Microorganisms

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12 pages, 562 KiB

Open AccessArticle

DNA Methylation Levels of the ACE2 Promoter Are Not Associated with Post-COVID-19 Symptoms in Individuals Who Had Been Hospitalized Due to COVID-19

by César Fernández-de-las-Peñas, Gema Díaz-Gil, Antonio Gil-Crujera, Stella M. Gómez-Sánchez, Silvia Ambite-Quesada, Juan Torres-Macho, Pablo Ryan-Murua, Anabel Franco-Moreno, Oscar J. Pellicer-Valero, Lars Arendt-Nielsen and Rocco Giordano

Microorganisms 2024, 12(7), 1304; https://doi.org/10.3390/microorganisms12071304 - 27 Jun 2024

Cited by 1 | Viewed by 4154

Abstract

It is known that SARS-CoV-2 can translocate via membrane ACE2 exopeptidase into the host cells, and thus hypomethylation of ACE2 possibly upregulates its expression, enhancing the risk of SARS-CoV-2 infection. This study investigated if DNA methylation levels of the ACE2 promoter are associated [...] Read more.

It is known that SARS-CoV-2 can translocate via membrane ACE2 exopeptidase into the host cells, and thus hypomethylation of ACE2 possibly upregulates its expression, enhancing the risk of SARS-CoV-2 infection. This study investigated if DNA methylation levels of the ACE2 promoter are associated with the development of post-COVID-19 symptomatology in a cohort of COVID-19 survivors who had been previously hospitalized. Non-stimulated saliva samples were obtained from 279 (51.5 male, mean age: 56.5 ± 13.0 years old) COVID-19 survivors who were hospitalized during the first wave of the pandemic. A face-to-face interview in which patients described the presence of post-COVID-19 symptoms (defined as a symptom that started no later than three months after SARS-CoV-2 infection) that they suffered from to an experienced healthcare trainer was conducted. Methylation of five CpG dinucleotides in the ACE2 promoter was quantified using bisulfite pyrosequencing. The percentage of methylation (%) was associated with the presence of the following reported post-COVID-19 symptoms: fatigue, dyspnea at rest, dyspnea at exertion, brain fog, memory loss, concentration loss, or gastrointestinal problems. Participants were assessed a mean of 17.8 (SD: 5.3) months after hospitalization. At that time, 88.1% of the patients experienced at least one post-COVID-19 symptom (mean number for each patient: 3.0; SD: 1.9 post-COVID-19 symptoms). Dyspnea at exertion (67.3%), fatigue (62.3%), and memory loss (31.2%) were the most frequent post-COVID-19 symptoms in the sample. Overall, the analysis did not reveal any difference in the methylation of the ACE2 promoter in any of the CpG locations according to the presence or absence of fatigue, dyspnea at rest, dyspnea at exertion, memory loss, brain fog, concentration loss, and gastrointestinal problems. This study did not find an association between methylation of ACE2 promoter and the presence of post-COVID-19 fatigue, dyspnea, cognitive or gastrointestinal problems in previously hospitalized COVID-19 survivors. Full article

(This article belongs to the Special Issue Coronaviruses: Past, Present, and Future)

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15 pages, 8226 KiB

Open AccessArticle

SARS-CoV-2 Infection and Anemia—A Focus on RBC Deformability and Membrane Proteomics—Integrated Observational Prospective Study

by Angelo D’Alessandro, Elena Krisnevskaya, Valentina Leguizamon, Ines Hernández, Carolina de la Torre, Joan-Josep Bech, Josep-Tomàs Navarro and Joan-Lluis Vives-Corrons

Microorganisms 2024, 12(3), 453; https://doi.org/10.3390/microorganisms12030453 - 23 Feb 2024

Cited by 2 | Viewed by 1737

Abstract

Introduction: The multifaceted impact of COVID-19 extends beyond the respiratory system, encompassing intricate interactions with various physiological systems. This study elucidates the potential association between SARS-CoV-2 infection and anemia, with a particular emphasis on the deformability of red blood cells (RBCs), stability of [...] Read more.

Introduction: The multifaceted impact of COVID-19 extends beyond the respiratory system, encompassing intricate interactions with various physiological systems. This study elucidates the potential association between SARS-CoV-2 infection and anemia, with a particular emphasis on the deformability of red blood cells (RBCs), stability of hemoglobin, enzymatic activities, and proteomic profiles. Methods: The study encompasses a cohort of 74 individuals, including individuals positive for COVID-19, a control group, and patients with other viral infections to discern the specific effects attributable to COVID-19. The analysis of red blood cells was focused on deformability measured by osmotic gradient ektacytometry, hemoglobin stability, and glycolytic enzyme activity. Furthermore, membrane proteins were examined using advanced proteomics techniques to capture molecular-level changes. Results: Findings from the study suggest a correlation between anemia and exacerbated outcomes in COVID-19 patients, marked by significant elevations in d-dimer, serum procalcitonin, creatinine, and blood urea nitrogen (BUN) levels. These observations suggest that chronic kidney disease (CKD) may play a role in the development of anemia in COVID-19 patients, particularly those of advanced age with comorbidities. Furthermore, the proteomic analyses have highlighted a complex relationship between omics data and RBC parameters, enriching our understanding of the mechanisms underlying the disease. Conclusions: This research substantiates the complex interrelationship between COVID-19 and anemia, with a specific emphasis on the potential repercussions of SARS-CoV-2 infection on RBCs. The findings contribute to the growing body of evidence supporting the extensive impact of COVID-19 on RBCs. Full article

(This article belongs to the Special Issue Coronaviruses: Past, Present, and Future)

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13 pages, 2691 KiB

Open AccessArticle

P53-Independent G1-Cell Cycle Arrest Increases SARS-CoV-2 RNA Replication

by Clara Husser, Hyesoo Kwon, Klara Andersson, Sofia Appelberg, Nuria Montserrat, Ali Mirazimi and Vanessa M. Monteil

Microorganisms 2024, 12(3), 443; https://doi.org/10.3390/microorganisms12030443 - 22 Feb 2024

Viewed by 1828

Abstract

While having already killed more than 7 million of people worldwide in 4 years, SARS-CoV-2, the etiological agent of COVID-19, is still circulating and evolving. Understanding the pathogenesis of the virus is of capital importance. It was shown that in vitro and in [...] Read more.

While having already killed more than 7 million of people worldwide in 4 years, SARS-CoV-2, the etiological agent of COVID-19, is still circulating and evolving. Understanding the pathogenesis of the virus is of capital importance. It was shown that in vitro and in vivo infection with SARS-CoV-2 can lead to cell cycle arrest but the effect of the cell cycle arrest on the virus infection and the associated mechanisms are still unclear. By stopping cells in the G1 phase as well as targeting several pathways involved using inhibitors and small interfering RNAs, we were able to determine that the cell cycle arrest in the late G1 is beneficial for SARS-CoV-2 replication. This cell cycle arrest is independent of p53 but is dependent on the CDC25A-CDK2/cyclin E pathway. These data give a new understanding in SARS-CoV-2 pathogenesis and highlight some possible targets for the development of novel therapeutic approaches. Full article

(This article belongs to the Special Issue Coronaviruses: Past, Present, and Future)

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14 pages, 3502 KiB

Open AccessArticle

Cold Atmospheric Helium Plasma in the Post-COVID-19 Era: A Promising Tool for the Disinfection of Silicone Endotracheal Prostheses

by Diego Morais da Silva, Fellype Do Nascimento, Noala Vicensoto Moreira Milhan, Maria Alcionéia Carvalho de Oliveira, Paulo Francisco Guerreiro Cardoso, Daniel Legendre, Fabio Gava Aoki, Konstantin Georgiev Kostov and Cristiane Yumi Koga-Ito

Microorganisms 2024, 12(1), 130; https://doi.org/10.3390/microorganisms12010130 - 9 Jan 2024

Cited by 2 | Viewed by 1293

Abstract

Despite the excellent properties of silicone endotracheal prostheses, their main limitation is the formation of a polymicrobial biofilm on their surfaces. It can cause local inflammation, interfering with the local healing process and leading to further complications in the clinical scenario. The present [...] Read more.

