COVID-19 Convalescent Plasma Therapy Research Articles

Cytokine, Anti-SARS-CoV-2 Antibody, and Neutralizing Antibody Levels in Conventional Blood Donors Who Have Recovered from COVID-19

Background: At the beginning of the pandemic, COVID-19 convalescent plasma (CCP) containing anti-SARS-CoV-2 antibodies was suggested as a source of therapy. In the last 3 years, many trials have demonstrated the limited usefulness of CCP therapy. This led us to the hypothesis that CCP could contain other elements, along with the desired neutralizing antibodies, which could potentially prevent it from having a therapeutic effect, among them cytokines, chemokines, growth factors, clotting factors, and autoantibodies. Methods: In total, 39 cytokines were analyzed in the plasma of 190 blood donors, and further research focused on the levels of 23 different cytokines in CCP (sCD40L, eotaxin, FGF-2, FLT-3L, ractalkine, GRO-α, IFNα2, IL-1β, IL-1RA, IL-5, IL-6, IL-8, IL-12, IL-13, IL-15, IL-17E, IP-10, MCP-1, MIP-1b, PDGF-AA, TGFα, TNFα, and TRAIL). Anti-SARS-CoV-2 antibodies and neutralizing antibodies were detected in CCP. Results: We found no significant differences between CCP taken within a maximum of 180 days from the onset of the first COVID-19 symptoms and the controls. We also made a comparison of the cytokine levels between the low neutralizing antibodies (<160) group and the high neutralizing antibodies (≥160) group and found there were no differences between the groups. Our research also showed no correlation either to levels of anti-SARS-CoV-2 IgG Ab or to the levels of neutralizing antibodies. There were also no significant changes in cytokine levels based on the period after the start of COVID-19 symptoms. Conclusions: No elements which could potentially be responsible for preventing CCP from having a therapeutic effect were found.

Convalescent Plasma Therapy for COVID-19: A Systematic Review and Meta-Analysis on Randomized Controlled Trials

Background: While passive immunotherapy has been considered beneficial for patients with severe respiratory viral infections, the treatment of COVID-19 cases with convalescent plasma produced mixed results. Thus, there is a lack of certainty and consensus regarding its effectiveness. This meta-analysis aims to assess the role of convalescent plasma treatment on the clinical outcomes of COVID-19 patients enrolled in randomized controlled trials (RCTs). Methods: A systematic search was conducted in the PubMed database (end-of-search: 29 December 2022) for RCTs on convalescent plasma therapy compared to supportive care\standard of care. Pooled relative risk (RR) and 95% confidence intervals were calculated with random-effects models. Subgroup and meta-regression analyses were also performed, in order to address heterogeneity and examine any potential association between the factors that varied, and the outcomes reported. The present meta-analysis was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results: A total of 34 studies were included in the meta-analysis. Per overall analysis, convalescent plasma treatment was not associated with lower 28-day mortality [RR = 0.98, 95% CI (0.91, 1.06)] or improved 28-day secondary outcomes, such as hospital discharge [RR = 1.00, 95% CI (0.97, 1.03)], ICU-related or score-related outcomes, with effect estimates of RR = 1.00, 95% CI (0.98, 1.05) and RR = 1.06, 95% CI (0.95, 1.17), respectively. However, COVID-19 outpatients treated with convalescent plasma had a 26% less risk of requiring hospital care, when compared to those treated with the standard of care [RR = 0.74, 95% CI (0.56, 0.99)]. Regarding subgroup analyses, COVID-19 patients treated with convalescent plasma had an 8% lower risk of ICU-related disease progression when compared to those treated with the standard of care (with or without placebo or standard plasma infusions) [RR = 0.92, 95% CI (0.85, 0.99)] based on reported outcomes from RCTs carried out in Europe. Finally, convalescent plasma treatment was not associated with improved survival or clinical outcomes in the 14-day subgroup analyses. Conclusions: Outpatients with COVID-19 treated with convalescent plasma had a statistically significantly lower risk of requiring hospital care when compared to those treated with placebo or the standard of care. However, convalescent plasma treatment was not statistically associated with prolonged survival or improved clinical outcomes when compared to placebo or the standard of care, per overall analysis in hospitalized populations. This hints at potential benefits, when used early, to prevent progression to severe disease. Finally, convalescent plasma was significantly associated with better ICU-related outcomes in trials carried out in Europe. Well-designed prospective studies could clarify its potential benefit for specific subpopulations in the post-pandemic era.

