By Martin Michaelis and Mark Wass. This blog discusses the findings of a study that we performed together with colleagues from the Goethe-University in Frankfurt am Main, Germany, the Dr Petra Joh Research Institute in Frankfurt am Main, Germany, and the Hannover Medical School, Germany. In particular, it was co-led by Professor Jindrich Cinatl (Institute of Medical Virology, Goethe-University, and Dr Petra Joh Research Institute). The study findings indicate that only SARS-CoV-2 Omicron but not Delta infection protects cells from influenza viruses, i.e. the viruses that cause the flu.
In addition to reducing the spread of SARS-CoV-2, the coronavirus that causes COVID-19, the pandemic prevention measures also suppressed many other pathogens (see e.g. [1]). Since these measures have been removed, we have experienced the return of many respiratory illnesses, including the flu. However, it is still not clear how different respiratory viruses interact, i.e. whether the combined impact may result in more serious disease or whether different viruses may compete and interfere with each other.
Previous research by us and others [2-7] had already shown that the Omicron and Delta variants of SARS-CoV-2 differ in their ability to antagonise the so-called interferon response, an innate immune mechanism that is a first-line defence of all body cells against virus infections. The Delta variant was much more effective in suppressing the host cell interferon response than the Omicron variant, which may explain why Delta causes more serious disease than Omicron.
In the current study, we investigated whether the enhanced interferon response in Omicron-infected cells may protect them from infection by additional viruses [8]. Indeed, influenza viruses (including highly pathogenic H5N1 bird flu viruses) were only able to infect Delta-infected cell cultures, in which the interferon response was suppressed, but not Omicron-infected cells. These findings suggest that Omicron but not Delta can suppress influenza virus infection.
We also performed an analysis of influenza virus spread in the autumn of 2021 in England. The initial Delta peak coincided with an increase in influenza cases. In agreement with the cell culture data, influenza virus transmission then rapidly declined, when Omicron replaced Delta later in the year. Notably, these findings agree with other epidemiological observations suggesting that Omicron interferes with influenza transmission [9-13].
Taken together, our findings suggest that the interferon response induced by Omicron but not by Delta interferes with influenza A virus infection and replication in tissue culture models. Based on these findings and some observational epidemiological data, acute Omicron infection may provide some level of clinical protection from influenza virus infection. However, this is probably a very short-term effect, and Omicron infections come with their own risks. Hence, nobody should try to become deliberately infected with Omicron.
References
1) Hayes LJ, Uri H, Bojkova D, Cinatl J Jr, Wass MN, Michaelis M. Impact of the COVID-19 pandemic on the circulation of other pathogens in England. J Med Virol. 2023 Jan;95(1):e28401. doi: 10.1002/jmv.28401.
2) Bojkova D, Widera M, Ciesek S, Wass MN, Michaelis M, Cinatl J Jr. Reduced interferon antagonism but similar drug sensitivity in Omicron variant compared to Delta variant of SARS-CoV-2 isolates. Cell Res. 2022 Mar;32(3):319-321. doi: 10.1038/s41422-022-00619-9.
3) Bojkova D, Rothenburger T, Ciesek S, Wass MN, Michaelis M, Cinatl J Jr. SARS-CoV-2 Omicron variant virus isolates are highly sensitive to interferon treatment. Cell Discov. 2022 May 10;8(1):42. doi: 10.1038/s41421-022-00408-z.
4) Bojkova D, Stack R, Rothenburger T, Kandler JD, Ciesek S, Wass MN, Michaelis M, Cinatl J Jr. Synergism of interferon-beta with antiviral drugs against SARS-CoV-2 variants. J Infect. 2022 Nov;85(5):573-607. doi: 10.1016/j.jinf.2022.07.023.
5) Singh J, Anantharaj A, Panwar A, Rani C, Bhardwaj M, Kumar P, Chattopadhyay P, Devi P, Maurya R, Mishra P, Pandey AK, Pandey R, Medigeshi GR. BA.1, BA.2 and BA.2.75 variants show comparable replication kinetics, reduced impact on epithelial barrier and elicit cross-neutralizing antibodies. PLoS Pathog. 2023 Feb 24;19(2):e1011196. doi: 10.1371/journal.ppat.1011196.
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7) Alfi O, Hamdan M, Wald O, Yakirevitch A, Wandel O, Oiknine-Djian E, Gvili B, Knoller H, Rozendorn N, Golan Berman H, Adar S, Vorontsov O, Mandelboim M, Zakay-Rones Z, Oberbaum M, Panet A, Wolf DG. SARS-CoV-2 Omicron Induces Enhanced Mucosal Interferon Response Compared to other Variants of Concern, Associated with Restricted Replication in Human Lung Tissues. Viruses. 2022 Jul 21;14(7):1583. doi: 10.3390/v14071583.
8) Bojkova D, Bechtel M, Rothenburger T, Kandler JD, Hayes L, Olmer R, Martin U, Jonigk D, Ciesek S, Wass MN, Michaelis M, Cinatl J Jr. Omicron-induced interferon signaling prevents influenza A H1N1 and H5N1 virus infection. J Med Virol. 2023 Mar;95(3):e28686. doi: 10.1002/jmv.28686.
9) Eldesouki RE, Uhteg K, Mostafa HH. The circulation of Non-SARS-CoV-2 respiratory viruses and coinfections with SARS-CoV-2 during the surge of the Omicron variant. J Clin Virol. 2022 Aug;153:105215. doi: 10.1016/j.jcv.2022.105215.
10) Sominina A, Danilenko D, Komissarov A, Karpova L, Pisareva M, Fadeev A, Konovalova N, Eropkin M, Stolyarov K, Shtro A, Burtseva E, Lioznov D. Resurgence of Influenza Circulation in the Russian Federation during the Delta and Omicron COVID-19 Era. Viruses. 2022 Aug 29;14(9):1909. doi: 10.3390/v14091909.
11) Fratty IS, Reznik-Balter S, Nemet I, Atari N, Kliker L, Sherbany H, Keller N, Stein M, Mendelson E, Mandelboim M. Outbreak of Influenza and Other Respiratory Viruses in Hospitalized Patients Alongside the SARS-CoV-2 Pandemic. Front Microbiol. 2022 Jun 13;13:902476. doi: 10.3389/fmicb.2022.902476.
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