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COVID-19 and Future Pathogens

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Microbiology".

Deadline for manuscript submissions: closed (30 December 2023) | Viewed by 23563

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Special Issue Editor

Dr. Sanjay Kumar Singh Patel

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Guest Editor

Department of Chemical Engineering, Konkuk University, Seoul 05029, Republic of Korea
Interests: Korea nanobiocatalyst; biosensors; anti-microbials; quorum sensing inhibition; microbial pathogen; microbial biotechnology; environmental biotechnology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This special issue on “COVID-19 and Future Pathogens” will cover a research topic focused on recent advancements in the approaches to combat pathogens, including viruses, bacteria, and fungi that cause infectious diseases in animals, humans, and plants by significantly influencing their health. A better understanding of such infectious agents and adaptation of biotechnological and nano-technological methodologies for their prevention are crucial for sustainable development.

The recent pandemic is caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2) acknowledged as COVID-19 has emerged as a potential threat to humans health either directly or indirectly mode. COVID-19 appears to have undergone adaptive evolution, which has shown multiple variants that enhanced the spreading of the viruses among the worldwide population. These different variants affect the diagnosis and treatment strategies for COVID-19 for sustainable development. Still, the major concerns are associated with COVID-19 as the limitations of rapid identification technique, inexpensive effective treatment procedures, including the role of diet and microbiota, designing and synthesis of therapeutic biomolecules, understanding of the viral mechanism and adaptation within the host, and its long term influence on human health, social and environmental status. Apart from the COVID-19, various other infectious diseases are caused by viruses, bacteria, and fungi or related organisms in plants, animals, and humans. The excessive use of antibiotics for treatment has led to multi-drug-resistant pathogens. A better understanding of pathogens, host-pathogen interactions, prediction of future pathogens, adaptive evolution (including non-pathogen conversion to pathogens), and sustainable treatment strategies, including management of microbial pathogens by uses of quorum sensing inhibitors derived from natural or biological origin.

Dr. Sanjay Kumar Singh Patel
Guest Editor

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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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

animal health
anti-microbial agents
bacteria
biomolecules
COVID-19
extracellular vesicles
fungi
host-pathogen interactions
human health
immune therapy
microbiota
plant health
quorum-sensing
quorum-sensing inhibitors
therapeutic agents
virus

Published Papers (14 papers)

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Research

12 pages, 1203 KiB

Open AccessArticle

SARS-CoV-2 Antibodies in Breastmilk Three and Six Months Postpartum in Relation to the Trimester of Maternal SARS-CoV-2 Infection—An Exploratory Study

by Line Fich, Ann-Marie Hellerung Christiansen, Anna Christine Nilsson, Johanna Lindman, Helle Gybel Juul-Larsen, Christine Bo Hansen, Nina la Cour Freiesleben, Mohammed Rohi Khalil and Henriette Svarre Nielsen

Int. J. Mol. Sci. 2024, 25(6), 3269; https://doi.org/10.3390/ijms25063269 - 13 Mar 2024

Viewed by 2263

Abstract

The immune system of neonates is immature and therefore knowledge of possible early-life protection against SARS-CoV-2 infection, such as breastfeeding, is of great importance. Few studies have investigated the presence and duration of SARS-CoV-2 antibodies in breastmilk in relation to the trimester of maternal infection during pregnancy, and none with successful participation from all three trimesters. This study has dual objectives (1) in relation to the trimester of infection to examine the frequency, concentration and duration of IgA and IgG antibodies in breastmilk and blood serum in the third and sixth month post-partum in former SARS-CoV-2-infected mothers and (2) to examine the association in pediatric emergency admission of children within the first six months of life compared to children of non-SARS-CoV-2-infected women. The first objective is based on a prospective cohort and the second is based on a nested case–control design. The study participants are women with a former SARS-CoV-2 infection during pregnancy, whose serology IgG tests at delivery were still positive. Maternal blood and breastmilk samples were collected at three and six months postpartum. Serum IgA frequency three months pp was 72.7% (50%, 90% and 60% in the first, second and third trimester) and 82% six months pp (67%, 91% and 82% in the first, second and third trimester). Breastmilk IgA frequency three months pp was 27% (16.6%, 36% and 20% in first, second and third trimester) and 28% six months pp (0%, 38% and 28% in the first, second and third trimester). The highest IgA concentration in breastmilk was found six months post-partum with infection in the third trimester. Serum IgA was detectable more than 400 days post infection, and serum IgG above threshold was found 430 days after date of infection. We found no correlation between serum IgA and breastmilk IgA, nor between serum IgG and breastmilk IgA regardless of the trimester of infection. Full article

