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Viruses
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COVID-19 Pharmacotherapy
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COVID-19 Pharmacotherapy

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "SARS-CoV-2 and COVID-19".

Deadline for manuscript submissions: closed (30 April 2023) | Viewed by 37380

Special Issue Editors

Dr. Karolina Akinosoglou

E-Mail Website
Guest Editor
Department of Internal Medicine, University of Patras, 26504 Patras, Greece
Interests: HIV, sepsis; COVID-19; multi-drug-resistant pathogens; urogenital infections; immunology of infection
Special Issues, Collections and Topics in MDPI journals
Dr. George T. Dimopoulos

E-Mail Website
Guest Editor
ICU, 1st Department of Pulmonary Medicine, Sotiria Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece
Interests: pulmonology; infection in ICU; mycosis in ICU
Prof. Dr. Wei Xu

E-Mail Website
Guest Editor
Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China
Interests: antiviral drug screening and development; structural pharmacology of antiviral drug; virus-host interaction

Special Issue Information

Dear Colleagues,

The COVID-19 pandemic represents a major challenge worldwide. It caused severe morbidity and mortality, posing a significant burden to our health systems around the globe. Initial bewilderment was followed by massive and determined efforts and investments, on behalf of the scientific society, as well as, pharmaceutical industry, to tackle this new disease. In parallel to disease prevention, developing a therapeutic armamentarium remained one of the main pillars of COVID-19 management. Since the end of 2019, clinical practice has come a long way through various regimens, initially immaturely adopted with enthusiasm, then abandoned in disappointment not much later due to unproven efficacy, safety concerns, but also in view of more in-depth understanding of disease pathogenesis. Even though therapeutic guidelines are currently available, much more is to be explored, since no therapy represents the golden standard to cope with mild or severe disease.  

We are pleased to invite you to the Special Issue of ‘Viruses: COVID-19 pharmacotherapy. Following 2.5 years within COVID-19 pandemic’. The Special Issue aims to review recent developments in the field of SARS-CoV-2 management and highlight existing advances, controversies, but also future directions in therapeutic modalities and supporting algorithms.  In this Special Issue, original research articles and reviews are welcome.

We look forward to receiving your contributions.

Dr. Karolina Akinosoglou
Dr. George Dimopoulos
Prof. Dr. Wei Xu
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. Viruses is an international peer-reviewed open access monthly 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
  • SARS-CoV-2
  • remdesivir
  • anakinra
  • antiviral therapy
  • immunomodulatory agents
  • tocilizumab
  • dexamethasone
  • corticosteroids
  • molnupiravir
  • nirmetrevir/ritonavir
  • monoclonal antibodies

Published Papers (18 papers)

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Editorial

Jump to: Research, Review

3 pages, 192 KiB  
Editorial
COVID-19 Pharmacotherapy: A Summary of Key Advances and Insights from the Special Issue
by Georgios Schinas and Karolina Akinosoglou
Viruses 2023, 15(12), 2286; https://doi.org/10.3390/v15122286 - 22 Nov 2023
Viewed by 1039
Abstract
The COVID-19 pandemic has presented unprecedented challenges for healthcare systems worldwide [...] Full article
(This article belongs to the Special Issue COVID-19 Pharmacotherapy)

