The Global Effort to Contain Covid-19

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19.02.2020, Japan, Yokohama: Busse mit australischen Passagieren von Bord des unter Quarantäne stehenden Kreuzfahrtschiffs «Diamond Princess» verlassen den Hafen. Nach zweiwöchiger Quarantäne durfte eine erste Gruppe von 500 meist älteren Reisenden das Schiff verlassen. Die Ausschiffung der noch rund 3000 Menschen an Bord sollte mindestens drei Tage dauern. Foto: Eugene Hoshiko/AP/dpa +++ dpa-Bildfunk +++

Epidemiologists and doctors around the world are doing all they can to slow the spread of the new coronavirus. But new hotspots continue to pop up, indicating that it may already be too late.

By Matthias Bartsch, Uwe Buse, Lukas Eberle, Georg Fahrion, Jan Friedmann, Johann Grolle, Veronika Hackenbroch, Marc Hujer, Martin U. Müller, Fritz Schaap

It was a knock at the door on day 10 of the quarantine that had Jerri and Mark Jorgensen fearing that it may now be their turn to changes sides — from the healthy passengers of the Diamond Princess to those who were infected and sick. To those who had been separated from their spouses and families and sent to hospitals in and around Yokohama. To those left to hope that their experience with the new coronavirus would not be severe.

The knocking was not a good omen.

Three days earlier, two Japanese, a man and a woman, had entered the married couple’s cabin. They were wearing protective suits, face masks and gloves and they took samples from the throats of the two Jorgensens before disappearing again. They didn’t speak much: The visitors seemed to know about as much English as the Jorgensens could speak Japanese.

The two Americans from the U.S. state of Utah were naturally concerned about what their test results would reveal. Jerri Jorgensen had been feeling unwell for a few days, but she kept trying to tell herself that it was nothing. At least nothing connected to the strange, new virus.

She was more concerned about her husband. Mark Jorgensen was feeling fine, but he had two transplanted kidneys and had been taking medication since the operation to suppress his immune system so that his body wouldn’t reject the new organs. Jerri and Mark were both fully aware that a coronavirus infection could prove deadly for him.

The Jorgensens opened the door, and again found themselves facing two people covered head-to-toe in protective clothing. They were bearing bad news: Jerri’s test had come back positive.

She would like to have been given time to pack a small bag, but the two health workers told her she could not. She was only permitted to take along a daypack with the essentials. And a short time later, Jerri Jorgensen was on her way to the quarantine, a hospital in Fukushima. Her husband stayed behind all alone in the cabin.

Mark Jorgensen found himself wondering: If the virus had spent three days multiplying in his wife’s throat, how great was the danger that he was now infected as well?

The ease with which the novel coronavirus SARS-CoV-2 was able to spread throughout the cruise ship Diamond Princess triggered global concern. One day, there were 99 new infections discovered on board, on another it was 88, and on still another, 79 new patients were identified. Ultimately, almost a third of the 3,700 passengers and crew had tested positive for the virus during the 14-day quarantine.

Two of the passengers have since died from the lung infection triggered by the virus. And it is quite possible that additional infections have been discovered among the passengers, who have now been allowed to return home, where they can expect another two weeks of quarantine.

Many Open Questions

But how was it allowed to happen? Was it because important quarantine and hygiene rules were disregarded aboard the ship, as the Japanese epidemiologist Kentaro Iwata, from the Center of Infectious Diseases at Kobe University, suspects? Or was the ship’s ventilation system to blame? Either way, the infected passengers and the two who have died were victims of a quarantine that was imposed for their protection but maintained to their detriment. There are a lot of open questions.

What is clear, however, is that wherever large numbers of people are in close quarters – on cruise ships, in hospitals, in prisons, on buses and subways, in open-plan office spaces and at festivals and trade shows – the virus is presented with ideal conditions to spread. It looks as though SARS-CoV-2 has no trouble jumping from person to person.

