researchers at UC San Diego refocus to address COVID-19 in myriad ways

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For this episode of the Microsamplify Podcast from Neoteryx, host Christa Nuber spoke with Mohit Jain, MD, PhD, an Associate Professor of Medicine and Pharmacology at UC San Diego. Dr. Jain directs the Jain Laboratory at UC San Diego, which has recently pivoted to expand its focus beyond understanding the underpinnings of non-genetic disease to also understanding the causes, influences and impacts of COVID-19. Dr. Jain told us how remote microsampling is supporting these efforts, and discussed the many ways he and his lab colleagues are collaborating with other researchers at UC San Diego and beyond to battle SARS-CoV-2.

Neoteryx: Hello Dr. Jain, and welcome to the Microsamplify Podcast from Neoteryx. You and your colleagues at UC San Diego Health Sciences are working on several COVID-19 studies, and we’re excited to learn more about all that you are doing. Thank you for joining us today!

Dr. Jain: Thanks, it’s my pleasure, and thank you for your time today.

Neoteryx: Before we discuss your COVID-19 studies, can you give us some context by telling us about your role at UC San Diego and the type of research that your lab does? 

Dr. Jain: My lab is based at UC San Diego in the Health Sciences Medical School. What our lab focuses on is understanding what we term as, “The Non-genetic Landscape of Disease.” We have a pretty good handle on, through next-generation sequencing, the genetic variants that pre-dispose to disease. This has come from millions of genetic sequences that are available around the world. However, we have very little understanding of the non-genetic causes of disease.
The issue is that these are not problems that we can sequence our way out of. Rather, the way we think about these exposures, whether they be dietary, microbiome, a toxicant—essentially everything you are exposed to over the course of your life—is that they may influence your health through the introduction of small molecules into circulation. In our lab we operate mass spectrometry systems that allow us to assay those molecules from blood samples, and map those molecules back to underlying etiology to understand which ones come from microbes, diet, or toxicants, and also which molecules are geographically influenced. And then, ultimately, understand how these molecules influence disease over time. This is what our lab has been focused on for the past decade.

Neoteryx: You and your colleagues at UC San Diego have pivoted quickly to adjust your research focus to address COVID-19. I know that our company, Neoteryx, provided you and your research colleagues with our Mitra^® microsampling devices for remote blood collection. Can you explain how you are using the Mitra blood samples you are collecting for COVID-19 research work in your lab to meet new demands posed by the coronavirus public health crisis?

Dr. Jain: We actually started using the Mitra devices from Neoteryx several years ago, because we were very interested in collecting biosamples in regions of the world in which refrigeration and centrifugation are not readily available. We were interested in collecting samples in the developing world and in low-income settings to understand the underpinnings of nongenetic disease. At that time, we began exploring the use of blood spots and other similar systems that allow remote blood collection and storage at ambient temperature environments, as well as mailing to a centralized laboratory for analysis. We began looking at the Mitra devices and optimizing our systems about two and a half years ago, and had success in doing so.

As you mentioned, several months ago the coronavirus pandemic hit worldwide, and we pivoted in order to be able to use these systems as part of our COVID-19 research. Our research at UC San Diego is divided into two basic areas. One is remote collection of samples from individuals for doing serologic testing—measuring IgG and IgM antibodies to the SARS-CoV-2 virus—as indices for exposure and potential immunity. The other is going back to our metabolomic and mass spectrometry approaches to using these Mitra devices for point-of-care and home sampling from individuals in order to understand the molecules that may influence risk for both acquiring COVID-19 infection, and subsequent outcomes related to COVID-19 infection.

I think the pandemic highlights why it is so important to be able to have remote sampling systems. Collecting human bio-samples in centralized laboratories or centralized phlebotomy centers is quite risky, given the stay-at-home orders. Being able to collect blood samples at home is absolutely essential to the worldwide pandemic effort.

Neoteryx: Are you using blood microsampling to help with UC San Diego Health’s clinical trial to assess an antiviral drug as a potential COVID-19 treatment? And, if so, how has blood microsampling contributed to that effort?

Dr. Jain: There are a number of these efforts both at UC San Diego and externally within the US and abroad in other countries that are attempting to not only understand the pathobiology of COVID-19 infection, but also to examine antivirals, antibodies and many other emerging therapeutics. With regard to these studies, there is a lot of interest in being able to use remote sampling, particularly given the stay-at-home orders and the risk of infection, and to be able to assay both serologies as well as circulating biomarkers, whether they be metabolites and/or proteins that may influence response to certain therapies. We are involved in a number of these operations through UC San Diego as well as externally.

