Editorial

5 pages, 223 KiB

Open AccessEditorial

Implementing Translational Research to Understand the Future of COVID-19 and Its Long-Term Consequences: A Degrowth Perspective or the Transformation of a Global Emergency?

by Pasquale Ambrosino, Pasquale Moretta, Anna Lanzillo, Roberto Formisano and Mauro Maniscalco

Biomedicines 2023, 11(1), 117; https://doi.org/10.3390/biomedicines11010117 - 03 Jan 2023

Viewed by 1529

Abstract

It has now been three years since the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) first gave rise to a global health crisis [...] Full article

(This article belongs to the Special Issue COVID-19 and Post-acute COVID-19 Syndrome: From Pathophysiology to Novel Translational Applications (Volume II))

Research

Jump to: Editorial, Review, Other

28 pages, 13013 KiB

Open AccessArticle

Comprehensive Analysis of Disease Pathology in Immunocompetent and Immunocompromised Hosts following Pulmonary SARS-CoV-2 Infection

by Santhamani Ramasamy, Afsal Kolloli, Ranjeet Kumar, Seema Husain, Patricia Soteropoulos, Theresa L. Chang and Selvakumar Subbian

Biomedicines 2022, 10(6), 1343; https://doi.org/10.3390/biomedicines10061343 - 07 Jun 2022

Cited by 10 | Viewed by 2453

Abstract

The Coronavirus disease 2019 (COVID-19) pandemic disproportionately affects immunocompetent and immunocompromised individuals, with the latter group being more vulnerable to severe disease and death. However, the differential pathogenesis of SARS-CoV-2 in the context of a specific immunological niche remains unknown. Similarly, systematic analysis [...] Read more.

The Coronavirus disease 2019 (COVID-19) pandemic disproportionately affects immunocompetent and immunocompromised individuals, with the latter group being more vulnerable to severe disease and death. However, the differential pathogenesis of SARS-CoV-2 in the context of a specific immunological niche remains unknown. Similarly, systematic analysis of disease pathology in various extrapulmonary organs in immunocompetent and immunocompromised hosts during SARS-CoV-2 infection is not fully understood. We used a hamster model of SARS-CoV-2 infection, which recapitulates the pathophysiology of patients with mild-to-moderate COVID-19, to determine the dynamics of SARS-CoV-2 replication and histopathology at organ-level niches and map how COVID-19 symptoms vary in different immune contexts. Hamsters were intranasally infected with low (LD) or high (HD) inoculums of SARS-CoV-2, and the kinetics of disease pathology and viral load in multiple organs, antibody response, inflammatory cytokine expression, and genome-wide lung transcriptome by RNAseq analysis were determined and compared against corresponding responses from chemically induced immunocompromised hamsters. We observed transient body weight loss proportional to the SARS-CoV-2 infectious dose in immunocompetent hamsters. The kinetics of viral replication and peak viral loads were similar between LD and HD groups, although the latter developed more severe disease pathology in organs. Both groups generated a robust serum antibody response. In contrast, infected immunocompromised animals showed more prolonged body weight loss and mounted an inadequate SARS-CoV-2-neutralizing antibody response. The live virus was detected in the pulmonary and extrapulmonary organs for extended periods. These hamsters also had persistent inflammation with severe bronchiolar-alveolar hyperplasia/metaplasia. Consistent with the differential disease presentation, distinct changes in inflammation and immune cell response pathways and network gene expression were seen in the lungs of SARS-CoV-2-infected immunocompetent and immunocompromised animals. Full article

(This article belongs to the Special Issue COVID-19 and Post-acute COVID-19 Syndrome: From Pathophysiology to Novel Translational Applications (Volume II))