COVID-19 convalescent plasma therapy through the lens of the third year of the pandemic

Serum obtained from recovered persons (convalescent serum) was the inaugural form of antimicrobial therapy for infectious diseases. Its efficacy required the administration of a sufficient amount of microbe-specific serum to mediate a biological effect early in the course of disease. Although serum therapy was discontinued when antibiotics were introduced early in the 20th century, the principles that governed its efficacy were prescient as they apply to the use of COVID-19 convalescent plasma (CCP) to treat COVID-19. Lessons learned from studies of CCP therapy for COVID-19 dating to the onset of the pandemic provide further proof of the principles of serum therapy. Analysis of these studies shows that like serum therapy, the efficacy of CCP in patients with COVID-19 depends on the administration of a high titer of SARSCoV-2 antibodies early in the course of disease.

Nucleocapsid-specific antibody function is associated with therapeutic benefits from COVID-19 convalescent plasma therapy

COVID-19 convalescent plasma (CCP), a passive polyclonal antibody therapeutic, has had mixed clinical results. Though, antibody neutralization is the predominant approach to benchmarking CCP’s efficacy, CCP may also influence the evolution of the endogenous antibody response. Using systems serology to comprehensive profile SARS-CoV-2 functional antibodies of hospitalized COVID-19 participants enrolled in a randomized controlled trial of CCP (ClinicalTrials.gov Identifier NCT04397757), we find the clinical benefit of CCP is associated with both a shift towards reduced inflammatory Spike (S) responses and enhanced Nucleocapsid (N) humoral responses. We find CCP has the greatest clinical benefit in participants with low pre-existing anti-SARS-CoV-2 antibody function and CCP-induced immunomodulatory Fc glycan profiles and N immunodominant profiles persist for at least two months. We highlight a potential mechanism of action of CCP associated with durable immunomodulation, outline optimal patient characteristics for CCP treatment, and provide guidance for the development of a different class of COVID-19 hyperflammation-targeting antibody therapeutics.

A Review on Effectiveness of Plasma Therapy in Severe COVID-19 Patients.

Coronavirus 2019 has created a big threat to the modern world. Many researchers and scientists had taken the burden of finding information about this entity, its structure, its transmission, and also about the treatment that can be given to individuals infected by it. There has been use of different medicines at different times simultaneously researching about them, starting with only symptomatic and supportive treatment, then antimalarial agents like chloroquine and hydroxychloroquine, then going to favipavir, and other antivirals, then came the use of vaccines and also convalescent plasma therapy for COVID-19. The most advanced is convalescent plasma use for the treating coronavirus. Using plasma of patients who have remitted from this disease and putting it into those individuals who are dealing with the disease or are critically ill for improvement of their health status. This treatment has been used for many other diseases too and has been proven efficacious. So, this technique is being used and studied for coronavirus 2019 as well. There have been set certain criteria for those who can donate plasma and also criteria for the recipients of this technique. Also, there can be adverse reactions or even side effects with this, like transfusion-related acute lung injury (TRALI), so they should also be kept in mind during treatment with this method. So, though there are many methods to date to treat these individuals but one of the latest ones is using plasma, which is proven to be efficacious but still many studies are under process for the same.