Despite the excellent properties of silicone endotracheal prostheses, their main limitation is the formation of a polymicrobial biofilm on their surfaces. It can cause local inflammation, interfering with the local healing process and leading to further complications in the clinical scenario. The present study evaluated the inhibitory effect of cold atmospheric plasma (CAP) on multispecies biofilms grown on the silicone protheses’ surfaces. In addition to silicone characterization before and after CAP exposure, CAP cytotoxicity on immortalized human bronchial epithelium cell line (BEAS-2B) was evaluated. The aging time test reported that CAP could temporarily change the silicone surface wetting characteristics from hydrophilic (80.5°) to highly hydrophilic (<5°). ATR-FTIR showed no significant alterations in the silicone surficial chemical composition after CAP exposure for 5 min. A significant log reduction in viable cells in monospecies biofilms (log CFU/mL) of C. albicans, S. aureus, and P. aeruginosa (0.636, 0.738, and 1.445, respectively) was detected after CAP exposure. Multispecies biofilms exposed to CAP showed significant viability reduction for C. albicans and S. aureus (1.385 and 0.831, respectively). The protocol was not cytotoxic to BEAS-2B. CAP can be a simple and effective method to delay multispecies biofilm formation inside the endotracheal prosthesis. Full article

(This article belongs to the Special Issue Coronaviruses: Past, Present, and Future)

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15 pages, 4455 KiB

Open AccessArticle

Development and Validation of a Highly Sensitive Multiplex Immunoassay for SARS-CoV-2 Humoral Response Monitorization: A Study of the Antibody Response in COVID-19 Patients with Different Clinical Profiles during the First and Second Waves in Cadiz, Spain

by Lucia Olvera-Collantes, Noelia Moares, Ricardo Fernandez-Cisnal, Juan P. Muñoz-Miranda, Pablo Gonzalez-Garcia, Antonio Gabucio, Carolina Freyre-Carrillo, Juan de Dios Jordan-Chaves, Teresa Trujillo-Soto, Maria P. Rodriguez-Martinez, Maria I. Martin-Rubio, Eva Escuer, Manuel Rodriguez-Iglesias, Cecilia Fernandez-Ponce and Francisco Garcia-Cozar

Microorganisms 2023, 11(12), 2997; https://doi.org/10.3390/microorganisms11122997 - 16 Dec 2023

Viewed by 1682

Abstract

There is still a long way ahead regarding the COVID-19 pandemic, since emerging waves remain a daunting challenge to the healthcare system. For this reason, the development of new preventive tools and therapeutic strategies to deal with the disease have been necessary, among [...] Read more.

There is still a long way ahead regarding the COVID-19 pandemic, since emerging waves remain a daunting challenge to the healthcare system. For this reason, the development of new preventive tools and therapeutic strategies to deal with the disease have been necessary, among which serological assays have played a key role in the control of COVID-19 outbreaks and vaccine development. Here, we have developed and evaluated an immunoassay capable of simultaneously detecting multiple IgG antibodies against different SARS-CoV-2 antigens through the use of Bio-Plex^TM technology. Additionally, we have analyzed the antibody response in COVID-19 patients with different clinical profiles in Cadiz, Spain. The multiplex immunoassay presented is a high-throughput and robust immune response monitoring tool capable of concurrently detecting anti-S1, anti-NC and anti-RBD IgG antibodies in serum with a very high sensitivity (94.34–97.96%) and specificity (91.84–100%). Therefore, the immunoassay proposed herein may be a useful monitoring tool for individual humoral immunity against SARS-CoV-2, as well as for epidemiological surveillance. In addition, we show the values of antibodies against multiple SARS-CoV-2 antigens and their correlation with the different clinical profiles of unvaccinated COVID-19 patients in Cadiz, Spain, during the first and second waves of the pandemic. Full article

(This article belongs to the Special Issue Coronaviruses: Past, Present, and Future)

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14 pages, 2761 KiB

Open AccessArticle

Natural Product Cordycepin (CD) Inhibition for NRP1/CD304 Expression and Possibly SARS-CoV-2 Susceptibility Prevention on Cancers

by Ting Li, Na Luo, Jiewen Fu, Jiaman Du, Zhiying Liu, Qi Tan, Meiling Zheng, Jiayue He, Jingliang Cheng, Dabing Li and Junjiang Fu

Microorganisms 2023, 11(12), 2953; https://doi.org/10.3390/microorganisms11122953 - 10 Dec 2023

Cited by 3 | Viewed by 1976

Abstract

NRP1/CD304 is a typical membrane-bound co-receptor for the vascular endothelial cell growth factor (VEGF), semaphorin family members, and viral SARS-CoV-2. Cordycepin (CD) is a natural product or active gradient from traditional Chinese medicine (TCM) from Cordyceps militaris Link and Ophiocordyceps sinensis (Berk.). [...] Read more.

NRP1/CD304 is a typical membrane-bound co-receptor for the vascular endothelial cell growth factor (VEGF), semaphorin family members, and viral SARS-CoV-2. Cordycepin (CD) is a natural product or active gradient from traditional Chinese medicine (TCM) from Cordyceps militaris Link and Ophiocordyceps sinensis (Berk.). However, NRP1 expression regulation via CD in cancers and the potential roles and mechanisms of SARS-CoV-2 infection are not clear. In this study, online databases were analyzed, Western blotting and quantitative RT-PCR were used for NRP1 expression change via CD, molecular docking was used for NRP/CD interaction, and a syncytial formation assay was used for CD inhibition using a pseudovirus SARS-CoV-2 entry. As a result, we revealed that CD inhibits NRP1 expressed in cancer cells and prevents viral syncytial formation in 293T-hACE2 cells, implying the therapeutic potential for both anti-cancer and anti-viruses, including anti-SARS-CoV-2. We further found significant associations between NRP1 expressions and the tumor–immune response in immune lymphocytes, chemokines, receptors, immunostimulators, immune inhibitors, and major histocompatibility complexes in most cancer types, implying NRP1’s roles in both anti-cancer and anti-SARS-CoV-2 entry likely via immunotherapy. Importantly, CD also downregulated the expression of NRP1 from lymphocytes in mice and downregulated the expression of A2AR from the lung cancer cell line H1975 when treated with CD, implying the NRP1 mechanism probably through immuno-response pathways. Thus, CD may be a therapeutic component for anti-cancer and anti-viral diseases, including COVID-19, by targeting NRP1 at least. Full article

(This article belongs to the Special Issue Coronaviruses: Past, Present, and Future)

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18 pages, 3681 KiB

Open AccessArticle

Introduction, Dispersal, and Predominance of SARS-CoV-2 Delta Variant in Rio Grande do Sul, Brazil: A Retrospective Analysis

by Thaís Regina y Castro, Bruna C. Piccoli, Andressa A. Vieira, Bruna C. Casarin, Luíza F. Tessele, Richard S. Salvato, Tatiana S. Gregianini, Leticia G. Martins, Paola Cristina Resende, Elisa C. Pereira, Filipe R. R. Moreira, Jaqueline G. de Jesus, Ana Paula Seerig, Marcos Antonio O. Lobato, Marli M. A. de Campos, Juliana S. Goularte, Mariana S. da Silva, Meriane Demoliner, Micheli Filippi, Vyctoria M. A. Góes Pereira, Alexandre V. Schwarzbold, Fernando R. Spilki and Priscila A. Trindade Show full author list Hide full author list

Microorganisms 2023, 11(12), 2938; https://doi.org/10.3390/microorganisms11122938 - 7 Dec 2023

Viewed by 1667

Abstract

Mutations in the SARS-CoV-2 genome can alter the virus’ fitness, leading to the emergence of variants of concern (VOC). In Brazil, the Gamma variant dominated the pandemic in the first half of 2021, and from June onwards, the first cases of Delta infection [...] Read more.

Mutations in the SARS-CoV-2 genome can alter the virus’ fitness, leading to the emergence of variants of concern (VOC). In Brazil, the Gamma variant dominated the pandemic in the first half of 2021, and from June onwards, the first cases of Delta infection were documented. Here, we investigate the introduction and dispersal of the Delta variant in the RS state by sequencing 1077 SARS-CoV-2-positive samples from June to October 2021. Of these samples, 34.7% were identified as Gamma and 65.3% as Delta. Notably, 99.2% of Delta sequences were clustered within the 21J lineage, forming a significant Brazilian clade. The estimated clock rate was 5.97 × 10⁻⁴ substitutions per site per year. The Delta variant was first reported on 17 June in the Vinhedos Basalto microregion and rapidly spread, accounting for over 70% of cases within nine weeks. Despite this, the number of cases and deaths remained stable, possibly due to vaccination, prior infections, and the continued mandatory mask use. In conclusion, our study provides insights into the Delta variant circulating in the RS state, highlighting the importance of genomic surveillance for monitoring viral evolution, even when the impact of new variants may be less severe in a given region. Full article

(This article belongs to the Special Issue Coronaviruses: Past, Present, and Future)

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11 pages, 12493 KiB

Open AccessArticle

T Cell Response in Tuberculosis-Infected Patients Vaccinated against COVID-19

by Luiz Henrique Agra Cavalcante-Silva, Ericka Garcia Leite, Fernanda Silva Almeida, Arthur Gomes de Andrade, Fernando Cézar Comberlang, Cintya Karina Rolim Lucena, Anna Stella Cysneiros Pachá, Bárbara Guimarães Csordas and Tatjana S. L. Keesen

Microorganisms 2023, 11(11), 2810; https://doi.org/10.3390/microorganisms11112810 - 19 Nov 2023

Cited by 1 | Viewed by 1793

Abstract

Many studies have focused on SARS-CoV-2 and Mycobacterium tuberculosis (Mtb) co-infection consequences. However, after a vaccination plan against COVID-19, the cases of severe disease and death are consistently controlled, although cases of asymptomatic and mild COVID-19 still happen together with tuberculosis [...] Read more.