Research

Jump to: Editorial, Review

18 pages, 3354 KiB  
Article
Phenothiazines Inhibit SARS-CoV-2 Entry through Targeting Spike Protein
by Taizhen Liang, Shiqi Xiao, Ziyao Wu, Xi Lv, Sen Liu, Meilin Hu, Guojie Li, Peiwen Li and Xiancai Ma
Viruses 2023, 15(8), 1666; https://doi.org/10.3390/v15081666 - 31 Jul 2023
Cited by 2 | Viewed by 1010
Abstract
Novel coronavirus disease 2019 (COVID-19), a respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has brought an unprecedented public health crisis and continues to threaten humanity due to the persistent emergence of new variants. Therefore, developing more effective and broad-spectrum [...] Read more.
Novel coronavirus disease 2019 (COVID-19), a respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has brought an unprecedented public health crisis and continues to threaten humanity due to the persistent emergence of new variants. Therefore, developing more effective and broad-spectrum therapeutic and prophylactic drugs against infection by SARS-CoV-2 and its variants, as well as future emerging CoVs, is urgently needed. In this study, we screened several US FDA-approved drugs and identified phenothiazine derivatives with the ability to potently inhibit the infection of pseudotyped SARS-CoV-2 and distinct variants of concern (VOCs), including B.1.617.2 (Delta) and currently circulating Omicron sublineages XBB and BQ.1.1, as well as pseudotyped SARS-CoV and MERS-CoV. Mechanistic studies suggested that phenothiazines predominantly inhibited SARS-CoV-2 pseudovirus (PsV) infection at the early stage and potentially bound to the spike (S) protein of SARS-CoV-2, which may prevent the proteolytic cleavage of the S protein, thereby exhibiting inhibitory activity against SARS-CoV-2 infection. In summary, our findings suggest that phenothiazines can serve as a potential broad-spectrum therapeutic drug for the treatment of SARS-CoV-2 infection as well as the infection of future emerging human coronaviruses (HCoVs). Full article
(This article belongs to the Special Issue COVID-19 Pharmacotherapy)
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15 pages, 847 KiB  
Article
Impact of Alteplase on Mortality in Critically Ill Patients with COVID-19 and Pulmonary Embolism
by Oleksandr Valentynovych Oliynyk, Marta Rorat, Serhij Oleksandrovych Solyarik, Vitaliy Andrijovych Lukianchuk, Serhij Oleksandrovych Dubrov, Vitaliy Hrygorovych Guryanov, Yanina Volodymyrivna Oliynyk, Svitlana Mykolaivna Yaroslavskaya, Roman Szalast and Wojciech Barg
Viruses 2023, 15(7), 1513; https://doi.org/10.3390/v15071513 - 7 Jul 2023
Cited by 3 | Viewed by 1306
Abstract
COVID-19 is an independent risk factor for pulmonary embolism (PE). Little is known about alteplase therapy in this patient group. A retrospective study analyzed 74 patients with PE and acute respiratory distress syndrome (ARDS) due to COVID-19 who were hospitalized in the intensive [...] Read more.
COVID-19 is an independent risk factor for pulmonary embolism (PE). Little is known about alteplase therapy in this patient group. A retrospective study analyzed 74 patients with PE and acute respiratory distress syndrome (ARDS) due to COVID-19 who were hospitalized in the intensive care unit in 2021. Patients with or without confirmed right heart thrombi (RHT) were treated with unfractionated heparin or alteplase. The mortality rate in patients with RHT treated with heparin was 100% compared to 37.9% and 55.2% in those treated with alteplase without RHT and alteplase with RHT, respectively. The risk of death in the alteplase group increased with delayed thrombolysis (p = 0.009, odds ratio (OR) = 1.73 95% CI (confidence interval) 1.14–2.62), increased D-dimer concentration (p = 0.02, OR = 1.43 95% CI 1.06–1.93), and decreased PaO2/FiO2 ratio (p = 0.001, OR = 0.56 95% CI 0.41–0.78). The receiver operating characteristic method determined that a 1-day delay in thrombolytic treatment, D-dimer concentration >5.844 mg/L, and PaO2/FiO2 <144 mmHg predicted a fatal outcome. The risk of death in patients with severe COVID-19 with ARDS and PE increases with higher D-dimer levels, decreased PaO2/FiO2, and delayed thrombolytic treatment. Thrombolysis seems to be treatment of choice in severe COVID-19 with PE and RHT. It should be carried out as soon as possible after the diagnosis is established. Full article
(This article belongs to the Special Issue COVID-19 Pharmacotherapy)
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23 pages, 3878 KiB  
Article
Glycemic Dysregulation, Inflammation and Disease Outcomes in Patients Hospitalized with COVID-19: Beyond Diabetes and Obesity
by Angelos Liontos, Dimitrios Biros, Aikaterini Kavakli, Rafail Matzaras, Ilias Tsiakas, Lazaros Athanasiou, Valentini Samanidou, Revekka Konstantopoulou, Ioannis Vagias, Aikaterini Panteli, Christiana Pappa, Nikolaos-Gavriel Kolios, Maria Nasiou, Eleni Pargana, Haralampos Milionis and Eirini Christaki
Viruses 2023, 15(7), 1468; https://doi.org/10.3390/v15071468 - 28 Jun 2023
Cited by 2 | Viewed by 1232
Abstract
Introduction: During the COVID-19 pandemic, diabetes mellitus (DM) and obesity were associated with high rates of morbidity and mortality. The aim of this study was to investigate the relationship between markers of inflammation, disease severity, insulin resistance, hyperglycemia, and outcomes in COVID-19 patients [...] Read more.