Drugs and convalescent plasma therapy for COVID-19: a survey of the interventional clinical studies in Italy after 1 year of pandemic

BackgroundThe 2019 novel coronavirus disease (COVID-19) pandemic has highlighted the importance of health research and fostered clinical research as never before. A huge number of clinical trials for potential COVID-19 interventions have been launched worldwide. Therefore, the effort of monitoring and characterizing the ongoing research portfolio of COVID-19 clinical trials has become crucial in order to fill evidence gaps that can arise, define research priorities and methodological issues, and eventually, formulate valuable recommendations for investigators and sponsors. The main purpose of the present work was to analyze the landscape of COVID-19 clinical research in Italy, by mapping and describing the characteristics of planned clinical trials investigating the role of drugs and convalescent plasma for treatment or prevention of COVID-19 disease.MethodsDuring an 11-month period between May 2020 and April 2021, we performed a survey of the Italian COVID-19 clinical trials on therapeutic and prophylactic drugs and convalescent plasma. Clinical trials registered in the Italian Medicines Agency (AIFA) and ClinicalTrials.gov websites were regularly monitored. In the present paper, we report an analysis of study design characteristics and other trial features at 6 April 2021.ResultsNinety-four clinical trials planned to be carried out in Italy were identified. Almost all of them (91%) had a therapeutic purpose; as for the study design, the majority of them adopted a parallel group (74%) and randomized (76%) design. Few of them were blinded (33%). Eight multiarm studies were identified, and two of them were multinational platform trials. Many therapeutic strategies were investigated, mostly following a drug repositioning therapeutic approach.ConclusionsOur study describes the characteristics of COVID-19 clinical trials planned to be carried out in Italy over about 1 year of pandemic emergency.High level quality clinical trials were identified, although some weaknesses in study design and replications of experimental interventions were observed, particularly in the early phase of the pandemic.Our findings provide a critical view of the clinical research strategies adopted for COVID-19 in Italy during the early phase of the pandemic. Further actions could include monitoring and follow-up of trial results and publications and focus on non-pharmacological research areas.

A role for Nucleocapsid-specific antibody function in Covid-19 Convalescent plasma therapy

A role for Nucleocapsid-specific antibody function in Covid-19 Convalescent plasma therapy

Early high-titer convalescent plasma therapy in patients with moderate and severe COVID-19

Background and objectivesThe use of COVID-19 convalescent plasma (CCP) has been approved by the FDA. We assessed the outcome of patients with moderate and severe COVID-19 following convalescent plasma therapy and the association with variables such as antibody titer in CCP units and transfusion time. Materials and methodsIn this prospective cohort study, 3097 patients with moderate and severe COVID-19 (according to WHO Progression Scale) had heterogeneous demographic and clinical characteristics received plasma with an unknown titer at the transfusion time. Firstly, information about age, sex, blood group, the time interval from hospitalization to CCP transfusion, underlying disease, and antibody titer with the outcome were investigated. Then, multivariate logistic regression and area under the curve (AUC) were performed for the association between disease severity and intubation variables with transfusion time and outcome. ResultsPatients with younger age receiving CCP in the first five days of hospitalization had lower mortality (P < 0.0001). Moreover, patients without the underlying disease had lower mortality (P < 0.001). The mortality rate also decreased in severe patients who were intubated receiving CCP for less than five days (P < 0.001). In patients with moderate severity (score less than 5) who received IgG antibody levels above 1:320 in less than five days had lower mortality (P < 0.0001). ConclusionOur findings suggested that COVID-19 patients with the moderate type of disease receiving CCP units with high antibody titers in the early stages of the disease experienced greater effectiveness of CCP therapy.

