On a bright morning in May, Isabel Klugherz, a medical student at Ludwig-Maximilians University, in Munich, arrived at the geographical center of the city’s Milbertshofen district. Over the previous month, as Munich’s streets emptied under lockdown orders, an exception had been granted for roving medical students in mint-green scrubs and face masks. The university’s department for infectious diseases was screening for the seroprevalence of SARS-CoV-2—antibody testing—by sending police-escorted teams on the winding pattern of a predetermined algorithm, otherwise known as a random walk. Start in the center of an electoral district, continue past a few houses, cross to the other side of the street, select the third house, and knock. In the past month, Klugherz had knocked on nearly a thousand doors, and residents had been overwhelmingly enthusiastic about participating; one man had pronounced it more important than his Sunday celebration of the Holy Mass. That morning, the algorithm led Klugherz into a quiet road of whitewashed modernist buildings. The day before, she had texted a friend who lived nearby to let him know that she would be in the area. Now, unexpectedly, the algorithm led her to his door. She rang the bell. When her friend answered, and found Klugherz standing outside, he was still in his pajamas
In late March, the government of the state of Bavaria, which includes Munich, was trying to decide how to respond to what appeared to be an accelerating community spread of COVID-19. Michael Hoelscher, the director of the Department of Infectious Diseases and Tropical Medicine at L.M.U., was involved in official debates about whether to impose a citywide lockdown. That, to him, was a foregone conclusion. Considering the disease’s rate of transmission, under the most extreme scenarios, it could take about two and a half years to reach herd immunity in Germany. “Not an option,” Hoelscher said. What was less clear was how the city could effectively track the disease’s spread. Because so many cases of COVID-19 appeared asymptomatic, as Hoelscher had first noted in a paper published in January, diagnostic testing alone would only provide a partial measurement. “So I said, ‘O.K., we need something,’ he told me. The only way to get an accurate measurement of the epidemic, he reasoned, was to implement wide-scale antibody testing. Within six hours, just before the lockdown was announced, on March 21st, he received a million euros from the government.
Hoelscher is tall, with a wave of blond hair that he keeps brushed back cleanly from his face; on the day we met, he was dressed in slim-fitting jeans and a normcore sweater layered over a blue Oxford shirt. Like many infectious-disease researchers of his generation, Hoelscher began his career working on H.I.V. and AIDS. In the early two-thousands, he ran a study on sex workers and bar workers in Tanzania to learn whether it was possible to be infected with H.I.V. more than once. (Deborah Birx, the coördinator of the White House Coronavirus Task Force, was one of his collaborators.) “Take H.I.V.,” Hoelscher said. “You have the disease, you produce an immune response, and that immune response, No. 1, is not able to kill the virus itself. But it can also not protect you from getting a second H.I.V. infection.” The H.I.V. virus, his team discovered, was able to “hide” itself in the immune response, transcribing its genome into the cells. “So that’s an example where the antibody doesn’t help against it,” he said. “In history so far, we only have been able to produce or manufacture a vaccine if the natural immune response would be able to prevent a secondary infection.”
Michael Hoelscher, the director of Ludwig-Maximilians University’s Department of Infectious Diseases and Tropical Medicine, has studied H.I.V. and AIDS.
SARS-CoV-2 is obviously different. But it is also exhibiting unusual features. “It can affect multiple organs,” Hoelscher said. “Not only the lower respiratory tract. It can replicate in the upper respiratory tract, it can most likely replicate in different organs.” The course of the disease, the time that it remains in the body, is long, and in some cases, his team found, the immune response does not develop until nearly two months after an infection. “Absolutely surprising or frightening,” Hoelscher said, “is that there might be really some reason to believe that you cannot eliminate it from your body.”
