Between Christmas and New Year, Alexandra Trkola heard the first unsettling reports of a dangerous respiratory disease in central China. Given the similarities between the symptoms of the new disease and those seen in the SARS outbreak of 2002 and 2003, suspicion soon turned to a coronavirus. When Chinese scientists isolated the virus and in the second week of January made its genetic sequence available to the scientific community on the web, this suspicion was confirmed – and the alarm bells went off with virologists: “We’ve always had to reckon with a development of this sort, but a new viral pathogen is naturally very worrying,” is how the director of the UZH Institute of Medical Virology put it.
Ever since SARS (severe acute respiratory syndrome) and MERS (Middle East respiratory syndrome), it’s been clear just how dangerous coronaviruses can be for humans. Trkola and her specialists took the published genetic data and set about developing a test as quickly as possible. It works by making millions of copies of sections of genetic material, enabling the virus to be detected in throat swabs of infected people. These PCR tests were already available by the last week of January, and since then have allowed the analysis of tens of thousands of samples.
“Extremely ingenious and efficient”
The novel SARS-CoV-2 virus is spreading fear and panic all over the world. But seen from an evolutionary perspective the pathogen is simply “extremely ingenious and efficient,” as Trkola describes it. The virus is a lifeless particle with a strand of genetic material (RNA), whose only goal is to infiltrate human cells and reprogram them to produce new viruses.
The virus is successful when it infests as many people as possible without killing the host; otherwise it deprives itself of a way of multiplying. In this respect, SARS-CoV-2 is almost perfect. Compared with other viruses such as the Aids-causing HIV and the Ebola virus, SARS-CoV-2 is considerably less virulent, with a mortality rate in the single-digit percentage range. By way of comparison this figure is 50 percent for Ebola, and HIV-1 is almost always fatal if left untreated.
On the other hand Covid-19 affects many more people because the highly infectious coronavirus is spread by droplets. While HIV and Ebola require the exchange of bodily fluids, direct contact with infected people isn’t necessary for SARS-CoV-2 to be transmitted. A particularly insidious characteristic of the novel coronavirus is that infected people can spread it before the first symptoms even appear. Studies even suggest that infected people give off the most viruses one day before the disease actually manifests. The coronavirus responsible for the outbreak of SARS in 2002/03 did not yet have this characteristic, which meant it was easier to stem its spread even though the disease itself was more dangerous.
Especially surprising for virologists and physicians has been the huge variety of forms SARS-CoV-2 disease can take. A large proportion of those who become infected (probably up to half) don’t display any symptoms at all. While infected young people in particular are asymptomatic, older people and those in vulnerable groups can have severe symptoms and even die. What’s striking is that in many countries men are more seriously affected. “The differences between cases of the disease are extreme,” say Trkola, “and largely not understood.” It’s suspected that younger people have more flexible immune systems that respond more vigorously and are thus better able to neutralize the virus. Specialists at the Institute of Medical Virology (IMV) are doing serological experiments to look into these questions.
They’ve developed antibody tests that can assess the (humoral) immune response in both quantitative and qualitative terms. After an infection, the immune system’s B cells produce various classes of antibodies (immunoglobulins or Igs) to defend against the invading foreign bodies. In the initial wave, after a few days so-called IgMs and IgAs are produced, followed by IgGs later on. The ratios of these antibodies can be used to work out the moment of infection. In collaboration with the UniversityHospital, the University Children’s Hospital and family doctors, the IMV is analyzing the immune response among different groups of people. The resulting time series will provide information on the development of the immune defenses and help clarify one of the most important unanswered questions: how long does immunity last after infection?
Living with Covid-19
How many people are infected and whether they develop sustained immunity are crucial pieces of information in efforts to control the Covid-19 pandemic. “As long as we don’t have a vaccine we need the best data we can get,” says infectiologist Jan Fehr. This information also helps assess who will need the future vaccination and who won’t. Fehr directs the Department of Public & Global Health at the Epidemiology, Biostatistics and Prevention Institute at UZH. Under the umbrella of the national Corona Immunitas Study, he and other universities across Switzerland are tracking the occurrence of antibodies against the novel SARS-CoV-2 among the population (more in the interview on page 54). The study is a mainstay of the strategy for exiting the lockdown.
“Test, isolate, track: that’s the only way we can gradually emerge from the virus crisis,” explains Fehr. It’s particularly important to know the reproduction number (R), which represents the number of people that one infected person will pass the virus on to. An R number of below one indicates that the spread is slowing. The number changes continually, and varies depending on the population group and region. “We should determine these figures as precisely as we can and do as many blood tests as possible on representative sections of the population,” says Fehr. Only this way will it be possible to ease measures on a controlled basis and live with Covid-19 without putting people at too much risk.
Scientists can’t say for sure how long the new normal of Covid-19 and the pandemic will last. Sooner or later, effective drugs and vaccines will make the disease less terrifying. We can also assume that people will build up a certain level of basic immunity to SARS-CoV-2. It remains to be seen whether the virus will at some point mutate into a harmless cold germ as the other coronaviruses have, or whether, like influenza, it becomes a recurring threat. Are there any clues from experience of pandemics in the past?
