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Molecular Advances in SARS-CoV-2 Transmission, Infection and Pathology 2.0

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (30 June 2023) | Viewed by 29548

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Dr. João R. Mesquita

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1. Abel Salazar Biomedical Institute of Sciences (ICBAS), University of Porto, Porto, Portugal
2. EPIUnit–Instituto de Saúde Pública, Universidade do Porto, 4050-313 Porto, Portugal
Interests: transmissible diseases; zoonosis; epidemiology; infectious diseases
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Dear Colleagues,

In December 2019, in Wuhan, China, a new coronavirus was isolated for the first time from patients with acute pneumonia of unrecognizable origin. The newly identified virus was termed SARS-CoV-2, and has since spread worldwide to such an extent that it is now responsible for the ongoing coronavirus disease 2019 (COVID-19) pandemic.

This is in part due to the virus transmission, known to occur not only in an airborne manner but also through indirect contact transmission, involving contact between a susceptible host and a contaminated object or surface (fomite transmission). Over one year has elapsed since the discovery of SARS-CoV-2, and still very little information is available on the molecular aspects of viral transmission. Hence, a molecular approach to SARS-CoV-2 transmission is of the utmost importance.

This Special Issue is a continuation of the Special Issue "Molecular Advances in SARS-CoV-2 Transmission, Infection, and Pathology", and plans to collect the most recent advances in the molecular detection and pathology of SARS-CoV-2. Original research articles and comprehensive reviews that cover the molecular aspects of SARS-CoV-2 transmission, infection, and pathology are welcomed in this Special Issue.

Dr. João R. Mesquita
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

SARS-CoV-2
COVID-19
molecular pathology
infection

Related Special Issue

Molecular Advances in SARS-CoV-2 Transmission, Infection and Pathology in International Journal of Molecular Sciences (8 articles)

Published Papers (10 papers)

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Editorial

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5 pages, 211 KiB

Open AccessEditorial

From Spike to Symptom: A Contribution to Decoding the Molecular Mechanisms Underlying SARS-CoV-2 Transmission, Infection, and Disease Pathology

by João R. Mesquita

Int. J. Mol. Sci. 2023, 24(15), 12294; https://doi.org/10.3390/ijms241512294 - 01 Aug 2023

Viewed by 626

Abstract

In December 2019, a novel coronavirus, SARS-CoV-2, was identified in Wuhan, China, from patients with severe pneumonia of unknown origin [...] Full article

(This article belongs to the Special Issue Molecular Advances in SARS-CoV-2 Transmission, Infection and Pathology 2.0)

Research

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15 pages, 2900 KiB

Open AccessArticle

Comparative Analysis of Library Preparation Approaches for SARS-CoV-2 Genome Sequencing on the Illumina MiSeq Platform

by Anna Gladkikh, Ekaterina Klyuchnikova, Polina Pavlova, Valeriya Sbarzaglia, Nadezhda Tsyganova, Margarita Popova, Tatiana Arbuzova, Alena Sharova, Edward Ramsay, Andrei Samoilov, Vladimir Dedkov and Areg Totolian

Int. J. Mol. Sci. 2023, 24(3), 2374; https://doi.org/10.3390/ijms24032374 - 25 Jan 2023

Viewed by 1810

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been responsible for over two years of the COVID-19 pandemic and a global health emergency. Genomic surveillance plays a key role in overcoming the ongoing COVID-19 pandemic despite its relative successive waves and the continuous emergence of new variants. Many technological approaches are currently applied for the whole genome sequencing (WGS) of SARS-CoV-2. They differ in key stages of the process, and they feature some differences in genomic coverage, sequencing depth, and in the accuracy of variant-calling options. In this study, three different protocols for SARS-CoV-2 WGS library construction are compared: an amplicon-based protocol with a commercial primer panel; an amplicon-based protocol with a custom panel; and a hybridization capture protocol. Specific differences in sequencing depth and genomic coverage as well as differences in SNP number were found. The custom panel showed suitable results and a predictable output applicable for the epidemiological surveillance of SARS-CoV-2 variants. Full article

(This article belongs to the Special Issue Molecular Advances in SARS-CoV-2 Transmission, Infection and Pathology 2.0)

