Agrippa: end of pandemic and threat of a « double epidemic

From the end of the summer of 2020, the media of different countries relayed the fear of a « double epidemic » coronavirus and influenza, experts insisting on the importance of vaccination against influenza⁽¹⁾. Indeed, the New York Times reported that the Centers for Disease Control and Prevention (the U.S. federal public health agency) had ordered an additional 9.3 million doses to the 500,000 annual doses of flu vaccine in 2020⁽²⁾. If the widespread concern of a double epidemic, bearing the neologism of « twindemic », has faded with the total absence of influenza during the COVID-19 pandemic (not only in Belgium and Europe, but all over the world⁽³⁾, the alarm bell has been rung again at the beginning of the year 2022. Indeed, Reuters news agency announced the return of the flu that could threaten the European Union according to the experts of the European Centre for Disease Prevention and Control (ECDC), leading to a prolonged epidemic with SARS-CoV‑2, which would result, as one could guess, in a dangerous pressure on our health care system⁽⁴⁾. With 650,000 annual deaths attributed to influenza in the world (including 72,000 in Europe)⁽⁵⁾, the synergistic effects with the coronavirus epidemic to be feared would be of two kinds:

1. Higher mortality related to coronavirus + influenza co-infection, as well as to the virulent nature of the influenza strain (H3 of Influenza A)^{(6) (7)}
2. A shift in the seasonal influenza season leading to an unusual extension of influenza virus circulation beyond the spring and a lengthening of respiratory epidemics⁽⁸⁾

The statement of the fear of a « twindemic » is thus accompanied by a call for vaccination as well as by the implicit maintenance of sanitary measures⁽⁹⁾. It should be remembered that the effectiveness of influenza vaccines, estimated at around 30–60% depending on the year⁽¹⁰⁾, is mainly based on the ability to predict the viral strain that will arrive on our territory, deduced from observations made in other countries. In fact, it would be very difficult to develop these vaccines at this time because influenza was absent during the pandemic. Despite this, this would not prevent health authorities from inviting the population to get vaccinated against the flu, while respecting the sanitary measures for a stronger protection.

But what about the science behind the apprehension of a double epidemic?

As is often the case, there are elements of truth in the statements from which apocalyptic predictions are then extrapolated (Neil Ferguson, epidemiologist at theImperial College in England, is a specialist in this sinister field and is responsible, through his modelling, for lockdown of the current pandemic⁽¹¹⁾. However, it should be granted that indeed it is quite possible to simultaneously contract COVID-19 and influenza⁽¹²⁾, just as it is possible to be co-infected with SARS-CoV‑2 and another respiratory virus (clinical cases in early 2020 have been documented on these multiple infections)⁽¹³⁾. However, these data must be put into context by taking several factors into account:

• The epidemiology of viral co-infections (of respiratory diseases) is an understudied area⁽¹⁴⁾
• The available data do not allow to conclude on the dangerousness of the diseases caused by these multiple infections, several studies not observing a difference in mortality and/or morbidity between these last ones and the simple infections⁽¹⁵⁾
• The phenomenon of « viral interference » could have the opposite effect: one virus could keep out another

The concept of viral interference is that viruses causing similar symptoms can compete with each other, resulting in the exclusion of one or more viruses by a dominant virus. In biology, this type of phenomenon has been well described and theorized in the concept of the « ecological niche ». According to the latter, living organisms occupy their own ecological niche (food sources, predators, reproduction sites, etc.). However, during a change of environment, organisms may compete with each other if their habitats have been disrupted. For example, if a species finds itself in a new territory, it may find itself in conflict with the organism that occupies the same ecological niche, leading to a separation of the invader or the native. This is particularly true of invasive species in general (often observed in insects) that colonize entire territories. Another well known example is the American grey squirrel which was introduced in England in the 19th century and colonized the country, pushing the red squirrel to near extinction⁽¹⁶⁾.

The arrival of the COVID-19 epidemic disrupted the circulation of several respiratory viruses, often attributed to sanitary measures that would have influenced/separated the circulation of other viruses⁽¹⁷⁾, but also to the viral interference phenomenon ⁽¹⁸⁾. The viral interference has been described in some publications with frequently the rhinovirus (one of the many viruses responsible for the common cold) excluding other viruses, including the influenza virus ⁽¹⁹⁾, and more specifically the one responsible for the 2009 epidemic, the H1N1 ⁽²⁰⁾, the coronaviruses in general^(21)(22) and probably SARS-CoV‑2⁽²³⁾. But there is naturally less data between influenza and SARS-CoV‑2…The few observations available are for the arrival of the pandemic in early 2020, when the 2019–2020 season influenza was present. A publication studying influenza + coronavirus co-infections also observed a 68% decrease in the risk of contracting SARS-CoV‑2 if one was already infected with influenza⁽²⁴⁾. Other observational studies⁽²⁵⁾ and conducted at⁽²⁶⁾ have also concluded that coronaviruses (including SARS-CoV‑2) and influenza viruses have an antagonistic relationship.

