Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Department of Pathology, University of Maryland School of Medicine, Baltimore.
JAMA Neurol. 2022 Jun 1;79(6):544-553. doi: 10.1001/jamaneurol.2022.0154.
Loss of smell is an early and common presentation of COVID-19 infection. Although it has been speculated that viral infection of olfactory neurons may be the culprit, it is unclear whether viral infection causes injuries in the olfactory bulb region.
To characterize the olfactory pathology associated with COVID-19 infection in a postmortem study.
DESIGN, SETTING, AND PARTICIPANTS: This multicenter postmortem cohort study was conducted from April 7, 2020, to September 11, 2021. Deceased patients with COVID-19 and control individuals were included in the cohort. One infant with congenital anomalies was excluded. Olfactory bulb and tract tissue was collected from deceased patients with COVID-19 and appropriate controls. Histopathology, electron microscopy, droplet digital polymerase chain reaction, and immunofluorescence/immunohistochemistry studies were performed. Data analysis was conducted from February 7 to October 19, 2021.
(1) Severity of degeneration, (2) losses of olfactory axons, and (3) severity of microvasculopathy in olfactory tissue.
Olfactory tissue from 23 deceased patients with COVID-19 (median [IQR] age, 62 [49-69] years; 14 men [60.9%]) and 14 control individuals (median [IQR] age, 53.5 [33.25-65] years; 7 men [50%]) was included in the analysis. The mean (SD) axon pathology score (range, 1-3) was 1.921 (0.569) in patients with COVID-19 and 1.198 (0.208) in controls (P < .001), whereas axon density was 2.973 (0.963) × 104/mm2 in patients with COVID-19 and 3.867 (0.670) × 104/mm2 in controls (P = .002). Concomitant endothelial injury of the microvasculature was also noted in olfactory tissue. The mean (SD) microvasculopathy score (range, 1-3) was 1.907 (0.490) in patients with COVID-19 and 1.405 (0.233) in control individuals (P < .001). Both the axon and microvascular pathology was worse in patients with COVID-19 with smell alterations than those with intact smell (mean [SD] axon pathology score, 2.260 [0.457] vs 1.63 [0.426]; P = .002; mean [SD] microvasculopathy score, 2.154 [0.528] vs 1.694 [0.329]; P = .02) but was not associated with clinical severity, timing of infection, or presence of virus.
This study found that COVID-19 infection is associated with axon injuries and microvasculopathy in olfactory tissue. The striking axonal pathology in some cases indicates that olfactory dysfunction in COVID-19 infection may be severe and permanent.
嗅觉丧失是 COVID-19 感染的早期和常见表现。尽管有人推测病毒感染嗅神经元可能是罪魁祸首，但尚不清楚病毒感染是否会导致嗅球区域的损伤。
在一项尸检研究中描述与 COVID-19 感染相关的嗅觉病理学。
设计、地点和参与者：这是一项多中心尸检队列研究，于 2020 年 4 月 7 日至 2021 年 9 月 11 日进行。队列纳入了 COVID-19 死亡患者和对照个体。排除了一名患有先天性异常的婴儿。从 COVID-19 死亡患者和适当的对照中收集嗅球和嗅束组织。进行了组织病理学、电子显微镜、液滴数字聚合酶链反应和免疫荧光/免疫组织化学研究。数据分析于 2021 年 2 月 7 日至 10 月 19 日进行。
（1）变性严重程度，（2）嗅轴突丢失，（3）嗅组织中小血管病变严重程度。
分析了 23 名 COVID-19 死亡患者（中位数[IQR]年龄，62 [49-69] 岁；14 名男性[60.9%]）和 14 名对照个体（中位数[IQR]年龄，53.5 [33.25-65] 岁；7 名男性[50%]）的嗅组织。COVID-19 患者的平均（SD）轴突病理评分（范围，1-3）为 1.921（0.569），对照组为 1.198（0.208）（P<.001），而 COVID-19 患者的轴突密度为 2.973（0.963）×104/mm2，对照组为 3.867（0.670）×104/mm2（P=.002）。在嗅组织中也观察到伴随的微血管内皮损伤。COVID-19 患者的平均（SD）微血管病变评分（范围，1-3）为 1.907（0.490），对照组为 1.405（0.233）（P<.001）。与嗅觉正常的 COVID-19 患者相比，嗅觉改变的 COVID-19 患者的轴突和微血管病变更严重（平均[SD]轴突病理评分，2.260[0.457]与 1.63[0.426]；P=.002；平均[SD]微血管病变评分，2.154[0.528]与 1.694[0.329]；P=.02），但与临床严重程度、感染时间或病毒存在无关。
本研究发现 COVID-19 感染与嗅组织中的轴突损伤和微血管病有关。在某些情况下，明显的轴突病理学表明 COVID-19 感染中的嗅觉功能障碍可能严重且永久性的。