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20 pages, 3399 KiB

Open AccessArticle

T-Cell Immunity in COVID-19-Recovered Individuals and Individuals Vaccinated with the Combined Vector Vaccine Gam-COVID-Vac

by Sergey Petrovich Krechetov, Valentina Valentinovna Vtorushina, Evgenia Vladimirovna Inviyaeva, Elena Aleksandrovna Gorodnova, Svetlana Vladimirovna Kolesnik, Dmitry Anatolievich Kudlay, Pavel Igorevich Borovikov, Liubov Valentinovna Krechetova, Nataliya Vitalievna Dolgushina and Gennady Tikhonovich Sukhikh

Int. J. Mol. Sci. 2023, 24(3), 1930; https://doi.org/10.3390/ijms24031930 - 18 Jan 2023

Viewed by 1596

Abstract

The COVID-19 pandemic has required extensive research on the new coronavirus SARS-CoV-2 and the creation of new highly effective vaccines. The presence of T-cells in the body that respond to virus antigens suggests adequate antiviral immunity. We investigated T-cell immunity in individuals who recovered from mild and moderate COVID-19 and in individuals vaccinated with the Gam-COVID-Vac combined vector vaccine. The ELISPOT method was used to determine the number of T-cells responding with IFN-γ synthesis to stimulation by peptides containing epitopes of the S-protein or N-, M-, ORF3, and ORF7 proteins, using peripheral blood mononuclear cells (PBMCs). At the same time, the multiplex method was used to determine the accumulation of IFN-γ and other cytokines in the culture medium. According to the data obtained, the proportion of positive conclusions about the T-cell immune response to SARS-CoV-2 antigens in control, recovered, and vaccinated individuals was 12%, 70%, and 52%, respectively. At the same time, more than half of the vaccinated individuals with a T-cell response were sensitized to the antigens of N-, M-, ORF3, and ORF7 proteins not produced by Gam-COVID-Vac, indicating a high likelihood of asymptomatic SARS-CoV-2 infection. Increased IFN-γ release by single sensitized T-cells in response to specific stimulation in recovered and vaccinated individuals did not result in the accumulation of this and other cytokines in the culture medium. These findings suggest a balance between cytokine production and utilization by immunocompetent cells as a prerequisite for providing a controlled cytokine signal and avoiding a “cytokine storm”. Full article

(This article belongs to the Special Issue Molecular Advances in SARS-CoV-2 Transmission, Infection and Pathology 2.0)

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17 pages, 2838 KiB

Open AccessArticle

Prediction of Recurrent Mutations in SARS-CoV-2 Using Artificial Neural Networks

by Bryan Saldivar-Espinoza, Guillem Macip, Pol Garcia-Segura, Júlia Mestres-Truyol, Pere Puigbò, Adrià Cereto-Massagué, Gerard Pujadas and Santiago Garcia-Vallve

Int. J. Mol. Sci. 2022, 23(23), 14683; https://doi.org/10.3390/ijms232314683 - 24 Nov 2022

Cited by 5 | Viewed by 3191

Abstract

Predicting SARS-CoV-2 mutations is difficult, but predicting recurrent mutations driven by the host, such as those caused by host deaminases, is feasible. We used machine learning to predict which positions from the SARS-CoV-2 genome will hold a recurrent mutation and which mutations will be the most recurrent. We used data from April 2021 that we separated into three sets: a training set, a validation set, and an independent test set. For the test set, we obtained a specificity value of 0.69, a sensitivity value of 0.79, and an Area Under the Curve (AUC) of 0.8, showing that the prediction of recurrent SARS-CoV-2 mutations is feasible. Subsequently, we compared our predictions with updated data from January 2022, showing that some of the false positives in our prediction model become true positives later on. The most important variables detected by the model’s Shapley Additive exPlanation (SHAP) are the nucleotide that mutates and RNA reactivity. This is consistent with the SARS-CoV-2 mutational bias pattern and the preference of some host deaminases for specific sequences and RNA secondary structures. We extend our investigation by analyzing the mutations from the variants of concern Alpha, Beta, Delta, Gamma, and Omicron. Finally, we analyzed amino acid changes by looking at the predicted recurrent mutations in the M-pro and spike proteins. Full article

(This article belongs to the Special Issue Molecular Advances in SARS-CoV-2 Transmission, Infection and Pathology 2.0)

