Smoking increases the severity of SARS-CoV-2 infection

Report by : Gan Yung Chyan, KUCINTA SETIA

 

Cigarette smoke appears to be associated with more severe covid (short for novel coronavirus pneumonia, coronavirus disease, COVID-19) cases (Reference 1), but its underlying mechanism has not been deciphered. The results of experimental studies on SARS-CoV-2 (covi, novel coronavirus, CCP virus) infection of cultured respiratory cells provide some intuitive explanations (Reference 2).

Smoking is the most important cause of chronic lung disease, and chronic lung disease is a risk factor for severe covid. Some studies have confirmed that smoking is a risk factor for severe covid, and long-term exposure to smoke seems to trigger the expansion of respiratory cell types, and these cells produce SARS-CoV-2 receptor ACE2. However, there is no direct study to determine how cigarette smoke affects SARS-CoV-2 infection of the respiratory epithelium.

In order to solve this problem, Purkayastha of the University of California, Los Angeles, etc. studied the air-liquid interface cultures of non-smokers' respiratory epithelial cells (Reference 2). This culture starts by spreading cells taken from the human respiratory tract on a permeable membrane. When the medium is removed from the upper part of the monolayer cells, these cells develop into mucociliary pseudostratified epithelium, similar to respiratory epidermal cells. When treated with cigarette smoke and then infected with SARS-CoV-2, these cells in culture produced 2-3 times more viral RNA than unexposed cells. In addition, the number of infected cells also increased in cultures treated with cigarette smoke.

In order to understand the mechanism by which cigarette smoke treatment leads to increased viral replication, single-cell RNA sequencing was performed to determine the mRNA changes caused by viral infection. The analysis determined that the transcription of a set of genes was triggered by viral infection in untreated cells, while the transcription of these genes was down-regulated in cells treated with cigarette smoke. These genes code for interferon-inducing proteins, indicating that exposure to cigarette smoke weakens the effective innate immune response to infection. To support this hypothesis, after treatment with cigarette smoke, interferon was added to the culture before virus infection, which prevented the production of infectious virus.

These observations provide some reasonable explanations for studying the effect of cigarette smoke on covi infection of respiratory epithelial cells. The finding that viral RNA increases in smoke-treated cells should be expanded to determine whether the number of infectious viruses also increases. Interferon blocking virus production does not fully explain the effects of smoke treatment, because this cytokine also blocks infection in untreated cells. Specifically, it may be more meaningful to restore the expression of interferon-induced genes that are reduced by smoke treatment.

After these respiratory cultures were treated with cigarette smoke, the virus production increased by 2-3 times, and the number of infected cells also increased similarly. Does this explain why smokers may be at risk of severe covid?  The weakening innate immune response of the smoker's body may allow covi to multiply in the respiratory tract, which in turn stimulates an excessively vigorous immune response, leading to severe covid.

However, the single factor of increased covi production seems too simple to fully explain the link between serious illness and smoking. An interesting hint is the effect of cigarette smoke on the basal stem cells of the respiratory tract, which is important for the repair of damaged respiratory tract. Smoking not only increases the number of these cells, but also causes their deaths. This effect will aggravate the tissue damage of the infected respiratory tract, leading to more serious diseases.

References:

1. Smith, J., et al., Cigarette Smoke Exposure and Inflammatory Signaling Increase the Expression of the SARS-CoV-2 Receptor ACE2 in the Respiratory Tract, Developmental Cell, 53, 514–529, June 8, 2020 Elsevier Inc. https://doi.org/10.1016/j.devcel.2020.05.012ll

2. Purkayastha, A., et al., Direct exposure to SARS-CoV-2 and cigarette smoke increases infection severity and alters the stem cell-derived airway repair response, Stem Cell (2020), doi: https://doi. org/10.1016/j.stem.2020.11.010.