(This article belongs to the Special Issue COVID-19 and Future Pathogens)

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17 pages, 6032 KiB

Open AccessArticle

T Cell Responses in Pregnant Women Who Received mRNA-Based Vaccination to Prevent COVID-19 Revealed Unknown Exposure to the Natural Infection and Numerous SARS-CoV-2-Specific CD4- CD8- Double Negative T Cells and Regulatory T Cells

by Christina D. Chambers, Jaeyoon Song, Ricardo da Silva Antunes, Alessandro Sette and Alessandra Franco

Int. J. Mol. Sci. 2024, 25(4), 2031; https://doi.org/10.3390/ijms25042031 - 07 Feb 2024

Viewed by 982

Abstract

We studied T-cell responses to SARS-CoV-2 in 19 pregnant subjects at different gestational weeks who received three doses of mRNA-based vaccination to prevent COVID-19. SARS-CoV-2 peptide pools were used for T-cell recognition studies: peptides were 15 amino acids long and had previously been defined in COVID-19-convalescent subjects. T-cell activation was evaluated with the AIM assay. Most subjects showed coordinated, spike-specific CD4+ and CD8+ T-cell responses and the development of T cell memory. Non-spike-specific T cells in subjects who were not aware of previous COVID-19 infection suggested a prior undetected, asymptomatic infection. CD4- CD8- double negative (DN) T cells were numerous, of which a percentage was specific for SARS-CoV-2 spike peptides. Regulatory T cells (Treg), both spike- and non-spike-specific, were also greatly expanded. Two Treg populations were defined: a population differentiated from naïve T cells, and pTreg, reverting from pro-inflammatory T cells. The Treg cells expressed CCR6, suggesting homing to the endometrium and vaginal epithelial cells. The pregnant women responded to SARS-CoV-2 vaccination. Asymptomatic COVID-19 was revealed by the T cell response to the non-spike peptides. The numerous DN T cells and Treg pointed our attention to new aspects of the adaptive immune response in vaccine recipients. Full article

(This article belongs to the Special Issue COVID-19 and Future Pathogens)

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11 pages, 1655 KiB

Open AccessArticle

Placental Transfer Efficiency of Neutralizing Antibodies on SARS-CoV-2 Vaccination before and after Pregnancy in Mexican Women

by Rebeca Martínez-Quezada, Carlos Emilio Miguel-Rodríguez, Tito Ramírez-Lozada, Omar Esteban Valencia-Ledezma and Gustavo Acosta-Altamirano

Int. J. Mol. Sci. 2024, 25(3), 1516; https://doi.org/10.3390/ijms25031516 - 26 Jan 2024

Viewed by 746

Abstract

The protection of the neonate against pathogens depends largely on the antibodies transferred placentally from the mother; for this reason, maternal vaccination against emerging viruses, such as SARS-CoV-2, is of vital importance. Knowing some of the immunogenic factors that could alter the placental transfer of antibodies could aid in understanding the immune response and neonatal protection after maternal vaccination. In this study, we analyzed the efficiency of the placental transfer of binding and neutralizing antibodies, as well as some factors that could alter the passive immune response, such as the trimester of gestation at the time of immunization, the number of doses received by the mother and the type of vaccine. Binding IgG antibodies were detected by ELISA, and the detection of neutralizing antibodies was carried out using flow cytometry. Our results show efficient transfer rates (>1), which are higher when maternal vaccination occurs during the third trimester of gestation. Antibodies are detectable in mothers and their neonates after 12 months of maternal immunization, suggesting than the vaccination against COVID-19 before and during pregnancy in the Mexican population induces a lasting neutralizing response in mothers and their newborns. Full article

(This article belongs to the Special Issue COVID-19 and Future Pathogens)

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18 pages, 3443 KiB

Open AccessArticle

Monoclonal Antibodies as SARS-CoV-2 Serology Standards: Experimental Validation and Broader Implications for Correlates of Protection

by Lili Wang, Paul N. Patrone, Anthony J. Kearsley, Jerilyn R. Izac, Adolfas K. Gaigalas, John C. Prostko, Hyung Joon Kwon, Weichun Tang, Martina Kosikova, Hang Xie, Linhua Tian, Elzafir B. Elsheikh, Edward J. Kwee, Troy Kemp, Simon Jochum, Natalie Thornburg, L. Clifford McDonald, Adi V. Gundlapalli and Sheng Lin-Gibson

