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Effect of COVID-19 on Lungs: Focusing on Prospective

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Effect of COVID-19 on Lungs: Focusing on Prospective cancers Review Effect of COVID-19 on Lungs: Focusing on Prospective Malignant Phenotypes 1, 1, 1,2,3, Pritam Sadhukhan y , M. Talha Ugurlu y and Mohammad O. Hoque * 1 Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; [email protected] (P.S.); [email protected] (M.T.U.) 2 Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA 3 Department of Urology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA * Correspondence: [email protected]; Tel.: +1-410-502-8778; Fax: +1-410-614-1411 Authors have contributed equally. y Received: 11 November 2020; Accepted: 15 December 2020; Published: 18 December 2020 Simple Summary: According to the coronavirus virus resource center of Johns Hopkins Medicine, more than 75 million people are presently affected worldwide, including 1.7 million deaths due to severe acute respiratory syndrome since December 2019. Apart from the common symptoms similar to the common flu, a characteristic computed tomography (CT) feature i.e., Ground Glass Opacity (GGO) is highlighted in this article. GGOs have been observed in COVID-19 patients with severe symptoms including pneumonia in both lungs. It is important to reflect that GGO may indicate the onset of lung fibrosis and may be an indicative feature of high-risk subjects for developing lung cancer. In this article, the causes of the appearance of GGOs and their effects are mainly discussed, along with the brief immunopathogenesis of COVID-19 in comparison with other oncogenic viruses. In this pandemic situation, it is also important to consider the long-term effects of coronavirus infection and the ways to follow-up the patients who recovered from this disease. Abstract: Currently, the healthcare management systems are shattered throughout the world, even in the developed nations due to the COVID-19 viral outbreak. A substantial number of patients infected with SARS-CoV2 develop acute respiratory distress syndrome (ARDS) and need advanced healthcare facilities, including invasive mechanical ventilation. Intracellular infiltration of the SARS-CoV2 virus particles into the epithelial cells in lungs are facilitated by the spike glycoprotein (S Protein) on the outer side of the virus envelope, a membrane protein ACE2 (angiotensin-converting enzyme 2) and two proteases (TMPRSS2 and Furin) in the host cell. This virus has unprecedented effects on the immune system and induces a sudden upregulation of the levels of different pro-inflammatory cytokines. This can be a cause for the onset of pulmonary fibrosis in the lungs. Existence of a high concentration of inflammatory cytokines and viral load can also lead to numerous pathophysiological conditions. Although it is well established that cancer patients are among the high-risk population due to COVID-19-associated mortality, it is still unknown whether survivors of COVID-19-infected subjects are at high-risk population for developing cancer and whether any biologic and clinical features exist in post-COVID-19 individuals that might be related to carcinogenesis. Keywords: COVID-19; lungs; acute respiratory distress syndrome; ground glass opacity; inflammation 1. Introduction The outbreak of COVID-19 infection was first reported in a Chinese city (Wuhan, Hubei province) and since then, this viral infection has been spreading throughout the world [1] The symptoms of COVID-19 infection were related to the previously known SARS (Severe Acute Respiratory Syndrome), Cancers 2020, 12, 3822; doi:10.3390/cancers12123822 www.mdpi.com/journal/cancers Cancers 2020, 12, x FOR PEER REVIEW 1 of 17 Cancers 2020, 12, 3822 2 of 17 COVID-19 infection were related to the previously known SARS (Severe Acute Respiratory Syndrome), MERSMERS (Middle (Middle East East Respiratory Respiratory Syndrome), Syndrome), and and influenza influenza infections, infections, which which present present with with fever, fever, sore throat,sore throat, nasal congestion, nasal congestion, body ache, body and ache, dry cough. and dry Some cough. of the SomeCOVID-19 of the patients COVID-19 also develop patients severe also clinicaldevelop disorders severe clinical such as disorders breathlessness, such as chest breathlessness, pain, and diarrhea. chest pain, As of and November diarrhea. 