Neoteryx: As a comparison to give our audience an idea of your lab’s “before” and “after” experience with blood microsampling — what type of technology were you using for serology studies before, and how have your lab’s workflow and serology studies changed after you began using Mitra with volumetric absorptive microsampling, or VAMS^®, technology? 

Dr. Jain: Thankfully, the adjustment has been relatively minor in that our laboratory has always done a lot of high throughput handling of bio-samples, whether they be blood, urine, tissues, etc. Typically, we handle 2,000 samples over a 24-hour period. We’ve been very used to liquid handling and other systems.

Neoteryx: Dr. Jain, you are also involved in The Microsetta Initiative, a University of California San Diego School of Medicine research effort that recently started recruiting citizens around the world to use our Mitra devices to collect their own blood samples at home. The Microsetta team is sending participants, or “Citizen Scientists,” collection kits so people can collect their specimens and ship them back to UC San Diego for analysis. Can you tell us how these samples may help you uncover crucial information about SARS-CoV-2, the novel coronavirus causing the COVID-19 pandemic?

Dr. Jain: The Microsetta Initiative is a project that is led by Dr. Rob Knight, who is a professor of medicine and pediatrics, and a professor of computer science here at UC San Diego. He is a world leader in the microbiome. Initially, The Microsetta project was borne out of a number of earlier initiatives that had been run by Rob, including The American Gut Project, and the European Gut Project.

The “Citizen Science” projects are those in which individuals sign up remotely for collection of human samples, typically fecal samples for microbiome sequencing, to understand microbial diversity around the world and how that may influence health and disease. People were signing up over a website, a fecal kit would be sent to them so they could collect a fecal sample, these would be mailed back and analyzed in a central laboratory. There is a questionnaire that goes along with it that allows us to help people understand their own individual microbiome and how that may be optimized for human health.

As in so many cases, we were interested in how the Mitra devices could help us add blood sampling at the same time that fecal samples were being collected. There have been discussions about doing this with Rob, who is a close colleague of mine, as this would allow us to not only measure microbes that were present in the stool, but also the secondary metabolites that are made by these microbes and that are introduced into human circulation. These may play a role in how these microbes affect health and disease over time. We were excited by microsampling systems that would allow us to assay microbial dried molecules. That’s why the Mitra devices were introduced into The Microsetta Kits.

With the COVID-19 pandemic, there is a lot of interest in understanding how the microbiome may influence risk of developing infection as well as response to the underlying infection. There is a decent amount of evidence in the literature that microbes within the gut and the secondary molecules that these microbes make can have a profound influence on your response to viral infection. So in the same way that our lab has pivoted, The Microsetta Initiative has slightly pivoted not only to measure microbes in the gut, but also to be able to understand how these may influence risk of SARS-CoV-2 infection. This is a worldwide initiative that should provide some key insights in understanding the microbiome and microbial dried molecules in health.

Neoteryx: I’ll be really interested to read the results because I read about a woman who presented at hospital with some kind of a gut infection which did, in fact, turn out to be a COVID-19 case and they didn’t initially interpret it as such, because it presented as an intestinal issue.

Dr. Jain: It’s estimated that 15-20% of individuals that present with COVID-19 don’t have classic fever and cough, but have secondary sequela that may include GI upset, diarrhea, nausea and vomiting. The thought is that the infection, and the SARS-CoV-2 virus, is present and quite prevalent in the GI tract, and can infect the gut epithelial cells. There have been a number of publications in the past month demonstrating this. The infection of those epithelial cells can impact the lining of the gut, which can influence gut health and alter the microbiome itself.
  
Neoteryx: You mentioned a lot of collaborators, and it’s my understanding that you’re working with a lot of external groups, and you have a lot of external interest in everything you are doing. Can you talk about the collaborators you are working with outside of UC San Diego?

Dr. Jain: Myself and a number of others at UC San Diego are working together as part of The Microsetta Initiative and also with external entities who are interested in the same questions and doing this as a consortium-based program. There are a number of entities we have spoken to and that we are working closely with. This includes individuals at the NIH, particularly at the NIEHS, which is the environmental health section of the NIH, to understand what we call “the exposome” and how that may influence SARS-CoV-2 infection.