Int. J. Mol. Sci. 2023, 24(21), 15705; https://doi.org/10.3390/ijms242115705 - 28 Oct 2023

Cited by 1 | Viewed by 943

Abstract

COVID-19 has highlighted challenges in the measurement quality and comparability of serological binding and neutralization assays. Due to many different assay formats and reagents, these measurements are known to be highly variable with large uncertainties. The development of the WHO international standard (WHO IS) and other pool standards have facilitated assay comparability through normalization to a common material but does not provide assay harmonization nor uncertainty quantification. In this paper, we present the results from an interlaboratory study that led to the development of (1) a novel hierarchy of data analyses based on the thermodynamics of antibody binding and (2) a modeling framework that quantifies the probability of neutralization potential for a given binding measurement. Importantly, we introduced a precise, mathematical definition of harmonization that separates the sources of quantitative uncertainties, some of which can be corrected to enable, for the first time, assay comparability. Both the theory and experimental data confirmed that mAbs and WHO IS performed identically as a primary standard for establishing traceability and bridging across different assay platforms. The metrological anchoring of complex serological binding and neuralization assays and fast turn-around production of an mAb reference control can enable the unprecedented comparability and traceability of serological binding assay results for new variants of SARS-CoV-2 and immune responses to other viruses. Full article

(This article belongs to the Special Issue COVID-19 and Future Pathogens)

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14 pages, 3927 KiB

Open AccessArticle

Surveillance of SARS-CoV-2 Genetic Variants in the Polish Armed Forces Using Whole Genome Sequencing Analysis

by Katarzyna Skuza, Pawel Rutyna, Lukasz Krzowski, Lukasz Rabalski and Tomasz Lepionka

Int. J. Mol. Sci. 2023, 24(19), 14851; https://doi.org/10.3390/ijms241914851 - 03 Oct 2023

Viewed by 881

Abstract

Military operations involve the global movement of personnel and equipment, increasing the risk of spreading infectious pathogens such as SARS-CoV-2. Given the continuous engagement of the Polish Armed Forces in overseas operations, an active surveillance program targeting Variants of Concern (VOC) of SARS-CoV-2 was implemented among military personnel. Screening using RT-qPCR tests was conducted on 1699 soldiers between November 2021 and May 2022. Of these, 84 SARS-CoV-2 positive samples met the criteria for whole genome sequencing analysis and variant identification. Whole genome sequencing was performed using two advanced next-generation sequencing (NGS) technologies: sequencing by synthesis and nanopore sequencing. Our analysis revealed eleven SARS-CoV-2 lineages belonging to 21K, 21L, and 21J. The predominant lineage was BA.1.1 (57% of the samples), followed by BA.1 (23%) and BA.2 (6%). Notably, all identified lineages detected in post-deployment screening tests were classified as VOC and were already present in Poland, showing the effectiveness of the Military Sanitary Inspection measures in mitigating the COVID-19 spread. Pre-departure and post-mission screening and isolation successfully prevented SARS-CoV-2 VOC exportation and importation. Proactive measures are vital in minimizing the impact of COVID-19 in military settings, emphasizing the need for continued vigilance and response strategies. Full article

(This article belongs to the Special Issue COVID-19 and Future Pathogens)

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11 pages, 1507 KiB

Open AccessArticle

Meta-Analysis of COVID-19 Metabolomics Identifies Variations in Robustness of Biomarkers

by Anthony Onoja, Johanna von Gerichten, Holly-May Lewis, Melanie J. Bailey, Debra J. Skene, Nophar Geifman and Matt Spick

Int. J. Mol. Sci. 2023, 24(18), 14371; https://doi.org/10.3390/ijms241814371 - 21 Sep 2023

