COVID-19 Prevention and Treatment: 2nd Edition

A special issue of Life (ISSN 2075-1729). This special issue belongs to the section "Epidemiology".

Deadline for manuscript submissions: closed (31 December 2023) | Viewed by 17986

Special Issue Editors

Department of Biological and Clinical Sciences, University of Turin, S. Luigi Gonzaga Hospital, 10043 Orbassano, Italy
Interests: pharmacology; sex and gender medicine; pharmacokinetics; pharmacodynamics; pharmacogenomics; personalized therapy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This second volume of this Special Issue follows on from the success of the first, we invite you to publish your research in this edition of “COVID-19 Prevention and Treatment” (https://www.mdpi.com/journal/life/special_issues/COVID_19_prevention_treatment).

What started as a cluster of patients with a mysterious respiratory illness in December 2019 was later identified as COVID-19. A novel Betacoronavirus was subsequently isolated as the causative disease agent of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Within a few months, the world found itself in the midst of a pandemic. The cause of this crisis has been attributed to an infectious disease. All our interventions have focused on cutting lines of viral transmission to control the spread of the pathogen. This approach, adopted by many governments, has been driven mostly by epidemic modelers and infectious disease specialists, who understandably frame the present health emergency in centuries-old terms of the plague. However, what we have learned thus far tells us that the story of COVID-19 is not so simple. COVID-19 is not a pandemic; it is a syndemic. This indicates that a wider approach is needed to protect the health of our communities. This Special Issue arises from the need for a new approach both in the clinical setting and in therapeutic regimens developed through the exchange of results from clinical and preclinical studies on COVID-19.

Original research articles, reviews, and short reports on various aspects of COVID-19 are welcome. With this Special Issue, we aim to create an interdisciplinary consensus from a new perspective.

Dr. Silvia De Francia
Dr. Sarah Allegra
Guest Editors

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Keywords

  • COVID-19
  • SARS-CoV-2
  • therapies
  • drug repurposing
  • tailored treatment
  • personalized medicine

Published Papers (14 papers)

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11 pages, 234 KiB  
Article
Treatment with Remdesivir of Children with SARS-CoV-2 Infection: Experience from a Clinical Hospital in Romania
by Maria-Elena Cocuz, Iuliu Gabriel Cocuz, Ligia Rodina, Elena Tataranu, Olga Adriana Caliman-Sturdza and Florin Filip
Life 2024, 14(3), 410; https://doi.org/10.3390/life14030410 - 20 Mar 2024
Viewed by 321
Abstract
Background: The COVID-19 pandemic was characterized by mild-to-moderate disease in children and adolescents, with low incidences of severe cases and mortality. Most of the information on drug therapy in COVID-19-positive children was derived from research in adult patients. Remdesivir, an inhibitor of viral [...] Read more.
Background: The COVID-19 pandemic was characterized by mild-to-moderate disease in children and adolescents, with low incidences of severe cases and mortality. Most of the information on drug therapy in COVID-19-positive children was derived from research in adult patients. Remdesivir, an inhibitor of viral RNA polymerase, was shown to be effective in COVID-19 patients with moderate-to-severe disease. In this study, we present our experience of the use of remdesivir in pediatric patients hospitalized with COVID-19. Materials and methods: This retrospective study was based on the early use of remdesivir in 14 children with mild, moderate, and severe clinical forms of COVID-19, who were hospitalized between 1 January 2022, and 30 September 2023. Results: The patients included eight infants and six children older than 1 day (the age range was 2 months to 17 years). Most of them (92.85%) had documented pneumonia. Four patients had associated acute laryngitis, and another had bronchiolitis. Coinfections with Streptococcus pneumoniae were diagnosed in two patients. The clinical course was favorable in 12/14 (85.71%) children. Two patients were transferred to the pediatric intensive care unit because of aggravation of associated acute diseases (acute laryngitis and bronchiolitis, respectively). Mild increases in alanine aminotransferase levels occurred in two patients, with no increase in serum creatinine, during treatment with remdesivir. Conclusion: The appropriate use of remdesivir proved safe and efficient in our group of patients. However, further studies are required to support the efficiency, tolerability, and safety of remdesivir in children. Full article
(This article belongs to the Special Issue COVID-19 Prevention and Treatment: 2nd Edition)
12 pages, 714 KiB  
Article
COVID-19 Clinical Features and Outcome in Italian Patients Treated with Biological Drugs Targeting Type 2 Inflammation
by Giada Sambugaro, Elena Brambilla, Giulia Costanzo, Vera Bonato, Andrea Giovanni Ledda, Stefano Del Giacco, Riccardo Scarpa, Marcello Rattazzi, Elisabetta Favero, Francesco Cinetto and Davide Firinu
Life 2024, 14(3), 378; https://doi.org/10.3390/life14030378 - 13 Mar 2024
Viewed by 490
Abstract
This is a multicentric investigation involving two Italian centers that examined the clinical course of COVID-19 in patients receiving biological therapy targeting type 2 inflammation and those not receiving biologicals. Since the beginning of the COVID-19 pandemic, the management of respiratory and allergic [...] Read more.
