College of Medicine and Medical Research Institute, Chungbuk National Universitygrid.254229.a, Cheongju, Republic of Korea.
Vinmec Research Institute of Stem Cell and Gene Technology, Vinmec Healthcare System, Hanoi, Vietnam.
J Virol. 2022 Mar 23;96(6):e0187321. doi: 10.1128/jvi.01873-21. Epub 2022 Feb 2.
Given the current coronavirus disease 2019 (COVID-19) pandemic, coinfection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza A virus (IAV) is a major concern for public health. However, the immunopathogenic events occurring with coinfections of SARS-CoV-2 and IAV remain unclear. Here, we report the pathogenic and immunological consequences of SARS-CoV-2 and IAV H1N1 coinfection in the K18-hACE2 transgenic mouse model. Compared with a single infection with SARS-CoV-2 or IAV, coinfections not only prolonged the primary virus infection period but also increased immune cell infiltration and inflammatory cytokine levels in bronchoalveolar lavage fluid leading to severe pneumonia and lung damage. Moreover, coinfections caused severe lymphopenia in peripheral blood, resulting in reduced total IgG, neutralizing antibody titers, and CD4 T cell responses against each virus. This study sheds light on the immunopathogenesis of SARS-CoV-2 and IAV coinfection, which may guide the development of effective therapeutic strategies for the treatment of patients coinfected with these viruses. The cocirculation of influenza virus merging with the COVID-19 pandemic raises a potentially severe threat to public health. Recently, increasing numbers of SARS-CoV-2 and influenza virus coinfection have been reported from many countries. It is a worrisome issue that SARS-CoV-2 coinfection with other pathogens may worsen the clinical outcome and severity of COVID-19 and increase fatality. Here, we evaluated SARS-CoV-2 and IAV coinfection using the K18-hACE2 mouse model. Coinfected mice exhibited increased mortality with prolonged IAV shedding. Furthermore, coinfected mice showed a higher level of cytokines and chemokines than a single infection condition. Interestingly, our data show that coinfected mice showed significantly fewer virus-specific and neutralizing antibodies than the mice with a single infection. Overall, this study suggests that coinfection aggravates viral pathology by impaired neutralizing antibody response.
鉴于当前的 2019 年冠状病毒病（COVID-19）大流行，严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）和甲型流感病毒（IAV）的合并感染是公共卫生的主要关注点。然而，SARS-CoV-2 和 IAV 合并感染时发生的免疫发病事件尚不清楚。在这里，我们报告了 SARS-CoV-2 和 IAV H1N1 合并感染在 K18-hACE2 转基因小鼠模型中的发病机制和免疫学后果。与单独感染 SARS-CoV-2 或 IAV 相比，合并感染不仅延长了原发性病毒感染期，而且增加了支气管肺泡灌洗液中的免疫细胞浸润和炎症细胞因子水平，导致严重肺炎和肺损伤。此外，合并感染导致外周血严重的淋巴细胞减少，导致每种病毒的总 IgG、中和抗体滴度和 CD4 T 细胞反应降低。这项研究阐明了 SARS-CoV-2 和 IAV 合并感染的免疫发病机制，这可能为治疗这些病毒合并感染患者的有效治疗策略的制定提供指导。 流感病毒与 COVID-19 大流行的同时流行对公共卫生构成了潜在的严重威胁。最近，越来越多的国家报告了 SARS-CoV-2 和流感病毒的合并感染。令人担忧的是，SARS-CoV-2 与其他病原体合并感染可能会使 COVID-19 的临床结果和严重程度恶化，并增加死亡率。在这里，我们使用 K18-hACE2 小鼠模型评估了 SARS-CoV-2 和 IAV 的合并感染。合并感染的小鼠表现出更高的死亡率和更长的 IAV 脱落。此外，与单一感染相比，合并感染的小鼠表现出更高水平的细胞因子和趋化因子。有趣的是，我们的数据表明，与单一感染的小鼠相比，合并感染的小鼠产生的病毒特异性和中和抗体明显减少。总体而言，这项研究表明，合并感染通过抑制中和抗体反应加重病毒病理学。