Many studies have focused on SARS-CoV-2 and Mycobacterium tuberculosis (Mtb) co-infection consequences. However, after a vaccination plan against COVID-19, the cases of severe disease and death are consistently controlled, although cases of asymptomatic and mild COVID-19 still happen together with tuberculosis (TB) cases. Thus, in this context, we sought to compare the T cell response of COVID-19-non-vaccinated and -vaccinated patients with active tuberculosis exposed to SARS-CoV-2 antigens. Flow cytometry was used to analyze activation markers (i.e., CD69 and CD137) and cytokines (IFN-γ, TNFα, IL-17, and IL-10) levels in CD4⁺ and CD8⁺ T cells upon exposure to SARS-CoV-2 peptides. The data obtained showed that CD8⁺ T cells from non-vaccinated TB patients present a high frequency of CD69 and TNF-α after viral challenge compared to vaccinated TB donors. Conversely, CD4⁺ T cells from vaccinated TB patients show a high frequency of IL-10 after spike peptide stimulus compared to non-vaccinated patients. No differences were observed in the other parameters analyzed. The results suggest that this reduced immune balance in coinfected individuals may have consequences for pathogen control, necessitating further research to understand its impact on clinical outcomes after COVID-19 vaccination in those with concurrent SARS-CoV-2 and Mtb infections. Full article

(This article belongs to the Special Issue Coronaviruses: Past, Present, and Future)

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15 pages, 7071 KiB

Open AccessArticle

Anomaly Detection Models for SARS-CoV-2 Surveillance Based on Genome k-mers

by Haotian Ren, Yixue Li and Tao Huang

Microorganisms 2023, 11(11), 2773; https://doi.org/10.3390/microorganisms11112773 - 15 Nov 2023

Cited by 1 | Viewed by 1496

Abstract

Since COVID-19 has brought great challenges to global public health governance, developing methods that track the evolution of the virus over the course of an epidemic or pandemic is useful for public health. This paper uses anomaly detection models to analyze SARS-CoV-2 virus [...] Read more.

Since COVID-19 has brought great challenges to global public health governance, developing methods that track the evolution of the virus over the course of an epidemic or pandemic is useful for public health. This paper uses anomaly detection models to analyze SARS-CoV-2 virus genome k-mers to predict possible new critical variants in the collected samples. We used the sample data from Argentina, China and Portugal obtained from the Global Initiative on Sharing All Influenza Data (GISAID) to conduct multiple rounds of evaluation on several anomaly detection models, to verify the feasibility of this virus early warning and surveillance idea and find appropriate anomaly detection models for actual epidemic surveillance. Through multiple rounds of model testing, we found that the LUNAR (learnable unified neighborhood-based anomaly ranking) and LUNAR+LUNAR stacking model performed well in new critical variants detection. The results of simulated dynamic detection validate the feasibility of this approach, which can help efficiently monitor samples in local areas. Full article

(This article belongs to the Special Issue Coronaviruses: Past, Present, and Future)

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21 pages, 2569 KiB

Open AccessArticle

Characterization of SARS-CoV-2 Variants in Military and Civilian Personnel of an Air Force Airport during Three Pandemic Waves in Italy

by Michele Equestre, Cinzia Marcantonio, Nadia Marascio, Federica Centofanti, Antonio Martina, Matteo Simeoni, Elisabetta Suffredini, Giuseppina La Rosa, Giusy Bonanno Ferraro, Pamela Mancini, Carolina Veneri, Giovanni Matera, Angela Quirino, Angela Costantino, Stefania Taffon, Elena Tritarelli, Carmelo Campanella, Giulio Pisani, Roberto Nisini, Enea Spada, Paola Verde, Anna Rita Ciccaglione and Roberto Bruni Show full author list Hide full author list

Microorganisms 2023, 11(11), 2711; https://doi.org/10.3390/microorganisms11112711 - 5 Nov 2023

Cited by 2 | Viewed by 2014

Abstract

We investigated SARS-CoV-2 variants circulating, from November 2020 to March 2022, among military and civilian personnel at an Air Force airport in Italy in order to classify viral isolates in a potential hotspot for virus spread. Positive samples were subjected to Next-Generation Sequencing [...] Read more.

We investigated SARS-CoV-2 variants circulating, from November 2020 to March 2022, among military and civilian personnel at an Air Force airport in Italy in order to classify viral isolates in a potential hotspot for virus spread. Positive samples were subjected to Next-Generation Sequencing (NGS) of the whole viral genome and Sanger sequencing of the spike coding region. Phylogenetic analysis classified viral isolates and traced their evolutionary relationships. Clusters were identified using 70% cut-off. Sequencing methods yielded comparable results in terms of variant classification. In 2020 and 2021, we identified several variants, including B.1.258 (4/67), B.1.177 (9/67), Alpha (B.1.1.7, 9/67), Gamma (P.1.1, 4/67), and Delta (4/67). In 2022, only Omicron and its sub-lineage variants were observed (37/67). SARS-CoV-2 isolates were screened to detect naturally occurring resistance in genomic regions, the target of new therapies, comparing them to the Wuhan Hu-1 reference strain. Interestingly, 2/30 non-Omicron isolates carried the G15S 3CLpro substitution responsible for reduced susceptibility to protease inhibitors. On the other hand, Omicron isolates carried unusual substitutions A1803V, D1809N, and A949T on PLpro, and the D216N on 3CLpro. Finally, the P323L substitution on RdRp coding regions was not associated with the mutational pattern related to polymerase inhibitor resistance. This study highlights the importance of continuous genomic surveillance to monitor SARS-CoV-2 evolution in the general population, as well as in restricted communities. Full article

(This article belongs to the Special Issue Coronaviruses: Past, Present, and Future)

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16 pages, 1569 KiB

Open AccessArticle

Development of a Melting-Curve-Based Multiplex Real-Time PCR Assay for the Simultaneous Detection of Viruses Causing Respiratory Infection

by Eliandro Reis Tavares, Thiago Ferreira de Lima, Guilherme Bartolomeu-Gonçalves, Isabela Madeira de Castro, Daniel Gaiotto de Lima, Paulo Henrique Guilherme Borges, Gerson Nakazato, Renata Katsuko Takayama Kobayashi, Emerson José Venancio, César Ricardo Teixeira Tarley, Elaine Regina Delicato de Almeida, Marsileni Pelisson, Eliana Carolina Vespero, Andrea Name Colado Simão, Márcia Regina Eches Perugini, Gilselena Kerbauy, Marco Aurélio Fornazieri, Maria Cristina Bronharo Tognim, Viviane Monteiro Góes, Tatiana de Arruda Campos Brasil de Souza, Danielle Bruna Leal Oliveira, Edison Luiz Durigon, Lígia Carla Faccin-Galhardi, Lucy Megumi Yamauchi and Sueli Fumie Yamada-Ogatta Show full author list Hide full author list

Microorganisms 2023, 11(11), 2692; https://doi.org/10.3390/microorganisms11112692 - 2 Nov 2023

Cited by 4 | Viewed by 2933

Abstract

The prompt and accurate identification of the etiological agents of viral respiratory infections is a critical measure in mitigating outbreaks. In this study, we developed and clinically evaluated a novel melting-curve-based multiplex real-time PCR (M-m-qPCR) assay targeting the RNA-dependent RNA polymerase (RdRp) and [...] Read more.

The prompt and accurate identification of the etiological agents of viral respiratory infections is a critical measure in mitigating outbreaks. In this study, we developed and clinically evaluated a novel melting-curve-based multiplex real-time PCR (M-m-qPCR) assay targeting the RNA-dependent RNA polymerase (RdRp) and nucleocapsid phosphoprotein N of SARS-CoV-2, the Matrix protein 2 of the Influenza A virus, the RdRp domain of the L protein from the Human Respiratory Syncytial Virus, and the polyprotein from Rhinovirus B genes. The analytical performance of the M-m-qPCR underwent assessment using in silico analysis and a panel of reference and clinical strains, encompassing viral, bacterial, and fungal pathogens, exhibiting 100% specificity. Moreover, the assay showed a detection limit of 10 copies per reaction for all targeted pathogens using the positive controls. To validate its applicability, the assay was further tested in simulated nasal fluid spiked with the viruses mentioned above, followed by validation on nasopharyngeal swabs collected from 811 individuals. Among them, 13.4% (109/811) tested positive for SARS-CoV-2, and 1.1% (9/811) tested positive for Influenza A. Notably, these results showed 100% concordance with those obtained using a commercial kit. Therefore, the M-m-qPCR exhibits great potential for the routine screening of these respiratory viral pathogens. Full article

(This article belongs to the Special Issue Coronaviruses: Past, Present, and Future)

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15 pages, 2315 KiB

Open AccessArticle

Utilizing Protein–Peptide Hybrid Microarray for Time-Resolved Diagnosis and Prognosis of COVID-19

by Peiyan Zheng, Baolin Liao, Jiao Yang, Hu Cheng, Zhangkai J. Cheng, Huimin Huang, Wenting Luo, Yiyue Sun, Qiang Zhu, Yi Deng, Lan Yang, Yuxi Zhou, Wenya Wu, Shanhui Wu, Weiping Cai, Yueping Li, Xiaoneng Mo, Xinghua Tan, Linghua Li, Hongwei Ma and Baoqing Sun Show full author list Hide full author list

Microorganisms 2023, 11(10), 2436; https://doi.org/10.3390/microorganisms11102436 - 28 Sep 2023

Viewed by 1380

Abstract

The COVID-19 pandemic has highlighted the urgent need for accurate, rapid, and cost-effective diagnostic methods to identify and track the disease. Traditional diagnostic methods, such as PCR and serological assays, have limitations in terms of sensitivity, specificity, and timeliness. To investigate the potential [...] Read more.

