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A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Pharmacology".

Deadline for manuscript submissions: closed (31 May 2024) | Viewed by 11000

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Special Issue Editors

Dr. Kiriakos Karkoulias

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Guest Editor

Department of Respiratory Medicine, University Hospital of Patras, Patras, Greece
Interests: COVID-19; obstructive sleep apnea; lung cancer; COPD

Dr. Dimosthenis Lykouras

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Guest Editor

Department of Respiratory Medicine, University Hospital of Patras, Patras, Greece
Interests: asthma; COPD; sleep apnea; CPAP treatment; lung cancer; pharmacology; infectious diseases
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Special Issue Information

Dear Colleagues,

It is my pleasure to invite you to take part in the upcoming Special Issue entitled “COVID-19 Treatments and Therapeutics” in the Journal of Clinical Medicine (ISSN 2077-0383), an international, peer-reviewed, open access journal listed under PubMed on clinical and preclinical research with an impact factor of 3.9.

In recent years, the COVID-19 pandemic has spread throughout the world and has put a lot of pressure on health systems. Much attention has been paid towards the development of safe and effective ways to either prevent infection or treat patients. In a time-constricted and competitive environment, a number of new treatments and therapeutic options have already been developed, and others are in the pipeline.

This Special Issue is open to original research papers, case series, and reviews. The objective of this Special Issue is to provide expert analysis of the current and evolving treatments and other therapeutic modalities for COVID-19. We are particularly interested in manuscripts that report the importance of preventing options against SARS-CoV-2 (vaccines, protective measures), available treatments for COVID-19 patients, and the importance of post-COVID follow-up. The main topics include, but are not limited to: (1) vaccines against SARS-CoV-2; (2) drugs for patients at home; (3) treatments for hospitalized patients; (4) oxygen delivery systems; (5) treatment options for the critically ill; (6) post-COVID management; and (7) treating interstitial lung disease due to COVID-19.

Along with the journal staff, I will personally be available to assist you in preparing your manuscript for this Special Issue. International collaborations and knowledge sharing are highly encouraged. You are welcome to contact me directly with any questions you may have. Thank you in advance.

Dr. Kiriakos Karkoulias
Dr. Dimosthenis Lykouras
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Clinical Medicine is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

COVID-19
vaccines
remdesivir
molnupiravir
post-COVID
high-flow nasal oxygen
NIV
CPAP

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Published Papers (6 papers)

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Research

17 pages, 582 KiB

Open AccessArticle

Safety of High-Dose Vitamin C in Non-Intensive Care Hospitalized Patients with COVID-19: An Open-Label Clinical Study

by Salvatore Corrao, Massimo Raspanti, Federica Agugliaro, Francesco Gervasi, Francesca Di Bernardo, Giuseppe Natoli and Christiano Argano

J. Clin. Med. 2024, 13(13), 3987; https://doi.org/10.3390/jcm13133987 - 8 Jul 2024

Cited by 1 | Viewed by 2524

Abstract

Background: Vitamin C has been used as an antioxidant and has been proven effective in boosting immunity in different diseases, including coronavirus disease (COVID-19). An increasing awareness was directed to the role of intravenous vitamin C in COVID-19. Methods: In this study, we aimed to assess the safety of high-dose intravenous vitamin C added to the conventional regimens for patients with different stages of COVID-19. An open-label clinical trial was conducted on patients with COVID-19. One hundred four patients underwent high-dose intravenous administration of vitamin C (in addition to conventional therapy), precisely 10 g in 250 cc of saline solution in slow infusion (60 drops/min) for three consecutive days. At the same time, 42 patients took the standard-of-care therapy. Results: This study showed the safety of high-dose intravenous administration of vitamin C. No adverse reactions were found. When we evaluated the renal function indices and estimated the glomerular filtration rate (eGRF, calculated with the CKD-EPI Creatinine Equation) as the main side effect and contraindication related to chronic renal failure, no statistically significant differences between the two groups were found. High-dose vitamin C treatment was not associated with a statistically significant reduction in mortality and admission to the intensive care unit, even if the result was bound to the statistical significance. On the contrary, age was independently associated with admission to the intensive care unit and in-hospital mortality as well as noninvasive ventilation (N.I.V.) and continuous positive airway pressure (CPAP) (OR 2.17, 95% CI 1.41–3.35; OR 7.50, 95% CI 1.97–28.54; OR 8.84, 95% CI 2.62–29.88, respectively). When considering the length of hospital stay, treatment with high-dose vitamin C predicts shorter hospitalization (OR −4.95 CI −0.21–−9.69). Conclusions: Our findings showed that an intravenous high dose of vitamin C is configured as a safe and promising therapy for patients with moderate to severe COVID-19. Full article