Viewed by 1075

Abstract

The global COVID-19 pandemic resulted in widespread harms but also rapid advances in vaccine development, diagnostic testing, and treatment. As the disease moves to endemic status, the need to identify characteristic biomarkers of the disease for diagnostics or therapeutics has lessened, but lessons can still be learned to inform biomarker research in dealing with future pathogens. In this work, we test five sets of research-derived biomarkers against an independent targeted and quantitative Liquid Chromatography–Mass Spectrometry metabolomics dataset to evaluate how robustly these proposed panels would distinguish between COVID-19-positive and negative patients in a hospital setting. We further evaluate a crowdsourced panel comprising the COVID-19 metabolomics biomarkers most commonly mentioned in the literature between 2020 and 2023. The best-performing panel in the independent dataset—measured by F1 score (0.76) and AUROC (0.77)—included nine biomarkers: lactic acid, glutamate, aspartate, phenylalanine, β-alanine, ornithine, arachidonic acid, choline, and hypoxanthine. Panels comprising fewer metabolites performed less well, showing weaker statistical significance in the independent cohort than originally reported in their respective discovery studies. Whilst the studies reviewed here were small and may be subject to confounders, it is desirable that biomarker panels be resilient across cohorts if they are to find use in the clinic, highlighting the importance of assessing the robustness and reproducibility of metabolomics analyses in independent populations. Full article

(This article belongs to the Special Issue COVID-19 and Future Pathogens)

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11 pages, 1457 KiB

Open AccessCommunication

rs71327024 Associated with COVID-19 Hospitalization Reduces CXCR6 Promoter Activity in Human CD4⁺ T Cells via Disruption of c-Myb Binding

by Aksinya N. Uvarova, Ekaterina M. Stasevich, Alina S. Ustiugova, Nikita A. Mitkin, Elina A. Zheremyan, Savely A. Sheetikov, Ksenia V. Zornikova, Apollinariya V. Bogolyubova, Mikhail A. Rubtsov, Ivan V. Kulakovskiy, Dmitry V. Kuprash, Kirill V. Korneev and Anton M. Schwartz

Int. J. Mol. Sci. 2023, 24(18), 13790; https://doi.org/10.3390/ijms241813790 - 07 Sep 2023

Cited by 2 | Viewed by 1387

Abstract

Single-nucleotide polymorphism rs71327024 located in the human 3p21.31 locus has been associated with an elevated risk of hospitalization upon SARS-CoV-2 infection. The 3p21.31 locus contains several genes encoding chemokine receptors potentially relevant to severe COVID-19. In particular, CXCR6, which is prominently expressed in T lymphocytes, NK, and NKT cells, has been shown to be involved in the recruitment of immune cells to non-lymphoid organs in chronic inflammatory and respiratory diseases. In COVID-19, CXCR6 expression is reduced in lung resident memory T cells from patients with severe disease as compared to the control cohort with moderate symptoms. We demonstrate here that rs71327024 is located within an active enhancer that augments the activity of the CXCR6 promoter in human CD4⁺ T lymphocytes. The common rs71327024(G) variant makes a functional binding site for the c-Myb transcription factor, while the risk rs71327024(T) variant disrupts c-Myb binding and reduces the enhancer activity. Concordantly, c-Myb knockdown in PMA-treated Jurkat cells negates rs71327024’s allele-specific effect on CXCR6 promoter activity. We conclude that a disrupted c-Myb binding site may decrease CXCR6 expression in T helper cells of individuals carrying the minor rs71327024(T) allele and thus may promote the progression of severe COVID-19 and other inflammatory pathologies. Full article

(This article belongs to the Special Issue COVID-19 and Future Pathogens)

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13 pages, 2054 KiB

Open AccessCommunication

Potentiating the Cross-Reactive IFN-γ T Cell and Polyfunctional T Cell Responses by Heterologous GX-19N DNA Booster in Mice Primed with Either a COVID-19 mRNA Vaccine or Inactivated Vaccine

by Yong Bok Seo, Ara Ko, Duckhyang Shin, Junyoung Kim, You Suk Suh, Juyoung Na, Ji In Ryu, Suyeon Lee, Min Ji Oh and Young Chul Sung

Int. J. Mol. Sci. 2023, 24(11), 9753; https://doi.org/10.3390/ijms24119753 - 05 Jun 2023