This is a multicentric investigation involving two Italian centers that examined the clinical course of COVID-19 in patients receiving biological therapy targeting type 2 inflammation and those not receiving biologicals. Since the beginning of the COVID-19 pandemic, the management of respiratory and allergic disorders and the potential impact of biological therapy in the most severe forms has been a point of uncertainty. Our multicentric investigation aimed to compare the clinical course of COVID-19 and the impact of vaccination in an Italian cohort of patients with atopic disorders caused by a type 2 inflammation, such as eosinophilic asthma, chronic rhinosinusitis with nasal polyposis (CRSwNP), atopic dermatitis (AD), and chronic spontaneous urticaria (CSU). A questionnaire was given to patients coming to our outpatient clinic for the first evaluation or follow-up visit, asking for the clinical characteristics of the infection, the ongoing therapy during the infection, any relevant change, and the patient’s vaccination status. We enrolled 132 atopic patients from two Italian centers; 62 patients were on biological therapy at the time of infection (omalizumab 31%, mepolizumab 26%, benralizumab 19%, and dupilumab 24%). The median age was 56 (IQR 22.8) for patients on biologicals and 48 (IQR 26.5) for those not on biologicals (p = 0.028). The two groups were comparable in terms of sex, body mass index (BMI), smoking history, and systemic oral corticosteroid use (OCS). There were no significant differences in non-biological therapy and comorbidity between the two groups. The patients not on biological therapy had a prevalence of 87% for asthma, 52% for CRSwNP, 10% for CSU, and 6% for AD. The patients on biologicals had a prevalence of 93% for asthma, 17% for CRSwNP, and 10% for CSU. In our work, we observed that mAbs targeting type 2 inflammation in patients with COVID-19 appeared to be safe, with no worsening of symptoms, prolongation of infection, or increase in hospitalizations. Between the two groups, there were no significant differences in the duration of swab positivity (p = 0.45) and duration of symptoms (p = 0.38). During COVID-19, patients on biologicals experienced a significant increase in common cold-like symptoms (p = 0.038), dyspnea (p = 0.016), and more, but not significant, asthma exacerbations, with no significant differences between the different biologicals. Regarding the vaccination status, we observed that there was an increased number of hospitalizations among unvaccinated patients in both groups, although the difference did not reach statistical significance. No patients on biologicals reported safety issues or adverse effects associated with the use of biological treatments during COVID-19. Our investigation showed that mAbs against type 2 inflammation given during Coronavirus Disease 2019 are safe and do not impact the clinical course or main outcomes. Therefore, we found no signals suggesting that anti-Th2 biological therapy should be discontinued during SARS-CoV-2 infection. Controlled studies and analysis, including data from registries and real-life studies, are required to draw firm conclusions regarding the safety or possible advantages that anti-type 2 mAbs could offer in particular clinical contexts, such as infections. Full article
(This article belongs to the Special Issue COVID-19 Prevention and Treatment: 2nd Edition)
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11 pages, 1174 KiB  
Article
Age and Sex-Related Differences in Teicoplanine Isoform Concentrations in SARS-CoV-2 Patients
by Sarah Allegra, Francesco Chiara, Marina Zanatta, Giulio Mengozzi, Maria Paola Puccinelli and Silvia De Francia
Life 2023, 13(9), 1792; https://doi.org/10.3390/life13091792 - 22 Aug 2023
Viewed by 741
Abstract
Teicoplanin, a glycopeptide antibiotic commonly used to treat bacterial infections, was discovered to be active in vitro against SARS-CoV-2. The aim of this study was to assess the levels of teicoplanin and its components in a cohort of adult and pediatric SARS-CoV-2 patients, [...] Read more.
