CST BLOG: Lab Expectations

The official blog of Cell Signaling Technology (CST) where we discuss what to expect from your time at the bench, share tips, tricks, and information.

COVID-19 and Fibrosis: Long-term damage beyond acute respiratory symptoms

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At the time of writing the SARS-CoV-2 virus, responsible for COVID-19, has infected more than 28 million people worldwide, with nearly a million deaths attributed to the virus (source: Johns Hopkins Coronavirus Resource Center). One of the most striking aspects of SARS-CoV-2 infection is the diversity of symptoms that have been reported in patients [Kwon, 2020].

20-EMG-97563 Mechanisms of Fibrosis the context of Covid

SARS-CoV-2 was first identified, and remains primarily described, as a respiratory virus, eliciting an “Acute Respiratory Distress Syndrome” (ARDS), in similar fashion to the SARS and MERS coronavirus outbreaks in 2003 and 2010, respectively. It has become apparent however, as the SARS-CoV-2 virus has spread incessantly throughout the globe, that the effects of infection can extend well beyond an acute respiratory infection [32293910]. Potentially serious symptoms attributed to COVID-19 include: cardiovascular complications, including hypertension, blood clots, strokes and embolisms [32200663]; heart damage (e.g., myocarditis), attributed primarily to inflammation of the heart muscle [32139904]; and neurological damage, eliciting effects ranging from a diminished sense of taste and/or smell to more severe neurological events such as dizziness, confusion, and even coma [reviewed in 32494853].

            Due to its relatively recent emergence in the human population, it remains difficult for scientists to predict the long-term health effects of COVID-19, particularly considering its diversity of effects during acute infection. The most severe impacts appear to manifest in tissues with high levels of vascularization (e.g., lungs, heart, kidney, liver), and it is evident that the virus elicits a significant inflammatory response in infected tissues [32217834]. What scientists do know is that the wound healing response elicited during severe inflammation can lead to permanent tissue and organ damage, through a process of scarring called fibrosis. Similar to what was reported for both SARS and MERS, there is now evidence emerging from patients infected with SARS-CoV-2 that fibrotic damage to infected tissues can lead to health complications that persist well beyond the period of viral infection [32422178].

            Fibrosis is fundamentally a pathological wound healing response that results in significant architectural remodeling of the extracellular environment. A primary outcome of fibrosis is reduced tissue elasticity, leading to organ dysfunction where elasticity is required for normal function (e.g., lungs, heart). Key biomarkers of fibrotic onset include myofibroblast activation (α-smooth muscle actin) and increased deposition of extracellular matrix (ECM) proteins such as collagens (e.g., COL1A1, COL3A1, COL11A1), fibronectins (e.g., FN-1), and various associated matrix molecules (LOX, MMPs, hydroxyproline). Fibrosis is also associated the activation of pro-inflammatory signaling pathways, including TNF-α, interferons and interleukins, key drivers of the wound healing response.

            CST has built a robust portfolio of antibody reagents to enable to research into fibrotic diseases and inflammation. These reagents are designed to help researchers understand the etiology of fibrotic diseases, leading to better treatments to minimize its impact. These efforts have now assumed ever more urgency; as the SARS-CoV-2 virus spreads throughout the globe, tragically taking many lives, it is also leaving in its wake a population of survivors potentially facing long-term health complications associated with SARS-CoV-2-induced fibrosis.

References:

Kwon D. From Headaches to ‘COVID Toes’, Coronvirus Symptoms Are a Bizarre Mix. Scientific American, 18 May 2020.

Liu et al., 2020. The Science Underlying COVID-19: Implications for the Cardiovascular System. Circulation 142(1): 68-78. PMID 32293910

Clerkin et al. 2020. COVID-19 and Cardiovascular Disease. Circulation 141(20): 1648-1655. PMID 32200663

Zheng et al. 2020. COVID-19 and the cardiovascular system. Nat. Rev. Cardiol. 17(5): 259-260. PMID 32139904

Pryce-Roberts et al. Neurological complications of COVID-19 : a preliminary review. J. Neurol. 267(6): 1870-1873. PMID 32494853

Pedersen and Ho 2020. SARS-CoV-2: a storm is raging. J. Clin. Invest. 130(5): 2202-2205. PMID 32217834

George et al. 2020. Pulmonary fibrosis and COVID-19: the potential role of antifibrotic therapy. Lancet Respir. Med. 8(8): 807-815 PMID 32422178

Antony Wood, PhD
Antony Wood, PhD
Antony (Tony) Wood, PhD, is the Senior Director, Product Design & Strategy at CST. The passion palate of this Canadian transplant includes cycling, adventure travel, and any food involving hot peppers.

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