Viewed by 1247

Abstract

Waning vaccine-induced immunity, coupled with the emergence of SARS-CoV-2 variants, has inspired the widespread implementation of COVID-19 booster vaccinations. Here, we evaluated the potential of the GX-19N DNA vaccine as a heterologous booster to enhance the protective immune response to SARS-CoV-2 in mice primed with either an inactivated virus particle (VP) or an mRNA vaccine. We found that in the VP-primed condition, GX-19N enhanced the response of both vaccine-specific antibodies and cross-reactive T Cells to the SARS-CoV-2 variant of concern (VOC), compared to the homologous VP vaccine prime-boost. Under the mRNA-primed condition, GX-19N induced higher vaccine-induced T Cell responses but lower antibody responses than the homologous mRNA vaccine prime-boost. Furthermore, the heterologous GX-19N boost induced higher S-specific polyfunctional CD4⁺ and CD8⁺ T cell responses than the homologous VP or mRNA prime-boost vaccinations. Our results provide new insights into booster vaccination strategies for the management of novel COVID-19 variants. Full article

(This article belongs to the Special Issue COVID-19 and Future Pathogens)

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12 pages, 1232 KiB

Open AccessArticle

Effects of Different Types of Recombinant SARS-CoV-2 Spike Protein on Circulating Monocytes’ Structure

by Marco Vettori, Francesco Dima, Brandon Michael Henry, Giovanni Carpenè, Matteo Gelati, Giovanni Celegon, Gian Luca Salvagno and Giuseppe Lippi

Int. J. Mol. Sci. 2023, 24(11), 9373; https://doi.org/10.3390/ijms24119373 - 27 May 2023

Cited by 1 | Viewed by 1548

Abstract

This study investigated the biological effects on circulating monocytes after challenge with SARS-CoV-2 recombinant spike protein. Whole blood collected from seven ostensibly healthy healthcare workers was incubated for 15 min with 2 and 20 ng/mL final concentration of recombinant spike protein of Ancestral, Alpha, Delta, and Omicron variants. Samples were analyzed with Sysmex XN and DI-60 analyzers. Cellular complexity (i.e., the presence of granules, vacuoles and other cytoplasmic inclusions) increased in all samples challenged with the recombinant spike protein of the Ancestral, Alpha, and Delta variants, but not in those containing Omicron. The cellular content of nucleic acids was constantly decreased in most samples, achieving statistical significance in those containing 20 ng/mL of Alpha and Delta recombinant spike proteins. The heterogeneity of monocyte volumes significantly increased in all samples, achieving statistical significance in those containing 20 ng/mL of recombinant spike protein of the Ancestral, Alpha and Delta variants. The monocyte morphological abnormalities after spike protein challenge included dysmorphia, granulation, intense vacuolization, platelet phagocytosis, development of aberrant nuclei, and cytoplasmic extrusions. The SARS-CoV-2 spike protein triggers important monocyte morphological abnormalities, more evident in cells challenged with recombinant spike protein of the more clinically severe Alpha and Delta variants. Full article

(This article belongs to the Special Issue COVID-19 and Future Pathogens)

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14 pages, 2324 KiB

Open AccessArticle

Electrochemical Biosensor for the Determination of Specific Antibodies against SARS-CoV-2 Spike Protein

by Sarunas Zukauskas, Alma Rucinskiene, Vilma Ratautaite, Almira Ramanaviciene, Greta Pilvenyte, Mikhael Bechelany and Arunas Ramanavicius

Int. J. Mol. Sci. 2023, 24(1), 718; https://doi.org/10.3390/ijms24010718 - 31 Dec 2022

Cited by 8 | Viewed by 2277

Abstract

In this article, we report the development of an electrochemical biosensor for the determination of the SARS-CoV-2 spike protein (rS). A gold disc electrode was electrochemically modified to form the nanocrystalline gold structure on the surface. Then, it was further altered by a self-assembling monolayer based on a mixture of two alkane thiols: 11-mercaptoundecanoic acid (11-MUA) and 6-mercapto-1-hexanol (6-MCOH) (SAM_mix). After activating carboxyl groups using a N-(3-dimethylaminopropyl)-N’-ethyl-carbodiimide hydrochloride and N-hydroxysuccinimide mixture, the rS protein was covalently immobilized on the top of the SAM_mix. This electrode was used to design an electrochemical sensor suitable for determining antibodies against the SARS-CoV-2 rS protein (anti-rS). We assessed the association between the immobilized rS protein and the anti-rS antibody present in the blood serum of a SARS-CoV-2 infected person using three electrochemical methods: cyclic voltammetry, differential pulse voltammetry, and potential pulsed amperometry. The results demonstrated that differential pulse voltammetry and potential pulsed amperometry measurements displayed similar sensitivity. In contrast, the measurements performed by cyclic voltammetry suggest that this method is the most sensitive out of the three methods applied in this research. Full article

