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Coronavirus Disease (COVID-19): Pathophysiology
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Coronavirus Disease (COVID-19): Pathophysiology

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 (28 February 2022) | Viewed by 102113

Special Issue Editors

Prof. Dr. Jacek Z. Kubiak

E-Mail Website
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
Prof. Dr. Malgorzata Kloc

E-Mail Website
Guest Editor
Transplant Immunology, The Houston Methodist Research Institute, Houston, TX 77030, USA
Interests: macrophages; actin cytoskeleton; RhoA pathway; chronic rejection; transplantation; germ cells; stem cells; Xenopus laevis; development
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 during 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 disease and save human lives during this pandemic. Genetic research allows the identification of continuously evolving novel variants of the virus, and epidemiological studies characterize and 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 the 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 response 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 goes 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 these questions and many other 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. Jacek Z Kubiak
Prof. Dr. Malgorzata Kloc
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. 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
  • coronavirus, pandemic
  • viral diseases
  • pediatrics
  • inflammation
  • immune cells, macrophages
  • pneumonia
  • vaccines
  • cytokines
  • cytokine storm
  • PIMS
  • immunity

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Published Papers (15 papers)

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Editorial

Jump to: Research, Review

4 pages, 192 KiB  
Editorial
Dissecting Physiopathology of COVID-19
by Jacek Z. Kubiak and Malgorzata Kloc
Int. J. Mol. Sci. 2022, 23(17), 9602; https://doi.org/10.3390/ijms23179602 - 24 Aug 2022
Viewed by 1512
Abstract
The COVID-19 pandemic declared on 11 March 2020 by WHO [...] Full article
(This article belongs to the Special Issue Coronavirus Disease (COVID-19): Pathophysiology)

Research

Jump to: Editorial, Review

14 pages, 2112 KiB  
Article
AKR1B10, One of the Triggers of Cytokine Storm in SARS-CoV2 Severe Acute Respiratory Syndrome
by Clovis Chabert, Anne-Laure Vitte, Domenico Iuso, Florent Chuffart, Candice Trocme, Marlyse Buisson, Pascal Poignard, Benjamin Lardinois, Régis Debois, Sophie Rousseaux, Jean-Louis Pepin, Jean-Benoit Martinot and Saadi Khochbin
Int. J. Mol. Sci. 2022, 23(3), 1911; https://doi.org/10.3390/ijms23031911 - 8 Feb 2022
Cited by 10 | Viewed by 3150
Abstract
Preventing the cytokine storm observed in COVID-19 is a crucial goal for reducing the occurrence of severe acute respiratory failure and improving outcomes. Here, we identify Aldo-Keto Reductase 1B10 (AKR1B10) as a key enzyme involved in the expression of pro-inflammatory cytokines. The analysis [...] Read more.
Preventing the cytokine storm observed in COVID-19 is a crucial goal for reducing the occurrence of severe acute respiratory failure and improving outcomes. Here, we identify Aldo-Keto Reductase 1B10 (AKR1B10) as a key enzyme involved in the expression of pro-inflammatory cytokines. The analysis of transcriptomic data from lung samples of patients who died from COVID-19 demonstrates an increased expression of the gene encoding AKR1B10. Measurements of the AKR1B10 protein in sera from hospitalised COVID-19 patients suggests a significant link between AKR1B10 levels and the severity of the disease. In macrophages and lung cells, the over-expression of AKR1B10 induces the expression of the pro-inflammatory cytokines Interleukin-6 (IL-6), Interleukin-1β (IL-1β) and Tumor Necrosis Factor a (TNFα), supporting the biological plausibility of an AKR1B10 involvement in the COVID-19-related cytokine storm. When macrophages were stressed by lipopolysaccharides (LPS) exposure and treated by Zopolrestat, an AKR1B10 inhibitor, the LPS-induced production of IL-6, IL-1β, and TNFα is significantly reduced, reinforcing the hypothesis that the pro-inflammatory expression of cytokines is AKR1B10-dependant. Finally, we also show that AKR1B10 can be secreted and transferred via extracellular vesicles between different cell types, suggesting that this protein may also contribute to the multi-organ systemic impact of COVID-19. These experiments highlight a relationship between AKR1B10 production and severe forms of COVID-19. Our data indicate that AKR1B10 participates in the activation of cytokines production and suggest that modulation of AKR1B10 activity might be an actionable pharmacological target in COVID-19 management. Full article
(This article belongs to the Special Issue Coronavirus Disease (COVID-19): Pathophysiology)
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19 pages, 2303 KiB  
Article
“Molecular Masks” for ACE2 to Effectively and Safely Block SARS-CoV-2 Virus Entry
by Satya Prakash Shukla, Kwang Bog Cho, Vineeta Rustagi, Xiang Gao, Xinping Fu, Shaun Xiaoliu Zhang, Bin Guo and D. Gomika Udugamasooriya
Int. J. Mol. Sci. 2021, 22(16), 8963; https://doi.org/10.3390/ijms22168963 - 20 Aug 2021
Cited by 9 | Viewed by 4594
Abstract
Coronavirus Disease 2019 (COVID-19) remains a global health crisis, despite the development and success of vaccines in certain countries. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19, uses its spike protein to bind to the human cell surface receptor [...] Read more.
Coronavirus Disease 2019 (COVID-19) remains a global health crisis, despite the development and success of vaccines in certain countries. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19, uses its spike protein to bind to the human cell surface receptor angiotensin-converting enzyme 2 (ACE2), which allows the virus to enter the human body. Using our unique cell screening technology, we identified two ACE2-binding peptoid compounds and developed dimeric derivatives (ACE2P1D1 and ACE2P2D1) that effectively blocked spike protein-ACE2 interaction, resulting in the inhibition of SARS-CoV-2 pseudovirus entry into human cells. ACE2P1D1 and ACE2P2D1 also blocked infection by a D614G mutant pseudovirus. More importantly, these compounds do not decrease ACE2 expression nor its enzyme activity (which is important in normal blood pressure regulation), suggesting safe applicability in humans Full article
(This article belongs to the Special Issue Coronavirus Disease (COVID-19): Pathophysiology)
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Graphical abstract