(This article belongs to the Special Issue COVID-19 Treatments and Therapeutics)

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19 pages, 1772 KiB

Open AccessArticle

Association between Dexmedetomidine Use and Mortality in Patients with COVID-19 Receiving Invasive Mechanical Ventilation: A U.S. National COVID Cohort Collaborative (N3C) Study

by John L. Hamilton, Rachel Baccile, Thomas J. Best, Pankaja Desai, Alan Landay, Juan C. Rojas, Markus A. Wimmer, Robert A. Balk and on behalf of the N3C Consortium

J. Clin. Med. 2024, 13(12), 3429; https://doi.org/10.3390/jcm13123429 - 12 Jun 2024

Viewed by 1074

Abstract

(1) Background/Objectives: Dexmedetomidine is a sedative for patients receiving invasive mechanical ventilation (IMV) that previous single-site studies have found to be associated with improved survival in patients with COVID-19. The reported clinical benefits include dampened inflammatory response, reduced respiratory depression, reduced agitation and delirium, improved preservation of responsiveness and arousability, and improved hypoxic pulmonary vasoconstriction and ventilation-perfusion ratio. Whether improved mortality is evident in large, multi-site COVID-19 data is understudied. (2) Methods: The association between dexmedetomidine use and mortality in patients with COVID-19 receiving IMV was assessed. This retrospective multi-center cohort study utilized patient data in the United States from health systems participating in the National COVID Cohort Collaborative (N3C) from 1 January 2020 to 3 November 2022. The primary outcome was 28-day mortality rate from the initiation of IMV. Propensity score matching adjusted for differences between the group with and without dexmedetomidine use. Adjusted hazard ratios (aHRs) for 28-day mortality were calculated using multivariable Cox proportional hazards models with dexmedetomidine use as a time-varying covariate. (3) Results: Among the 16,357,749 patients screened, 3806 patients across 17 health systems met the study criteria. Mortality was lower with dexmedetomidine use (aHR, 0.81; 95% CI, 0.73–0.90; p < 0.001). On subgroup analysis, mortality was lower with earlier dexmedetomidine use—initiated within the median of 3.5 days from the start of IMV—(aHR, 0.67; 95% CI, 0.60–0.76; p < 0.001) as well as use prior to standard, widespread use of dexamethasone for patients on respiratory support (prior to 30 July 2020) (aHR, 0.54; 95% CI, 0.42–0.69; p < 0.001). In a secondary model that was restricted to 576 patients across six health system sites with available PaO₂/FiO₂ data, mortality was not lower with dexmedetomidine use (aHR 0.95, 95% CI, 0.72–1.25; p = 0.73); however, on subgroup analysis, mortality was lower with dexmedetomidine use initiated earlier than the median dexmedetomidine start time after IMV (aHR, 0.72; 95% CI, 0.53–0.98; p = 0.04) and use prior to 30 July 2020 (aHR, 0.22; 95% CI, 0.06–0.78; p = 0.02). (4) Conclusions: Dexmedetomidine use was associated with reduced mortality in patients with COVID-19 receiving IMV, particularly when initiated earlier, rather than later, during the course of IMV as well as use prior to the standard, widespread usage of dexamethasone during respiratory support. These particular findings might suggest that the associated mortality benefit with dexmedetomidine use is tied to immunomodulation. However, further research including a large randomized controlled trial is warranted to evaluate the potential mortality benefit of DEX use in COVID-19 and evaluate the physiologic changes influenced by DEX that may enhance survival. Full article

(This article belongs to the Special Issue COVID-19 Treatments and Therapeutics)

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13 pages, 2089 KiB

Open AccessArticle

Antithrombotic Use Patterns in COVID-19 Patients from Spain: A Real-World Data Study

by Karen Lizzette Ramirez-Cervantes, Salvador Campillo-Morales, Patricia García-Poza, Manuel Quintana-Díaz and Consuelo Huerta-Álvarez

