Hubei AIDS Clinical Training Center, Department of Infectious Disease, Zhongnan Hospital of Wuhan University, Wuhan, PR China.
Hubei AIDS Clinical Training Center, Department of Infectious Disease, Zhongnan Hospital of Wuhan University, Wuhan, PR China; Lichuan People's Hospital, Lichuan, Hubei, PR China.
Pathol Res Pract. 2021 Nov;227:153610. doi: 10.1016/j.prp.2021.153610. Epub 2021 Sep 8.
The coronavirus disease 2019(COVID-19) is recognized as systemic inflammatory response syndrome. It was demonstrated that a rapid increase of cytokines in the serum of COVID-19 patients is associated with the severity of disease. However, the mechanisms of the cytokine release are not clear. By using immunofluorescence staining we found that the number of CD11b positive immune cells including macrophages in the spleens of died COVID-19 patients, was significantly higher than that of the control patients. The incidence of apoptosis as measured by two apoptotic markers, TUNEL and cleaved caspase-3, in COVID-19 patients' spleen cells is higher than that in control patients. By double immunostaining CD11b or CD68 and SARS-CoV-2 spike protein, it was found that up to 67% of these immune cells were positive for spike protein, suggesting that viral infection might be associated with apoptosis in these cells. Besides, we also stained the autophagy-related molecules (p-Akt、p62 and BCL-2) in spleen tissues, the results showed that the number of positive cells was significantly higher in COVID-19 group. And compared with non-COVID-19 patients, autophagy may be inhibited in COVID-19 patients. Our research suggest that SARS-CoV-2 may result in a higher rate of apoptosis and a lower rate of autophagy of immune cells in the spleen of COVID-19 patients. These discoveries may increase our understanding of the pathogenesis of COVID-19.
新型冠状病毒肺炎（COVID-19）被认为是一种全身性炎症反应综合征。有研究表明，COVID-19 患者血清中细胞因子的快速增加与疾病的严重程度有关。然而，细胞因子释放的机制尚不清楚。通过免疫荧光染色，我们发现死亡 COVID-19 患者脾脏中包括巨噬细胞在内的 CD11b 阳性免疫细胞数量明显高于对照组。COVID-19 患者脾脏细胞中凋亡的发生率（通过两个凋亡标志物 TUNEL 和 cleaved caspase-3 测量）高于对照组。通过双重免疫染色 CD11b 或 CD68 和 SARS-CoV-2 刺突蛋白，发现高达 67%的这些免疫细胞对刺突蛋白呈阳性，表明病毒感染可能与这些细胞的凋亡有关。此外，我们还对脾脏组织中的自噬相关分子（p-Akt、p62 和 BCL-2）进行了染色，结果表明 COVID-19 组阳性细胞数量明显更高。与非 COVID-19 患者相比，COVID-19 患者的自噬可能受到抑制。我们的研究表明，SARS-CoV-2 可能导致 COVID-19 患者脾脏中免疫细胞的凋亡率升高和自噬率降低。这些发现可能有助于我们更好地理解 COVID-19 的发病机制。