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18 pages, 2435 KiB

Open AccessArticle

Cytokine Profiling in Different SARS-CoV-2 Genetic Variants

by Zoia R. Korobova, Natalia A. Arsentieva, Natalia E. Liubimova, Oleg K. Batsunov, Vladimir G. Dedkov, Anna S. Gladkikh, Alena A. Sharova, Zhansaya Adish, Ekaterina I. Chernykh, Victor A. Kaschenko, Vyacheslav A. Ratnikov, Victor P. Gorelov, Oksana V. Stanevich, Alexandr N. Kulikov, Dmitry E. Pevtsov and Areg A. Totolian

Int. J. Mol. Sci. 2022, 23(22), 14146; https://doi.org/10.3390/ijms232214146 - 16 Nov 2022

Cited by 11 | Viewed by 2984

Abstract

This study is a successor of our previous work concerning changes in the chemokine profile in infection that are associated with different SARS-CoV-2 genetic variants. The goal of our study was to take into account both the virus and the host immune system by assessing concentrations of cytokines in patients infected with different SARS-CoV-2 variants (ancestral Wuhan strain, Alpha, Delta and Omicron). Our study was performed on 340 biological samples taken from COVID-19 patients and healthy donors in the timespan between May 2020 and April 2022. We performed genotyping of the virus in nasopharyngeal swabs, which was followed by assessment of cytokines’ concentration in blood plasma. We noted that out of nearly 30 cytokines, only four showed stable elevation independently of the variant (IL-6, IL-10, IL-18 and IL-27), and we believe them to be ‘constant’ markers for COVID-19 infection. Cytokines that were studied as potential biomarkers lose their diagnostic value as the virus evolves, and the specter of potential targets for predictive models is narrowing. So far, only four cytokines (IL-6, IL-10, IL-18, and IL-27) showed a consistent rise in concentrations independently of the genetic variant of the virus. Although we believe our findings to be of scientific interest, we still consider them inconclusive; further investigation and comparison of immune responses to different variants of SARS-CoV-2 is required. Full article

(This article belongs to the Special Issue Molecular Advances in SARS-CoV-2 Transmission, Infection and Pathology 2.0)

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15 pages, 2722 KiB

Open AccessArticle

A Comparative Study of the Plasma Chemokine Profile in COVID-19 Patients Infected with Different SARS-CoV-2 Variants

by Zoia R. Korobova, Natalia A. Arsentieva, Natalia E. Liubimova, Vladimir G. Dedkov, Anna S. Gladkikh, Alena A. Sharova, Ekaterina I. Chernykh, Victor A. Kashchenko, Vyacheslav A. Ratnikov, Victor P. Gorelov, Oksana V. Stanevich, Alexandr N. Kulikov, Dmitriy E. Pevtsov and Areg A. Totolian

Int. J. Mol. Sci. 2022, 23(16), 9058; https://doi.org/10.3390/ijms23169058 - 13 Aug 2022

Cited by 9 | Viewed by 2313

Abstract

Background. Infection caused by SARS-CoV-2 mostly affects the upper and lower respiratory tracts and causes symptoms ranging from the common cold to pneumonia with acute respiratory distress syndrome. Chemokines are deeply involved in the chemoattraction, proliferation, and activation of immune cells within inflammation. It is crucial to consider that mutations within the virion can potentially affect the clinical course of SARS-CoV-2 infection because disease severity and manifestation vary depending on the genetic variant. Our objective was to measure and assess the different concentrations of chemokines involved in COVID-19 caused by different variants of the virus. Methods. We used the blood plasma of patients infected with different variants of SARS-CoV-2, i.e., the ancestral Wuhan strain and the Alpha, Delta, and Omicron variants. We measured the concentrations of 11 chemokines in the samples: CCL2/MCP-1, CCL3/MIP-1α, CCL4/MIP-1β, CCL7/MCP-3, CCL11/Eotaxin, CCL22/MDC, CXCL1/GROα, CXCL8/IL-8, CXCL9/MIG, CXCL10/IP-10, and CX3CL1/Fractalkine. Results. We noted a statistically significant elevation in the concentrations of CCL2/MCP-1, CXCL8/IL-8, and CXCL1/IP-10 independently of the variant, and a drop in the CCL22/MDC concentrations. Conclusions. The chemokine concentrations varied significantly depending on the viral variant, leading us to infer that mutations in viral proteins play a role in the cellular and molecular mechanisms of immune responses. Full article

