Center for Vaccines and Immunology, University of Georgiagrid.213876.9, Athens, GA, USA.
Department of Pathology, University of Georgiagrid.213876.9, Athens, GA, USA.
J Virol. 2022 Mar 9;96(5):e0179121. doi: 10.1128/JVI.01791-21. Epub 2021 Dec 22.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and seasonal influenza viruses are cocirculating in the human population. However, only a few cases of viral coinfection with these two viruses have been documented in humans with some people having severe disease and others mild disease. To examine this phenomenon, ferrets were coinfected with SARS-CoV-2 and human seasonal influenza A viruses (IAVs; H1N1 or H3N2) and were compared to animals that received each virus alone. Ferrets were either immunologically naive to both viruses or vaccinated with the 2019 to 2020 split-inactivated influenza virus vaccine. Coinfected naive ferrets lost significantly more body weight than ferrets infected with each virus alone and had more severe inflammation in both the nose and lungs compared to that of ferrets that were single infected with each virus. Coinfected, naive animals had predominantly higher IAV titers than SARS-CoV-2 titers, and IAVs were efficiently transmitted by direct contact to the cohoused ferrets. Comparatively, SARS-CoV-2 failed to transmit to the ferrets that cohoused with coinfected ferrets by direct contact. Moreover, vaccination significantly reduced IAV titers and shortened the viral shedding but did not completely block direct contact transmission of the influenza virus. Notably, vaccination significantly ameliorated influenza-associated disease by protecting vaccinated animals from severe morbidity after IAV single infection or IAV and SARS-CoV-2 coinfection, suggesting that seasonal influenza virus vaccination is pivotal to prevent severe disease induced by IAV and SARS-CoV-2 coinfection during the COVID-19 pandemic. Influenza A viruses cause severe morbidity and mortality during each influenza virus season. The emergence of SARS-CoV-2 infection in the human population offers the opportunity to potential coinfections of both viruses. The development of useful animal models to assess the pathogenesis, transmission, and viral evolution of these viruses as they coinfect a host is of critical importance for the development of vaccines and therapeutics. The ability to prevent the most severe effects of viral coinfections can be studied using effect coinfection ferret models described in this report.
严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 和季节性流感病毒在人群中共同传播。然而，仅有少数几例这两种病毒的病毒合并感染病例在人群中被记录下来，一些人病情严重，而另一些人病情较轻。为了研究这一现象，我们将 SARS-CoV-2 与人类季节性流感 A 病毒（IAV；H1N1 或 H3N2）合并感染雪貂，并将其与单独感染每种病毒的动物进行比较。雪貂对这两种病毒均无免疫或接种了 2019 年至 2020 年裂解灭活流感疫苗。合并感染的雪貂体重下降明显高于单独感染每种病毒的雪貂，并且与单独感染每种病毒的雪貂相比，鼻腔和肺部的炎症更严重。合并感染、无免疫的动物的 IAV 滴度明显高于 SARS-CoV-2 滴度，并且 IAV 通过直接接触有效地传播给同笼饲养的雪貂。相比之下，SARS-CoV-2 未能通过直接接触传播给与合并感染雪貂同笼饲养的雪貂。此外，疫苗接种显著降低了 IAV 滴度并缩短了病毒脱落时间，但不能完全阻断流感病毒的直接接触传播。值得注意的是，疫苗接种通过保护接种动物在 IAV 单独感染或 IAV 和 SARS-CoV-2 合并感染后免受严重发病，显著改善了流感相关疾病，表明季节性流感病毒疫苗接种对于预防 COVID-19 大流行期间由 IAV 和 SARS-CoV-2 合并感染引起的严重疾病至关重要。IAV 在每个流感病毒季节都会导致严重的发病率和死亡率。SARS-CoV-2 在人群中的出现为这两种病毒的潜在合并感染提供了机会。开发有用的动物模型来评估这些病毒在宿主中合并感染的发病机制、传播和病毒进化对于疫苗和治疗方法的开发至关重要。本报告中描述的效应合并感染雪貂模型可用于研究预防病毒合并感染的最严重影响。