► Show Figures

Graphical abstract

27 pages, 4201 KiB

Open AccessArticle

Evaluation in a Cytokine Storm Model In Vivo of the Safety and Efficacy of Intravenous Administration of PRS CK STORM (Standardized Conditioned Medium Obtained by Coculture of Monocytes and Mesenchymal Stromal Cells)

by Juan Pedro Lapuente, Gonzalo Gómez, Joaquín Marco-Brualla, Pablo Fernández, Paula Desportes, Jara Sanz, Mario García-Gil, Fernando Bermejo, Juan Víctor San Martín, Alicia Algaba, Juan Carlos De Gregorio, Daniel Lapuente, Almudena De Gregorio, Belén Lapuente, Sergio Gómez, María de las Viñas Andrés and Alberto Anel

Biomedicines 2022, 10(5), 1094; https://doi.org/10.3390/biomedicines10051094 - 08 May 2022

Cited by 2 | Viewed by 2699

Abstract

Our research group has been developing a series of biological drugs produced by coculture techniques with M2-polarized macrophages with different primary tissue cells and/or mesenchymal stromal cells (MSC), generally from fat, to produce anti-inflammatory and anti-fibrotic effects, avoiding the overexpression of pro-inflammatory cytokines [...] Read more.

Our research group has been developing a series of biological drugs produced by coculture techniques with M2-polarized macrophages with different primary tissue cells and/or mesenchymal stromal cells (MSC), generally from fat, to produce anti-inflammatory and anti-fibrotic effects, avoiding the overexpression of pro-inflammatory cytokines by the innate immune system at a given time. One of these products is the drug PRS CK STORM, a medium conditioned by allogenic M2-polarized macrophages, from coculture, with those macrophages M2 with MSC from fat, whose composition, in vitro safety, and efficacy we studied. In the present work, we publish the results obtained in terms of safety (pharmacodynamics and pharmacokinetics) and efficacy of the intravenous application of this biological drug in a murine model of cytokine storm associated with severe infectious processes, including those associated with COVID-19. The results demonstrate the safety and high efficacy of PRS CK STORM as an intravenous drug to prevent and treat the cytokine storm associated with infectious processes, including COVID-19. Full article

(This article belongs to the Special Issue COVID-19 and Post-acute COVID-19 Syndrome: From Pathophysiology to Novel Translational Applications (Volume II))

► Show Figures

Figure 1

12 pages, 2196 KiB

Open AccessArticle

The Evolution of Blood Cell Phenotypes, Intracellular and Plasma Cytokines and Morphological Changes in Critically Ill COVID-19 Patients

by Elisabeth Berghäll, Michael Hultström, Robert Frithiof, Miklos Lipcsey and Victoria Hahn-Strömberg

Biomedicines 2022, 10(5), 934; https://doi.org/10.3390/biomedicines10050934 - 19 Apr 2022

Cited by 4 | Viewed by 2340 | Correction

Abstract

Background: Severe coronavirus disease 2019 (COVID-19) causes a strong inflammatory response. To obtain an overview of inflammatory mediators and effector cells, we studied 25 intensive-care-unit patients during the timeframe after off-label chloroquine treatment and before an introduction of immunomodulatory drugs. Material and methods: [...] Read more.