Teicoplanin, a glycopeptide antibiotic commonly used to treat bacterial infections, was discovered to be active in vitro against SARS-CoV-2. The aim of this study was to assess the levels of teicoplanin and its components in a cohort of adult and pediatric SARS-CoV-2 patients, evaluating the effect of sex and age on analyte concentrations. The levels of AST, ALT and leukocytes were shown to be higher in females, while the C reactive protein was higher in males. Evaluating the absence/presence of teicoplanin isoforms, we observed that A2-2_3 is the only one consistently present in pediatrics and adults. In adult men and all pediatrics, A2-4_5 is always present. In pediatrics, except for A3-1, median isoform concentrations were higher in females; on the contrary, in adult patients, males showed higher levels. This is the first study to describe levels of teicoplanin isoforms in SARS-CoV-2 infected patients in males and females, and pediatrics and adults, despite the small sample size of our cohort. The observed results imply that additional testing, via therapeutic drug monitoring, may be helpful to more effectively manage infections, particularly those caused by the most recent viruses. Full article
(This article belongs to the Special Issue COVID-19 Prevention and Treatment: 2nd Edition)
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11 pages, 1790 KiB  
Article
Tocilizumab Is Associated with Increased Risk of Fungal Infections among Critically Ill Patients with COVID-19 and Acute Renal Failure: An Observational Cohort Study
by Barrett J. Burger, Sarenthia M. Epps, Victor M. Cardenas, Rajani Jagana, Nikhil K. Meena and William T. Atchley
Life 2023, 13(8), 1752; https://doi.org/10.3390/life13081752 - 16 Aug 2023
Cited by 1 | Viewed by 974
Abstract
Research Question: Does treatment with tocilizumab increase the risk of a fungal infection in critically ill patients with coronavirus-19? Background: Numerous therapies have been evaluated as possible treatments for coronavirus-2019 caused by severe acute respiratory syndrome coronavirus-2. Tocilizumab is a humanized monoclonal antibody [...] Read more.
Research Question: Does treatment with tocilizumab increase the risk of a fungal infection in critically ill patients with coronavirus-19? Background: Numerous therapies have been evaluated as possible treatments for coronavirus-2019 caused by severe acute respiratory syndrome coronavirus-2. Tocilizumab is a humanized monoclonal antibody directed against the interleukin-6 receptor that has found a role as a therapy for patients with severe coronavirus-19 pneumonia. The immunomodulatory effects of tocilizumab may have the unintended consequence of predisposing recipients to secondary infections. We sought to assess the risk of invasive fungal disease and the therapeutic impact of tocilizumab on the hospital length of stay, duration of mechanical ventilation, and intensive-care-unit length of stay in critically ill patients with severe coronavirus-19 pneumonia. Methods: Records of critically ill patients with coronavirus-2019 admitted from March to September 2020 at our institution were reviewed. The risk for fungal infections, intensive-care-unit length of stay, hospital length of stay, and duration of mechanical ventilation in those that received tocilizumab in addition to standard coronavirus-2019 treatments was assessed. Results: Fifty-six critically ill patients treated with dexamethasone and remdesivir for coronavirus-2019 were included, of which 16 patients also received tocilizumab. The majority of the cohort was African American, Asian, or of other ethnic minorities (53.6%). Invasive fungal infections occurred in 10.7% of all patients, and infection rates were significantly higher in the tocilizumab group than in the control group (31.2% vs. 2.5%, risk difference [RD] = 28.8%, p < 0.01). The increased risk in the tocilizumab group was strongly associated with renal replacement therapy. There was a dose–response relationship between the risk of fungal infection and number of tocilizumab doses received, with 2.5% of infections occurring with zero doses, 20% with a single dose (RD = 17.5%), and 50% with two doses (RD = 47.5%) (trend test p < 0.001). In addition, ICU LOS (23.4 days vs. 9.0 days, p < 0.01), the duration of mechanical ventilation (18.9 vs. 3.5 days, p = 0.01), and hospital length of stay (LOS) (29.1 vs. 15.5, p < 0.01) were increased in patients that received tocilizumab. Conclusions: Repurposed immunomodulator therapies, such as tocilizumab, are now recommended treatments for severe coronavirus-2019 pneumonia, but safety concerns remain. In this early pandemic cohort, the addition of tocilizumab to dexamethasone was associated with an increased risk of fungal infection in those that were critically ill and received renal replacement therapy. Tocilizumab use was also associated with increased ICU and hospital LOSs and duration of mechanical ventilation. Full article
(This article belongs to the Special Issue COVID-19 Prevention and Treatment: 2nd Edition)
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11 pages, 225 KiB  
Article
Utilization of Instrumentation in Swallowing Assessment of Surgical Patients during COVID-19
by Heather Warner, Jennifer M. Coutinho and Nwanmegha Young
Life 2023, 13(7), 1471; https://doi.org/10.3390/life13071471 - 29 Jun 2023
Cited by 1 | Viewed by 817
Abstract
The aim of this study is to describe a measured return to instrumental dysphagia assessments for our vulnerable surgical patient population, such that best practice patterns could be resumed and our staff kept safe from transmission of COVID-19. A retrospective medical record review [...] Read more.
