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Emerging Issues in COVID-19: From Diagnosis to Inhibitors

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A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Molecular and Translational Medicine".

Deadline for manuscript submissions: closed (31 December 2023) | Viewed by 20673

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Dr. Erika Cione

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Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, Italy
Interests: vitamin A and its provitamin; microRNAs; gene expression; ketogenic diet; lipedema; cognitive and neurodegeneration
Special Issues, Collections and Topics in MDPI journals

Dr. Manuela Colosimo

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Department of Virology and Microbiology, Pugliese Ciaccio’s Hospital, 88100 Catanzaro, CZ, Italy
Interests: microbiology and virology

Special Issue Information

Dear Colleagues,

The COVID-19 outbreak has been recognized as a global threat to public health. It is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and no effective therapies currently exist against this novel viral agent. Strategies to combat pandemics, such as contact tracking, rapid antigenic testing, and biosensors, are still needed. Genetic research allows for the identification of continuously evolving novel variants of the virus, and epidemiological studies characterize and follow their propagation in various regions of the world in which reinfections are now occuring. This Special Issue aims to describe scientific works with novel antiviral or repositioned drugs that can decrease the severity of the disease but also hopes to focus on the relationship between COVID-19 and clinical outcomes, as well as methods for diagnostic procedures. Authors are welcome to submit articles, communications, opinions, and reviews.

Dr. Erika Cione
Dr. Manuela Colosimo
Guest Editors

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Keywords

COVID-19
novel antiviral drugs
drug reposition
diagnostic
rapid test
biosensor

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Published Papers (8 papers)

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Research

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10 pages, 852 KiB

Open AccessArticle

Monoclonal Antibodies and Antivirals against SARS-CoV-2 Reduce the Risk of Long COVID: A Retrospective Propensity Score-Matched Case–Control Study

by Antonio Cimellaro, Desirée Addesi, Michela Cavallo, Francesco Spagnolo, Edoardo Suraci, Raffaella Cordaro, Ines Spinelli, Francesco Passafaro, Manuela Colosimo, Medea Pintaudi, Carmelo Pintaudi and on behalf of the CATAnzaro LOng COVID (CATALOCO) Study Group

Biomedicines 2022, 10(12), 3135; https://doi.org/10.3390/biomedicines10123135 - 5 Dec 2022

Cited by 5 | Viewed by 2702

Abstract

Long COVID is a complex condition affecting quality of life, with limited therapeutic options. We investigated the occurrence of long COVID in subjects receiving early therapy with monoclonal antibodies (mAbs) or antivirals to reduce the risk of COVID-19 progression. In this retrospective study we enrolled 737 adult patients (aged 65.16 ± 13.46; 361F), who experienced COVID-19 between January 2021 and March 2022. Antiviral or mAbs were administered to symptomatic patients who did not require oxygen therapy or hospital admission for SARS-CoV-2 infection, and who were at high risk of progression to severe disease, as identified by age > 65 years or the presence of comorbidities. Long COVID, defined as newly or persistent long-term symptoms 4 weeks after the onset of the acute illness, was reported in 204 cases (28%). Age (OR 1.03; p < 0.001), gender (OR 1.88; p < 0.001) and at least three comorbidities (OR 3.49; p = 0.049) were directly associated with long COVID; conversely, vaccination (OR 0.59; p = 0.005) and mAbs/antivirals (OR 0.44; p = 0.002) were independently associated with a reduced risk of long COVID. At a propensity-score-matched analysis, the mAbs/antivirals group had a significantly lower occurrence of long COVID in comparison with untreated controls (11% vs. 34%; p = 0.001). In conclusion, mAbs and antivirals administered against the progression of COVID-19 were associated with a reduced risk of long COVID. Full article

(This article belongs to the Special Issue Emerging Issues in COVID-19: From Diagnosis to Inhibitors)

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14 pages, 562 KiB

Open AccessArticle

SARS-CoV-2 Serology: Utility and Limits of Different Antigen-Based Tests through the Evaluation and the Comparison of Four Commercial Tests

by Mariem Gdoura, Habib Halouani, Donia Sahli, Mehdi Mrad, Wafa Chamsa, Manel Mabrouk, Nahed Hogga, Kamel Ben-Salem and Henda Triki

Biomedicines 2022, 10(12), 3106; https://doi.org/10.3390/biomedicines10123106 - 1 Dec 2022