As a result, it appears that a pandemic has become almost unavoidable. Increasing numbers of experts are beginning to wonder whether the global spread of the virus can still be stopped, and the sudden uptick of cases in Italy has underlined that concern. “There are many scenarios imaginable for a worldwide spread,” says Marc Lipsitch, an epidemiologist at Harvard University. He is, however, prepared to make one prediction: “The assertions that by April everything will be over, are not true.”

There is some cause for some optimism though: The warmer seasons are slowly approaching, and it could very well be that the virus will loosen its grip, similarly to how most flu and cold pathogens behave. Furthermore, the number of new infections reported each day by China is dropping. The problem, though, is that nobody knows if those numbers can be trusted.

The news from the sealed off province of Hubei, which is primarily disseminated via social media channels, continues to be horrifying. Most of the 2,000 deaths thus far caused by the virus have occurred in the provincial capital of Wuhan. And it is particularly concerning how many health-care workers have become infected. Some 3,000 of them have tested positive for the virus across China.

Sports arenas, hotels and cultural centers have all been transformed into quarantine stations where the infected are interned. The Chinese government has sent several thousand soldiers to Wuhan in addition to an army of nurses. One widely shared video shows some women having their long hair shaved off before being pressed into service – symbolic of the fact that just like members of the military, soldiers in the fight against the virus in Wuhan must sacrifice their individuality.

The city, with a population of 11 million, is involved in nothing less than a war against the epidemic, a war declared by no less a personage than Chinese President Xi Jinping. Those who have become infected may no longer be cared for by family members at home. Everyone is required to report suspected cases. Functionaries have been tasked with finding all those who have bought cough or fever medicine in the last several weeks.

Myriad provisions and decrees have been imposed across China as all levels of bureaucracy seek to prove their assiduousness. They are all united by fear: In late January, Xi threatened that all those who did not fulfill their obligation in the battle against the disease would be punished. He also warned that the economy cannot be made to suffer for an extended period.

According to the official numbers, the mixture of fear, sacrifice, surveillance and rigorous quarantining is having some effect. After weeks of paralysis, public life in many parts of China is also returning to something approaching normal. Social media users have begun posting their relief at once again seeing traffic jams on city streets.

The Beijing leadership is also displaying growing self-confidence in the fight against the disease. Just over a week ago, the party periodical Quishi published a speech by Xi in which he praised his own leadership in the fight against the coronavirus. The word “I” appears 13 times in the speech, a sign that the president is optimistic and is no longer concerned about having to take personal responsibility for the spread of the disease.

Bad News from the Front Lines

It is precisely that optimism, however, that has triggered concern in the international community of disease experts. It seems doubtful, after all, whether a leader posing as the savior of his country would be willing to accept bad news from the front lines.

Because the data from China cannot be trusted, experts are left to wait and see where the virus pops up next. Cities in East and Southeast Asia are particularly at risk, believes Andrew Tatem from the University of Southampton in England. Using international traffic patterns, he and his team assembled a ranking of cities where the risk of a coronavirus outbreak is greatest. Bangkok, Hong Kong, Taipei, Seoul, Tokyo and Singapore are at the very top. The first German city on the list is Frankfurt, way down in 28th place.

Experts have, in fact, been focusing most of their attentions on countries in the Far East, apparently with good reason. Last Thursday, it was announced that more than 100 new cases were found in a single church in the South Korean city of Daegu, located three hours south of the capital Seoul. “We are involved in an unprecedented crisis,” said the mayor of the city, which has a population of 2.5 million. The streets quickly emptied out and one 28-year-old resident told the news agency Reuters: “It looks like someone dropped a bomb in the middle of the city. It looks like a zombie apocalypse.” On Sunday, South Korea announced that 556 cases had been identified.

In Japan, the health minister said the country was entering a “new phase” in the spread of the virus. For the first time, the country has identified cases in which officials were unable to determine where the infection had taken place.