Not far from Hoelscher’s office, L.M.U. had set up a testing tent near the poplar trees of Leopoldstrasse, an imperious boulevard that runs through town. Test subjects who preferred to have their blood drawn outside of their home could come here instead. Outside the tent’s entrance, I met Michael Pritsch, a young infectious-disease doctor who works in Hoelscher’s lab. Pritsch is helping to run the study, but he had come to the tent to get tested himself. In late April, medical students he’d trained had followed the algorithm and ended up at his front door. “My home was my castle,” Pritsch told me. “When I came home after sixteen hours of work, I had my five minutes of free time.” And then they rang his bell. “Even at home, I’m not without this coronavirus thing,” he said. Two students in scrubs and masks welcomed him into the tent and offered him a new mask. He signed a consent form, which he’d helped write, and then pushed up his sleeve as one of the students knotted a rubber tourniquet around his upper arm. Pritsch suggested, wryly, that he would probably check his own data. (“Don’t write that!” he said.
The blood samples are delivered to a laboratory that Andreas Wieser, the study’s head virologist, set up in late March. When I met Wieser in the first room of his lab, crowded with two large deep freezers, a big refrigerator, and a bio-safety cabinet, he held out a vial for me to see. The material had separated into a lower, dark-reddish “dense part,” that contains the cellular material, and an upper, putrid-yellow “liquid” section, containing, potentially, the antibodies. In an adjoining room were two separate antibody-testing machines, one manufactured by Roche, which resembled a giant photocopier, and another by Euroimmun, which looked more like a bulky plastic printer. The Roche and Euroimmun tests check for different immune responses to the virus, so that they can do a kind of “cross-sectional” examination to correct for some of the statistical unreliability still inherent in the antibody tests; by doubling up, Wieser gets a more accurate result. “Mixing tests which have a different target protein on the virus gives you superior information,” he told me. “We take the best of both worlds.”
In late March, the government of the state of Bavaria, which includes Munich, was trying to decide how to respond to what appeared to be an accelerating community spread of COVID-19. Michael Hoelscher, the director of the Department of Infectious Diseases and Tropical Medicine at L.M.U., was involved in official debates about whether to impose a citywide lockdown. That, to him, was a foregone conclusion. Considering the disease’s rate of transmission, under the most extreme scenarios, it could take about two and a half years to reach herd immunity in Germany. “Not an option,” Hoelscher said. What was less clear was how the city could effectively track the disease’s spread. Because so many cases of COVID-19 appeared asymptomatic, as Hoelscher had first noted in a paper published in January, diagnostic testing alone would only provide a partial measurement. “So I said, ‘O.K., we need something,’ he told me. The only way to get an accurate measurement of the epidemic, he reasoned, was to implement wide-scale antibody testing. Within six hours, just before the lockdown was announced, on March 21st, he received a million euros from the government.
Hoelscher is tall, with a wave of blond hair that he keeps brushed back cleanly from his face; on the day we met, he was dressed in slim-fitting jeans and a normcore sweater layered over a blue Oxford shirt. Like many infectious-disease researchers of his generation, Hoelscher began his career working on H.I.V. and AIDS. In the early two-thousands, he ran a study on sex workers and bar workers in Tanzania to learn whether it was possible to be infected with H.I.V. more than once. (Deborah Birx, the coördinator of the White House Coronavirus Task Force, was one of his collaborators.) “Take H.I.V.,” Hoelscher said. “You have the disease, you produce an immune response, and that immune response, No. 1, is not able to kill the virus itself. But it can also not protect you from getting a second H.I.V. infection.” The H.I.V. virus, his team discovered, was able to “hide” itself in the immune response, transcribing its genome into the cells. “So that’s an example where the antibody doesn’t help against it,” he said. “In history so far, we only have been able to produce or manufacture a vaccine if the natural immune response would be able to prevent a secondary infection.”
Michael Hoelscher, the director of Ludwig-Maximilians University’s Department of Infectious Diseases and Tropical Medicine, has studied H.I.V. and AIDS.
SARS-CoV-2 is obviously different. But it is also exhibiting unusual features. “It can affect multiple organs,” Hoelscher said. “Not only the lower respiratory tract. It can replicate in the upper respiratory tract, it can most likely replicate in different organs.” The course of the disease, the time that it remains in the body, is long, and in some cases, his team found, the immune response does not develop until nearly two months after an infection. “Absolutely surprising or frightening,” Hoelscher said, “is that there might be really some reason to believe that you cannot eliminate it from your body.”
