Pathogenesis of SARS-CoV-2 and Potential Therapeutic Strategies: A Scoping Review
5 affiliations
- 1Research Affiliate, Canadian Global Medical Education Initiative (CGMEI), Vancouver, Canada.
- 2Department of Nursing, School of Nursing and Midwifery, Torbat Heydariyeh University of Medical Sciences, Torbat Heydariyeh, Iran.
- 3Department of Surgery, University of British Columbia, Vancouver, Canada.
- 4Shahid Hasheminejad Educational, Research and Treatment Center, Mashhad University of Medical Sciences, Mashhad, Iran.
- 5Department of Biology, Mashhad Branch, Islamic Azad University, Mashhad, Iran.
Abstract
Background: This scoping review synthesizes available evidence on the pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), its potential association with acute respiratory distress syndrome (ARDS), and its broader impact on respiratory health and immune function.
Methods: This scoping review followed a structured nine-step process in alignment with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, the Cochrane Handbook, and the Joanna Briggs Institute (JBI) Manual for Evidence Synthesis. A comprehensive search was conducted across multiple databases, including PubMed/Medline, Scopus, Embase, and Web of Science, supplemented by grey literature sources, targeting English-language studies published from 2016 to November 2024. Rayyan was used for literature screening and selection. Eligibility criteria encompassed diverse research designs, including randomized controlled trials, observational studies, molecular dynamics simulations, hypotheses, and case studies, without geographic restrictions. The PRISMA Extension for Scoping Reviews (PRISMA-ScR) checklist guided data extraction, and a structured Excel sheet was used for this purpose.
Results: From an initial pool of 4,778 screened records, 46 primary studies were selected for thematic analysis, supplemented by three review articles used for background context. The studies were categorized into nine thematic groups addressing corticosteroid therapy, surfactant disruption, angiotensin-converting enzyme 2 (ACE2) receptor biology, calcium signaling, lysophosphatidylserine, cannabinoid effects, metabolic alterations, hypocalcemia, and neurological outcomes. The review summarizes evidence on the virus's effects on the respiratory system and other organs, detailing symptom presentation and severe complications. The literature suggests potential therapeutic roles for corticosteroids in severe cases, gender-specific differences in immune responses, and the involvement of lipid metabolism and calcium dynamics in disease progression. Evidence on immune-targeting therapies, cannabinoid effects, and metabolic and epigenetic changes is also examined. Neurological and cognitive outcomes associated with COVID-19 are discussed.
Conclusion: Synthesizing the reviewed evidence, we propose a conceptual model in which SARS-CoV-2 may disrupt surfactant homeostasis and modulate apoptotic pathways, including Janus kinase–signal transducer and activator of transcription (JAK-STAT) and p53-associated mechanisms in type II pneumocytes, potentially creating a permissive environment for inflammatory cascades. Clinical trial evidence supports the use of corticosteroids (particularly dexamethasone) in severe coronavirus disease 2019 (COVID-19) cases requiring respiratory support, though the benefit is not established in milder disease. Preliminary clinical studies suggest that exogenous surfactant may improve oxygenation parameters in select patients with ARDS, but these findings require confirmation in larger randomized trials. Hypocalcemia observed in COVID-19 patients appears independent of vitamin D and parathyroid hormone levels and warrants further mechanistic investigation. Several preclinical hypotheses—including calcium chelation, antibody-mediated spike protein S1 subunit (S1) blockade, and cannabidiol administration—have emerged from in vitro and in silico studies; however, none have yet been validated in clinical settings. The observed gender-based differences in immune responses and the cognitive changes associated with altered glutamine metabolism highlight important areas for future translational and clinical research.
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BibTeX
@article{haghighi2026pathogenesis,
title = {{Pathogenesis of SARS-CoV-2 and Potential Therapeutic Strategies: A Scoping Review}},
author = {Elnaz Haghighi and Seyedeh Toktam Masoumian Hosseini and Karim Qayumi and Mohsen Masoumian Hosseini and Masoud Homayouni Tabrizi},
journal = {Journal of Practical Emergency Medicine},
year = {2026},
month = oct,
doi = {10.22037/jpem.v13i1.48725},
url = {https://doi.org/10.22037/jpem.v13i1.48725},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Pathogenesis of SARS-CoV-2 and Potential Therapeutic Strategies: A Scoping Review
AU - Elnaz Haghighi
AU - Seyedeh Toktam Masoumian Hosseini
AU - Karim Qayumi
AU - Mohsen Masoumian Hosseini
AU - Masoud Homayouni Tabrizi
PY - 2026
DA - 2026/10/23
JO - Journal of Practical Emergency Medicine
DO - 10.22037/jpem.v13i1.48725
UR - https://doi.org/10.22037/jpem.v13i1.48725
AB - Background: This scoping review synthesizes available evidence on the pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), its potential association with acute respiratory distress syndrome (ARDS), and its broader impact on respiratory health and immune function. Methods: This scoping review followed a structured nine-step process in alignment with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, the Cochrane Handbook, and the Joanna Briggs Institute (JBI) Manual for Evidence Synthesis. A comprehensive search was conducted across multiple databases, including PubMed/Medline, Scopus, Embase, and Web of Science, supplemented by grey literature sources, targeting English-language studies published from 2016 to November 2024. Rayyan was used for literature screening and selection. Eligibility criteria encompassed diverse research designs, including randomized controlled trials, observational studies, molecular dynamics simulations, hypotheses, and case studies, without geographic restrictions. The PRISMA Extension for Scoping Reviews (PRISMA-ScR) checklist guided data extraction, and a structured Excel sheet was used for this purpose. Results: From an initial pool of 4,778 screened records, 46 primary studies were selected for thematic analysis, supplemented by three review articles used for background context. The studies were categorized into nine thematic groups addressing corticosteroid therapy, surfactant disruption, angiotensin-converting enzyme 2 (ACE2) receptor biology, calcium signaling, lysophosphatidylserine, cannabinoid effects, metabolic alterations, hypocalcemia, and neurological outcomes. The review summarizes evidence on the virus's effects on the respiratory system and other organs, detailing symptom presentation and severe complications. The literature suggests potential therapeutic roles for corticosteroids in severe cases, gender-specific differences in immune responses, and the involvement of lipid metabolism and calcium dynamics in disease progression. Evidence on immune-targeting therapies, cannabinoid effects, and metabolic and epigenetic changes is also examined. Neurological and cognitive outcomes associated with COVID-19 are discussed. Conclusion: Synthesizing the reviewed evidence, we propose a conceptual model in which SARS-CoV-2 may disrupt surfactant homeostasis and modulate apoptotic pathways, including Janus kinase–signal transducer and activator of transcription (JAK-STAT) and p53-associated mechanisms in type II pneumocytes, potentially creating a permissive environment for inflammatory cascades. Clinical trial evidence supports the use of corticosteroids (particularly dexamethasone) in severe coronavirus disease 2019 (COVID-19) cases requiring respiratory support, though the benefit is not established in milder disease. Preliminary clinical studies suggest that exogenous surfactant may improve oxygenation parameters in select patients with ARDS, but these findings require confirmation in larger randomized trials. Hypocalcemia observed in COVID-19 patients appears independent of vitamin D and parathyroid hormone levels and warrants further mechanistic investigation. Several preclinical hypotheses—including calcium chelation, antibody-mediated spike protein S1 subunit (S1) blockade, and cannabidiol administration—have emerged from in vitro and in silico studies; however, none have yet been validated in clinical settings. The observed gender-based differences in immune responses and the cognitive changes associated with altered glutamine metabolism highlight important areas for future translational and clinical research.
SN - 3115-7289
ER -