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.

Stage 1: Asymptomatic state                           

The inhaled virus SARS-CoV-2 likely binds to epithelial cells in the nasal cavity and starts replicating. ACE2 is the main receptor for both SARS-CoV2 and SARS-CoV. In vitro data with SARS-CoV indicate that the ciliated cells are primary cells infected in the conducting airways. However, this concept might need some revision, since single-cell RNA indicates low level of ACE2 expression in conducting airway cells and no obvious cell type preference. There is local propagation of the virus but a limited innate immune response. At this stage the virus can be detected by nasal swabs. Although the viral burden may be low, these individuals are infectious.

Stage 2: Upper airway and conducting airway response

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 as well as early markers of the innate immune response. At this time, the disease COVID-19 is clinically manifest. The level of CXCL10 may be predictive of the subsequent clinical course.

Stage 3: Hypoxia, ground glass infiltrates, and progression to ARDS Unfortunately, about 20% of the infected patients will progress to stage 3 diseases and will develop pulmonary infiltrates and some of these will develop very severe disease. Initial estimates of the fatality rate are around 2%, but this varies markedly with age. The fatality and morbidity rates may be revised once the prevalence of mild and asymptomatic cases is better defined. The virus now reaches the gas exchange units of the lung and infects alveolar type II cells.

Journal of Surgical Pathology and Diagnosis is a peer-reviewed medical journal published by Oxford University Press covering research on the pathogenesis, clinical investigation, medical microbiology, diagnosis, immune mechanisms, and treatment of diseases.

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Journal of Surgical Pathology and Diagnosis