Not far from Hoelscher’s office, L.M.U. had set up a testing tent near the poplar trees of Leopoldstrasse, an imperious boulevard that runs through town. Test subjects who preferred to have their blood drawn outside of their home could come here instead. Outside the tent’s entrance, I met Michael Pritsch, a young infectious-disease doctor who works in Hoelscher’s lab. Pritsch is helping to run the study, but he had come to the tent to get tested himself. In late April, medical students he’d trained had followed the algorithm and ended up at his front door. “My home was my castle,” Pritsch told me. “When I came home after sixteen hours of work, I had my five minutes of free time.” And then they rang his bell. “Even at home, I’m not without this coronavirus thing,” he said. Two students in scrubs and masks welcomed him into the tent and offered him a new mask. He signed a consent form, which he’d helped write, and then pushed up his sleeve as one of the students knotted a rubber tourniquet around his upper arm. Pritsch suggested, wryly, that he would probably check his own data. (“Don’t write that!” he said.
The blood samples are delivered to a laboratory that Andreas Wieser, the study’s head virologist, set up in late March. When I met Wieser in the first room of his lab, crowded with two large deep freezers, a big refrigerator, and a bio-safety cabinet, he held out a vial for me to see. The material had separated into a lower, dark-reddish “dense part,” that contains the cellular material, and an upper, putrid-yellow “liquid” section, containing, potentially, the antibodies. In an adjoining room were two separate antibody-testing machines, one manufactured by Roche, which resembled a giant photocopier, and another by Euroimmun, which looked more like a bulky plastic printer. The Roche and Euroimmun tests check for different immune responses to the virus, so that they can do a kind of “cross-sectional” examination to correct for some of the statistical unreliability still inherent in the antibody tests; by doubling up, Wieser gets a more accurate result. “Mixing tests which have a different target protein on the virus gives you superior information,” he told me. “We take the best of both worlds.”
Locally run antibody studies, coördinated by the Robert Koch Institute, the German counterpart to the U.S. Centers for Disease Control and Prevention, are being carried out across Germany in an orchestrated effort to construct an over-all picture of the disease’s penetration in the country. Hoelscher’s department is one of the best-resourced, in one of the wealthiest regions, in Germany. It processed the country’s first COVID-19 cases, in January, and produced widely cited studies on asymptomatic transmission in Europe. Since then, Hoelscher’s department has worked to track, record, observe, and quantify the disease, aiding the German government in efforts to at once study and contain SARS-CoV-2. “We feel that there is an enormous number of questions that will only come after” the initial outbreak, Hoelscher told me:
Do antibodies provide immunity? If so, for how long? Can people who’ve been infected become reinfected?
Germany’s first COVID-19 cluster emerged just outside Munich on the morning of Monday, January 27th. The C.E.O. of Webasto, an auto-parts manufacturer, received an e-mail from a manager in Shanghai: an employee who had visited the Munich office the previous week had become feverish during the return flight to China and tested positive upon landing. A German employee who’d sat next to her during a presentation had felt sick over the weekend, and went to Hoelscher’s lab to be tested. Within hours, he had his results: positive for SARS-CoV-2. As soon as Webasto’s C.E.O. found out, on Monday afternoon, he called the local public-health authorities at the Bavarian Health and Food Safety Authority. “It was a bit of luck for Germany that the first case was in Bavaria,” Merle Böhmer, an epidemiologist who works on a seven-person task force in the Bavaria office, told me.
According to Böhmer, Bavaria, with thirteen million inhabitants, is the only federal state in Germany with such a rapid-response task force; it was put in place in 2014, during the Ebola epidemic. Two days after the country confirmed its first case of COVID-19, Böhmer’s team sent a group of doctors to Webasto to swab employees—fifteen more tested positive. Every high-risk contact at the company, which ended up being more than two hundred people, was placed into a strict two-week quarantine. “We were able to contain this outbreak,” Böhmer told me. “And that granted Germany, I think, two to three weeks of time for preparation.” Munich did not go into lockdown until nearly two months later. By that time, residents had seen the virus’s potential in northern Italy, about a hundred miles away. They were easily persuaded to stay at home.