9 pages, 9778 KiB  
Communication
Interactions of Spike-RBD of SARS-CoV-2 and Platelet Factor 4: New Insights in the Etiopathogenesis of Thrombosis
by Margherita Passariello, Cinzia Vetrei, Felice Amato and Claudia De Lorenzo
Int. J. Mol. Sci. 2021, 22(16), 8562; https://doi.org/10.3390/ijms22168562 - 9 Aug 2021
Cited by 20 | Viewed by 4340
Abstract
The rare but dangerous adverse events evidenced after massive vaccination against SARS-CoV-2 are represented by thrombosis and thrombocytopenia. The patients diagnosed with severe COVID-19 may develop a pro-thrombotic state with a much higher frequency, thus we decided to investigate the role of Spike [...] Read more.
The rare but dangerous adverse events evidenced after massive vaccination against SARS-CoV-2 are represented by thrombosis and thrombocytopenia. The patients diagnosed with severe COVID-19 may develop a pro-thrombotic state with a much higher frequency, thus we decided to investigate the role of Spike protein (the only common product of the two conditions) or the anti-Spike antibodies in the etiopathogenesis of thrombosis. A pathogenic Platelet Factor 4 (PF4)-dependent syndrome, unrelated to the use of heparin therapy, has been reported after the administration of vaccines in the patients manifesting acute thrombocytopenia and thrombosis. Thus, we aimed at shedding light on the structural similarities of Spike of SARS-CoV-2 and PF4 on their eventual biochemical interactions and on the role of their specific antibodies. The similarities between PF4 and Spike-RBD proteins were evaluated by a comparison of the structures and by testing the cross-reactivity of their specific antibodies by ELISA assays. We found that the anti-Spike antibodies do not recognize PF4, on the contrary, the anti-PF4 antibodies show some cross-reactivity for Spike-RBD. More interestingly, we report for the first time that the PF4 and Spike-RBD proteins can bind each other. These data suggest that the interaction of the two proteins could be involved in the generation of anti-PF4 antibodies, their binding to Spike-RBD, which could lead to platelets aggregation due also to their high expression of ACE2. Full article
(This article belongs to the Special Issue Coronavirus Disease (COVID-19): Pathophysiology)
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Review

