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Past, Present and Future of COVID-19

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A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Immunology and Immunotherapy".

Deadline for manuscript submissions: closed (30 November 2022) | Viewed by 37465

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Special Issue Editors

Prof. Dr. Melchor Álvarez de Mon

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1. Department of Medicine and Medical Specialities, IRYCYS, Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcala de Henares, Spain
2. Immune System Diseases-Rheumatology and Internal Medicine Service, University Hospital Príncipe de Asturias, (CIBEREHD), 28806 Alcala de Henares, Spain
Interests: immune system; systemic diseases; semiology; cytokines; translational medicine
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Dr. Miguel Ortega

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Department of Medicine and Medical Specialities, IRYCYS, Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcala de Henares, Spain
Interests: vascular diseases; artery; venous disease; venous hypertension; heart; lymph; diabetes; immune system; translational medicine
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Prof. Dr. José-Antonio Girón-González

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Department of Internal Medicine, Hospital Universitario Puerta del Mar, Faculty of Medicine, University of Cádiz, Institute for Research and Innovation in Biomedical Sciences of Cádiz (INiBICA), Avda Ana de Viya s/n, 11009 Cádiz, Spain
Interests: immune system; systemic diseases; internal medicine; cytokines; translational medicine
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Dr. Miguel Ángel Alvarez de Mon

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Department of Medicine and Medical Specialities, IRYCYS, Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcala de Henares, Spain
Interests: personalized medicine; clinical medicine; new therapies; medical–patient relationship
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Prof. Dr. Jorge Monserrat

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Department of Medicine and Medical Specialities, IRYCYS, Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcala de Henares, Spain
Interests: inflammation; T, B and NK cells; monocytes and dendritic cells functions applied to immune system and infection (multiorgan failure syndrome, COVID-19); autoimmunity (rheumatoid arthritis and lupus); cancer (leukemia and lung cancer); hepatology; fibromyalgia and mayor depression; expert in flow cytometry
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Prof. Dr. Natalio García-Honduvilla

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Department of Medicine and Medical Specialities, IRYCYS, Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcala de Henares, Spain
Interests: tissue engineering; vascular medicine; targeted therapies; translational medicine
Special Issues, Collections and Topics in MDPI journals

Prof. Dr. Luis G Guijarro

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Unit of Biochemistry and Molecular Biology, Department of System Biology (CIBEREHD), University of Alcalá, 28801 Alcala de Henares, Spain
Interests: Pharmacogenomics, new therapeutic targets, cell signaling, exosomes, molecular diagnosis.
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Special Issue Information

Dear Colleagues,

The COVID-19 pandemic has brought about a paradigm shift in many aspects of medicine and society. Research in this field has been intense, and great results have been achieved. However, our knowledge of SARS‑CoV‑2 is not complete. Thus, it is necessary to continue delving into this virus from a biomedical perspective. Having complete and integrative knowledge is essential to be able to respond to possible future threats. The connection between research and clinical practice is essential in order to achieve effective and efficient knowledge generation.

This Special Issue is intended to bring together biomedical and clinical knowledge with a translational perspective for a better understanding of SARS‑CoV‑2.

Prof. Dr. Melchor Álvarez de Mon
Prof. Dr. Miguel A Ortega
Prof. Dr. José-Antonio Girón-González
Prof. Dr. Miguel A Alvarez-Mon
Prof. Dr. Jorge Monserrat
Prof. Dr. Natalio García-Honduvilla
Prof. Dr. Luis G Guijarro
Guest Editors

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomedicines 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

COVID-19
SARS-CoV-2
cytokines
inflammatory response, new therapeutic targets, pregnancy, vaccines, post-covid syndrome

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Published Papers (13 papers)

