An Update on the Coronavirus

As all kinds of news and information are being exposed to people, a clear comprehension must be made, particularly about what the coronavirus (COVID-19) really is, its pervasiveness and effects on the worldwide population, as well as potential post-infectious diseases.

To make it easy for all to understand, the virus is often being commonly referred to as the “coronavirus” or “COVID-19.” However, that is not the case. COVID-19 is the abbreviation for the term “coronavirus disease 2019”. The virus that causes all this chaos, meanwhile, is coined the name “severe acute respiratory syndrome coronavirus 2” (SARS-CoV-2). This virus, which is similar to the SARS-CoV in many aspects, differs in some major structures. Anyway, both of them are types of coronaviruses, and in this article, let’s still refer to the SARS-CoV-2 as the coronavirus, for the sake of concision. 

Typical coronavirus symptoms include coughing, fever, and shortness of breath. Since such symptoms are not indicative of lung infection, or pneumonia, people who are infected with the coronavirus very often do not have pneumonia. The majority of COVID-19 cases, in fact, are mild and only a small percentage of patients will require hospitalization. It is true, however, that COVID-19 can lead to pneumonia for some patients, especially those over the age of 60 and those with pre-existing lung diseases, such as asthma, emphysema, or any form of fibrosis, which make them prone to the development of pneumonia. This explains why the number of deaths in Italy soar above that of many other countries (Italy has an elderly population of roughly 23%).

According to the statistics provided by the World Health Organization (WHO), currently over 99,027 patients have recovered from the COVID-19 infection. However, multiple sources, such as doctors from Taiwan and Hong Kong, suggest that there are roughly 3%-5% of chances for patients who recovered from the coronavirus infection to be found with post-infectious diseases, most likely pulmonary fibrosis. Pulmonary fibrosis is a condition in which the lungs become scarred and tissues around and between the alveoli thickens over time, in this case, due to the repairing of the lungs after the coronavirus infection. Fibroblasts, which are responsible for the repairing of the lungs, tend to synthesize abundant amounts of extracellular matrix (this phenomenon is also called exaggerated ECM production), thus induces scarring and organ failure. This makes it more difficult for oxygen to pass into bloodstreams in the lungs, and the thickened alveoli results in a weakened lung capacity.

While it's too early to establish long-term effects of the disease, several scans released by a Hong Kong hospital have revealed "patterns similar to frosted glass [in the patients’ lungs], suggesting there was organ damage” (Fig.1). What appears in these patients’ CT scans are "ground glass," a phenomenon in which fluid builds up in lungs and presents itself as white patches. 

The coronavirus pandemic is still in its heights, and frankly, there are not much that we can do about. However, it is no longer something that we can underestimate or underrate. Despite no evidence in proving its effects against the prevention of the coronavirus, masks can prevent droplet transmissions and therefore should be wore, at least in crowded and confined spaces. Wash hands and use alcohol disinfectants after handling public objects and before eating. Most importantly, keep yourself healthy no matter what. 

Fig.1 CT scans of patients reveal the accumulation of fluids in lungs after the SARS-CoV-2 infection

Reference:

“False Claim: Doctors Offer Advice for Preventing COVID-19, Symptoms like Coughing and Fever Indicate Pulmonary Fibrosis, Fibrosis Is Detectable by Holding Your Breath for 10 Seconds, Drinking Water Every 15 Minutes Repels Coronavirus.” Reuters, Thomson Reuters, 17 Mar. 2020, www.reuters.com/article/uk-factcheck-covid-advice-self-test-drin/false-claim-doctors-offer-advice-for-preventing-covid-19-symptoms-like-coughing-and-fever-indicate-pulmonary-fibrosis-fibrosis-is-detectable-by-holding-your-breath-for-10-seconds-drinking-water-every-15-minutes-repels-coronavirus-idUSKBN2142B6.

Bostock, Bill. “Those Who Recover From Coronavirus Can Be Left With Reduced Lung Function, Say Doctors.” ScienceAlert, 14 Mar. 2020, www.sciencealert.com/even-those-who-recover-from-corona-can-be-left-gasping-for-breath-afterwards.

G M-K Tse, K-F To, et al. Pulmonary pathological features in coronavirus associated severe acute respiratory syndrome (SARS). NCBI, 2004.

Ryan T. Kendall, Carol A. Feghali-Bostwick. Fibroblasts in fibrosis: novel roles and mediators. NCBI, 2014.

Inflammation and Insulin Resistance

Recently I've read a few papers about inflammation-induced insulin resistance, and here’s a brief summary of what it’s all about.

In the first paper Inflammation and Insulin Resistance, it says that “proinflammatory cytokines such as TNF-α and chemokines can activate intracellular pathways that promote the development of insulin resistance and T2D” (Steven E. Shoelson, et al. 2006).

In the second paper Intestinal Microbiota and Type 2 Diabetes: From Mechanism Insights to Therapeutic Perspective, the author claims that “a change in gut microbiota induces low-grade inflammation that promote metabolic endotoxemia and triggers the development of inflammation via a lipopolysaccharide (LPS) and CD14/toll-like receptor (TLR) 4-dependent mechanism” (Jung-Ling Han. 2014). He also notes that "Many typical proinflammatory stimuli, including LPS, lipids, fatty acids, and chemokines activate c-Jun N-terminal kinase (JNK) and IκB kinase (IKK)-β pathways intracellularly... [increasing] the expression of numerous mediators of inflammation that can cause insulin resistance. JNK activation promotes the phosphorylation of insulin receptor substrate (IRS)-1 at serine sites, which inhibits normal signal transduction through the insulin receptor/IRS-1 axis, which also can result in insulin resistance."

Wow, that's confusing, isn't it?

Let me summarize it into a sequence.

1.      A change in gut microbiota leads to an increase in gut permeability.

2.      The increase in gut permeability leads to an increase in the amount of LPS in the bloodstream (known as metabolic endotoxemia).

3.      LPS binds to the complex mCD14 and TLR4 at the surface of innate immune cells, triggering the inflammation cascade.

4.      Cytokines such as TNF-α and chemokines secreted by macrophages and antigen-presenting cells (APC) promote inflammation of cells as well as insulin resistance through the activation of c-Jun N-terminal kinase (JNK) and IκB kinase (IKK)-β pathways, which the insulin receptor substrate-1 (IRS-1) is activated intracellularly.

Now get it?

It’s not that complicated after all, right?

Inflammation cascade

A change in gut microbiome increases gut permeability and leads to an LPS leak (metabolic endotoxemia) that results in inflammation and insulin resistance.

Reference

Jun-Ling Han, Hui-Ling Lin. 2014. Intestinal Microbiota and Type 2 Diabetes: From Mechanism Insights to Therapeutic Perspective.

Steven E. Shoelson, et al. 2006. Inflammation and Insulin Resistance.
Image 1: https://www.researchgate.net/figure/Fig-1-Schematic-illustration-of-inflammation-cascade-in-psoriasis-skin-lesion_fig1_51592687
Image 2: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4273124/