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When SARS ‐CoV‐2 comes knocking on your lab door

2020; Springer Nature; Volume: 21; Issue: 7 Linguagem: Inglês

10.15252/embr.202050946

1469-3178

Howard Wolinsky,

Biomedical and Engineering Education

Science & Society15 June 2020free access When SARS-CoV-2 comes knocking on your lab door Individual scientists’ experiences during the pandemic Howard Wolinsky Corresponding Author Howard Wolinsky freelance journalist [email protected] Chicago, IL, USA Search for more papers by this author Howard Wolinsky Corresponding Author Howard Wolinsky freelance journalist [email protected] Chicago, IL, USA Search for more papers by this author Author Information Howard Wolinsky *,1 1Chicago, IL, USA *Corresponding author. E-mail: [email protected] EMBO Reports (2020)21:e50946https://doi.org/10.15252/embr.202050946 PDFDownload PDF of article text and main figures. ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinked InMendeleyWechatReddit Figures & Info SARS-CoV-2 has had an enormous impact on research and scientists, whether they study viruses or not. Some have caught the disease, struggling with fevers and strained breathing. Most researchers, except those who work on COVID-19, have been sent home, only venturing outside to pick up medications and food, while coping with shortages of toilet paper, beans, and flour. Mice colonies had to be “sacrificed” to save costs. Cell lines have been destroyed. Many scientists said their work has been set back 6–12 months—even before they can reopen the doors to their laboratories. The pandemic has dislocated the careers of postdoctoral and doctoral students who can no longer run the experiments they need to complete their theses. Students and postdocs whose contracts run out are facing a job freeze that could delay into next year or beyond. Many scientists said their work has been set back 6–12 months—even before they can reopen the doors to their laboratories. Following are snapshots of what molecular biologists have been facing during the COVID-19 pandemic. Return to the laboratories in the empty streets of Madrid The streets of Madrid were nearly devoid of traffic save for a few people on the sidewalks. Molecular biologist Balbino Alarcón Sanchez said the vistas reminded him of the paintings of Madrid by the Spanish artist Antonio López García. Now, the painter would not need to rise at dawn to see the deserted streets of Madrid, the epicenter of the coronavirus outbreak in Spain, which was second only to the US in April in terms of the number of COVID-19 cases. The streets were desolate all day, and the air was clear of pollution. Alarcón saw eagles, falcons, and rabbits freely roaming the skies and roads. His colleagues saw wild boar on the campus of the National Research Council of Spain (CSIC), University Autónoma, north of Madrid. “All these animals that we can see now were there already”, Alarcón said. “So, if we humans disappear – we are not in this world any longer as a species – the animals will be there”. Alarcón has one of the rare permits to work in his laboratory. He was developing antibodies against the coronavirus with a €150,000 grant from his institution and more forthcoming from the Ministry of Health. The funding has enabled him to extend the contracts of a postdoc and two students—about a quarter of the staff in his laboratory—for 6 months. Until he started this research, Alarcón, like most other researchers and virtually everyone else except hospital and public safety workers, was quarantined. In fact, he had a confirmed mild case of coronavirus that only affected him with a brief cough and a low-grade fever. His girlfriend Tina Sierra, a banker, fared worse and was sidelined for 10 days. “She had a really mild fever, between 37.5 and 38.5 celsius, no more than that, and a bit of a cough. And myself, for 1 day, I had 37.5 degrees, a very, very small fever”, he said. “It was like a cold for me and a flu for her”. Alarcón is convinced that the quarantine saved lives. “Without the quarantine, everybody would have been infected. Although most people in my lab are theoretically not in a group of risk, one never knows”, he commented. “Indeed, a PhD student in my lab has Chronic Variable Immunodeficiency. He could have been in trouble. Fortunately, he was the first to stay at home and avoid contacts”. While on lockdown, Alarcón worked on some papers with freshly produced data and stayed in touch with students via email and WhatsApp. He said most of his doctoral students and postdocs are working from home, analyzing data: “Of course, there is going to be a delay in their projects to present a thesis or to write papers for their CVs. But I hope that they will be able to return to their work [by June]”. While on lockdown, Alarcón worked on some papers with freshly produced data and stayed in touch with students via email and WhatsApp. An encounter with coronavirus Hisse Martien van Santen, an immunology researcher at the Centro Biologia Molecular Severo Ochoa in Madrid, developed a fever above 39C and a cough in late March. While his wife and daughter came down with a milder form of the infection, van Santen was admitted to the hospital de la Cruz Roja in Madrid where blood analyses and chest X-rays by the emergency staff showed a bilateral pneumonia, reduced lymphocyte count, and strongly elevated inflammation-associated markers. He never underwent a throat or nasal swab. “There's a specific pattern of lung damage that differs very much from normal