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Research

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9 pages, 2672 KiB

Open AccessArticle

Correlation between Thyroid Responses and Inflammatory Cytokines in Critically Ill COVID-19 Patients

by Albert Figueras Castilla, María A. Ballesteros Vizoso, Amanda Iglesias Coma, Antonia Barceló, Jesús A. Barea-Mendoza, Paula Argente del Castillo, Begoña Guardiola, Jon Pérez-Bárcena and Juan A. Llompart-Pou

Biomedicines 2023, 11(1), 26; https://doi.org/10.3390/biomedicines11010026 - 22 Dec 2022

Cited by 1 | Viewed by 1717

Abstract

Mechanisms involved in thyroid dysfunction in critically ill coronavirus disease 2019 (COVID-19) patients are not clear. Our objective was to correlate the thyroid response with the pro- and anti-inflammatory cytokines profile in critically ill COVID-19 patients. This was a prospective single-center study. We studied the relationship between continuous variables by using Pearson correlation and simple linear regression. Multiple logistic regression analysis was performed to analyze the factors independently associated with mortality. Seventy-eight patients were included in the study at intensive care unit (ICU) admission and 72 had a measurement of the thyroid and inflammatory profile at day 5. No significant correlations were found between thyroid stimulating hormone (TSH), free triiodothyronine (fT3) and free thyroxine (fT4) and inflammatory cytokines at ICU admission. At day 5, fT4, was inversely correlated with IL-10 (p = 0.035). IL-10 was associated with maximum lactate (p < 0.001) and SOFA score values (p = 0.012). The multiple logistic regression analysis showed that there was a significant relationship between IL-10 (day 5) and in-hospital mortality after adjusting by age and severity of illness. In conclusion, we found that the thyroid hormone profile and inflammatory cytokines had a weak correlation at ICU admission. Associations of interest between fT4 and IL-10 were found at day 5. IL-10 at day 5 was found to be correlated with low fT4 and markers of organ failure and death. Full article

(This article belongs to the Special Issue Past, Present and Future of COVID-19)

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12 pages, 3792 KiB

Open AccessArticle

Conformational Dynamics of the Receptor-Binding Domain of the SARS-CoV-2 Spike Protein

by Aleksandra A. Mamchur, Tatiana B. Stanishneva-Konovalova, Yuliana A. Mokrushina, Viktoria A. Abrikosova, Yu Guo, Hongkai Zhang, Stanislav S. Terekhov, Ivan V. Smirnov and Igor A. Yaroshevich

Biomedicines 2022, 10(12), 3233; https://doi.org/10.3390/biomedicines10123233 - 12 Dec 2022

Cited by 1 | Viewed by 1900

Abstract

Variants of SARS-CoV-2 keep emerging and causing new waves of COVID-19 around the world. Effective new approaches in drug development are based on the binding of agents, such as neutralizing monoclonal antibodies to a receptor-binding domain (RBD) of SARS-CoV-2 spike protein. However, mutations in RBD may lower the affinity of previously developed antibodies. Therefore, rapid analysis of new variants and selection of a binding partner with high affinity is of great therapeutic importance. Here, we explore a computational approach based on molecular dynamics simulations and conformational clusterization techniques for the wild-type and omicron variants of RBD. Biochemical experiments support the hypothesis of the presence of several conformational states within the RBD assembly. The development of such an approach will facilitate the selection of neutralization drugs with higher affinity based on the primary structure of the target antigen. Full article

(This article belongs to the Special Issue Past, Present and Future of COVID-19)

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11 pages, 1912 KiB

Open AccessArticle

Immune Response after COVID-19 mRNA Vaccination in Multiple Sclerosis Patients Treated with DMTs

by Valentina Mazziotti, Francesco Crescenzo, Agnese Tamanti, Caterina Dapor, Stefano Ziccardi, Maddalena Guandalini, Annalisa Colombi, Valentina Camera, Angela Peloso, Francesco Pezzini, Ermanna Turano, Damiano Marastoni and Massimiliano Calabrese

Biomedicines 2022, 10(12), 3034; https://doi.org/10.3390/biomedicines10123034 - 24 Nov 2022

