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Coronavirus Disease (COVID-19): Pathophysiology (6th 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: 20 November 2025 | Viewed by 11193

Special Issue Editors


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Guest Editor
1. The Houston Methodist Research Institute, Houston, TX 77030, USA
2. Department of Surgery, The Houston Methodist Hospital, Houston, TX 77030, USA
Interests: immunology; structural RNA; cellular cytoskeleton; macrophages
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Guest Editor
Dynamics and Mechanics of Epithelia Group, Faculty of Medicine, Institute of Genetics and Development of Rennes, University of Rennes, CNRS, UMR 6290, 35043 Rennes, France
Interests: embryo development; cell cycle; gene regulation; cancer; stem cells; gonads; genetic diseases
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The COVID-19 pandemic triggered an astounding wave of research on all aspects of this novel viral disease. The pace of research on this completely unprecedented situation has been remarkable, resulting in the explosion of scientific reports and extraordinary achievements in the areas of treatment and prevention. The number of novel and efficient vaccines created is the best example of this. The avalanche of research in just one year vastly increased our knowledge of SARS-CoV-2 and other coronaviruses. We uncovered and understood some of the hitherto unknown mechanisms involved in the immune response to SARS-CoV-2 infection. Scientific research delivered novel antiviral drugs and treatments to decrease the severity of the disease and save human lives during the pandemic. Genetic research allows for the identification of continuously evolving novel variants of the virus, and epidemiological studies characterize as well as follow their propagation in various regions of the world. Unprecedented phenomena were discovered, such as enormous differences in viral infectivity and the course of the disease in children and adults or between different individuals. Although new observations and research continue to expand our knowledge about this disease, we still have many unanswered questions. Does COVID-19 provoke diabetes? Does it cause orchitis? Why are most children quite resistant to SARS-CoV-2 infection, while some of them develop pediatric inflammatory multisystem syndrome (PIMS)? Why do some COVID-19 patients continue to experience symptoms after their initial recovery? These people suffer from the so-called post-COVID-19 syndrome or "long COVID-19." What causes these long-term effects? Why do some patients, a long time after their purported recovery, suffer from nervous system and brain damage? Another area that is still not fully understood is the responses of different types of immune cells to the initial infection and their role in both the halting and propagation of the virus within the patient’s body. Additionally, why in some, but not all, patients does the immune system go into overdrive, causing a cytokine storm?

In this Special Issue, entitled “Coronavirus Disease (COVID-19): Pathophysiology”, we aim to present research and theoretical papers addressing all these questions in addition to many others related to COVID-19. Thus, we invite colleagues working in any field related to COVID-19, from viral genetics to epidemiology and computer modeling, to submit their research for publication in this Special Issue. We believe that this Special Issue of the International Journal of Molecular Sciences will be not only very timely but also scientifically innovative and exciting.

Prof. Dr. Malgorzata Kloc
Prof. Dr. Jacek Z. Kubiak
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • SARS-CoV-2
  • coronavirus
  • pandemic
  • viral diseases
  • pediatrics
  • inflammation
  • immune cells
  • macrophages
  • pneumonia
  • vaccines
  • cytokines
  • cytokine storm
  • PIMS
  • immunity

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Published Papers (4 papers)

