In addition, CFRs vary widely from country to country. This may be due to an incomplete coverage of cases, e.g. due to differences in testing procedures and capacities, as well as differences in the ability to provide high-quality intensive care. For example, of the 35,713 confirmed cases in Italy, 2978 (as of 19.3.2020 [3]) died, corresponding to a CFR of 8.4%, while in Germany only 28 of 12,327 died (CFR 0.2%). However, in contrast to Italy, Germany is only at the beginning of the exponential expansion and the intensive care capacity limit does not yet play a role in Germany. The widely divergent figures make it clear that it is not yet possible to reliably estimate the CFR.

What can be said with great reliability, however, is that deaths primarily occur in older people, mainly elderly people with pre-existing cardiovascular and pulmonary conditions. In an analysis published in February 2020 by the Chinese Center of Disease Control, 81% of COVID-19 deaths were in people over the age of 60 [8]. None of the 416 children <10 years were among those who died. However, the CFR was 0.6% even for those <60 years old.

The numbers in Italy are somewhat different. Only one person under the age of 50 died, while almost 60% of deaths involved people over the age of 80 [9].

In contrast to COVID-19, for example, almost 50% of deaths in the 1918/19 influenza pandemic affected those aged between 20 and 40 [10].

Concomitant diseases also represent a significant risk factor. In the Chinese study, 67.2% of those who died had at least one chronic concomitant disease, most frequently hypertension (39.7%), cardiovascular disease (22.7%), diabetes mellitus (19.7%), and chronic respiratory diseases (7.9%) [8]. Persons without pre-existing or concomitant diseases had a CFR of 0.9%. Here again, COVID-19 differs markedly from the 1918/19 influenza pandemic, in which many young people died without any major concomitant diseases [10].

In summary, the damage caused by COVID-19-associated premature deaths is considerable and is very likely to increase dramatically. However, the CFR of 0.2% currently measured for Germany is below the Robert Koch-Institute's (RKI) calculated influenza CFRs of 0.5% in 2017/18 [11] and 0.4% in 2018/19 [12], but above the widely accepted figure of 0.1% for which there is no reliable evidence. More threatening than the CFR of COVID-19 itself therefore is the absolute number of deaths to be expected if the disease continues to spread at doubling rates of two to three days. From the perspective of evidence-based medicine (EbM), however, all these figures are of limited use if the total mortality of the population, or the total burden of disease caused by influenza-like infections and their CFRs are not available as reference values.

Effectiveness of non-pharmacological interventions (NPI)

At this point, the main focus of this paper will be on the currently practiced and planned measures of "social distancing", i.e. state interventions ranging from the closure of educational institutions to a complete curfew.

As a historical example of the effectiveness of NPI, we refer to the different reactions of American cities to the 1918 influenza pandemic. In St. Louis, drastic measures were taken three days after the first cases of influenza occurred to contain the spread of the virus (closure of schools, churches, theatres, bars, cancellation of public events, etc.). In contrast, in Philadelphia a large parade was held after the outbreak and effective containment measures were not implemented until two weeks later [13]. The consequences were dramatic: in St. Louis the death rate peaked at 31/100,000 inhabitants, while in Philadelphia it rose to 257/100,000 inhabitants, resulting in a collapse of the health care system. The total number of deaths in St. Louis reached 347/100,000 inhabitants, about half that of Philadelphia (719/100,000 inhabitants) [13]. It is completely unclear, however, whether the experiences from the 1918/19 influenza pandemic are transferable to COVID-19. The fact that, at that time, the deaths were mainly among young people, and that neither hygiene standards nor medical care in 1918/19 are comparable with today, rather indicates that this is not the case.

Beyond the (rather questionable) conclusions drawn from the historical example, there is little evidence that NPIs for COVID-19 actually lead to a reduction in overall mortality. A Cochrane Review from 2011 found no robust evidence for the effectiveness of border control screenings or social distancing. However, this was mainly due to a lack of studies and poor study quality [14]. A systematic review from 2015 found moderate evidence that school closures delay the spread of an influenza epidemic, but at high cost. Isolation at home slows down the spread of influenza but leads to increased infection of family members [15]. It is questionable whether these findings can be transferred from influenza to COVID-19.

It is completely unclear how long the NPIs must be maintained and what effects could be achieved depending on their duration and intensity. The number of deaths might only be postponed to a later point in time, without any change in the total number. In contrast to seasonal influenza, we do not know how SARS-CoV-2 will continue to behave, whether the approaching spring in the northern hemisphere will lead to a natural halt to the spread of the virus, or whether the virus will continue to spread continuously and indefinitely until a large part of the population has been infected and become immune. The latter currently seems more likely.

A model calculation by the COVID-19 working group at Imperial College predicts that the implementation of radical NPIs - as currently planned or already implemented - could lead to a second, equally severe pandemic wave in autumn 2020 if the NPIs are relaxed after three months [16]. Alternatively, an "on-off strategy" could be pursued, which would have to be sustained until about 60-70% of the population has acquired the disease and become immune, and herd immunity has developed. However, this would mean that drastic NPIs would be in force at intervals for two thirds of the time over the course of an entire year [16].

Possible indirect damage from COVID-19 and NPIs

There is also little evidence of the possible indirect damage of the pandemic. In any case, the damage caused by the pandemic goes beyond the death toll. The disease not only places a serious burden on the health care system with possibly reduced or worse care for patients who are not ill with COVID-19, but also leads to major absences from work.

On the other hand, the current NPIs have massive effects that go far beyond the economic slump and the fall in stock prices. What are the psychological and social effects of social isolation? How many foreign caretakers do not want to or are no longer able to work with our elderly people in need of care because of the border closures and the requirements for coronavirus protection, such as the 14-day quarantine after returning home, and what are the consequences? How many jobs will be lost? How many companies will collapse? Whom will the economic consequences hit hardest? Will the NPIs contribute to greater social disparities?

Closing schools may reduce transmission rates among children, but will it really help to stop the pandemic and, most importantly, reduce death rates? Won't children meet outside of school, keep parents from working in the absence of childcare, and then visit grandparents - putting at risk the very group of people who most need protection?

At this stage, it is impossible to assess whether the unhindered rapid spread of the disease, or the delay of its spread and therefore prolongment of the total period of illness, would cause greater damage. Damage which may also have indirect effects on health, quality of life, and life expectancy.