COVID-19: an ‘extraterrestrial’ disease?

Open AccessPublished:July 25, 2021DOI:https://doi.org/10.1016/j.ijid.2021.07.051

      Highlights

      • The COVID-19 response should no longer be considered an exceptional task
      • It should be managed following long-proven principles of medicine and public health
      • A complex zoonotic disease cannot be solved through a magic bullet cure or vaccine
      • Disease heterogeneity requires targeted measures and reduction of comorbidities
      • The response should also mitigate the risk of transition from infection to disease

      Abstract

      Background

      Since the beginning of the pandemic, COVID-19 has been regarded as an exceptional disease. Control measures have exclusively focused on ‘the virus’, while failing to account for other biological and social factors that determine severe forms of the disease.

      Aim

      We argue that although COVID-19 was initially considered a new challenge, justifying extraordinary response measures, this situation has changed — and so should our response.

      Main arguments

      We now know that COVID-19 shares many features of common infectious respiratory diseases, and can now ascertain that SARS-CoV-2 has not suddenly presented new problems. Instead, it has exposed and exacerbated existing problems in health systems and the underlying health of the population. COVID-19 is evidently not an ‘extraterrestrial’ disease. It is a complex zoonotic disease, and it needs to be managed as such, following long-proven principles of medicine and public health.

      Conclusion

      A complex disease cannot be solved through a simple, magic-bullet cure or vaccine. The heterogeneity of population profiles susceptible to developing a severe form of COVID-19 suggests the need to adopt varying, targeted measures that are able to address risk profiles in an appropriate way. The critical role of comorbidities in disease severity calls for short-term, virus-targeted interventions to be complemented with medium-term policies aimed at reducing the burden of comorbidities, as well as mitigating the risk of transition from infection to disease. Strategies required include upstream prevention, early treatment, and consolidation of the health system.

      Keywords

      Background

      Although the threat of a pandemic had been present for many years, COVID-19 triggered frantic and uncoordinated reactions worldwide (

      Independent Panel for Pandemic Preparedness and Response, 2021. COVID-19: Make it the last pandemic.

      ;
      • Paul E.
      • Brown G.W.
      • Ridde V.
      COVID-19: time for paradigm shift in the nexus between local, national and global health.
      ). Since being declared a public health emergency in January 2020, COVID-19 has been regarded as an exceptional disease, almost as if it came from outer space. For the first time in history, billions of people were locked down, denied the right to go to school or to earn their living, and/or to see their loved ones, while an unprecedented race for treatment and vaccine discovery was launched. The collateral damage from these response measures was largely ignored, even if it may have been greater than the positive effects of the implemented policies (
      • Hrynick T.A.
      • Ripoll Lorenzo S.
      • Carter S.E.
      COVID-19 response: mitigating negative impacts on other areas of health.
      ). It ranged from economic recession and loss of education, to increases in domestic violence and mental health problems, and the worsening of chronic conditions from a lack of access to care (
      • Bavli I.
      • Sutton B.
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      Harms of public health interventions against COVID-19 must not be ignored.
      ). The effects weighed particularly heavily on young people, and hit the most vulnerable disproportionately, aggravating inequities (
      • Chakrabarti S.
      • Hamlet L.C.
      • Kaminsky J.
      • Subramanian S.V.
      Association of human mobility restrictions and race/ethnicity–based, sex-based, and income-based factors with inequities in well-being during the COVID-19 pandemic in the United States.
      ). In many countries, primary healthcare professionals were denied the right to treat their patients. Without effective primary healthcare, hospitals were left with the task of treating severe cases, notwithstanding the absence of a specific recommended drug. This led to the further exacerbation of existing disparities in health systems and services, especially in low- and middle-income countries (
      • Baral P.
      Health systems and services during COVID-19: lessons and evidence from previous crises: a rapid scoping review to inform the United Nations research roadmap for the COVID-19 recovery.
      ).
      Despite the fact that COVID-19 could be categorised as a ‘syndemic’ () — a synergy of epidemics that ‘co-occur in time and place, interact with each other to produce complex sequelae, and share common underlying societal drivers’ (
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      ) — control measures were exclusively focused on ‘the virus’ and delay tactics, while not taking into account other biological and social factors that contribute to determining severe forms of the disease (
      • Paul E.
      • Brown G.W.
      • Kalk A.
      • Van Damme W.
      • Ridde V.
      • Sturmberg J.P.
      When my information changes, I alter my conclusions.” What can we learn from the failures to adaptively respond to the SARS-Cov-2 pandemic and the under preparedness of health systems to manage COVID-19?.
      ). After several inconclusive results, it was only in July 2020 that one of the two large international randomized controlled trials aimed at testing the efficacy of existing treatments against COVID-19 published a preliminary report showing that dexamethasone (a glucocorticoid) resulted, on average, in lower mortality rates in patients requiring supplemental oxygen or invasive mechanical ventilation (
      The RECOVERY Collaborative Group
      Dexamethasone in hospitalized patients with COVID-19 — preliminary report.
      ). The lack of evidence on more effective medical treatments, coupled with projections suggesting high disease loads and death tolls, led to the perception that this was a one-off disease. This, unfortunately, led to proven and traditional medical and public-health practices being largely ignored. For instance, the longstanding concept of ‘herd immunity’, which has always represented an objective, or an achievement, is now considered by many as a ‘strategy’ — not to be acquired naturally, but only through vaccination (