J. Clin. Med. 2024, 13(8), 2403; https://doi.org/10.3390/jcm13082403 - 20 Apr 2024

Viewed by 1045

Abstract

Antithrombotics have been widely used to treat and prevent COVID-19-related thrombosis; however, studies on their use at population levels are limited. We aimed to describe antithrombotic use patterns during the pandemic in Spanish primary care and hospital-admitted patients with COVID-19. Methods: A real-world data study was performed. Data were obtained from BIFAP’s electronic health records. We investigated the antithrombotic prescriptions made within ±14 days after diagnosis between March 2020 and February 2022, divided their use into prior and new/naive groups, and reported their post-discharge use. Results: We included 882,540 individuals (53.4% women), of whom 78,499 were hospitalized. The median age was 44.7 (IQR 39–59). Antithrombotics were prescribed in 37,183 (4.6%) primary care subjects and 42,041 (53.6%) hospital-admitted patients, of whom 7505 (20.2%) and 20,300 (48.3%), respectively, were naive users. Prior users were older and had more comorbidities than new users. Enoxaparin was the most prescribed antithrombotic in hospitals, with higher prescription rates in new than prior users (2348.2, IQR 2390–3123.1 vs. 1378, IQR 1162–1751.6 prescriptions per 10,000 cases, p = 0.002). In primary care, acetylsalicylic acid was the most used antithrombotic, with higher use rates in prior than in naïve users. Post-discharge use occurred in 6686 (15.9%) subjects (median use = 10 days, IQR 9-30). Conclusions: Our study identified a consensus on prescribing antithrombotics in COVID-19 patients, but with low use rates in hospitals. Full article

(This article belongs to the Special Issue COVID-19 Treatments and Therapeutics)

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25 pages, 5150 KiB

Open AccessArticle

Personalized Assessment of Mortality Risk and Hospital Stay Duration in Hospitalized Patients with COVID-19 Treated with Remdesivir: A Machine Learning Approach

by Antonio Ramón, Andrés Bas, Santiago Herrero, Pilar Blasco, Miguel Suárez and Jorge Mateo

J. Clin. Med. 2024, 13(7), 1837; https://doi.org/10.3390/jcm13071837 - 22 Mar 2024

Cited by 2 | Viewed by 1308

Abstract

Background: Despite advancements in vaccination, early treatments, and understanding of SARS-CoV-2, its impact remains significant worldwide. Many patients require intensive care due to severe COVID-19. Remdesivir, a key treatment option among viral RNA polymerase inhibitors, lacks comprehensive studies on factors associated with its effectiveness. Methods: We conducted a retrospective study in 2022, analyzing data from 252 hospitalized COVID-19 patients treated with remdesivir. Six machine learning algorithms were compared to predict factors influencing remdesivir’s clinical benefits regarding mortality and hospital stay. Results: The extreme gradient boost (XGB) method showed the highest accuracy for both mortality (95.45%) and hospital stay (94.24%). Factors associated with worse outcomes in terms of mortality included limitations in life support, ventilatory support needs, lymphopenia, low albumin and hemoglobin levels, flu and/or coinfection, and cough. For hospital stay, factors included vaccine doses, lung density, pulmonary radiological status, comorbidities, oxygen therapy, troponin, lactate dehydrogenase levels, and asthenia. Conclusions: These findings underscore XGB’s effectiveness in accurately categorizing COVID-19 patients undergoing remdesivir treatment. Full article

(This article belongs to the Special Issue COVID-19 Treatments and Therapeutics)

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15 pages, 753 KiB

Open AccessArticle

Effects of Aerobic Exercise Therapy through Nordic Walking Program in Lactate Concentrations, Fatigue and Quality-of-Life in Patients with Long-COVID Syndrome: A Non-Randomized Parallel Controlled Trial

by Sofía Laguarta-Val, David Varillas-Delgado, Ángel Lizcano-Álvarez, Alberto Molero-Sánchez, Alberto Melian-Ortiz, Roberto Cano-de-la-Cuerda and Carmen Jiménez-Antona