Germany, like the U.S., is a hub of global travel, and the supply lines for its auto-manufacturing industry are intimately connected to China. It’s also a federal system, designed in the postwar era to prevent the concentration of power in Berlin. When I initially e-mailed the Robert Koch Institute for information about how contact tracing had worked in Munich, they referred me to the local department. “RKI does support local health authorities when it is asked to,” an R.K.I. rep wrote to me, “but the local health authorities are always the ones in charge here.” With the biggest pharmaceutical industry in Europe (and a medical technology industry second only to the U.S.), Germany had developed its first diagnostic test in mid-January, and scaled up to a robust testing infrastructure by the end of February. But when it comes to containment, testing is only as good as the ability to follow up with swift tracing measures. This method was successful in Japan, for example, which, with its teams of contact-tracing “cluster busters,” has managed one of the lowest death rates in the world without resorting to draconian restrictions. “It’s crucial in such a situation to talk to other experts, to exchange information very quickly and to get other opinions,” Böhmer told me. “You have a globally spreading disease which was not known until December last year. You have to be open-minded and get experts in and combine all the expertise.”
Much speculation about the factors behind Germany’s relatively low death rate has pointed to high public-health spending. As a recent Deutsche Bank report observed, in many cases, the underlying and pre-existing conditions that, elsewhere, have led to bad outcomes with COVID-19 are often diagnosed early and well treated in Germany. But robust access to health care can’t fully account for how little of the country’s I.C.U.-bed capacity, in the end, proved necessary. Wolfgang Greiner, a health-care economist at the University of Bielefeld, told me, “It’s not so much that we cared for so many patients, because, at the end of the day, we haven’t had so many as we expected.”
The government made a broad effort to encourage sick patients to first contact their primary-care doctors and to avoid overloading the hospitals. A friend who worked in the intensive-care unit at a Berlin hospital told me that, because the facility remained well under capacity, its doctors were able to spend several hours each day carefully tracking and calibrating the respiratory treatments of each individual patient. A number of German cities came up with other innovative interventions—a program in Heidelberg, which became known as the Corona Taxis, sent teams of doctors to visit patients in their homes, monitoring the advance of pneumonia and treating them with oxygen to prevent the need for hospitalization. These were all small, local efforts. But, with a disease that is highly localized, they amounted to an effective means of keeping Germany’s death rate well below those of some neighboring countries. Many experts I spoke with speculated that the early containment efforts in Munich, and other cities, allowed Germany to stay in front of the virus’s spread rather than having to play catch-up. Lockdown came at the right moment.
Angela Merkel, the German Chancellor, who has a Ph.D. in quantum chemistry, has been praised, both inside and outside Germany, for her focussed, apolitical, data-driven management of the pandemic. Even as regional leaders across Germany bickered over shutdown procedures, with some of them vying for national attention in the face of upcoming elections, Merkel effectively held them in line. She has also urged exacting regulations as the country gradually reopened, which it began to do only when infections were below seven hundred and fifty on average per day: all passengers on flights entering Germany must fill out a form stating which seat they occupied, and where they will be staying; restaurants in Berlin, which have moved most of their dining outside, have been strongly encouraged to take down the names and telephone numbers of all patrons, and note where each of them sits. If more than fifty out of every hundred thousand test results in a region come back positive, localized “emergency brakes” will re-impose social restrictions, which has already happened in the German state of North Rhine-Westphalia, where an outbreak sent seven thousand workers at a meatpacking plant into quarantine. (The state’s Higher Administrative Court cut the renewed quarantine period short in response to a legal objection.) A video of Merkel stoically explaining the “R-naught” went viral.
People going about their business in downtown Munich, in late May.