      World Health Organization, 2020. WHO Director-General’s opening remarks at the media briefing on COVID-19 — 12 October 2020. https://www.who.int/director-general/speeches/detail/who-director-general-s-opening-remarks-at-the-media-briefing-on-covid-19–12-october-2020.

      ). In spite of all its potential risks, limitations, and considerable uncertainties regarding long-term side effects, the duration of protection, and its effectiveness against viral variants, vaccination quickly became the only salvation option promoted by key governments and international institutions.
      Although it is understandable that COVID-19 was considered an exceptional disease in early 2020, justifying exceptional response measures — particularly since SARS-CoV-2 can trigger a variety of symptoms, some of them extremely severe (
      • Hu Y.
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      • Li X.
      • Huang Q.
      • Wu Y.
      • Sun L.
      • Xu Y.
      Prevalence and severity of corona virus disease 2019 (COVID-19): a systematic review and meta-analysis.
      ;
      • Wiersinga W.J.
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      • Cheng A.C.
      • Peacock S.J.
      • Prescott H.C.
      Pathophysiology, transmission, diagnosis, and treatment of coronavirus disease 2019 (COVID-19): a review.
      ) — the situation has changed. So should our response (
      • Paul E.
      • Brown G.W.
      • Kalk A.
      • Van Damme W.
      • Ridde V.
      • Sturmberg J.P.
      When my information changes, I alter my conclusions.” What can we learn from the failures to adaptively respond to the SARS-Cov-2 pandemic and the under preparedness of health systems to manage COVID-19?.
      ). In this article, we argue that now that we far better understand the complex functioning of COVID-19, we should adapt our response strategy in a way that addresses its heterogeneity, and embraces proven and traditional medical and public-health practices.

      Analytical approach

      Various areas of expertise are relevant to approaching the complexity of the COVID-19 response. This article is based on a collaboration of clinicians, researchers, and experts in public-health policies based in three continents (America, Africa, and Europe) who are concerned by the COVID-19 response strategies in their respective countries — Belgium, Democratic Republic of the Congo, France, Germany, UK, USA — and at the global level. Together, they combine expertise in intensive care practice, biophysics, public health, virology, and health policies and systems. This paper adopts a reflexive analytical approach — where reflexivity can be defined ‘as an intentional intellectual activity in which individuals explore or examine a situation, an issue, or a particular object on the basis of their past experiences to develop new understandings that will ultimately influence their actions’ (
      • Tremblay M.-C.
      • Richard L.
      • Brousselle A.
      • Beaudet N.
      Learning reflexively from a health promotion professional development program in Canada.
      ) — to critically analyze, from a multidisciplinary point of view, the COVID-19 response strategy at the global level.

