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COVID-19: Current Understanding of Its Pathophysiology, Clinical Presentation and Treatment
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COVID-19: Current Understanding of Its Pathophysiology, Clinical Presentation and Treatment

A special issue of Journal of Personalized Medicine (ISSN 2075-4426). This special issue belongs to the section "Mechanisms of Diseases".

Deadline for manuscript submissions: closed (15 December 2021) | Viewed by 7587

Special Issue Editors

Prof. Dr. Raffaele Bruno

E-Mail Website
Guest Editor
1. U.O.C. Malattie Infettive I Fondazione IRCCS Policlinico San Matteo, Università di Pavia, Pavia, Italy
2. Dipartimento di scienze clinico-chirurgiche, diagnostiche e pediatriche, Università di Pavia, Pavia, Italy
Interests: infectious diseases; COVID-19; SARS-CoV-2
Dr. Valentina Zuccaro

E-Mail Website
Guest Editor
U.O.C. Malattie Infettive I Fondazione IRCCS Policlinico San Matteo - Università di Pavia, Pavia, Italy
Interests: infectious diseases; COVID-19; SARS-CoV-2
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Since December 2019, there has been an outbreak of coronavirus-2 (CoV-2) disease (COVID-19), responsible for a severe acute respiratory syndrome, often requiring hospital admission for ventilatory and medical support. Investigation of COVID-19 characteristics and outcomes has resulted in an increasing awareness and fast-growing knowledge about the management of the disease. This Special Issues of Journal of Personalized Medicine aims to update the current evidence and collect the latest findings on COVID19 pathophysiology. Particular attention will be paid to original research articles and state-of-the-art reviews focused on COVID-19 clinical presentation, pathophysiology, and therapeutic approaches.

Prof. Dr. Raffaele Bruno
Dr. Valentina Zuccaro
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. Journal of Personalized Medicine is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). 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
  • Clinical aspects
  • Management
  • Therapeutic approaches

Published Papers (3 papers)

