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(searched for: doi:10.1016/j.intimp.2020.107262)
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Published: 9 May 2022
by MDPI
Abstract:
Coronavirus 2019 disease (COVID-19) represents one of the largest pandemics the world has faced, and it is producing a global health crisis. To date, the availability of drugs to treat COVID-19 infections remains limited to supportive care although therapeutic options are being explored. Some of them are old strategies for treating infectious diseases. convalescent plasma (CP) therapy has been used successfully in other viral outbreaks in the 20th century. In this study, we systematically evaluated the effect and safety of CP therapy on hospitalized COVID-19 patients. A structured search was conducted following the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines using Medline (PubMed), SciELO, Cochrane Library Plus, Web of Science, and Scopus. The search included articles published up to January 2022 and was restricted to English- and Spanish-language publications. As such, investigators identified six randomized controlled trials that met the search criteria. The results determined that in hospitalized COVID-19 patients the administration of CP therapy with a volume between 200–500 mL and a single transfusion performed in 1–2 h, compared to the control group, decreased viral load, symptomatology, the period of infection, and mortality, without serious adverse effects. CP did influence clinical outcomes and may be a possible treatment option, although further studies will be necessary.
Ladan Ghadami, Mehrdad Hasibi, Ali Asadollahi-Amin, Behzad Asanjarani, Mohammad Farahmand,
Published: 12 March 2022
Microbial Pathogenesis, Volume 165; https://doi.org/10.1016/j.micpath.2022.105482

The publisher has not yet granted permission to display this abstract.
International Journal of Environmental Research and Public Health, Volume 18; https://doi.org/10.3390/ijerph182413201

Abstract:
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for the coronavirus disease 2019 (COVID-19) pandemic, affecting all age groups with a wide spectrum of clinical presentation ranging from asymptomatic to severe interstitial pneumonia, hyperinflammation, and death. Children and infants generally show a mild course of the disease, although infants have been observed to have a higher risk of hospitalization and severe outcomes. Here, we report the case of a preterm infant with a severe form of SARS-CoV-2 infection complicated by cerebral venous thrombosis successfully treated with steroids, hyperimmune plasma, and remdesivir.
Published: 11 September 2021
by MDPI
Abstract:
Convalescent plasma (CP) from patients recovered from COVID-19 is one of the most studied anti-viral therapies against SARS-COV-2 infection. The aim of this study is to summarize the evidence from the available systematic reviews on the efficacy and safety of CP in COVID-19 through an overview of the published systematic reviews (SRs). A systematic literature search was conducted up to August 2021 in Embase, PubMed, Web of Science, Cochrane and Medrxiv databases to identify systematic reviews focusing on CP use in COVID-19. Two review authors independently evaluated reviews for inclusion, extracted data and assessed quality of evidence using AMSTAR (A Measurement Tool to Assess Reviews) and GRADE tools. The following outcomes were analyzed: mortality, viral clearance, clinical improvement, length of hospital stay, adverse reactions. In addition, where possible, subgroup analyses were performed according to study design (e.g., RCTs vs. non-RCTs), CP neutralizing antibody titer and timing of administration, and disease severity. The methodological quality of included studies was assessed using the checklist for systematic reviews AMSTAR-2 and the GRADE assessment. Overall, 29 SRs met the inclusion criteria based on 53 unique primary studies (17 RCT and 36 non-RCT). Limitations to the methodological quality of reviews most commonly related to absence of a protocol (11/29) and funding sources of primary studies (27/29). Of the 89 analyses on which GRADE judgements were made, effect estimates were judged to be of high/moderate certainty in four analyses, moderate in 38, low in 38, very low in nine. Despite the variability in the certainty of the evidence, mostly related to the risk of bias and inconsistency, the results of this umbrella review highlight a mortality reduction in CP over standard therapy when administered early and at high titer, without increased adverse reactions.
Lennox Chitsike,
Published: 23 July 2021
Virology Journal, Volume 18, pp 1-17; https://doi.org/10.1186/s12985-021-01624-x