Introduction: During the COVID-19 pandemic, diabetes mellitus (DM) and obesity were associated with high rates of morbidity and mortality. The aim of this study was to investigate the relationship between markers of inflammation, disease severity, insulin resistance, hyperglycemia, and outcomes in COVID-19 patients with and without diabetes and obesity. Materials and Methods: Epidemiological, clinical, and laboratory data were collected from the University Hospital of Ioannina COVID-19 Registry and included hospitalized patients from March 2020 to December 2022. The study cohort was divided into three subgroups based on the presence of DM, obesity, or the absence of both. Results: In diabetic patients, elevated CRP, IL-6, TRG/HDL-C ratio, and TyG index, severe pneumonia, and hyperglycemia were associated with extended hospitalization. Increased IL-6, NLR, and decreased PFR were associated with a higher risk of death. In the obese subgroup, lower levels of PFR were associated with longer hospitalization and a higher risk of death, while severe lung disease and hyperglycemia were associated with extended hospitalization. In patients without DM or obesity severe pneumonia, NLR, CRP, IL-6, insulin resistance indices, and hyperglycemia during hospitalization were associated with longer hospitalization. Conclusion: Inflammatory markers and disease severity indices were strongly associated with disease outcomes and hyperglycemia across all subgroups. Full article
(This article belongs to the Special Issue COVID-19 Pharmacotherapy)
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17 pages, 2198 KiB  
Article
Efficacy of Remdesivir and Neutralizing Monoclonal Antibodies in Monotherapy or Combination Therapy in Reducing the Risk of Disease Progression in Elderly or Immunocompromised Hosts Hospitalized for COVID-19: A Single Center Retrospective Study
by Davide Fiore Bavaro, Lucia Diella, Alessandra Belati, Giuliana Metrangolo, Laura De Santis, Vito Spada, Michele Camporeale, Angelo Dargenio, Gaetano Brindicci, Flavia Balena, Deborah Fiordelisi, Fabio Signorile, Giacomo Loseto, Crescenza Pasciolla, Carla Minoia, Immacolata Attolico, Tommasina Perrone, Simona Simone, Maria Rendina, Nicoletta Giovine, Francesco Di Gennaro, Pellegrino Musto, Attilio Guarini, Alfredo Di Leo, Loreto Gesualdo, Maria Dell’Aera and Annalisa Saracinoadd Show full author list remove Hide full author list
Viruses 2023, 15(5), 1199; https://doi.org/10.3390/v15051199 - 19 May 2023
Cited by 4 | Viewed by 1540
Abstract
Introduction: Remdesivir (REM) and monoclonal antibodies (mAbs) could alleviate severe COVID-19 in at-risk outpatients. However, data on their use in hospitalized patients, particularly in elderly or immunocompromised hosts, are lacking. Methods: All consecutive patients hospitalized with COVID-19 at our unit from 1 July [...] Read more.
Introduction: Remdesivir (REM) and monoclonal antibodies (mAbs) could alleviate severe COVID-19 in at-risk outpatients. However, data on their use in hospitalized patients, particularly in elderly or immunocompromised hosts, are lacking. Methods: All consecutive patients hospitalized with COVID-19 at our unit from 1 July 2021 to 15 March 2022 were retrospectively enrolled. The primary outcome was the progression to severe COVID-19 (P/F < 200). Descriptive statistics, a Cox univariate–multivariate model, and an inverse probability treatment-weighted (IPTW) analysis were performed. Results: Overall, 331 subjects were included; their median (q1–q3) age was 71 (51–80) years, and they were males in 52% of the cases. Of them, 78 (23%) developed severe COVID-19. All-cause in-hospital mortality was 14%; it was higher in those with disease progression (36% vs. 7%, p < 0.001). REM and mAbs resulted in a 7% (95%CI = 3–11%) and 14% (95%CI = 3–25%) reduction in the risk of severe COVID-19, respectively, after adjusting the analysis with the IPTW. In addition, by evaluating only immunocompromised hosts, the combination of REM and mAbs was associated with a significantly lower incidence of severe COVID-19 (aHR = 0.06, 95%CI = 0.02–0.77) when compared with monotherapy. Conclusions: REM and mAbs may reduce the risk of COVID-19 progression in hospitalized patients. Importantly, in immunocompromised hosts, the combination of mAbs and REM may be beneficial. Full article
(This article belongs to the Special Issue COVID-19 Pharmacotherapy)
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11 pages, 1630 KiB  
Article
Efficacy of Sildenafil in Patients with Severe COVID-19 and Pulmonary Arterial Hypertension
by Oleksandr Valentynovych Oliynyk, Marta Rorat, Olena Vadymivna Strepetova, Serhij Oleksandrovych Dubrov, Vitaliy Grygorovych Guryanov, Yanina Volodymyrivna Oliynyk, Oleksii Serhijovych Kulivets, Anna Ślifirczyk and Wojciech Barg
Viruses 2023, 15(5), 1157; https://doi.org/10.3390/v15051157 - 11 May 2023
Cited by 2 | Viewed by 2137
Abstract
Pulmonary arterial hypertension (PAH) is common in severe coronavirus disease 2019 (COVID-19) and worsens the prognosis. Sildenafil, a phosphodiesterase-5 inhibitor, is approved for PAH treatment but little is known about its efficacy in cases of severe COVID-19 with PAH. This study aimed to [...] Read more.