But in Italy, too, the situation seems to be getting out of hand. On Monday, Italy reported that six people have now died of the disease and the number of infected people has risen to more than 200, most of them in the northern regions of Veneto and Lombardy. On Sunday, the government made the decision to seal off several municipalities in northern Italy. None of those who initially tested positive had been in China recently.

For epidemiologists, such a transmission is considered a key moment — if the path of the virus can no longer be followed, then are hardly any effective measures available to block its spread.

Once that stage is reached, experts fear, it doesn’t take long before the pathogen will find its way into countries where the health-care system is not prepared to handle an epidemic. The concern was therefore significant when Iran reported last Wednesday that two people had died from Covid-19 in the city of Qom. None of the two had recently traveled abroad and contact to Chinese tourists could also not be found. According to news reports, the situation has only worsened since then, with the number of officially reported deaths in the country having risen to 12.

Such a rapid climb in the number of cases is exactly the kind of scenario that Michel Yao is afraid of. In the World Health Organization regional headquarters in Brazzaville, the capital of the Republic of Congo, he is responsible for emergency coordination in a region that is widely considered to be the Achilles heel when it comes to the global response to epidemics. The region encompasses 47 African countries and it’s his job to develop strategies the prevent or slow the spread of epidemics there.

Developing Criteria for Hospitals

“Coronavirus could become a huge challenge here,” Yao says. Health-care systems are weak in the region, he says, and they could easily be overwhelmed. Just 100 sudden cases, he says, would be enough.

The day before we spoke to Yao last week, the alarm had been sounded in Sierra Leone, with 29 travelers from China stuck in the airport. Two of them were suffering from a fever. There were other suspicious cases in Burkina Faso, Kenya and Equatorial Guinea. “We are expecting the first confirmed case at any time,” Yao said.

Many experts believe that the virus has long since found its way into central and southern Africa, and Yao says he can’t rule it out. “It is a new virus and we don’t know how it behaves here.”

And then, he has to go. He has more on his plate than just coronavirus, after all. He must also address outbreaks of Lassa fever, measles and Ebola.

About 6,000 kilometers to the north, Christian Drosten is sitting at his giant, note-covered desk drinking tea on a recent Friday. A tall man with dark, curly hair, Drosten is director of the Institute of Virology at Berlin’s Charité and had cancelled all appointments that day to finally write the scientific paper that many experts around the world had been waiting for. The focus was on how long Covid-19 patients remain infectious and when they can be released from hospital without posing a danger to others.

Virus measurements in discharge and stool samples provided Drosten with the definitive clues. On the basis of those measurements, he says, he was able to develop clear criteria for hospitals, which is vital for the clinical treatment of any disease outbreak. “If the virus spreads around the world, we will have to free up beds as fast as possible,” Drosten says.

Drosten grew up on a farm near the border with the Netherlands and became interested in medicine during his mandatory civil service. He realized before long that he wasn’t cut out for working in the intensive care unit and ultimately decided to work in the lab as a virologist.

He became famous overnight in 2003 when he was able to identify the SARS virus more quickly than the U.S. authorities. He is now seen as a leading coronavirus expert and a specialist when it comes to analyzing samples.

The two monitors on his desk display patient data on which his arguments rest. “Unfortunately,” he says, “I am constantly distracted by emails.” He is receiving around 300 of them a day at the moment, “and about 100 of them need to be answered that same day.”

Positive or Negative

Ever since it became known in January that the new lung infection from Wuhan was caused by a coronavirus, Drosten has been working long hours, with barely enough time in the morning to take his son to daycare. His goal is that of learning as much as possible about the virus, which can only be seen with an electron microscope – and he hopes to do so before the pathogen has spread around the world. Only if doctors know their opponent, after all, can they prescribe the correct treatment.

One of the next projects that Drosten intends to embark on is the development of a test for the virus which can, similar to a pregnancy test, identify the illness immediately, positive or negative. One of the problems facing medical professionals at the moment is that many of those infected show only very mild symptoms or none at all. Without a quick test to identify the pathogen’s presence, controlling and monitoring its spread is virtually impossible. “Such a test could, for example, be used in rural areas of Africa,” Drosten says. “But also in totally normal family practices and emergency rooms.”

