Coinfection with influenza A virus enhances SARS-CoV-2 infectivity

Bai, Lei; Zhao, Yongliang; Dong, Jiazhen; Liang, Simeng; Guo, Ming; Liu, Xinjin; Wang, Xin; Huang, Zhixiang; Sun, Xiaoyi; Zhang, Zhen; Dong, Lianghui; Liu, Qianyun; Zheng, Yuanrun; Niu, Danping; Xiang, Min; Song, Kun; Ye, Jiajie; Zheng, Wenchao; Tang, Zhidong; Tang, Mingliang; Zhou, Yu; Shen, Chao; Dai, Ming; Zhou, Li; Chen, Yu; Yan, Huan; Lan, Ke; Xu, Ke

doi:10.1038/s41422-021-00473-1

Cited by 176 publications

(162 citation statements)

References 33 publications

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“…Due to the seasonality of influenza outbreaks and the continuous prevalence of COVID-19, influenza could circulate in parallel with COVID-19, which largely increases the potential risk of co-infection. Though little is known about the epidemiology and clinical outcomes of co-infection, extant literature has found that the co-infection with influenza A virus enhances the infectivity of COVID-19 in a broad range of cell types [3], whereas co-infected patients seem to present similar clinical symptoms and radiological images compared with patients infected with COVID-19 alone [4,5]. In the context of the COVID-19 pandemic, the dual infection of influenza and COVID-19 could bring extra burden to health care services by utilizing limited medical resources, increasing the difficulty of treatment and the uncertainty of prognosis.…”

Section: Introductionmentioning

confidence: 99%

The Association between Influenza Vaccination and COVID-19 and Its Outcomes: A Systematic Review and Meta-Analysis of Observational Studies

Wang

Liu

2021

Vaccines

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Influenza could circulate in parallel with COVID-19. In the context of COVID-19, some studies observed inverse associations between influenza vaccination and SARS-CoV-2 infection and clinical outcomes, while others did not. We conducted a meta-analysis to assess the association between influenza vaccination and SARS-CoV-2 infection and clinical outcomes, aiming to provide evidence for COVID-19 prevention and vaccination promotion. We searched four databases from inception to 10 March, 2021. Random effects and fixed effects models were used to pool odds ratios (ORs) and adjusted estimates with 95% confidence intervals (CIs). We used funnel plots to evaluate the publication bias, I2 statistics to evaluate the heterogeneity, and conducted subgroup analyses. Sixteen observational studies involving 290,327 participants were included. Influenza vaccination was associated with a lower risk of SARS-CoV-2 infection (pooled adjusted OR: 0.86, 95%CI: 0.81–0.91), while not significantly associated with adverse outcomes (intensive care: adjusted OR 0.63, 95%CI: 0.22–1.81; hospitalization: adjusted OR 0.74, 95%CI: 0.51–1.06; mortality: adjusted OR 0.89, 95%CI: 0.73–1.09). Our findings suggest that influenza vaccination is associated with a lower risk of SARS-CoV-2 infection. It is crucial for policy makers to implement strategies on influenza vaccination, for it may also have benefits for COVID-19 prevention.

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Section: Introductionmentioning

confidence: 99%

The Association between Influenza Vaccination and COVID-19 and Its Outcomes: A Systematic Review and Meta-Analysis of Observational Studies

Wang

Liu

2021

Vaccines

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“…In previous studies we and others have shown that IAV pre-infection of hACE2 mice results in more severe SARS-CoV-2 associated pulmonary changes and higher amounts of infectious virus at or 7 days post SARS-CoV-2 infection (Bai et al, 2021;Clark et al, 2021). Interestingly though, viral loads in the brain were not found to be increased (Bai et al, 2021), although we observed higher frequency and more widespread brain infection after the lower SARS-CoV-2 dose in animals that were infected with IAV. Also, the inflammatory response was slightly more intense in these animals.…”

Section: Resultsmentioning

confidence: 73%

“…Also, the inflammatory response was slightly more intense in these animals. It is currently unclear which direct impact IAV infection has for the subsequent SARS-CoV-2 challenge, but more efficient virus entry could be an option, since IAV infection was shown to upregulate ACE2 expression in vitro (Bai et al, 2021).…”

Section: Resultsmentioning

confidence: 99%

Neuroinvasion and neurotropism by SARS-CoV-2 variants in the K18-hACE2 mouse

Seehusen

Clark

Sharma

et al. 2021

Preprint

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Coronavirus disease 2019 (COVID-19) is a primarily respiratory disease with variable clinical courses for which animal models are needed to gather insights into the pathogenesis of its causative virus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), in human patients. SARS-CoV-2 not only affects the respiratory tract but also the central nervous system (CNS), leading to neurological symptoms such as loss of smell and taste, headache, fatigue or severe complications like cerebrovascular diseases. Transgenic mice expressing human angiotensin-converting enzyme 2 (hACE2) under the cytokeratin 18 promoter (K18-hACE2) represent a well-known model of SARS-CoV-2 infection. In the present study, it served to investigate the spatiotemporal distribution and pathomorphological features in the CNS following intranasal infection with relatively low SARS-CoV-2 doses and after prior influenza A virus infection. In K18-hACE2 mice, SARS-CoV-2 was found to frequently spread to and within the CNS during the later phase (day 7) of infection. Infection was restricted to neurons and appeared to first affect the olfactory bulb and spread from there mainly in basally orientated regions in the brain and into the spinal cord, in a dose dependent manner and independent of ACE2 expression. Neuronal infection was not associated with cell death, axonal damage or demyelination. However, microglial activation, microgliosis and a mild macrophage and T cell dominated inflammatory response was consistently observed. This was accompanied by apoptotic death of endothelial, microglial and immune cells, without evidence of viral infection of glial cells, endothelial cells and leukocytes. Taken together, microgliosis and immune cell apoptosis indicate a potential important role of microglial cells for the pathogenesis and viral effect in COVID-19 and possible impairment of neurological functions, especially in long COVID. These data may also be informative for the selection of therapeutic candidates, and broadly support investigation of agents with adequate penetration into relevant regions of the CNS.

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“…In a recent report in Cell Research, Bai et al 2 found that cells, whether susceptible or not to SARS-CoV-2, became significantly more sensitive to SARS-CoV-2 after infection with IAV (A/WSN/ 1933(H1N1)). In addition, coinfection of IAV and SARS-CoV-2 in mice resulted in increased viral load of SARS-CoV-2 and more severe lung damage.…”

mentioning

confidence: 99%

“…Bai et al 2 also found that other respiratory viruses, such as human respiratory syncytial virus (HRSV), human parainfluenzavirus (HPIV), and human rhinovirus 3 (HRV3), did not appear to promote SARS-CoV-2 infection, thus providing a tentative diagnostic basis for pathogen co-monitoring, alongside SARS-CoV-2, in the clinic. This study also reported that the auxo-action of IAV to SARS-CoV-2 infection may come from the elevated ACE2 expression induced by IAV (Fig.…”

mentioning

confidence: 99%