As SARS-CoV‑2 competes with influenza and was probably responsible for the disappearance of influenza by viral interference, the recent reappearance of influenza in Belgium⁽²⁷⁾ (end of 2021-beginning of 2022) would be rather good news. This would mean that the current SARS-CoV‑2 variants no longer pose the same threat as their predecessors, failing to ward off influenza viruses…Which, in turn, would mean that the COVID-19 pandemic would be over. This is also consistent with observations of mortality caused by successive variants, which are increasingly less virulent⁽²⁸⁾. Moreover, the historian of science David Robertson and the editor of the prestigious scientific journal British Medical JournalPeter Doshi, recently reminded us that the end of past pandemics was not related to disease transmission or pathogenicity, but rather to sociological aspects and more specifically to the attention paid by the general public, the media and policy makers to the current epidemic⁽²⁹⁾. Indeed, it is a question of questioning the arguments which would make it possible to declare the end of a pandemic: the circulation of the virus? Mortality? Successive variants have been less and less lethal… And the virus could become endemic (natural in humans). If it is up to the general public to lose interest in this disease, which is becoming less of a threat every day, then it is up to us to decide when the pandemic will end…

But announcing the end of the pandemic would have strong economic consequences for the pharmaceutical companies that supply the vaccines. Clinging to the vaccine strategy, the company Moderna (whose revenues had increased by 4708.44% in 2021 compared to 2020⁽³⁰⁾ announced on September 09, 2021 that it was developing a polyvalent vaccine combining 6 different mRNAs⁽³¹⁾ against COVID-19, influenza and respiratory syncytial virus (RSV), a virus causing bronchiolitis that has also been disrupted by SARS-CoV‑2⁽³²⁾. In addition, Novavax has also initiated the development of a dual vaccine against SARS-CoV‑2 and influenza⁽³³⁾. It is easy to imagine the promotion of these vaccines by health authorities. On the one hand, calling to avoid a future epidemic of a hypothetical variant of SARS-CoV‑2 and on the other hand, to benefit simultaneously from a protection against seasonal flu and RSV. However, several problems in the effectiveness of these vaccines can already be raised:

• Seasonal flu vaccines are based on viral strains circulating elsewhere in the world (which is one of the reasons they are ineffective), but influenza was absent during the pandemic. Even the vaccines administered for COVID-19 are still based on the original « wuhan » strain despite all the variants that have emerged since the beginning of the epidemic, which shows the difficulty of updating
• mRNA vaccines are still at an early stage of use (and in the study phase⁽³⁴⁾) and their side effects are still being identified
• Influenza can cause heart problems⁽³⁵⁾, such as myocarditis⁽³⁶⁾, probably related to the nature of its surface proteins⁽³⁷⁾ (their equivalent of the « spike » protein). It should be remembered that similar to influenza, the spike protein of SARS-CoV‑2 has been shown to be harmful and the observed vaccine side effects are most likely related to it⁽³⁸⁾. It is therefore not unreasonable to question the toxicity of new mRNA vaccines if they are based on the surface proteins of these viruses. Widespread vaccination could cause problems for people who are not at risk. In this context, it is worth recalling the side effects of the H1N1 vaccines, which included narcolepsy (for the Pandemrix vaccine)⁽³⁹⁾. This underscores the critical importance of conducting robust clinical studies, taking the time necessary to obtain effective and safe vaccines (as much as possible), and administering them to people at risk.

Agrippa is a name of Roman origin meaning « born with feet forward ». In the ancient Romans, this type of birth was considered a bad sign for the future. Announcing a double epidemic at the end of a pandemic, which would be COVID-19 and  influenza (A?) seems to me to be a very bad sign of a will to maintain sanitary measures (including vaccination), when all scientific data indicate that it is time to whistle the end of the pandemic.