Abstract:
The COVID-19 pandemic has put healthcare infrastructures and our social and economic lives under unprecedented strain. Effective solutions are needed to end the pandemic while significantly lessening its further impact on mortality and social and economic life. Effective and widely-available vaccines have appropriately long been seen as the best way to end the pandemic. Indeed, the current availability of several effective vaccines are already making a significant progress towards achieving that goal. Nevertheless, concerns have risen due to new SARS-CoV-2 variants that harbor mutations against which current vaccines are less effective. Furthermore, some individuals are unwilling or unable to take the vaccine. As health officials across the globe scramble to vaccinate their populations to reach herd immunity, the challenges noted above indicate that COVID-19 therapeutics are still needed to work alongside the vaccines. Here we describe the impact that neutralizing antibodies have had on those with early or mild COVID-19, and what their approval for early management of COVID-19 means for other viral entry inhibitors that have a similar mechanism of action. Importantly, we also highlight studies that show that therapeutic strategies involving various viral entry inhibitors such as multivalent antibodies, recombinant ACE2 and miniproteins can be effective not only for pre-exposure prophylaxis, but also in protecting against SARS-CoV-2 antigenic drift and future zoonotic sarbecoviruses.
Zetong Ma, Mengmei Zhu, Shuyi Zhang, Kewen Qian, Chuqi Wang, Wenyan Fu, Changhai Lei,
Published: 12 July 2021
The publisher has not yet granted permission to display this abstract.
, Xin Huang, Derry Alvarez, Wenshu He, Can Baysal, Changfu Zhu, Victoria Armario‐Najera, Amaya Blanco Perera, Pedro Cerda Bennasser, Andera Saba‐Mayoral, et al.
Published: 28 June 2021
Plant Biotechnology Journal, Volume 19, pp 1901-1920; https://doi.org/10.1111/pbi.13657

The publisher has not yet granted permission to display this abstract.
, Sarah C Keithly, Katherine E Kurgansky, , Hanna Gerlovin, Helen Marucci-Wellman, Annie Doubleday, Eva R Thomas, YoJin Park, Yuk-Lam Anne Ho, et al.
Journal of Infectious Diseases, Volume 224, pp 967-975; https://doi.org/10.1093/infdis/jiab330

Abstract:
Background Early convalescent plasma transfusion may reduce mortality in patients with nonsevere coronavirus disease 2019 (COVID-19). Methods This study emulates a (hypothetical) target trial using observational data from a cohort of US veterans admitted to a Department of Veterans Affairs (VA) facility between 1 May and 17 November 2020 with nonsevere COVID-19. The intervention was convalescent plasma initiated within 2 days of eligibility. Thirty-day mortality was compared using cumulative incidence curves, risk differences, and hazard ratios estimated from pooled logistic models with inverse probability weighting to adjust for confounding. Results Of 11 269 eligible person-trials contributed by 4755 patients, 402 trials were assigned to the convalescent plasma group. Forty and 671 deaths occurred within the plasma and nonplasma groups, respectively. The estimated 30-day mortality risk was 6.5% (95% confidence interval [CI], 4.0%–9.7%) in the plasma group and 6.2% (95% CI, 5.6%–7.0%) in the nonplasma group. The associated risk difference was 0.30% (95% CI, −2.30% to 3.60%) and the hazard ratio was 1.04 (95% CI, .64–1.62). Conclusions Our target trial emulation estimated no meaningful differences in 30-day mortality between nonsevere COVID-19 patients treated and untreated with convalescent plasma. Clinical Trials Registration. NCT04545047.
Sun Bean Kim,
Journal of the Korean Medical Association, Volume 64, pp 375-385; https://doi.org/10.5124/jkma.2021.64.5.375

Abstract:
Since the coronavirus disease 2019 (COVID-19) outbreak, more than 150 million people in over 200 countries have been infected, with over 3 million people dying due to it, as of May 1, 2021. Many researchers are working continuously to find effective drug treatments for COVID-19; however, the optimal treatment approach remains unclear. In this article, current advances in pharmacological treatments for patients with COVID-19 are discussed. Data obtained from recent studies indicate a mortality benefit with the administration of dexamethasone or adjunctive tocilizumab and potential clinical benefits with remdesivir (with or without baricitinib). Several monoclonal antibodies against severe acute respiratory syndrome coronavirus 2 have been developed. The US Food and Drug Administration issued two emergency use authorizations: one for bamlanivimab/etesevimab and another for casirivimab/imdevimab for patients with mild to moderate COVID-19, at high risk of progression to severe disease and/or hospitalization. The pathogenesis of COVID-19 indicates that antiviral treatments would be most beneficial in the early phase of the infection that is primarily driven by replication of severe acute respiratory syndrome coronavirus 2, whereas immunosuppressive/anti-inflammatory therapies are likely to be more beneficial during the late phase of the infection, when the disease is driven by an exaggerated immune/inflammatory response to the virus that causes tissue damage.
Published: 7 May 2021
by MDPI
Viruses, Volume 13; https://doi.org/10.3390/v13050849

