What’s COVID-19 got to do with T1D?
In our current viral pandemic, data suggests that diabetes is not only a severe risk factor for COVID-19, but that COVID-19 can actually trigger diabetes. This blog will review current thinking around these two notions as well as their implications.
A number of studies have discovered that diabetes ranks highly on the list of common comorbidities in patients infected with SARS-CoV-2. This is not entirely shocking, as there has been a similar theme with previous coronavirus strains and respiratory illnesses, such as SARS-CoV-1 (the Severe Acute Respiratory Syndrome outbreak in 2002-2003), MERS-CoV (the Middle East Respiratory Syndrome Coronavirus that emerged in 2012), pneumonia and the flu. Experts suggest that diabetes causes worse infection because of a generally impaired innate immune function.
The point of entry
Importantly, the coronavirus’ doorway into human cells is through its “spike” protein that docks onto a receptor cell, identified as ACE2 (angiotensin-converting enzyme-2).
- The anti-inflammatory actor, ACE2 is widely found on cell membranes of the body’s organs, including the lungs and upper respiratory tract, heart, intestinal epithelium and the pancreas.
- COVID-19 reduces ACE2 expression, triggering a hyperinflammatory response with the potential to escalate to full-blown multi-organ failure.
Clues from stem-cell biology
One study published in Cell Stem Cell in June 2020 uses human pluripotent stem cells (hPSCs) to grow a model pancreas organ to gain insight as to why T1D patients are at a higher risk for infection AND how COVID-19 can cause T1D. Let’s break down the findings:
- The liver organoids, pancreatic alpha and beta cells and dopaminergic neurons were discovered to be extremely susceptible to COVID-19 infection.
- After infection, pancreatic alpha and beta cell functional pathways were subsequently all down-regulated due to increased cell apoptosis, while there was an upregulation of chemokine proteins (which can cause an autoimmune response).
- This dysregulation and loss of pancreatic cells can make patients more susceptible to diabetes.
- Why this study matters: this study gets the closest to modeling human biology (rather than using animal models of clinical data) to provide evidence for SARS-CoV-2’s role in worsening and/or causing diabetes.
A recent study has discovered that, after initial COVID-19 infection, patients are losing their antibodies within 2-3 months – an alarmingly high rate. While the study’s sample size is fairly small and there are other modes of building immunity against the infection (by targeting T-cells), this phenomenon has yet to be fully explained.
This leaves us with a burning question: Once we understand how COVID-19 antibodies are fading away, could our approach to solving T1D perhaps employ this same “fading” mechanism?
- Long, Q. X., Tang, X. J., Shi, Q. L., Li, Q., Deng, H. J., Yuan, J., … & Su, K. (2020). Clinical and immunological assessment of asymptomatic SARS-CoV-2 infections. Nature medicine, 1-5.
- Singh, A. K., Gupta, R., Ghosh, A., & Misra, A. (2020). Diabetes in COVID-19: Prevalence, pathophysiology, prognosis and practical considerations. Diabetes & Metabolic Syndrome: Clinical Research & Reviews.
- Yang, L., Han, Y., Nilsson-Payant, B. E., Gupta, V., Wang, P., Duan, X., … & Zhang, T. (2020). A Human Pluripotent Stem Cell-based Platform to Study SARS-CoV-2 Tropism and Model Virus Infection in Human Cells and Organoids. Cell Stem Cell.
- Yang, J. K., Lin, S. S., Ji, X. J., & Guo, L. M. (2010). Binding of SARS coronavirus to its receptor damages islets and causes acute diabetes. Acta diabetologica, 47(3), 193-199.