No 2b - 2021

2020 - Year of the pandemic

This issue of EPI-NEWS looks back at the pandemic year 2020. The COVID-19 pandemic is the third global outbreak with a novel corona virus in the past 20 years.

The first warning was SARS, severe acute respiratory syndrome, detected in China in November of 2002. SARS was infectious from human to human in the symptomatic phase of the condition. Within months, a global outbreak had evolved counting a total of about 8,000 cases, including around 800 deaths, in the 2002-2003 period.

The second warning was MERS, Middle East Respiratory Syndrome, detected in 2012 among persons who had stayed on the Arabian Peninsula. The condition is caused by MERS-CoV, which transmits from human to human, but only through close contact during the symptomatic phase. MERS-CoV, like SARS-CoV, originated from animals. MERS-CoV has, among others, been detected in dromedaries. Since 2012, several thousands MERS-CoV cases have been observed among persons living on the Arabian Peninsula, in a disease outbreak in Korea and in several travel-related cases. On this backdrop it was not unexpected that coronavirus was capable of causing a pandemic, even though the global pandemic preparedness measures had focused primarily on the threat from pandemic influenza.

Strategies in existing pandemic planning

Until 2020, the Danish and global pandemic planning focused on the expected influenza pandemics. New influenza A viruses evolve in animals or humans, typically by reassortment of existing influenza A viruses or by gradual mutation. If these viruses adapt in ways allowing for efficient transmission between humans, a new influenza pandemic can evolve. Recently, this occurred in the swine influenza pandemic caused by influenza A/H1N1 in 2009, which was a very mild epidemic. The pandemics of 1957 and 1968 are other examples, but the best known example is the Spanish flu from 1918, hitherto used as a worst-case scenario in pandemic planning. The mitigation strategy described below and the red versus green curve were very much based on lessons learned from the Spanish flu. Thus, different strategies and scenarios were described as part of the planning efforts.

The aim of the containment strategy is to impede or delay the introduction of a new virus into the Danish population. This is done by testing people returning from affected areas, thereby curbing transmission by use of classic anti-epidemic principles: Isolation of patients and quarantining of exposed persons. One of the prerequisites to a successful containment strategy is that a case definition is available to delimit possible cases. Based on this definition, it can be decided who should be tested and who should not. This principle was used to determine that patients from China and subsequently from North Italy were to be tested for SARS-CoV-2 in the early phases of the COVID-19 pandemic. Containment was employed successfully against SARS in 2002-3 and against MERS-CoV-2.

In the current COVID-19 pandemic, the containment strategy used in Denmark and many other countries was brought to its knees already by late February because it became increasingly difficult to delimit the areas from which the infection came. Community transmission was starting to occur in several locations within Europe and other parts of the world in addition to the already well-known transmission among ski sports tourists from Austria and Italy. A second cause was that the infection was being transmitted from patients in the pre-symptomatic phase or patients who had no symptoms. This “hidden” transmission made it difficult to employ a case definition for work-up. Finally, hospitals did not have sufficient work-up capacity and capacity to test the large group of patients who had mild airway symptoms only, but who could not be seen in general practice as they had a relevant travel history in relation to COVID-19 exposure. Additionally, personal protection gear and testing equipment were out of stock, e.g. plastic products were unavailable due to the production shut down in China.

By early March, changing to a mitigation strategy had therefore become necessary. The objective of the mitigation strategy was to protect the vulnerable part of the population against serious infections but not necessarily to curb the spreading of the infection among persons not belonging to the risk groups. Testing was offered to people who belonged to risk groups or were seriously ill. Furthermore, a wide range of non-pharmaceutical measures were implemented, first and foremost the major shut-down on 11 March 2020. The objective of these measures was to delay the entire epidemic to avoid overloading the healthcare system (“the green curve”). Unnecessary activity in society was limited, which effectively limited transmission. The mitigation strategy is based on experiences from influenza pandemics, indicating that timely action is needed to flatten the epidemic curve. Influenza epidemics had also made it clear that the epidemic would subside at some pointas herd immunity was established in the community.