      COVID-19 exposed existing problems

      We now know that COVID-19 shares many features of common infectious respiratory diseases in terms of its transmission process — it is caused by a coronavirus whose transmission is airborne (
      • Greenhalgh T.
      • Jimenez J.L.
      • Prather K.A.
      • Tufekci Z.
      • Fisman D.
      • Schooley R.
      Ten scientific reasons in support of airborne transmission of SARS-CoV-2.
      ). Its immunopathology is better understood (
      • Cao X.
      COVID-19: immunopathology and its implications for therapy.
      ) and may entail vascular and immune system dysfunctions, possibly leading to a cytokine storm (
      • Garvin M.R.
      • Alvarez C.
      • Miller J.I.
      • Prates E.T.
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      • Mast A.E.
      • Justice A.
      • Aronow B.
      • Jacobson D.
      A mechanistic model and therapeutic interventions for COVID-19 involving a RAS-mediated bradykinin storm.
      ;
      • Varga Z.
      • Flammer A.J.
      • Steiger P.
      • Haberecker M.
      • Andermatt R.
      • Zinkernagel A.S.
      • Mehra M.R.
      • Schuepbach R.A.
      • Ruschitzka F.
      • Moch H.
      Endothelial cell infection and endotheliitis in COVID-19.
      ). Its severity and lethality are largely related to age, social determinants, and comorbidities (
      • Williamson E.J.
      • Walker A.J.
      • Bhaskaran K.
      • Bacon S.
      • Bates C.
      • Morton C.E.
      • Curtis H.J.
      • Mehrkar A.
      • Evans D.
      • Inglesby P.
      • Cockburn J.
      • McDonald H.I.
      • MacKenna B.
      • Tomlinson L.
      • Douglas I.J.
      • Rentsch C.T.
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      • Forbes H.
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      • Perera R.
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      • Smeeth L.
      • Goldacre B.
      Factors associated with COVID-19-related death using OpenSAFELY.
      ), while its infection–fatality rate, which averages around 0.2–0.3%, is extremely low for young people (
      • Ioannidis J.P.A.
      Infection fatality rate of COVID-19 inferred from seroprevalence data.
      ;
      • O'Driscoll M.
      • Dos Santos G.R.
      • Wang L.
      • Cummings D.A.T.
      • Azman A.S.
      • Paireau J.
      • Fontanet A.
      • Cauchemez S.
      • Salje H.
      Age-specific mortality and immunity patterns of SARS-CoV-2.
      ). Overall, SARS-CoV-2 has not created new problems out of the blue, but rather has exposed and exacerbated existing problems in the context in which it finds itself. For instance, in the USA, COVID-19 has revealed the poor health status of a large proportion of the population, with two-thirds of COVID-19 hospitalizations attributable to four major cardiometabolic conditions (
      • O'Hearn Meghan
      • Junxiu Liu
      • Frederick Cudhea
      • Renata Micha
      • Dariush Mozaffarian
      Coronavirus disease 2019 hospitalizations attributable to cardiometabolic conditions in the United States: a comparative risk assessment analysis.
      ), the critical role of social determinants of health (
      • Karmakar M.
      • Lantz P.M.
      • Tipirneni R.
      Association of social and demographic factors with COVID-19 incidence and death rates in the US.
      ), as well as ‘deep underlying problems in the healthcare system’ (
      • Blumenthal D.
      • Fowler E.J.
      • Abrams M.
      • Collins S.R.
      COVID-19 — implications for the health care system.
      ). In Europe, the pandemic has highlighted the ageing population, a lack of healthcare personnel resources, and the insufficiency of quality primary healthcare (
      OECD/European Union
      Health at a glance: Europe 2020.
      ). In Brazil, existing socioeconomic inequalities have driven epidemic outcomes more than any other risk factor (
      • Rocha R.
      • Atun R.
      • Massuda A.
      • Rache B.
      • Spinola P.
      • Nunes L.
      • Lago M.
      • Castro M.C.
      Effect of socioeconomic inequalities and vulnerabilities on health-system preparedness and response to COVID-19 in Brazil: a comprehensive analysis.
      ). Above all, COVID-19 has revealed the lack of health-system preparedness for pandemics, with inept global policies, non-existent and outdated national plans, a lack of health-system adaptability, equipment shortages, unreliable availability of medicines, poor communication strategies, fragmented diagnostic capabilities, and poor governance structures (
      • Baral P.
      Health systems and services during COVID-19: lessons and evidence from previous crises: a rapid scoping review to inform the United Nations research roadmap for the COVID-19 recovery.
      ;
      • Paul E.
      • Brown G.W.
      • Ridde V.
      COVID-19: time for paradigm shift in the nexus between local, national and global health.
      ).