Abstract:
More than one year into the novel coronavirus disease 2019 (COVID-19) pandemic, healthcare systems across the world continue to be overwhelmed with soaring daily cases. The treatment spectrum primarily includes ventilation support augmented with repurposed drugs and/or convalescent plasma transfusion (CPT) from recovered COVID-19 patients. Despite vaccine variants being recently developed and administered in several countries, challenges in global supply chain logistics limit their timely availability to the wider world population, particularly in developing countries. Given the measured success of conventional CPT in treating several infections over the past decade, recent studies have reported its effectiveness in decreasing the duration and severity of COVID-19 symptoms. In this review, we conduct a literature search of published studies investigating the use of CPT to treat COVID-19 patients from January 2020 to January 2021. The literature search identified 181 records of which 39 were included in this review. A random-effects model was used to aggregate data across studies, and mortality rates of 17 vs. 32% were estimated for the CPT and control patient groups, respectively, with an odds ratio (OR) of 0.49. The findings indicate that CPT shows potential in reducing the severity and duration of COVID-19 symptoms. However, early intervention (preferably within 3 days), recruitment of donors, and plasma potency introduce major challenges for its scaled-up implementation. Given the low number of existing randomized clinical trials (RCTs, four with a total of 319 patients), unanticipated risks to CPT recipients are highlighted and discussed. Nevertheless, CPT remains a promising COVID-19 therapeutic option that merits internationally coordinated RCTs to achieve a scientific risk–benefit consensus.
Giorgio Costagliola, Erika Spada,
Published: 4 May 2021
Pediatric Rheumatology, Volume 19, pp 1-11; https://doi.org/10.1186/s12969-021-00559-5

Abstract:
Background SARS-CoV-2 can induce an immune impairment and dysregulation, finally resulting in the massive release of inflammatory mediators (cytokine storm), strongly contributing to the pulmonary and systemic manifestations in severe coronavirus disease 2019 (COVID-19). As a consequence, different drugs active on the immune system have been proposed for the treatment of the disease in adults. Role of the anti-rheumatic agents in children Children are more likely to develop a mild disease course, as the severe form of COVID-19 is identified in less than 5% of the pediatric patients. Moreover, in children a peculiar disease phenotype, defined as multisystem inflammatory syndrome in children (MIS-C) is observed, representing the most severe expression of the inflammatory dysregulation caused by SARS-CoV-2. The limited experience with the severe pediatric COVID-19 and MIS-C does not allow conclusions about the role of the immune pharmacological approach, and therefore the treatment of these conditions represents a considerable clinical challenge. The use of chloroquine, hydroxychloroquine, and colchicine in the early disease stages is not sufficiently supported by evidence, and there is an increasing interest in the role of biologic agents, including anti-IL-1 and anti-IL-6 agents, in the prevention and treatment of the severe manifestations of COVID-19. Conclusion The therapeutic approach to pediatric COVID-19 is multidisciplinary, and anti-rheumatic agents have a prominent role in severe disease. This paper reviews the rationale for the use of anti-rheumatic agents in pediatric COVID-19 and MIS-C and the clinical experience with the single drugs. Finally, the areas of potential improvement in the use of anti-rheumatic agents, including the optimization of the drug choice and the timing of administration, are discussed.
Zachary A. Krumm, Grace M. Lloyd, Connor P. Francis, Lith H. Nasif, Duane A. Mitchell, Todd E. Golde, ,
Published: 29 March 2021
Virology Journal, Volume 18, pp 1-22; https://doi.org/10.1186/s12985-021-01526-y