Pulmonary arterial hypertension (PAH) is common in severe coronavirus disease 2019 (COVID-19) and worsens the prognosis. Sildenafil, a phosphodiesterase-5 inhibitor, is approved for PAH treatment but little is known about its efficacy in cases of severe COVID-19 with PAH. This study aimed to investigate the clinical efficacy of sildenafil in patients with severe COVID-19 and PAH. Intensive care unit (ICU) patients were randomly assigned to receive sildenafil or a placebo, with 75 participants in each group. Sildenafil was administered orally at 0.25 mg/kg t.i.d. for one week in a placebo-controlled, double-blind manner as an add-on therapy alongside the patient’s routine treatment. The primary endpoint was one-week mortality, and the secondary endpoints were the one-week intubation rate and duration of ICU stay. The mortality rate was 4% vs. 13.3% (p = 0.078), the intubation rate was 8% and 18.7% (p = 0.09), and the length of ICU stay was 15 vs. 19 days (p < 0.001) for the sildenafil and placebo groups, respectively. If adjusted for PAH, sildenafil treatment significantly reduced mortality and intubation risks: OR = 0.21 (95% CI: 0.05–0.89) and OR = 0.26 (95% CI: 0.08–0.86), respectively. Sildenafil demonstrated some clinical efficacy in patients with severe COVID-19 and PAH and should be considered as an add-on therapy in these patients. Full article
(This article belongs to the Special Issue COVID-19 Pharmacotherapy)
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13 pages, 287 KiB  
Article
The Antiviral Effect of Nirmatrelvir/Ritonavir during COVID-19 Pandemic Real-World Data
by Vasilios Petrakis, Petros Rafailidis, Grigorios Trypsianis, Dimitrios Papazoglou and Periklis Panagopoulos
Viruses 2023, 15(4), 976; https://doi.org/10.3390/v15040976 - 16 Apr 2023
Cited by 7 | Viewed by 2044
Abstract
Introduction: Vaccination against SARS-CoV-2 and the prevalence of Omicron variants have reduced the risk of the severe clinical progress of COVID-19. However, the risk of breakthrough infections has increased, and early administration of an effective antiviral treatment is significant in order to prevent [...] Read more.
Introduction: Vaccination against SARS-CoV-2 and the prevalence of Omicron variants have reduced the risk of the severe clinical progress of COVID-19. However, the risk of breakthrough infections has increased, and early administration of an effective antiviral treatment is significant in order to prevent the severe progression of COVID-19 in vulnerable patients with comorbidities. Patients and methods: Adults with confirmed SARS-CoV-2 infection were included in a matched-pair retrospective study based on age, gender, comorbidities and vaccination status. They were divided into two groups: group A (n = 200) consisted of outpatients at increased risk of severe clinical progress who were treated with nirmatrelvir/ritonavir and group B (n = 200) consisted of non-hospitalized patients who did not receive antiviral treatment. Demographic data, clinical outcome (death, intubation), days of hospitalization, time for recovery, adverse events and treatment compliance were reported. Results: The median age (75.24 ± 13.12 years in the study group and 76.91 ± 14.02 years in the comparison group) and the proportion of males (59% vs. 60.5%, respectively) were similar between the two groups. A total of 6.5% of patients in group A and 10.5% in group B were unvaccinated against SARS-CoV-2. Three patients from group A (1.5%) and one hundred eleven (55.5%) from group B required hospitalization. The duration of hospitalization (3 days vs. 10 days in group B, p < 0.001) and the total time needed for recovery (5 days vs. 9 days, p < 0.001) was shorter in the study group. A rebound of SARS-CoV-2 infection within 8–12 days after diagnosis was documented in 6.5% of patients in group A and 8% of patients in group B. Conclusion: Oral treatment with nirmatrelvir/ritonavir in high-risk non-hospitalized patients was safe and effective in preventing the severe clinical progress of COVID-19 pneumonia. Early administration of antiviral agents in vulnerable outpatients combined with a full vaccination scheme is significant in order to avoid hospitalization and severe clinical outcomes. Full article
(This article belongs to the Special Issue COVID-19 Pharmacotherapy)
12 pages, 296 KiB  
Article
Convalescent Plasma Treatment of Patients Previously Treated with B-Cell-Depleting Monoclonal Antibodies Suffering COVID-19 Is Associated with Reduced Re-Admission Rates
by Petros Ioannou, Athanasios Katsigiannis, Ioanna Papakitsou, Ioannis Kopidakis, Eirini Makraki, Dimitris Milonas, Theodosios D. Filippatos, George Sourvinos, Marina Papadogiannaki, Evaggelia Lydaki, Georgios Chamilos and Diamantis P. Kofteridis
Viruses 2023, 15(3), 756; https://doi.org/10.3390/v15030756 - 15 Mar 2023
Cited by 1 | Viewed by 1874
Abstract
Patients receiving treatment with B-cell-depleting monoclonal antibodies, such as anti-CD20 monoclonal antibodies, such as rituximab and obinutuzumab, either for hematological disease or another diagnosis, such as a rheumatological disease, are at an increased risk for medical complications and mortality from COVID-19. Since inconsistencies [...] Read more.
Patients receiving treatment with B-cell-depleting monoclonal antibodies, such as anti-CD20 monoclonal antibodies, such as rituximab and obinutuzumab, either for hematological disease or another diagnosis, such as a rheumatological disease, are at an increased risk for medical complications and mortality from COVID-19. Since inconsistencies persist regarding the use of convalescent plasma (CP), especially in the vulnerable patient population that has received previous treatment with B-cell-depleting monoclonal antibodies, further studies should be performed in thisdirection. The aim of the present study was to describe the characteristics of patients with previous use of B-cell-depleting monoclonal antibodies and describe the potential beneficial effects of CP use in terms of mortality, ICU admission and disease relapse. In this retrospective cohort study, 39 patients with previous use of B-cell-depleting monoclonal antibodies hospitalized in the COVID-19 department of a tertiary hospital in Greece were recorded and evaluated. The mean age was 66.3 years and 51.3% were male. Regarding treatment for COVID-19, remdesivir was used in 89.7%, corticosteroids in 94.9% and CP in 53.8%. In-hospital mortality was 15.4%. Patients who died were more likely to need ICU admission and also had a trend towards a longer hospital stay, even though the last did not reach statistical significance. Patients treated with CP had a lower re-admission rate for COVID-19 after discharge. Further studies should be performed to identify the role of CP in patients with treatment with B-cell-depleting monoclonal antibodies suffering from COVID-19. Full article