Every virus has its own modus operandi, says Drosten, and that of the Covid-19 pathogen was initially misidentified by him and by many other scientists around the world. “I was immediately thinking: SARS.” The new virus and the SARS pathogen, after all, belong to the same family of viruses.

But then, Drosten and his team made a discovery that completely changed the prevailing view of the virus. In contrast to the SARS virus, the Covid-19 pathogen can be isolated in the throats of patients, and not just in their lungs. That could explain why it is much more contagious than SARS, but also much less dangerous.

Drosten and his colleagues are focused on comparing the two pathogens on a molecular level. Both of them are currently in storage at minus 80 degrees Celsius in the so-called S3 Laboratory of the Institute of Virology in Berlin. The security precautions are tight, exceeded only by those surrounding super-dangerous pathogens such as the Ebola virus.

Marcel Müller, who heads up the laboratory, briefly has a look at a display that monitors the negative air pressure inside the laboratory, a measure to ensure that air can go in, but never out. He then opens a heavy door with a large, circular window leading to the lab’s airlock entry before donning his protective clothing: two pairs of blue gloves, yellow rubber boots, a green micro-fiber protective suit, waterproof arm coverings and, at the very end, a gray mask with a visor that covers his entire head.

Müller’s task for the day is contaminating a cell culture with Drosten’s old SARS virus so the pathogen can multiply and provide sufficient viral material for experiments to be conducted later. It is astounding, says Müller, how unreliable it is to draw conclusions about a virus’s behavior on the basis of its genome. That is why it is important to not just compare the genome of the novel coronavirus with that of the SARS virus, but to compare the two pathogens to themselves as well.

The journal Science just published a paper about the most important surface protein of the pathogen that causes Covid-19. According to the team behind the paper, the protein binds much more strongly to human cells than the comparable protein from the SARS pathogen. That could be an additional explanation for why the novel coronavirus is so much more contagious than SARS.

No Panic

Müller and Drosten now want to find out why SARS-CoV-2, as the new coronavirus pathogen is called, is able to multiply in the throats of patients, in contrast to the old SARS pathogen. On that search, Müller uses a pipette to introduce virus samples into a bottle inside of which a cell culture is growing in a reddish nutrient solution. He then places the culture in an incubator. Within a few days, the virus will have multiplied significantly and triggered many cells to burst, with holes visible in the cell layer when looked at under a microscope.

Such cell cultures, says Müller, will also be used to test drugs targeting the new virus. Many of the drugs already proved a certain amount of effectiveness in the battle against the SARS virus. Now, they could become an important weapon should the new coronavirus develop into a pandemic.

It likely won’t be long until the global alarm over Covid-19 reaches Germany as well, and health officials in all German states are currently making preparations. Strangely, though, it seems almost as though the mood has grown increasingly placid the closer the virus comes.

Frankfurt is considered to be particularly exposed, with the international airport seen as a potential viral gateway. Local health authorities estimate that several thousand passengers land in Frankfurt everyday who could theoretically have come into contact with people infected with Covid-19. It seems unavoidable that one of them will eventually bring the virus into Germany.

In response, all passengers arriving from at-risk regions have had to fill out a questionnaire, in a precaution introduced last week. Those who say they had contact with someone infected are isolated in the plane and then examined by a doctor upon arrival in Frankfurt. If the doctor believes the suspicion of infection is credible, the passenger is then tested at the university clinic. Nobody, though, believes that the procedure offers much in the way of reliable protection. Not a single Lufthansa passenger has yet responded “yes” to the relevant question. Other airlines report that some passengers have, in fact, answered in the affirmative, but it later turned out that they only did so because they had misunderstood the question.

The airport’s ability to respond to the disease was put on full display in mid-January, when almost 130 Germans flew in after being evacuated from Wuhan. A medical center was quickly set up so that people could be examined – and two of them were even found to be carrying the disease. But in both cases, the disease proved unharmful, and one of them didn’t end up having any symptoms at all.