There are foreign government organizations, including in Canada, Italy and India, that we are in discussions with to help them as part of their ongoing COVID-19 efforts. We’re discussing how to help them assay blood for serology assays as well as for understanding of metabolites and microbes. Then there are other state organizations, both in California and outside of California that are interested in being able to sample large portions of the population in order to keep an eye on seroprevalence, meaning those individuals that demonstrate IgG antibodies to SARS-CoV-2 over time. We are also aiding in those efforts.

It seems like this is changing daily in a positive way. There have been more and more individuals who are excited to work together for a common good, and we’ve been quite happy to be part of these endeavors.

Neoteryx: You are both an MD and a PhD, I believe, and you once practiced as a cardiologist. I’m wondering if as a clinician who cares for patients and as someone who also runs an analytical laboratory, do you feel that one lends itself to the other in how you’re handling these projects that you’re directing?

Dr. Jain: That’s a great question that has a complicated answer. I was trained formally as a clinician—as a cardiologist—and I absolutely loved cardiology medicine and taking care of patients. Learning to take care of patients was one of the most exciting aspects of my professional life. Admittedly, as my lab has gotten busier and my personal life has gotten busier (my wife is also a professor and we have two young children), I have learned the hard way that there are only so many hours in a day. I’ve had to give up some aspects of my professional career, including seeing patients directly. This was tough to do, but it has allowed me to have some degree of work-life balance, and also for my academic endeavors and my research laboratory to grow. I absolutely like to think that having been trained in clinical medicine allows me to see the problems in a slightly different light.

I’m very excited about the MD-PhD track for education. It is a long training period, but if you are able to make it through the entire training, it provides a very different perspective on the world and allows you to ask very different questions. I like to think that most of the questions we approach in the lab—even though they may be more fundamental around chemistry and human diversity, and understanding health from a very fundamental level—really are all based in human disease biology.

Neoteryx: Have I missed anything that you’d like to share with our audience about microsampling and your work at UC San Diego? Perhaps about how your lab is unique from other labs or if it has any special services or features you’d like to mention?

Dr. Jain: I think there are a couple of aspects of our lab that make it unique. For one, I’ve been incredibly fortunate to work with people who are remarkable, both in their individual talents and in their ability to work together to solve really large problems. We’ve been able to develop new technologies and then deploy them to answer very fundamental questions. Just the way our lab is designed, [makes it] exciting to work with others.

The vast majority of what we do is outward-facing, in that we have this very unique tool with which we can do very high throughput mass spec analysis of thousands of blood samples a day. We have a very large repository of human chemistry and human blood, which we’ve analyzed. All this lends itself to collaborations with other entities around the world. At any given time, we have two to three dozen projects that are ongoing with investigators around the globe.

When I first started my lab, I’m not sure I planned it this way, but this has become the crux of what we do—open collaboration with the scientific community. [I enjoy] being able to work with clinicians who are at the front lines collecting samples—whether from COVID-19 patients or from those in the developing world—who know their disease areas better than we will ever know them. At the same time, we can lend high throughput chemistry and really complex computational analysis to their individual problems and work seamlessly together. These are the types of projects and relationships that wake me up in the morning and make me excited to go to work!

Being able to do this with microsampling, in my opinion, is going to be transformative for the world. I would be surprised if, in a decade from now, anyone goes to a phlebotomist for a blood draw. I have no evidence for this, but these are my personal predictions. We have found that the vast majority of things can be well-assayed and well-measured in a very robust manner using microsampling systems. This removes the need to have healthcare providers in close contact [during risky times] and allows for sampling in areas of the world where refrigeration and centrifugation are not feasible.

All this is what makes our lab unique and we are always looking for additional folks to work with. Our barometer for working together is simply that if they are good people with good samples and great questions, then we are excited to jump in together and find a way in which we can collaborate for the betterment of science. If there are other individuals, laboratories, and centers out there in learning about our experience, we’re very open and happy to share our experience with microsampling systems, including the Mitra device and VAMS.

We have a tremendous amount of data that is shared in the open community that people can access. If anyone is interested in learning more, I encourage them to reach out to us. Our lab’s information is on the UC San Diego website, and also at: http://www.jainlaboratory.org.

Neoteryx: Thank you, Dr. Jain, for taking the time to speak with us about the research you are doing in the Jain Laboratory at UC San Diego. All of us at Neoteryx are excited to support your efforts so thank you! And thank you to our audience for listening to this episode of the Microsamplify Podcast, a partner to The Microsampling Blog from Neoteryx.

Image Credit: The featured image of Dr. Mohit Jain, courtesy of UC San Diego