      Implications for policy

      COVID-19 is not an extraterrestrial disease that appeared from nowhere. It is a complex zoonotic disease and it needs to be managed as such (
      • Wernli D.
      • Tediosi F.
      • Blanchet K.
      • Lee K.
      • Morel C.
      • Pittet D.
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      A complexity lens on the COVID-19 pandemic.
      ), following long-proven principles of medicine and public health. A complex disease cannot be solved through a simple magic-bullet cure or vaccine. This especially true when the infectious agent is an airborne virus with not only one, but many animal reservoirs, being a known zoonosis that can be found in numerous species around human habitats (
      • Shi J.
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      • Bu Z.
      Susceptibility of ferrets, cats, dogs, and other domesticated animals to SARS-coronavirus 2.
      ;
      • Ye Z.-W.
      • Yuan S.
      • Yuen K.-S.
      • Fung S.-Y.
      • Chan C.-P.
      • Jin D.-Y.
      Zoonotic origins of human coronaviruses.
      ;
      • Wardeh M.
      • Baylis M.
      • Blagrove M.S.C.
      Predicting mammalian hosts in which novel coronaviruses can be generated.
      ;
      • He S.
      • Han J.
      • Lichtfouse E.
      Backward transmission of COVID-19 from humans to animals may propagate reinfections and induce vaccine failure.
      ). As a result, claims for its eradication are naïve. In fact, some scientists are suggesting that ‘full’ herd immunity to end this pandemic is probably impossible because of new variants arising, doubts over whether the vaccines can prevent transmission, signs of waning immunity, and inequities in the global distribution of vaccines (
      • Aschwanden C.
      Five reasons why COVID herd immunity is probably impossible.
      ). This simple fact also renders viral control policies via the increased use of lockdowns unsustainable. According to 50 years of coronavirus research, as well as knowledge accumulated on respiratory viral infections, we should expect new waves of the virus, or of a variant, probably more regularly in fall and winter, particularly in the northern hemisphere (
      • Estola T.
      Coronaviruses, a new group of animal RNA viruses.
      ;
      • Moriyama M.
      • Hugentobler W.J.
      • Iwasaki A.
      Seasonality of respiratory viral infections.
      ). This calls for a shift in policy from a ‘zero-risk’ strategy, which is imposed top–down via ‘command-and-control’ lockdowns, to ‘risk-mitigation’ and ‘harm-reduction’ strategies through educating and empowering people, especially the most vulnerable (
      • Arnold C.
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      ,
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      • Méndez C.A.
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      Reclaiming comprehensive public health.
      ).
      The heterogeneity of population profiles susceptible to developing a severe form of COVID-19 calls for the adoption of varying, targeted measures, which are able to reach risk groups in an appropriate way. The critical role of comorbidities in disease severity calls for complementing short-term virus-targeted interventions — including prophylaxis in high-transmission settings (
      • Seet R.C.S.
      • Quek A.M.L.
      • Ooi D.S.Q.
      • Sengupta S.
      • Lakshminarasappa S.R.
      • Koo C.Y.
      • So J.B.Y.
      • Goh B.C.
      • Loh K.S.
      • Fisher D.
      • Teoh H.L.
      • Sun J.
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      • Tambyah P.A.
      • Hartman M.
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      ) — with medium-term procedures aimed at reducing the burden of comorbidities, as well as SARS-CoV-2 infection-to-COVID-19 disease transition risks, at an early stage. The heterogeneity of COVID-19 symptoms suggests that we should not simply wait for a specific cure that works ‘on average’ against SARS-CoV-2, at a late stage of the disease. With such heterogeneity, most people’s disease development profiles lie far from the average. Moreover, viral infections follow a well-known path from their entry point to ultimate outcomes, requiring the adaptation of treatment to each patient’s stage in infection. It is better to start treating before inflammation sets in and to adapt treatments to individual needs, through primary and patient-centred care. For instance, while it has been known since the first wave that COVID-19 causes blood clots, it is only recently that a study has confirmed that prophylactic anticoagulation treatment is probably ‘optimal therapy’ for COVID-19 patients (
      • Vaughn V.M.
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      ). Likewise, we should not delay empirical antimicrobial therapy in cases of suspected co-infection prior to the worsening of clinical conditions; the potential benefits of pre-emptive antimicrobial therapy at the time of COVID-19 symptom onset need to be explored appropriately (
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      ). This point had already been promoted by Dr A Fauci as a conclusion to the flu pandemics of 2008–2009 (
      • Morens D.M.
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      ). Evidence is now emerging for the potential effectiveness of repurposed drugs, including ivermectin (
      • Hill A.
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      • Qavi A.
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      ), amantadine (
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      ), and cofloctol (