Cited by 1 | Viewed by 1812

Abstract

The impact of disease-modifying therapies (DMTs) on the immune response to coronavirus disease-2019 (COVID-19) vaccines in persons with multiple sclerosis (pwMS) needs further elucidation. We investigated BNT162b2 mRNA COVID-19 vaccine effects concerning antibody seroconversion, inflammatory mediators’ level and immunophenotype assessment in pwMS treated with cladribine (c-pwMS, n = 29), fingolimod (f-pwMS, n = 15) and ocrelizumab (o-pwMS, n = 54). Anti-spike immunoglobulin (Ig)-G detection was performed by an enzyme immunoassay; molecular mediators (GrB, IFN-γ and TNF-α) were quantified using the ELLA platform, and immunophenotype was assessed by flow cytometry. ANCOVA, Student’s t-test and Pearson correlation analyses were applied. Only one o-pwMS showed a mild COVID-19 infection despite most o-pwMS lacking seroconversion and showing lower anti-spike IgG titers than c-pwMS and f-pwMS. No significant difference in cytokine production and lymphocyte count was observed in c-pwMS and f-pwMS. In contrast, in o-pwMS, a significant increase in GrB levels was detected after vaccination. Considering non-seroconverted o-pwMS, a significant increase in GrB serum levels and CD4+ T lymphocyte count was found after vaccination, and a negative correlation was observed between anti-spike IgG production and CD4+ T cells count. Differences in inflammatory mediators’ production after BNT162b2 vaccination in o-pwMS, specifically in those lacking anti-spike IgG, suggest a protective cellular immune response. Full article

(This article belongs to the Special Issue Past, Present and Future of COVID-19)

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15 pages, 1711 KiB

Open AccessArticle

A Highly Sensitive Immunoassay for Determination of Immune Response to SARS-CoV-2 in Capillary Blood Samples

by Belén G. Sánchez, Alicia Bort, José María Mora-Rodríguez, Alba Díaz-Yuste, José Manuel Gasalla, Manuel Sánchez-Chapado, Alba Sebastián-Martín and Inés Díaz-Laviada

Biomedicines 2022, 10(11), 2897; https://doi.org/10.3390/biomedicines10112897 - 11 Nov 2022

Cited by 1 | Viewed by 1927

Abstract

Throughout the pandemic, serological assays have been revealed as crucial for detecting previous exposures to the virus and determining the timing of antibody maintenance after vaccination or natural infection. This study aimed to develop an optimized enzyme-linked immunosorbent assay (ELISA)-based serology, which could be used in case of reagent shortages, such as that occurred in the beginning of this health emergency. As a result, we present a high-sensitive immunoassay for the determination of IgG levels in venous serum samples, using 2 μg/mL antigen (receptor-binding domain of the spike protein S1) for coating the plate and utilizing human samples at a dilution 1:1000. This method showed non-inferiority features versus a commercial kit, is less expensive, and has a higher spectrophotometric range that allows for a better quantification of the antibody titers. The optical density values before and after heating venous serum samples at 56 °C during 30 min was quite similar, showing that heat inactivation can be used to reduce the biohazardous risks while handling samples. Furthermore, we show that finger-stick capillary blood samples can also serve as a suitable source for IgG detection, bypassing the need for serum isolation and being suitable for point-of-care application (Pearson’s coefficient correlation with capillary serum was 0.95, being statistically significant). Full article

(This article belongs to the Special Issue Past, Present and Future of COVID-19)

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12 pages, 733 KiB

Open AccessArticle

Validation of the T-Lymphocyte Subset Index (TLSI) as a Score to Predict Mortality in Unvaccinated Hospitalized COVID-19 Patients

by Andrea Di Lorenzo, Simona Tedde, Pier Giorgio Pace, Laura Campogiani, Lorenzo Ansaldo, Alessandra Lodi, Marta Zordan, Filippo Barreca, Federica Caldara, Benedetta Rossi, Alessandra Imeneo, Grazia Alessio, Angela Maria Antonia Crea, Davide Checchi, Vincenzo Malagnino, Elisabetta Teti, Luigi Coppola, Raffaele Palmieri, Francesco Buccisano, Massimo Andreoni, Loredana Sarmati and Marco Iannetta Show full author list Hide full author list