pneumonia. That, together with the blood analyses, is, from a clinical point of view, sufficient to establish that somebody is infected with coronavirus”, he explained. Does van Santen believe hydroxychloroquine helped him? “Well, as a good scientist I cannot say yes nor no”, he said. While in hospital, he was given several drugs to help fight the virus. One was hydroxychloroquine, the controversial antimalarial drug used to treat lupus and rheumatoid arthritis. US President Donald Trump, who has a vested personal interest in the drug, publicly recommended hydroxychloroquine based on the reading of a flawed French study and in May announced he was taking it. It triggered a rush on supplies as physicians self-prescribed the medication in the USA and elsewhere. Does van Santen believe hydroxychloroquine helped him? “Well, as a good scientist I cannot say yes nor no”, he said. “I guess I'm sort of part of a clinical trial, a worldwide clinical trial in a certain way”. He was also given Kaletra, a mix of anti-HIV protease inhibitors, along with azithromycin, an antibiotic with immune-boosting properties. “At the time of my admission to hospital, data on the usefulness of treatment with hydroxychloroquine and Kaletra were still not very solid, and no other successful treatments were available”, van Santen noted. “These were a few of the drugs available where at least some in vitro data showed effect on viral replication. As such, the medics at the hospital and elsewhere in the world were providing at that point the best available care possible”. “After about a week, the fever came down, and things started getting better. The treating physician checked the sounds in the lungs via stethoscope, and he said the lung function seemed to be starting to recover well”, he said to a reporter a few days after his hospital release. Van Santen said the experience raised many questions for him about coronavirus. “It's not clear what the corona infection really does with your body, whether it's just plain pneumonia, or whether it's actually an immune response – the degree to which the immune system reacts causes many of the pathologies associated with this infection”, he mused. “Either my immune system was lousy at getting rid of the virus, or maybe I had too strong of an initial reaction which gave rise to various complications”. Racing home to the “red zone” Cosimi Baldari, a researcher and chair of the Department of Life Sciences at the Università degli Studi di Siena, Italy, went to the Florence airport on March 1 for a reunion with her children in Sydney, Australia, where her oldest son Andrew lives. There were only 10 cases of COVID-19 in Tuscany when she and her husband left. “And, then, out of the blue, 2 days later, we opened the newspapers and it was frightening”, she recalled. “During the whole of our 2-week stay, it was scary because every day there was an exponential curve in the growth of this virus. In the north, there were thousands of deaths that were starting to occur, and then the disease spread all over the place. On March 10, they started a complete lockdown, the so-called ‘red zone’”. Australia was having problems of its own as people started to hoard toilet paper. “That's quite a feat to accomplish in Sydney”, Baldari said. “The Australians were crazy about this toilet paper business. You couldn't find a single roll of toilet paper anywhere”. Meanwhile, the family stopped speaking Italian in public to not draw attention to themselves, and they worried about how to go home. Baldari said several airlines had canceled their flights for March 17, when they planned to leave Sydney and routes were tightening for international travelers. “We had to pass through Singapore. Singapore had closed borders”, she recalled. “So instead we had to go through Tokyo to another route. And the final message was that the last flight – one from Munich to Rome – was canceled altogether, and they couldn't rebook us anywhere else”. Baldari said international airports such as Munich's are usually bustling with people in a hurry. “But this was something really surreal. It was like living in one of those science fiction stories”, she described her experience. “These airports like Tokyo and Munich, which are usually buzzing and noisy, were just deserted. Nobody was there. Just a very few gates were open, where there were people trying to get back home. All the shops were shut, and there were just a few attendants with their masks and gloves on taking care of routing the people to their gates and so on”. In the end, she and her husband got lucky and booked the last flight to Rome. They finally got home to Siena on March 19, more than 50 h after leaving Sydney. After arriving home, Baldari and her husband went on a 2-week quarantine and were not allowed to leave home even to shop for food. After that, they simply went on lockdown like everyone else. [Baldari] said some defenses are being conducted on Zoom and that, once the lockdown ends, masters and doctoral students may have to take on non-experimental projects. Baldari, who studies lymphoproliferative immunodeficiency, was allowed to visit her laboratory infrequently to check on cell lines and mice. “Otherwise, we are at home”, she said. “Ongoing projects are just on standby, and we hope at some point to start on that again. I hope the funding agencies are going to be open to extensions”. Her new crop of Master's students usually starts in March. But the lockdown has kept them out and in financial trouble. “We had the