Pandemics and paradoxes
What immediately springs to mind is the Spanish flu epidemic of 1918. As we now know, it was unleashed by a dangerous influenza virus that had evolved from a strain of avian flu. Medical historian Flurin Condrau at the UZH Institute of Biomedical Ethics and History of Medicine is cautious: “The situation in Switzerland at the end of World War I isn’t comparable with the present reality.” A hundred years ago the authorities weren’t aware of the nature of the pathogen. As in most countries, Switzerland was swept by two waves of Spanish flu, with the second round of infection in winter 1918/19 claiming more lives than the first in summer 1918. Hardest hit were younger adults. There were around 25,000 deaths in total in Switzerland, and between 25 and 50 million worldwide, with other estimates putting the figure at up to 100 million.
Unlike now, combating the pandemic wasn’t a federal matter, but was delegated to the cantons and municipalities. A hundred years ago Switzerland’s healthcare system wasn’t as well organized as it is today. Even so, schools were closed and there was a ban on gatherings. Businesses remained open, as did the lecture halls at the University of Zurich, and members of the public were exhorted to observe good hygiene.
“Pandemics reveal a paradox,” says Flurin Condrau. On the one hand, infectious diseases know no bounds, especially pandemic strains like SARS-CoV-2 that rapidly spread all over the world. On the other hand, the first measure to try and contain them is to create boundaries: literal boundaries between nation states, and metaphorical ones between people who isolate themselves in their homes. The trouble is that the global nature of infectious diseases calls for an internationally coordinated response. As Condrau remarks, the World Health Organization (WHO), which is actually responsible for such coordination, is no longer really capable of delivering this.
The WHO might have called years ago for governments to draw up pandemic plans, and currently serves as an important source of advice on medical and health policy measures to combat SARS-CoV-2, “but it’s not able to help and execute its own campaigns locally,” says Condrau. After it was established in 1948 the WHO was still able to do so, for example with campaigns to combat malaria. Condrau believes that while the United States’ decision to cut off funding to the UN body during, of all times, the Covid-19 crisis will have dire consequences, it’s merely the continuation of a development that began back in the 1980s.
Jan Fehr, who in ordinary times primarily looks after the Travel Clinic and is familiar with healthcare systems in African countries from his own projects, shares this opinion. “The WHO should be strengthened: ultimately we can only get the current crisis under control by cooperating globally.” While it’s essential to act locally and impose quarantine measures to break transmission chains, there’s a direct interplay between local interventions and the global situation. What’s the use of Switzerland and its neighbors becoming virus-free if countries with limited resources on other continents fail to do so? We could be caught by a renewed wave, rendering our efforts futile. “We need to adopt a One Health approach that covers different aspects of the pandemic on a global basis,” explains Fehr. For him this also includes addressing the root of the pandemic problem: the emergence of dangerous pathogens in the animal world (see box).
Worldwide cooperation among researchers
For virologist Alexandra Trkola, it goes without saying that international cooperation is important. “In this crisis we’ve seen unprecedented collaboration within the scientific community.” Since publication of the genetic sequence of the virus on 11 January, researchers have been exchanging their data and findings all over the world, with journals offering open access to work with no paywalls. An impressive example of international cooperation is the website Nextstrain, where genomic data from thousands of SARS-CoV-2 cases is updated on an ongoing basis to document its genetic evolution.
Trkola’s lab has also contributed genetic sequences of viruses it has sequenced. Family trees show how local outbreaks are connected globally and whether novel strains are emerging that will require new tests and responses. There’s no sign of this at the moment, but Trkola spells it out: the new virus could still spring many surprises on us.
Rats, Pigs and Bats
The novel SARS coronavirus is only the most recent dangerous pathogen that’s made the leap from animals to humans. The list of dangerous zoonoses, as these infectious germs from the animal kingdom are called, is long: SARS, Zika, swine flu, avian flu, HIV/Aids, hantavirus, Lassa fever, Lyme disease and Ebola hemorrhagic fever are only some of the diseases we’ve seen in recent years. Looking further back, rabies, tuberculosis, smallpox and naturally the bubonic plague spring to mind.
Around two thirds of all human pathogens are of animal origin. In the case of the novel SARS-CoV-2, the source viruses most probably originated in wild bats, which are well known for their strong immune system and ability to tolerate aggressive germs without getting sick. Over time, the viruses increased their radius of infection by mutating, and attacked humans. The question is whether an interim host – pangolins are a prime suspect – was involved.
What’s certain is that when wild animals and people come into close proximity, the risk of transmission to humans is great. Clearing forests and trapping wild animals create good conditions for a species jump, as has repeatedly been the case with Ebola. With SARS-CoV-2 too, suspicion has turned to the wild animal markets in the Chinese city of Wuhan, which have now been closed and banned. However, domesticated livestock and animals such as rats that live in close proximity to humans also play a key role in zoonoses.
Anthropologists and evolutionary biologists are therefore convinced that the curse of zoonotic pathogens began with human settlement. During the Neolithic Revolution around 12,000 years ago, former hunter-gatherers started cultivating plants and breeding animals. From that point on they lived side by side with their livestock, which of course were home to pathogens of their own.
In his “Tagebuch der Menschheit” (Diary of Humankind), UZH professor emeritus and evolutionary biologist Carel van Schaik describes how Adam and Eve’s expulsion from paradise can be read as an allegory of the new and arduous life in the first settlements, which were repeatedly plagued by serious disease. The outbreaks continue to this day – and with globalization and the cultivation of even the most remote regions, are even gathering pace.
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