Reference no: EM133524407

Part 1: Introduction

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the global pandemic of coronavirus disease 2019 (COVID-19). While the majority of patients with COVID-19 experience mild symptoms, serious complications including acute respiratory distress syndrome (ARDS), hemodynamic shock, acute kidney injury, cardiac injury, and arrhythmia, contributing to the COVID-19 high mortality rate (1).

There is a growing recognition of an increased rate of thrombotic complications in patients: many COVID-19 patients in the ICU are developing blood clots, including clots in small vessels, deep vein thromboses in the legs, clots in the lungs, and stroke-causing clots in cerebral arteries. This has been happening even though these patients, in accordance with standard intensive care practice, are put on blood thinner drugs such as heparin to prevent clots as soon as they come to the ICU. This COVID-19-related clotting often does not respond well to standard prevention methods and, in some cases, to standard treatments, even with high doses of blood thinners (2).

These complications are particularly notable among patients with underlying medical problems such as diabetes, obesity, or high blood pressure (3). Dozens of studies have revealed similar patterns of vascular damage in people who died of COVID-19: many patients had acute kidney failure, organ damage, and mysterious blood clots. Tiny clots and dead cells littered the capillaries of the lungs, and inflammation had distended blood vessels supplying every organ in the body. The virus had targeted their blood vessels (4, 5).

Using differential gene analysis, the researchers found that SARS-CoV-2, the virus that causes COVID-19, appears to trigger genetic changes in platelets. In laboratory studies, they studied platelet aggregation, an important component of blood clot formation, and observed COVID-19 platelets aggregated more readily. They also noted that these changes significantly altered how platelets interacted with the immune system, likely contributing to inflammation of the respiratory tract that may, in turn, result in more severe lung injury. Evidence of the virus in the vast majority of platelets, suggesting that it could be promoting the genetic changes within these cells indirectly (3).

Autopsies on seven individuals (four female, three male) that died from COVID-19 complications were observed to have unusually higher numbers of megakaryocytes in the microvasculature of the heart, in some glomeruli, and in the lungs (6).

Another possible mechanism of the effect of the SARS-CoV-2 virus is inflammation. In theory, inflammation caused by COVID-19 could affect megakaryocytes, the cells that produce platelets. As a result, critical genetic alterations are passed down from megakaryocytes to the platelets, which, in turn, make them hyperactive. In test tube studies, the researchers found that pre-treating platelets from SARS-CoV-2 infected patients with aspirin did prevent this hyperactivity (3).

Changes in blood platelets triggered by COVID-19 could contribute to the onset of heart attacks, strokes, and other serious complications in some patients who have the disease. Inflammatory proteins produced during infection significantly alter the function of platelets, making them "hyperactive" and more prone to form dangerous and potentially deadly blood clots (7).

Questions

1. How are platelets formed?

2. Which organs and tissues produce megakaryocytes? Name four.

3. What protein signals the production of megakaryocytes?

4. Elevated levels of Interleukin-6 (IL-6) is observed in severe COVID-19 infections (hospitalized patients). What is the potential relationship between IL-6 and elevated levels of platelets?

5. What is the relationship between IL-6 and inflammation?