Biomedicines 2022, 10(11), 2788; https://doi.org/10.3390/biomedicines10112788 - 2 Nov 2022

Cited by 1 | Viewed by 1863

Abstract

Lymphopenia has been consistently reported as associated with severe coronavirus disease 2019 (COVID-19). Several studies have described a profound decline in all T-cell subtypes in hospitalized patients with severe and critical COVID-19. The aim of this study was to assess the role of T-lymphocyte subset absolute counts measured at ward admission in predicting 30-day mortality in COVID-19 hospitalized patients, validating a new prognostic score, the T-Lymphocyte Subset Index (TLSI, range 0–2), based on the number of T-cell subset (CD4+ and CD8+) absolute counts that are below prespecified cutoffs. These cutoff values derive from a previously published work of our research group at Policlinico Tor Vergata, Rome, Italy: CD3+CD4+ < 369 cells/μL, CD3+CD8+ < 194 cells/μL. In the present single-center retrospective study, T-cell subsets were assessed on admission to the infectious diseases ward. Statistical analysis was performed using JASP (Version 0.16.2. JASP Team, 2022, Amsterdam, The Netherlands) and Prism8 (version 8.2.1. GraphPad Software, San Diego, CA, USA). Clinical and laboratory parameters of 296 adult patients hospitalized because of COVID-19 were analyzed. The overall mortality rate was 22.3% (66/296). Survivors (S) had a statistically significant lower TLSI score compared to non-survivors (NS) (p < 0.001). Patients with increasing TLSI scores had proportionally higher rates of 30-day mortality (p < 0.0001). In the multivariable logistic analysis, the TLSI was an independent predictor of in-hospital 30-day mortality (OR: 1.893, p = 0.003). Survival analysis showed that patients with a TLSI > 0 had an increased risk of death compared to patients with a TLSI = 0 (hazard ratio: 2.83, p < 0.0001). The TLSI was confirmed as an early and independent predictor of COVID-19 in-hospital 30-day mortality. Full article

(This article belongs to the Special Issue Past, Present and Future of COVID-19)

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10 pages, 1111 KiB

Open AccessArticle

Distribution of Viral Respiratory Infections during the COVID-19 Pandemic Using the FilmArray Respiratory Panel

by Ying-Ju Chen and Tze-Kiong Er

Biomedicines 2022, 10(11), 2734; https://doi.org/10.3390/biomedicines10112734 - 28 Oct 2022

Cited by 4 | Viewed by 2292

Abstract

This study was conducted to evaluate the distribution of respiratory viral pathogens in the emergency department during the coronavirus disease 2019 (COVID-19) pandemic. Between May 2020 and September 2022, patients aged between 0.1 and 98 years arrived at the emergency department of Asia University Hospital, and samples from nasopharyngeal swabs were tested by the FilmArray^TM Respiratory Panel (RP). SARS-CoV-2 positivity was subsequently retested by the cobas Liat system. There were 804 patients for whom the FilmArray^TM RP was tested, and 225 (27.9%) of them had positive results for respiratory viruses. Rhinovirus/enterovirus was the most commonly detected pathogen, with 170 (61.8%) cases, followed by adenovirus with 38 (13.8%), SARS-CoV-2 with 16 (5.8%) cases, and coronavirus 229E, with 16 (5.8%) cases. SARS-CoV-2 PCR results were positive in 16 (5.8%) cases, and there were two coinfections of SARS-CoV-2 with adenovirus and rhinovirus/enterovirus. A total of 43 (5.3%) patients were coinfected; the most coinfection was adenovirus plus rhinovirus/enterovirus, which was detectable in 18 (41.9%) cases. No atypical pathogens were found in this study. Intriguingly, our results showed that there was prefect agreement between the detection of SARS-CoV-2 conducted with the cobas Liat SARS-CoV-2 and influenza A/B nucleic acid test and the FilmArray^TM RP. Therefore, the FilmArray^TM RP assay is a reliable and feasible method for the detection of SARS-CoV-2. In summary, FilmArray^TM RP significantly broadens our capability to detect multiple respiratory infections due to viruses and atypical bacteria. It provides a prompt evaluation of pathogens to enhance patient care and clinical selection strategies in emergency departments during the COVID-19 pandemic. Full article

