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Coronavirus Disease (COVID-19): Pathophysiology 4.0

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 (31 January 2024) | Viewed by 11528

Special Issue Editors


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Guest Editor
Transplant Immunology, The Houston Methodist Research Institute, Houston, TX 77030, USA
Interests: macrophages; actin cytoskeleton; RhoA pathway; chronic rejection; transplantation; germ cells; Xenopus laevis; development
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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 came to understand 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 the viral infectivity and 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 the majority of children so 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 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 of 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 work 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

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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.

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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 (10 papers)

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Research

11 pages, 507 KiB  
Article
Increased Levels of Galectin-3 in Critical COVID-19
by Ioanna Nikitopoulou, Alice G. Vassiliou, Nikolaos Athanasiou, Edison Jahaj, Karolina Akinosoglou, Ioanna Dimopoulou, Stylianos E. Orfanos, Vasiliki Dimakopoulou, Georgios Schinas, Argyrios Tzouvelekis, Vassilis Aidinis and Anastasia Kotanidou
Int. J. Mol. Sci. 2023, 24(21), 15833; https://doi.org/10.3390/ijms242115833 - 31 Oct 2023
Viewed by 836
Abstract
Severe COVID-19 is related to hyperinflammation and multiple organ injury, including respiratory failure, thus requiring intensive care unit (ICU) admission. Galectin-3, a carbohydrate-binding protein exhibiting pleiotropic effects, has been previously recognized to participate in inflammation, the immune response to infections and fibrosis. The [...] Read more.
Severe COVID-19 is related to hyperinflammation and multiple organ injury, including respiratory failure, thus requiring intensive care unit (ICU) admission. Galectin-3, a carbohydrate-binding protein exhibiting pleiotropic effects, has been previously recognized to participate in inflammation, the immune response to infections and fibrosis. The aim of this study was to evaluate the relationship between galectin-3 and the clinical severity of COVID-19, as well as assess the prognostic accuracy of galectin-3 for the probability of ICU mortality. The study included 235 COVID-19 patients with active disease, treated in two different Greek hospitals in total. Our results showed that median galectin-3 serum levels on admission were significantly increased in critical COVID-19 patients (7.2 ng/mL), as compared to the median levels of patients with less severe disease (2.9 ng/mL, p = 0.003). Galectin-3 levels of the non-survivors hospitalized in the ICU were significantly higher than those of the survivors (median 9.1 ng/mL versus 5.8 ng/mL, p = 0.001). The prognostic accuracy of galectin-3 for the probability of ICU mortality was studied with a receiver operating characteristic (ROC) curve and a multivariate analysis further demonstrated that galectin-3 concentration at hospital admission could be assumed as an independent risk factor associated with ICU mortality. Our results were validated with galectin-3 measurements in a second patient cohort from a different Greek university hospital. Our results, apart from strongly confirming and advancing previous knowledge with two patient cohorts, explore the possibility of predicting ICU mortality, which could provide useful information to clinicians. Therefore, galectin-3 seems to establish its involvement in the prognosis of hospitalized COVID-19 patients, suggesting that it could serve as a promising biomarker in critical COVID-19. Full article
(This article belongs to the Special Issue Coronavirus Disease (COVID-19): Pathophysiology 4.0)
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14 pages, 2595 KiB  
Article
Age-Related COVID-19 Influence on Male Fertility
by Anastasiia D. Shcherbitskaia, Evgeniia M. Komarova, Yulia P. Milyutina, Yanina M. Sagurova, Mariia A. Ishchuk, Anastasiia V. Mikhel, Ksenia V. Ob’edkova, Elena A. Lesik, Alexander M. Gzgzyan, Natalya I. Tapilskaya, Olesya N. Bespalova and Igor Y. Kogan
Int. J. Mol. Sci. 2023, 24(21), 15742; https://doi.org/10.3390/ijms242115742 - 30 Oct 2023
Viewed by 1000
Abstract
The impact of coronavirus on the reproductive health of men attracts the special attention of many researchers. While studies suggest changes in sperm parameters and the possibility of testicular inflammation, further studies are needed to elucidate any potential age-related changes in these findings, [...] Read more.