Interferon-\u03b12 Auto-antibodies in Convalescent Plasma Therapy for COVID-19

PurposeTo study the effect of interferon-α2 auto-antibodies (IFN-α2 Abs) on clinical and virological outcomes in critically ill COVID-19 patients and the risk of IFN-α2 Abs transfer during convalescent plasma treatment.MethodsSera from healthy controls, cases of COVID-19, and other respiratory illness were tested for IFN-α2 Abs by ELISA and a pseudo virus–based neutralization assay. The effects of disease severity, sex, and age on the risk of having neutralizing IFN-α2 Abs were determined. Longitudinal analyses were performed to determine association between IFN-α2 Abs and survival and viral load and whether serum IFN-α2 Abs appeared after convalescent plasma transfusion.ResultsIFN-α2 neutralizing sera were found only in COVID-19 patients, with proportions increasing with disease severity and age. In the acute stage of COVID-19, all sera from patients with ELISA-detected IFN-α2 Abs (13/164, 7.9%) neutralized levels of IFN-α2 exceeding physiological concentrations found in human plasma and this was associated with delayed viral clearance. Convalescent plasma donors that were anti-IFN-α2 ELISA positive (3/118, 2.5%) did not neutralize the same levels of IFN-α2. Neutralizing serum IFN-α2 Abs were associated with delayed viral clearance from the respiratory tract.ConclusionsIFN-α2 Abs were detected by ELISA and neutralization assay in COVID-19 patients, but not in ICU patients with other respiratory illnesses. The presence of neutralizing IFN-α2 Abs in critically ill COVID-19 is associated with delayed viral clearance. IFN-α2 Abs in COVID-19 convalescent plasma donors were not neutralizing in the conditions tested.

Development of a COVID-19 Convalescent Plasma Curriculum Amongst Students: An Initial Pilot Study

Abstract Introduction/Objective Since December 2019, the World Health Organization has documented over 145 million COVID-19 infections with more than 3 million deaths worldwide. Considering this unprecedented pandemic, potential treatments including COVID-19 Convalescent Plasma (CP) received an emergency use authorization (EUA) for hospitalized patients from the Food and Drug Administration (FDA) in August 2020. CP is a form of passive immunization in which antibody-rich blood taken from recovered COVID-19 patients is used for transfusion into other patients. CP therapy is a temporary treatment that is meant to help hospitalized COVID-19 patients recover. Although there has been significant interest in CP, the peer-reviewed English literature is sparse on education initiatives on CP and appears absent regarding undergraduates and other students outside the laboratory or blood bank. Therefore, we present a first presentation of a pilot education initiative on CP for students. Methods/Case Report Information for the educational presentation was obtained from AABB guidelines, meta- analyses, and published clinical studies. Presented was a broad overview algorithm of when CP may be considered starting with symptomatic patients hospitalized with moderate to severe disease who have been diagnosed with COVID-19, including a brief review of the gold standard for COVID-19 diagnosis by reverse transcriptase polymerase chain reaction. As part of this pilot study, this presentation was given to a group of high school students. Results (if a Case Study enter NA) In this study, 22 high school students were briefly taught about convalescent plasma, including its use as a therapeutic agent to treat COVID-19. Before the presentation, 0 of the 22 students knew how CP was involved in COVID-19 or even what CP was. After the presentation, a survey was taken in order to learn about knowledge retention and after, all were understood CP’s general use in COVID-19. Therefore, this presentation improved knowledge on CP and was well accepted. Conclusion Educational initiatives on information related to CP have critical potential to improve the knowledge base of students. This presentation represents a pilot study for additional educational initiatives to improve the knowledge of CP amongst students.

Convalescent Plasma Therapy for COVID-19 is a Challenging Option Review

The guiding principle of plasma therapy can be utilized for prophylaxis and treatment reasons, taking into account non-availability of suitable vaccination for prevention or no settled conclusive cure for SARS-CoV-2, plasma therapy is obtaining importance in a current pandemic as one of the treatment options of COVID-19. Despite the fact that, it has been said to be a useful approach in exceptional preliminary studies, convalescent plasma (CP) treatment has various limitations. In this review, an attempt has been made to audit positive viewpoints, negative views and specific limitations of the CP therapy for COVID-19 cases. The outcomes of various studies show that CP treatment would possibly be considered one of the alternatives but while questioning about it as a therapeutic approach, thinking about beneficial aspects, the negative aspects and barriers are to be considered before its administration as a therapeutic agent.

