Coinfection with SARS-CoV-2 and Influenza A Virus Increases Disease Severity and Impairs Neutralizing Antibody and CD4(+) T Cell Responses.
Coinfection with SARS-CoV-2 and Influenza A Virus Increases Disease Severity and Impairs Neutralizing Antibody and CD4(+) T Cell Responses.
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DOI：
10.1128/jvi.01873-21
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发表时间：
2022-03-23
影响因子：
5.4
通讯作者：
Choi YK
中科院分区：
文献类型：
--
作者：
Kim EH;Nguyen TQ;Casel MAB;Rollon R;Kim SM;Kim YI;Yu KM;Jang SG;Yang J;Poo H;Jung JU;Choi YK
鉴于当前 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) 的双重感染是公共卫生的一个主要问题。然而，SARS-CoV-2 和 IAV 混合感染时发生的免疫致病事件仍不清楚。在此，我们报告了 K18-hACE2 转基因小鼠模型中 SARS-CoV-2 和 IAV H1N1 共感染的致病和免疫学后果。与单一感染SARS-CoV-2或IAV相比，合并感染不仅延长了原发病毒感染期，而且增加了支气管肺泡灌洗液中的免疫细胞浸润和炎性细胞因子水平，导致严重肺炎和肺部损伤。此外，混合感染会导致外周血严重淋巴细胞减少，导致总 IgG、中和抗体滴度和针对每种病毒的 CD4+ T 细胞反应降低。这项研究揭示了 SARS-CoV-2 和 IAV 合并感染的免疫发病机制，可能指导开发治疗同时感染这些病毒的患者的有效治疗策略。重要性 流感病毒与 COVID-19 大流行的共同传播对公共健康构成潜在的严重威胁。最近，许多国家报告了越来越多的 SARS-CoV-2 和流感病毒双重感染。令人担忧的是，SARS-CoV-2 与其他病原体合并感染可能会恶化 COVID-19 的临床结果和严重程度并增加死亡率。在这里，我们使用 K18-hACE2 小鼠模型评估了 SARS-CoV-2 和 IAV 共感染。共感染小鼠的死亡率随着 IAV 排毒时间的延长而增加。此外，与单一感染条件相比，共感染小鼠表现出更高水平的细胞因子和趋化因子。有趣的是，我们的数据显示，与单一感染的小鼠相比，共感染的小鼠表现出明显更少的病毒特异性和中和抗体。总体而言，这项研究表明，共感染通过受损的中和抗体反应而加剧病毒病理学。
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. IMPORTANCE 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.
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