Background: Severe coronavirus disease 2019 (COVID-19) causes a strong inflammatory response. To obtain an overview of inflammatory mediators and effector cells, we studied 25 intensive-care-unit patients during the timeframe after off-label chloroquine treatment and before an introduction of immunomodulatory drugs. Material and methods: Blood samples were weekly examined with flow cytometry (FCM) for surface and intracytoplasmic markers, cytokine assays were analyzed for circulating interleukins (ILs), and blood smears were evaluated for morphological changes. Samples from healthy volunteers were used for comparison. Organ function data and 30-day mortality were obtained from medical records. Results: Compared to that of the healthy control group, the expression levels of leukocyte surface markers, i.e., the cluster of differentiation (CD) markers CD2, CD4, CD8, CD158d, CD25, CD127, and CD19, were lower (p < 0.001), while those of leukocytes expressing CD33 were increased (p < 0.05). An aberrant expression of CD158d on granulocytes was found on parts of the granulocyte population. The expression levels of intracellular tumor necrosis factor alpha (TNFα) and IL-1 receptor type 2 in leukocytes were lower (p < 0.001), and the plasma levels of TNFα, IL-2, IL-6, IL-8, IL-10 (p < 0.001), interferon gamma (IFNγ) (p < 0.01), and granulocyte-macrophage colony-stimulating factor (GM-CSF) (p < 0.05) were higher in patients with severe COVID-19 than in the control group. The expression levels of CD33+ leukocytes and circulating IL-6 were higher (p < 0.05) among patients with arterial oxygen partial pressure-to-fractional inspired oxygen (PaO₂/FiO₂) ratios below 13.3 kPa compared to in the remaining patients. The expression levels of TNFα, IL-2, IL-4, IL-6, IL-8, and IL-10 were higher in patients treated with continuous renal replacement therapy (CRRT) (p < 0.05), and the levels of the maximum plasma creatinine and TNFα Spearman’s rank-order correlation coefficient (rho = 0.51, p < 0.05) and IL-8 (rho = 0.44, p < 0.05) correlated. Blood smears revealed neutrophil dysplasia with pseudo-Pelger forms being most common. Conclusion: These findings suggest that patients with severe COVID-19, in addition to augmented ILs, lymphopenia, and increased granulocytes, also had effects on the bone marrow. Full article

(This article belongs to the Special Issue COVID-19 and Post-acute COVID-19 Syndrome: From Pathophysiology to Novel Translational Applications (Volume II))

► Show Figures

Figure 1

15 pages, 2669 KiB

Open AccessArticle

Immune-Mediated Inflammatory Responses of Alveolar Epithelial Cells: Implications for COVID-19 Lung Pathology

by Amelia Barilli, Rossana Visigalli, Francesca Ferrari, Massimiliano G. Bianchi, Valeria Dall’Asta and Bianca Maria Rotoli

Biomedicines 2022, 10(3), 618; https://doi.org/10.3390/biomedicines10030618 - 07 Mar 2022

Cited by 16 | Viewed by 2797

Abstract

Background. Clinical and experimental evidence point to a dysregulated immune response caused by SARS-CoV-2 as the primary mechanism of lung disease in COVID-19. However, the pathogenic mechanisms underlying COVID-19-associated ARDS (Acute Respiratory Distress Syndrome) remain incompletely understood. This study aims to explore the [...] Read more.

Background. Clinical and experimental evidence point to a dysregulated immune response caused by SARS-CoV-2 as the primary mechanism of lung disease in COVID-19. However, the pathogenic mechanisms underlying COVID-19-associated ARDS (Acute Respiratory Distress Syndrome) remain incompletely understood. This study aims to explore the inflammatory responses of alveolar epithelial cells to either the spike S1 protein or to a mixture of cytokines secreted by S1-activated macrophages. Methods and Results. The exposure of alveolar A549 cells to supernatants from spike-activated macrophages caused a further release of inflammatory mediators, with IL-8 reaching massive concentrations. The investigation of the molecular pathways indicated that NF-kB is involved in the transcription of IP-10 and RANTES, while STATs drive the expression of all the cytokines/chemokines tested, with the exception of IL-8 which is regulated by AP-1. Cytokines/chemokines produced by spike-activated macrophages are also likely responsible for the observed dysfunction of barrier integrity in Human Alveolar Epithelial Lentivirus-immortalized cells (hAELVi), as demonstrated by an increased permeability of the monolayers to mannitol, a marked decrease of TEER and a disorganization of claudin-7 distribution. Conclusion. Upon exposure to supernatants from S1-activated macrophages, A549 cells act both as targets and sources of cytokines/chemokines, suggesting that alveolar epithelium along with activated macrophages may orchestrate lung inflammation and contribute to alveolar injury, a hallmark of ARDS. Full article

