Pathogenesis of COVID-19 From A Cell Biology Perspective: Robert J. Mason
Pathogenesis of COVID-19 From A Cell Biology Perspective: Robert J. Mason
Pathogenesis of COVID-19 From A Cell Biology Perspective: Robert J. Mason
INFECTIOUS DISEASE
Robert J. Mason
Correspondence: Robert J. Mason, National Jewish Health, Dept of Medicine, 1400 Jackson Street, Denver,
CO 80206, USA. E-mail: masonb@njhealth.org
@ERSpublications
COVID-19 can be understood by the region of the lung that is infected. Mild disease will be confined
to the conducting airways and severe disease will involve the gas exchange portion of the lung. https://
bit.ly/2vGndRQ
Cite this article as: Mason RJ. Pathogenesis of COVID-19 from a cell biology perspective. Eur Respir J
2020; 55: 2000607 [https://doi.org/10.1183/13993003.00607-2020].
Introduction
Coronavirus disease 2019 (COVID-19) is a major health concern and can be devastating, especially for the
elderly. COVID-19 is the disease caused by the SARS-CoV-2 virus. Although much is known about
the mortality of the clinical disease, much less is known about its pathobiology. Although details of the
cellular responses to this virus are not known, a probable course of events can be postulated based on past
studies with SARS-CoV. A cellular biology perspective is useful for framing research questions and
explaining the clinical course by focusing on the areas of the respiratory tract that are involved. Based on
the cells that are likely infected, COVID-19 can be divided into three phases that correspond to different
clinical stages of the disease [1].
Stage 2: Upper airway and conducting airway response (next few days)
The virus propagates and migrates down the respiratory tract along the conducting airways, and a more
robust innate immune response is triggered. Nasal swabs or sputum should yield the virus (SARS-CoV-2)
as well as early markers of the innate immune response. At this time, the disease COVID-19 is clinically
manifest. The level of CXCL10 (or some other innate response cytokine) may be predictive of the
subsequent clinical course [6]. Viral infected epithelial cells are a major source of beta and lambda
interferons [7]. CXCL10 is an interferon responsive gene that has an excellent signal to noise ratio in the
alveolar type II cell response to both SARS-CoV and influenza [8, 9]. CXCL10 has also been reported to
be useful as disease marker in SARS [6, 10]. Determining the host innate immune response might improve
predictions on the subsequent course of the disease and need for more aggressive monitoring.
For about 80% of the infected patients, the disease will be mild and mostly restricted to the upper and
conducting airways [1]. These individuals may be monitored at home with conservative symptomatic therapy.
a) b)
FIGURE 1 Human alveolar type II cells infected with SARS-CoV. Human type II cells were isolated, cultured
in vitro, and then infected with SARS-CoV. Viral particles are seen in double membrane vesicles in the type II
cells (a) and along the apical microvilli (b). Reproduced with permission from the American Thoracic Society [8].
https://doi.org/10.1183/13993003.00607-2020 2
INFECTIOUS DISEASE | R.J. MASON ET AL.
monitored carefully and supported to the best of our ability, as we await the development and testing of
specific antiviral drugs.
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