The impact of coronavirus on the reproductive health of men attracts the special attention of many researchers. While studies suggest changes in sperm parameters and the possibility of testicular inflammation, further studies are needed to elucidate any potential age-related changes in these findings, which is the purpose of the present study. The semen quality parameters, cytokine concentration, and markers of the pro- and antioxidant system were assessed in 60 men five to seven months after the coronavirus infection and in 77 controls (without a history of coronavirus infection). Additionally, participants were divided into two age groups: less than 35 years and 35 years or older. Notably increased round cell count in ejaculate and reduced sperm hyaluronan binding ability were observed among post-infection patients younger than 35 years. In the same group, a decline in seminal plasma zinc levels and nitrotyrosine in the cell fraction was found. In men over 35 years of age, Coronavirus Disease 2019 (COVID-19) led to increased sperm DNA fragmentation, a decrease in the total antioxidant capacity, and an elevation in the levels of interleukin-1β and interleukin-10. The concentration of interleukin-1β decreased over time following recovery in all affected patients. The data obtained suggest the potential adverse impact of the coronavirus infection on male reproductive health; however, these effects appear to be age-dependent. Full article
(This article belongs to the Special Issue Coronavirus Disease (COVID-19): Pathophysiology 4.0)
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19 pages, 2073 KiB  
Article
Validation of a SARS-CoV-2 Surrogate Neutralization Test Detecting Neutralizing Antibodies against the Major Variants of Concern
by Eveline Santos da Silva, Jean-Yves Servais, Michel Kohnen, Vic Arendt, Therese Staub, the CON-VINCE Consortium, the CoVaLux Consortium, Rejko Krüger, Guy Fagherazzi, Paul Wilmes, Judith M. Hübschen, Markus Ollert, Danielle Perez-Bercoff and Carole Seguin-Devaux
Int. J. Mol. Sci. 2023, 24(19), 14965; https://doi.org/10.3390/ijms241914965 - 06 Oct 2023
Cited by 2 | Viewed by 1028
Abstract
SARS-CoV-2 infection and/or vaccination elicit a broad range of neutralizing antibody responses against the different variants of concern (VOC). We established a new variant-adapted surrogate virus neutralization test (sVNT) and assessed the neutralization activity against the ancestral B.1 (WT) and VOC Delta, Omicron [...] Read more.
SARS-CoV-2 infection and/or vaccination elicit a broad range of neutralizing antibody responses against the different variants of concern (VOC). We established a new variant-adapted surrogate virus neutralization test (sVNT) and assessed the neutralization activity against the ancestral B.1 (WT) and VOC Delta, Omicron BA.1, BA.2, and BA.5. Analytical performances were compared against the respective VOC to the reference virus neutralization test (VNT) and two CE-IVD labeled kits using three different cohorts collected during the COVID-19 waves. Correlation analyses showed moderate to strong correlation for Omicron sub-variants (Spearman’s r = 0.7081 for BA.1, r = 0.7205 for BA.2, and r = 0.6042 for BA.5), and for WT (r = 0.8458) and Delta-sVNT (r = 0.8158), respectively. Comparison of the WT-sVNT performance with two CE-IVD kits, the “Icosagen SARS-CoV-2 Neutralizing Antibody ELISA kit” and the “Genscript cPass, kit” revealed an overall good correlation ranging from 0.8673 to −0.8773 and a midway profile between both commercial kits with 87.76% sensitivity and 90.48% clinical specificity. The BA.2-sVNT performance was similar to the BA.2 Genscript test. Finally, a correlation analysis revealed a strong association (r = 0.8583) between BA.5-sVNT and VNT sVNT using a double-vaccinated cohort (n = 100) and an Omicron-breakthrough infection cohort (n = 91). In conclusion, the sVNT allows for the efficient prediction of immune protection against the various VOCs. Full article
(This article belongs to the Special Issue Coronavirus Disease (COVID-19): Pathophysiology 4.0)
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17 pages, 2025 KiB  
Article
The Effect of Potassium Canrenoate (Mineralocorticoid Receptor Antagonist) on the Markers of Inflammation in the Treatment of COVID-19 Pneumonia and Fibrosis—A Secondary Analysis of Randomized Placebo-Controlled Clinical Trial
by Igor Karolak, Rafał Hrynkiewicz, Paulina Niedźwiedzka-Rystwej, Kacper Lechowicz, Jerzy Sieńko, Aleksandra Szylińska, Wojciech Dabrowski and Katarzyna Kotfis
Int. J. Mol. Sci. 2023, 24(18), 14247; https://doi.org/10.3390/ijms241814247 - 18 Sep 2023
Viewed by 959
Abstract
In March 2020, the World Health Organization (WHO) announced a global pandemic of coronavirus disease 2019 (COVID-19) that presented mainly as an acute infection of the lower respiratory tract (pneumonia), with multiple long-term consequences, including lung fibrosis. The aim of this study was [...] Read more.