(This article belongs to the Special Issue COVID-19 and Post-acute COVID-19 Syndrome: From Pathophysiology to Novel Translational Applications (Volume II))

► Show Figures

Figure 1

20 pages, 328 KiB

Open AccessArticle

The Role of Genetic Factors in the Development of Acute Respiratory Viral Infection COVID-19: Predicting Severe Course and Outcomes

by Mikhail M. Minashkin, Nataliya Y. Grigortsevich, Anna S. Kamaeva, Valeriya V. Barzanova, Alexey A. Traspov, Mikhail A. Godkov, Farkhad A. Ageev, Sergey S. Petrikov and Nataliya V. Pozdnyakova

Biomedicines 2022, 10(3), 549; https://doi.org/10.3390/biomedicines10030549 - 25 Feb 2022

Cited by 14 | Viewed by 2812

Abstract

The aim of this study was to identify single nucleotide variants in genes associated with susceptibility to or severe outcomes of COVID-19. A total of 319 genomic DNA samples from patients with varying degrees of disease severity and 78 control DNA samples from [...] Read more.

The aim of this study was to identify single nucleotide variants in genes associated with susceptibility to or severe outcomes of COVID-19. A total of 319 genomic DNA samples from patients with varying degrees of disease severity and 78 control DNA samples from people who had regular or prolonged contact with patients with COVID-19 but did not have clinical manifestations and/or antibodies to SARS-CoV-2. Seven SNPs were identified that were statistically associated with disease risk or severe course, rs1799864 in the CCR2 gene (OR = 2.21), rs1990760 in the IFIH1 gene (OR = 2.41), rs1800629 in the TNF gene (OR = 1.98), rs75603675 in the TMPRSS2 gene (OR = 1.86), rs7842 in the C3AR1 gene (OR = 2.08), rs179008 in the gene TLR7 (OR = 1.85), rs324011 in the C3AR1 gene (OR = 2.08), rs179008 in the TLR7 gene (OR = 1.85), and rs324011 in the STAT6 gene (OR = 1.84), as well as two variants associated with protection from COVID-19, rs744166 in the STAT3 gene (OR = 0.36) and rs1898830 in the TLR2 gene (OR = 0.47). The genotype in the region of these markers can be the criterion of the therapeutic approach for patients with COVID-19. Full article

(This article belongs to the Special Issue COVID-19 and Post-acute COVID-19 Syndrome: From Pathophysiology to Novel Translational Applications (Volume II))

Review

Jump to: Editorial, Research, Other

16 pages, 1149 KiB

Open AccessReview

Endothelial Dysfunction in COVID-19: A Unifying Mechanism and a Potential Therapeutic Target

by Pasquale Ambrosino, Ilenia Lorenza Calcaterra, Marco Mosella, Roberto Formisano, Silvestro Ennio D’Anna, Tiziana Bachetti, Giuseppina Marcuccio, Brurya Galloway, Francesco Paolo Mancini, Antimo Papa, Andrea Motta, Matteo Nicola Dario Di Minno and Mauro Maniscalco

Biomedicines 2022, 10(4), 812; https://doi.org/10.3390/biomedicines10040812 - 30 Mar 2022

Cited by 31 | Viewed by 7050

Abstract

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) generated a worldwide emergency, until the declaration of the pandemic in March 2020. SARS-CoV-2 could be responsible for coronavirus disease 2019 (COVID-19), which goes from a flu-like illness to a potentially fatal condition that [...] Read more.