The COVID-19 pandemic has highlighted the urgent need for accurate, rapid, and cost-effective diagnostic methods to identify and track the disease. Traditional diagnostic methods, such as PCR and serological assays, have limitations in terms of sensitivity, specificity, and timeliness. To investigate the potential of using protein–peptide hybrid microarray (PPHM) technology to track the dynamic changes of antibodies in the serum of COVID-19 patients and evaluate the prognosis of patients over time. A discovery cohort of 20 patients with COVID-19 was assembled, and PPHM technology was used to track the dynamic changes of antibodies in the serum of these patients. The results were analyzed to classify the patients into different disease severity groups, and to predict the disease progression and prognosis of the patients. PPHM technology was found to be highly effective in detecting the dynamic changes of antibodies in the serum of COVID-19 patients. Four polypeptide antibodies were found to be particularly useful for reflecting the actual status of the patient’s recovery process and for accurately predicting the disease progression and prognosis of the patients. The findings of this study emphasize the multi-dimensional space of peptides to analyze the high-volume signals in the serum samples of COVID-19 patients and monitor the prognosis of patients over time. PPHM technology has the potential to be a powerful tool for tracking the dynamic changes of antibodies in the serum of COVID-19 patients and for improving the diagnosis and prognosis of the disease. Full article

(This article belongs to the Special Issue Coronaviruses: Past, Present, and Future)

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18 pages, 846 KiB

Open AccessArticle

SARS-CoV-2 Rapid Antigen Test Based on a New Anti-Nucleocapsid Protein Monoclonal Antibody: Development and Real-Time Validation

by Fabiana Fioravante Coelho, Miriam Aparecida da Silva, Thiciany Blener Lopes, Juliana Moutinho Polatto, Natália Salazar de Castro, Luis Adan Flores Andrade, Karine Lima Lourenço, Hugo Itaru Sato, Alex Fiorini de Carvalho, Helena Perez Coelho, Flávia Fonseca Bagno, Daniela Luz, Vincent Louis Viala, Pedro Queiroz Cattony, Bruna de Sousa Melo, Ana Maria Moro, Wagner Quintilio, Ana Paula Barbosa, Camila Gasque Bomfim, Camila Pereira Soares, Cristiane Rodrigues Guzzo, Flavio Guimarães Fonseca, Edison Luiz Durigon, Ricardo Tostes Gazzinelli, Santuza M. Ribeiro Teixeira, Roxane Maria Fontes Piazza and Ana Paula Fernandes Show full author list Hide full author list

Microorganisms 2023, 11(10), 2422; https://doi.org/10.3390/microorganisms11102422 - 28 Sep 2023

Viewed by 1660

Abstract

SARS-CoV-2 diagnostic tests have become an important tool for pandemic control. Among the alternatives for COVID-19 diagnosis, antigen rapid diagnostic tests (Ag-RDT) are very convenient and widely used. However, as SARS-CoV-2 variants may continuously emerge, the replacement of tests and reagents may be [...] Read more.

SARS-CoV-2 diagnostic tests have become an important tool for pandemic control. Among the alternatives for COVID-19 diagnosis, antigen rapid diagnostic tests (Ag-RDT) are very convenient and widely used. However, as SARS-CoV-2 variants may continuously emerge, the replacement of tests and reagents may be required to maintain the sensitivity of Ag-RDTs. Here, we describe the development and validation of an Ag-RDT during an outbreak of the Omicron variant, including the characterization of a new monoclonal antibody (anti-DTC-N 1B3 mAb) that recognizes the Nucleocapsid protein (N). The anti-DTC-N 1B3 mAb recognized the sequence TFPPTEPKKDKKK located at the C-terminus of the N protein of main SARS-CoV-2 variants of concern. Accordingly, the Ag-RDT prototypes using the anti-DTC-N 1B3 mAB detected all the SARS-CoV-2 variants—Wuhan, Alpha, Gamma, Delta, P2 and Omicron. The performance of the best prototype (sensitivity of 95.2% for samples with Ct ≤ 25; specificity of 98.3% and overall accuracy of 85.0%) met the WHO recommendations. Moreover, results from a patients’ follow-up study indicated that, if performed within the first three days after onset of symptoms, the Ag-RDT displayed 100% sensitivity. Thus, the new mAb and the Ag-RDT developed herein may constitute alternative tools for COVID-19 point-of-care diagnosis and epidemiological surveillance. Full article

(This article belongs to the Special Issue Coronaviruses: Past, Present, and Future)

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15 pages, 2614 KiB

Open AccessArticle

Humoral Immune Responses in Patients with Severe COVID-19: A Comparative Pilot Study between Individuals Infected by SARS-CoV-2 during the Wild-Type and the Delta Periods

by Maria Sukhova, Maria Byazrova, Artem Mikhailov, Gaukhar Yusubalieva, Irina Maslova, Tatyana Belovezhets, Nikolay Chikaev, Ivan Vorobiev, Vladimir Baklaushev and Alexander Filatov

Microorganisms 2023, 11(9), 2347; https://doi.org/10.3390/microorganisms11092347 - 20 Sep 2023

Viewed by 1565

Abstract

Since the onset of the COVID-19 pandemic, humanity has experienced the spread and circulation of several SARS-CoV-2 variants that differed in transmissibility, contagiousness, and the ability to escape from vaccine-induced neutralizing antibodies. However, issues related to the differences in the variant-specific immune responses [...] Read more.

Since the onset of the COVID-19 pandemic, humanity has experienced the spread and circulation of several SARS-CoV-2 variants that differed in transmissibility, contagiousness, and the ability to escape from vaccine-induced neutralizing antibodies. However, issues related to the differences in the variant-specific immune responses remain insufficiently studied. The aim of this study was to compare the parameters of the humoral immune responses in two groups of patients with acute COVID-19 who were infected during the circulation period of the D614G and the Delta variants of SARS-CoV-2. Sera from 48 patients with acute COVID-19 were tested for SARS-CoV-2 binding and neutralizing antibodies using six assays. We found that serum samples from the D614G period demonstrated 3.9- and 1.6-fold increases in RBD- and spike-specific IgG binding with wild-type antigens compared with Delta variant antigens (p < 0.01). Cluster analysis showed the existence of two well-separated clusters. The first cluster mainly consisted of D614G-period patients and the second cluster predominantly included patients from the Delta period. The results thus obtained indicate that humoral immune responses in D614G- and Delta-specific infections can be characterized by variant-specific signatures. This can be taken into account when developing new variant-specific vaccines. Full article

(This article belongs to the Special Issue Coronaviruses: Past, Present, and Future)

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8 pages, 241 KiB

Open AccessCommunication

Diagnosis and Outcomes of Fungal Co-Infections in COVID-19 Infections: A Retrospective Study

by Richard Swaney, Rutendo Jokomo-Nyakabau, Anny A. N. Nguyen, Dorothy Kenny, Paul G. Millner, Mohammad Selim, Christopher J. Destache and Manasa Velagapudi

Microorganisms 2023, 11(9), 2326; https://doi.org/10.3390/microorganisms11092326 - 15 Sep 2023

Cited by 1 | Viewed by 1231

Abstract

The SARS-CoV-2 pandemic has resulted in a public health emergency with unique complications such as the development of fungal co-infections. The diagnosis of fungal infections can be challenging due to confounding imaging studies and difficulty obtaining histopathology. In this retrospective study, 173 patients [...] Read more.

The SARS-CoV-2 pandemic has resulted in a public health emergency with unique complications such as the development of fungal co-infections. The diagnosis of fungal infections can be challenging due to confounding imaging studies and difficulty obtaining histopathology. In this retrospective study, 173 patients with COVID-19 receiving antifungal therapy due to concern for fungal co-infection were evaluated. Patient characteristics, clinical outcomes, and the utility of fungal biomarkers were then evaluated for continuation of antifungal therapy. Data were collected from the electronic health record (EPIC) and analyzed using SPSS (version. 28, IBM, Inc., Armonk, NY, USA) Data are presented as mean ± SD or percentages. A total of 56 COVID-19 patients were diagnosed with fungal co-infection and 117 COVID-19 + patients had no fungal infection. Significantly fewer female patients were in the fungal+ group compared to COVID-19 control patients (29% in fungal+ compared to 51% in controls p = 0.005). Fungal diagnostics were all significantly higher in fungal+ patients. These include 1,4-beta-D-glucan (BDG), fungal culture, and bronchoalveolar lavage galactomannan (BAL GM). Intensive care unit hospitalization, mechanical ventilation, and mortality in fungal+ patients with COVID-19 were significantly higher than in control patients. Finally, significantly more fungal+ patients received voriconazole, isavuconazonium, or amphotericin B therapies, whereas control patients received significantly more short-course fluconazole. COVID-19+ patients with fungal co-infection were significantly more likely to be in the ICU and mechanically ventilated, and they result in higher mortality compared to control COVID-19 patients. The use of fungal diagnostics markers were helpful for diagnosis. Full article

(This article belongs to the Special Issue Coronaviruses: Past, Present, and Future)

11 pages, 291 KiB

Open AccessArticle

Analyzing the Interplay between COVID-19 Viral Load, Inflammatory Markers, and Lymphocyte Subpopulations on the Development of Long COVID

by Andrea Rivera-Cavazos, José Antonio Luviano-García, Arnulfo Garza-Silva, Devany Paola Morales-Rodríguez, Mauricio Kuri-Ayache, Miguel Ángel Sanz-Sánchez, Juan Enrique Santos-Macías, Maria Elena Romero-Ibarguengoitia and Arnulfo González-Cantú

Microorganisms 2023, 11(9), 2241; https://doi.org/10.3390/microorganisms11092241 - 6 Sep 2023

Cited by 1 | Viewed by 1995

Abstract

The global impact of the SARS-CoV-2 infection has been substantial, affecting millions of people. Long COVID, characterized by persistent or recurrent symptoms after acute infection, has been reported in over 40% of patients. Risk factors include age and female gender, and various mechanisms, [...] Read more.

