Guan Sophie Y, Ogger Patricia P, Farias Ana, Garcia Martín Minerva, Nakawesi Joy, Bedard Olivia, Baker Candice, Rosenthal Nadia, Johansson Cecilia
Respiratory Infections Section, National Heart and Lung Institute, Imperial College, London, UK.
The Jackson Laboratory, Bar Harbor, Maine, USA.
Eur J Immunol. 2025 Aug;55(8):e70043. doi: 10.1002/eji.70043.
Many SARS-CoV-2 patients experience chronic pulmonary symptoms and long-term inflammation despite viral clearance. While these clinical manifestations have been linked to the dysregulation of the adaptive immune response, the underlying immunopathology remains poorly understood due to a lack of suitable animal models. To investigate long-term pulmonary consequences of SARS-CoV-2 infection, we used a genetic cross of 129 mice and C57BL/6 (B6)-K18-hACE2 transgene mice, a model previously shown to survive infection. 129xB6-K18-hACE2 mice or littermate controls were infected with a low dose (5 × 10 PFU) of ancestral SARS-CoV-2. Complete viral clearance and full recovery from weight loss occurred by day 8 post-infection. However, prolonged inflammation in the lung and airways persisted up to day 28 post-infection and was associated with the presence of CD4 and CD8 T cells, particularly CD8 effector T cells. This model may therefore prove valuable for further understanding of drivers of long-term lung inflammation and for testing therapeutic strategies and clinically relevant interventions that can target long-term pulmonary inflammation following SARS-CoV-2 infection.
许多新冠病毒患者在病毒清除后仍会出现慢性肺部症状和长期炎症。虽然这些临床表现与适应性免疫反应失调有关，但由于缺乏合适的动物模型，潜在的免疫病理学仍知之甚少。为了研究新冠病毒感染的长期肺部后果，我们使用了129小鼠和C57BL/6（B6）-K18-hACE2转基因小鼠的遗传杂交，这是一种先前已证明能在感染后存活的模型。129xB6-K18-hACE2小鼠或同窝对照小鼠感染低剂量（5×10 PFU）的原始新冠病毒。感染后第8天实现了病毒的完全清除和体重减轻的完全恢复。然而，肺部和气道的炎症持续延长至感染后第28天，并与CD4和CD8 T细胞尤其是CD8效应T细胞的存在有关。因此，该模型可能对进一步了解长期肺部炎症的驱动因素以及测试针对新冠病毒感染后长期肺部炎症的治疗策略和临床相关干预措施具有重要价值。