The aim of this study is to describe a measured return to instrumental dysphagia assessments for our vulnerable surgical patient population, such that best practice patterns could be resumed and our staff kept safe from transmission of COVID-19. A retrospective medical record review provided data on clinical practice patterns of swallowing assessment in an at-risk surgical patient population. Outcomes of this study support protocols that allow clinicians to safely resume the use of instrumental assessment and return to best practice in dysphagia assessment for our surgical patient population. Full article
(This article belongs to the Special Issue COVID-19 Prevention and Treatment: 2nd Edition)
20 pages, 5061 KiB  
Article
Machine Learning Classification of Time since BNT162b2 COVID-19 Vaccination Based on Array-Measured Antibody Activity
by Qing-Lan Ma, Fei-Ming Huang, Wei Guo, Kai-Yan Feng, Tao Huang and Yu-Dong Cai
Life 2023, 13(6), 1304; https://doi.org/10.3390/life13061304 - 31 May 2023
Viewed by 1678
Abstract
Vaccines trigger an immunological response that includes B and T cells, with B cells producing antibodies. SARS-CoV-2 immunity weakens over time after vaccination. Discovering key changes in antigen-reactive antibodies over time after vaccination could help improve vaccine efficiency. In this study, we collected [...] Read more.
Vaccines trigger an immunological response that includes B and T cells, with B cells producing antibodies. SARS-CoV-2 immunity weakens over time after vaccination. Discovering key changes in antigen-reactive antibodies over time after vaccination could help improve vaccine efficiency. In this study, we collected data on blood antibody levels in a cohort of healthcare workers vaccinated for COVID-19 and obtained 73 antigens in samples from four groups according to the duration after vaccination, including 104 unvaccinated healthcare workers, 534 healthcare workers within 60 days after vaccination, 594 healthcare workers between 60 and 180 days after vaccination, and 141 healthcare workers over 180 days after vaccination. Our work was a reanalysis of the data originally collected at Irvine University. This data was obtained in Orange County, California, USA, with the collection process commencing in December 2020. British variant (B.1.1.7), South African variant (B.1.351), and Brazilian/Japanese variant (P.1) were the most prevalent strains during the sampling period. An efficient machine learning based framework containing four feature selection methods (least absolute shrinkage and selection operator, light gradient boosting machine, Monte Carlo feature selection, and maximum relevance minimum redundancy) and four classification algorithms (decision tree, k-nearest neighbor, random forest, and support vector machine) was designed to select essential antibodies against specific antigens. Several efficient classifiers with a weighted F1 value around 0.75 were constructed. The antigen microarray used for identifying antibody levels in the coronavirus features ten distinct SARS-CoV-2 antigens, comprising various segments of both nucleocapsid protein (NP) and spike protein (S). This study revealed that S1 + S2, S1.mFcTag, S1.HisTag, S1, S2, Spike.RBD.His.Bac, Spike.RBD.rFc, and S1.RBD.mFc were most highly ranked among all features, where S1 and S2 are the subunits of Spike, and the suffixes represent the tagging information of different recombinant proteins. Meanwhile, the classification rules were obtained from the optimal decision tree to explain quantitatively the roles of antigens in the classification. This study identified antibodies associated with decreased clinical immunity based on populations with different time spans after vaccination. These antibodies have important implications for maintaining long-term immunity to SARS-CoV-2. Full article
(This article belongs to the Special Issue COVID-19 Prevention and Treatment: 2nd Edition)
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13 pages, 998 KiB  
Article
Laryngotracheal Complications after Intubation for COVID-19: A Multicenter Study
by Estefanía Hernández-García, Rosa Hernández-Sandemetrio, Ana Quintana-Sanjuás, Enrique Zapater-Latorre, Ramón González-Herranz, Lorena Sanz, Rosa Reboll, Beatriz Pallarés-Martí, Montserrat Ollé-Moliner, Paula Martínez-Pascual, Itziar Gotxi, Araly Chacón-Uribe and Guillermo Plaza
Life 2023, 13(5), 1207; https://doi.org/10.3390/life13051207 - 18 May 2023
Cited by 1 | Viewed by 1479
Abstract
Many of the patients with COVID-19 have suffered respiratory distress requiring prolonged endotracheal intubation (ETI) resulting in laryngotracheal complication with an impact on breathing, phonation, and swallowing. Our aim is to describe laryngeal injuries diagnosed after ETI in patients with COVID-19 in a [...] Read more.