Merkel’s performance, however, hardly excuses shortcomings elsewhere. “There was an entire narrative of ‘America could never do this because we are so independent-minded,’ ” Ashish Jha, the director of the Harvard Global Health Institute, told me. “And I’m like, ‘I know a lot of Germans—they’re pretty independent-minded.’ ” Laura Olbrich, another doctor on Hoelscher’s team, is originally from Duisburg, a struggling post-industrial town in northern Germany. She speculated that scientists knocking on doors wouldn’t work so easily there, especially if they were accompanied by police officers. Even in Munich, careful precautions have been taken to establish public trust: after the initial knock, the team members explained who they were and what they would be doing. Residents don’t have to immediately agree to participate, as a separate team would return to take the first blood samples. The study also attracted a great deal of press attention, so residents often already knew about it. “There was a woman that actually screamed, ‘I was hoping so much that you guys would come to my door!’ ” Olbrich told me. “ ‘This is really funny, like winning the lottery.’ ”
The study in Munich is, among other things, testing for genetic indications that may help explain why some people get extremely sick from COVID-19, and others have only a mild disease course. (Already, scientists have found that there is some evidence that certain blood types may play a role.) “We see that there’s a correlation between whether you have symptoms and your level of antibodies,” Hoelscher said. “If people have COVID—very mild, asymptomatic or whatever—some of them seem to have less antibodies than those who are severely sick.” Many people who’d had the virus but only a mild case, in other words, appeared to have a comparably weak immune response. So far, no one could say exactly what that meant. But, in either case, the antibodies appeared not to last, which suggests a second infection could be possible. “That’s a bad sign for a vaccine,” Hoelscher told me.
At the very least, to provide ongoing protection, an inoculation that relies on the antibody response would need to be routinely readministered, perhaps every two years or so. The cellular immune response to COVID—so-called natural-killer cells—which can reduce the severity of a disease course, lasts longer, but it does not appear to provide protection against infection. Eventually, an effective vaccine, Hoelscher thinks, might try to combine both immune responses. “The optimal outcome would be that we have something that is protective,” Hoelscher said. “But most researchers do not believe that we will get a sterilizing immunity. So having immunity that prevents a severe case of disease is already something quite good.”
The day after I visited Hoelscher’s lab, I met Jakob Reich and Lara Schneider on a deserted street lined with slatted wooden fences and carefully angled hedges. This was where, a few weeks earlier, Isabel Klugherz had completed her random walk and wound up at her friend’s door. Reich and Schneider, both in green scrubs and droplet-filtering masks, carried a large yellow plastic bin and a folding chair. In the entryway of the building, one of the participants suggested that, since the weather was nice, they set up in the back yard. The open air would reduce any unnecessary risks.
The protocol for the home visits is, unsurprisingly, strict. The priority is to prevent researchers from bringing anything in or taking anything out. They are instructed not to touch anything. One researcher reads aloud all the information requiring consent, while the other pulls on a gown and gloves. After the participants have signed off, the gloved researcher retrieves the papers and slips them into a plastic sleeve held out by the non-gloved researcher. The gloved researcher sets up the folding chair and lays out a protective sheet on top of the best surface available.
Some of the medical equipment that is used in home visits.
The tenants, four grad students, had a picnic table stored in a shed behind the building, and they unfolded it in the middle of the yard. A European Union flag was draped across the back door, concealing stacks of books and empty beer bottles inside. Next door, two children bounced on a trampoline as they watched the scene unfolding at their neighbors’ house. Reich inserted a cannula into the crook of the first subject’s elbow, and then followed up with a finger prick. (The team hopes that participants will eventually be able to collect their own samples with a finger prick at home.) Feeling a little woozy, one of the students, a master’s candidate in physics, lay on his back, knees in the air, in the shade on the other side of the bench.
I asked the study’s newest participants what their reaction had been to masked medical students showing up at their door; they shrugged nonchalantly. It was exciting to be a part of this massive community effort, they said, and it was also a kind of free civic service, delivered right to your home. Reich and Schneider told me they were frequently approached while walking through Munich by people wanting to be included in the study. Each of them had felt, more or less, a similar sense of enthusiasm. Early on in the pandemic response, both of them, though not yet accredited doctors, had volunteered to work in the hospitals. In the end, they weren’t needed. But travelling through the city, visiting people in their homes, collecting data on the patterns of the disease had offered them another way to contribute. “In this situation you can’t keep your ears shut,” Schneider said. “It’s strange to see history happening.”
Elisabeth Zerofsky