(This article belongs to the Special Issue Molecular Advances in SARS-CoV-2 Transmission, Infection and Pathology 2.0)

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Review

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17 pages, 6606 KiB

Open AccessReview

Molecular Mechanisms Responsible for Diabetogenic Effects of COVID-19 Infection—Induction of Autoimmune Dysregulation and Metabolic Disturbances

by Barbara Grubišić, Luka Švitek, Klara Ormanac, Dea Sabo, Ivica Mihaljević, Ines Bilić-Ćurčić and Tea Omanović Kolarić

Int. J. Mol. Sci. 2023, 24(14), 11576; https://doi.org/10.3390/ijms241411576 - 18 Jul 2023

Cited by 2 | Viewed by 2357

Abstract

The COVID-19 pandemic has revealed a significant association between SARS-CoV-2 infection and diabetes, whereby individuals with diabetes are more susceptible to severe disease and higher mortality rates. Interestingly, recent findings suggest a reciprocal relationship between COVID-19 and diabetes, wherein COVID-19 may contribute to developing new-onset diabetes and worsen existing metabolic abnormalities. This narrative review aims to shed light on the intricate molecular mechanisms underlying the diabetogenic effects of COVID-19. Specifically, the review explores the potential role of various factors, including direct damage to

β

-cells, insulin resistance triggered by systemic inflammation, and disturbances in hormonal regulation, aiming to enhance our understanding of the COVID-19 impact on the development and progression of diabetes. By analysing these mechanisms, the aim is to enhance our understanding of the impact of COVID-19 on the development and progression of diabetes. The binding of SARS-CoV-2 to angiotensin-converting enzyme 2 (ACE2) receptors, which are present in key metabolic organs and tissues, may interfere with glucometabolic pathways, leading to hyperglycaemia, and potentially contribute to the development of new disease mechanisms. The virus’s impact on

β

-cells through direct invasion or systemic inflammation may induce insulin resistance and disrupt glucose homeostasis. Furthermore, glucocorticoids, commonly used to treat COVID-19, may exacerbate hyperglycaemia and insulin resistance, potentially contributing to new-onset diabetes. The long-term effects of COVID-19 on glucose metabolism are still unknown, necessitating further research into the possibility of developing a novel type of diabetes. This article provides a comprehensive overview of the current understanding of the interaction between COVID-19 and diabetes, highlighting potential areas for future research and therapeutic interventions. Full article

(This article belongs to the Special Issue Molecular Advances in SARS-CoV-2 Transmission, Infection and Pathology 2.0)

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19 pages, 1018 KiB

Open AccessReview

Possible Pathogenesis and Prevention of Long COVID: SARS-CoV-2-Induced Mitochondrial Disorder

by Tsung-Hsien Chen, Chia-Jung Chang and Peir-Haur Hung

Int. J. Mol. Sci. 2023, 24(9), 8034; https://doi.org/10.3390/ijms24098034 - 28 Apr 2023

Cited by 14 | Viewed by 6881

Abstract

Patients who have recovered from coronavirus disease 2019 (COVID-19) infection may experience chronic fatigue when exercising, despite no obvious heart or lung abnormalities. The present lack of effective treatments makes managing long COVID a major challenge. One of the underlying mechanisms of long COVID may be mitochondrial dysfunction. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections can alter the mitochondria responsible for energy production in cells. This alteration leads to mitochondrial dysfunction which, in turn, increases oxidative stress. Ultimately, this results in a loss of mitochondrial integrity and cell death. Moreover, viral proteins can bind to mitochondrial complexes, disrupting mitochondrial function and causing the immune cells to over-react. This over-reaction leads to inflammation and potentially long COVID symptoms. It is important to note that the roles of mitochondrial damage and inflammatory responses caused by SARS-CoV-2 in the development of long COVID are still being elucidated. Targeting mitochondrial function may provide promising new clinical approaches for long-COVID patients; however, further studies are needed to evaluate the safety and efficacy of such approaches. Full article

