DataSheet_1_Severe acute respiratory syndrome coronavirus 2 pathology and cell tropism in tongue tissues of COVID-19 autopsies.docx

Since 2019, Coronavirus Disease 2019(COVID-19) has affected millions of people worldwide. Except for acute respiratory distress syndrome, dysgeusis is also a common symptom of COVID-19 that burdens patients for weeks or permanently. However, the mechanisms underlying taste dysfunctions remain unclear. Here, we performed complete autopsies of five patients who died of COVID-19. Integrated tongue samples, including numerous taste buds, salivary glands, vessels, and nerves were collected to map the pathology, distribution, cell tropism, and receptor distribution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the tongue. Our results revealed that all patients had moderate lymphocyte infiltration around the salivary glands and in the lamina propria adjacent to the mucosa, and pyknosis in the epithelia of taste buds and salivary glands. This may be because the serous acini, salivary gland ducts, and taste buds are the primary sites of SARS-CoV-2 infection. Multicolor immunofluorescence showed that SARS-CoV-2 readily infects Keratin (KRT)7+ taste receptor cells in taste buds, secretory cells in serous acini, and inner epithelial cells in the ducts. The major receptors, angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine subtype 2 (TMPRSS2), were both abundantly expressed in these cells. Viral antigens and receptor were both rarely detected in vessels and nerves. This indicates that SARS-CoV-2 infection triggers pathological injury in the tongue, and that dysgeusis may be directly related to viral infection and cellular damage.

自2019年起，新型冠状病毒肺炎（COVID-19）已在全球波及数百万人。除急性呼吸窘迫综合征外，味觉障碍（dysgeusis）也是COVID-19的常见症状之一，会使患者承受数周乃至永久性的病痛负担。然而，味觉功能障碍背后的发病机制仍不明确。本研究对5名死于COVID-19的患者进行了完整尸检，收集了包含大量味蕾、唾液腺、血管及神经的完整舌组织样本，以解析严重急性呼吸综合征冠状病毒2（SARS-CoV-2）在舌部的病理特征、分布规律、细胞嗜性与受体分布情况。研究结果显示，所有患者的唾液腺周围及黏膜邻近固有层均出现中度淋巴细胞浸润，且味蕾与唾液腺上皮细胞存在核固缩现象。这可能是因为浆液性腺泡、唾液腺导管及味蕾是SARS-CoV-2感染的主要靶点。多色免疫荧光实验结果表明，SARS-CoV-2易感染味蕾中的角蛋白7（KRT7）阳性味觉受体细胞、浆液性腺泡中的分泌细胞以及导管内上皮细胞。主要受体血管紧张素转换酶2（ACE2）与跨膜丝氨酸蛋白酶2（TMPRSS2）在上述细胞中均呈高表达。在血管与神经组织中则几乎未检测到病毒抗原与相关受体。上述结果表明，SARS-CoV-2感染可引发舌部病理损伤，而味觉障碍可能与病毒感染及细胞损伤直接相关。