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) generated a worldwide emergency, until the declaration of the pandemic in March 2020. SARS-CoV-2 could be responsible for coronavirus disease 2019 (COVID-19), which goes from a flu-like illness to a potentially fatal condition that needs intensive care. Furthermore, the persistence of functional disability and long-term cardiovascular sequelae in COVID-19 survivors suggests that convalescent patients may suffer from post-acute COVID-19 syndrome, requiring long-term care and personalized rehabilitation. However, the pathophysiology of acute and post-acute manifestations of COVID-19 is still under study, as a better comprehension of these mechanisms would ensure more effective personalized therapies. To date, mounting evidence suggests a crucial endothelial contribution to the clinical manifestations of COVID-19, as endothelial cells appear to be a direct or indirect preferential target of the virus. Thus, the dysregulation of many of the homeostatic pathways of the endothelium has emerged as a hallmark of severity in COVID-19. The aim of this review is to summarize the pathophysiology of endothelial dysfunction in COVID-19, with a focus on personalized pharmacological and rehabilitation strategies targeting endothelial dysfunction as an attractive therapeutic option in this clinical setting. Full article

(This article belongs to the Special Issue COVID-19 and Post-acute COVID-19 Syndrome: From Pathophysiology to Novel Translational Applications (Volume II))

► Show Figures

Figure 1

Other

Jump to: Editorial, Research, Review

2 pages, 179 KiB

Open AccessCorrection

Correction: Berghäll et al. The Evolution of Blood Cell Phenotypes, Intracellular and Plasma Cytokines and Morphological Changes in Critically Ill COVID-19 Patients. Biomedicines 2022, 10, 934

by Elisabeth Berghäll, Michael Hultström, Robert Frithiof, Miklos Lipcsey and Victoria Hahn-Strömberg

Biomedicines 2023, 11(11), 2965; https://doi.org/10.3390/biomedicines11112965 - 03 Nov 2023

Viewed by 342

Abstract

In original publication [...] Full article

(This article belongs to the Special Issue COVID-19 and Post-acute COVID-19 Syndrome: From Pathophysiology to Novel Translational Applications (Volume II))

15 pages, 2979 KiB

Open AccessSystematic Review

Putative Role of the Lung–Brain Axis in the Pathogenesis of COVID-19-Associated Respiratory Failure: A Systematic Review

by Francesco Gentile, Tommaso Bocci, Silvia Coppola, Tommaso Pozzi, Leo Modafferi, Alberto Priori and Davide Chiumello

Biomedicines 2022, 10(3), 729; https://doi.org/10.3390/biomedicines10030729 - 21 Mar 2022

Cited by 5 | Viewed by 4037

Abstract

The emergence of SARS-CoV-2 and its related disease caused by coronavirus (COVID-19) has posed a huge threat to the global population, with millions of deaths and the creation of enormous social and healthcare pressure. Several studies have shown that besides respiratory illness, other [...] Read more.

The emergence of SARS-CoV-2 and its related disease caused by coronavirus (COVID-19) has posed a huge threat to the global population, with millions of deaths and the creation of enormous social and healthcare pressure. Several studies have shown that besides respiratory illness, other organs may be damaged as well, including the heart, kidneys, and brain. Current evidence reports a high frequency of neurological manifestations in COVID-19, with significant prognostic implications. Importantly, emerging literature is showing that the virus may spread to the central nervous system through neuronal routes, hitting the brainstem and cardiorespiratory centers, potentially exacerbating the respiratory illness. In this systematic review, we searched public databases for all available evidence and discuss current clinical and pre-clinical data on the relationship between the lung and brain during COVID-19. Acknowledging the involvement of these primordial brain areas in the pathogenesis of the disease may fuel research on the topic and allow the development of new therapeutic strategies. Full article

(This article belongs to the Special Issue COVID-19 and Post-acute COVID-19 Syndrome: From Pathophysiology to Novel Translational Applications (Volume II))

► Show Figures

Figure 1

Journal Menu

Journal Browser

COVID-19 and Post-acute COVID-19 Syndrome: From Pathophysiology to Novel Translational Applications (Volume II)

Share This Special Issue

Special Issue Editor

Special Issue Information

Keywords

Related Special Issue

Published Papers (9 papers)

Editorial

Research

Review

Other

Further Information

Guidelines

MDPI Initiatives

Follow MDPI