Jump to: Editorial, Research

26 pages, 1637 KiB  
Review
Immune Signature of COVID-19: In-Depth Reasons and Consequences of the Cytokine Storm
by Paulina Niedźwiedzka-Rystwej, Adam Majchrzak, Sara Kurkowska, Paulina Małkowska, Olga Sierawska, Rafał Hrynkiewicz and Miłosz Parczewski
Int. J. Mol. Sci. 2022, 23(9), 4545; https://doi.org/10.3390/ijms23094545 - 20 Apr 2022
Cited by 12 | Viewed by 3626
Abstract
In the beginning of the third year of the fight against COVID-19, the virus remains at least still one step ahead in the pandemic “war”. The key reasons are evolving lineages and mutations, resulting in an increase of transmissibility and ability to evade [...] Read more.
In the beginning of the third year of the fight against COVID-19, the virus remains at least still one step ahead in the pandemic “war”. The key reasons are evolving lineages and mutations, resulting in an increase of transmissibility and ability to evade immune system. However, from the immunologic point of view, the cytokine storm (CS) remains a poorly understood and difficult to combat culprit of the extended number of in-hospital admissions and deaths. It is not fully clear whether the cytokine release is a harmful result of suppression of the immune system or a positive reaction necessary to clear the virus. To develop methods of appropriate treatment and therefore decrease the mortality of the so-called COVID-19-CS, we need to look deeply inside its pathogenesis, which is the purpose of this review. Full article
(This article belongs to the Special Issue Coronavirus Disease (COVID-19): Pathophysiology)
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21 pages, 820 KiB  
Review
Potential Role of the Antidepressants Fluoxetine and Fluvoxamine in the Treatment of COVID-19
by Mohamed Mahdi, Levente Hermán, János M. Réthelyi and Bálint László Bálint
Int. J. Mol. Sci. 2022, 23(7), 3812; https://doi.org/10.3390/ijms23073812 - 30 Mar 2022
Cited by 25 | Viewed by 7330
Abstract
Mapping non-canonical cellular pathways affected by approved medications can accelerate drug repurposing efforts, which are crucial in situations with a global impact such as the COVID-19 pandemic. Fluoxetine and fluvoxamine are well-established and widely-used antidepressive agents that act as serotonin reuptake inhibitors (SSRI-s). [...] Read more.
Mapping non-canonical cellular pathways affected by approved medications can accelerate drug repurposing efforts, which are crucial in situations with a global impact such as the COVID-19 pandemic. Fluoxetine and fluvoxamine are well-established and widely-used antidepressive agents that act as serotonin reuptake inhibitors (SSRI-s). Interestingly, these drugs have been reported earlier to act as lysosomotropic agents, inhibitors of acid sphingomyelinase in the lysosomes, and as ligands of sigma-1 receptors, mechanisms that might be used to fight severe outcomes of COVID-19. In certain cases, these drugs were administered for selected COVID-19 patients because of their antidepressive effects, while in other cases, clinical studies were performed to assess the effect of these drugs on treating COVID-19 patients. Clinical studies produced promising data that encourage the further investigation of fluoxetine and fluvoxamine regarding their use in COVID-19. In this review, we summarize experimental data and the results of the performed clinical studies. We also provide an overview of previous knowledge on the tissue distribution of these drugs and by integrating this information with the published experimental results, we highlight the real opportunity of using these drugs in our fight against COVID-19. Full article
(This article belongs to the Special Issue Coronavirus Disease (COVID-19): Pathophysiology)
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13 pages, 975 KiB  
Review
What Is Currently Known about the Role of CXCL10 in SARS-CoV-2 Infection?
by Monika Gudowska-Sawczuk and Barbara Mroczko
Int. J. Mol. Sci. 2022, 23(7), 3673; https://doi.org/10.3390/ijms23073673 - 27 Mar 2022
Cited by 51 | Viewed by 4756
Abstract
Dysregulation of the immune response plays an important role in the progression of SARS-CoV-2 infection. A “cytokine storm”, which is a phenomenon associated with uncontrolled production of large amounts of cytokines, very often affects patients with COVID-19. Elevated activity of chemotactic cytokines, called [...] Read more.