Many of the patients with COVID-19 have suffered respiratory distress requiring prolonged endotracheal intubation (ETI) resulting in laryngotracheal complication with an impact on breathing, phonation, and swallowing. Our aim is to describe laryngeal injuries diagnosed after ETI in patients with COVID-19 in a multicentre study. Methods: A prospective descriptive observational study was conducted from January 2021 to December 2021, including COVID-19 patients with laryngeal complications due to ETI diagnosed in several Spanish hospitals. We analyzed the epidemiological data, previous comorbidities, mean time to ICU admission and ETI, need for tracheostomy, mean time on invasive mechanical ventilation until tracheostomy or weaning, mean time in ICU, type of residual lesions, and their treatment. Results: We obtained the collaboration of nine hospitals during the months of January 2021 to December 2021. A total of 49 patients were referred. Tracheostomy was performed in 44.9%, being late in most cases (more than 7–10 days). The mean number of days of ETI until extubation was 17.63 days, and the main post-intubation symptoms were dysphonia, dyspnea, and dysphagia, in 87.8%, 34.7%, and 42.9%, respectively. The most frequent injury was altered laryngeal mobility, present in 79.6%. Statistically, there is a greater amount of stenosis after late ETI and after delayed tracheostomy, not observing the data with the immobility alterations. Conclusion: The mean number of days of ETI was long, according to the latest guidelines, with the need for several cycles of pronation. This long ETI may have had an impact on the increase of subsequent laryngeal sequelae, such as altered laryngeal mobility or stenosis. Full article
(This article belongs to the Special Issue COVID-19 Prevention and Treatment: 2nd Edition)
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11 pages, 414 KiB  
Article
Comparing the Impact of COVID-19 on Vaccinated and Unvaccinated Patients Affected by Myasthenia Gravis
by Elena Scarsi, Sara Massucco, Pilar M. Ferraro, Arianna Cella, Stefano G. Grisanti, Andrea Assini, Alessandro Beronio, Fabio Della Cava, Chiara Gemelli, Fabio Bandini, Carlo Serrati, Massimo Del Sette, Angelo Schenone, Luana Benedetti, Valeria Prada and Marina Grandis
Life 2023, 13(4), 1064; https://doi.org/10.3390/life13041064 - 21 Apr 2023
Viewed by 1273
Abstract
We evaluated 13 patients affected by myasthenia gravis (MG) who had coronavirus disease 2019 (COVID-19) before vaccination and 14 myasthenic patients who contracted severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection after vaccination to evaluate factors related to different COVID-19 outcomes. We compared the two [...] Read more.
