Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) , otherwise known as COVID-19, is an emerging coronavirus that has resulted in more than 1,846,960 reported cases globally (as of April 12, 2020 ) including more than 22,000 deaths in the US (as of April 12, 2020) (3). Although SARS and COVID-19 are similar viruses, COVID-19 appears to be highly efficient in person-to-person transmission and can cause asymptomatic infections. COVID-19 shows a wide range: asymptomatic or mild cases, progressive pneumonia, acute respiratory distress syndrome (ARDS), and multi-organ failure (which leads to death).
COVID-19 is a novel enveloped RNA beta-corona virus. Viral particles enter healthy human cells through interactions with specific receptor proteins in the host cells. Once entered, viral particles utilize the host cells to ramp up productions of its own protein machinery. This enables the virus to duplicate inside the host. After a period of incubation (Typically 1-5 days for cold/flu; COVID-19 has shown 1-14 days), host immune responses begin to react. The host/patient develops a cough and fever. Patients with underlying conditions may require ventilation equipments to provide oxygen to the lungs and other vital organs such as the kidney.
What are airway cells?
Airway cells are entry points for the COVID-19 viral particles–mouth, nose, throat, and lungs. One of the most important cell types is the human bronchial epithelial cells. The epithelial cells form “sheets like” structures — 2^21 to 2^23 branches of the human airways are covered with epithelial sheets (1). The major cell types are ciliated, columnar, undifferentiated, secretory and basal cells. In a healthy adult, these cells vary in population depending on the airway level (upper vs. lower respiratory tract). As powerful and functional as the “sheets” are, they are part of an even greater interdependent unit of epithelial cells, mesenchymal cells, endothelial cells, and the bronchial walls (1-2).
COVID-19 is thought to be able to travel up and down the airway and attacks the lung epithelial cells. Viral particles can reach as far down as the lower respiratory tract (That’s much farther down the tract than a common cold can reach.). The viral attacks on the cells lead to debris and fluid buildup in the lungs. This leads to pneumonia in the patients. If the lung damages continue to build, patients can experience respiratory failure. Currently, many studies state that a gene, angiotensin converting enzyme 2 (ACE2), is the presumed genetic target of COVID-19, expressed in bronchial transient secretary cells (4). We will cover drug development progress and clinical trials in another post!
Interesting facts — Did you know?
1) The airway epithelial cells can turnover every 30-50 days.
2) There are circulating airway stem/progenitor cells in the lung.
3) There are pulmonary neuroendocrine cells in the airway epithelium — they are neuronal by nature.
1) Crystal RG, Randell SH, Engelhardt JF, Voynow J, Sunday ME. Proc Am Thorac Soc. 2008 Sep 15;5(7):772-7.
2) Kotton DN, Fine A. Cell Tissue Res. 2008 Jan;331(1):145-56. Epub 2007 Sep 6.
3) Johns Hopkins University, Coronavirus Resource Center, <https://coronavirus.jhu.edu>
4) Lukassen S, Lorenz Chua R, Trefzer T, Kahn NC, Schneider MA, Muley T, Winter H, Meister M, Veith C, Boots AW, Hennig BP, Kreuter M, Conrad C, Eils R. EMBO J. 2020 Apr 4.