The third option, the suppression strategy was presented in relation to the COVID-19 epidemic in a report published by the Imperial College, London. The report stresses that establishing herd immunity against COVID-19 through natural infection would be a lengthy process and associated with considerable social costs in terms of disease burden and mortality. Rather, the authors proposed a strategy designed to suppress the epidemic as much as possibly while allowing social and economic activities to continue concurrently. To the extent possible, this strategy should remain in place until a vaccine is available. Thereby, herd immunity may be achieved with a considerably lower healthcare load and a reduced disease burden and mortality compared with the classic mitigation strategy described in the international pandemic plans.

The suppression strategy was inspired by experiences from several Asian countries where testing, infection tracing and isolation were combined with a range of measures and restrictions aiming to limit community contact and transmission. This strategy and the “toolbox” that comes with it had not been described in European pandemic plans but was developed during the epidemic. We paved the road while driving. The positive experiences from the Danish shut-down showed that it was also possible to limit community transmission in Europe. Even so, the shut-down was associated with large economic and human costs, why additional tools were needed: Testing

Testing-testing-testing

The first element of the suppression strategy is to maintain in place preventive measures such as hand hygiene, coughing etiquette, self-isolation when symptoms are observed, use of surgical masks, etc. along with some restrictions of community activities, i.e. number of people allowed at gatherings, the degree and frequency of interpersonal contact, travel restrictions, etc. The second element, promoted by the WHO as “testing-testing-testing”, was an ambitious effort to test, undertake infection tracing and isolate people who may have been exposed to infection to stop these people from passing it on to others. The third element is focused control of infection during outbreaks. The last two elements are possible only if citizens can be tested on a much broader indication than usually used in clinical diagnostics. In the classic mitigation strategy, testing is mainly a tool used when it is necessary to diagnose for clinical reasons. In the suppression strategy, mass testing is an important tool because it is necessary to break as many infection chains as possible. This became a paradigm shift that was hard to follow for many people.

One additional problem was that the clinical microbiology laboratories were seriously challenged as from March 2020. Many different supplies were out of stock, and liberal testing was therefore impossible. Thus, for several weeks, it was impossible to fulfill the “testing-testing-testing” ambition. However, in late March 2020, Statens Serum Institut (SSI) started to establish the test track that would subsequently be coined the community track, which now allows for testing of more than 100,000 samples daily. The white tents started appearing, which was initially a mysterious new occurrence for the general public. But establishing the community track and underpinning tracing efforts proved to be a decisive prerequisite to the slow, controlled re-opening of Denmark that was implemented in the spring and summer of 2020.

Dancing with corona

Another image illustrating the strategy started being used: the hammer and the dance. The hammer was the lock-down imposed in early March, and the dance designates the many initiatives taken to reduce transmission in specific communities and contexts. As months passed, we witnessed transmission among abattoir workers, persons of non-Danish origin, students initiating their courses at educational institutions and other party-craving young people, etc. In the course of the summer and early autumn, these outbreaks were managed mainly through local measures. A good example of this is the transmission observed in Aarhus in the first half of August 2020, where municipal measures underpinned by comprehensive testing curbed transmission.

The dance includes transmission through mink, which stressed that SARS-CoV-2 is an active zoonosis, i.e. a virus which, in this case, may be transmitted from humans to animals and vice versa in the form of comprehensive occupational transmission. The mink industry proved to be associated with a higher risk than any other industry in Denmark with respect to transmission of SARS-CoV-2. Subsequently, mink variants of SARS-CoV-2 spread in the community. This occurred more frequently in areas with infected mink. In these areas, mink variants became a new strand of the epidemic. On 3 November 2020, the SSI published a risk assessment concluding that continuing to breed mink during the current COVID-19 epidemic was associated with a considerable public health risk, including a risk of limiting prevention by use of COVID-19 vaccines. On this basis, the Danish government decided to cull Danish mink. Subsequently, the occurrence of mink variants has receded.