(This article belongs to the Special Issue COVID-19 Pharmacotherapy)
11 pages, 435 KiB  
Article
Real-World Study on Effectiveness of Molnupiravir and Nirmatrelvir–Ritonavir in Unvaccinated Patients with Chronic Respiratory Diseases with Confirmed SARS-CoV-2 Infection Managed in Out-Patient Setting
by Wang Chun Kwok, Man Fung Tsoi, Sze Him Isaac Leung, Chung Ki Tsui, Terence Chi Chun Tam, James Chung Man Ho, David Chi Leung Lam, Mary Sau Man Ip and Pak Leung Ho
Viruses 2023, 15(3), 610; https://doi.org/10.3390/v15030610 - 23 Feb 2023
Cited by 8 | Viewed by 2114
Abstract
While molnupiravir (MOV) and nirmatrelvir–ritonavir (NMV-r) were developed for treatment of mild to moderate COVID-19 infection, there has been a lack of data on the efficacy among unvaccinated adult patients with chronic respiratory diseases, including asthma, chronic obstructive pulmonary disease (COPD) and bronchiectasis. [...] Read more.
While molnupiravir (MOV) and nirmatrelvir–ritonavir (NMV-r) were developed for treatment of mild to moderate COVID-19 infection, there has been a lack of data on the efficacy among unvaccinated adult patients with chronic respiratory diseases, including asthma, chronic obstructive pulmonary disease (COPD) and bronchiectasis. A territory-wide retrospective cohort study was conducted in Hong Kong to investigate the efficacy of MOV and NMV-r against severe outcomes of COVID-19 in unvaccinated adult patients with chronic respiratory diseases. A total of 3267 patients were included. NMV-r was effective in preventing respiratory failure (66.6%; 95% CI, 25.6–85.0%, p = 0.007), severe respiratory failure (77.0%; 95% CI, 6.9–94.3%, p = 0.039) with statistical significance, and COVID-19 related hospitalization (43.9%; 95% CI, −1.7–69.0%, p = 0.057) and in-hospital mortality (62.7%; 95% CI, −0.6–86.2, p = 0.051) with borderline statistical significance. MOV was effective in preventing COVID-19 related severe respiratory failure (48.2%; 95% CI 0.5–73.0, p = 0.048) and in-hospital mortality (58.3%; 95% CI 22.9–77.4, p = 0.005) but not hospitalization (p = 0.16) and respiratory failure (p = 0.10). In summary, both NMV-r and MOV are effective for reducing severe outcomes in unvaccinated COVID-19 patients with chronic respiratory diseases. Full article
(This article belongs to the Special Issue COVID-19 Pharmacotherapy)
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10 pages, 753 KiB  
Article
Early Treatments of Fragile Children with COVID-19—Results of CLEVER (Children COVID Early Treatment), a Retrospective, Observational Study
by Chiara Minotti, Daniele Mengato, Marica De Pieri, Sabrina Trivellato, Andrea Francavilla, Costanza Di Chiara, Cecilia Liberati, Raffaele Mattera, Alessandra Biffi, Carlo Giaquinto, Francesca Venturini and Daniele Donà
Viruses 2023, 15(1), 192; https://doi.org/10.3390/v15010192 - 10 Jan 2023
Cited by 4 | Viewed by 2330
Abstract
(1) Background: SARS-CoV-2 infection is notably mild in children, though comorbidities may increase the risk of hospitalization and may represent a risk for increased disease severity. There is an urgent need for targeted therapies with an acceptable efficacy and safety profile. To date, [...] Read more.
(1) Background: SARS-CoV-2 infection is notably mild in children, though comorbidities may increase the risk of hospitalization and may represent a risk for increased disease severity. There is an urgent need for targeted therapies with an acceptable efficacy and safety profile. To date, most of the medicines for COVID-19-specific treatment are prescribed off-label for children due to a lack of clinical trials and consequent evidence in this population. (2) Methods: This was a retrospective, observational study investigating the safety of treatments for the prevention of severe COVID-19 in fragile pediatric patients who received monoclonal antibodies and antivirals for mild-to-moderate symptoms between December 2021 and July 2022. (3) Results: Thirty-two patients were included. Monoclonal antibodies were prescribed to 62%, intravenous antivirals to 22%, and oral antivirals to 16% of children. Sotrovimab was the most frequently prescribed drug among monoclonal antibodies and overall (59%). The second most prescribed drug was remdesivir (22%). No severe adverse drug reaction was reported. There was no progression to severe disease and no death cases due to COVID-19 or drug administration. At drug-type stratification, resolution of symptoms and swab positivity time showed no difference between the two groups at 7 and 28 days. Off-label prescriptions were 84% overall, and in similar proportions between the two groups. (4) Conclusions: in this small sample, antivirals seemed safe and showed no differences in efficacy as compared to MAbs for the early treatment of COVID-19 in fragile children, thus representing a valuable choice, even when administered off-label. Full article
(This article belongs to the Special Issue COVID-19 Pharmacotherapy)
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Review