possibility of freezing their salaries so that they would have the time later”, Baldari commented. “As the supervisor, I did not choose that option because I thought it was unfair because it was not their fault that they couldn't do the work and many of them – the majority are relying on their salary to keep their flat and to live. I could not deprive them of their living resources. So I'll try to help them with my funds to finish up later”. She said some defenses are being conducted on Zoom and that, once the lockdown ends, masters and doctoral students may have to take on non-experimental projects. “We finally have time to work without stress. So, we are peaceful at home”, Baldari summarizes her situation. “We can write papers without having continuous interruptions or phone calls and meetings and whatever. But then at some point, you don't have any result to write anymore. So, you only can write whatever you have accumulated until then”. Strangers in Paris At the end of January, Juan José Sáez, who then was finishing his doctoral studies in molecular biology at Universidad de Chile, attended the NIF (Network of Immunology Frontier) Winter School on Advanced Immunology in Osaka, Japan. He spoke to a colleague who had researched another coronavirus, SARS (severe acute respiratory syndrome) that caused an epidemic in 2002. “She was reassuring. She said she didn't consider this new coronavirus to be important”, Sáez said. “I believed her and assumed the same view that it wasn't so complicated, that it wouldn't escalate so quickly. I never expected it to be so bad”. Sáez was stuck at his place with his family in a new city, where they did not know a soul. Just a month later, Sáez and his wife Claudia and their 1 ½-year-old son Dante arrived in Paris where Sáez was beginning his postdoc in the laboratory of Claire Hivroz at the Institut Curie. He started meeting his laboratory mates and was planning experiments to study the role of protein trafficking during T-cell activation. They settled into an apartment in Massy, a southern suburb about 30 min from the city. “Then, the virus started to get out of control in France, so they were talking about the lockdown, and Monday the 16th they told us to not go to the lab, and then on Tuesday they started the official lockdown”, he recalled. His work, along with that of the rest of the group, was shut down. There were other problems as well. Producers of reagents shut down to protect their employees. Sáez had been applying for funding for his work, but the funding offices were closed. Sáez was stuck at his place with his family in a new city, where they did not know a soul. “I was able to help Claudia at home with Dante. We took turns taking care of the kid”, he said. They stayed in touch with their families in Chile via Skype. “Every week, we have seen different problems. The first week was funny with the toilet paper crisis. They were out of toilet paper in the supermarket. So weird”, he joked. He was shocked to find aisles empty of flour, sugar, rice, noodles, packaged bread, and toilet paper. Now, Sáez keeps himself busy with childcare and regular laboratory meetings on Zoom and a journal club to discuss what's new in the scientific press using Microsoft Teams. They held meetings to share their latest results—until they had no new results left to discuss. The group continues to share ideas and new publications. “We have a ton of ideas but no way to start working on them”, Sáez said. Catch-22s in the year of a pandemic Like so many other scientists, Janis Burkhardt, Professor of Pathology and Laboratory Medicine at Children's Hospital of Philadelphia and The University of Pennsylvania, had to close down her laboratory, which studies the actin regulatory networks that control immune cell function. “We had to sacrifice a lot of our mice and keep just those that are irreplaceable. It's understandable because they want us to keep the animal husbandry requirements and costs to a minimum”, she said. “The trouble is that it will cost us a lot of time when we do get back to work”. Burkhardt estimates that it will take 6 months to a year to restore mouse colonies once their laboratories are reopened. But the shutdown has even impacted finished work. “We also had a paper – that's probably the most heartbreaking thing from a personal research standpoint – that had been already held up for a year because of a technical problem”, Burkhardt explained. “We solved the problem and resubmitted the manuscript, but just before the shutdown, it came back from the journal asking us to do a few minor things. It will only take about 10 days of work to complete that paper, but we can't because the lab isn't open”. Burkhardt added a 6-month delay also impacts on trainees as they need to conduct research and write theses. “My PhD student has been fortunate. He's finished all his experiments and is home now writing his thesis. It's worked as well for him as humanly possible”, she said. “But I have heard of cases where students have defended their thesis and then their committee wanted them to do a few more experiments. Those students are truly stuck until they can get back into the lab”. Burkhardt herself is “incredibly busy” working from home, writing three papers and consulting weekly with her trainees, and talking to colleagues. “I have 6 h’ worth of Zoom calls ahead for me today”, she said. … once or twice a week he visited the laboratory to care for the surviving rodents after he had “sacrificed” about half of the mice and used bleach to destroy cell lines at the lockdown. “The two-body problem” It was late April and COVID-19 had claimed Philadelphia as a new “hot spot”, after the pandemic's epicenter in New York City. Nathan Roy, 36, who would soon finish his postdoc in Burkhardt's laboratory, rode his bike on nearly car-free streets in Center Philadelphia. The few pedestrians he passed all wore face coverings. Roy had already finished most of his experiments and laboratory work, but once or twice a week he visited the laboratory to care for the surviving rodents after he had “sacrificed” about half of the mice and used bleach to destroy cell lines at the lockdown.