The global impact of the SARS-CoV-2 infection has been substantial, affecting millions of people. Long COVID, characterized by persistent or recurrent symptoms after acute infection, has been reported in over 40% of patients. Risk factors include age and female gender, and various mechanisms, including chronic inflammation and viral persistence, have been implicated in long COVID’s pathogenesis. However, there are scarce studies in which multiple inflammatory markers and viral load are analyzed simultaneously in acute infection to determine how they predict for long COVID at long-term follow-up. This study explores the association between long COVID and inflammatory markers, viral load, and lymphocyte subpopulation during acute infection in hospitalized patients to better understand the risk factors of this disease. This longitudinal retrospective study was conducted in patients hospitalized with COVID-19 in northern Mexico. Inflammatory parameters, viral load, and lymphocyte subpopulation during the acute infection phase were analyzed, and long COVID symptoms were followed up depending on severity and persistence (weekly or monthly) and assessed 1.5 years after the acute infection. This study analyzed 79 patients, among them, 41.8% presented long COVID symptoms, with fatigue being the most common (45.5%). Patients with long COVID had higher lymphocyte levels during hospitalization, and NK cell subpopulation levels were also associated with long COVID. ICU admission during acute COVID-19 was also linked to the development of long COVID symptoms. Full article

(This article belongs to the Special Issue Coronaviruses: Past, Present, and Future)

19 pages, 6026 KiB

Open AccessArticle

Type I Interferon Pathway-Related Hub Genes as a Potential Therapeutic Target for SARS-CoV-2 Omicron Variant-Induced Symptoms

by Zhiwei Lin, Mingshan Xue, Ziman Wu, Ze Liu, Qianyue Yang, Jiaqing Hu, Jiacong Peng, Lin Yu and Baoqing Sun

Microorganisms 2023, 11(8), 2101; https://doi.org/10.3390/microorganisms11082101 - 17 Aug 2023

Viewed by 1849

Abstract

Background: The global pandemic of COVID-19 is caused by the rapidly evolving severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The clinical presentation of SARS-CoV-2 Omicron variant infection varies from asymptomatic to severe disease with diverse symptoms. However, the underlying mechanisms responsible for these [...] Read more.

Background: The global pandemic of COVID-19 is caused by the rapidly evolving severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The clinical presentation of SARS-CoV-2 Omicron variant infection varies from asymptomatic to severe disease with diverse symptoms. However, the underlying mechanisms responsible for these symptoms remain incompletely understood. Methods: Transcriptome datasets from peripheral blood mononuclear cells (PBMCs) of COVID-19 patients infected with the Omicron variant and healthy volunteers were obtained from public databases. A comprehensive bioinformatics analysis was performed to identify hub genes associated with the Omicron variant. Hub genes were validated using quantitative RT-qPCR and clinical data. DSigDB database predicted potential therapeutic agents. Results: Seven hub genes (IFI44, IFI44L, MX1, OAS3, USP18, IFI27, and ISG15) were potential biomarkers for Omicron infection’s symptomatic diagnosis and treatment. Type I interferon-related hub genes regulated Omicron-induced symptoms, which is supported by independent datasets and RT-qPCR validation. Immune cell analysis showed elevated monocytes and reduced lymphocytes in COVID-19 patients, which is consistent with retrospective clinical data. Additionally, ten potential therapeutic agents were screened for COVID-19 treatment, targeting the hub genes. Conclusions: This study provides insights into the mechanisms underlying type I interferon-related pathways in the development and recovery of COVID-19 symptoms during Omicron infection. Seven hub genes were identified as promising biological biomarkers for diagnosing and treating Omicron infection. The identified biomarkers and potential therapeutic agent offer valuable implications for Omicron’s clinical manifestations and treatment strategies. Full article

(This article belongs to the Special Issue Coronaviruses: Past, Present, and Future)

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11 pages, 288 KiB

Open AccessArticle

Early Fluvoxamine Reduces the Risk for Clinical Deterioration in Symptomatic Outpatients with COVID-19: A Real-World, Retrospective, before–after Analysis

by Aristotelis Tsiakalos, Panayiotis D. Ziakas, Eleni Polyzou, Georgios Schinas and Karolina Akinosoglou

Microorganisms 2023, 11(8), 2073; https://doi.org/10.3390/microorganisms11082073 - 12 Aug 2023

Cited by 5 | Viewed by 2070

Abstract

Fluvoxamine, a selective serotonin reuptake inhibitor with anti-inflammatory properties, has gained attention as a repurposed drug to treat COVID-19. We aimed to explore the potential benefit of fluvoxamine on outpatients with early SARS-CoV-2 infection. We performed a retrospective study of fluvoxamine adult outpatients [...] Read more.

Fluvoxamine, a selective serotonin reuptake inhibitor with anti-inflammatory properties, has gained attention as a repurposed drug to treat COVID-19. We aimed to explore the potential benefit of fluvoxamine on outpatients with early SARS-CoV-2 infection. We performed a retrospective study of fluvoxamine adult outpatients with symptomatic COVID-19 disease of early onset (<5 days), in the context of an infectious diseases private practice, between September–December 2021, in Greece. Patients with disease duration ≥5 days, dyspnea and/or hypoxemia with oxygen saturation <94% in room air and pregnancy were excluded from the analysis. In total, 103 patients, 54 males/49 females with a median age of 47 years (39–56), were included in this study. Patient characteristics were balanced before and after the introduction of fluvoxamine. Two patients in the fluvoxamine arm (3.8%; 95% CI 0.4–13) had clinical deterioration compared to 8 patients in the standard of care group (16%; 95% CI 7.2–29.1, p < 0.04). After controlling for age, sex, body mass index > 30 and vaccination status, fluvoxamine was independently associated with a lower risk of clinical deterioration (adj. OR 0.12; 95% CI 0.02–0.70, p < 0.02). Adding on fluvoxamine to treatment for early symptomatic COVID-19 patients may protect them from clinical deterioration and hospitalization, and it is an appealing low-cost, low-toxicity option in the community setting and warrants further investigation. Full article

(This article belongs to the Special Issue Coronaviruses: Past, Present, and Future)

18 pages, 2135 KiB

Open AccessArticle

Exploring the Synergistic Potential of Radiomics and Laboratory Biomarkers for Enhanced Identification of Vulnerable COVID-19 Patients

by Catharina Gerhards, Verena Haselmann, Samuel F. Schaible, Volker Ast, Maximilian Kittel, Manfred Thiel, Alexander Hertel, Stefan O. Schoenberg, Michael Neumaier and Matthias F. Froelich

Microorganisms 2023, 11(7), 1740; https://doi.org/10.3390/microorganisms11071740 - 3 Jul 2023

Viewed by 1433

Abstract

Background: Severe courses and high hospitalization rates were ubiquitous during the first pandemic SARS-CoV-2 waves. Thus, we aimed to examine whether integrative diagnostics may aid in identifying vulnerable patients using crucial data and materials obtained from COVID-19 patients hospitalized between 2020 and 2021 [...] Read more.