(This article belongs to the Special Issue Molecular Advances in SARS-CoV-2 Transmission, Infection and Pathology 2.0)

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21 pages, 745 KiB

Open AccessReview

COVID-19 Biomarkers at the Crossroad between Patient Stratification and Targeted Therapy: The Role of Validated and Proposed Parameters

by Manuela Rizzi, Davide D’Onghia, Stelvio Tonello, Rosalba Minisini, Donato Colangelo, Mattia Bellan, Luigi Mario Castello, Francesco Gavelli, Gian Carlo Avanzi, Mario Pirisi and Pier Paolo Sainaghi

Int. J. Mol. Sci. 2023, 24(8), 7099; https://doi.org/10.3390/ijms24087099 - 12 Apr 2023

Cited by 6 | Viewed by 1926

Abstract

Clinical knowledge about SARS-CoV-2 infection mechanisms and COVID-19 pathophysiology have enormously increased during the pandemic. Nevertheless, because of the great heterogeneity of disease manifestations, a precise patient stratification at admission is still difficult, thus rendering a rational allocation of limited medical resources as well as a tailored therapeutic approach challenging. To date, many hematologic biomarkers have been validated to support the early triage of SARS-CoV-2-positive patients and to monitor their disease progression. Among them, some indices have proven to be not only predictive parameters, but also direct or indirect pharmacological targets, thus allowing for a more tailored approach to single-patient symptoms, especially in those with severe progressive disease. While many blood test-derived parameters quickly entered routine clinical practice, other circulating biomarkers have been proposed by several researchers who have investigated their reliability in specific patient cohorts. Despite their usefulness in specific contexts as well as their potential interest as therapeutic targets, such experimental markers have not been implemented in routine clinical practice, mainly due to their higher costs and low availability in general hospital settings. This narrative review will present an overview of the most commonly adopted biomarkers in clinical practice and of the most promising ones emerging from specific population studies. Considering that each of the validated markers reflects a specific aspect of COVID-19 evolution, embedding new highly informative markers into routine clinical testing could help not only in early patient stratification, but also in guiding a timely and tailored method of therapeutic intervention. Full article

(This article belongs to the Special Issue Molecular Advances in SARS-CoV-2 Transmission, Infection and Pathology 2.0)

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15 pages, 1818 KiB

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Nanoparticles in Clinical Trials: Analysis of Clinical Trials, FDA Approvals and Use for COVID-19 Vaccines

by Eugenia D. Namiot, Aleksandr V. Sokolov, Vladimir N. Chubarev, Vadim V. Tarasov and Helgi B. Schiöth

Int. J. Mol. Sci. 2023, 24(1), 787; https://doi.org/10.3390/ijms24010787 - 02 Jan 2023

Cited by 26 | Viewed by 4770

Abstract

Nanoparticles are heterologous small composites that are usually between 1 and 100 nanometers in size. They are applied in many areas of medicine with one of them being drug delivery. Nanoparticles have a number of advantages as drug carriers which include reduced toxic effects, increased bioavailability, and their ability to be modified for specific tissues or cells. Due to the exciting development of nanotechnology concomitant with advances in biotechnology and medicine, the number of clinical trials devoted to nanoparticles for drug delivery is growing rapidly. Some nanoparticles, lipid-based types, in particular, played a crucial role in the developing and manufacturing of the two COVID-19 vaccines—Pfizer and Moderna—that are now being widely used. In this analysis, we provide a quantitative survey of clinical trials using nanoparticles during the period from 2002 to 2021 as well as the recent FDA-approved drugs (since 2016). A total of 486 clinical trials were identified using the clinicaltrials.gov database. The prevailing types of nanoparticles were liposomes (44%) and protein-based formulations (26%) during this period. The most commonly investigated content of the nanoparticles were paclitaxel (23%), metals (11%), doxorubicin (9%), bupivacaine and various vaccines (both were 8%). Among the FDA-approved nanoparticle drugs, polymeric (29%), liposomal (22%) and lipid-based (21%) drugs were the most common. In this analysis, we also discuss the differential development of the diverse groups of nanoparticles and their content, as well as the underlying factors behind the trends. Full article

(This article belongs to the Special Issue Molecular Advances in SARS-CoV-2 Transmission, Infection and Pathology 2.0)

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