There’s a lot of really interesting work left to be done in this area. In our company’s other life we’re involved in CAR-T research, which involves exploiting natural pathways in our immune systems to target them at cancer cells. It’s a super exciting area of research and is bleeding edge in terms of breakthrough therapies coming into the clinic. These therapies[0][1] cure upwards of 90% of what would otherwise be incurable cancers, but they also induce severe inflammatory responses (cytokine storm) which results in respiratory failure and neurological adverse events (that’s a nice clean clinical way of saying putting them in a coma).
I think we're up against many of the same challenges everyone else (Roche, Abbott, et al.) is up against. At the end of the day if we could all wave a magic wand and fix supply chains we would. Technically, we (the collective diagnostics hive-mind) know how to detect viruses. We haven't yet figured out how to deploy these technologies on scales orders of magnitude above our baseline implementations.
I agree that reliable antibody tests will be a help to policymakers in how they model the continued stay-at-home posture and begin to open things back up.
I think the jury is still out on 1. The persistence of the antibody response post-infection and 2. the neutralization/protection afforded by these antibodies.
The development of antibodies requires either a vaccine or you to be infected. The rate of antibody protection in populations is certainly rising, but to get to meaningful levels of herd-immunity it would require all of us to get infected, lets say ~70%+ (obviously problematic), or rapid and major strides to be made in vaccination.
Anecdotally, significant therapeutic, vaccination and diagnostic approaches are required to effectively respond to COVID-19. Its been incredible to be a part of such a widespread, organized movement within both the healthcare and tech communities as we collectively mobilize to respond.
Good sleuthing! As you suspect we functionalize the our sensor surface to specifically bind the virus. We've partnered with a therapeutics company developing highly specific monoclonal mAbs against SARS-CoV-2 which we leverage in our diagnostic platform.
Couple of things at play here. First is we are developing a non-PCR based viral detection test. Many of the molecular tests approved rely on many of the same ancillary components (RNA extraction kits, flocked nasal swabs, viral transport media) as well as instrument systems. What we are developing is a non-molecular based test to directly detect SARS-CoV-2 particles in fluids, specifically saliva.
We've just begun our clinical testing so don't have specificity/sensitivity metrics yet, but will be sharing them when they're available.
Hi there. We are developing a saliva (e.g., spit in tube) type test. There are a couple of reasons for this including:
- supply chain issues with flocked nasal swabs and viral transport media
- enable self-sampling limiting healthcare workers SARS-CoV-2 exposures and PPE utilization
I'm not familiar with the acronym PSM. Can you expand?
Are you familiar with the work of Dr. Chui at UCSF? His group has done some really cool work using mNGS to detect/diagnose emerging/rare infections in critically-ill patients with refractory encephalopathy
Test complexity (sample prep, test workflow) is a real challenge to achieving testing scales at orders of magnitude above what is presently available.
We should hopefully have boring old ELISA antigen tests shortly, thanks to Abbott and many of the other folks we've all heard from. The real challenge is scaling testing beyond what can be reasonably implemented from central lab facilities.
A regular ELISA/immunoassay is: surface->Ab->protein<-Ab+signal. In school these are taught as "sandwich-assays". Basically you have one antibody to bind your molecule of interest to your substrate, and then another second which binds the bound molecule... which has been bound to the surface. This second antibody is decorated with an enzyme which will do something fancy (color-change) or a fluorescent protein to light-up if we shoot it with a laser. SPR is a label-free approach which results in an optical response in real-time as molecules associate with the SPR sensor. Detection is then a function of how long you need to let things bind to the sensor before your ability to detect the signal optically.
Sounds like your undergrad kid has been paying attention in class...
This is one of the implementations we're actually developing. One of the challenges with the implementation of testing on this scale is not necessarily on the technology/assay but on implementation. How do you reasonably test millions of folks each and every day, or said another way actually get millions of nasal swabs, saliva, etc on 384 well plate?
I think our ultimate approach is much more akin, albeit with a bit more sensor voodoo magic, to a at home pregnancy test than 384-well plate qPCR tests at central labs.
Hi, Walker here, one of the PreDxion Bio co-founders. Heres a some more information on the technology underlying the test we are developing: https://pubmed.ncbi.nlm.nih.gov/25790830/.
Unfortunately, up until about a month ago us like many folks, were blissfully minding our business developing a rapid point of care cytokine detection platform for use in monitoring patients experiencing certain immune responses following cancer immunothereapies, you can read more here: https://pubmed.ncbi.nlm.nih.gov/31597044/.
Currently, we are very much focused on techical/clinical validation. We will have many more details to share on our approach, the technology, as we continue to move things forward.
Hi, Walker here, one of the PreDxion co-founders. Up until recently we've been focused on developing our technogy as a point of care biosensor for us in patients experiencing dysfunctional immune responses (e.g., sepsis, ARDS, and the immune responses induced by certain cancer immumotherapies).
The technical implementation of a viral detection assay is much simiplier to implement than our quantitative, multiplexed small MW biomarker sensors... But there are certainly many other hurdles that remain as you point out as well as the additional biological uncertainty that remind around SARS-CoV-2 it's infectious course as well as our bodies subsequent immune responses.
There are certainly many hurdles left to be tackled but that's exactly what we're working towards.
0) From a clinical perspective this is data we are generating on an on going basis. Analytically this is a largely a function of the characteristics of the affinity, specificity of the capture molecule used to capture the target (viral particle). As you point out EUA gives opportunities to launch sooner... But it's still critical to validate technogies both internally and externally probably to a greater extent than the de minimus EUA reqs
1) great question. Our approach is novel which allows us to tap into new supply chains that are inherently more scalable (think semi-conductor Fab) but the trade off is execution risk.
The holy grail would be real-time targeted therapeutics to modulate our immune systems up and down in response to various cues. We’re a long way off from that but it’s an idea that’s beginning to get wider acceptance in the medical community. [0] - https://www.novartis.us/sites/www.novartis.us/files/kymriah.... [1] - https://www.gilead.com/-/media/files/pdfs/medicines/oncology...