SARS-CoV-2 Brain Regional Detection, Histopathology, Gene Expression, and Immunomodulatory Changes in Decedents with COVID-19.
SARS-CoV-2 Brain Regional Detection, Histopathology, Gene Expression, and Immunomodulatory Changes in Decedents with COVID-19.
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DOI：
10.1093/jnen/nlac056
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发表时间：
2022-08-16
影响因子：
3.2
通讯作者：
中科院分区：
文献类型：
--
作者：
研究了42名COVID-19死亡者和107名非COVID-19对照者的大脑。对20例COVID-19尸检的16个区域进行RT-PCR筛查，在7个区域（320例样本的2.5%）发现了SARS-CoV-2 E基因病毒序列，集中在4/20例受试者（20%）中。对嗅球（OB）、杏仁核（AMY）和内嗅区进行E、N1、N2、RNA依赖性RNA聚合酶和S基因序列的额外筛查，在8/21例受试者（38%）的OB中检测到其中一种或多种。目前还不确定这些RNA序列是否代表活病毒。显著的组织病理学仅限于2/42例（4.8%），1例为大面积急性脑梗死，1例为出血性脑炎。OB和AMY的病例对照RNAseq分别发现了5000和700多个差异表达的基因，这些基因与RT-PCR结果无关;这些基因涉及免疫反应、神经元成分和嗅觉/味觉受体基因。嗅觉标志物蛋白-1减少表明与COVID-19相关的OB嗅粘膜传入损失。在COVID-19病例中，Iba-1免疫反应性小胶质细胞在小脑皮质和AMY中的面积分数减少，细胞因子阵列显示AMY普遍下调，血清中上调。虽然OB是SARS-CoV-2的主要脑门户，但COVID-19的脑变化更可能是由于血液传播的免疫介质和OB传入神经阻滞引起的跨突触基因表达变化。
Brains of 42 COVID-19 decedents and 107 non-COVID-19 controls were studied. RT-PCR screening of 16 regions from 20 COVID-19 autopsies found SARS-CoV-2 E gene viral sequences in 7 regions (2.5% of 320 samples), concentrated in 4/20 subjects (20%). Additional screening of olfactory bulb (OB), amygdala (AMY) and entorhinal area for E, N1, N2, RNA-dependent RNA polymerase, and S gene sequences detected one or more of these in OB in 8/21 subjects (38%). It is uncertain whether these RNA sequences represent viable virus. Significant histopathology was limited to 2/42 cases (4.8%), one with a large acute cerebral infarct and one with hemorrhagic encephalitis. Case-control RNAseq in OB and AMY found more than 5000 and 700 differentially expressed genes, respectively, unrelated to RT-PCR results; these involved immune response, neuronal constituents, and olfactory/taste receptor genes. Olfactory marker protein-1 reduction indicated COVID-19-related loss of OB olfactory mucosa afferents. Iba-1-immunoreactive microglia had reduced area fractions in cerebellar cortex and AMY, and cytokine arrays showed generalized downregulation in AMY and upregulation in blood serum in COVID-19 cases. Although OB is a major brain portal for SARS-CoV-2, COVID-19 brain changes are more likely due to blood-borne immune mediators and trans-synaptic gene expression changes arising from OB deafferentation.
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影响因子：
7.1
作者：
Bachstetter AD;Van Eldik LJ;Schmitt FA;Neltner JH;Ighodaro ET;Webster SJ;Patel E;Abner EL;Kryscio RJ;Nelson PT
通讯作者：
Nelson PT
影响因子：
3.5
作者：
Barra GB;Santa Rita TH;Mesquita PG;Jácomo RH;Nery LFA
通讯作者：
Nery LFA
影响因子：
12.7
作者：
Baba, Y;Ghetti, B;Wszolek, ZK
通讯作者：
Wszolek, ZK
影响因子：
2.9
作者：
Bhattacheryay, Suranjan
通讯作者：
Bhattacheryay, Suranjan
影响因子：
16.2
作者：
Allnutt, Mary Alice;Johnson, Kory;Jacobson, Steven
通讯作者：
Jacobson, Steven