Dysregulation of the immune response plays an important role in the progression of SARS-CoV-2 infection. A “cytokine storm”, which is a phenomenon associated with uncontrolled production of large amounts of cytokines, very often affects patients with COVID-19. Elevated activity of chemotactic cytokines, called chemokines, can lead to serious consequences. CXCL10 has an ability to activate its receptor CXCR3, predominantly expressed on macrophages, T lymphocytes, dendritic cells, natural killer cells, and B cells. So, it has been suggested that the chemokine CXCL10, through CXCR3, is associated with inflammatory diseases and may be involved in the development of COVID-19. Therefore, in this review paper, we focus on the role of CXCL10 overactivity in the pathogenesis of COVID-19. We performed an extensive literature search for our investigation using the MEDLINE/PubMed database. Increased concentrations of CXCL10 were observed in COVID-19. Elevated levels of CXCL10 were reported to be associated with a severe course and disease progression. Published studies revealed that CXCL10 may be a very good predictive biomarker of patient outcome in COVID-19, and that markedly elevated CXCL10 levels are connected with ARDS and neurological complications. It has been observed that an effective treatment for SARS-CoV-2 leads to inhibition of “cytokine storm”, as well as reduction of CXCL10 concentrations. It seems that modulation of the CXCL10–CXCR3 axis may be an effective therapeutic target of COVID-19. This review describes the potential role of CXCL10 in the pathogenesis of COVID-19, as well as its potential immune–therapeutic significance. However, future studies should aim to confirm the prognostic, clinical, and therapeutic role of CXCL10 in SARS-CoV-2 infection. Full article
(This article belongs to the Special Issue Coronavirus Disease (COVID-19): Pathophysiology)
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17 pages, 1846 KiB  
Review
Malnutrition and Dietary Habits Alter the Immune System Which May Consequently Influence SARS-CoV-2 Virulence: A Review
by Ashmika Foolchand, Terisha Ghazi and Anil A. Chuturgoon
Int. J. Mol. Sci. 2022, 23(5), 2654; https://doi.org/10.3390/ijms23052654 - 28 Feb 2022
Cited by 23 | Viewed by 6550
Abstract
COVID-19, resulting from the SARS-CoV-2 virus, is a major pandemic that the world is fighting. SARS-CoV-2 primarily causes lung infection by attaching to the ACE2 receptor on the alveolar epithelial cells. However, the ACE2 receptor is also present in intestinal epithelial cells, suggesting [...] Read more.
COVID-19, resulting from the SARS-CoV-2 virus, is a major pandemic that the world is fighting. SARS-CoV-2 primarily causes lung infection by attaching to the ACE2 receptor on the alveolar epithelial cells. However, the ACE2 receptor is also present in intestinal epithelial cells, suggesting a link between nutrition, virulence and clinical outcomes of COVID-19. Respiratory viral infections perturb the gut microbiota. The gut microbiota is shaped by our diet; therefore, a healthy gut is important for optimal metabolism, immunology and protection of the host. Malnutrition causes diverse changes in the immune system by repressing immune responses and enhancing viral vulnerability. Thus, improving gut health with a high-quality, nutrient-filled diet will improve immunity against infections and diseases. This review emphasizes the significance of dietary choices and its subsequent effects on the immune system, which may potentially impact SARS-CoV-2 vulnerability. Full article
(This article belongs to the Special Issue Coronavirus Disease (COVID-19): Pathophysiology)
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13 pages, 978 KiB  
Review
An Insight into the Role of Postmortem Immunohistochemistry in the Comprehension of the Inflammatory Pathophysiology of COVID-19 Disease and Vaccine-Related Thrombotic Adverse Events: A Narrative Review
by Chiara Stassi, Cristina Mondello, Gennaro Baldino, Luigi Cardia, Alessio Asmundo and Elvira Ventura Spagnolo
Int. J. Mol. Sci. 2021, 22(21), 12024; https://doi.org/10.3390/ijms222112024 - 6 Nov 2021
Cited by 5 | Viewed by 3504
Abstract
On 11 March 2020, the World Health Organization (WHO) declared a pandemic due to the spread of COVID-19 from Wuhan, China, causing high mortality rates all over the world. The related disease, which mainly affects the lungs, is responsible for the onset of [...] Read more.