Jump to: Editorial, Research

16 pages, 2108 KiB  
Review
Immune-Cell-Based Therapy for COVID-19: Current Status
by Yiyuan Wang, Qinghe Liang, Fengsheng Chen, Jiehuang Zheng, Yan Chen, Ziye Chen, Ruopeng Li and Xiaojuan Li
Viruses 2023, 15(11), 2148; https://doi.org/10.3390/v15112148 - 25 Oct 2023
Viewed by 1312
Abstract
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic. The interplay between innate and adaptive immune responses plays a crucial role in managing COVID-19. Cell therapy has recently emerged as a promising strategy to [...] Read more.
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic. The interplay between innate and adaptive immune responses plays a crucial role in managing COVID-19. Cell therapy has recently emerged as a promising strategy to modulate the immune system, offering immense potential for the treatment of COVID-19 due to its customizability and regenerative capabilities. This review provides an overview of the various subsets of immune cell subsets implicated in the pathogenesis of COVID-19 and a comprehensive summary of the current status of immune cell therapy in COVID-19 treatment. Full article
(This article belongs to the Special Issue COVID-19 Pharmacotherapy)
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15 pages, 548 KiB  
Review
Status and Developing Strategies for Neutralizing Monoclonal Antibody Therapy in the Omicron Era of COVID-19
by Zuning Ren, Chenguang Shen and Jie Peng
Viruses 2023, 15(6), 1297; https://doi.org/10.3390/v15061297 - 31 May 2023
Cited by 1 | Viewed by 1947
Abstract
The monoclonal antibody (mAb)-based treatment is a highly valued therapy against COVID-19, especially for individuals who may not have strong immune responses to the vaccine. However, with the arrival of the Omicron variant and its evolving subvariants, along with the occurrence of remarkable [...] Read more.
The monoclonal antibody (mAb)-based treatment is a highly valued therapy against COVID-19, especially for individuals who may not have strong immune responses to the vaccine. However, with the arrival of the Omicron variant and its evolving subvariants, along with the occurrence of remarkable resistance of these SARS-CoV-2 variants to the neutralizing antibodies, mAbs are facing tough challenges. Future strategies for developing mAbs with improved resistance to viral evasion will involve optimizing the targeting epitopes on SARS-CoV-2, enhancing the affinity and potency of mAbs, exploring the use of non-neutralizing antibodies that bind to conserved epitopes on the S protein, as well as optimizing immunization regimens. These approaches can improve the viability of mAb therapy in the fight against the evolving threat of the coronavirus. Full article
(This article belongs to the Special Issue COVID-19 Pharmacotherapy)
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17 pages, 497 KiB  
Review
Targeting CMV Reactivation to Optimize Care for Critically Ill COVID-19 Patients: A Review on the Therapeutic Potential of Antiviral Treatment
by Georgios Schinas, Vasiliki Moustaka, Eleni Polyzou, Maria Panagiota Almyroudi, George Dimopoulos and Karolina Akinosoglou
Viruses 2023, 15(5), 1165; https://doi.org/10.3390/v15051165 - 13 May 2023
Cited by 2 | Viewed by 1583
Abstract
Cytomegalovirus (CMV) reactivation has been linked to adverse clinical outcomes in critically ill patients, with emerging evidence suggesting a potential connection with severe COVID-19. Mechanisms driving this association may include primary lung injury, amplification of systemic inflammation, and secondary immunosuppression. Diagnostic challenges in [...] Read more.
Cytomegalovirus (CMV) reactivation has been linked to adverse clinical outcomes in critically ill patients, with emerging evidence suggesting a potential connection with severe COVID-19. Mechanisms driving this association may include primary lung injury, amplification of systemic inflammation, and secondary immunosuppression. Diagnostic challenges in detecting and assessing CMV reactivation necessitate a comprehensive approach to improve accuracy and inform treatment decisions. Currently, there is limited evidence on the efficacy and safety of CMV pharmacotherapy in critically ill COVID-19 patients. Although insights from non-COVID-19 critical illness studies suggest a potential role for antiviral treatment or prophylaxis, the risks and benefits must be carefully balanced in this vulnerable patient population. Understanding the pathophysiological role of CMV in the context of COVID-19 and exploring the advantages of antiviral treatment are crucial for optimizing care in critically ill patients. This review provides a comprehensive synthesis of available evidence, emphasizing the need for additional investigation to establish the role of CMV treatment or prophylaxis in the management of severe COVID-19 and to develop a framework for future research on this topic. Full article
(This article belongs to the Special Issue COVID-19 Pharmacotherapy)
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16 pages, 687 KiB  
Review
COVID-19 Pharmacotherapy in Pregnancy: A Literature Review of Current Therapeutic Choices
by Karolina Akinosoglou, Georgios Schinas, Emmanouil-Angelos Rigopoulos, Eleni Polyzou, Argyrios Tzouvelekis, George Adonakis and Charalambos Gogos
Viruses 2023, 15(3), 787; https://doi.org/10.3390/v15030787 - 19 Mar 2023
Cited by 5 | Viewed by 2521