Viewed by 1739

Abstract

Introduction: SARS-CoV-2 serology have several indications. Currently, as there are various types available, it is important to master their performance in order to choose the best test for the indication. We evaluated and compared four different commercial serology tests, three of them had the Food and Drug Administration Emergency Use Authorization (FDA-EUA). Our goal was to provide new data to help guide the interpretation and the choice of the serological tests. Methods: Four commercial tests were studied: Elecsys^® Roche^® on Cobas^® (total anti-nucleocapsid (N) antibodies), VIDAS^® Biomerieux^® (IgM and IgG anti- receptor binding domain (RBD) antibodies), Mindray^® (IgM and IgG anti-N and anti-RBD antibodies) and Access^® Beckman Coulter^® (IgG anti-RBD antibodies). Two panels were tested: a positive panel (n = 72 sera) obtained from COVID-19-confirmed patients with no vaccination history and a negative panel (n = 119) of pre-pandemic sera. The analytical performances were evaluated and the ROC curve was drawn to assess the manufacturer’s cut-off for each test. Results: A large range of variability between the tests was found. The Mindray^®IgG and Cobas^® tests showed the best overall sensitivity, which was equal to 79.2% CI 95% (67.9–87.8). The Cobas^® test showed the best sensitivity after 14 days of COVID-19 molecular confirmation; which was equal to 85.4% CI 95% (72.2–93.9). The Access^® test had a lower sensitivity, even after day 14 (55.5% CI 95% (43.4–67.3)). The best specificity was noted for the Cobas^®, VIDAS^®IgG and Access^® IgG tests (100% CI 95% (96.9–100)). The IgM tests, VIDAS^®IgM and Mindray^®IgM, showed the lowest specificity and sensitivity rates. Overall, only 43 out of 72 sera (59.7%) showed concordant results by all tests. Retained cut-offs for a significantly better sensitivity and accuracy, without significant change in the specificity, were: 0.87 for Vidas^®IgM (p = 0.01) and 0.14 for Access^® (p < 10⁻⁴). The combination of Cobas^® with Vidas^® IgM and IgG offered the best accuracy in comparison with all other tests combinations. Conclusion: Although using an FDA-EUA approved serology test, each laboratory should carry out its own evaluation. Tests variability may raise some concerns that seroprevalence studies may vary significantly based on the used serology test. Full article

(This article belongs to the Special Issue Emerging Issues in COVID-19: From Diagnosis to Inhibitors)

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10 pages, 2319 KiB

Open AccessArticle

Feasibility of Self-Performed Lung Ultrasound with Remote Teleguidance for Monitoring at Home COVID-19 Patients

by Emanuele Pivetta, Anna Ravetti, Giulia Paglietta, Irene Cara, Federico Buggè, Gitana Scozzari, Milena M. Maule, Fulvio Morello, Stefania Locatelli and Enrico Lupia

Biomedicines 2022, 10(10), 2569; https://doi.org/10.3390/biomedicines10102569 - 13 Oct 2022

Cited by 7 | Viewed by 1735

Abstract

During the COVID-19 pandemic, use of telemedicine with the aim of reducing the rate of viral transmission increased. This proof-of-concept observational study was planned to test the feasibility of a home-based lung ultrasound (LUS) follow-up performed by patients with mild COVID-19 infection on themselves. We enrolled patients presenting to the emergency department with SARS-CoV-2 infection without signs of pneumonia and indication to discharge. Each patient received a brief training on how to perform LUS and a handheld ultrasound probe. Then, patients were contacted on a daily basis, and LUS images were acquired by the patients themselves under “teleguidance” by the investigator. Twenty-one patients were enrolled with a median age of 44 years. All evaluations were of sufficient quality for a follow up. Probability of a better LUS quality was related to higher degree (odds ratio, OR, 1.42, 95% CI 0.5–3.99) and a lower quality to evaluation time (from 0.71, 95% CI 0.55–0.92 for less than 7 min, to 0.52, 95% CI 0.38–0.7, between 7 and 10 min, and to 0.29, 95% CI 0.2–0.43, for evaluations longer than 10 min). No effect related to gender or age was detected. LUS performed by patients and remotely overseen by expert providers seems to be a feasible and reliable telemedicine tool. Full article

(This article belongs to the Special Issue Emerging Issues in COVID-19: From Diagnosis to Inhibitors)

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10 pages, 456 KiB

Open AccessArticle

Safety Profile and Outcomes of Early COVID-19 Treatments in Immunocompromised Patients: A Single-Centre Cohort Study

by Simona Biscarini, Simone Villa, Camilla Genovese, Mara Tomasello, Anna Tonizzo, Marco Fava, Nathalie Iannotti, Matteo Bolis, Bianca Mariani, Antonia Grazia Valzano, Letizia Corinna Morlacchi, Francesca Donato, Giuseppe Castellano, Ramona Cassin, Maria Carrabba, Antonio Muscatello, Andrea Gori, Alessandra Bandera and Andrea Lombardi

Biomedicines 2022, 10(8), 2002; https://doi.org/10.3390/biomedicines10082002 - 18 Aug 2022

