Importance 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. Objective 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. Main Outcomes and Measures (1) Severity of degeneration, (2) losses of olfactory axons, and (3) severity of microvasculopathy in olfactory tissue. Results 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. Conclusions and Relevance 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.

中文翻译：

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COVID-19 患者嗅觉组织退化和微血管病变的死后评估。

重要性 嗅觉丧失是 COVID-19 感染的早期常见表现。虽然有人推测嗅觉神经元的病毒感染可能是罪魁祸首，但尚不清楚病毒感染是否会导致嗅球区域的损伤。目的 在尸检研究中表征与 COVID-19 感染相关的嗅觉病理学。设计、设置和参与者 这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。已故的 COVID-19 患者和对照个体被纳入该队列。一名患有先天性异常的婴儿被排除在外。嗅球和嗅道组织是从已故的 COVID-19 患者和适当的对照中收集的。组织病理学、电子显微镜、液滴数字聚合酶链反应、并进行了免疫荧光/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。主要结果和测量结果（1）变性的严重程度，（2）嗅觉轴突的损失，以及（3）嗅觉组织微血管病变的严重程度。结果 23 名已故 COVID-19 患者（中位 [IQR] 年龄，62 [49-69] 岁；14 名男性 [60.9%]）和 14 名对照个体（中位 [IQR] 年龄，53.5 [33.25-65] 岁）的嗅觉组织年；7 名男性 [50%]) 被纳入分析。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），而轴突密度为 2.973 (0.963) × 104 /mm2 在 COVID-19 患者中，在对照组中为 3.867 (0.670) × 104/mm2 (P = .002)。在嗅觉组织中也注意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）。具有气味改变的 COVID-19 患者的轴突和微血管病理学比具有完整气味的患者更差（平均 [SD] 轴突病理学评分，2.260 [0.457] vs 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、感染时间或病毒的存在无关。结论和相关性 本研究发现，COVID-19 感染与嗅觉组织的轴突损伤和微血管病变有关。