(This article belongs to the Special Issue Past, Present and Future of COVID-19)

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13 pages, 1821 KiB

Open AccessArticle

Implication of Neutrophils Extracellular Traps in the Pathogenesis of SARS-CoV-2 pneumonia

by Patricia Pérez-Guerrero, Francisco Illanes-Álvarez, Denisse Márquez-Ruiz, Irene Campaña-Gómez, Sara Cuesta-Sancho, Mercedes Márquez-Coello and José-Antonio Girón-González

Biomedicines 2022, 10(10), 2638; https://doi.org/10.3390/biomedicines10102638 - 20 Oct 2022

Cited by 3 | Viewed by 1811

Abstract

Peripheral blood polymorphonuclear neutrophils (PMNs) forming extracellular traps (NETs), as well as endothelial- and platelet-derived parameters, have been analyzed in patients with SARS-CoV-2 pneumonia, and their prognostic role has been evaluated. Eighty-seven consecutive patients hospitalized with SARS-CoV-2 pneumonia were prospectively selected. A sample of 30 healthy individuals served as the control group. Clinical and oxygenation (oxygen saturation to fraction of inspired oxygen ratio—SpO²/FiO²) characteristics and PMNs forming NETs, serum levels of myeloperoxidase, E-selectin, vascular cell adhesion molecule 1—VCAM1—vascular endothelial growth factor, P-selectin, platelet factor 4 and plasma concentrations of D-dimer were evaluated at hospital admission, at discharge and 14 days after discharge. Intensive care unit admission or death was the primary composite endpoint. Patients showed a higher number of PMNs forming NETs than healthy controls. The absolute number of PMNs forming NETs was inversely correlated with oxygen status (SpO²/FiO²) and positively with inflammatory (C-reactive protein, ferritin) markers and VCAM1. A decrease in, but not a normalization of NETs and endothelial-derived parameters was observed in patients who survived. In conclusion, the formation of NETs runs parallel to that of other inflammatory and endothelial activation markers, and is inverse to the oxygenation parameters, supporting a pathogenic role for PMNs in this entity. Full article

(This article belongs to the Special Issue Past, Present and Future of COVID-19)

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16 pages, 1077 KiB

Open AccessArticle

Predicting In-Hospital Mortality in Severe COVID-19: A Systematic Review and External Validation of Clinical Prediction Rules

by Modesto M. Maestre-Muñiz, Ángel Arias and Alfredo J. Lucendo

Biomedicines 2022, 10(10), 2414; https://doi.org/10.3390/biomedicines10102414 - 27 Sep 2022