Abstract:
Beginning in late 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged as a novel pathogen that causes coronavirus disease 2019 (COVID-19). SARS-CoV-2 has infected more than 111 million people worldwide and caused over 2.47 million deaths. Individuals infected with SARS-CoV-2 show symptoms of fever, cough, dyspnea, and fatigue with severe cases that can develop into pneumonia, myocarditis, acute respiratory distress syndrome, hypercoagulability, and even multi-organ failure. Current clinical management consists largely of supportive care as commonly administered treatments, including convalescent plasma, remdesivir, and high-dose glucocorticoids. These have demonstrated modest benefits in a small subset of hospitalized patients, with only dexamethasone showing demonstrable efficacy in reducing mortality and length of hospitalization. At this time, no SARS-CoV-2-specific antiviral drugs are available, although several vaccines have been approved for use in recent months. In this review, we will evaluate the efficacy of preclinical and clinical drugs that precisely target three different, essential steps of the SARS-CoV-2 replication cycle: the spike protein during entry, main protease (MPro) during proteolytic activation, and RNA-dependent RNA polymerase (RdRp) during transcription. We will assess the advantages and limitations of drugs that precisely target evolutionarily well-conserved domains, which are less likely to mutate, and therefore less likely to escape the effects of these drugs. We propose that a multi-drug cocktail targeting precise proteins, critical to the viral replication cycle, such as spike protein, MPro, and RdRp, will be the most effective strategy of inhibiting SARS-CoV-2 replication and limiting its spread in the general population.
Published: 17 March 2021
by MDPI
Abstract:
Despite the enormous advances in knowledge about the SARS-CoV-2 infection, the optimal treatment for COVID-19 is still not well defined. The use of convalescent plasma seems to be a promising method of treatment but requires further evaluation. Although it is usually mild, in children with underlying chronic diseases, the course of SARS-CoV-2 infection may be very severe. We described a series of 13 pediatric patients (mean age 10.4 years, median 12) treated with convalescent plasma as a method of COVID-19 therapy. Medical history, with particular emphasis on comorbidities, clinical course, laboratory parameters, supportive treatment and virus elimination time, were analyzed. The mean hospitalization time was 22.6 days (median 20). The most common abnormalities included increased levels of C-reactive protein, D-dimer, and lymphopenia. Median time from symptom onset to convalescent plasma transfusion was 10.6 days (median 7 days). Six patients (46.2%) had a viral clearance on RT-PCR method from a nasopharyngeal swab within 3 days of transfusion, while in the remaining patients the mean elimination time was 12.1 days (median 6 days). Clinical improvement was achieved in all patients; no adverse effects were found in any of the cases. Convalescent plasma may be a promising treatment for COVID-19 in children.
, Ruth Ana María González Villoria, María Vanesa Elizondo, Anel Yaneli Nicolás Osorio, Silvia Mercedes Coca
Published: 22 January 2021
Abstract:
Given the variability of previously reported results, this systematic review aims to determine the clinical effectiveness of convalescent plasma employed in the treatment of hospitalized patients with diagnosis of COVID-19.We conducted a systematic review of controlled clinical trials assessing treatment with convalescent plasma for hospitalized patients with a diagnosis of SARS-CoV-2 infection. The outcomes were mortality, clinical improvement, and ventilation requirement.A total of 50 studies were retrieved from the databases. Four articles were finally included in the data extraction, qualitative and quantitative synthesis of results. The meta-analysis suggests that there is no benefit of convalescent plasma compared to standard care or placebo in the reduction of the overall mortality and in the ventilation requirement; but there could be a benefit for the clinical improvement in patients treated with plasma.We can conclude that the convalescent plasma transfusion cannot reduce the mortality or ventilation requirement in hospitalized patients diagnosed with SARS-CoV-2 infection. More controlled clinical trials conducted with methodologies that ensure a low risk of bias are still needed.
, Ruth Ana María González-Villoria, María Vanesa Elizondo, Anel Yaneli Nicolás Osorio, David Gómez Martínez, Silvia Mercedes Coca
Therapeutic Advances in Respiratory Disease, Volume 15; https://doi.org/10.1177/17534666211028077

Abstract:
Aims: Given the variability of previously reported results, this systematic review aims to determine the clinical effectiveness of convalescent plasma employed in the treatment of hospitalized patients diagnosed with COVID-19. Methods: We conducted a systematic review of controlled clinical trials assessing treatment with convalescent plasma for hospitalized patients diagnosed with SARS-CoV-2 infection. The outcomes were mortality, clinical improvement, and ventilation requirement. Results: A total of 51 studies were retrieved from the databases. Five articles were finally included in the data extraction and qualitative and quantitative synthesis of results. The overall risk of bias in the reviewed articles was established at low-risk only in two trials. The meta-analysis suggests that there is no benefit of convalescent plasma compared with standard care or placebo in reducing the overall mortality and the ventilation requirement. However, there could be a benefit for the clinical improvement in patients treated with plasma. Conclusion: Current results led to assume that the convalescent plasma transfusion cannot reduce the mortality or ventilation requirement in hospitalized patients diagnosed with SARS-CoV-2 infection. More controlled clinical trials conducted with methodologies that ensure a low risk of bias are still needed. The reviews of this paper are available via the supplemental material section.
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