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Recent Advances in Pathophysiology and Immunology Related to SARS-CoV-2 Infection
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Recent Advances in Pathophysiology and Immunology Related to SARS-CoV-2 Infection

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 2024) | Viewed by 2627

Special Issue Editor

Dr. Vito D’Agnano

E-Mail Website
Guest Editor
Department of Translational Medical Sciences, University of Campania “L. Vanvitelli”, 80131 Naples, Italy
Interests: COVID-19; lung cancer; NSCLC; immune checkpoint inhibitors; ICIs; interstitial lung diseases; IPF; immunopathology

Special Issue Information

Dear Colleagues,

It has been three years since the worldwide spread of COVID-19, an extremely severe pandemic caused by a newly identified virus, termed SARS-CoV-2, a highly contagious betacoronavirus. The clinical spectrum of COVID-19 is extremely heterogeneous, ranging from an asymptomatic course to a very severe clinical scenario, with respiratory failure and death.

From a pathophysiological perspective, the chain of events from the first viral contact to the clinical manifestation, although known, may be unpredictable from one subject to another. In addition, the resolution phase of COVID-19 is not homogenous amongst patients. Whilst innate as well as adaptive immunity are crucial to combat infection, an excessive and dysregulated immune response is recognized to be counter-productive.

To enhance our comprehension of the pathophysiology and immunology of COVID-19, this Special Issue aims to collect the most recent evidence and advances in this specific field. Original research articles and comprehensive reviews covering the pathophysiological and immunological biomolecular aspects of SARS-CoV-2 infection and its clinical manifestations are welcomed in this Special Issue.

Dr. Vito D’Agnano
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

  • SARS-CoV-2
  • COVID-19
  • immunology
  • pathophysiology
  • immunopathology

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Published Papers (3 papers)

