SARS-CoV-2 (the virus that causes COVID-19) is menacing. This is a given. But, how does it affect the body and cause all the problems we are seeing? This question has launched a herculean effort in the research community to quickly learn the attack strategy and get that information out as quickly as possible. This allows others to build on that newfound knowledge, as seen with the deluge of preprints (scientific manuscripts made publicly available before being peer-reviewed).

It all begins with angiotensin-converting enzyme 2 (ACE2), a “receptor” protein that can be found on the surface of cells in our intestines, heart, brain, lungs, kidneys and arteries (Hamming et al., 2004). The protein has also been found in the liver (Paizis et al., 2005). ACE2 serves as the gatekeeper for the virus’s master key, a.k.a. the spikes on the virus’s surface (Yan et al., 2020). Once inside cells, the virus hijacks the host machinery to create more viruses (Bojkova et al., 2020).

The onslaught happens on many fronts and not just in the lungs. In autopsies of 27 patients who lost the COVID-19 fight, the virus could be detected in the heart, brain, liver and blood (Puelles et al., 2020). All places where ACE2 can be found. It was also found that ACE2 is enriched in many kidney cells, which may explain why kidney injuries are a common occurrence for COVID-19 sufferers.

Humans, however, are not sitting ducks. Our bodies put up an impressive fight, but some may be using too strong of arsenal (think nuclear bomb to take out a mosquito) and may wind up damaging the body even more – leading to death. This is what is being observed in some young COVID-19 patients who were previously healthy/fit (Glaser, 2020). The immune system mounts up a defense that involves cytokines (includes chemokines, interleukins, interferons, colony-stimulating factors and tumor necrosis factors) and leads to a cascade of events in the body during the fight (Tisoncik et al., 2012).

Although there is a test to say whether there is a cytokine storm (too many cytokines being released), the test cannot tell how to treat it in the person/patient. Get the medication wrong, the patient will become vulnerable to infections, etc. Perhaps, seeing the storm develop and its dynamics using proteomics may offer the best way to find new treatments or avert the storm all together. Proteomics has already helped discover different types of storms for those with Castleman disease (Pierson et al., 2018). Monitoring protein dynamics has also identified therapeutic targets for which a FDA-approved medications exist and might aid in treatment (Bodewes et al., 2019; Guerrero et al., 2020; Sullivan et al., 2017; Wasiak et al., 2018).

Proteomics (particularly our technology with the ability to look at 5,000 proteins, including >800 proteins involved in immune/inflammatory response) has the power to turn the tide in the COVID-19 war. Aside from the power of aiding in repurposing existing medications that can help, our technology can help observe so much more. In fact, a significant portion of the proteins that interact with the virus are included in those 5,000 proteins (Gordon et al., 2020). It may even be possible to see the effects on the heart, brain, lungs or kidneys (places where ACE2 can be found) and point to the development of possible tests that would allow the patient to get earlier treatment.

Until a vaccine or a cure is found, the battle against COVID-19 continues. People in the process of developing tests and treatments will need to have the ability to widely sample what is going on in the whole body (particularly where ACE2 can be found) and detect when the immune system is going into overdrive. We are ready when you are!

 

References

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Bojkova, D., Klann, K., Koch, B., Widera, M., Krause, D., Ciesek, S., . . . Munch, C. (2020). Proteomics of SARS-CoV-2-infected host cells reveals therapy targets. Nature. doi:10.1038/s41586-020-2332-7

Glaser, G. (2020). He ran marathons and was fit. So why did Covid-19 almost kill him? STAT. Retrieved from https://www.statnews.com/2020/04/21/he-ran-marathons-why-did-coronavirus-almost-kill-him/

Gordon, D. E., Jang, G. M., Bouhaddou, M., Xu, J., Obernier, K., White, K. M., . . . Krogan, N. J. (2020). A SARS-CoV-2 protein interaction map reveals targets for drug repurposing. Nature. doi:10.1038/s41586-020-2286-9

Guerrero, C. L. H., Yamashita, Y., Miyara, M., Imaizumi, N., Kato, M., Sakihama, S., . . . Fukushima, T. (2020). Proteomic profiling of HTLV-1 carriers and ATL patients reveals sTNFR2 as a novel diagnostic biomarker for acute ATL. Blood Adv, 4(6), 1062-1071. doi:10.1182/bloodadvances.2019001429

Hamming, I., Timens, W., Bulthuis, M. L., Lely, A. T., Navis, G., & van Goor, H. (2004). Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol, 203(2), 631-637. doi:10.1002/path.1570

Paizis, G., Tikellis, C., Cooper, M. E., Schembri, J. M., Lew, R. A., Smith, A. I., . . . Angus, P. W. (2005). Chronic liver injury in rats and humans upregulates the novel enzyme angiotensin converting enzyme 2. Gut, 54(12), 1790-1796. doi:10.1136/gut.2004.062398

Pierson, S. K., Stonestrom, A. J., Shilling, D., Ruth, J., Nabel, C. S., Singh, A., . . . Fajgenbaum, D. C. (2018). Plasma proteomics identifies a ‘chemokine storm’ in idiopathic multicentric Castleman disease. Am J Hematol, 93(7), 902-912. doi:10.1002/ajh.25123

Puelles, V. G., Lutgehetmann, M., Lindenmeyer, M. T., Sperhake, J. P., Wong, M. N., Allweiss, L., . . . Huber, T. B. (2020). Multiorgan and Renal Tropism of SARS-CoV-2. N Engl J Med. doi:10.1056/NEJMc2011400

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