Cited by 9 | Viewed by 2178

Abstract

Background: Early treatment with remdesivir (RMD) or monoclonal antibodies (mAbs) could be a valuable tool in patients at risk of severe COVID-19 with unsatisfactory responses to vaccination. We aim to assess the safety and clinical outcomes of these treatments among immunocompromised subjects. Methods: We retrospectively reviewed all nonhospitalized patients who received an early treatment with RMD or mAbs for COVID-19, from 25 November 2021 to 25 January 2022, in a large tertiary hospital. Outcomes included frequency of adverse drug reaction (ADR), duration of symptoms and molecular swab positivity, emergency department access, hospital or intensive care unit admission, and mortality in the 14 days following treatment administration. Results: Early treatments were administered to 143 patients, 106/143 (74.1%) immunocompromised, including 41 solid organ and 6 hematopoietic stem cell transplant recipients. Overall, 23/143 (16.1%) subjects reported ADRs. Median time from treatment start to SARS-CoV-2 nasopharyngeal swab negativity and symptom resolution was 10 (IQR 6–16) and 2.5 days (IQR 1.0–6.0), respectively, without differences between immunocompromised and nonimmunocompromised patients. In the 14 days after treatment administration, 5/143 patients (3.5%) were hospitalized and one died as a result of causes related to COVID-19, all of them were immunocompromised. Conclusions: RMD and mAbs have minimal ADRs and favourable outcomes in immunocompromised patients. Full article

(This article belongs to the Special Issue Emerging Issues in COVID-19: From Diagnosis to Inhibitors)

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Review

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26 pages, 3279 KiB

Open AccessReview

Benzoindolizidine Alkaloids Tylophorine and Lycorine and Their Analogues with Antiviral, Anti-Inflammatory, and Anticancer Properties: Promises and Challenges

by Antonella Di Sotto, Mehdi Valipour, Aala Azari, Silvia Di Giacomo and Hamid Irannejad

Biomedicines 2023, 11(10), 2619; https://doi.org/10.3390/biomedicines11102619 - 24 Sep 2023

Cited by 9 | Viewed by 2427

Abstract

Ongoing viral research, essential for public health due to evolving viruses, gains significance owing to emerging viral infections such as the SARS-CoV-2 pandemic. Marine and plant alkaloids show promise as novel potential pharmacological strategies. In this narrative review, we elucidated the potential of tylophorine and lycorine, two naturally occurring plant-derived alkaloids with a shared benzoindolizidine scaffold, as antiviral agents to be potentially harnessed against respiratory viral infections. Possible structure-activity relationships have also been highlighted. The substances and their derivatives were found to be endowed with powerful and broad-spectrum antiviral properties; moreover, they were able to counteract inflammation, which often underpins the complications of viral diseases. At last, their anticancer properties hold promise not only for advancing cancer research but also for mitigating the oncogenic effects of viruses. This evidence suggests that tylophorine and lycorine could effectively counteract the pathogenesis of respiratory viral disease and its harmful effects. Although common issues about the pharmacologic development of natural substances remain to be addressed, the collected evidence highlights a possible interest in tylophorine and lycorine as antiviral and/or adjuvant strategies and encourages future more in-depth pre-clinical and clinical investigations to overcome their drawbacks and harness their power for therapeutic purposes. Full article

(This article belongs to the Special Issue Emerging Issues in COVID-19: From Diagnosis to Inhibitors)

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22 pages, 1168 KiB

Open AccessReview

The Immunomodulatory Role of Cell-Free Approaches in SARS-CoV-2-Induced Cytokine Storm—A Powerful Therapeutic Tool for COVID-19 Patients

by Maria Csobonyeiova, Veronika Smolinska, Stefan Harsanyi, Michal Ivantysyn and Martin Klein

Biomedicines 2023, 11(6), 1736; https://doi.org/10.3390/biomedicines11061736 - 16 Jun 2023

Cited by 9 | Viewed by 2263

Abstract

Currently, there is still no effective and definitive cure for the coronavirus disease 2019 (COVID-19) caused by the infection of the novel highly contagious severe acute respiratory syndrome virus (SARS-CoV-2), whose sudden outbreak was recorded for the first time in China in late December 2019. Soon after, COVID-19 affected not only the vast majority of China’s population but the whole world and caused a global health public crisis as a new pandemic. It is well known that viral infection can cause acute respiratory distress syndrome (ARDS) and, in severe cases, can even be lethal. Behind the inflammatory process lies the so-called cytokine storm (CS), which activates various inflammatory cytokines that damage numerous organ tissues. Since the first outbreak of SARS-CoV-2, various research groups have been intensively trying to investigate the best treatment options; however, only limited outcomes have been achieved. One of the most promising strategies represents using either stem cells, such as mesenchymal stem cells (MSCs)/induced pluripotent stem cells (iPSCs), or, more recently, using cell-free approaches involving conditioned media (CMs) and their content, such as extracellular vesicles (EVs) (e.g., exosomes or miRNAs) derived from stem cells. As key mediators of intracellular communication, exosomes carry a cocktail of different molecules with anti-inflammatory effects and immunomodulatory capacity. Our comprehensive review outlines the complex inflammatory process responsible for the CS, summarizes the present results of cell-free-based pre-clinical and clinical studies for COVID-19 treatment, and discusses their future perspectives for therapeutic applications. Full article