Cited by 2 | Viewed by 1986

Abstract

Multiple prediction models for risk of in-hospital mortality from COVID-19 have been developed, but not applied, to patient cohorts different to those from which they were derived. The MEDLINE, EMBASE, Scopus, and Web of Science (WOS) databases were searched. Risk of bias and applicability were assessed with PROBAST. Nomograms, whose variables were available in a well-defined cohort of 444 patients from our site, were externally validated. Overall, 71 studies, which derived a clinical prediction rule for mortality outcome from COVID-19, were identified. Predictive variables consisted of combinations of patients′ age, chronic conditions, dyspnea/taquipnea, radiographic chest alteration, and analytical values (LDH, CRP, lymphocytes, D-dimer); and markers of respiratory, renal, liver, and myocardial damage, which were mayor predictors in several nomograms. Twenty-five models could be externally validated. Areas under receiver operator curve (AUROC) in predicting mortality ranged from 0.71 to 1 in derivation cohorts; C-index values ranged from 0.823 to 0.970. Overall, 37/71 models provided very-good-to-outstanding test performance. Externally validated nomograms provided lower predictive performances for mortality in their respective derivation cohorts, with the AUROC being 0.654 to 0.806 (poor to acceptable performance). We can conclude that available nomograms were limited in predicting mortality when applied to different populations from which they were derived. Full article

(This article belongs to the Special Issue Past, Present and Future of COVID-19)

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19 pages, 2111 KiB

Open AccessArticle

Increased mRNA Levels of ADAM17, IFITM3, and IFNE in Peripheral Blood Cells Are Present in Patients with Obesity and May Predict Severe COVID-19 Evolution

by Catalina A. Pomar, M. Luisa Bonet, Adrián Ferre-Beltrán, Pablo A. Fraile-Ribot, Mercedes García-Gasalla, Melchor Riera, Catalina Picó and Andreu Palou

Biomedicines 2022, 10(8), 2007; https://doi.org/10.3390/biomedicines10082007 - 18 Aug 2022

Cited by 1 | Viewed by 2299

Abstract

Gene expression patterns in blood cells from SARS-CoV-2 infected individuals with different clinical phenotypes and body mass index (BMI) could help to identify possible early prognosis factors for COVID-19. We recruited patients with COVID-19 admitted in Hospital Universitari Son Espases (HUSE) between March 2020 and November 2021, and control subjects. Peripheral blood cells (PBCs) and plasma samples were obtained on hospital admission. Gene expression of candidate transcriptomic biomarkers in PBCs were compared based on the patients’ clinical status (mild, severe and critical) and BMI range (normal weight, overweight, and obesity). mRNA levels of ADAM17, IFITM3, IL6, CXCL10, CXCL11, IFNG and TYK2 were increased in PBCs of COVID-19 patients (n = 73) compared with controls (n = 47), independently of sex. Increased expression of IFNE was observed in the male patients only. PBC mRNA levels of ADAM17, IFITM3, CXCL11, and CCR2 were higher in those patients that experienced a more serious evolution during hospitalization. ADAM17, IFITM3, IL6 and IFNE were more highly expressed in PBCs of patients with obesity. Interestingly, the expression pattern of ADAM17, IFITM3 and IFNE in PBCs was related to both the severity of COVID-19 evolution and obesity status, especially in the male patients. In conclusion, gene expression in PBCs can be useful for the prognosis of COVID-19 evolution. Full article

(This article belongs to the Special Issue Past, Present and Future of COVID-19)

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10 pages, 555 KiB

Open AccessArticle

Prevalence of Musculoskeletal Post-COVID Pain in Hospitalized COVID-19 Survivors Depending on Infection with the Historical, Alpha or Delta SARS-CoV-2 Variant

by César Fernández-de-las-Peñas, Ignacio Cancela-Cilleruelo, Paloma Moro-López-Menchero, Jorge Rodríguez-Jiménez, Víctor Gómez-Mayordomo, Juan Torres-Macho, Oscar J. Pellicer-Valero, José D. Martín-Guerrero, Valentín Hernández-Barrera and Lars Arendt-Nielsen

Biomedicines 2022, 10(8), 1951; https://doi.org/10.3390/biomedicines10081951 - 11 Aug 2022