Convalescent plasma therapy for COVID-19

The outbreak of severe acute respiratory syndrome COVID-19 caused by SARS-CoV-2 in China represents a significant threat to global health. Unfortunately, effective therapeutic drugs and vaccines to cure SARS-CoV-2 are still lacking. Convalescent Plasma therapy which induces passive immunization seems a successful treatment for COVID-19 patients and also proves to be of huge value in terms of saving the severely ill patient. Plasma therapy acts by Blocking the Virus (Neutralization), Enhancing Phagocytosis (Opsonization), Immune System Activation (Complement Activation), and finally killing Virus (Antibody-Dependent Cell-mediated Cytotoxicity). Food and Drug Administration (FDA) of the United States was also given the stamp of approval for use of plasma therapy on 23 August 2020. In this review, we introduced the effective level of antibodies, potential mechanisms of CPT, WHO criteria for donating the plasma as well as future uncertainties of convalescent plasma therapy in the treatment of COVID-19 patients.

Convalescent plasma therapy for COVID-19

Convalescent plasma therapy for COVID-19

COVID-19 Convalescent Plasma Is More than Neutralizing Antibodies: A Narrative Review of Potential Beneficial and Detrimental Co-Factors.

COVID-19 convalescent plasma (CCP) is currently under investigation for both treatment and post-exposure prophylaxis. The active component of CCP mediating improved outcome is commonly reported as specific antibodies, particularly neutralizing antibodies, with clinical efficacy characterized according to the level or antibody affinity. In this review, we highlight the potential role of additional factors in CCP that can be either beneficial (e.g., AT-III, alpha-1 AT, ACE2+ extracellular vesicles) or detrimental (e.g., anti-ADAMTS13, anti-MDA5 or anti-interferon autoantibodies, pro-coagulant extracellular vesicles). Variations in these factors in CCP may contribute to varied outcomes in patients with COVID-19 and undergoing CCP therapy. We advise careful, retrospective investigation of such co-factors in randomized clinical trials that use fresh frozen plasma in control arms. Nevertheless, it might be difficult to establish a causal link between these components and outcome, given that CCP is generally safe and neutralizing antibody effects may predominate.

Effect of time and titer in convalescent plasma therapy for COVID-19

SummaryThe clinical benefit of convalescent plasma (CP) for patients with coronavirus disease (COVID)-19 is still debated. In this systematic review and meta-analysis, we selected 10 randomized clinical trials (RCTs) and 15 non-randomized studies (total number of patients = 22,591) of CP treatment and evaluated two different scenarios: (1) disease stage of plasma recipients and (2) donated plasma antibody titer, considering all-cause mortality at the latest follow-up. Our results show that, when provided at early stages of the disease, CP significantly reduced mortality: risk ratio (RR) 0.72 (0.68, 0.77), p < 0.00001, while provided in severe or critical conditions, it did not (RR: 0.94 [0.86, 1.04], p = 0.22). On the other hand, the benefit on mortality was not increased by using plasma with a high-antibody titer compared with unselected plasma. This meta-analysis might promote CP usage in patients with early-stage COVID-19 in further RCTs to maximize its benefit in decreasing mortality, especially in less affluent countries.

Retraction Note to: Methylene blue photochemical treatment as a reliable SARS-CoV-2 plasma virus inactivation method for blood safety and convalescent plasma therapy for COVID-19

In 2020, a new coronavirus, SARS-CoV-2, quickly spread worldwide within a few months. Although coronaviruses typically infect the upper or lower respiratory tract, the virus RNA can be detected in plasma. The risk of transmitting coronavirus via transfusion of blood products remains. As more asymptomatic infections are identified in COVID-19 cases, blood safety has become particularly important. Methylene blue (MB) photochemical technology has been proven to inactivate lipid-enveloped viruses with high efficiency and safety. The present study aimed to investigate the SARS-CoV-2 inactivation effects of MB in plasma. The SARS-CoV-2 virus strain was isolated from Zhejiang University. The live virus was harvested from cultured VERO-E6 cells, and mixed with MB in plasma. The MB final concentrations were 0, 1, 2, and 4 μM. The “BX-1 AIDS treatment instrument” was used at room temperature, the illumination adjusted to 55,000 ± 0.5 million Lux, and the plasma was irradiated for 0, 2, 5, 10, 20, and 40 mins using light at a single wavelength of 630 nm. Virus load changes were measured using quantitative reverse transcription- PCR. BX-1 could effectively eliminate SARS-CoV-2 within 2 mins in plasma, and the virus titer declined to 4.5 log10 TCID50 (median tissue culture infectious dose)/mL. BX-1 is based on MB photochemical technology, which was designed to inactivate HIV-1 virus in plasma. It was proven to be safe and reliable in clinical trials of HIV treatment. In this study, we showed that BX-1 could also be applied to inactivate SARS-CoV-2. During the current outbreak, this technique it has great potential for ensuring the safety of blood transfusions, for plasma transfusion therapy in recovering patients, and for preparing inactivated vaccines.

