Text: Blandine Guignier

The race for treatment

How can we move fast without sacrificing scientific rigour? It’s a balancing act for hundreds of researchers in Switzerland.

In May 2020, about a hundred COVID-19-related investigations were under way in Switzerland. These investigations, which involved patients, were launched within the space of a few weeks. This downpour of projects reflects researchers’ extraordinary response to the pandemic. “At Lausanne University Hospital (CHUV), we received more than 50 proposals in one month,” says Marc Froissart, Director of the Clinical Research Centre.

Interventional or observational?

Interventional studies are therapeutic. That means they benefit patients directly. Observational research aims to better understand the virus and its effects. For COVID-19, both types of studies are being conducted at CHUV, with priority on interventional research.

CHUV created a special work group to sift through it all. “The group analyses and approves the research projects, which are then submitted to the Cantonal Commission on Ethics in Human Research,” says Manuel Pascual, Vice Dean of the Faculty of Biology and Medicine at the University of Lausanne. “The point is to avoid repeating the same work twice and to circumvent any logistics or ethical issues.”  For example, that means preventing taking too many blood samples from the patient or overworking the healthcare staff. “Our primary concern should always be patient care.”

The work group chaired by Benoit Guery, chief physician with the Infectious Diseases Service at CHUV, has set some priorities. “We have focused on interventional or therapeutic studies, which benefit the patient directly,” he says. That is why the large-scale Solidarity clinical trial was selected, along with the CORON-ACT study (see inset). To yield any convincing results, the research must be conducted on thousands of patients, under different conditions, and throughout the duration of the pandemic, says researcher Oriol Manuel, who coordinates Solidarity for Switzerland. “It will take several months before we can publish final results. But the WHO hopes to analyse the data continuously to help treat the world population as quickly as possible in case preliminary findings are positive.”

Observational studies, i.e. without intervention on the patient, have also been approved, says Benoit Guery. “Focus was on five fundamental aspects: analysis of blood coagulation, immune response, intestinal microbiota, genetic susceptibility and antibody response.”  If therapeutic trials do not produce results, experts will need to be able to go back to studies that help to better understand the virus and its effects.

Studies put together outside the hospital to examine the social effects of the coronavirus are also included in the list of research projects. They look at, for example, how technology has helped older adults cope with social isolation.

May the fastest win

Clinical research in the era of COVID-19 is different due to the variety of subjects and the speed of action needed. “Organising studies in one month, without compromising on quality standards, is quite a feat,” Marc Froissart says proudly. “Usually clinical trials take from nine months to a year to line up, drafting protocols, identifying participating sites, looking for funding, and engaging in consultation with the competent authorities (Swissmedic, ethics committee, etc.).”

If the epidemic slows, the data collected thus far should be useful in case of a resurgence of small-scale outbreaks, similar viruses or a second wave. Clinical trials should also benefit from the collective experience, making them more effective. “For example, we would propose an observational study with several focuses. We would have different investigative approaches as part of the same programme,” Marc Froissart says. “That would make for more solid research in terms of methodology and save time in dealing with regulatory aspects, all signed off on one patient consent form.”/

When scientists whisper into the ears of politicians

Epidemic experts are influencing the decisions of executive powers, irrespective of political beliefs. Several Swiss scientists consider that the government ignored the warning signs and have criticised the way the epidemic has been handled since early March. One of them is Marcel Salathé, director of the Digital Epidemiology Lab at the École Polytechnique Fédérale de Lausanne. On Twitter and in the press, he has argued in favour of large-scale testing. To better factor in the opinions of researchers, the Swiss Federal Council created a scientific advisory committee at the end of March made up of experts from top Swiss schools, including Marcel Salathé. Medical experts are also keeping the executive and legislative powers informed at the cantonal level. For example, officers of the Grand Council of Vaud attended a videoconference with Thierry Calandra, chief of the Infectious Diseases Service at CHUV. “This first-hand information has helped us better understand the scientific basis of decisions made by the Federal Council and their application by the Council of State,” says Sonya Butera, Vice President of the Vaud parliament. “It also offered the opportunity for some parliament members to rule out any false information they may have picked up, especially on social media.”
This closer collaboration between politicians and doctors has been essential in dealing with such unknown and complex circumstances as with COVID-19, says Pascal Sciarini, a political scientist from the University of Geneva. “In drawing up federal laws, experts on extra-parliamentary committees already play a key role in normal times.”  However, it is not the role of experts to replace political debate. “After doctors were omnipresent in the media and people’s minds during the first six weeks, other experts – in economics, psychology, sociology – began voicing their opinions. And politics, based mainly on this other expertise, came back into play.”  Proof of that is the decision to reopen shops and restaurants on 11 May, based on economic factors.



Two exemples of research

Global epidemic, global response.

The World Health Organization launched the Solidarity clinical trial to test four possible drugs to treat COVID-19: Remdesivir, Hydroxychloroquine, and two equally unpronounceable names (Lopinavir/Ritonavir and Lopinavir/Ritonavir with Interferon beta-1a). Switzerland’s participation in Solidarity is coordinated by Oriol Manuel, a research physician with the Infectious Diseases Service and Centre for Organ Transplantation at CHUV. “The WHO wants to be able to conduct research in different contexts: countries both in the middle of the health crisis and those already past the peak of the epidemic, both rich and developing countries, as well as in different kinds of facilities, both country hospitals and university hospitals.”  Since the end of April, each new patient hospitalised at any one of the 17 participating facilities in Switzerland is included in the study, as long as they have provided consent.

​Drug storm

Another project selected by CHUV is the CORON-ACT study. “Conducted with the University Hospital of Bern, this study analyses the effectiveness of Tocilizumab,” Marc Froissart explains. “This drug prevents the secondary aggravation in COVID-19, which generally occurs around the seventh day after onset of the illness.”  The immune system counters with a strong reaction, causing a so-called “cytokine storm” (excessive production of cytokines, proteins naturally secreted by immune cells), which often leads to acute respiratory distress syndrome.