Cited by 16 | Viewed by 2879

Abstract

We compared the prevalence of musculoskeletal post-COVID pain between previously hospitalized COVID-19 survivors infected with the historical, Alpha or Delta SARS-CoV-2 variant. Data about musculoskeletal post-COVID pain were systematically collected through a telephone interview involving 201 patients who had survived the historical variant, 211 who had survived the Alpha variant and 202 who had survived the Delta variant six months after hospital discharge. Participants were recruited from non-vaccinated individuals hospitalized due to SARS-CoV-2 infection in one hospital of Madrid (Spain) during three different waves of the pandemic (historical, Alpha or Delta variant). Hospitalization and clinical data were collected from hospital medical records. In addition, anxiety/depressive levels and sleep quality were also assessed. The prevalence of musculoskeletal post-COVID pain was higher (p = 0.003) in patients infected with the historical variant (47.7%) than in those infected with the Alpha (38.3%) or Delta (41%) variants. A significantly (p = 0.002) higher proportion of individuals infected with the historical variant reported generalized pain (20.5%) when compared with those infected with the other variants. The prevalence of new-onset post-COVID musculoskeletal pain reached 80.1%, 75.2% and 79.5% of patients infected with the historical, Alpha or Delta variants, respectively. No specific risk factors for developing post-COVID pain were identified depending on the SARS-CoV-2 variant. In conclusion, this study found that musculoskeletal post-COVID pain is highly prevalent in COVID-19 survivors six months after hospital discharge, with the highest prevalence and most generalized pain symptoms in individuals infected with the historical variant. Approximately 50% developed “de novo” post-COVID musculoskeletal pain symptoms. Full article

(This article belongs to the Special Issue Past, Present and Future of COVID-19)

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Review

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21 pages, 1130 KiB

Open AccessReview

Role of Dipeptidyl Peptidase-4 (DPP4) on COVID-19 Physiopathology

by Alba Sebastián-Martín, Belén G. Sánchez, José M. Mora-Rodríguez, Alicia Bort and Inés Díaz-Laviada

Biomedicines 2022, 10(8), 2026; https://doi.org/10.3390/biomedicines10082026 - 19 Aug 2022

Cited by 24 | Viewed by 6474

Abstract

DPP4/CD26 is a single-pass transmembrane protein with multiple functions on glycemic control, cell migration and proliferation, and the immune system, among others. It has recently acquired an especial relevance due to the possibility to act as a receptor or co-receptor for SARS-CoV-2, as it has been already demonstrated for other coronaviruses. In this review, we analyze the evidence for the role of DPP4 on COVID-19 risk and clinical outcome, and its contribution to COVID-19 physiopathology. Due to the pathogenetic links between COVID-19 and diabetes mellitus and the hyperinflammatory response, with the hallmark cytokine storm developed very often during the disease, we dive deep into the functions of DPP4 on carbohydrate metabolism and immune system regulation. We show that the broad spectrum of functions regulated by DPP4 is performed both as a protease enzyme, as well as an interacting partner of other molecules on the cell surface. In addition, we provide an update of the DPP4 inhibitors approved by the EMA and/or the FDA, together with the newfangled approval of generic drugs (in 2021 and 2022). This review will also cover the effects of DPP4 inhibitors (i.e., gliptins) on the progression of SARS-CoV-2 infection, showing the role of DPP4 in this disturbing disease. Full article

(This article belongs to the Special Issue Past, Present and Future of COVID-19)

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24 pages, 2991 KiB

Open AccessReview

SARS-CoV-2: A Master of Immune Evasion

by Alberto Rubio-Casillas, Elrashdy M. Redwan and Vladimir N. Uversky

Biomedicines 2022, 10(6), 1339; https://doi.org/10.3390/biomedicines10061339 - 7 Jun 2022

