Understanding the pathological features of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in an animal model is crucial for the treatment of coronavirus disease 2019 (COVID-19). Here, we compared immunopathological changes in young and old rhesus macaques (RMs) before and after SARS-CoV-2 infection at the tissue level. Quantitative analysis of multiplex immunofluorescence staining images of formalin-fixed paraffin-embedded (FFPE) sections showed that SARS-CoV-2 infection specifically induced elevated levels of apoptosis, autophagy, and nuclear factor kappa-B (NF-κB) activation of angiotensin-converting enzyme 2 (ACE2)+ cells, and increased interferon α (IFN-α)- and interleukin 6 (IL-6)-secreting cells and C-X-C motif chemokine receptor 3 (CXCR3)+ cells in lung tissue of old RMs. This pathological pattern, which may be related to the age-related pro-inflammatory microenvironment in both lungs and spleens, was significantly correlated with the systemic accumulation of CXCR3+ cells in lungs, spleens, and peripheral blood. Furthermore, the ratio of CXCR3+ to T-box protein expression in T cell (T-bet)+ (CXCR3+/T-bet+ ratio) in CD8+ cells may be used as a predictor of severe COVID-19. These findings uncovered the impact of aging on the immunopathology of early SARS-CoV-2 infection and demonstrated the potential application of CXCR3+ cells in predicting severe COVID-19.

了解动物模型中严重急性呼吸系统综合症冠状病毒 2 (SARS-CoV-2) 感染的病理特征对于治疗 2019 冠状病毒病 (COVID-19) 至关重要。在这里，我们在组织水平上比较了 SARS-CoV-2 感染前后年轻和年老恒河猴 (RM) 的免疫病理学变化。对福尔马林固定石蜡包埋 (FFPE) 切片的多重免疫荧光染色图像进行定量分析表明，SARS-CoV-2 感染特异性地诱导细胞凋亡、自噬和核因子 kappa-B (NF-κB) 激活血管紧张素的水平升高。转化酶 2 (ACE2)+ 细胞，并增加老 RM 肺组织中的干扰素 α (IFN-α) 和白细胞介素 6 (IL-6) 分泌细胞和 CXC 基序趋化因子受体 3 (CXCR3)+ 细胞。这种病理模式，可能与肺和脾中年龄相关的促炎微环境有关，与 CXCR3+ 细胞在肺、脾和外周血中的全身积累显着相关。此外，CD8+ 细胞中 T 细胞中 CXCR3+ 与 T-box 蛋白表达的比率（T-bet）+（CXCR3+/T-bet+ 比率）可用作严重 COVID-19 的预测指标。这些发现揭示了衰老对早期 SARS-CoV-2 感染免疫病理学的影响，并证明了 CXCR3+ 细胞在预测严重 COVID-19 中的潜在应用。CD8+ 细胞中 T 细胞中 CXCR3+ 与 T-box 蛋白表达的比率（T-bet）+（CXCR3+/T-bet+ 比率）可用作严重 COVID-19 的预测指标。这些发现揭示了衰老对早期 SARS-CoV-2 感染免疫病理学的影响，并证明了 CXCR3+ 细胞在预测严重 COVID-19 中的潜在应用。CD8+ 细胞中 T 细胞中 CXCR3+ 与 T-box 蛋白表达的比率（T-bet）+（CXCR3+/T-bet+ 比率）可用作严重 COVID-19 的预测指标。这些发现揭示了衰老对早期 SARS-CoV-2 感染免疫病理学的影响，并证明了 CXCR3+ 细胞在预测严重 COVID-19 中的潜在应用。