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Research

11 pages, 1607 KiB  
Article
Early Response of CD8+ T Cells in COVID-19 Patients
by Deni Ramljak, Martina Vukoja, Marina Curlin, Katarina Vukojevic, Maja Barbaric, Una Glamoclija, Bejana Purisevic, Olivera Peric and Violeta Soljic
J. Pers. Med. 2021, 11(12), 1291; https://doi.org/10.3390/jpm11121291 - 3 Dec 2021
Cited by 13 | Viewed by 2456
Abstract
Healthy and controlled immune response in COVID-19 is crucial for mild forms of the disease. Although CD8+ T cells play important role in this response, there is still a lack of studies showing the gene expression profiles in those cells at the beginning [...] Read more.
Healthy and controlled immune response in COVID-19 is crucial for mild forms of the disease. Although CD8+ T cells play important role in this response, there is still a lack of studies showing the gene expression profiles in those cells at the beginning of the disease as potential predictors of more severe forms after the first week. We investigated a proportion of different subpopulations of CD8+ T cells and their gene expression patterns for cytotoxic proteins (perforin-1 (PRF1), granulysin (GNLY), granzyme B (GZMB), granzyme A (GZMA), granzyme K (GZMK)), cytokine interferon-γ (IFN-γ), and apoptotic protein Fas ligand (FASL) in CD8+ T cells from peripheral blood in first weeks of SARS-CoV-2 infection. Sixteen COVID-19 patients and nine healthy controls were included. The absolute counts of total lymphocytes (p = 0.007), CD3+ (p = 0.05), and CD8+ T cells (p = 0.01) in COVID-19 patients were significantly decreased compared to healthy controls. In COVID-19 patients in CD8+ T cell compartment, we observed lower frequency effector memory 1 (EM1) (p = 0.06) and effector memory 4 (EM4) (p < 0.001) CD8+ T cells. Higher mRNA expression of PRF1 (p = 0.05) and lower mRNA expression of FASL (p = 0.05) at the fifth day of the disease were found in COVID-19 patients compared to healthy controls. mRNA expression of PRF1 (p < 0.001) and IFN-γ (p < 0.001) was significantly downregulated in the first week of disease in COVID-19 patients who progressed to moderate and severe forms after the first week, compared to patients with mild symptoms during the entire disease course. GZMK (p < 0.01) and FASL (p < 0.01) mRNA expression was downregulated in all COVID-19 patients compared to healthy controls. Our results can lead to a better understanding of the inappropriate immune response of CD8+ T cells in SARS-CoV2 with the faster progression of the disease. Full article
(This article belongs to the Special Issue COVID-19: Current Understanding of Its Pathophysiology, Clinical Presentation and Treatment)
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14 pages, 852 KiB  
Article
Cirrhosis-Associated RAS-Inflammation-Coagulation Axis Anomalies: Parallels to Severe COVID-19
by Lukas Hartl, Mathias Jachs, Benedikt Simbrunner, David J. M. Bauer, Georg Semmler, Daniela Gompelmann, Thomas Szekeres, Peter Quehenberger, Michael Trauner, Mattias Mandorfer, Bernhard Scheiner and Thomas Reiberger
J. Pers. Med. 2021, 11(12), 1264; https://doi.org/10.3390/jpm11121264 - 1 Dec 2021
Cited by 11 | Viewed by 2321
Abstract
(1) Background: Cirrhotic patients have an increased risk for severe COVID-19. We investigated the renin-angiotensin-aldosterone system (RAS), parameters of endothelial dysfunction, inflammation, and coagulation/fibrinolysis in cirrhotic patients and in COVID-19 patients. (2) Methods: 127 prospectively characterized cirrhotic patients (CIRR), along with nine patients [...] Read more.
(1) Background: Cirrhotic patients have an increased risk for severe COVID-19. We investigated the renin-angiotensin-aldosterone system (RAS), parameters of endothelial dysfunction, inflammation, and coagulation/fibrinolysis in cirrhotic patients and in COVID-19 patients. (2) Methods: 127 prospectively characterized cirrhotic patients (CIRR), along with nine patients with mild COVID-19 (mild-COVID), 11 patients with COVID-19 acute respiratory distress syndrome (ARDS; ARDS-COVID), and 10 healthy subjects (HS) were included in the study. Portal hypertension (PH) in cirrhotic patients was characterized by hepatic venous pressure gradient (HVPG). (3) Results: With increased liver disease severity (Child−Pugh stage A vs. B vs. C) and compared to HS, CIRR patients exhibited higher RAS activity (angiotensin-converting enzyme (ACE), renin, aldosterone), endothelial dysfunction (von Willebrand-factor (VWF) antigen), inflammation (C-reactive protein (CRP), interleukin-6 (IL-6)), and a disturbed coagulation/fibrinolysis profile (prothrombin fragment F1,2, D-dimer, plasminogen activity, antiplasmin activity). Increased RAS activity (renin), endothelial dysfunction (vWF), coagulation parameters (D-dimer, prothrombin fragment F1,2) and inflammation (CRP, IL-6) were significantly altered in COVID patients and followed similar trends from mild-COVID to ARDS-COVID. In CIRR patients, ACE activity was linked to IL-6 (ρ = 0.26; p = 0.003), independently correlated with VWF antigen (aB: 0.10; p = 0.001), and was inversely associated with prothrombin fragment F1,2 (aB: −0.03; p = 0.023) and antiplasmin activity (aB: −0.58; p = 0.006), after adjusting for liver disease severity. (4) Conclusions: The considerable upregulation of the RAS in Child−Pugh B/C cirrhosis is linked to systemic inflammation, endothelial dysfunction, and abnormal coagulation profile. The cirrhosis-associated abnormalities of ACE, IL-6, VWF antigen, and antiplasmin parallel those observed in severe COVID-19. Full article
(This article belongs to the Special Issue COVID-19: Current Understanding of Its Pathophysiology, Clinical Presentation and Treatment)
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10 pages, 1351 KiB  
Article
Impact of Pneumococcal Urinary Antigen Testing in COVID-19 Patients: Outcomes from the San Matteo COVID-19 Registry (SMACORE)
by Pietro Valsecchi, Marta Colaneri, Valentina Zuccaro, Erika Asperges, Filippo Costanzo, Bianca Mariani, Silvia Roda, Rita Minucci, Francesco Bertuccio, Elia Fraolini, Matteo Bosio, Claudio Tirelli, Tiberio Oggionni, Angelo Corsico and Raffaele Bruno
J. Pers. Med. 2021, 11(8), 762; https://doi.org/10.3390/jpm11080762 - 31 Jul 2021
Cited by 2 | Viewed by 1995
Abstract
Despite low rates of bacterial co-infections, most COVID-19 patients receive antibiotic therapy. We hypothesized that patients with positive pneumococcal urinary antigens (PUAs) would benefit from antibiotic therapy in terms of clinical outcomes (death, ICU admission, and length of stay). The San Matteo COVID-19 [...] Read more.
Despite low rates of bacterial co-infections, most COVID-19 patients receive antibiotic therapy. We hypothesized that patients with positive pneumococcal urinary antigens (PUAs) would benefit from antibiotic therapy in terms of clinical outcomes (death, ICU admission, and length of stay). The San Matteo COVID-19 Registry (SMACORE) prospectively enrolls patients admitted for COVID-19 pneumonia at IRCCS Policlinico San Matteo, Pavia. We retrospectively extracted the data of patients tested for PUA from October to December 2020. Demographic, clinical, and laboratory data were recorded. Of 469 patients, 42 tested positive for PUA (8.95%), while 427 (91.05%) tested negative. A positive PUA result had no significant impact on death (HR 0.53 CI [0.22–1.28] p-value 0.16) or ICU admission (HR 0.8; CI [0.25–2.54] p-value 0.70) in the Cox regression model, nor on length of stay in linear regression (estimate 1.71; SE 2.37; p-value 0.47). After adjusting for age, we found no significant correlation between urinary antigen positivity and variations in the WHO ordinal scale and laboratory markers at admission and after 14 days. We found that a positive PUA result was not frequent and had no impact on clinical outcomes or clinical improvement. Our results did not support the routine use of PUA tests to select COVID-19 patients who will benefit from antibiotic therapy. Full article
(This article belongs to the Special Issue COVID-19: Current Understanding of Its Pathophysiology, Clinical Presentation and Treatment)
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