The COVID-19 epidemic has tested the resilience not of not only public health systems, but of companies, supply chains, economies, and political systems. New pandemics and major social shocks will certainly occur in the future and it is important that we fully extract learnings and take the opportunity to enhance social resilience before memories fade. BCG will shortly convene the Meeting of Minds — an interdisciplinary forum of thought leaders in business, finance, epidemiology, public health, complex systems science, computer science, history, and other areas — to synthesize a perspective. Each was asked to prepare a short written stimulus for group discussion. Here Sir Roy M Anderson, Professor of Infectious Disease Epidemiology at Imperial College London and former Chief Scientist at the UK Ministry of Defense shares his thoughts on what we could learn from the pandemic.

Lesson 1. ‘You cannot have your cake and eat it’.

Scientific analyses conducted in 2010, which were stimulated by concerns over how best to control a novel strain of Influenza A, revealed a central dilemma in infectious disease outbreak control.^[1]Suggested reading: Anderson RM et al (2020) How will country-based mitigation measures influence the course of the Covid-19 epidemic? Lancet https://doi.org/10.1016/ S0140–6736(20)30567–5. If policymakers are asked what is the most urgent priority once the first stages of an outbreak have been detected from a shortlist of options: namely; minimise mortality, prevent the collapse of the tertiary care system (hospitals) with too many patients seeking urgent care during the exponential growth of the epidemic in relation to beds available, keep the economy fully functioning, and flattening the epidemic curve to create time for vaccine and drug development, they invariably respond — ‘ I would like to achieve all of these’. Analyses reveal that this is not possible for directly transmitted respiratory infections that transmit via aerosols and contaminated surfaces. Choosing one option, such as minimising mortality as the epidemic expands and before vaccines and drugs are available, requires social distancing measures to reduce rates of infection. This impacts the economy greatly — especially before adaptions emerge. Businesses do adapt to survive. The success of working remotely during the Covid-19 pandemic in early to mid-2020, and currently as new strains emerge, is a good example. Flattening the curve and avoiding the collapse of the tertiary care system similarly require social distancing measures that impact the economy.

Lesson 2. Vaccine development is not the problem — manufacturing on scale is

Current vaccine development platforms, and the newer RNA-based technologies, mean that vaccines can be developed very quickly (within 3 to 6 months) and adapted year by year as new strains emerge, as is the case for influenza A. In the past, development took many years to complete phase III trials and navigate through the vaccine/drug approval processes prevailing in Europe and North America, often of the order of 7 years or more. Covid-19 showed this time scale could be collapsed to 9 to 12 months. This lesson was also learnt during the 2014–16 West Africa Ebola outbreak by Merk and GSK. The problem is not vaccine development and testing via phase II and III trials (which are easier to conduct when infection rates are high), but manufacturing on scale to service the world. Much has been achieved during the Covid -19 pandemic to increase the world’s manufacturing capacity, but most is in North America, Europe, and India. Drug manufacturers predicted that 12 billion doses of covid-19 vaccine would be enough to fully immunise at least 70% of the world’s population, and they could be manufactured by the end of 2021 based on a report by the International Federation of Pharmaceutical Manufacturers and Associations. ^[2]Feinmann J (2021) Covid-19 global vaccine production is a mess and shortages are down to more than just hoarding. BMJ 2021; 375 doi: https://doi.org/10.1136/bmj.n2375. It did warn, however, that “most doses in the production queue are already allocated” to high-income countries.

Lesson 3. The unit for measuring success in vaccine uptake is the world — not any one country

Controlling effectively a pandemic of a novel pathogen worldwide is essential for a mutable pathogen that is continuously evolving and adapting both to its new human host and the environment created by the vaccines that are in use. The net rate of evolution is proportional to total population size (which influences the rate of spread) and most importantly, each transmission event is an opportunity for viral evolution. As such, in unvaccinated segments of the world, typically in resource-poor settings, viral evolution continues apace. To slow the evolution of new variants — much greater attention needs to be given to resource-poor countries. At present only 6% of people on the African continent have been fully vaccinated. A different evolutionary race takes place in highly vaccinated populations where the pace of evolution is driven by the need to evolve mutants that evade the protection offered by current vaccines. However, the pace of evolution is dictated by the net rate of new infections, and this will be much lower in vaccinated populations by comparison with unvaccinated communities.^[3]Suggested reading: Anderson RM et al (2020) Challenges in creating herd immunity to SARS-CoV-2 infection by mass vaccination. Lancet https/10–1016/S0140–6736(20)32318–7.

