Article

Meta-Analysis: Convalescent Blood Products for Spanish Influenza Pneumonia: A Future H5N1 Treatment?

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  • SAB BIOTHERAPEUTICS
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Abstract

Background: Studies from the Spanish influenza era reported that transfusion of influenza-convalescent human blood products reduced mortality in patients with influenza complicated by pneumonia. Treatments for H5N1 influenza are unsatisfactory, and convalescent human plasma containing H5N1 antibodies could be an effective therapy during outbreaks and pandemics. Purpose: To determine whether transfusion with influenza-convalescent human blood products reduced the risk for death in patients with Spanish influenza pneumonia. Data Sources: Manual search of English-language journals from 1918 to 1925. Citations from retrieved studies were also searched. Study Selection: Published English-language studies that had at least 10 patients in the treatment group, used convalescent blood products to treat Spanish influenza pneumonia in a hospital setting, and reported on a control or comparison group. Data Extraction: Two investigators independently extracted data on study characteristics, outcomes, adverse events, and quality. Data Synthesis: Eight relevant studies involving 1703 patients were found. Treated patients, who were often selected because of more severe illness, were compared with untreated controls with influenza pneumonia in the same hospital or ward. The overall crude case-fatality rate was 16% (54 of 336) among treated patients and 37% (452 of 1219) among controls. The range of absolute risk differences in mortality between the treatment and control groups was 8% to 26% (pooled risk difference, 21% [95% CI, 15% to 27%]). The overall crude case-fatality rate was 19% (28 of 148) among patients who received early treatment (after 4 days of pneumonia complications) and 59% (49 of 83) among patients who received late treatment (after 4 days of pneumonia complications). The range of absolute risk differences in mortality between the early treatment group and the late treatment group was 26% to 50% (pooled risk difference, 41% [CI, 29% to 54%]). Adverse effects included chill reactions and possible exacerbations of symptoms in a few patients. Limitations: Studies were few and had many methodologic limitations. No study was a blinded, randomized, or placebo-controlled trial. Some pertinent studies may have been missed. Conclusions: Patients with Spanish influenza pneumonia who received influenza-convalescent human blood products may have experienced a clinically important reduction in the risk for death. Convalescent human H5N1 plasma could be an effective, timely, and widely available treatment that should be studied in clinical trials.

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... [7,8] It supposedly engenders a temporary immune response against the viral particles, before the peak production of endogenous IgM and IgG antibodies by the native immune response is established in the patient. [9] The transient reduction in viral load reduces the stimulus for a hyperinflammatory cytokine storm that mediates further progression. Early administration of convalescent plasma in disease has been proven to be beneficial in some viral illnesses. ...
... Early administration of convalescent plasma in disease has been proven to be beneficial in some viral illnesses. [9,10] Numerous observational studies, randomised controlled trials (RCTs) and systematic reviews have been published thus far in patients with COVID-19, [11,12] with most recent reviews highlighting a lack of benefit of CP. [13] Multiple RCTs have been terminated early due to the decreasing prevalence of COVID-19, as well as refusal of consent from eligible patients. [14][15][16][17][18] As a result of this, the sample size of these RCTs are insufficient, and they are unable to provide strong evidence for or against CP in COVID- 19. ...
... Apart from its direct antiviral neutralising action, [9] CP therapy is postulated to provide additional benefit via immunomodulation of the infected host. [41] However, its effectiveness is confounded by the emergence of the newer alpha (B.1.1.7), ...