On 11 March 2020, the World Health Organization (WHO) declared a pandemic due to the spread of COVID-19 from Wuhan, China, causing high mortality rates all over the world. The related disease, which mainly affects the lungs, is responsible for the onset of Diffuse Alveolar Damage (DAD) and a hypercoagulability state, frequently leading to Severe Acute Respiratory Syndrome (SARS) and multiorgan failure, particularly in old and severe-critically ill patients. In order to find effective therapeutic strategies, many efforts have been made aiming to shed light on the pathophysiology of COVID-19 disease. Moreover, following the late advent of vaccination campaigns, the need for the comprehension of the pathophysiology of the fatal, although rare, thrombotic adverse events has become mandatory as well. The achievement of such purposes needs a multidisciplinary approach, depending on a correct interpretation of clinical, biochemical, biomolecular, and forensic findings. In this scenario, autopsies have helped in defining, on both gross and histologic examinations, the main changes to which the affected organs undergo and the role in assessing whether a patient is dead “from” or “with” COVID-19, not to mention whether the existence of a causal link exists between vaccination and thrombotic adverse events. In the present work, we explored the role of postmortem immunohistochemistry, and the increasingly used ancillary technique, in helping to understand the mechanism underlying the pathophysiology of both COVID-19 disease and COVID-19 vaccine-related adverse and rare effects. Full article
(This article belongs to the Special Issue Coronavirus Disease (COVID-19): Pathophysiology)
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37 pages, 4319 KiB  
Review
Anti-SARS-CoV-2 Strategies and the Potential Role of miRNA in the Assessment of COVID-19 Morbidity, Recurrence, and Therapy
by Maria Narożna and Błażej Rubiś
Int. J. Mol. Sci. 2021, 22(16), 8663; https://doi.org/10.3390/ijms22168663 - 12 Aug 2021
Cited by 18 | Viewed by 7605
Abstract
Recently, we have experienced a serious pandemic. Despite significant technological advances in molecular technologies, it is very challenging to slow down the infection spread. It appeared that due to globalization, SARS-CoV-2 spread easily and adapted to new environments or geographical or weather zones. [...] Read more.
Recently, we have experienced a serious pandemic. Despite significant technological advances in molecular technologies, it is very challenging to slow down the infection spread. It appeared that due to globalization, SARS-CoV-2 spread easily and adapted to new environments or geographical or weather zones. Additionally, new variants are emerging that show different infection potential and clinical outcomes. On the other hand, we have some experience with other pandemics and some solutions in virus elimination that could be adapted. This is of high importance since, as the latest reports demonstrate, vaccine technology might not follow the new, mutated virus outbreaks. Thus, identification of novel strategies and markers or diagnostic methods is highly necessary. For this reason, we present some of the latest views on SARS-CoV-2/COVID-19 therapeutic strategies and raise a solution based on miRNA. We believe that in the face of the rapidly increasing global situation and based on analogical studies of other viruses, the possibility of using the biological potential of miRNA technology is very promising. It could be used as a promising diagnostic and prognostic factor, as well as a therapeutic target and tool. Full article
(This article belongs to the Special Issue Coronavirus Disease (COVID-19): Pathophysiology)
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25 pages, 2282 KiB  
Review
Role of the Renin–Angiotensin–Aldosterone and Kinin–Kallikrein Systems in the Cardiovascular Complications of COVID-19 and Long COVID
by Samantha L. Cooper, Eleanor Boyle, Sophie R. Jefferson, Calum R. A. Heslop, Pirathini Mohan, Gearry G. J. Mohanraj, Hamza A. Sidow, Rory C. P. Tan, Stephen J. Hill and Jeanette Woolard
Int. J. Mol. Sci. 2021, 22(15), 8255; https://doi.org/10.3390/ijms22158255 - 31 Jul 2021
Cited by 37 | Viewed by 8286
Abstract
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the virus responsible for the COVID-19 pandemic. Patients may present as asymptomatic or demonstrate mild to severe and life-threatening symptoms. Although COVID-19 has a respiratory focus, there are major cardiovascular complications (CVCs) associated with infection. [...] Read more.
