I’m sure you’re overwhelmed with the amount of information out there about the current coronavirus outbreak but while it can be overwhelming, it’s really great to see the work that scientists are doing to tackle this outbreak. Having information that’s readily available to the general public is great and helps to bridge the gap between scientists and the public. I truly believe that our work as scientists should be translatable to the public!
I recently read a really interesting article about COVID-19 and platelets. As you’re probably aware by now that my PhD project involves studying platelet inhibitory signalling pathways in the context of cardiovascular disease, so I have a vested interest in all things platelet biology. I’d never really considered the effect that infection could have on our platelets and what that means for platelet function…until now.
The SARS-CoV-2 is the infection responsible for the 2019 Coronavirus (COVID-19) global pandemic. The current coronavirus is from a family of coronaviruses, where some strains cause “common cold” symptoms while others cause SARS and MERS which are much more serious diseases.
A recent study by Manne, et al (2020) found that thrombotic complications were common in COVID-19 patients. Thrombotic complications can contribute to organ failure and mortality, particularly among those with underlying medical conditions such as diabetes, obesity or high blood pressure.
Thrombotic complications refer to thrombosis which is the formation of an unwanted blood clot, known as a thrombus, within a blood vessel. The blood clot formed then prevents blood from flowing normally through the circulatory system, leading to potential heart attacks, deep vein thrombosis (DVT) or stroke.
How do platelets fit into this?
Under normal circumstances, platelets, which are cells of the blood, become active and aggregate upon vascular injury and along with coagulation factors, cause the formation of a blood clot. In this case, this is haemostasis as the blood clot formed is to protect us from bleeding out. For blood clots to occur platelets have to be involved somehow!
However, it has been shown through RNA sequencing that in patients with COVID-19, the SARS-CoV-2 infection can alter platelet gene expression and functional responses. These changes to platelet gene expression and function were found to increase the risk of thrombosis in COVID-19 patients.
The platelets in COVID-19 patients were hypereactive compared to controls. In resting platelets from COVID-19 patients, there was an increase in P-selectin expression. P-selectin is an important marker for activation and becomes expressed on the surface during platelet activation.
They also found that these changes altered how platelets interact with cells of the immune system such as neutrophils, monocytes and T-cells. They found that circulating platelet-immune cell aggregates were significantly elevated in COVID-19 patients compared to controls. This could potentially contribute to inflammation of the respiratory tract which can result in lung injury. The platelets in COVID-19 patients were also found to aggregate faster and show increased spreading on both fibrinogen and collagen.
Authors suggest that this increase in platelet activation and aggregation could be due to increased MAPK pathway activation and thromboxane (TxA2) generation. MAPK signalling pathway in platelets plays an important role in platelet granule secretion. Platelet granule secretion is a key step during platelet activation. During activation, platelets release many things including thromboxane which typically recruits platelets to the site of injury and amplifies activation.
Interestingly, this altered gene expression and function, however, was not due to SARS-CoV-2 binding to platelets. The SARS-CoV-2 binding receptor (ACE-2) did not appear to be present in platelets of COVID-19 patients or healthy controls.
To summarise, the SARS-CoV-2 infection is associated with platelet hypereactivity which may contribute to the pathophysiology of COVID-19 through increased platelet-platelet and platelet-leukocyte interactions, which could account for the many complications found in COVID-19 patients.
The authors do go on to say that platelet counts, mean platelet volume (MPV), and markers for platelet activation did not correlate with markers of inflammation in COVID-19 patients, to which they suggest that platelets are not the main driving force here. Other blood cells and soluble coagulation factors can also mediate inflammatory, immune and thrombotic responses that may result in injury.
There’s still so much that we don’t know but information like this can help us understand some more of the complexities of COVID-19 and the complications that can occur in COVID-19 patients. Earlier studies (Zhang et al., 2020, Xu et al., 2020) suggested a link between low platelet count and COVID-19 disease severity however this study showed no such link.
I hope you enjoyed this post.
Stay safe & thanks for reading!
MANNE, B. K., DENORME, F., MIDDLETON, E. A., PORTIER, I., ROWLEY, J. W., STUBBEN, C. J., PETREY, A. C., TOLLEY, N. D., GUO, L., CODY, M. J., WEYRICH, A. S., YOST, C. C., RONDINA, M. T. & CAMPBELL, R. A. 2020. Platelet Gene Expression and Function in COVID-19 Patients. Blood. https://doi.org/10.1182/blood.2020007214
XU, P., ZHOU, Q. & XU, J. 2020. Mechanism of thrombocytopenia in COVID-19 patients. Annals of Hematology, 99, 1205-1208. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7156897/
ZHANG, Y., ZENG, X., JIAO, Y., LI, Z., LIU, Q., YE, J. & YANG, M. 2020. Mechanisms involved in the development of thrombocytopenia in patients with COVID-19. Thrombosis research, 193, 110-115. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7274097/