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COVID-19: Advances in Pathophysiology and Therapeutics
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COVID-19: Advances in Pathophysiology and Therapeutics

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 (20 December 2024) | Viewed by 5698

Special Issue Editor

Dr. Karolina Akinosoglou

E-Mail Website
Guest Editor
Department of Medicine, University General Hospital of Patras, 26504 Rio, Greece
Interests: sepsis; infections in obstetrics and gynecology; antimicrobial resistance; hospital-acquired infections; COVID-19; HIV
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

While the official pandemic status of COVID-19 may have concluded, the impact of the disease, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is far from over. In fact, there are ongoing lessons to be learned and areas of research yet to be explored. The complexity of the disease, from its intricate pathophysiology and wide array of clinical presentations to the multiple therapeutic options available, continues to challenge the medical community. This Special Issue aims to serve as a comprehensive platform for the latest research findings that explore the advances in understanding the pathophysiology and developing new therapeutic interventions for COVID-19.

The objectives of this Special Issue are as follows: firstly, to collate research articles, reviews, and case reports that contribute to an evolving understanding of the immunological mechanisms specific to COVID-19; secondly, to feature evidence-based, clinically relevant updates on available treatment modalities and explore the current pharmacological landscape; and lastly, to facilitate a multidisciplinary discussion that aligns research outcomes with practical clinical applications, including the management of COVID-19 and its associated comorbid conditions.

Topics of interest may include:

Molecular and cellular mechanisms of SARS-CoV-2 infection and immune response underlying COVID-19;

Emerging therapeutic avenues and translational research findings that translate into clinical practice;

Biomarkers for disease severity and prognosis;

Advances in antiviral agents, monoclonal antibodies, and other pharmacotherapeutics;

Therapeutic management of comorbid conditions in COVID-19 patients;

Evaluations on the efficacy of existing and novel treatments.

Dr. Karolina Akinosoglou
Guest Editor

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

  • COVID-19
  • SARS-CoV-2
  • pathophysiology
  • immunology
  • pharmacotherapy
  • biomarkers
  • comorbidities
  • clinical management
  • disease severity
  • treatment efficacy

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Published Papers (4 papers)