Background: Severe courses and high hospitalization rates were ubiquitous during the first pandemic SARS-CoV-2 waves. Thus, we aimed to examine whether integrative diagnostics may aid in identifying vulnerable patients using crucial data and materials obtained from COVID-19 patients hospitalized between 2020 and 2021 (n = 52). Accordingly, we investigated the potential of laboratory biomarkers, specifically the dynamic cell decay marker cell-free DNA and radiomics features extracted from chest CT. Methods: Separate forward and backward feature selection was conducted for linear regression with the Intensive-Care-Unit (ICU) period as the initial target. Three-fold cross-validation was performed, and collinear parameters were reduced. The model was adapted to a logistic regression approach and verified in a validation naïve subset to avoid overfitting. Results: The adapted integrated model classifying patients into “ICU/no ICU demand” comprises six radiomics and seven laboratory biomarkers. The models’ accuracy was 0.54 for radiomics, 0.47 for cfDNA, 0.74 for routine laboratory, and 0.87 for the combined model with an AUC of 0.91. Conclusion: The combined model performed superior to the individual models. Thus, integrating radiomics and laboratory data shows synergistic potential to aid clinic decision-making in COVID-19 patients. Under the need for evaluation in larger cohorts, including patients with other SARS-CoV-2 variants, the identified parameters might contribute to the triage of COVID-19 patients. Full article

(This article belongs to the Special Issue Coronaviruses: Past, Present, and Future)

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13 pages, 826 KiB

Open AccessArticle

Assessing Continuity of Adherence to Precautionary Measures for COVID-19 among Vaccinated People in Jazan, Saudi Arabia

by Anwar Alameer, Yahya Maslamani, Ibrahim M. Gosadi, Mohammed Y. Elamin, Mohammed A. Muaddi, Ahmad Y. Alqassim, Abrar Doweri, Ibrahim Namis, Fatimah Busayli, Hussam Ahmadini, Yehya Hejri and Abdu Dahlan

Microorganisms 2023, 11(3), 800; https://doi.org/10.3390/microorganisms11030800 - 21 Mar 2023

Cited by 6 | Viewed by 1945

Abstract

Background: Adherence to behavioral respiratory hygiene practices is essential in preventing the transmission of COVID-19, especially given the appearance of new variants of the COVID-19 virus. This study estimated the pre- and post-vaccination levels of adherence to COVID-19 preventive behavioral measures among vaccinated [...] Read more.

Background: Adherence to behavioral respiratory hygiene practices is essential in preventing the transmission of COVID-19, especially given the appearance of new variants of the COVID-19 virus. This study estimated the pre- and post-vaccination levels of adherence to COVID-19 preventive behavioral measures among vaccinated people. Methods: This cross-sectional study assessed the sociodemographics and preventive behavioral measures, and pre- and post-vaccination data, via a questionnaire. Paired t-tests and Chi-squared tests were used to assess the variation in adherence levels. Results: Of the 480 participants, 57.9% were male, and 30.4% were aged between 30 and 39 years of age. After vaccination, there was a statistically significant decline in adherence to all the assessed behavioral protective measures (p < 0.05). Being 50 years old or older, female, a healthcare worker, and a smoker were associated with higher adherence levels compared with other groups in the same categories. Conclusions: A change in the behavior of the community members regarding COVID-19 after receiving the vaccination and a reduction in adherence to respiratory hygiene practices was observed. This indicates the importance of raising awareness about the possibility of reinfection with COVID-19 despite the vaccination, and the importance of behavioral respiratory hygiene for the prevention and control of COVID-19. Full article

(This article belongs to the Special Issue Coronaviruses: Past, Present, and Future)

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Review

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15 pages, 7699 KiB

Open AccessReview

Back to the Future: Immune Protection or Enhancement of Future Coronaviruses

by Merit Bartels, Eric Sala Solé, Lotte M. Sauerschnig and Ger T. Rijkers

Microorganisms 2024, 12(3), 617; https://doi.org/10.3390/microorganisms12030617 - 19 Mar 2024

Viewed by 2236

Abstract

Before the emergence of SARS-CoV-1, MERS-CoV, and most recently, SARS-CoV-2, four other coronaviruses (the alpha coronaviruses NL63 and 229E and the beta coronaviruses OC43 and HKU1) had already been circulating in the human population. These circulating coronaviruses all cause mild respiratory illness during [...] Read more.

Before the emergence of SARS-CoV-1, MERS-CoV, and most recently, SARS-CoV-2, four other coronaviruses (the alpha coronaviruses NL63 and 229E and the beta coronaviruses OC43 and HKU1) had already been circulating in the human population. These circulating coronaviruses all cause mild respiratory illness during the winter seasons, and most people are already infected in early life. Could antibodies and/or T cells, especially against the beta coronaviruses, have offered some form of protection against (severe) COVID-19 caused by infection with SARS-CoV-2? Related is the question of whether survivors of SARS-CoV-1 or MERS-CoV would be relatively protected against SARS-CoV-2. More importantly, would humoral and cellular immunological memory generated during the SARS-CoV-2 pandemic, either by infection or vaccination, offer protection against future coronaviruses? Or rather than protection, could antibody-dependent enhancement have taken place, a mechanism by which circulating corona antibodies enhance the severity of COVID-19? Another related phenomenon, the original antigenic sin, would also predict that the effectiveness of the immune response to future coronaviruses would be impaired because of the reactivation of memory against irrelevant epitopes. The currently available evidence indicates that latter scenarios are highly unlikely and that especially cytotoxic memory T cells directed against conserved epitopes of human coronaviruses could at least offer partial protection against future coronaviruses. Full article

(This article belongs to the Special Issue Coronaviruses: Past, Present, and Future)

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17 pages, 1305 KiB

Open AccessReview

The Renin–Angiotensin System (RAS) in COVID-19 Disease: Where We Are 3 Years after the Beginning of the Pandemic

by Marco Prato, Natalia Tiberti, Cristina Mazzi, Federico Gobbi, Chiara Piubelli and Silvia Stefania Longoni

Microorganisms 2024, 12(3), 583; https://doi.org/10.3390/microorganisms12030583 - 14 Mar 2024

Viewed by 1576

Abstract

The RAS is a hormonal system playing a pivotal role in the control of blood pressure and electrolyte homeostasis, the alteration of which is associated with different pathologies, including acute respiratory distress syndrome (ARDS). As such, it is not surprising that a number [...] Read more.

The RAS is a hormonal system playing a pivotal role in the control of blood pressure and electrolyte homeostasis, the alteration of which is associated with different pathologies, including acute respiratory distress syndrome (ARDS). As such, it is not surprising that a number of studies have attempted to elucidate the role and balance of the renin–angiotensin system (RAS) in COVID-19. In this review article, we will describe the evidence collected regarding the two main enzymes of the RAS (i.e., ACE and ACE2) and their principal molecular products (i.e., AngII and Ang1-7) in SARS-CoV-2 infection, with the overarching goal of drawing conclusions on their possible role as clinical markers in association with disease severity, progression, and outcome. Moreover, we will bring into the picture new experimental data regarding the systemic activity of ACE and ACE2 as well as the concentration of AngII and Ang1-7 in a cohort of 47 COVID-19 patients hospitalized at the IRCCS Sacro Cuore-Don Calabria Hospital (Negrar, Italy) between March and April 2020. Finally, we will discuss the possibility of considering this systemic pathway as a clinical marker for COVID-19. Full article

(This article belongs to the Special Issue Coronaviruses: Past, Present, and Future)

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20 pages, 1389 KiB

Open AccessReview

Indirect Effects of the COVID-19 Pandemic on Routine Childhood Vaccination in Low-Income Countries: A Systematic Review to Set the Scope for Future Pandemics

by Jessica E. Beetch, Amanda Janitz, Laura A. Beebe, Mary Gowin, Chao Xu, Shari Clifton and Katrin Gaardbo Kuhn

Microorganisms 2024, 12(3), 573; https://doi.org/10.3390/microorganisms12030573 - 13 Mar 2024

Viewed by 1418

Abstract

The COVID-19 pandemic halted progress in global vaccine coverage and disrupted routine childhood vaccination practices worldwide. While there is ample evidence of the vaccination decline experienced during the pandemic, it is less clear how low-income countries were affected. We executed a systematic review [...] Read more.

The COVID-19 pandemic halted progress in global vaccine coverage and disrupted routine childhood vaccination practices worldwide. While there is ample evidence of the vaccination decline experienced during the pandemic, it is less clear how low-income countries were affected. We executed a systematic review to synthesize the current literature on the impacts of routine childhood vaccinations in low-income countries from 1 January 2020 to 8 February 2023. We collected data using an extraction form on Covidence and assessed the quality of studies included in the review using the Risk of Bias in Non-Randomized Studies of Interventions (ROBINS-I) tool. Effect estimates for changes in vaccination during the pandemic were reported and summarized. Factors that influenced changes were grouped into descriptive themes. Thirteen studies, encompassing 18 low-income countries and evaluating 15 vaccines at varying doses, were included in the final review. We found that routine childhood vaccinations during the COVID-19 pandemic varied considerably by vaccine type, location, and phase of the pandemic. Nine different themes were identified as factors that influenced changes in vaccination. Documenting past experiences and lessons learned is crucial for informing preparedness efforts in anticipation of future public health emergencies. Failure to effectively address these things in the next public health emergency could result in a recurrence of declining routine childhood vaccinations. Full article

(This article belongs to the Special Issue Coronaviruses: Past, Present, and Future)

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21 pages, 1901 KiB

Open AccessReview

SARS-CoV-2 and Other Respiratory Viruses in Human Olfactory Pathophysiology

by Serigne Fallou Wade, Abou Abdallah Malick Diouara, Babacar Ngom, Fatou Thiam and Ndongo Dia

Microorganisms 2024, 12(3), 540; https://doi.org/10.3390/microorganisms12030540 - 7 Mar 2024

Cited by 1 | Viewed by 1759

Abstract

Acute respiratory viruses (ARVs) are the leading cause of diseases in humans worldwide. High-risk individuals, including children and the elderly, could potentially develop severe illnesses that could result in hospitalization or death in the worst case. The most common ARVs are the Human [...] Read more.