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Current evidence from randomised controlled trials (RCTs) and systematic reviews on the utility of convalescent plasma (CP) in patients with coronavirus disease 2019 (COVID-19) suggests a lack of benefit. We conducted an updated meta-analysis of RCTs with trial sequential analysis to investigate whether convalescent plasma is futile in reducing mortality in patients hospitalized with COVID-19. We searched six databases from 1st December 2019 to 1st August 2021 for RCTs comparing the use of CP with standard of care or transfusion of non-CP standard plasma in patients with COVID-19. The risk of bias was assessed using the Cochrane Risk-of-Bias 2 Tool. Random effects (DerSimonian and Laird) meta-analyses were conducted. The primary outcome was the aggregate risk for in-hospital mortality between both arms. We conducted a trial sequential analysis (TSA) based on the pooled relative risks (RRs) for in-hospital mortality. Secondary outcomes included the pooled RR for receipt of mechanical ventilation and mean difference in hospital length of stay. We included 18 RCTs (8702 CP, 7906 control). CP was not associated with a significant mortality benefit (RR: 0.95, 95%-CI: 0.86-1.04, p=0.27, high certainty). Subgroup analysis did not find any significant differences (pinteraction=0.30) between patients who received CP within 8 days of symptom onset (RR: 0.97, 95%-CI: 0.79-1.19, p=0.80), or after 8 days (RR: 0.79, 95%-CI: 0.57-1.10, p=0.16). TSA based on a RR reduction of 10% from a baseline mortality of 20% found that CP was not effective, with the pooled effect within the boundary for futility. CP did not significantly reduce the requirement for mechanical ventilation (RR: 1.00, 95%-CI: 0.91-1.10, p=0.99, moderate certainty) or hospital length of stay (+1.32, 95%-CI: -1.86 to +4.52, p=0.42, low certainty). CP does not improve relevant clinical outcomes in patients with COVID-19, especially in severe disease. The pooled effect of mortality was within the boundary of futility, suggesting the lack of benefit of CP in patients hospitalised with COVID-19.
... A metaanalysis of eight reports contributed by physicians at that time, demonstrates that patients who received early CP transfusion (after less than 4 days of pneumonia complications) had a statistically significant reduction in mortality and also showed general improvement of symptoms. 18 While some adverse effects like chills and aggravation of symptoms were noted in a few seriously ill patients, it could be due to the lack of proper quality control of the transfused CP. Since 1918, three additional pandemics in 1957, 1968, and 2009 were caused by H2N2, H3N2, and H1N1 influenza virus strains, respectively. ...
... Severe respiratory illness in humans due to the avian influenza virus, especially the H5N1 subtype, first appeared in Hong Kong in 1997, 20 and has continued to occur over the years. Convalescent H5N1 plasma has been considered as a therapeutic approach to lower the mortality rate 18 in a few studies with small sample size. A global approach and largescale population-based investigations are required to successfully utilize the potential of CP therapy in tackling H5N1 influenza outbreaks. ...
Article
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Convalescent plasma therapy provides a useful therapeutic tool to treat infectious diseases, especially where no specific therapeutic strategies have been identified. The ongoing pandemic puts back the spotlight on this age-old method as a viable treatment option. In this review, we discuss the usage of this therapy in different diseases including COVID-19, and the possible mechanisms of action. The current review also discusses the progress of therapeutic applications of blood-derivatives, from the simple transfer of immunized animal sera, to the more target-specific intravenous administration of human immunoglobulins from a pool of convalescent individuals, in both infectious and non-infectious diseases of various etiologies.
... In 2006, a meta-analysis of 1703 patients concluded that convalescent human H5N1 plasma could be an effective treatment for patients with Spanish influenza pneumonia (9). Another metaanalysis has been performed on 32 studies exploring the effectiveness of convalescent plasma in the treatment of severe acute respiratory infections. ...
... A meta-analysis of 32 studies on CP treatment in SARS patients also confirmed the consistent evidence of reduced mortality, especially when CP was administered early after symptom onset (9). Moreover, the survival rate was much higher in patients who were not on mechanical ventilation prior to CP transfusion. ...
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Background: Convalescent plasma (CP) transfusion is one of the suggested treatments for Coronavirus disease 2019 (COVID-19) especially in critically ill patients. Objectives: This study aimed to investigate the efficacy and safety of CP transfusion were investigated in severe/critically ill COVID-19 patients. Methods: This study was performed on 50 consecutive COVID-19 patients with severe/critically ill disease. Severe disease was defined as having at least one of the following symptoms: shortness of breath, respiratory frequency ≥ 20/min, blood oxygen saturation ≤ 93%, partial pressure of arterial oxygen to fraction of inspired oxygen ratio < 300, lung infiltrates > 50% within the last 24-48 h. Critically ill disease was identified by intensive care unit admission, respiratory failure, septic shock, or multiple organ dysfunction or failure. Primary outcomes included the safety of CP transfusion, 14-day and 30-day survival rate, and change in lung computed tomography (CT) scan score. Several other clinical and laboratory features were evaluated as the secondary outcomes. Results: Based on the results, 21 out of 50 consecutive patients were on mechanical ventilation at the time of CP transfusion. In total, 32 patients (64%) survived 30 days after CP transfusion. The survival rates were 74% and 44% in patients who received CP < 7 and ≥ 7 days after admission, respectively. While 92% of patients without mechanical ventilation survived, the survival rate of patients on mechanical ventilation was 29%. Moreover, the CT scan score and some other clinical features were improved in the group that received CP transfusion, and no adverse effects were observed. Conclusion: The CP transfusion is a safe and effective treatment in severe/critically ill COVID-19 patients. The best outcome can be achieved in patients who are not on mechanical ventilation, especially early in the disease course.
