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Molecular Research and Insights into COVID-19: Third Edition

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (30 September 2025) | Viewed by 11314

Special Issue Editors


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Guest Editor

Special Issue Information

Dear Colleagues,

We are now entering the fifth year of the COVID-19 pandemic, but the molecular mechanisms underlying SARS-CoV-2 infections, host immune responses, and the rationale of therapeutic interventions are still not fully understood. Though the worldwide mass vaccination campaign that was carried out reduced the risk of people developing severe disease symptoms, the frequency with which SARS-CoV-2 undergoes genetic mutation is a barrier to the development of an effective therapy for COVID-19.

This Special Issue aims to publish papers on the most recent advances in the molecular research on COVID-19 in terms of its pathogenic mechanisms, the host’s immune response, and the molecular pathways activated by therapeutic interventions. This Special Issue welcomes the submission of both original articles and comprehensive reviews concerning the molecular pathways involved in COVID-19’s pathophysiology and resolution.

Dr. Manuela Rizzi
Dr. Pier Paolo Sainaghi
Guest Editors

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Keywords

  • SARS-CoV-2
  • COVID-19
  • prognostic and diagnostic biomarkers
  • molecular mechanism of infection
  • molecular pathophysiology
  • immune response

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Published Papers (3 papers)

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Research

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13 pages, 1074 KB  
Article
Global and Sex-Stratified Genome-Wide Association Study of Long COVID Based on Patient-Driven Symptom Recall
by Sara Polo-Alonso, Álvaro Hernáez, Irene R. Dégano, Ruth Martí-Lluch, Mel·lina Pinsach-Abuin, Roberto Elosua, Isaac Subirana, Marta Puigmulé, Alexandra Pérez, Raquel Cruz, Silvia Diz-de Almeida, Eulàlia Puigdecant, Elisabet Selga, Xavier Nogues, Joan Ramon Masclans, Roberto Güerri-Fernández, Héctor Cubero-Gallego, Helena Tizon-Marcos, Beatriz Vaquerizo, Ramon Brugada, Rafel Ramos, Anna Camps-Vilaró and Jaume Marrugatadd Show full author list remove Hide full author list
Int. J. Mol. Sci. 2025, 26(18), 9252; https://doi.org/10.3390/ijms26189252 - 22 Sep 2025
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Abstract
We aimed to explore the global and sex-specific genetic variants associated with long COVID, as defined by patient-driven symptom recall. A 1-year cohort study of 2411 COVID-19 patients collected long COVID symptoms with an open-ended, non-directed questionnaire, and long COVID incidence was determined [...] Read more.
We aimed to explore the global and sex-specific genetic variants associated with long COVID, as defined by patient-driven symptom recall. A 1-year cohort study of 2411 COVID-19 patients collected long COVID symptoms with an open-ended, non-directed questionnaire, and long COVID incidence was determined according to the World Health Organization definition. Global and sex-stratified genome-wide association analyses were conducted by logistic regression models adjusted for age, sex (in the global analysis), and the first 10 principal components. We assessed sex-variant interactions and performed gene-based analyses, gene mapping, and gene-set enrichment analyses. When comparing the 1392 long COVID cases with the non-cases, we identified 23 lead variants from suggestive signals: 13 from the global analysis, 5 from females, and 5 from males. Five variants showed a significant interaction with sex (two in females, three in males). We mapped 15 protein-coding genes related to diseases of the immune and nervous systems and tumoral processes. Notably, CD5 and VPS37C, linked to immune function, were significantly associated with long COVID in men. Our results suggest that persistent immune dysregulation may be involved in the development of precisely defined long COVID. Full article
(This article belongs to the Special Issue Molecular Research and Insights into COVID-19: Third Edition)
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Review

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40 pages, 1277 KB  
Review
Do Long COVID and COVID Vaccine Side Effects Share Pathophysiological Picture and Biochemical Pathways?
by Jean-François Lesgards, Dominique Cerdan and Christian Perronne
Int. J. Mol. Sci. 2025, 26(16), 7879; https://doi.org/10.3390/ijms26167879 - 15 Aug 2025
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Abstract
COVID affects around 400 million individuals today with a strong economic impact on the global economy. The list of long COVID symptoms is extremely broad because it is derived from neurological, cardiovascular, respiratory, immune, and renal dysfunctions and damages. We review here these [...] Read more.
COVID affects around 400 million individuals today with a strong economic impact on the global economy. The list of long COVID symptoms is extremely broad because it is derived from neurological, cardiovascular, respiratory, immune, and renal dysfunctions and damages. We review here these pathophysiological manifestations and the predictors of this multi-organ pathology like the persistence of the virus, altered endothelial function, unrepaired tissue damage, immune dysregulation, and gut dysbiosis. We also discuss the similarities between long COVID and vaccine side effects together with possible common immuno-inflammatory pathways. Since the spike protein is present in SARS-CoV-2 (and its variants) but also produced by the COVID vaccines, its toxicity may also apply to all mRNA or adenoviral DNA vaccines as they are based on the production of a very similar spike protein to the virus. After COVID infection or vaccination, the spike protein can last for months in the body and may interact with ACE2 receptors and mannan-binding lectin (MBL)/mannan-binding lectin serine protease 2 (MASP-2), which are present almost everywhere in the organism. As a result, the spike protein may be able to trigger inflammation in a lot of organs and systems similar to COVID infection. We suggest that three immuno-inflammatory pathways are particularly key and responsible for long COVID and COVID vaccine side effects, as it has been shown for COVID, which may explain in large part their strong similarities: the renin–angiotensin–aldosterone system (RAAS), the kininogen–kinin–kallikrein system (KKS), and the lectin complement pathway. We propose that therapeutic studies should focus on these pathways to propose better cures for both long COVID as well as for COVID vaccine side effects. Full article
(This article belongs to the Special Issue Molecular Research and Insights into COVID-19: Third Edition)
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Other

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2 pages, 147 KB  
Correction
Correction: Lesgards et al. Do Long COVID and COVID Vaccine Side Effects Share Pathophysiological Picture and Biochemical Pathways? Int. J. Mol. Sci. 2025, 26, 7879
by Jean-François Lesgards, Dominique Cerdan and Christian Perronne
Int. J. Mol. Sci. 2025, 26(19), 9513; https://doi.org/10.3390/ijms26199513 - 29 Sep 2025
Abstract
In the original publication [...] Full article
(This article belongs to the Special Issue Molecular Research and Insights into COVID-19: Third Edition)
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