(This article belongs to the Special Issue Emerging Issues in COVID-19: From Diagnosis to Inhibitors)

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18 pages, 835 KiB

Open AccessReview

Overview of Antiviral Drug Therapy for COVID-19: Where Do We Stand?

by Renata Esposito, Davida Mirra, Liberata Sportiello, Giuseppe Spaziano and Bruno D’Agostino

Biomedicines 2022, 10(11), 2815; https://doi.org/10.3390/biomedicines10112815 - 4 Nov 2022

Cited by 8 | Viewed by 4497

Abstract

The vaccine weapon has resulted in being essential in fighting the COVID-19 outbreak, but it is not fully preventing infection due to an alarming spreading of several identified variants of concern. In fact, the recent emergence of variants has pointed out how the SARS-CoV-2 pandemic still represents a global health threat. Moreover, oral antivirals also develop resistance, supporting the need to find new targets as therapeutic tools. However, cocktail therapy is useful to reduce drug resistance and maximize vaccination efficacy. Natural products and metal-drug-based treatments have also shown interesting antiviral activity, representing a valid contribution to counter COVID-19 outbreak. This report summarizes the available evidence which supports the use of approved drugs and further focuses on significant clinical trials that have investigated the safety and efficacy of repurposing drugs and new molecules in different COVID-19 phenotypes. To date, there are many individuals vulnerable to COVID-19 exhibiting severe symptoms, thus characterizing valid therapeutic strategies for better management of the disease is still a challenge. Full article

(This article belongs to the Special Issue Emerging Issues in COVID-19: From Diagnosis to Inhibitors)

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Other

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10 pages, 1897 KiB

Open AccessBrief Report

The First Identification in Italy of SARS-CoV-2 Omicron BA.4 Harboring KSF141_del: A Genomic Comparison with Omicron Sub-Variants

by Cinzia Peronace, Rossana Tallerico, Manuela Colosimo, Marco De Fazio, Federica Pasceri, Ilenia Talotta, Giuseppina Panduri, Letizia Pintomalli, Rosaria Oteri, Valeria Calantoni, Maria Teresa Fiorillo, Maria Cristina Caroleo, Rosita Curcio, Vincenza Dolce, Erika Cione and Pasquale Minchella

Biomedicines 2022, 10(8), 1839; https://doi.org/10.3390/biomedicines10081839 - 30 Jul 2022

Cited by 6 | Viewed by 2123

Abstract

The rapid emergence and worldwide detection of the SARS-CoV-2 Omicron variant underscore the importance of robust genomic surveillance systems and prompt information sharing among global public health partners. The Omicron variant has rapidly replaced the Delta variant as a dominating SARS-CoV-2 variant because of natural selection, favoring the variant with higher infectivity and stronger vaccine breakthrough capability. The Omicron variant is also known as B.1.1.529. It has four sub-variants, indicated as BA.1, BA.2, BA.3 and BA.4. Among them, BA.1 is the currently prevailing sub-variant, and BA.2 has been found to be able to alarmingly re-infect patients initially infected by Omicron BA.1. The BA.3 sub-variant is a combination of mutations of BA.1 and BA.2, especially in the spike protein. Today, the BA.4 variant is emerging, which is herein described, and it was the first detected in Italy. Via bioinformatic analysis, we are reporting that the BA.4 that was identified harbors a new mutation, specifically a deletion in the ORF1ab gene, corresponding to KSF141_del in non-structural protein 1 (nsp1), a critical virulence factor able to suppress host translation. The bioinformatics comparison analysis with the other three sub-variants reveals that the deletion was not present before and was never reported until now. Therefore, we can speculate that Omicron BA.4 will become a new dominating “variant of concern” and may also break vaccine protection. Moreover, we show that other proteins are mutated in the BA.4. In particular, seven mutations are recognized in the nucleocapsid (N) protein, and the capability of five different types of rapid antigenic tests are used to identify it. Full article

(This article belongs to the Special Issue Emerging Issues in COVID-19: From Diagnosis to Inhibitors)

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