2020, As of United November States has2020, reported United the States greatest has number reported of the infected greatest patients number followed of infected by India, patients Brazil, followed Russia, byand India, many Brazil, others withRussia, over and 75 million many others infected with individuals over 75 million and more infected than individuals 1.7 million deaths. and more According than 1.7 to million the reports deaths. of WorldAccording Health to theOrganization reports of World(WHO), Health Centers Organization for Disease (WHO), Control Centers and Prevention for Disease (CDC), Control Johns and Hopkins,Prevention Mayo (CDC), Clinic, Johns and Hopkins, other medical Mayo institutions Clinic, and and other organizations, medical institutions older adults, and organizations,males, and the patientsolder adults, with comorbid males, and conditions the patients such with as comorbidcardiovascular conditions disorders, such asdiab cardiovascularetes, chronic respiratory disorders, disease,diabetes, and chronic cancer respiratory are more likely disease, to andhave cancer life-threatening are more likely conditions to have including life-threatening pneumonia conditions in both lungs,including multi-organ pneumonia failure, in both and lungs, various multi-organ neurological failure, disorders and various than others. neurological disorders than others. SARS-CoV2SARS-CoV2 is is a a member member of of the coronaviridae family virusvirus andand hashas beenbeen reportedreported to to be be associated associated withwith numerous numerous coronavirus-associated coronavirus-associated diseases diseases [2]. [2 ].It Itis isa single a single stranded stranded RNA RNA virus virus with with a 5′ a cap 50 cap and 3and′ poly 30 Apoly tail A(30–32 tail (30–32 kb). According kb). According to the toNational the National Cancer Cancer Institute Institute (NCI),(NCI), this virus this can virus affect can almost affect allalmost organs all and, organs most and, importantly, most importantly, it causes it acute causes respiratory acute respiratory disorder, disorder, as depicted as depicted in Figure in 1. Figure It is well1. establishedIt is well established that numerous that numerous viral infections viral infections are causative are causative to carcinogenesis to carcinogenesis [3] and [3previous] and previous reports suggestreports suggestthat viral that infection-associated viral infection-associated inflammation inflammation can can initiate initiate cellular cellular transformation transformation throughthrough activating/modulatingactivating/modulating several several oncogenic oncogenic signal transductiontransduction pathwayspathways [[4].4]. Therefore,Therefore, thethe association association betweenbetween COVID-19 COVID-19 survivals andand cancercancer incidenceincidence in in di differentfferent organs organs may may be be a major a major point point of concern of concern to tothe the cancer cancer research research community. community. Although Although no clinical no cl andinical experimental and experimental data yet available,data yet weavailable, speculate we speculatethat SARS-CoV2 that SARS-CoV2 infection mayinfection activate may some activate oncogenic some oncogenic pathways thatpathways may remain that may active remain even active after eventhe infection after the subsided.infection subsided. FigureFigure 1. 1. EffectEffect of of SARS-CoV-2 SARS-CoV-2 infection infection on on the the alveolar alveolar cells cells depending depending the the severity severity of of the the infection. infection. AA group group of of scientists scientists performed performed complete complete genome genome sequencing sequencing of a novel of a novelcoronavirus coronavirus strain (SARS- strain CoV2)(SARS-CoV2) in the first in the week first of week January of January 2020. Since 2020. then Since, 1000 then, more 1000 moresequences sequences (complete (complete and partial) and partial) have beenhave submitted been submitted to the to NCBI the NCBI database database by bydifferent different scientists scientists from from several several countries [[5,6].5,6]. TheThe viralviral genomegenome typically consistsconsists of of 6 open6 open reading reading frames fram (ORFs).es (ORFs). Although Although very few very functional few functional data available data Cancers 2020, 12, 3822 3 of 17 of these ORFs, ORF1a and ORF1b are comparatively more virulent [7]. These two ORFs transcribe and ultimately produce two polypeptides, pp1a and pp1b, respectively. Subsequently, these polypeptides are further processed by viral proteases to form 16 non-structural proteins (NSPs) [7,8]. The remaining ORFs are found to regulate the synthesis of different structural proteins of the viral capsid, including the spike, envelop, accessory protein chains etc. [9]. The structural proteins of the virus are very critical for the pathogenesis of the virus, and the NSPs are also known to blocking the host immune response [8]. In this review article, we have focused on the oncogenic viruses, the effect of COVID-19 on the immune system, ground glass opacity (GGO) and the potential neoplastic changes in the lungs due to SARS-CoV2 infection. Since the lungs are one of the most affected organs,
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