Corresponding author:
Taher Entezari-Maleki Pharm.D., PhD
Associated Professor of Clinical Pharmacy
tentezari@gmail.com or
entezarim@tbzmed.ac.ir
Department of clinical pharmacy, Faculty of pharmacy, Tabriz University
of Medical Sciences, Tabriz, Iran.
As of 16 July 2020, globally about 13.4 million cases of coronavirus
disease 2019 (COVID-19) have been confirmed with nearly 600000 deaths.
One of the main concerns about COVID-19 is long-term complications.
Viruses account for about one-fifth of human cancer cases [1, 2].
Herein, three possible mechanisms of the novel severe acute respiratory
syndrome coronavirus 2 (SARS-CoV-2) as an oncogenic virus in the lung
have been discussed briefly.
First, available data have been shown a chronic involvement of pulmonary
tissue in patients with the previous zoonotic coronaviruses mainly
severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East
respiratory syndrome coronavirus (MERS-CoV).2-4 For
example, a 15-year follow-up of 71 patients with SARS-CoV infection
showed a chronic involvement of lung tissues with interstitial
abnormalities [3]. Das et al. in a study of 36 recovered patients
with MERS-CoV infection with a median follow-up of 43 days (ranged from
32-320 days) showed radiographic findings indicating pulmonary fibrosis
in about one-third of patients [4]. Recently, Spagnolo et al. are
presumed pulmonary fibrosis as a long-term complication of COVID-19
[2]. Mounting evidence showed a direct link as well as common
cellular processes and molecular pathways between pulmonary fibrosis and
lung cancer. Pulmonary fibrosis is a risk factor for developing lung
cancer, and the prevalence of lung cancer in patients with idiopathic
pulmonary fibrosis ranges from 2.7% to 48% [5]. For the second
mechanism, COVID-19 hyperinflation and cytokines storm induced
pathologic changes should be considered as well. Also, the
pro-inflammatory cytokines such as interleukin 1 (IL-1), IL-6, and tumor
necrosis factor-α (TNF- α), which play a key role in COVID-19 related
hyper-inflammation pathogenesis, are involved in the tumor promotion and
cell transformation of lung cancer pathogenesis. Hyperinflammation is a
critical response by the host from the first stages of cancer
development. Besides, chronic inflammation not only has a critical
function in tumorigenesis, but also could make an ideal environment for
carcinogenesis [6, 7]. Third, similar to patients suffering from
non-small-cell lung carcinoma (NSCLC), a down-regulation of
angiotensin-converting enzyme 2 (ACE2) occurs after COVID-19 ensuing.
ACE2 gene has been confirmed as the functional receptor for SARS-CoV-2,
and it has a crucial role in virus entry into the target cell. It
degrades angiotensin II (Ang II) and generates angiotensin (1-7).
Considerable evidence indicated that the renin-angiotensin system (RAS)
components including ACE2, Ang (1-7), and Ang II play a key role in
malignancies from the early stages. Low levels of ACE2 expression has
been demonstrated as an indicator of malignancies and poor prognostic
cancers. ACE2 has an inhibitory effect on cancer cell proliferation,
metastasis, invasion, migration, and angiogenesis, especially in NSCLC.
Additionally, Ang (1-7) reduces lung cancer cell proliferation and
angiogenesis as well and also has an inhibitory effect on A549 human
lung adenocarcinoma cells. On the contrary, angiotensin II/ angiotensin
II type I receptor (AT1R) axis has a regulatory effect on almost every
feature of cancer, including angiogenesis, cell proliferation,
dissemination, desmoplasia, tumor growth, cancer-related inflammation
induction and promoting immunosuppressive milieu, and tumor
progression[8-10].
We hypothesized that SARS-CoV-2 infection could be a trigger for lung
cancer. Considering the large number of infected individuals and lack of
data regarding postinfection immunity, even a weak association of
SARS-CoV-2 infection with lung cancer should be considered in public
health policy and evaluated in the future studies.
Funding: None
Conflicting interest: None
Disclosure: The authors have nothing to disclose.