      Belouzard, S., Machelart, A., Sencio, V., Vausselin, T., Hoffmann, E., Deboosere, N., Rouillé, Y., Desmarets, L., Séron, K., Danneels, A., Robil, C., Belloy, L., Moreau, C., Piveteau, C., Biela, A., Vandeputte, A., Heumel, S., Deruyter, L., Dumont, J., Leroux, F., Engelmann, I., Alidjinou, E.K., Hober, D., Brodin, P., Beghyn, T., Trottein, F., Déprez, B., Dubuisson, J., 2021. Large scale screening discovers clofoctol as an inhibitor of SARS-CoV-2 replication that reduces COVID-19-like pathology. bioRxiv 2021.06.30.450483. doi:10.1101/2021.06.30.450483

      ), as well as nutritional supplementation (
      • Alzaabi M.M.
      • Hamdy R.
      • Ashmawy N.S.
      • Hamoda A.M.
      • Alkhayat F.
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      • Al Joud S.M.A.
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      ;
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      ) and new molecules, such as plitidepsin (
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      ), at early stages of disease. More research is required at this level. Furthermore, when dealing with patients with known comorbidities, it would be medically sound and therapeutically helpful to carry out typing of the human leukocyte antigen (HLA) for susceptibility, so as to identify those who truly need swifter and deeper care (
      • de Sousa E.
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      • Zhang C.
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      Mortality in COVID-19 disease patients: correlating the association of major histocompatibility complex (MHC) with severe acute respiratory syndrome 2 (SARS-CoV-2) variants.
      ;

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      ).
      Vaccines are an important part of the response strategy, but only if they follow a precautionary principle, with continuous appraisal of the benefit–risk balance. Doing so is necessary to maintain confidence in vaccines and to avoid adverse effects — as with vaccines against dengue and the influenza H1N1 pandemic (
      • Forcades i Vila T.
      Flu vaccination: the gap between evidence and public policy.
      ;
      The Lancet Infectious Diseases
      The dengue vaccine dilemma.
      ) — that could reinforce vaccine hesitancy on the part of people who need it most. However, vaccines alone will not solve the COVID-19 pandemic (
      The Lancet COVID-19 Commission, Task Force on Public Health Measures to Suppress the Pandemic
      SARS-CoV-2 variants: the need for urgent public health action beyond vaccines.
      ). Thus, additional complementary strategies are needed, including prevention, early treatment, and the consolidation of the health system (
      • Paul E.
      • Brown G.W.
      • Kalk A.
      • Ridde V.
      Playing vaccine roulette: Why the current strategy of staking everything on Covid-19 vaccines is a high-stakes wager.
      ). Even if it is not recommended by the World Health Organization as a ‘strategy’, innate and already naturally acquired immunity, including T-cell immunity (
      • Braun J.
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      ;
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      ). This suggests that individuals previously infected by SARS-CoV-2 are unlikely to benefit from COVID-19 vaccination, so that vaccines can be safely prioritised to those who have not been infected before (