Abstract
The clinical management of COVID-19 in pregnant women, who are considered a vulnerable population, remains uncertain even as the pandemic subsides. SARS-CoV-2 affects pregnant individuals in multiple ways and has been associated with severe maternal morbidity and mortality, as well as neonatal complications. [...] Read more.
The clinical management of COVID-19 in pregnant women, who are considered a vulnerable population, remains uncertain even as the pandemic subsides. SARS-CoV-2 affects pregnant individuals in multiple ways and has been associated with severe maternal morbidity and mortality, as well as neonatal complications. The unique anatomy and physiology of gestation make managing COVID-19 in this population a complex and challenging task, emphasizing the importance of spreading knowledge and expertise in this area. Therapeutic interventions require distinct clinical consideration, taking into account differences in pharmacokinetics, vertical transmission, drug toxicities, and postnatal care. Currently, there is limited data on antiviral and immunomodulating COVID-19 pharmacotherapy in pregnancy. Some medication has been shown to be safe and well tolerated among pregnant women with COVID-19; however, the lack of randomized clinical trials and studies in this patient population is evident. Available vaccines are considered safe and effective, with no evidence of harm to the fetus, embryo development, or short-term postnatal development. Pregnant women should be counseled about the risks of SARS-CoV-2 infection and informed of available ways to protect themselves and their families. Effective treatments for COVID-19 should not be withheld from pregnant individuals, and more research is needed to ensure the best outcomes. Full article
(This article belongs to the Special Issue COVID-19 Pharmacotherapy)
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21 pages, 563 KiB  
Review
HIV and COVID-19 Co-Infection: Epidemiology, Clinical Characteristics, and Treatment
by Dimitris Basoulis, Elpida Mastrogianni, Pantazis-Michail Voutsinas and Mina Psichogiou
Viruses 2023, 15(2), 577; https://doi.org/10.3390/v15020577 - 20 Feb 2023
Cited by 5 | Viewed by 3211
Abstract
The COVID-19 pandemic has been a global medical emergency with a significant socio-economic impact. People with HIV (PWH), due to the underlying immunosuppression and the particularities of HIV stigma, are considered a vulnerable population at high risk. In this review, we report what [...] Read more.
The COVID-19 pandemic has been a global medical emergency with a significant socio-economic impact. People with HIV (PWH), due to the underlying immunosuppression and the particularities of HIV stigma, are considered a vulnerable population at high risk. In this review, we report what is currently known in the available literature with regards to the clinical implications of the overlap of the two epidemics. PWH share the same risk factors for severe COVID-19 as the general population (age, comorbidities), but virological and immunological status also plays an important role. Clinical presentation does not differ significantly, but there are some opportunistic infections that can mimic or co-exist with COVID-19. PWH should be prime candidates for preventative COVID-19 treatments when they are available, but in the setting of resistant strains, this might be not easy. When considering small-molecule medications, physicians need to always remember to address potential interactions with ART, and when considering immunosuppressants, they need to be aware of potential risks for opportunistic infections. COVID-19 shares similarities with HIV in how the public perceives patients—with fear of the unknown and prejudice. There are opportunities for HIV treatment hidden in COVID-19 research with the leaps gained in both monoclonal antibody and vaccine development. Full article
(This article belongs to the Special Issue COVID-19 Pharmacotherapy)
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19 pages, 759 KiB  
Review
Tixagevimab/Cilgavimab in SARS-CoV-2 Prophylaxis and Therapy: A Comprehensive Review of Clinical Experience
by Karolina Akinosoglou, Emmanouil-Angelos Rigopoulos, Georgia Kaiafa, Stylianos Daios, Eleni Karlafti, Eleftheria Ztriva, Georgios Polychronopoulos, Charalambos Gogos and Christos Savopoulos
Viruses 2023, 15(1), 118; https://doi.org/10.3390/v15010118 - 30 Dec 2022
Cited by 17 | Viewed by 3013
Abstract
Effective treatments and vaccines against COVID-19 used in clinical practice have made a positive impact on controlling the spread of the pandemic, where they are available. Nevertheless, even if fully vaccinated, immunocompromised patients still remain at high risk of adverse outcomes. This has [...] Read more.