(This article belongs to the Special Issue COVID-19 and Future Pathogens)

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18 pages, 3438 KiB

Open AccessArticle

Dysbiosis: An Indicator of COVID-19 Severity in Critically Ill Patients

by Silvia Cuenca, Zaida Soler, Gerard Serrano-Gómez, Zixuan Xie, Jordi Barquinero, Joaquim Roca, Jose-Maria Sirvent and Chaysavanh Manichanh

Int. J. Mol. Sci. 2022, 23(24), 15808; https://doi.org/10.3390/ijms232415808 - 13 Dec 2022

Cited by 3 | Viewed by 1525

Abstract

Here, we examined the dynamics of the gut and respiratory microbiomes in severe COVID-19 patients in need of mechanical ventilation in the intensive care unit (ICU). We recruited 85 critically ill patients (53 with COVID-19 and 32 without COVID-19) and 17 healthy controls (HCs) and monitored them for up to 4 weeks. We analyzed the bacterial and fungal taxonomic profiles and loads of 232 gut and respiratory samples and we measured the blood levels of Interleukin 6, IgG, and IgM in COVID-19 patients. Upon ICU admission, the bacterial composition and load in the gut and respiratory samples were altered in critically ill patients compared with HCs. During their ICU stay, the patients experienced increased bacterial and fungal loads, drastic decreased bacterial richness, and progressive changes in bacterial and fungal taxonomic profiles. In the gut samples, six bacterial taxa could discriminate ICU-COV(+) from ICU-COV(−) cases upon ICU admission and the bacterial taxa were associated according to age, PaO2/FiO2, and CRP levels. In the respiratory samples of the ICU-COV(+) patients, bacterial signatures including Pseudomonas and Streptococcus were found to be correlated with the length of ICU stay. Our findings demonstrated that the gut and respiratory microbiome dysbiosis and bacterial signatures associated with critical illness emerged as biomarkers of COVID-19 severity and could be a potential predictor of ICU length of stay. We propose using a high-throughput sequencing approach as an alternative to traditional isolation techniques to monitor ICU patient infection. Full article

(This article belongs to the Special Issue COVID-19 and Future Pathogens)

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8 pages, 818 KiB

Open AccessArticle

SARS-CoV-2 RNA Testing Using Different Assays—Impact on Testing Strategies in a Clinical Setting

by Gerald M. Eibinger, Harald H. Kessler, Evelyn Stelzl, Klaus Vander, Anita Weber-Lassacher, Wilfried Renner and Markus Herrmann

Int. J. Mol. Sci. 2022, 23(21), 12845; https://doi.org/10.3390/ijms232112845 - 25 Oct 2022

Cited by 1 | Viewed by 956

Abstract

In order to assess SARS-CoV-2 real time quantitative polymerase chain reaction (RT-qPCR) results in a real-life setting, three independent laboratories in Graz (Austria) set up a continuous cross comparison schedule. The following test systems were used: The QIAGEN NeuMoDx SARS-CoV-2 Assay, the Allplex™ 2019-nCoV Assay (Seegene) on a MicroLab Nimbus (Hamilton) platform combined with RealStar SARS-CoV-2 RT-PCR Assay (Altona Diagnostics GmbH), and the cobas SARS-CoV-2 test on a fully automated cobas 6800 system (Roche). A total of 200 samples were analysed, 184 (92%) were found to be concordant with all testing platforms, 14 (7%) discordant. Two (1%) samples tested invalid on a single platform and were excluded from further analysis. Discordant results were distributed randomly across the assays. The Ct values from all assays correlated closely with each other. All discordant samples showed Ct values ≥ 26. SARS-CoV-2 RT-qPCR assays may show considerable variability, especially in samples with low viral RNA concentrations. Decision makers should thus balance the advantages and disadvantages of RT-qPCR for mass screening and adopt suitable strategies that ensure a rational management of positive samples with high Ct values. Full article

(This article belongs to the Special Issue COVID-19 and Future Pathogens)

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17 pages, 2446 KiB

Open AccessArticle

Proteomic Analysis Identifies Molecular Players and Biological Processes Specific to SARS-CoV-2 Exposure in Endothelial Cells

by Thatiana Corrêa de Melo, Dilza Trevisan-Silva, Miryam P. Alvarez-Flores, Renata Nascimento Gomes, Marcelo Medina de Souza, Hellen Paula Valerio, Douglas S. Oliveira, Carlos DeOcesano-Pereira, Viviane Fongaro Botosso, Soraia Attie Calil Jorge, Mirta Schattner, Ricardo M. Gomez and Ana Marisa Chudzinski-Tavassi