Acute respiratory viruses (ARVs) are the leading cause of diseases in humans worldwide. High-risk individuals, including children and the elderly, could potentially develop severe illnesses that could result in hospitalization or death in the worst case. The most common ARVs are the Human respiratory syncytial virus, Human Metapneumovirus, Human Parainfluenza Virus, rhinovirus, coronaviruses (including SARS and MERS CoV), adenoviruses, Human Bocavirus, enterovirus (-D68 and 71), and influenza viruses. The olfactory deficits due to ARV infection are a common symptom among patients. This review provides an overview of the role of SARS-CoV-2 and other common ARVs in the development of human olfactory pathophysiology. We highlight the critical need to understand the signaling underlying the olfactory dysfunction and the development of therapeutics for this wide-ranging category of AVRs to restore the altered or loss of smell in affected patients. Full article

(This article belongs to the Special Issue Coronaviruses: Past, Present, and Future)

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19 pages, 851 KiB

Open AccessReview

A Dual Pharmacological Strategy against COVID-19: The Therapeutic Potential of Metformin and Atorvastatin

by Luis Adrián De Jesús-González, Rosa María del Ángel, Selvin Noé Palacios-Rápalo, Carlos Daniel Cordero-Rivera, Adrián Rodríguez-Carlos, Juan Valentin Trujillo-Paez, Carlos Noe Farfan-Morales, Juan Fidel Osuna-Ramos, José Manuel Reyes-Ruiz, Bruno Rivas-Santiago, Moisés León-Juárez, Ana Cristina García-Herrera, Adriana Clara Ramos-Cortes, Erika Alejandra López-Gándara and Estefanía Martínez-Rodríguez

Microorganisms 2024, 12(2), 383; https://doi.org/10.3390/microorganisms12020383 - 13 Feb 2024

Cited by 3 | Viewed by 3163

Abstract

Metformin (MET) and atorvastatin (ATO) are promising treatments for COVID-19. This review explores the potential of MET and ATO, commonly prescribed for diabetes and dyslipidemia, respectively, as versatile medicines against SARS-CoV-2. Due to their immunomodulatory and antiviral capabilities, as well as their cost-effectiveness [...] Read more.

Metformin (MET) and atorvastatin (ATO) are promising treatments for COVID-19. This review explores the potential of MET and ATO, commonly prescribed for diabetes and dyslipidemia, respectively, as versatile medicines against SARS-CoV-2. Due to their immunomodulatory and antiviral capabilities, as well as their cost-effectiveness and ubiquitous availability, they are highly suitable options for treating the virus. MET’s effect extends beyond managing blood sugar, impacting pathways that can potentially decrease the severity and fatality rates linked with COVID-19. It can partially block mitochondrial complex I and stimulate AMPK, which indicates that it can be used more widely in managing viral infections. ATO, however, impacts cholesterol metabolism, a crucial element of the viral replicative cycle, and demonstrates anti-inflammatory characteristics that could modulate intense immune reactions in individuals with COVID-19. Retrospective investigations and clinical trials show decreased hospitalizations, severity, and mortality rates in patients receiving these medications. Nevertheless, the journey from observing something to applying it in a therapeutic setting is intricate, and the inherent diversity of the data necessitates carefully executed, forward-looking clinical trials. This review highlights the requirement for efficacious, easily obtainable, and secure COVID-19 therapeutics and identifies MET and ATO as promising treatments in this worldwide health emergency. Full article

(This article belongs to the Special Issue Coronaviruses: Past, Present, and Future)

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25 pages, 2199 KiB

Open AccessReview

Potential Beneficial Effects of Naringin and Naringenin on Long COVID—A Review of the Literature

by Siqi Liu, Mengli Zhong, Hao Wu, Weiwei Su, Yonggang Wang and Peibo Li

Microorganisms 2024, 12(2), 332; https://doi.org/10.3390/microorganisms12020332 - 4 Feb 2024

Cited by 1 | Viewed by 5088

Abstract

Coronavirus disease 2019 (COVID-19) caused a severe epidemic due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Recent studies have found that patients do not completely recover from acute infections, but instead, suffer from a variety of post-acute sequelae of SARS-CoV-2 infection, known as [...] Read more.

Coronavirus disease 2019 (COVID-19) caused a severe epidemic due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Recent studies have found that patients do not completely recover from acute infections, but instead, suffer from a variety of post-acute sequelae of SARS-CoV-2 infection, known as long COVID. The effects of long COVID can be far-reaching, with a duration of up to six months and a range of symptoms such as cognitive dysfunction, immune dysregulation, microbiota dysbiosis, myalgic encephalomyelitis/chronic fatigue syndrome, myocarditis, pulmonary fibrosis, cough, diabetes, pain, reproductive dysfunction, and thrombus formation. However, recent studies have shown that naringenin and naringin have palliative effects on various COVID-19 sequelae. Flavonoids such as naringin and naringenin, commonly found in fruits and vegetables, have various positive effects, including reducing inflammation, preventing viral infections, and providing antioxidants. This article discusses the molecular mechanisms and clinical effects of naringin and naringenin on treating the above diseases. It proposes them as potential drugs for the treatment of long COVID, and it can be inferred that naringin and naringenin exhibit potential as extended long COVID medications, in the future likely serving as nutraceuticals or clinical supplements for the comprehensive alleviation of the various manifestations of COVID-19 complications. Full article

(This article belongs to the Special Issue Coronaviruses: Past, Present, and Future)

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16 pages, 293 KiB

Open AccessReview

Vaccinating against a Novel Pathogen: A Critical Review of COVID-19 Vaccine Effectiveness Evidence

by Bernard Black and David B. Thaw

Microorganisms 2024, 12(1), 89; https://doi.org/10.3390/microorganisms12010089 - 31 Dec 2023

Cited by 2 | Viewed by 2167

Abstract

We study the experience with COVID-19 vaccination of an initially naïve population, which can inform planning for vaccination against the next novel, highly transmissible pathogen. We focus on the first two pandemic years (wild strain through Delta), because after the Omicron wave in [...] Read more.

We study the experience with COVID-19 vaccination of an initially naïve population, which can inform planning for vaccination against the next novel, highly transmissible pathogen. We focus on the first two pandemic years (wild strain through Delta), because after the Omicron wave in early 2022, very few people were still SARS-CoV-2-naïve. Almost all were vaccinated, infected, or often both. We review the evidence on COVID-19 vaccine effectiveness (VE) and waning effectiveness over time and the relative effectiveness of the four principal vaccines used in developed Western countries: BNT162b2 (Pfizer-BioNTech), mRNA1273 (Moderna), Ad26.CoV2.S (Johnson&Johnson), and ChAdOx1-S (AstraZeneca). As a basis for our analysis, we conducted a PRISMA-compliant review of all studies on PubMed through 15 August 2022, reporting VE against four endpoints for these four vaccines: any infection, symptomatic infection, hospitalization, and death. The mRNA vaccines (BNT162b2, mRNA1273) had high initial VE against all endpoints but protection waned after approximately six months, with BNT162b2 declining faster than mRNA1273. Both mRNA vaccines outperformed the viral vector vaccines (Ad26.CoV2.S and ChAdOx1-S). A third “booster” dose, roughly six months after the initial doses, substantially reduced symptomatic infection, hospitalization, and death. In hindsight, a third dose should be seen as part of the normal vaccination schedule. Our analysis highlights the importance of the real-time population-level surveillance needed to assess evidence for waning, and the need for rapid regulatory response to this evidence. Full article

(This article belongs to the Special Issue Coronaviruses: Past, Present, and Future)

18 pages, 1146 KiB

Open AccessReview

Long COVID or Post-COVID-19 Condition: Past, Present and Future Research Directions

by César Fernández-de-las-Peñas, Arkiath Veettil Raveendran, Rocco Giordano and Lars Arendt-Nielsen

Microorganisms 2023, 11(12), 2959; https://doi.org/10.3390/microorganisms11122959 - 11 Dec 2023

Cited by 19 | Viewed by 3402

Abstract

The presence of symptoms after an acute SARS-CoV-2 infection (long-COVID) has become a worldwide healthcare emergency but remains underestimated and undertreated due to a lack of recognition of the condition and knowledge of the underlying mechanisms. In fact, the prevalence of post-COVID symptoms [...] Read more.

