by Katja Wolthers, clinical virologist at Department Medical Microbiology, Amsterdam UMC/AMC.
May 18. Only one positive patient in the late-night run, between over a hundred negative test results of the last days in our hospital laboratory. SARS-CoV2, causing Covid-19. It’s like my life as a clinical virologist suddenly became all about just one virus. Did I think I had seen it with the pandemic flu of 2009? Did I think the Ebola outbreak of 2014 was the worst I would ever see? Maybe it was, but SARS-CoV2 is the only virus I’ve seen so far with such an impact on daily life for people everywhere around the planet.
When at the beginning of January a colleague told me what went on in China, I could not have imagined what was in front of us. It was not the first time a new virus started causing mayhem somewhere, and most of the times it’s either contained or it dies out. Not this time, and the chain of events happened so fast that I can hardly recall the timelines anymore. We had Italy, carnival, ski holidays, case definitions, doctors calling us with suspected patients to be tested. A matter of time and we knew it.
End of February, the first 2 positive patients in the Netherlands. While I was waiting on confirmation of our first positive test of “the Diemer patient”, I was watching the first positive patient from Tilburg announced in that special television broadcasting on corona. And the rest is history, as they say.
Quick search on Covid-19 in PubMed: >10,000 articles. Covid-19 and organoids: 5. Covid-19 and Organ-on-Chip: zero. But I know there is at least one paper where a Lung-on-Chip was used to study virus pathogenesis and antiviral responses of both Covid-19 and influenza. This paper shows that OoC technology can be particularly useful as a tool to better understand the pathogenesis and to quickly test existing antivirals in a physiological system.
The technology is available, how come it’s not implemented in virology on a much larger scale than what we see today in the Covid-19 papers? As a clinical virologist, I like studying virus infections in humans. I am a big fan of human organoids, and therefore me and others formed this EU network OrganoVIR, Organoids for Virology (organovir.com), a training network to propagate application of organoids and 3D cell cultures in virology research.
Brain organoids in a dish.
Photographer: Ivan Pel for ZonMw.
In my research group we work with gut organoids, airway cultures and brain organoids, but not with OoCs. Maybe virologists favour organoids because they are closer to what we are already using in the lab, and we welcome organoids because they add something new: real human tissue in the lab! OoCs containing cell lines are therefore not that interesting since we had that already. We want primary tissue, and preferably in an open system such as transwells, not in a closed chip device that we can’t manipulate. It might be that I don’t fully understand what is possible with OoC technology, or maybe OoC developers do not fully understand what I as a virologist need?
I believe that if we bring together the wonderful expertise in OoCs with the principles and practices known to virologists, we can design better tools to understand virus spread and to swiftly test antivirals, making us ready for the next pandemic.
But what we need right now is to get the last Covid-19 patient out of the intensive care. Not there yet, but on the way, hopefully. I go back to my test results for the day.