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the virus responsible for the COVID-19 pandemic. Patients may present as asymptomatic or demonstrate mild to severe and life-threatening symptoms. Although COVID-19 has a respiratory focus, there are major cardiovascular complications (CVCs) associated with infection. The reported CVCs include myocarditis, heart failure, arrhythmias, thromboembolism and blood pressure abnormalities. These occur, in part, because of dysregulation of the Renin–Angiotensin–Aldosterone System (RAAS) and Kinin–Kallikrein System (KKS). A major route by which SARS-CoV-2 gains cellular entry is via the docking of the viral spike (S) protein to the membrane-bound angiotensin converting enzyme 2 (ACE2). The roles of ACE2 within the cardiovascular and immune systems are vital to ensure homeostasis. The key routes for the development of CVCs and the recently described long COVID have been hypothesised as the direct consequences of the viral S protein/ACE2 axis, downregulation of ACE2 and the resulting damage inflicted by the immune response. Here, we review the impact of COVID-19 on the cardiovascular system, the mechanisms by which dysregulation of the RAAS and KKS can occur following virus infection and the future implications for pharmacological therapies. Full article
(This article belongs to the Special Issue Coronavirus Disease (COVID-19): Pathophysiology)
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24 pages, 3873 KiB  
Review
Mitochondrial Modulations, Autophagy Pathways Shifts in Viral Infections: Consequences of COVID-19
by Shailendra Pratap Singh, Salomon Amar, Pinky Gehlot, Sanjib K. Patra, Navjot Kanwar and Abhinav Kanwal
Int. J. Mol. Sci. 2021, 22(15), 8180; https://doi.org/10.3390/ijms22158180 - 30 Jul 2021
Cited by 26 | Viewed by 5636
Abstract
Mitochondria are vital intracellular organelles that play an important role in regulating various intracellular events such as metabolism, bioenergetics, cell death (apoptosis), and innate immune signaling. Mitochondrial fission, fusion, and membrane potential play a central role in maintaining mitochondrial dynamics and the overall [...] Read more.
Mitochondria are vital intracellular organelles that play an important role in regulating various intracellular events such as metabolism, bioenergetics, cell death (apoptosis), and innate immune signaling. Mitochondrial fission, fusion, and membrane potential play a central role in maintaining mitochondrial dynamics and the overall shape of mitochondria. Viruses change the dynamics of the mitochondria by altering the mitochondrial processes/functions, such as autophagy, mitophagy, and enzymes involved in metabolism. In addition, viruses decrease the supply of energy to the mitochondria in the form of ATP, causing viruses to create cellular stress by generating ROS in mitochondria to instigate viral proliferation, a process which causes both intra- and extra-mitochondrial damage. SARS-COV2 propagates through altering or changing various pathways, such as autophagy, UPR stress, MPTP and NLRP3 inflammasome. Thus, these pathways act as potential targets for viruses to facilitate their proliferation. Autophagy plays an essential role in SARS-COV2-mediated COVID-19 and modulates autophagy by using various drugs that act on potential targets of the virus to inhibit and treat viral infection. Modulated autophagy inhibits coronavirus replication; thus, it becomes a promising target for anti-coronaviral therapy. This review gives immense knowledge about the infections, mitochondrial modulations, and therapeutic targets of viruses. Full article
(This article belongs to the Special Issue Coronavirus Disease (COVID-19): Pathophysiology)
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20 pages, 2911 KiB  
Review
Innate Immune Response to SARS-CoV-2 Infection: From Cells to Soluble Mediators
by Daniela Ricci, Marilena Paola Etna, Fabiana Rizzo, Silvia Sandini, Martina Severa and Eliana Marina Coccia
Int. J. Mol. Sci. 2021, 22(13), 7017; https://doi.org/10.3390/ijms22137017 - 29 Jun 2021
Cited by 46 | Viewed by 10525
Abstract
The vulnerability of humankind to SARS-CoV-2 in the absence of a pre-existing immunity, the unpredictability of the infection outcome, and the high transmissibility, broad tissue tropism, and ability to exploit and subvert the immune response pose a major challenge and are likely perpetuating [...] Read more.