Int. J. Mol. Sci. 2022, 23(18), 10452; https://doi.org/10.3390/ijms231810452 - 09 Sep 2022

Cited by 6 | Viewed by 3927

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been responsible for the severe pandemic of acute respiratory disease, coronavirus disease 2019 (COVID-19), experienced in the 21st century. The clinical manifestations range from mild symptoms to abnormal blood coagulation and severe respiratory failure. In severe cases, COVID-19 manifests as a thromboinflammatory disease. Damage to the vascular compartment caused by SARS-CoV-2 has been linked to thrombosis, triggered by an enhanced immune response. The molecular mechanisms underlying endothelial activation have not been fully elucidated. We aimed to identify the proteins correlated to the molecular response of human umbilical vein endothelial cells (HUVECs) after exposure to SARS-CoV-2, which might help to unravel the molecular mechanisms of endothelium activation in COVID-19. In this direction, we exposed HUVECs to SARS-CoV-2 and analyzed the expression of specific cellular receptors, and changes in the proteome of HUVECs at different time points. We identified that HUVECs exhibit non-productive infection without cytopathic effects, in addition to the lack of expression of specific cell receptors known to be essential for SARS-CoV-2 entry into cells. We highlighted the enrichment of the protein SUMOylation pathway and the increase in SUMO2, which was confirmed by orthogonal assays. In conclusion, proteomic analysis revealed that the exposure to SARS-CoV-2 induced oxidative stress and changes in protein abundance and pathways enrichment that resembled endothelial dysfunction. Full article

(This article belongs to the Special Issue COVID-19 and Future Pathogens)

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21 pages, 2902 KiB

Open AccessArticle

The Entero-Mammary Pathway and Perinatal Transmission of Gut Microbiota and SARS-CoV-2

by Carmen Josefina Juárez-Castelán, Juan Manuel Vélez-Ixta, Karina Corona-Cervantes, Alberto Piña-Escobedo, Yair Cruz-Narváez, Alejandro Hinojosa-Velasco, María Esther Landero-Montes-de-Oca, Eduardo Davila-Gonzalez, Eduardo González-del-Olmo, Fernando Bastida-Gonzalez, Paola Berenice Zárate-Segura and Jaime García-Mena

Int. J. Mol. Sci. 2022, 23(18), 10306; https://doi.org/10.3390/ijms231810306 - 07 Sep 2022

Cited by 5 | Viewed by 2744

Abstract

COVID-19 is a severe respiratory disease threatening pregnant women, which increases the possibility of adverse pregnancy outcomes. Several recent studies have demonstrated the ability of SARS-CoV-2 to infect the mother enterocytes, disturbing the gut microbiota diversity. The aim of this study was to characterize the entero-mammary microbiota of women in the presence of the virus during delivery. Fifty mother–neonate pairs were included in a transversal descriptive work. The presence of SARS-CoV-2 RNA was detected in nasopharyngeal, mother rectal swabs (MRS) and neonate rectal swabs (NRS) collected from the pairs, and human colostrum (HC) samples collected from mothers. The microbiota diversity was characterized by high-throughput DNA sequencing of V3-16S rRNA gene libraries prepared from HC, MRS, and NRS. Data were analyzed with QIIME2 and R. Our results indicate that several bacterial taxa are highly abundant in MRS positive for SARS-CoV-2 RNA. These bacteria mostly belong to the Firmicutes phylum; for instance, the families Bifidobacteriaceae, Oscillospiraceae, and Microbacteriaceae have been previously associated with anti-inflammatory effects, which could explain the capability of women to overcome the infection. All samples, both positive and negative for SARS-CoV-2, featured a high abundance of the Firmicutes phylum. Further data analysis showed that nearly 20% of the bacterial diversity found in HC was also identified in MRS. Spearman correlation analysis highlighted that some genera of the Proteobacteria and Actinobacteria phyla were negatively correlated with MRS and NRS (p < 0.005). This study provides new insights into the gut microbiota of pregnant women and their potential association with a better outcome during SARS-CoV-2 infection. Full article

(This article belongs to the Special Issue COVID-19 and Future Pathogens)

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