Lesson 4. Contact tracing only works when infection rates are low — unless you have very intrusive surveillance

We have learnt painfully, and often at great cost, that once infection has spread widely, contact tracing involves so much labour that it takes too long and is too expensive to be an effective control measure.^[4]Keeling MJ, Hollingsworth TD, Read JM (2020). The efficacy of contact tracing for the containment of the 2019 novel coronavirus (COVID-19). medRxiv 2020; published online Feb 17. … Continue reading If populations permit complete access to personal information, such as location-based mobile phone tracking, then tracing can work in some settings such as China where individual activity and location surveillance is extensive. In most high-income countries, data protection rules do not permit this sort of data collection.

Lesson 5. SARS-CoV-2 will become endemic worldwide and its evolution will be continuous — evolutionary forces will act to increase the basic reproductive number R₀ — this may or may not be linked to changes in pathogenicity

The virus is unlikely to be eradicated in the foreseeable future — it will be endemic in large regions of the world. Mass vaccination coverage of a vaccine with 90% efficacy (to prevent disease and onward transmission) would have to reach nearly 100% in large populations to completely block transmission given the high basic reproductive number of the currently dominant Delta variant (R₀ is 5 or above, and the new Omicron variant may have a higher value).³

Past scientific analyses have shown that pathogens do not evolve to become less pathogenic over time since emergence in a new host — they evolve to maximize the magnitude of the reproductive number, R (the average number of new cases generated by each primary case of infection) since in a population with co-circulating strains where infection with one strain confers some protection against other strains — the strain with the biggest R₀ value wins and becomes dominant. Increased or decreased pathogenicity may be involved in increasing the magnitude of R. The ‘just so’ story (an untested narrative explanation) that pathogens always evolve to be less pathogenic to their host (why kill your host?) although popular, is incorrect. If a viral strain is more pathogenic due to generating much higher viral loads in your host which results in increased transmissibility, the strain will out-compete its lower pathogenic and less transmissible competitors despite eventually killing its host.^[5]Anderson RM and May RM (1982) Coevolution of host and parasites. Parasitology 85: 411–42.

Lesson 6. Vaccine hesitancy is a huge problem — making vaccination mandatory and developing vaccine passports must be considered early in any pandemic of a directly transmitted respiratory pathogen

Worldwide there is great heterogeneity in mandating vaccination and in the creation of vaccine passports. Uniformity is required for the latter with some international guidance of what is needed. For the former, education of the public must start early and continue unabated. The history of modern medicine show clearly that vaccines rank as one of the top interventions of all in protecting human life — the public needs to be made aware of this fact and it should be taught to children at a young age.^[6]Sallam M (2021) Vaccine hesitancy worldwide: a concise systematic review of vaccine acceptance rates. Vaccines 9,160 https//doi.org/10.3390/vaccines9020160.

Lesson 7. Once a new strain is detected — closing borders to travellers from specific countries has little impact

Experience and analyses show that closing borders to stop new virus entry (such as the Omicron strain) — only works if you do it both completely and before the virus has evolved. By the time a new strain is detected by molecular sequencing methods linked to case detection, it has typically spread widely and between countries given modern air travel networks. Country-based contingency plans for the pandemic should therefore largely focus resources on facilitating treatment, monitoring and control of new cases at home. Once case numbers of a new strain exceed a few hundred in source areas, only rapidly implemented and almost total restriction of international travel can prevent the export of cases and the triggering of epidemics of the new strain (given its R₀ value is greater that existing dominant strains) in unaffected areas. The efforts of the WHO and the international community should be targeted at bringing any emerging strain with a high transmissibility under control as rapidly as possible in the country in which the new strain first emerges. Success in this task is likely to be the dominant factor in restricting international spread.^[7]Hollingsworth D, Ferguson N & Anderson RM (2004) Will travel restrictions control the international spread of pandemic influenza? Nature Medicine 5; 498–499. ^[8]Ferguson et al (2004) Public health risk from the avian H5N1 influenza epidemic Science 304: 968–969.

Lesson 8. Accurate and cheap diagnostics are central to effective control

The development of diagnostic methods is central to control efforts for novel infectious agents. In the early stages it is diagnosis and isolate, in later stages it may be diagnose and treat to try and limit morbidity/mortality and stop or limit onward transmission if anti-viral agents become widely available. New methods have been pioneered in the Covid-pandemic, not just PCR-based but also lateral flow technologies. Lateral flow tests (LFTs), also known as lateral flow immunochromatographic assays or rapid tests, are simple devices intended to detect the presence of a target substance in a liquid sample without the need for specialized and costly equipment. These need further development (and for other common infections such as influenza A and B strains) and what is the basis of the test (which parts of the viral sequence are targeted) need to be made public — it should not be IPR protected. This is of particular importance as new strains emerge and need identification. Each test’s accuracy needs clearly specifying when many strains are co-circulating.^[9]Mardian et al (2021) Review of current Covid-19 diagnostics and opportunities for further development. Front Med 07 May 2021 https://doi.org/10.3389/fmed.2021.615099.