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Research

15 pages, 1731 KiB  
Article
Role of Artificial Intelligence in Identifying Vital Biomarkers with Greater Precision in Emergency Departments During Emerging Pandemics
by Nicolás J. Garrido, Félix González-Martínez, Ana M. Torres, Pilar Blasco-Segura, Susana Losada, Adrián Plaza and Jorge Mateo
Int. J. Mol. Sci. 2025, 26(2), 722; https://doi.org/10.3390/ijms26020722 - 16 Jan 2025
Viewed by 1640
Abstract
The COVID-19 pandemic has accelerated advances in molecular biology and virology, enabling the identification of key biomarkers to differentiate between severe and mild cases. Furthermore, the use of artificial intelligence (AI) and machine learning (ML) to analyze large datasets has been crucial for [...] Read more.
The COVID-19 pandemic has accelerated advances in molecular biology and virology, enabling the identification of key biomarkers to differentiate between severe and mild cases. Furthermore, the use of artificial intelligence (AI) and machine learning (ML) to analyze large datasets has been crucial for rapidly identifying relevant biomarkers for disease prognosis, including COVID-19. This approach enhances diagnostics in emergency settings, allowing for more accurate and efficient patient management. This study demonstrates how machine learning algorithms in emergency departments can rapidly identify key biomarkers for the vital prognosis in an emerging pandemic using COVID-19 as an example by analyzing clinical, epidemiological, analytical, and radiological data. All consecutively admitted patients were included, and more than 89 variables were processed using the Random Forest (RF) algorithm. The RF model achieved the highest balanced accuracy at 92.61%. The biomarkers most predictive of mortality included procalcitonin (PCT), lactate dehydrogenase (LDH), and C-reactive protein (CRP). Additionally, the system highlighted the significance of interstitial infiltrates in chest X-rays and D-dimer levels. Our results demonstrate that RF is crucial in identifying critical biomarkers in emerging diseases, accelerating data analysis, and optimizing prognosis and personalized treatment, emphasizing the importance of PCT and LDH in high-risk patients. Full article
(This article belongs to the Special Issue COVID-19: Advances in Pathophysiology and Therapeutics)
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12 pages, 1035 KiB  
Article
Prolactin Role in COVID-19 and Its Association with the Underlying Inflammatory Response
by Eleni Polyzou, Georgios Schinas, Panagiotis Bountouris, Dimitra Georgakopoulou, Anne-Lise de Lastic, Anastasia Parthymou, Charalambos Gogos, Venetsana Kyriazopoulou, Athanasia Mouzaki, Anastasia Theodoropoulou and Karolina Akinosoglou
Int. J. Mol. Sci. 2024, 25(22), 11905; https://doi.org/10.3390/ijms252211905 - 6 Nov 2024
Viewed by 807
Abstract
The COVID-19 pandemic has prompted interest in identifying reliable biomarkers to predict disease severity and guide clinical decisions. Prolactin (PRL), a hormone traditionally associated with lactation, has gained attention for its role in immune modulation. This study aimed to assess PRL as a [...] Read more.
The COVID-19 pandemic has prompted interest in identifying reliable biomarkers to predict disease severity and guide clinical decisions. Prolactin (PRL), a hormone traditionally associated with lactation, has gained attention for its role in immune modulation. This study aimed to assess PRL as a biomarker for disease severity in COVID-19. A prospective cohort of 142 patients with moderate to severe COVID-19, defined as a WHO-CPS 5 or 6, was recruited from the University General Hospital of Patras. Baseline PRL levels were measured using an electrochemiluminescence immunoassay, and serum cytokines, including IL-1β, IL-6, IL-8, IL-10, IL-12p70, and TNF-α, were quantified through flow cytometry. Clinical outcomes, including mortality and the need for invasive mechanical ventilation (IMV), were recorded. Results indicated that PRL levels were significantly higher in female patients (12.95 ng/mL vs. 9.40 ng/mL, p < 0.001) but they did not correlate with key severity indices such as CCI, SOFA score upon admission or inflammatory markers. No significant associations between baseline PRL levels, cytokine concentrations, and clinical outcomes in COVID-19 were noted. Our findings suggest that PRL may lack prognostic reliability for disease severity compared to more established predictive markers and that its role in the immune response remains uncertain. Full article
(This article belongs to the Special Issue COVID-19: Advances in Pathophysiology and Therapeutics)
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13 pages, 2486 KiB  
Article
Immune Profile in COVID-19: Unveiling TR3-56 Cells in SARS-CoV-2 Infection
by Flavia Carriero, Valentina Rubino, Monica Gelzo, Giulia Scalia, Maddalena Raia, Massimo Ciccozzi, Ivan Gentile, Biagio Pinchera, Giuseppe Castaldo, Giuseppina Ruggiero and Giuseppe Terrazzano
Int. J. Mol. Sci. 2024, 25(19), 10465; https://doi.org/10.3390/ijms251910465 - 28 Sep 2024
Viewed by 1279
Abstract
The emergence of COronaVIrus Disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), presented a global health challenge since its identification in December 2019. With clinical manifestations ranging from mild respiratory symptoms to severe multi-organ dysfunction, COVID-19 continues to affect [...] Read more.
The emergence of COronaVIrus Disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), presented a global health challenge since its identification in December 2019. With clinical manifestations ranging from mild respiratory symptoms to severe multi-organ dysfunction, COVID-19 continues to affect populations worldwide. The complex interactions between SARS-CoV-2 variants and the human immune system are crucial for developing effective therapies, vaccines, and preventive measures. Understanding these immune responses highlights the intricate nature of COVID-19 pathogenesis. This retrospective study analyzed, by flow cytometry approach, a cohort of patients infected with SARS-CoV-2 during the initial pandemic waves from 2020 to 2021. It focused on untreated individuals at the time of hospital admission and examined the presence of TR3-56 cells in their immune profiles during the anti-viral immune response. Our findings provide additional insights into the complex immunological dynamics of SARS-CoV-2 infection and highlight the potential role of TR3-56 cells as crucial components of the immune response. We suggest that TR3-56 cells could serve as valuable biomarkers for identifying more severe cases of COVID-19, aiding in the assessment and management of the disease. Full article
(This article belongs to the Special Issue COVID-19: Advances in Pathophysiology and Therapeutics)
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13 pages, 5377 KiB  
Article
Development of a Biosafety Level 1 Cellular Assay for Identifying Small-Molecule Antivirals Targeting the Main Protease of SARS-CoV-2: Evaluation of Cellular Activity of GC376, Boceprevir, Carmofur, Ebselen, and Selenoneine
by Yasunori Fukumoto, Noriyuki Suzuki, Reina Hara, Yu-ki Tanaka and Yasumitsu Ogra
Int. J. Mol. Sci. 2024, 25(11), 5767; https://doi.org/10.3390/ijms25115767 - 25 May 2024
Viewed by 1358
Abstract
While research has identified several inhibitors of the main protease (Mpro) of SARS-CoV-2, a significant portion of these compounds exhibit reduced activity in the presence of reducing agents, raising concerns about their effectiveness in vivo. Furthermore, the conventional biosafety level 3 (BSL-3) for [...] Read more.
While research has identified several inhibitors of the main protease (Mpro) of SARS-CoV-2, a significant portion of these compounds exhibit reduced activity in the presence of reducing agents, raising concerns about their effectiveness in vivo. Furthermore, the conventional biosafety level 3 (BSL-3) for cellular assays using viral particles poses a limitation for the widespread evaluation of Mpro inhibitor efficacy in a cell-based assay. Here, we established a BSL-1 compatible cellular assay to evaluate the in vivo potential of Mpro inhibitors. This assay utilizes mammalian cells expressing a tagged Mpro construct containing N-terminal glutathione S-transferase (GST) and C-terminal hemagglutinin (HA) tags and monitors Mpro autodigestion. Using this method, GC376 and boceprevir effectively inhibited Mpro autodigestion, suggesting their potential in vivo activity. Conversely, carmofur and ebselen did not exhibit significant inhibitory effects in this assay. We further investigated the inhibitory potential of selenoneine on Mpro using this approach. Computational analyses of binding energies suggest that noncovalent interactions play a critical role in facilitating the covalent modification of the C145 residue, leading to Mpro inhibition. Our method is straightforward, cost-effective, and readily applicable in standard laboratories, making it accessible to researchers with varying levels of expertise in infectious diseases. Full article
(This article belongs to the Special Issue COVID-19: Advances in Pathophysiology and Therapeutics)
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