We evaluated 13 patients affected by myasthenia gravis (MG) who had coronavirus disease 2019 (COVID-19) before vaccination and 14 myasthenic patients who contracted severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection after vaccination to evaluate factors related to different COVID-19 outcomes. We compared the two groups’ previous stability of MG and the severity of SARS-CoV-2 infection. Vaccinated and non-vaccinated patients were comparable in terms of severity of the previous MG course (mean maximum myasthenia gravis Foundation of America–MGFA–Class III) and during SARS-CoV-2 infection (mean MGFA Class II). In non-vaccinated patients, the hospitalization and severe course percentages were 61.5%, while the mortality reached 30.8%. The hospitalization, severe course, and mortality percentages in vaccinated patients were 7.1%. In deceased, non-vaccinated patients, greater myasthenia severity in the past clinical history, but not at the time of infection, was observed. Similarly, older age at MG onset and at the time of infection correlated with a more severe COVID-19 course in non-vaccinated patients (p = 0.03 and p = 0.04), but not in the group of vaccinated patients. In summary, our data support a protective role of vaccination in myasthenic patients, even if anti-CD20 therapy might be associated with a poor immune response to vaccines. Full article
(This article belongs to the Special Issue COVID-19 Prevention and Treatment: 2nd Edition)
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13 pages, 634 KiB  
Article
The Revived Interest in Ageusia Research during the COVID-19 Pandemic: A Bibliometric Analysis
by Andy Wai Kan Yeung
Life 2023, 13(4), 1062; https://doi.org/10.3390/life13041062 - 21 Apr 2023
Cited by 3 | Viewed by 1469
Abstract
The evolution of ageusia research literature has yet to be investigated. This bibliometric study analyzed the entire ageusia research literature indexed in Web of Science, to reveal its growth and the most productive entities in terms of authors, institutions, countries, journals, and journal [...] Read more.
The evolution of ageusia research literature has yet to be investigated. This bibliometric study analyzed the entire ageusia research literature indexed in Web of Science, to reveal its growth and the most productive entities in terms of authors, institutions, countries, journals, and journal categories. In addition, this study aimed to identify medical conditions (and their treatments) that were frequently associated with ageusia. On 7 March 2022, the Web of Science Core Collection database was accessed with the following search query: TS = (ageusia OR “taste loss” OR “loss of taste” OR “loss of gustat*” OR “gustatory loss”). The search identified publications mentioning these terms in their title, abstract, or keywords. No additional filters were placed on publication year, language, etc. The basic publication and citation counts were extracted from the in-built functions of the database. The complete record of the publications was exported into VOSviewer, a bibliometric software for visualizations. The search yielded 1170 publications. The cumulative publication and citation counts of the ageusia research sharply increased in 2020. The most productive author was Professor Thomas Hummel from Technische Universität Dresden. Ageusia research had heavy contributions from the United States, Italy, the United Kingdom, Germany, and India. The top 5 most productive journals mainly belonged to the otorhinolaryngology and medicine categories. The medical conditions frequently investigated in ageusia research included COVID-19, cancers (head and neck, and advanced basal cell), Guillain-Barré syndrome, neurodegenerative diseases, diabetes, and Sjogren’s syndrome. This study could act as a begvinner’s guide for (1) clinicians who are not familiar with ageusia so that they might better understand which scenarios they need to be more aware of since ageusia could be a co-morbidity of a patient’s underlying disease, and (2) for those who wish to search for relevant authors and journals for suitable publications related to the topic. Full article
(This article belongs to the Special Issue COVID-19 Prevention and Treatment: 2nd Edition)
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11 pages, 452 KiB  
Article
Long-Term Follow-Up of Patients Needing Extracorporeal Membrane Oxygenation Following a Critical Course of COVID-19
by Samuel Genzor, Pavol Pobeha, Martin Šimek, Petr Jakubec, Jan Mizera, Martin Vykopal, Milan Sova, Jakub Vaněk and Jan Praško
Life 2023, 13(4), 1054; https://doi.org/10.3390/life13041054 - 20 Apr 2023
Viewed by 1469
Abstract
Introduction: Severe respiratory failure is one of the most serious complications of coronavirus disease 2019 (COVID-19). In a small proportion of patients, mechanical ventilation fails to provide adequate oxygenation and extracorporeal membrane oxygenation (ECMO) is needed. The surviving individuals need long-term follow-up as [...] Read more.