Lesson 9. Vaccines are not the only need — therapeutics are required — both small molecule and biologicals

Given vaccine hesitancy in some communities — plus a small fraction of individuals who cannot be adequately protected by vaccines due perhaps to a compromised immune system resulting from treatments to mitigate other diseases, therapeutics are required — the pace of development in this area has been good (i.e. trials to show that corticosteroids such as dexamethasone can reduce mortality due to SARS-CoV-2 infection). However, more needs to be done with biologicals (antibody treatments) and possible small molecule drugs to inhibit viral replication.^[10]Welte et al (2021) Current evidence for Covid-19 therapies: a systematic literature review. European Respiratory Review 2021 30: 200384; DOI: 10.1183/16000617.0384–2020. Only one tablet, Molnupiravir produced by Merk which interferes with viral replication, has been approved in the USA and the UK to treat vulnerable patients with SARS-CoV-2. Much mortality could still be prevented if such treatments were available worldwide.

Lesson 10. Mathematical models of viral spread have their limitations, but simple concepts such as the reproductive number of infection, R, worked well in helping to inform the public about intervention impact

Mathematical models of viral transmission (both simple and complex) work well in predicting the magnitude of an epidemic in the absence of control interventions — they work less well as heterogeneity in human behaviour and control policy implementation in response to the threat, evolves community by community and country by country. The concept of a reproductive number of infection, R, has proved to be a useful communication tool for keeping the public informed. The number R defines the average number of secondary cases generated by each primary case. If R>1 the epidemic is expanding, and when R<1, it is contracting. This simple number serves to communicate if measures such as social distancing or mass vaccination are succeeding in controlling viral spread.

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Appendix — What enabling measures should we take before the next pandemic?

What actions can governments, businesses and international agencies take to prepare for the next pandemic. Another pandemic will occur with certainty, and if it is a directly transmitted respiratory virus with high pathogenicity, it will be serious. The only unknown is when it will happen. Some examples of urgent enabling measures for the next pandemic are listed below — but many more could be listed. The challenge will be to persuade policy makers to focus on these needs once the current Covid-19 threat abates.

(i) The most obvious is vaccine manufacturing capabilities and the locations of any new facilities in resource poor settings. China and India have large facilities, as do Europe and North America, so the needs are in Africa and South plus Central America.

(ii) Vaccine passports need discussion at an international level — both their form, their security (to avoid forgery), what content is desirable, and how should they be updated as vaccines change to increase efficacy and breadth in terms of what strains do the vaccines protect against.

(iii) Agree internationally on how regulatory procedures and clinical trial data approval can be harmonised between countries and approval speeded up for promising products.

(iv) Diagnostic manufacturing facilities (PCR, lateral flow and antibody test)– same problem as vaccine manufacture — more facilities in Africa and South plus Central America. International manufacturing standards regulation is also important — much profiteering took place for Covid-19 tests and many products were of poor sensitivity and specificity.

(v) Start educating the young about the huge importance of vaccination to protect themselves, their families and friends.

(vi) Personal Protective Equipment (PPE) — again manufacturing, quality and regulation are required to set international standards. Standards for face masks of particular importance for respiratory infections. There is a need to seek agreement internationally on why mask wearing is an important tool for combating viral spread.

(vii) Encourage adaptability of businesses and government for working at home and addressing social distancing needs, concomitant with schemes to protect the parts of the economy and government administration that cannot easily function in a ‘socially distanced’ world.

(viii) Ensuring fast and secure internet connections are available nationwide to facilitate working remotely and encourage software development to make remote meetings more capable of stimulating people to people creative interactions.

(ix) Discuss in advance if populations would permit enhanced surveillance during the early stages of a pandemic to try and limit spread and control clusters of infection.

(x) Agree internationally on real time data collection procedures for cases, hospitalisations and deaths, and the sharing of information between countries.

(xi) Set up international surveillance systems to track pathogen evolution via whole genome sequencing in a manner akin to the influenza surveillance structure, but on a larger scale and with much more sampling in resource poor countries, speeding up data collection and analysis, and facilitate rapid information sharing with governments and vaccine manufacturers.

(xii) Plan for the creation of international data bases of large longitudinal (over time) long duration studies of patients who have recovered from infection but have persistent morbidity (e.g. long Covid) to facilitate clinical trials of possible treatments and further understanding of the consequences of infection.