COVID-19 symptoms to death was a median of 31 days. The authors found the presence of SARS-CoV-2 RNA and protein in the brain and nasopharynx. Intact virus particles were also detected in the nasopharynx. The highest levels of viral RNA were found in the olfactory mucous membrane. They noted that disease duration was inversely correlated with the amount of detectable virus, indicating that higher SARS-CoV-2 RNA levels were found in cases with shorter disease duration.

The authors also found SARS-CoV-2 spike protein in certain types of cells within the olfactory mucous layer, where it may exploit the proximity of endothelial and nervous tissue to gain entry to the brain. In some patients, SARS-CoV-2 spike protein was found in cells expressing markers of neurons, suggesting that olfactory sensory neurons may be infected, as well as in the brain areas that receive smell and taste signals. SARS-CoV-2 was also found in other areas of the nervous system, including the medulla oblongata — the primary respiratory and cardiovascular control center of the brain.

Further COVID-19 autopsy studies that include a broad range of sampling are needed to identify the precise mechanisms that mediate the virus’s entry into the brain, and examine other potential ports of entry.

doi: 10.1038/s41593-020-00758-5

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