Notes et références

1. Quelques exemples d’articles de la presse internationale relayant la crainte d’une double épidémie grippe+corona: En Belgique: La Grippe risque de se mêler au coronavirus, cette année: les experts insistent sur la vaccination. RTL, 28 août 2020: https://www.rtl.be/info/magazine/sante/la-grippe-risque-de-se-meler-au-coronavirus-cette-annee-les-experts-insistent-sur-la-vaccination-1240356.aspx , En France: Coronavirus et grippe: l’inquiétude d’une double épidémie hivernale. Top Santé, 19 août 2020: https://www.topsante.com/medecine/troubles-orl/grippe/double-epidemie-hivernale-vaccin-grippe-638140 , Au Canada: Grippe et COVID-19: vers une épidémie double à l’automne? Québec Science, 27 août 2020: https://www.quebecscience.qc.ca/sciences/grippe-covid-19-epidemie-double-automne/
2. Fearing a « twindemic » Health Experts Push Urgently for Flu Shots. New York Times, 16 août 2020: https://www.nytimes.com/2020/08/16/health/coronavirus-flu-vaccine-twindemic.htm
3. Bulletin hebdomadaire infections respiratoires. Semaine / week 02 (10/01/2022–16/01/2022). Sciensano: https://www.sciensano.be/sites/default/files/influenza_2022_02.pdf , Seasonal influenza 2020−2021. Annual Epidemiological Report. Centre Européen de Prévention et de Contrôle des Maladies: https://www.ecdc.europa.eu/sites/default/files/documents/AER-seasonal-influenza-2020-final.pdf , Spantideas N, Bougea A M, Drosou E G, et al. (September 15, 2021) COVID-19 and Seasonal Influenza: No Room for Two. Cureus 13(9): e18007. doi:10.7759/cureus.18007 , Hagen, A., 2021. COVID-19 and the Flu. American Society for Microbiology.
4. Return of the flu: EU faces threat of prolonged ‘twindemic’. Reuters, 17 janvier 2022: https://www.reuters.com/world/europe/return-flu-eu-faces-threat-prolonged-twindemic-2022–01-17/
5. Influenza – estimating burden of disease. Organisation Mondial de la Santé: https://www.euro.who.int/en/health-topics/communicable-diseases/influenza/seasonal-influenza/burden-of-influenza
6. Idem référence n°4
7. COVID-19: People who catch coronavirus and flu at same time this winter ‘twice as likely to die’, Jenny Harries warns, amid fears of ‘twindemic’. Skynews, 10 octobre 2021: https://news.sky.com/story/covid-19-people-who-catch-coronavirus-and-flu-at-same-time-this-winter-twice-as-likely-to-die-jenny-harries-warns-12430502
8. Idem référence n°4
9. Idem référence N°1 et 4, ainsi que Devra-t-on se faire vacciner contre la grippe en même temps que contre le Covid? Le Parisien, 15 septembre 2021: https://www.leparisien.fr/societe/sante/devra-t-on-se-faire-vacciner-contre-la-grippe-en-meme-temps-que-contre-le-covid-15–09-2021-KRY36EXODFHH3PTPB3IG56ODXU.php
10. Influenza vaccine effectiveness. Centre Européen de Prévention et de Contrôle des Maladies: https://www.ecdc.europa.eu/en/seasonal-influenza/prevention-and-control/vaccine-effectiveness
11. Ad Doxa per Aspera: https://www.kairospresse.be/ad-doxa-per-aspera/
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21. Idem référence n°18
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23. Idem référence n°19 , Kiseleva I, Ksenafontov A. COVID-19 Shuts Doors to Flu but Keeps Them Open to Rhinoviruses. Biology (Basel). 2021 Jul 31;10(8):733. doi: 10.3390/biology10080733. PMID: 34439965; PMCID: PMC8389621.
24. Stowe J, Tessier E, Zhao H, Guy R, Muller-Pebody B, Zambon M, Andrews N, Ramsay M, Lopez Bernal J. Interactions between SARS-CoV‑2 and influenza, and the impact of coinfection on disease severity: a test-negative design. Int J Epidemiol. 2021 Aug 30;50(4):1124–1133. doi: 10.1093/ije/dyab081. PMID: 33942104; PMCID: PMC8135706.
25. Spantideas N, Bougea AM, Drosou EG, Khanderia N, Rai S. COVID-19 and Seasonal Influenza: No Room for Two. Cureus. 2021 Sep 15;13(9):e18007. doi: 10.7759/cureus.18007. PMID: 34667682; PMCID: PMC8516323.
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27. Idem référence n°3
28. Données consultables par exemple sur le site Our World in Data ou John Hoptkins Coronavirus Resource Center
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33. https://www.reuters.com/business/healthcare-pharmaceuticals/novavax-begins-early-stage-trial-combined-influenzacovid-19-vaccine-2021–09-08/
34. Exemple pour Pfizer BioNTech: https://clinicaltrials.gov/ct2/show/NCT04368728
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