Introduction: Severe respiratory failure is one of the most serious complications of coronavirus disease 2019 (COVID-19). In a small proportion of patients, mechanical ventilation fails to provide adequate oxygenation and extracorporeal membrane oxygenation (ECMO) is needed. The surviving individuals need long-term follow-up as it is not clear what their prognosis is. Aim: To provide a complex clinical picture of patients during follow-up exceeding one year after the ECMO therapy due to severe COVID-19. Methods: All subjects involved in the study required ECMO in the acute stage of COVID-19. The survivors were followed-up for over one year at a specialized respiratory medical center. Results: Of the 41 patients indicated for ECMO, 17 patients (64.7% males) survived. The average age of survivors was 47.8 years, and the average BMI was 34.7 kg·m−2. The duration of ECMO support was 9.4 days. A mild decrease in vital capacity (VC) and transfer factor (DLCO) was observed on the initial follow-up visit (82.1% and 60%, respectively). VC improved by 6.2% and by an additional 7.5% after 6 months and 1 year, respectively. DLCO improved by 21.1% after 6 months and remained stable after 1 year. Post-intensive care consequences included psychological problems and neurological impairment in 29% of patients; 64.7% of the survivors got vaccinated against SARS-CoV-2 within 12 months of hospitalization and 17.6% experienced reinfection with a mild course. Conclusion: The COVID-19 pandemic has significantly increased the need for ECMO. Patients’ quality of life after ECMO is temporarily significantly reduced but most patients do not experience permanent disability. Full article
(This article belongs to the Special Issue COVID-19 Prevention and Treatment: 2nd Edition)
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15 pages, 2296 KiB  
Article
Identification of Genes Associated with the Impairment of Olfactory and Gustatory Functions in COVID-19 via Machine-Learning Methods
by Jingxin Ren, Yuhang Zhang, Wei Guo, Kaiyan Feng, Ye Yuan, Tao Huang and Yu-Dong Cai
Life 2023, 13(3), 798; https://doi.org/10.3390/life13030798 - 15 Mar 2023
Cited by 16 | Viewed by 1982
Abstract
The coronavirus disease 2019 (COVID-19), as a severe respiratory disease, affects many parts of the body, and approximately 20–85% of patients exhibit functional impairment of the senses of smell and taste, some of whom even experience the permanent loss of these senses. These [...] Read more.
The coronavirus disease 2019 (COVID-19), as a severe respiratory disease, affects many parts of the body, and approximately 20–85% of patients exhibit functional impairment of the senses of smell and taste, some of whom even experience the permanent loss of these senses. These symptoms are not life-threatening but severely affect patients’ quality of life and increase the risk of depression and anxiety. The pathological mechanisms of these symptoms have not been fully identified. In the current study, we aimed to identify the important biomarkers at the expression level associated with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection-mediated loss of taste or olfactory ability, and we have suggested the potential pathogenetic mechanisms of COVID-19 complications. We designed a machine-learning-based approach to analyze the transcriptome of 577 COVID-19 patient samples, including 84 COVID-19 samples with a decreased ability to taste or smell and 493 COVID-19 samples without impairment. Each sample was represented by 58,929 gene expression levels. The features were analyzed and sorted by three feature selection methods (least absolute shrinkage and selection operator, light gradient boosting machine, and Monte Carlo feature selection). The optimal feature sets were obtained through incremental feature selection using two classification algorithms: decision tree (DT) and random forest (RF). The top genes identified by these multiple methods (H3-5, NUDT5, and AOC1) are involved in olfactory and gustatory impairments. Meanwhile, a high-performance RF classifier was developed in this study, and three sets of quantitative rules that describe the impairment of olfactory and gustatory functions were obtained based on the optimal DT classifiers. In summary, this study provides a new computation analysis and suggests the latent biomarkers (genes and rules) for predicting olfactory and gustatory impairment caused by COVID-19 complications. Full article
(This article belongs to the Special Issue COVID-19 Prevention and Treatment: 2nd Edition)
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15 pages, 1048 KiB  
Article
Target Trial Emulation Using Hospital-Based Observational Data: Demonstration and Application in COVID-19
by Oksana Martinuka, Maja von Cube, Derek Hazard, Hamid Reza Marateb, Marjan Mansourian, Ramin Sami, Mohammad Reza Hajian, Sara Ebrahimi and Martin Wolkewitz
Life 2023, 13(3), 777; https://doi.org/10.3390/life13030777 - 13 Mar 2023
Cited by 2 | Viewed by 2864
Abstract
Methodological biases are common in observational studies evaluating treatment effectiveness. The objective of this study is to emulate a target trial in a competing risks setting using hospital-based observational data. We extend established methodology accounting for immortal time bias and time-fixed confounding biases [...] Read more.