J. Clin. Med. 2024, 13(4), 1035; https://doi.org/10.3390/jcm13041035 - 11 Feb 2024

Cited by 4 | Viewed by 2484

Abstract

Background: Long-COVID syndrome comprises a variety of signs and symptoms that develop during or after infection with COVID-19 which may affect the physical capabilities. However, there is a lack of studies investigating the effects of Long-COVID syndrome in sport capabilities after suffering from COVID-19 infection. The purpose of the study was to evaluate and compare lactate concentration and quality of life (QoL) in patients with Long-COVID with those who have not developed non-Long-COVID during Nordic walking exercise therapy. Methods: Twenty-nine patients (25.5 ± 7.1 years) took part in a non-randomized controlled trial, divided into two groups: a Long-COVID group (n = 16) and a non-Long-COVID control (n = 13). Patients were confirmed as having Long-COVID syndrome if they experienced fatigue or tiredness when performing daily activities and worsening of symptoms after vigorous physical or mental activity. All participants underwent a 12-week Nordic Walking program. Lactate concentration after exercise and distance covered during all sessions were measured. Pre- and Long-Nordic Walking program, the Modified Fatigue Impact Scale (MFIS), the Short Form 36 Health Survey (SF-36), and EURO QoL-5D (EQ-ED) were administered to assess fatigue and quality of life, respectively. Results: There was a lactate concentration effect between groups (F = 5.604; p = 0.024). However, there was no significant effect as a result of the session (F = 3.521; p = 0.121) with no interaction of group × session (F = 1.345; p = 0.414). The group main effect (F = 23.088; p < 0.001), time effect (F = 6.625; p = 0.026), and group × time (F = 4.632; p = 0.002) interaction on the SF-36 scale were noted. Also, there were a significant group main effect (F = 38.372; p < 0.001), time effect (F = 12.424; p = 0.005), and group × time interaction (F = 4.340; p = 0.014) on EQ-5D. However, there was only a significant group main effect (F = 26.235; p < 0.001) with no effect on time (F = 2.265; p = 0.160) and group × time (F = 1.584; p = 0.234) interaction on the MFIS scale. Conclusions: The Long-COVID group showed higher lactate concentration compared with the control group during the 12 weeks of the Nordic Walking program. The Long-COVID group presented a decrease in fatigue with respect to the control group according to the MFIS scale, as well as improvement in quality of life after aerobic exercise therapy. Full article

(This article belongs to the Special Issue COVID-19 Treatments and Therapeutics)

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17 pages, 323 KiB

Open AccessArticle

Extracorporeal Photopheresis as a Possible Therapeutic Approach for Adults with Severe and Critical COVID-19 Non-Responsive to Standard Treatment: A Pilot Investigational Study

by Bálint Gergely Szabó, Péter Reményi, Szabolcs Tasnády, Dorina Korózs, László Gopcsa, Marienn Réti, Andrea Várkonyi, János Sinkó, Botond Lakatos, János Szlávik, Gabriella Bekő, Ilona Bobek and István Vályi-Nagy

J. Clin. Med. 2023, 12(15), 5000; https://doi.org/10.3390/jcm12155000 - 29 Jul 2023

Viewed by 1841

Abstract

Background: The optimal approach for adult patients hospitalized with severe and critical coronavirus disease 2019 (COVID-19), non-responsive to antiviral and immunomodulatory drugs, is not well established. Our aim was to evaluate feasibility and safety of extracorporeal photopheresis (ECP) in this setting. Methods: A prospective, single-center investigational study was performed between 2021 and 2022 at a tertiary referral center for COVID-19. Patients diagnosed with COVID-19 were screened, and cases with severe or critical disease fulfilling pre-defined clinical and biochemical criteria of non-response for >5 days, despite remdesivir, dexamethasone and immunomodulation (tocilizumab, baricitinib, ruxolitinib), were consecutively enrolled. After patient inclusion, two ECP sessions on two consecutive days per week for 2 weeks were applied. Patients were followed-up per protocol from study inclusion, and clinical, virological and radiological outcomes were assessed at the end of treatment (EOT) +28 days. Results: A total of seven patients were enrolled. At inclusion, four out of seven (57.1%) were admitted to the ICU, all patients had ongoing cytokine storm. Additionally, 3/7 (42.9%) had radiological progression on chest CT. At EOT+28 days, 2/7 (28.6%) patients died due to non-ECP-related causes. Among the survivors, no additional requirement for intensive care unit admission or radiological progression was observed, and invasive mechanical ventilation could be weaned off in 1/5 (20.0%). All patients achieved whole-blood SARS-CoV-2 RNAemia clearance, while 3/7 (42.9%) no longer showed detectable respiratory SARS-CoV-2 RNA. According to immune biomarker profiling, ECP mainly facilitated a decrease in plasma IL-6 and IL-17A levels, as well as the physiological regeneration of peripheral blood immunocyte subpopulations, notably CD8+/CD45RO+ memory T-cells. No safety signals were identified. Conclusions: ECP appears to be a safe and feasible option for adults hospitalized with severe or critical COVID-19 who do not respond to pharmacological interventions. Further trial data are warranted to assess its optimal use. Trial registration: ClinicalTrials.gov NCT05882331 (retrospectively registered). Full article

(This article belongs to the Special Issue COVID-19 Treatments and Therapeutics)

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