In March 2020, the World Health Organization (WHO) announced a global pandemic of coronavirus disease 2019 (COVID-19) that presented mainly as an acute infection of the lower respiratory tract (pneumonia), with multiple long-term consequences, including lung fibrosis. The aim of this study was to evaluate the influence of potassium canrenoate on inflammatory markers in the treatment of COVID-19 pneumonia. A randomized clinical trial (RCT) of intravenous potassium canrenoate vs. placebo was performed between December 2020 and November 2021. This study is a secondary analysis of that RCT. In the final analysis, a total of 49 hospitalized patients were included (24 allocated to the potassium canrenoate group and 25 to the placebo group). Patients were assessed by serum testing and blood cell cytometry on day 1 and day 7 of the intervention. Age, sex, and body mass index were not significantly different between the placebo group and intervention group. Although there was a significantly higher rate of ischemic heart disease in the placebo group, rates of other preexisting comorbidities were not significantly different. There were no significant differences in the inflammatory parameters between the potassium canrenoate and placebo groups on day 1 and day 7. However, the intragroup comparisons using Wilcoxon’s test showed significant differences between day 1 and day 7. The CD3% for potassium canrenoate increased significantly between day 1 and day 7 (12.85 ± 9.46; 11.55 vs. 20.50 ± 14.40; 17.80; p = 0.022), while the change in the placebo group was not significant (15.66 ± 11.39; 12.65 vs. 21.16 ± 15.37; 16.40; p = 0.181). The IL-1ß total count [%] increased over time for both potassium canrenoate (0.68 ± 0.58; 0.45 vs. 1.27 ± 0.83; 1.20; p = 0.004) and placebo (0.61 ± 0.59; 0.40 vs. 1.16 ± 0.91; 1.00; p = 0.016). The TNF-α total count (%) decreased significantly between day 1 and day 7 for potassium canrenoate (0.54 ± 0.45; 0.40 vs. 0.25 ± 0.23; 0.10; p = 0.031), but not for placebo (0.53 ± 0.47; 0.35 vs. 0.26 ± 0.31; 0.20; p = 0.056). Interleukin-6 (pg/mL) showed a significant decrease between day 1 and day 7 for potassium canrenoate (64.97 ± 72.52; 41.00 vs. 24.20 ± 69.38; 5.30; p = 0.006), but not the placebo group. This RCT has shown that the administration of potassium canrenoate to patients with COVID-19-induced pneumonia may be associated with significant changes in certain inflammatory markers (interleukin-6, CD3%, TNF-α), potentially related to pulmonary fibrosis. Although some positive trends were observed in the potassium canrenoate group, none of these observations reached statistical significance. Any possible benefits from the use of potassium canrenoate as an anti-inflammatory or antifibrotic drug in COVID-19 patients require further investigation. Full article
(This article belongs to the Special Issue Coronavirus Disease (COVID-19): Pathophysiology 4.0)
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15 pages, 2828 KiB  
Article
Serum Pentraxin 3 as Promising Biomarker for the Long-Lasting Inflammatory Response of COVID-19
by Anna Paola Capra, Lelio Crupi, Giuseppe Pantò, Alberto Repici, Fabrizio Calapai, Raffaele Squeri, Alessio Ardizzone and Emanuela Esposito
Int. J. Mol. Sci. 2023, 24(18), 14195; https://doi.org/10.3390/ijms241814195 - 17 Sep 2023
Cited by 1 | Viewed by 1220
Abstract
Currently, biological markers for COVID-19 disease severity still constitute the main goal of enhancing an efficient treatment to reduce critical consequences such as an abnormal systemic inflammatory response. In this regard, the latest research has shown that Pentraxin 3 (PTX3), a highly conserved [...] Read more.