§ Roy and his wife Allison, a gynecological oncology fellow at the University of Pennsylvania, had a “two-body problem”: both were trying to find jobs at least in the same city and, ideally, at the same institution. One university medical center had extended a contract to Allison, who is pregnant and due in July, creating in effect a three-body problem and extra concerns and precautions for her safety at the hospital. Roy had a hot prospect for an academic job at the same institution in March. Then, he got word in April that because of COVID-19 all jobs like his were immediately frozen. “My position is now completely on hold indefinitely. They don't even know when it will come back. But I was a top candidate, and I had really good feedback from them”, he said. Meanwhile, Roy said his department at Penn agreed to continue funding until the end of the year. He said there are 300 academic institutions listed online that have frozen job hirings, putting the careers of future academics on hold. “There's a lot of people like me who are probably ready to make the transition into the job market, but now have nowhere to go. So I'm going to be in the applicant pool next year with all the people who applied this year”, he said. “A lot of universities are not hiring. We'll see how it plays out”. In the end, he expects his family may move regardless, so his wife can take her job: “It's most likely, because of the sort of high-powered nature of her job, that we will go anyway. She has a pretty solid financial outlook”. Locked down in Spain Carla García-Fernández, a third-year year doctoral student at University Pompeu Fabra in Barcelona, Spain, is one of the lucky biologists. She is studying bioinformatics, so she has been able to work on her projects at home while on lockdown. Garcia-Fernandez added the deadlines for thesis submissions have been extended, but not the funding of the students. Spain has been hard hit by the COVID-19 pandemic. The first patient in Spain was diagnosed on January 31. The first person in Garcia-Fernandez's region, Catalonia, was diagnosed on February 25. Things deteriorated quickly after that. “Cases and deaths have followed an exponential growth until Spain became the country with the second-highest cases in the world”, García-Fernández commented. “Hospital's intensive care units totally collapsed. New temporary ICU units have been built in a few weeks and public buildings are converted into hospitals or morgues”. Since, Russia has had the second-highest number of cases after the USA. A total lockdown of the country started March 15, and it was extended until April 26. “Our lab, as well as all the labs of the department, were shut down from the 15th until the end of the lockdown”, Garcia-Fernandez said. “PhD students who do experimental research are going to be one of the first to go back to the lab once the lockdown ends, with all the possible risks that this implies due to the fear of the consequences this pause will have on their theses. We have to take into account that this is not only a pause in an individual experiment, but in most of the scientific facilities and companies and the effects are going to last a lot more than the quarantine extension”. She noted on May 8: “The lockdown is still going, but from Monday, May 11th, we are going to be able to come back to the labs, in shifts of three people for half a day. They are implementing different safety protocols for all the buildings, such as mandatory face masks delivered at the entry, and non-use of the elevators or water fountains”. Garcia-Fernandez added the deadlines for thesis submissions have been extended, but not the funding of the students. “If we want to use this extended period, we will have to do it without payment”, she said. §Correction added on 16 July 2020, after first online publication: the sentence has been corrected. Previous ArticleNext Article Read MoreAbout the coverClose modalView large imageVolume 21,Issue 7,03 July 2020This month's cover highlights the article EphA2 Phosphorylates NLRP3 and Inhibits Inflammasomes in Airway Epithelial Cells by Ao Zhang, Junji Xing and Tianliang Xia, Zhiqiang Zhang, Mu-Sheng Zeng and colleagues. The cover is inspired by an ancient Chinese legend: long ago, there were ten suns. Each day God placed one sun in the sky to give light and warmth to life. However, the suns disobeyed and decided to all shine at one, scorching the forests and drying the ground. To save the earth, a hero named Hou Yi shot down nine suns with his gigantic bow, leaving just one sun to provide normal heat and light. In the illustration, the archer Hou Yi represents EphA2, arrows represent tyrosine phosphorylation, and suns represent NLRP3 inflammasomes. (Scientific image by Mu-Sheng Zeng, Ao Zhang and Lei Fan, Sun Yat-sen University Cancer Center.) Volume 21Issue 73 July 2020In this issue RelatedDetailsLoading ...