Cited by 32 | Viewed by 6492

Abstract

Viruses and their hosts have coevolved for a long time. This coevolution places both the pathogen and the human immune system under selective pressure; on the one hand, the immune system has evolved to combat viruses and virally infected cells, while viruses have developed sophisticated mechanisms to escape recognition and destruction by the immune system. SARS-CoV-2, the pathogen that is causing the current COVID-19 pandemic, has shown a remarkable ability to escape antibody neutralization, putting vaccine efficacy at risk. One of the virus’s immune evasion strategies is mitochondrial sabotage: by causing reactive oxygen species (ROS) production, mitochondrial physiology is impaired, and the interferon antiviral response is suppressed. Seminal studies have identified an intra-cytoplasmatic pathway for viral infection, which occurs through the construction of tunneling nanotubes (TNTs), hence enhancing infection and avoiding immune surveillance. Another method of evading immune monitoring is the disruption of the antigen presentation. In this scenario, SARS-CoV-2 infection reduces MHC-I molecule expression: SARS-CoV-2’s open reading frames (ORF 6 and ORF 8) produce viral proteins that specifically downregulate MHC-I molecules. All of these strategies are also exploited by other viruses to elude immune detection and should be studied in depth to improve the effectiveness of future antiviral treatments. Compared to the Wuhan strain or the Delta variant, Omicron has developed mutations that have impaired its ability to generate syncytia, thus reducing its pathogenicity. Conversely, other mutations have allowed it to escape antibody neutralization and preventing cellular immune recognition, making it the most contagious and evasive variant to date. Full article

(This article belongs to the Special Issue Past, Present and Future of COVID-19)

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Other

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15 pages, 2474 KiB

Open AccessSystematic Review

Association of Patients’ Epidemiological Characteristics and Comorbidities with Severity and Related Mortality Risk of SARS-CoV-2 Infection: Results of an Umbrella Systematic Review and Meta-Analysis

by Eduardo Reyna-Villasmil, Maria Giulia Caponcello, Natalia Maldonado, Paula Olivares, Natascia Caroccia, Cecilia Bonazzetti, Beatrice Tazza, Elena Carrara, Maddalena Giannella, Evelina Tacconelli, Jesús Rodríguez-Baño and Zaira R. Palacios-Baena

Biomedicines 2022, 10(10), 2437; https://doi.org/10.3390/biomedicines10102437 - 29 Sep 2022

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Abstract

The objective of this study was to assess the association between patients’ epidemiological characteristics and comorbidities with SARS-CoV-2 infection severity and related mortality risk. An umbrella systematic review, including a meta-analysis examining the association between patients’ underlying conditions and severity (defined as need for hospitalization) and mortality of COVID-19, was performed. Studies were included if they reported pooled risk estimates of at least three underlying determinants for hospitalization, critical disease (ICU admission, mechanical ventilation), and hospital mortality in patients diagnosed with SARS-CoV-2 infection. Evidence was summarized as pooled odds ratios (pOR) for disease outcomes with 95% confidence intervals (95% CI). Sixteen systematic reviews investigating the possible associations of comorbidities with severity or death from COVID-19 disease were included. Hospitalization was associated with age > 60 years (pOR 3.50; 95% CI 2.97–4.36), smoking habit (pOR 3.50; 95% CI 2.97–4.36), and chronic pulmonary disease (pOR 2.94; 95% CI 2.14–4.04). Chronic pulmonary disease (pOR 2.82; 95% CI 1.92–4.14), cerebrovascular disease (pOR 2.74; 95% CI 1.59–4.74), and cardiovascular disease (pOR 2.44; 95% CI 1.97–3.01) were likely to be associated with increased risk of critical COVID-19. The highest risk of mortality was associated with cardiovascular disease (pOR 3.59; 95% CI 2.83–4.56), cerebrovascular disease (pOR 3.11; 95% CI 2.35–4.11), and chronic renal disease (pOR 3.02; 95% CI 2.61–3.49). In conclusion, this umbrella systematic review provides a comprehensive summary of meta-analyses examining the impact of patients’ characteristics on COVID-19 outcomes. Elderly patients and those cardiovascular, cerebrovascular, and chronic renal disease should be prioritized for pre-exposure and post-exposure prophylaxis and early treatment. Full article

(This article belongs to the Special Issue Past, Present and Future of COVID-19)

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