Methodological biases are common in observational studies evaluating treatment effectiveness. The objective of this study is to emulate a target trial in a competing risks setting using hospital-based observational data. We extend established methodology accounting for immortal time bias and time-fixed confounding biases to a setting where no survival information beyond hospital discharge is available: a condition common to coronavirus disease 2019 (COVID-19) research data. This exemplary study includes a cohort of 618 hospitalized patients with COVID-19. We describe methodological opportunities and challenges that cannot be overcome applying traditional statistical methods. We demonstrate the practical implementation of this trial emulation approach via clone–censor–weight techniques. We undertake a competing risk analysis, reporting the cause-specific cumulative hazards and cumulative incidence probabilities. Our analysis demonstrates that a target trial emulation framework can be extended to account for competing risks in COVID-19 hospital studies. In our analysis, we avoid immortal time bias, time-fixed confounding bias, and competing risks bias simultaneously. Choosing the length of the grace period is justified from a clinical perspective and has an important advantage in ensuring reliable results. This extended trial emulation with the competing risk analysis enables an unbiased estimation of treatment effects, along with the ability to interpret the effectiveness of treatment on all clinically important outcomes. Full article
(This article belongs to the Special Issue COVID-19 Prevention and Treatment: 2nd Edition)
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12 pages, 455 KiB  
Review
Hyperimmune Plasma and Immunoglobulins against COVID-19: A Narrative Review
by Massimo Franchini and Daniele Focosi
Life 2024, 14(2), 214; https://doi.org/10.3390/life14020214 - 01 Feb 2024
Viewed by 677
Abstract
Since late 2019, the new SARS-CoV-2 virus belonging to the Coronaviridae family has been responsible for COVID-19 pandemic, a severe acute respiratory syndrome. Several antiviral therapies, mostly derived from previous epidemics, were initially repurposed to fight this not rarely life-threatening respiratory illness. Among [...] Read more.
Since late 2019, the new SARS-CoV-2 virus belonging to the Coronaviridae family has been responsible for COVID-19 pandemic, a severe acute respiratory syndrome. Several antiviral therapies, mostly derived from previous epidemics, were initially repurposed to fight this not rarely life-threatening respiratory illness. Among them, however, the only specific antibody-based therapy available against SARS-CoV-2 infection during the first year of the pandemic was represented by COVID-19 convalescent plasma (CCP). CCP, collected from recovered individuals, contains high levels of polyclonal antibodies of different subclasses able to neutralize SARS-CoV-2 infection. Tens of randomized controlled trials have been conducted during the last three years of the pandemic to evaluate the safety and the clinical efficacy of CCP in both hospitalized and ambulatory COVID-19 patients, whose main results will be summarized in this narrative review. In addition, we will present the current knowledge on the development of anti-SARS-CoV-2 hyperimmune polyclonal immunoglobulins. Full article
(This article belongs to the Special Issue COVID-19 Prevention and Treatment: 2nd Edition)
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6 pages, 236 KiB  
Commentary
The Role of Convalescent Plasma in COVID-19: A Conclusive Post-Pandemic Review
by Massimo Franchini and Daniele Focosi
Life 2023, 13(12), 2322; https://doi.org/10.3390/life13122322 - 11 Dec 2023
Viewed by 706
Abstract
COVID-19 convalescent plasma (CCP) has represented the frontline response to the COVID-19 pandemic, largely because of encouraging historical evidences in previous pandemics, biological plausibility, and the initial unavailability of targeted antivirals. Unfortunately, investigator-initiated randomized clinical trials in 2020, launched during a stressful pandemic [...] Read more.
COVID-19 convalescent plasma (CCP) has represented the frontline response to the COVID-19 pandemic, largely because of encouraging historical evidences in previous pandemics, biological plausibility, and the initial unavailability of targeted antivirals. Unfortunately, investigator-initiated randomized clinical trials in 2020, launched during a stressful pandemic peak, were designed mostly at addressing the main unmet need, i.e., treating critically ill hospitalized patients who were unlikely to benefit from any antiviral therapy. The failure of most of these drugs, in combination with the lack of any sponsor, led to the false belief that convalescent plasma was useless. With the relaxing pandemic stages, evidences have instead mounted that, when administered properly (i.e., within 5 days from onset of symptoms and at high titers of neutralizing antibodies), CCP is as effective as other antivirals at preventing disease progression in outpatients, and also reduces mortality in hospitalized patients. Recently, the focus of clinical use has been on immunosuppressed patients with persistent seronegativity and infection, where a randomized clinical trial has shown a reduction in mortality. Lessons learnt during the COVID-19 pandemic will be of utmost importance for future pandemics. Full article
(This article belongs to the Special Issue COVID-19 Prevention and Treatment: 2nd Edition)
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