Indeed, the new virus is fortunately not at all like the aggressive SARS pathogen, says infectious disease specialist Antoni Walczok from the Frankfurt Health Office. When it comes to how the illness is likely to progress, he says he is reminded more of the swine flu pandemic in 2009.

A Certain Amount of Optimism

Many of the emergency plans developed back then have been pulled back out of the drawer, including options for the cancellation of public events, school closures and the reduction of public transportation. Still, Walczok says, it took months before sporadic isolated cases ultimately became a larger outbreak.

Walczok, though, still doesn’t think that such measures will become necessary this time. Schools and kindergartens, for example, could likely remain open even should the illness spread through Germany: Thus far, it appears that children only rarely come down with Covid-19.

Nobody in Germany has accumulated as much experience with the new virus thus far as the Bavarians. In late January, 14 people connected to the auto supplies company Webasto in Stockdorf, just southeast of Munich, became infected with SARS-CoV-2. And here, too, the experience with the virus has led to a certain amount of optimism.

“The disease was quite mild,” says Clemens Wendtner, who was chief physician at the Munich clinic that treated nine of the patients. Wendtner and his team monitored the patients’ flu-like symptoms and dry coughs. Some of the patients reported difficulties smelling and tasting their food.

The strategy of admitting infected patients while home-quarantining those with whom they had been in close contact worked, says Wendtner. “Hardly any infections were imported,” he says. And hardly anyone else was infected by the patients. He says he didn’t even need to make use of his clinic’s quarantine station. “I currently believe that we won’t experience a large corona wave in the country,” Wendtner says.

Such experiences could be a reason why precautionary measures in North Rhine-Westphalia, Germany’s most populous state, have been anything but draconian. As of late last week, four people had been classified as “Category I Contact Persons” and were being monitored. The four of them were among the 57 Germans who had sailed with the cruise ship Westerdam. Passengers of the ship had been allowed to disembark in Cambodia, after the shipping company had said the ship was not infected with Covid-19. Only after many had already left was it made public that an 83-year-old American woman had tested positive for the disease.

Four of the ship’s passengers have now returned to their homes in North Rhine-Westphalia, but they were not subjected to strict quarantines as were those who had returned from Wuhan. Health officials felt that just keeping them in their homes would be sufficient. They have been asked, however, to take their temperatures twice a day and to keep a journal about how they feel and with whom they have contact. Food is being brought to them by a delivery service.

A week ago on Saturday, American officials with the Centers for Disease Control then announced that there actually was no infection: The test of the 83-year-old woman had actually produced a negative result, a spokesperson said.

The world is essentially in a holding pattern. The SARS-CoV-2 virus is in the process of circling the globe, and yet many questions remain unanswered. Perhaps too many.

Indeed, the lack of knowledge about the pathogen remains the most serious of the challenges. For as long as medical experts, health officials and political representatives don’t know all they need to know about the virus, they will continue to make disastrous mistakes.

Such as those made aboard the Diamond Princess.

Two days after Jerri Jorgensen was led out of the cabin she shared with her husband and brought to the hospital in Fukushima, her husband and all other U.S. citizens from Diamond Princess were evacuated. Buses brought them to the Haneda airport and Mark Jorgensen was flown to California seated in the hastily repurposed cabin of a cargo plane.

He is now in a second quarantine – a three-room apartment at Travis Air Force Base just outside of San Francisco. He is doing his best to keep his sense of humor, referring to his new lodgings as his “bachelor pad.” Thus far, he has shown no symptoms. But he won’t know for sure whether he is carrying the disease inside until the 14-day incubation period has passed.

His wife in Fukushima, meanwhile, is no longer showing any symptoms. She merely complains of the food and that she has no internet. The two Jorgensens are forced to remain in touch over the phone, and they talk daily. And they are forced to wait. Just like the rest of us.

Der Spiegel

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