Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Influenza Viral Infection is a High-Risk Factor for Developing Coronavirus Disease 2019 (COVID-19)

Version 1 : Received: 19 March 2020 / Approved: 20 March 2020 / Online: 20 March 2020 (06:56:25 CET)
Version 2 : Received: 16 October 2020 / Approved: 16 October 2020 / Online: 16 October 2020 (11:49:13 CEST)

How to cite: Zhang, L.; Zhang, Y. Influenza Viral Infection is a High-Risk Factor for Developing Coronavirus Disease 2019 (COVID-19). Preprints 2020, 2020030307. Zhang, L.; Zhang, Y. Influenza Viral Infection is a High-Risk Factor for Developing Coronavirus Disease 2019 (COVID-19). Preprints 2020, 2020030307.


Coronavirus disease 2019 (COVID-19) is caused by infection with the 2019 novel coronavirus 2 (2019-nCoV, now referred to as SARS-CoV-2). COVID-19 has become a global pandemic since its outbreak at the end of Dec 2019. COVID-19 could lead to severe acute respiratory disease, especially to those who have reduced immunity. Binding of the viral Spike protein (S) to its receptor ACE2 (Angiotensin Converting Enzyme 2) on the surface of target cells has been proven to be key for virus entry and infection. Although ACE2 expression in the respiratory system is necessary for pneumonia infection by SARS-CoV-2, the regulation of ACE2 gene expression remains poorly investigated, especially for patients that are in pre-pathological conditions. Here, by analyzing The Gene Expression Omnibus (GEO) database, we investigated the expression regulation of ACE2 in various kinds of primary epithelial cells from the respiratory system after influenza A or respiratory Syncytial Virus (RSV) infection. Our analyses reveal that infection of influenza A, RSV or influenza vaccines greatly increased ACE2 expression, suggesting that influenza viral infection could represent a high risk factor for developing COVID-19. We also found that the regulatory effect of influenza A virus on ACE2 expression is associated with activation of the interferon beta-induced pathway and viral RNA-activated host response. Together, our data provide a theoretical framework for clinical classification for SARS-CoV-2 infection susceptibility and could be used for future prevention and therapy treatment for COVID-19.


COVID-19; influenza; SARS-CoV-2; ACE2; risk factor


Biology and Life Sciences, Cell and Developmental Biology

Comments (0)

Comment 1
Received: 1 May 2020
The commenter has declared there is no conflict of interests.
Comment: In the 1950's a Polio vaccine was contaminated with SV40. The vaccine was a live virus using Vero cells. After some investigation I've found certain influenza vaccines use animal cells. Some use MDKC cells. Canine and bovine(serum) coronavirus are in the same betacoronavirus group. However, these vaccines are supposed to be inactive. But the live influenza vaccine also uses Vero cells. It's been confirm that green African monkeys were infected with Sars-cov2 in a zoo too. There are certain countries who have very low figures, who don't offer the live vaccine or flu vaccine at all. The recent development of kawasaki syndrome is increasing the possibility this is man made, either deliberate or accidental. Italy and the UK have confirmed cases of kawasaki disease, yet Switzerland are saying children are not infectious and can visit grandparents. I can tell you Switzerland do not vaccinate all children like the UK do. Finally, I'm wondering if the adjuvant vaccine in old people could be boosting cytokine storms causing fatalities.

Children are infectious for three days after live vaccination and some children have the flu vaccine twice. I propose over the festive period especially, children infected the older generation. Most countries in Europe are starting to level off. The change seemed to come 14 days after flu vaccination ended. The US seem to be in a lot of trouble. They use the the live vaccine in adults too.
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