Currently, biological markers for COVID-19 disease severity still constitute the main goal of enhancing an efficient treatment to reduce critical consequences such as an abnormal systemic inflammatory response. In this regard, the latest research has shown that Pentraxin 3 (PTX3), a highly conserved innate immunity protein, may serve as a valuable biochemical marker. Based on this evidence, we conducted a case–control study to compare the PTX3 serum levels and several immune-inflammatory mediators of 80 healthcare workers who were subdivided into subjects who were previously infected with SARS-CoV-2 (n = 40) and individuals who were never infected (n = 40). Using a commercially available Enzyme-Linked Immunosorbent Assay (ELISA), PTX3 and various immune-inflammatory protein levels were assessed in serum samples, while also considering possible variables (e.g., gender-related differences). We have shown elevated levels of PTX3 and other inflammatory proteins in previously infected COVID-19-positive subjects (p < 0.001). Moreover, the obtained data also indicate a degree of severity influenced by gender, as shown by the subgroup analysis, in which PTX3 expression was more pronounced in previously COVID-19-positive males (p < 0.001) than in females (p < 0.05) compared to the respective controls. In addition, our data further validate, through a direct comparison of previously COVID-19-positive subjects, greater pro-inflammatory levels in males than in females. Overall, our results may support the validity of PTX3 as a systemic biomarker in prolonged systemic inflammatory responses in the context of COVID-19. Thus, PTX3 modulation could constitute an effective therapeutic strategy for improving the recovery from COVID-19 and its systemic long-term consequences. Full article
(This article belongs to the Special Issue Coronavirus Disease (COVID-19): Pathophysiology 4.0)
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12 pages, 10573 KiB  
Article
Exploring the Syndecan-Mediated Cellular Internalization of the SARS-CoV-2 Omicron Variant
by Annamária Letoha, Anett Hudák and Tamás Letoha
Int. J. Mol. Sci. 2023, 24(18), 14140; https://doi.org/10.3390/ijms241814140 - 15 Sep 2023
Viewed by 1077
Abstract
SARS-CoV-2 variants evolve to rely more on heparan sulfate (HS) for viral attachment and subsequent infection. In our earlier work, we demonstrated that the Delta variant’s spike protein binds more strongly to HS compared to WT SARS-CoV-2, leading to enhanced cell internalization via [...] Read more.
SARS-CoV-2 variants evolve to rely more on heparan sulfate (HS) for viral attachment and subsequent infection. In our earlier work, we demonstrated that the Delta variant’s spike protein binds more strongly to HS compared to WT SARS-CoV-2, leading to enhanced cell internalization via syndecans (SDCs), a family of transmembrane HS proteoglycans (HSPGs) facilitating the cellular entry of the original strain. Using our previously established ACE2- or SDC-overexpressing cellular models, we now compare the ACE2- and SDC-dependent cellular uptake of heat-inactivated WT SARS-CoV-2 with the Delta and Omicron variants. Internalization studies with inactivated virus particles showed that ACE2 overexpression could not compensate for the loss of HS in Omicron’s internalization, suggesting that this variant primarily uses HSPGs to enter cells. Although SDCs increased the internalization of all three viruses, subtle differences could be detected between their SDC isoform preferences. The Delta variant particularly benefitted from SDC1, 2, and 4 overexpression for cellular entry, while SDC4 had the most prominent effect on Omicron internalization. The SDC4 knockdown (KD) in Calu-3 cells reduced the cellular uptake of all three viruses, but the inhibition was the most pronounced for Omicron. The polyanionic heparin also hindered the cellular internalization of all three viruses with a dominant inhibitory effect on Omicron. Omicron’s predominant HSPG affinity, combined with its preference for the universally expressed SDC4, might account for its efficient transmission yet reduced pathogenicity. Full article
(This article belongs to the Special Issue Coronavirus Disease (COVID-19): Pathophysiology 4.0)
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15 pages, 1458 KiB  
Article
Endothelial Damage, Neutrophil Extracellular Traps and Platelet Activation in COVID-19 vs. Community-Acquired Pneumonia: A Case–Control Study
by Paula González-Jiménez, Raúl Méndez, Ana Latorre, Noé Mengot, Mónica Piqueras, Soledad Reyes, Antonio Moscardó, Ricardo Alonso, Isabel Amara-Elori and Rosario Menéndez
Int. J. Mol. Sci. 2023, 24(17), 13194; https://doi.org/10.3390/ijms241713194 - 25 Aug 2023
Cited by 1 | Viewed by 897
Abstract
COVID-19 has been a diagnostic and therapeutic challenge. It has marked a paradigm shift when considering other types of pneumonia etiology. We analyzed the biomarkers related to endothelial damage and immunothrombosis in COVID-19 in comparison to community-acquired pneumonia (CAP) through a case–control study [...] Read more.