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Research

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14 pages, 1360 KB  
Article
IL-24 in COVID-19 Patients: Correlations with Disease Progression
by Richard Vollenberg, Katharina Schütte-Nütgen, Markus Strauss, Jonel Trebicka, Julia Fischer and Phil-Robin Tepasse
Int. J. Mol. Sci. 2025, 26(17), 8403; https://doi.org/10.3390/ijms26178403 - 29 Aug 2025
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Abstract
Interleukin-24 (IL-24) is a cytokine known for its role in immune regulation and apoptosis, with potential implications in viral infections like COVID-19. This study aimed to investigate the association between IL-24 serum levels and the severity of COVID-19 disease. In this prospective bi-center [...] Read more.
Interleukin-24 (IL-24) is a cytokine known for its role in immune regulation and apoptosis, with potential implications in viral infections like COVID-19. This study aimed to investigate the association between IL-24 serum levels and the severity of COVID-19 disease. In this prospective bi-center cross-sectional study, we enrolled 41 COVID-19 patients from two hospitals in Germany. Serial blood samples were collected from a subset of patients, resulting in 88 total blood samples. Patients were categorized into critical, severe, moderate, and mild disease groups based on WHO criteria. IL-24 serum levels were measured during the acute or convalescent phase using an ELISA assay. Inflammatory markers, and kidney and liver function parameters were also evaluated. Statistical analysis included non-parametric tests and correlation analysis. Elevated IL-24 serum levels were observed in ambulant patients (mild disease), compared to hospitalized patients (critical, severe, moderate disease, p < 0.05). IL-24 levels were also significantly higher in patients without oxygenation disorder compared to those with oxygenation therapy (p < 0.05). A negative correlation was found between IL-24 levels and markers of inflammation and liver/kidney function. Elevated IL-24 serum levels were associated with milder COVID-19 courses, suggesting a protective role in modulating immune responses and promoting antiviral apoptosis. Conversely, reduced IL-24 in severe cases may reflect impaired immune regulation, highlighting its potential as a biomarker and therapeutic target. Full article
(This article belongs to the Special Issue Coronavirus Disease (COVID-19): Pathophysiology (6th Edition))
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26 pages, 3939 KB  
Article
Clinical and Proteomic Associations of SARS-CoV-2 Infection and COVID-19 Vaccination in Multimorbid Patients: A Cross-Sectional Observational Study
by Anett Hudák, Aladár Pettko-Szandtner, Annamária Letoha and Tamás Letoha
Int. J. Mol. Sci. 2025, 26(16), 8007; https://doi.org/10.3390/ijms26168007 - 19 Aug 2025
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Abstract
Vaccines played a crucial role in the COVID-19 pandemic, but their long-term biological effects and efficacy in vulnerable populations remain under intensive investigation. This study assessed clinical outcomes, comorbidities, and systemic biomarker and proteomic profiles in 366 multimorbid patients, stratified into four groups [...] Read more.
Vaccines played a crucial role in the COVID-19 pandemic, but their long-term biological effects and efficacy in vulnerable populations remain under intensive investigation. This study assessed clinical outcomes, comorbidities, and systemic biomarker and proteomic profiles in 366 multimorbid patients, stratified into four groups based on SARS-CoV-2 infection and vaccination status (COV+ vac+, COV+ vac−, COV− vac+, COV− vac−). Clinical and laboratory data, including comorbidities and relevant biomarkers, were collected. Proteomic analysis using mass spectrometry was performed to identify molecular changes associated with infection and vaccination. Statistical analyses examined associations between clinical status, biomarkers, and patient outcomes. As most participants received mRNA-based vaccines, the results primarily reflect responses to spike protein-expressing platforms. Biomarkers of cardiac and renal stress—namely proBNP and carbamide—were elevated in vaccinated individuals. Five deaths occurred in the COV+ vac+ group and two in the COV+ vac− group, most of which were attributed to exacerbations of pre-existing chronic diseases rather than to COVID-19 pneumonia. Protection against breakthrough infections waned over time, particularly beyond 200 days post-vaccination. Mass spectrometry identified proteins such as actin, fibrinogen chains, and SAA2 as potential diagnostic targets. Although the cross-sectional observational design limits the ability to draw causal inferences, the observed waning immunity and potential systemic alterations in vaccinated multimorbid patients highlight the importance of longitudinal follow-up to guide tailored immunization strategies and post-vaccination monitoring in high-risk groups. Full article
(This article belongs to the Special Issue Coronavirus Disease (COVID-19): Pathophysiology (6th Edition))
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15 pages, 1692 KB  
Article
TNF/IFN-γ Co-Signaling Induces Differential Cellular Activation in COVID-19 Patients: Implications for Patient Outcomes
by Lucero A. Ramón-Luing, Laura Edith Martínez-Gómez, Carlos Martinez-Armenta, Gabriela Angélica Martínez-Nava, Karen Medina-Quero, Gloria Pérez-Rubio, Ramcés Falfán-Valencia, Ivette Buendia-Roldan, Julio Flores-Gonzalez, Ranferi Ocaña-Guzmán, Moisés Selman, Alberto López-Reyes and Leslie Chavez-Galan
Int. J. Mol. Sci. 2025, 26(3), 1139; https://doi.org/10.3390/ijms26031139 - 28 Jan 2025
Viewed by 2267
Abstract
TNF and IFN-γ are key proinflammatory cytokines implicated in the pathophysiology of COVID-19. Toll-like receptor (TLR)7 and TLR8 are known to recognize SARS-CoV-2 and induce TNF and IFN-γ production. However, it is unclear whether TNF and IFN-γ levels are altered through TLR-dependent pathways [...] Read more.
TNF and IFN-γ are key proinflammatory cytokines implicated in the pathophysiology of COVID-19. Toll-like receptor (TLR)7 and TLR8 are known to recognize SARS-CoV-2 and induce TNF and IFN-γ production. However, it is unclear whether TNF and IFN-γ levels are altered through TLR-dependent pathways and whether these pathways mediate disease severity during COVID-19. This study aimed to investigate the association between TNF/IFN-γ levels and immune cell activation to understand their role in disease severity better. We enrolled 150 COVID-19 patients, who were classified by their systemic TNF and IFN-γ levels (high (H) or normal–low (N-L)) as TNFHIFNγH, TNFHIFNγN-L, TNFN-LIFNγH, and TNFN-LIFNγN-L. Compared to patients with TNFN-LIFNγN-L, patients with TNFHIFNγH had high systemic levels of pro- and anti-inflammatory cytokines and cytotoxic molecules, and their T cells and monocytes expressed TNF receptor 1 (TNFR1). Patients with TNFHIFNγH presented the SNP rs3853839 to TLR7 and increased levels of MYD88, NFκB, and IRF7 (TLR signaling), FADD, and TRADD (TNFR1 signaling). Moreover, critical patients were observed in the four COVID-19 groups, but patients with TNFHIFNγH or TNFHIFNγN-L most required invasive mechanical ventilation. We concluded that increased TNF/IFN-γ levels are associated with hyperactive immune cells, whereas normal/low levels are associated with hypoactivity, suggesting a model to explain that the pathophysiology of critical COVID-19 may be mediated through different pathways depending on TNF and IFN-γ levels. These findings highlight the potential for exploring the modulation of TNF and IFN-γ as a therapeutic strategy in severe COVID-19. Full article
(This article belongs to the Special Issue Coronavirus Disease (COVID-19): Pathophysiology (6th Edition))
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Review