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Research

16 pages, 1431 KiB  
Article
Transpulmonary Plasma Endothelin-1 Arterial:Venous Ratio Differentiates Survivors from Non-Survivors in Critically Ill Patients with COVID-19-Induced Acute Respiratory Distress Syndrome
by Alice G. Vassiliou, Anastasia Roumpaki, Chrysi Keskinidou, Nikolaos Athanasiou, Stamatios Tsipilis, Edison Jahaj, Charikleia S. Vrettou, Vassiliki Giannopoulou, Asimenia Halioti, Georgios Ferentinos, Ioanna Dimopoulou, Anastasia Kotanidou, David Langleben and Stylianos E. Orfanos
Int. J. Mol. Sci. 2024, 25(19), 10640; https://doi.org/10.3390/ijms251910640 - 2 Oct 2024
Viewed by 480
Abstract
Endothelin-1 (ET-1) is a potent vasoconstrictor produced by endothelial cells and cleared from circulating blood mainly in the pulmonary vasculature. In a healthy pulmonary circulation, the rate of local production of ET-1 is less than its rate of clearance. In the present study, [...] Read more.
Endothelin-1 (ET-1) is a potent vasoconstrictor produced by endothelial cells and cleared from circulating blood mainly in the pulmonary vasculature. In a healthy pulmonary circulation, the rate of local production of ET-1 is less than its rate of clearance. In the present study, we aimed to investigate whether the abnormal pulmonary circulatory handling of ET-1 relates to poor clinical outcomes in patients with coronavirus disease 2019 (COVID-19)-induced acute respiratory distress syndrome (ARDS). To this end, central venous and systemic arterial ET-1 plasma levels were simultaneously measured on Days 1 and 3 following ICU admission in mechanically ventilated COVID-19 patients with ARDS (COVID-19 ARDS, N = 18). Central venous and systemic arterial ET-1 plasma levels were also measured in two distinct SARS-CoV-2-negative mechanically ventilated critically ill patient groups, matched for age, sex, and critical illness severity, with ARDS (non-COVID-19 ARDS, N = 14) or without ARDS (non-COVID-19 non-ARDS, N = 20). Upon ICU admission, COVID-19-induced ARDS patients had higher systemic arterial and central venous ET-1 levels compared to the non-COVID-19 ARDS and non-COVID-19 non-ARDS patients (p < 0.05), yet a normal systemic arterial:central venous (A:V) ET-1 ratio [0.63 (0.49–1.02)], suggesting that pulmonary ET-1 clearance is intact in these patients. On the other hand, the non-COVID-19 ARDS patients demonstrated abnormal ET-1 handling [A:V ET-1 ratio 1.06 (0.93–1.20)], while the non-COVID-19 non-ARDS group showed normal ET-1 handling [0.79 (0.52–1.11)]. On Day 3, the A:V ratio in all three groups was <1. When the COVID-19 ARDS patients were divided based on 28-day ICU mortality, while their systemic arterial and central venous levels did not differ, the A:V ET-1 ratio was statistically significantly higher upon ICU admission in the non-survivors [0.95 (0.78–1.34)] compared to the survivors [0.57 (0.48–0.92), p = 0.027]. Our results highlight the potential importance of ET-1 as both a biomarker and a therapeutic target in critically ill COVID-19 patients. The elevated A:V ET-1 ratio in non-survivors suggests that the early disruption of pulmonary ET-1 handling may be a key marker of poor prognosis. Full article
(This article belongs to the Special Issue Recent Advances in Pathophysiology and Immunology Related to SARS-CoV-2 Infection)
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14 pages, 973 KiB  
Article
Prospective Variation of Cytokine Trends during COVID-19: A Progressive Approach from Disease Onset until Outcome
by Marina de Castro Deus, Ana Carolina Gadotti, Erika Sousa Dias, Júlia Bacarin Monte Alegre, Beatriz Akemi Kondo Van Spitzenbergen, Gabriela Bohnen Andrade, Sara Soares Tozoni, Rebecca Benicio Stocco, Marcia Olandoski, Felipe Francisco Bondan Tuon, Ricardo Aurino Pinho, Lucia de Noronha, Cristina Pellegrino Baena and Andrea Novais Moreno-Amaral
Int. J. Mol. Sci. 2024, 25(19), 10578; https://doi.org/10.3390/ijms251910578 - 1 Oct 2024
Viewed by 721
Abstract
COVID-19 is characterized by pronounced hypercytokinemia. The cytokine switch, marked by an imbalance between pro-inflammatory and anti-inflammatory cytokines, emerged as a focal point of investigation throughout the COVID-19 pandemic. However, the kinetics and temporal dynamics of cytokine release remain contradictory, making the development [...] Read more.
COVID-19 is characterized by pronounced hypercytokinemia. The cytokine switch, marked by an imbalance between pro-inflammatory and anti-inflammatory cytokines, emerged as a focal point of investigation throughout the COVID-19 pandemic. However, the kinetics and temporal dynamics of cytokine release remain contradictory, making the development of new therapeutics difficult, especially in severe cases. This study collected serum samples from SARS-CoV-2 infected patients at 72 h intervals and monitored them for various cytokines at each timepoint until hospital discharge or death. Cytokine levels were analyzed based on time since symptom onset and patient outcomes. All cytokines studied prospectively were strong predictors of mortality, particularly IL-4 (AUC = 0.98) and IL-1β (AUC = 0.96). First-timepoint evaluations showed elevated cytokine levels in the mortality group (p < 0.001). Interestingly, IFN-γ levels decreased over time in the death group but increased in the survival group. Patients who died exhibited sustained levels of IL-1β and IL-4 and increased IL-6 levels over time. These findings suggest cytokine elevation is crucial in predicting COVID-19 mortality. The dynamic interplay between IFN-γ and IL-4 highlights the balance between Th1/Th2 immune responses and underscores IFN-γ as a powerful indicator of immune dysregulation throughout the infection. Full article
(This article belongs to the Special Issue Recent Advances in Pathophysiology and Immunology Related to SARS-CoV-2 Infection)
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14 pages, 1951 KiB  
Article
Antibody Responses in SARS-CoV-2-Exposed and/or Vaccinated Individuals Target Conserved Epitopes from Multiple CoV-2 Antigens
by David Yao, Raj S. Patel, Adrien Lam, Quarshie Glover, Cindy Srinivasan, Alex Herchen, Bruce Ritchie and Babita Agrawal
Int. J. Mol. Sci. 2024, 25(18), 9814; https://doi.org/10.3390/ijms25189814 - 11 Sep 2024
Viewed by 799
Abstract
There is a need to investigate novel strategies in order to create an effective, broadly protective vaccine for current and future severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreaks. The currently available vaccines demonstrate compromised efficacy against emerging SARS-CoV-2 variants of concern (VOCs), [...] Read more.
There is a need to investigate novel strategies in order to create an effective, broadly protective vaccine for current and future severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreaks. The currently available vaccines demonstrate compromised efficacy against emerging SARS-CoV-2 variants of concern (VOCs), short-lived immunity, and susceptibility to immune imprinting due to frequent boosting practices. In this study, we examined the specificity of cross-reactive IgG antibody responses in mRNA-vaccinated, AstraZeneca-vaccinated, and unvaccinated donors to identify potentially conserved, cross-reactive epitopes to target in order to create a broadly protective SARS-CoV-2 vaccine. Our study provides evidence for cross-reactive IgG antibodies specific to eight different spike (S) variants. Furthermore, the specificities of these cross-variant IgG antibody titers were associated to some extent with spike S1- and S2-subunit-derived epitopes P1 and P2, respectively. In addition, nucleocapsid (N)- and membrane (M)-specific IgG antibody titers correlated with N- and M-derived epitopes conserved across beta-CoVs, P3–7. This study reveals conserved epitopes of viral antigens, targeted by natural and/or vaccine-induced human immunity, for future designs of next-generation COVID-19 vaccines. Full article
(This article belongs to the Special Issue Recent Advances in Pathophysiology and Immunology Related to SARS-CoV-2 Infection)
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