      Shrestha, N.K., Burke, P.C., Nowacki, A.S., Terpeluk, P., Gordon, S.M., 2021. Necessity of COVID-19 vaccination in previously infected individuals. medRxiv 2021.06.01.21258176. https://doi.org/10.1101/2021.06.01.21258176

      ).
      Non-pharmaceutical interventions continue to be implemented in many countries despite progress in vaccinations — even strict lockdowns (e.g. in Australia) — in spite of lack of evidence on their overall efficiency (
      • McCartney M.
      We need better evidence on non-drug interventions for COVID-19.
      ). For example, nearly a year and a half after the beginning of the pandemic, there is still low evidence for the effectiveness of face mask wearing in community settings (
      • Chou R.
      • Dana T.
      • Jungbauer R.
      Update alert 6: masks for prevention of respiratory virus infections, including SARS-CoV-2, in health care and community settings.
      ). While some studies show that stay-at-home policies may have reduced virus transmission, others show that they have not impacted overall mortality (

      Agrawal, V., Cantor, J., Sood, N., Whaley, C.M., 2021. The impact of the COVID-19 pandemic and policy responses on excess mortality (working paper No. 28930), Working Paper Series. National Bureau of Economic Research.

      ). In any case, non-pharmaceutical interventions must be proportional to overall health needs and chosen to take into account local context specificities and existing alternatives, while aiming to maximize expected benefits for general health outcomes and minimize collateral damage. From this perspective, the most efficient measures probably include limiting mass gatherings, promoting outdoor activities, where transmission is very low (
      • Bulfone T.C.
      • Malekinejad M.
      • Rutherford G.W.
      • Razani N.
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      ), implementing sentinel surveillance and smart testing policies (
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      Pour une stratégie de dépistage efficace et objective des personnes susceptibles de transmettre le SARS-CoV-2.
      ), and ventilating public indoor places (
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      A guideline to limit indoor airborne transmission of COVID-19.
      ).
      In terms of the policy landscape, public health policies need to be decided and designed in a transparent way, in collaboration with all relevant disciplines and stakeholders, including populations, and social and healthcare workers, and regularly evaluated to ensure continuous adaptation and improvement (
      • Paul E.
      • Brown G.W.
      • Kalk A.
      • Van Damme W.
      • Ridde V.
      • Sturmberg J.P.
      When my information changes, I alter my conclusions.” What can we learn from the failures to adaptively respond to the SARS-Cov-2 pandemic and the under preparedness of health systems to manage COVID-19?.
      ). Moreover, there needs to be a normative shift in how we think about prevention and preparedness, particularly towards a mindset that understands long-term preventative healthcare as an investment, not an expense. Lastly, it is crucial to move beyond our current understanding of health security, which has traditionally favoured surveillance, exceptionalism, ‘countermeasures’, and an overreliance on vaccine discovery, often at the expense of routine health. As an alternative, the link between health-system strengthening and health security needs to be articulated more forcefully, with better multilevel governance mechanisms for coordinating efforts, integrating community, national, regional, and global levels (
      World Health Organization
      Health systems for health security: a framework for developing capacities for international health regulations, and components in health systems and other sectors that work in synergy to meet the demands imposed by health emergencies.
      ). If not, then the policy lessons from COVID-19 will have been ignored, and we will once again find ourselves confronting the next pandemic as if it were an unexpected and exceptional disease.

      Acknowledgements

      The authors thank Wim Van Damme for commenting on a previous version of this paper.
      Declaration of interest statement: The authors declare no conflicts of interest.
      Ethical approval: This was not required for this perspective paper.
      Funding: No specific funding was utilized. All authors are independent from funders.

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