From the dance to the second wave

In relation to many of the countries with which we normally compare Denmark, we were able to fend off the epidemic for several months using less comprehensive general measures and more comprehensive temporary local measures (the North Jutland shut-down and the measures implemented in the Aarhus area, for example) in conjunction with comprehensive testing activity. Even so, new increases were observed after the autumn break, and the situation in Copenhagen and suburbs was starting to cause concern. The increases observed from 23 November 2020 onwards, in particular, marked the second wave of the epidemic. Limiting the second wave by scaling testing activity alone has proven to be impossible. Even though Denmark is among the countries that test the most globally, further measures were needed. The current situation is characterised by a considerable load on Danish hospitals, extensive community transmission and a population that remains susceptible to infection.

The first wave arrived when spring started. The challenge now is that the second wave started in early winter. For a number of reasons, airway infections thrive in winter and autumn. Therefore, it is harder to maintain the same level of transmission limitation as in spring. Therefore, the only solution was to resort to the hammer once more.

Expectations for 2021

The first months will be challenging. Infection numbers remain high and the healthcare system is under heavy pressure. Furthermore, the last weeks of December brought excess mortality indicating that the pandemic is taking its toll. The situation is further aggravated by the appearance of a new variant of the SARS-CoV-2 coined cluster B.1.1.7. This type is approx. 50-70% more infectious than the usual SARS-CoV-2 variants. We expect this variant to become dominant by mid February. If we do not reverse the trend and reduce infection numbers considerably in the course of January, we may once more be facing exponentially growing infection numbers. Therefore, the continued popular support for restrictions and overall responsible behaviour are critical in months to come.

On the positive side, vaccines have been introduced. We are now busy vaccinating and expect that in large parts of the risk groups the protective effect of the vaccination efforts made will show already few weeks after vaccination has been completed. This is important to the people affected and will also reduce the load on the healthcare system. Large parts of the population will need vaccination or have to gain immunity following natural infection to limit transmission through herd immunity. Previously, it was assessed that a 60% vaccine coverage would be sufficient, but as a more infectious variant of the virus is now spreading, vaccination coverage may need to reach approx. 75%, even though this remains uncertain. Herd immunity is established gradually, and we expect that transmission will be dampened before this high vaccination coverage is reached.

Therefore, it is realistic to assume that the situation will appear more encouraging by the spring of 2021. Even so, we cannot yet know to which degree restrictions may be lifted. If the risk groups have been vaccinated and the infectious pressure is low, the consequences of “letting go” measures to limit infection will, all things being equal, be more limited both for the individual and for society as a whole. Even so, the risk of outbreaks will remain as long as only part of the population has been vaccinated.

And the longer term?

What may happen in the longer term? We should recall that the only human infectious disease to have ever been eradicated is smallpox. Smallpox is less infectious than COVID-19, genetically stable and does not exist (the human variant) as a zoonotic reservoir. Additionally, smallpox was infectious in the symptomatic phase only, it had distinct clinical characteristics and it was therefore easier to isolate and confine the infection. SARS-CoV-2 is more infectious than variola major, has not yet fully adapted to its human host, can replicate in animal reservoirs like mink and other animals of the marten family, and can be without symptoms. This means that, in the short run and medium term at least, eradicating SARS-CoV-2 is no more than a pie in the sky, an ambition which should be considered impossible. On the other hand, vaccines will become ever better, and we will learn to live with this new disease - as is the case for many other airway infections.

Thus, 2020 has witnessed the coming of a new disease. Although the conditions are different, a parallel may be drawn to the HIV epidemic, which also ended up forming part of our shared human destiny.

And with these words, I conclude my final issue of EPI-NEWS. I joined the SSI in 1983 as a student of Medicine. Many people considered a career dedicated to infections and epidemiology a niche that would not prove very relevant in an industrialised society where antibiotics could be used to “solve” any infection-related problems. If any doubters remained to this day, it should now have become clear that even our modern Western societies are fragile and vulnerable to infections. Therefore, it is of vital importance to have strong epidemic preparedness measures in place. I believe that Denmark will learn from the current challenges and overcome the pandemic having established even stronger research-based preparedness measures.

(K. Mølbak, Infection Preparedness)