Effective treatments and vaccines against COVID-19 used in clinical practice have made a positive impact on controlling the spread of the pandemic, where they are available. Nevertheless, even if fully vaccinated, immunocompromised patients still remain at high risk of adverse outcomes. This has driven the largely expanding field of monoclonal antibodies, with variable results. Tixagevimab/Cilgavimab (AZD7442), a long-acting antibody combination that inhibits the attachment of the SARS-CoV-2 spike protein to the surface of cells, has proved promising in reducing the incidence of symptomatic COVID-19 or death in high-risk individuals without major adverse events when given as prophylaxis, as well as early treatment. Real-world data confirm the antibody combination’s prophylaxis efficacy in lowering the incidence, hospitalization, and mortality associated with COVID-19 in solid organ transplant recipients, patients with immune-mediated inflammatory diseases and hematological malignancies, and patients in B-cell-depleting therapies. Data suggest a difference in neutralization efficiency between the SARS-CoV-2 subtypes in favor of the BA.2 over the BA.1. In treating COVID-19, AZD7442 showed a significant reduction in severe COVID-19 cases and mortality when given early in the course of disease, and within 5 days of symptom onset, without being associated with severe adverse events, even when it is used in addition to standard care. The possibility of the development of spike-protein mutations that resist monoclonal antibodies has been reported; therefore, increased vigilance is required in view of the evolving variants. AZD7442 may be a powerful ally in preventing COVID-19 and the mortality associated with it in high-risk individuals. Further research is required to include more high-risk groups and assess the concerns limiting its use, along the SARS-CoV-2 evolutionary trajectory. Full article
(This article belongs to the Special Issue COVID-19 Pharmacotherapy)
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9 pages, 265 KiB  
Review
COVID-19 Vaccination in Patients with Chronic Liver Disease
by Georgios Schinas, Eleni Polyzou, Fevronia Mitropetrou, Aristotelis Pazionis, Charalambos Gogos, Christos Triantos and Karolina Akinosoglou
Viruses 2022, 14(12), 2778; https://doi.org/10.3390/v14122778 - 13 Dec 2022
Cited by 6 | Viewed by 1900
Abstract
Vaccination against SARS-CoV-2 has become a central public health issue, primarily for vulnerable populations such as individuals with Chronic Liver Disease (CLD). Increased COVID-19-related mortality and disease severity has been noted in this subgroup of patients. Severe COVID-19 tends to further deregulate liver [...] Read more.
Vaccination against SARS-CoV-2 has become a central public health issue, primarily for vulnerable populations such as individuals with Chronic Liver Disease (CLD). Increased COVID-19-related mortality and disease severity has been noted in this subgroup of patients. Severe COVID-19 tends to further deregulate liver function in patients with chronic liver failure or cirrhosis and even reactivate hepatitis in people living with HBV or HCV. In addition, impaired hepatic function leads to several limitations in possible therapeutic interventions. Chronic hepatic dysregulation, along with the underlying cirrhosis-associated immune dysfunction (CAID), leads to a decreased immune response to vaccination that, in turn, may result in reduced efficacy rates and lowered lasting protection. According to current guidelines, timely vaccination and frequent booster shot administration are deemed necessary in this context. Vaccination-related adverse events are mostly mild in nature and similar to those reported in the general population, whereas the incidence of liver injury following vaccination is relatively rare. We aimed to review available evidence and recommendations associated with COVID-19 vaccination in patients with chronic liver disease, and provide insight to current issues and future directions. Full article
(This article belongs to the Special Issue COVID-19 Pharmacotherapy)
12 pages, 894 KiB  
Review
Oral Antiviral Treatment for COVID-19: A Comprehensive Review on Nirmatrelvir/Ritonavir
by Karolina Akinosoglou, Georgios Schinas and Charalambos Gogos
Viruses 2022, 14(11), 2540; https://doi.org/10.3390/v14112540 - 17 Nov 2022
Cited by 33 | Viewed by 3867
Abstract
Despite the rapid development of efficient and safe vaccines against COVID-19, the need to confine the pandemic and treat infected individuals on an outpatient basis has led to the approval of oral antiviral agents. Taking into account the viral kinetic pattern of SARS-CoV-2, [...] Read more.
Despite the rapid development of efficient and safe vaccines against COVID-19, the need to confine the pandemic and treat infected individuals on an outpatient basis has led to the approval of oral antiviral agents. Taking into account the viral kinetic pattern of SARS-CoV-2, it is of high importance to intervene at the early stages of the disease. A protease inhibitor called nirmatrelvir coupled with ritonavir (NMV/r), which acts as a CYP3A inhibitor, delivered as an oral formulation, has shown much promise in preventing disease progression in high-risk patients with no need for supplemental oxygen administration. Real-world data seem to confirm the drug combination’s efficacy and safety against all viral variants of concern in adult populations. Although, not fully clarified, viral rebound and recurrence of COVID-19 symptoms have been described following treatment; however, more data on potential resistance issues concerning the Mpro gene, which acts as the drug’s therapeutic target, are needed. NMV/r has been a gamechanger in the fight against the pandemic by preventing hospitalizations and halting disease severity; therefore, more research on future development and greater awareness on its use are warranted. Full article
(This article belongs to the Special Issue COVID-19 Pharmacotherapy)
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