The vulnerability of humankind to SARS-CoV-2 in the absence of a pre-existing immunity, the unpredictability of the infection outcome, and the high transmissibility, broad tissue tropism, and ability to exploit and subvert the immune response pose a major challenge and are likely perpetuating the COVID-19 pandemic. Nevertheless, this peculiar infectious scenario provides researchers with a unique opportunity for studying, with the latest immunological techniques and understandings, the immune response in SARS-CoV-2 naïve versus recovered subjects as well as in SARS-CoV-2 vaccinees. Interestingly, the current understanding of COVID-19 indicates that the combined action of innate immune cells, cytokines, and chemokines fine-tunes the outcome of SARS-CoV-2 infection and the related immunopathogenesis. Indeed, the emerging picture clearly shows that the excessive inflammatory response against this virus is among the main causes of disease severity in COVID-19 patients. In this review, the innate immune response to SARS-CoV-2 infection is described not only in light of its capacity to influence the adaptive immune response towards a protective phenotype but also with the intent to point out the multiple strategies exploited by SARS-CoV-2 to antagonize host antiviral response and, finally, to outline inborn errors predisposing individuals to COVID-19 disease severity. Full article
(This article belongs to the Special Issue Coronavirus Disease (COVID-19): Pathophysiology)
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25 pages, 4902 KiB  
Review
Nucleic Acid Testing of SARS-CoV-2
by Hee Min Yoo, Il-Hwan Kim and Seil Kim
Int. J. Mol. Sci. 2021, 22(11), 6150; https://doi.org/10.3390/ijms22116150 - 7 Jun 2021
Cited by 50 | Viewed by 9988
Abstract
The coronavirus disease 2019 (COVID-19) has caused a large global outbreak. It is accordingly important to develop accurate and rapid diagnostic methods. The polymerase chain reaction (PCR)-based method including reverse transcription-polymerase chain reaction (RT-PCR) is the most widely used assay for the detection [...] Read more.
The coronavirus disease 2019 (COVID-19) has caused a large global outbreak. It is accordingly important to develop accurate and rapid diagnostic methods. The polymerase chain reaction (PCR)-based method including reverse transcription-polymerase chain reaction (RT-PCR) is the most widely used assay for the detection of SARS-CoV-2 RNA. Along with the RT-PCR method, digital PCR has emerged as a powerful tool to quantify nucleic acid of the virus with high accuracy and sensitivity. Non-PCR based techniques such as reverse transcription loop-mediated isothermal amplification (RT-LAMP) and reverse transcription recombinase polymerase amplification (RT-RPA) are considered to be rapid and simple nucleic acid detection methods and were reviewed in this paper. Non-conventional molecular diagnostic methods including next-generation sequencing (NGS), CRISPR-based assays and nanotechnology are improving the accuracy and sensitivity of COVID-19 diagnosis. In this review, we also focus on standardization of SARS-CoV-2 nucleic acid testing and the activity of the National Metrology Institutes (NMIs) and highlight resources such as reference materials (RM) that provide the values of specified properties. Finally, we summarize the useful resources for convenient COVID-19 molecular diagnostics. Full article
(This article belongs to the Special Issue Coronavirus Disease (COVID-19): Pathophysiology)
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Review
Could Histamine H1 Receptor Antagonists Be Used for Treating COVID-19?
by Changbo Qu, Gwenny M. Fuhler and Yihang Pan
Int. J. Mol. Sci. 2021, 22(11), 5672; https://doi.org/10.3390/ijms22115672 - 26 May 2021
Cited by 17 | Viewed by 15624
Abstract
COVID-19 has rapidly become a pandemic worldwide, causing extensive and long-term health issues. There is an urgent need to identify therapies that limit SARS-CoV-2 infection and improve the outcome of COVID-19 patients. Unbalanced lung inflammation is a common feature in severe COVID-19 patients; [...] Read more.
COVID-19 has rapidly become a pandemic worldwide, causing extensive and long-term health issues. There is an urgent need to identify therapies that limit SARS-CoV-2 infection and improve the outcome of COVID-19 patients. Unbalanced lung inflammation is a common feature in severe COVID-19 patients; therefore, reducing lung inflammation can undoubtedly benefit the clinical manifestations. Histamine H1 receptor (H1 receptor) antagonists are widely prescribed medications to treat allergic diseases, while recently it has emerged that they show significant promise as anti-SARS-CoV-2 agents. Here, we briefly summarize the novel use of H1 receptor antagonists in combating SARS-CoV-2 infection. We also describe the potential antiviral mechanisms of H1 receptor antagonists on SARS-CoV-2. Finally, the opportunities and challenges of the use of H1 receptor antagonists in managing COVID-19 are discussed. Full article
(This article belongs to the Special Issue Coronavirus Disease (COVID-19): Pathophysiology)
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