The presence of symptoms after an acute SARS-CoV-2 infection (long-COVID) has become a worldwide healthcare emergency but remains underestimated and undertreated due to a lack of recognition of the condition and knowledge of the underlying mechanisms. In fact, the prevalence of post-COVID symptoms ranges from 50% during the first months after the infection up to 20% two-years after. This perspective review aimed to map the existing literature on post-COVID symptoms and to identify gaps in the literature to guide the global effort toward an improved understanding of long-COVID and suggest future research directions. There is a plethora of symptomatology that can be due to COVID-19; however, today, there is no clear classification and definition of this condition, termed long-COVID or post-COVID-19 condition. The heterogeneity in the symptomatology has led to the presence of groups/clusters of patients, which could exhibit different risk factors and different mechanisms. Viral persistence, long-lasting inflammation, immune dysregulation, autoimmune reactions, reactivation of latent infections, endothelial dysfunction and alteration in gut microbiota have been proposed as potential mechanisms explaining the complexity of long-COVID. In such an equation, viral biology (e.g., re-infections, SARS-CoV-2 variants), host biology (e.g., genetics, epigenetics) and external factors (e.g., vaccination) should be also considered. These various factors will be discussed in the current perspective review and future directions suggested. Full article

(This article belongs to the Special Issue Coronaviruses: Past, Present, and Future)

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Other

Jump to: Research, Review

11 pages, 1141 KiB

Open AccessBrief Report

Increased Expression of lncRNA AC000120.7 and SENP3-EIF4A1 in Patients with Acute Respiratory Distress Syndrome Induced by SARS-CoV-2 Infection: A Pilot Study

by Javier González-Ramírez, Ana Gabriela Leija-Montoya, Nicolás Serafín-Higuera, Carlos A. Guzmán-Martín, Luis M. Amezcua-Guerra, Carlos Olvera-Sandoval, Jesús René Machado-Contreras, Armando Ruiz-Hernández, Adrián Hernández-Díazcouder, Julia Dolores Estrada-Guzmán and Fausto Sánchez-Muñoz

Microorganisms 2023, 11(9), 2342; https://doi.org/10.3390/microorganisms11092342 - 19 Sep 2023

Cited by 2 | Viewed by 1470

Abstract

COVID-19, a disease caused by the SARS-CoV-2 virus, poses significant threats to the respiratory system and other vital organs. Long non-coding RNAs have emerged as influential epigenetic regulators and promising biomarkers in respiratory ailments. The objective of this study was to identify candidate [...] Read more.

COVID-19, a disease caused by the SARS-CoV-2 virus, poses significant threats to the respiratory system and other vital organs. Long non-coding RNAs have emerged as influential epigenetic regulators and promising biomarkers in respiratory ailments. The objective of this study was to identify candidate lncRNAs in SARS-CoV-2-positive individuals compared to SARS-CoV-2-negative individuals and investigate their potential association with ARDS-CoV-2 (acute respiratory distress syndrome). Employing qRT-PCR, we meticulously examined the expression profiles of a panel comprising 84 inflammation-related lncRNAs in individuals presenting upper respiratory infection symptoms, categorizing them into those testing negative or positive for SARS-CoV-2. Notably, first-phase PSD individuals exhibited significantly elevated levels of AC000120.7 and SENP3-EIF4A1. In addition, we measured the expression of two lncRNAs, AC000120.7 and SENP3-EIF4A1, in patients with ARDS unrelated to SARS-CoV-2 (n = 5) and patients with ARDS induced by SARS-CoV-2 (ARDS-CoV-2, n = 10), and interestingly, expression was also higher among patients with ARDS. Intriguingly, our interaction pathway analysis unveiled potential interactions between lncRNA AC000120.7, various microRNAs, and genes associated with inflammation. This study found higher expression levels of lncRNAs AC000120.7 and SENP3-EIF4A1 in the context of infection-positive COVID-19, particularly within the complex landscape of ARDS. Full article

(This article belongs to the Special Issue Coronaviruses: Past, Present, and Future)

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12 pages, 1629 KiB

Open AccessPerspective

COVID Variants, Villain and Victory: A Bioinformatics Perspective

by Nityendra Shukla, Neha Srivastava, Rohit Gupta, Prachi Srivastava and Jitendra Narayan

Microorganisms 2023, 11(8), 2039; https://doi.org/10.3390/microorganisms11082039 - 9 Aug 2023

Cited by 1 | Viewed by 2165

Abstract

The SARS-CoV-2 virus, a novel member of the Coronaviridae family, is responsible for the viral infection known as Coronavirus Disease 2019 (COVID-19). In response to the urgent and critical need for rapid detection, diagnosis, analysis, interpretation, and treatment of COVID-19, a wide variety [...] Read more.

The SARS-CoV-2 virus, a novel member of the Coronaviridae family, is responsible for the viral infection known as Coronavirus Disease 2019 (COVID-19). In response to the urgent and critical need for rapid detection, diagnosis, analysis, interpretation, and treatment of COVID-19, a wide variety of bioinformatics tools have been developed. Given the virulence of SARS-CoV-2, it is crucial to explore the pathophysiology of the virus. We intend to examine how bioinformatics, in conjunction with next-generation sequencing techniques, can be leveraged to improve current diagnostic tools and streamline vaccine development for emerging SARS-CoV-2 variants. We also emphasize how bioinformatics, in general, can contribute to critical areas of biomedicine, including clinical diagnostics, SARS-CoV-2 genomic surveillance and its evolution, identification of potential drug targets, and development of therapeutic strategies. Currently, state-of-the-art bioinformatics tools have helped overcome technical obstacles with respect to genomic surveillance and have assisted in rapid detection, diagnosis, and delivering precise treatment to individuals on time. Full article

(This article belongs to the Special Issue Coronaviruses: Past, Present, and Future)

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10 pages, 985 KiB

Open AccessBrief Report

CD147 rs8259T>A Variant Confers Susceptibility to COVID-19 Infection within the Mexican Population

by Luis M. Amezcua-Guerra, Carlos A. Guzmán-Martín, Isela Montúfar-Robles, Rashidi Springall, Adrián Hernández-Díazcouder, Rosa Elda Barbosa-Cobos, Fausto Sánchez-Muñoz and Julián Ramírez-Bello

Microorganisms 2023, 11(8), 1919; https://doi.org/10.3390/microorganisms11081919 - 28 Jul 2023

Cited by 1 | Viewed by 1421

Abstract

Background: Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Clinical manifestations of COVID-19 range from mild flu-like symptoms to severe respiratory failure. Nowadays, extracellular matrix metalloproteinase inducer (EMMPRIN), also known as cluster of differentiation 147 (CD147) [...] Read more.

Background: Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Clinical manifestations of COVID-19 range from mild flu-like symptoms to severe respiratory failure. Nowadays, extracellular matrix metalloproteinase inducer (EMMPRIN), also known as cluster of differentiation 147 (CD147) or BASIGIN, has been studied as enabling viral entry and replication within host cells. However, the impact of the CD147 rs8259T>A single nucleotide variant (SNV) on SARS-CoV-2 susceptibility remains poorly investigated. Objective: To investigate the impact of rs8259T>A on the CD147 gene in individuals from Mexico with COVID-19 disease. Methods: We genotyped the CD147 rs8359T>A SNV in 195 patients with COVID-19 and 185 healthy controls from Mexico. In addition, we also measured the expression levels of CD147 and TNF mRNA and miR-492 from whole blood of patients with COVID-19 through RT-q-PCR. Results: We observed a significant association between the CD147 rs8259T>A SNV and susceptibility to COVID-19: T vs. A; OR 1.36, 95% CI 1.02–1.81; p = 0.037; and TT vs. AA; OR 1.77, 95% CI 1.01–3.09; p = 0.046. On the other hand, we did not find differences in CD147, TNF or miR-492 expression levels when considering the genotypes of the CD147 rs8259T>A SNV. Conclusions: Our results suggest that the CD147 rs8259T>A variant is a risk factor for COVID-19. Full article

(This article belongs to the Special Issue Coronaviruses: Past, Present, and Future)

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6 pages, 807 KiB

Open AccessBrief Report

The Impact of the COVID-19 Pandemic on Cutaneous Drug Eruptions in a Swedish Health Region without Lockdown

by Maria Pissa and Sandra Jerkovic Gulin

Microorganisms 2023, 11(8), 1913; https://doi.org/10.3390/microorganisms11081913 - 27 Jul 2023

Viewed by 1147

Abstract

The incidence of severe cutaneous drug eruptions during the COVID-19 period in Sweden has not been studied previously. Our aim was to compare the incidence of these skin reactions in a Swedish health region during the COVID-19 pandemic period with that of the [...] Read more.

The incidence of severe cutaneous drug eruptions during the COVID-19 period in Sweden has not been studied previously. Our aim was to compare the incidence of these skin reactions in a Swedish health region during the COVID-19 pandemic period with that of the year after: we conducted a retrospective, observational cohort study using data from a national registry of patients diagnosed with cutaneous drug eruptions during the pandemic in Sweden. We included the number of patients diagnosed with severe cutaneous drug eruptions at the Department of Dermatology in the Jonkoping health region during the COVID-19 pandemic (1 April 2020 to 31 March 2021) and the reference period (1 April 2021 to 31 March 2022). We examined the monthly occurrences of cutaneous drug eruptions in three dermatology clinics within the Jonkoping health region. The frequency of these eruptions was determined for two distinct time periods: during the pandemic and post-pandemic. The study included 102 patients with cutaneous drug eruptions: 29 patients were diagnosed during the COVID-19 pandemic period and 73 were diagnosed during the reference period. The difference in the number of cutaneous drug eruptions cases (p-value = 0.0001, 95% CI 1.4995–3.5500, OR 2.3072) during the pandemic period compared to the post-pandemic period was significant. To our knowledge, the impact of the pandemic on cutaneous drug eruptions has not been investigated in EU countries. The increasing and differentiation of the number of diagnosed cutaneous drug eruptions cases after the pandemic could be explained by the removal of COVID-19 restrictions and the more frequent health-seeking behavior during the post-pandemic period. Full article

(This article belongs to the Special Issue Coronaviruses: Past, Present, and Future)

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