{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T15:29:09Z","timestamp":1788881349856,"version":"build-2803163510"},"reference-count":160,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,11,30]],"date-time":"2025-11-30T00:00:00Z","timestamp":1764460800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medical Sciences"],"abstract":"<jats:p>This review aims to discuss the apparent reduction in pulmonary cancer incidence in the general population during and shortly after the COVID-19 pandemic from a biological and pathophysiological mechanistic point of view. While the epidemiological evidence points to a disruption in the early- and mid-stage diagnostic process, which causes a shift to late-stage lung cancer discovery with no impact on its actual prevalence, an alternative hypothesis based on the intersection of viral and cancer biology could have a real effect on lung carcinogenesis as an independent phenomenon. By weaving together population-level trends, mechanistic insights, and translational oncology, we discuss whether the pandemic-associated decline in lung cancer diagnoses reflects primarily a temporary diagnostic artifact or whether it also reveals biologically relevant intersections between SARS-CoV-2 and pulmonary oncogenesis. The COVID-19 pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has exerted profound and multifaceted effects on global healthcare systems, altering patterns of disease detection, management, and outcomes across nearly all medical disciplines. These disruptions generated what has been termed a \u201cdiagnostic deficit\u201d, producing a backlog of undetected cancers that have only partially been recovered in subsequent years. This phenomenon, sometimes described as a \u201cCOVID-19 debt\u201d in oncology, is thought to contribute to excess late-stage diagnoses and potentially worse medium-term survival outcomes. Beyond the disruption of medical systems, the pandemic also raised a more speculative but biologically intriguing question: could SARS-CoV-2 infection itself, through direct or indirect mechanisms, influence lung cancer biology? Our review aims to critically synthesize the evidence across seven domains to address this dual hypothesis. (1) We examine the observed effects of the pandemic on cancer incidence, highlighting global registry and health-system data; (2) we review SARS-CoV-2 infection biology, including viral entry, replication, protein functions, and treatment implications; (3) we summarize the pathogenesis of lung cancer; (4) we explore the role of immune checkpoints in tumor immune evasion, followed by (5) analyses of immune dysregulation in acute infection and (6) in long COVID; and (7) finally, we evaluate proposed oncogenic mechanisms of SARS-CoV-2, integrating molecular virology with cancer immunology. We conclude that the \u201cdiagnostic deficit\u201d phenomenon was a reality during and immediately post-pandemic. However, a definitive answer to the questions related to the impact of the infection as an independent phenomenon would require advanced research information covering the biology of the viral infection and lung cancer oncogenesis: processes that are not currently implemented in routine clinical laboratory investigations.<\/jats:p>","DOI":"10.3390\/medsci13040295","type":"journal-article","created":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T15:31:46Z","timestamp":1764689506000},"page":"295","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["COVID-19 and Lung Cancer Interactions: A Literature Review"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-4560-4363","authenticated-orcid":false,"given":"Szabolcs-Attila","family":"L\u00e1szl\u00f3","sequence":"first","affiliation":[{"name":"Doctoral School of Medicine and Pharmacy, University of Medicine, Pharmacy, Science and Technology \u201cGeorge Emil Palade\u201d of T\u00e2rgu Mure\u0219, 540142 T\u00e2rgu Mure\u0219, Romania"},{"name":"Department of Pulmonology, University of Medicine and Pharmacy, Science and Technology \u201cGeorge Emil Palade\u201d of T\u00e2rgu Mure\u0219, 540139 T\u00e2rgu Mure\u0219, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-3558-2856","authenticated-orcid":false,"given":"Edith-Simona","family":"Iano\u0219i","sequence":"additional","affiliation":[{"name":"Department of Pulmonology, University of Medicine and Pharmacy, Science and Technology \u201cGeorge Emil Palade\u201d of T\u00e2rgu Mure\u0219, 540139 T\u00e2rgu Mure\u0219, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2880-4337","authenticated-orcid":false,"given":"Anca-Meda","family":"V\u0103sie\u0219iu","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease, University of Medicine, Pharmacy, Science and Technology \u201cGeorge Emil Palade\u201d of T\u00e2rgu Mure\u0219, 540139 T\u00e2rgu Mure\u0219, Romania"},{"name":"Infectious Diseases Clinic 1, Mure\u0219 Clinical County Hospital Mures, 540233 T\u00e2rgu Mure\u0219, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mioara","family":"Szathm\u00e1ry","sequence":"additional","affiliation":[{"name":"Department of Pulmonology, University of Medicine and Pharmacy, Science and Technology \u201cGeorge Emil Palade\u201d of T\u00e2rgu Mure\u0219, 540139 T\u00e2rgu Mure\u0219, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-7910-0123","authenticated-orcid":false,"given":"Maria Beatrice","family":"Iano\u0219i","sequence":"additional","affiliation":[{"name":"Pulmonology Clinic, Mure\u0219 County Clinical Hospital, 540011 T\u00e2rgu Mure\u0219, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Delia-Liana","family":"Rachi\u0219","sequence":"additional","affiliation":[{"name":"Pulmonology Clinic, Mure\u0219 County Clinical Hospital, 540011 T\u00e2rgu Mure\u0219, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel","family":"Nistor","sequence":"additional","affiliation":[{"name":"Aivita Biomedical Inc., Irvine, CA 92612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-1990-6767","authenticated-orcid":false,"given":"Gabriela","family":"Jimborean","sequence":"additional","affiliation":[{"name":"Doctoral School of Medicine and Pharmacy, University of Medicine, Pharmacy, Science and Technology \u201cGeorge Emil Palade\u201d of T\u00e2rgu Mure\u0219, 540142 T\u00e2rgu Mure\u0219, Romania"},{"name":"Department of Pulmonology, University of Medicine and Pharmacy, Science and Technology \u201cGeorge Emil Palade\u201d of T\u00e2rgu Mure\u0219, 540139 T\u00e2rgu Mure\u0219, Romania"},{"name":"Pulmonology Clinic, Mure\u0219 County Clinical Hospital, 540011 T\u00e2rgu Mure\u0219, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,30]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2025, September 07). 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