Covid-19 convalescent plasma therapy: Analyzing the factors that led to its failure in India.

Transfusion clinique et biologique - In corso di stampa. Prove corrette dall'autore. Disponibile online dal jeudi 17 juin 2021

Use of Convalescent Plasma Therapy for COVID-19: A Scientometric Assessment of Global Publications during 2020-21

Use of Convalescent Plasma Therapy for COVID-19: A Scientometric Assessment of Global Publications during 2020-21

RETRACTED ARTICLE: Methylene blue photochemical treatment as a reliable SARS-CoV-2 plasma virus inactivation method for blood safety and convalescent plasma therapy for COVID-19

BackgroundIn 2020, a new coronavirus, SARS-CoV-2, quickly spread worldwide within a few months. Although coronaviruses typically infect the upper or lower respiratory tract, the virus RNA can be detected in plasma. The risk of transmitting coronavirus via transfusion of blood products remains. As more asymptomatic infections are identified in COVID-19 cases, blood safety has become particularly important. Methylene blue (MB) photochemical technology has been proven to inactivate lipid-enveloped viruses with high efficiency and safety. The present study aimed to investigate the SARS-CoV-2 inactivation effects of MB in plasma.MethodsThe SARS-CoV-2 virus strain was isolated from Zhejiang University. The live virus was harvested from cultured VERO-E6 cells, and mixed with MB in plasma. The MB final concentrations were 0, 1, 2, and 4 μM. The “BX-1 AIDS treatment instrument” was used at room temperature, the illumination adjusted to 55,000 ± 0.5 million Lux, and the plasma was irradiated for 0, 2, 5, 10, 20, and 40 mins using light at a single wavelength of 630 nm. Virus load changes were measured using quantitative reverse transcription- PCR.ResultsBX-1 could effectively eliminate SARS-CoV-2 within 2 mins in plasma, and the virus titer declined to 4.5 log10 TCID50 (median tissue culture infectious dose)/mL.ConclusionBX-1 is based on MB photochemical technology, which was designed to inactivate HIV-1 virus in plasma. It was proven to be safe and reliable in clinical trials of HIV treatment. In this study, we showed that BX-1 could also be applied to inactivate SARS-CoV-2. During the current outbreak, this technique it has great potential for ensuring the safety of blood transfusions, for plasma transfusion therapy in recovering patients, and for preparing inactivated vaccines.

Bioethical perspective of convalescent plasma therapy for COVID-19: A systematic review.

Convalescent plasma therapy (CP) has long been used to prevent and treat various infectious diseases before COVID-19 such as SARS, MERS, and H1N1. Because the viral and clinical characteristics of COVID-19 share the similarities between SARS and MERS, CP treatment could be a promising treatment option to save COVID-19. With only low quality medical evidence, but massive media support and a very significant public demand for the use of convalescent plasma for COVID-19, we are now faced with an ethical dilemma. Therefore, this paper uses a structured analysis that focuses on the preferred reporting items for a systematic review of ethical issues regarding the use of Convalescent Plasma Therapy for COVID-19. The use of convalescent plasma must meet the ethical principles of autonomy; such as voluntary, informed consent, and confidentiality. Consideration of the risk-benefit ratio for potential donor recipients also needs to be considered in order to meet the beneficence and non-maleficence principles. The principle of justice also needs to be applied both to donors, donor recipients and health workers, such as determining the priority of donor recipients, due to the increasing demand for convalescent plasma amid the limited circumstances of patients who have recovered from Covid-19 who voluntarily donate.