COVID-19 has been a diagnostic and therapeutic challenge. It has marked a paradigm shift when considering other types of pneumonia etiology. We analyzed the biomarkers related to endothelial damage and immunothrombosis in COVID-19 in comparison to community-acquired pneumonia (CAP) through a case–control study of 358 patients with pneumonia (179 hospitalized with COVID-19 vs. 179 matched hospitalized with CAP). Endothelial damage markers (endothelin and proadrenomedullin), neutrophil extracellular traps (NETs) (citrullinated-3 histone, cell-free DNA), and platelet activation (soluble P-selectin) were measured. In-hospital and 1-year follow-up outcomes were evaluated. Endothelial damage, platelet activation, and NET biomarkers are significantly higher in CAP compared to COVID-19. In-hospital mortality in COVID-19 was higher compared to CAP whereas 1-year mortality and cardiovascular complications were higher in CAP. In the univariate analysis (OR 95% CIs), proADM and endothelin were associated with in-hospital mortality (proADM: CAP 3.210 [1.698–6.070], COVID-19 8.977 [3.413–23.609]; endothelin: CAP 1.014 [1.006–1.022], COVID-19 1.024 [1.014–1.034]), in-hospital CVE (proADM: CAP 1.623 [1.080–2.439], COVID-19 2.146 [1.186–3.882]; endothelin: CAP 1.005 [1.000–1.010], COVID-19 1.010 [1.003–1.018]), and 1-year mortality (proADM: CAP 2.590 [1.644–4.080], COVID-19 13.562 [4.872–37.751]; endothelin: CAP 1.008 [1.003–1.013], COVID-19 1.026 [1.016–1.037]). In conclusion, COVID-19 and CAP showed different expressions of endothelial damage and NETs. ProADM and endothelin are associated with short- and long-term mortality. Full article
(This article belongs to the Special Issue Coronavirus Disease (COVID-19): Pathophysiology 4.0)
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24 pages, 4086 KiB  
Article
Identification of Host PDZ-Based Interactions with the SARS-CoV-2 E Protein in Human Monocytes
by Antonia Ávila-Flores, Juan José Sánchez-Cabezón, Ane Ochoa-Echeverría, Ana I. Checa, Jorge Rosas-García, Mariana Téllez-Araiza, Sara Casado, Rosa Liébana, Teresa Santos-Mendoza and Isabel Mérida
Int. J. Mol. Sci. 2023, 24(16), 12793; https://doi.org/10.3390/ijms241612793 - 14 Aug 2023
Viewed by 1045
Abstract
Proteins containing PDZ (post-synaptic density, PSD-95/disc large, Dlg/zonula occludens, ZO-1) domains assemble signaling complexes that orchestrate cell responses. Viral pathogens target host PDZ proteins by coding proteins containing a PDZ-binding motif (PBM). The presence of a PBM in the SARS-CoV-2 E protein contributes [...] Read more.
Proteins containing PDZ (post-synaptic density, PSD-95/disc large, Dlg/zonula occludens, ZO-1) domains assemble signaling complexes that orchestrate cell responses. Viral pathogens target host PDZ proteins by coding proteins containing a PDZ-binding motif (PBM). The presence of a PBM in the SARS-CoV-2 E protein contributes to the virus’s pathogenicity. SARS-CoV-2 infects epithelia, but also cells from the innate immune response, including monocytes and alveolar macrophages. This process is critical for alterations of the immune response that are related to the deaths caused by SARS-CoV-2. Identification of E-protein targets in immune cells might offer clues to understanding how SARS-CoV-2 alters the immune response. We analyzed the interactome of the SARS-CoV-2 E protein in human monocytes. The E protein was expressed fused to a GFP tag at the amino terminal in THP-1 monocytes, and associated proteins were identified using a proteomic approach. The E-protein interactome provided 372 partners; only 8 of these harbored PDZ domains, including the cell polarity protein ZO-2, the chemoattractant IL-16, and syntenin. We addressed the expression and localization of the identified PDZ proteins along the differentiation of primary and THP-1 monocytes towards macrophages and dendritic cells. Our data highlight the importance of identifying the functions of PDZ proteins in the maintenance of immune fitness and the viral alteration of inflammatory response. Full article
(This article belongs to the Special Issue Coronavirus Disease (COVID-19): Pathophysiology 4.0)
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21 pages, 2977 KiB  
Article
No Evidence for Myocarditis or Other Organ Affection by Induction of an Immune Response against Critical SARS-CoV-2 Protein Epitopes in a Mouse Model Susceptible for Autoimmunity
by Rebecca Maria Ignatz, Vanessa Antje Zirkenbach, Mansur Kaya, Vera Stroikova, Renate Öttl, Norbert Frey and Ziya Kaya
Int. J. Mol. Sci. 2023, 24(12), 9873; https://doi.org/10.3390/ijms24129873 - 08 Jun 2023
Viewed by 1223
Abstract
After Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) developed into a global pandemic, not only the infection itself but also several immune-mediated side effects led to additional consequences. Immune reactions such as epitope spreading and cross-reactivity may also play a role in the [...] Read more.
After Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) developed into a global pandemic, not only the infection itself but also several immune-mediated side effects led to additional consequences. Immune reactions such as epitope spreading and cross-reactivity may also play a role in the development of long-COVID, although the exact pathomechanisms have not yet been elucidated. Infection with SARS-CoV-2 can not only cause direct damage to the lungs but can also lead to secondary indirect organ damage (e.g., myocardial involvement), which is often associated with high mortality. To investigate whether an immune reaction against the viral peptides can lead to organ affection, a mouse strain known to be susceptible to the development of autoimmune diseases, such as experimental autoimmune myocarditis (EAM), was used. First, the mice were immunized with single or pooled peptide sequences of the virus’s spike (SP), membrane (MP), nucleocapsid (NP), and envelope protein (EP), then the heart and other organs such as the liver, kidney, lung, intestine, and muscle were examined for signs of inflammation or other damage. Our results showed no significant inflammation or signs of pathology in any of these organs as a result of the immunization with these different viral protein sequences. In summary, immunization with different SARS-CoV-2 spike-, membrane-, nucleocapsid-, and envelope-protein peptides does not significantly affect the heart or other organ systems adversely, even when using a highly susceptible mouse strain for experimental autoimmune diseases. This suggests that inducing an immune reaction against these peptides of the SARS-CoV-2 virus alone is not sufficient to cause inflammation and/or dysfunction of the myocardium or other studied organs. Full article
(This article belongs to the Special Issue Coronavirus Disease (COVID-19): Pathophysiology 4.0)
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13 pages, 775 KiB  
Article
SARS-CoV-2 Positive Serology and Islet Autoantibodies in Newly Diagnosed Pediatric Cases of Type 1 Diabetes Mellitus: A Single-Center Cohort Study
by Anca Andreea Boboc, Carmen Nicoleta Novac, Alexandra Gabriela Marin, Mara Ioana Ieșanu, Cristina Plătică, Teodora Buzescu, Maria Teodora Coșoreanu and Felicia Galoș
Int. J. Mol. Sci. 2023, 24(10), 8885; https://doi.org/10.3390/ijms24108885 - 17 May 2023
Cited by 3 | Viewed by 1177
Abstract
Acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, although presenting less severe forms of the disease in children, seems to play a role in the development of other conditions, including type 1 diabetes mellitus (T1DM). After the beginning of the pandemic, an increase in [...] Read more.
Acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, although presenting less severe forms of the disease in children, seems to play a role in the development of other conditions, including type 1 diabetes mellitus (T1DM). After the beginning of the pandemic, an increase in the number of T1DM pediatric patients was observed in several countries, thus leading to many questions about the complex relationship between SARS-CoV-2 infection and T1DM. Our study aimed to highlight possible correlations between SARS-CoV-2 serology and T1DM onset. Therefore, we performed an observational retrospective cohort study that included 158 children diagnosed with T1DM in the period April 2021–April 2022. The presence or absence of SARS-CoV-2 and T1DM-specific antibodies and other laboratory findings were assessed. In the group of patients with positive SARS-CoV-2 serology, a higher percentage had detectable IA-2A antibodies, more children were positive for all three islet autoantibodies determined (GADA, ICA, and IA-2A), and a higher mean HbA1c value was found. No difference existed between the two groups regarding DKA presence and severity. A lower C-peptide level was found in the patients presenting diabetic ketoacidosis (DKA) at T1DM onset. When compared to a group of patients diagnosed before the pandemic, an increased incidence of both DKA and severe DKA, as well as a higher age at diagnosis and higher levels of HbA1c were present in our study group. These findings have important implications for the ongoing monitoring and management of children with T1DM after the COVID-19 pandemic and highlight the need for further research to better understand the complex relationship between SARS-CoV-2 infection and T1DM. Full article
(This article belongs to the Special Issue Coronavirus Disease (COVID-19): Pathophysiology 4.0)
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