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20 pages, 555 KB  
Review
Utility of Protein Markers in COVID-19 Patients
by Alicia López-Biedma, María Ángeles Onieva-García, Desirée Martín-García, Maximino Redondo and Marilina García-Aranda
Int. J. Mol. Sci. 2025, 26(2), 653; https://doi.org/10.3390/ijms26020653 - 14 Jan 2025
Viewed by 2010
Abstract
COVID-19 has been a challenge at the healthcare level not only in the early stages of the pandemic, but also in the subsequent appearance of long-term COVID-19. Several investigations have attempted to identify proteomic biomarkers in an attempt to improve clinical care, guide [...] Read more.
COVID-19 has been a challenge at the healthcare level not only in the early stages of the pandemic, but also in the subsequent appearance of long-term COVID-19. Several investigations have attempted to identify proteomic biomarkers in an attempt to improve clinical care, guide treatment and predict possible patient outcomes. Proteins such as C-reactive protein (CRP) or interleukin 6 (IL-6) are clear markers of severe disease, but many others have been proposed that could help in risk stratification and in the prediction of specific complications. This review aims to bring together the most relevant studies in this regard, providing information to identify the most notable biomarkers in relation to COVID-19 found to date. Full article
(This article belongs to the Special Issue Coronavirus Disease (COVID-19): Pathophysiology (6th Edition))
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