... 21 It has been using for patients with various viral infections, such as SARS, pandemic influenza and severe Ebola virus infection. 22,23,24 Shen et al. conducted a trial to determine the effects of CPT for five critically ill COVID and ARDS patients. 25 Despite a limited sample size and study design, they stated that CPT might be useful for critically ill patients. ...
... 62 Besides all these positive effects, plasma transfusion can also cause some side effects. The most common adverse reactions of CP treatment are tremors, fever, anaphylactic reactions, acute lung injury associated with transfusion, circulatory overload, and hemolysis, etc. 23,24 Meanwhile, the risk of the human immunodeficiency virus (HIV), hepatitis B virus, hepatitis C virus, and syphilis infections should not be ignored. Transfusion-related circulatory overload (TACO) is now recognized as the most common serious side effect of transfusions. ...
Article
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Objectives: The novel coronavirus disease 2019 pandemic is affecting all around the world, particularly healthcare systems. The most critical problem for the COVID-19 infection as an emerging acute respiratory disease is the lack of effective methods to control and treat the disease. To date, there is no specific therapeutic agent approved by the FDA, so treatment options are limited. There are more than 4034 interventional studies in progress listed in clinicaltrials.org (Access date: 21.12.2021). This number was 900 approximately in December 2020. These intensive studies, which have increased fourfold, are to find a safe and effective treatment method. Since absolute therapy has not been standardized globally, the treatment approach varies from country to country and even from hospital to hospital. In addition to the vaccine studies that have been finalized and the vaccines are available for use, additional studies are underway for existing drugs that can prevent this disease or improve outcomes for COVID patients. The potential toxicity of the drugs chosen for the treatment is one of the more critical limiting factors. Although the side effects of previously approved medicines are known, studies are needed to determine the side effect profiles for newly approved products such as remdesivir. In this review, we gathered the adverse and toxic effects of medications used against COVID-19 treatment according to the COVID guideline published by the Scientific Advisory Board of the Ministry of Health of Turkey.
... Pathogen-specific immunoglobulins isolated from plasma or whole blood of surviving patients can serve as a lifesaving therapy for those suffering from an infectious disease. This technique was used to treat diphtheria and bacterial infections in the 19 th century [279] and the Spanish influenza outbreak [279,280]. Moreover, plasma transfusion therapy has been used in H5N1 (Asian avian) influenza virus infection [280,281], H1N1 (swine flu) influenza virus infection [282,283], and Ebola virus infection [284][285][286][287]. Passive immunotherapy has also been favorable for treatment of SARS [288,289] and MERS [290,291]. ...
... Pathogen-specific immunoglobulins isolated from plasma or whole blood of surviving patients can serve as a lifesaving therapy for those suffering from an infectious disease. This technique was used to treat diphtheria and bacterial infections in the 19 th century [279] and the Spanish influenza outbreak [279,280]. Moreover, plasma transfusion therapy has been used in H5N1 (Asian avian) influenza virus infection [280,281], H1N1 (swine flu) influenza virus infection [282,283], and Ebola virus infection [284][285][286][287]. Passive immunotherapy has also been favorable for treatment of SARS [288,289] and MERS [290,291]. ...
... Therapeutic use of plasma from individuals who have recovered from Covid-19 has been hypothesized to show clinical benefits, particularly in immunocompromised patients and when used early in the course of the disease (1). The treatment rationale behind the use of convalescent plasma is to bridge the critical time period until a sufficient immune response is established in the infected patient (2). The use of convalescent plasma for the treatment of patients with Covid-19 has attracted widespread attention, yet definitive evidence of its efficacy is missing. ...
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Convalescent plasma is a suggested treatment for Coronavirus disease 2019 (Covid-19), but its efficacy is uncertain. We aimed to evaluate whether the use of convalescent plasma is associated with improved clinical outcomes in patients with Covid-19.In this systematic review and meta-analysis, we searched randomized controlled trials investigating the use of convalescent plasma in patients with Covid-19 in Medline, Embase, Web of Science, Cochrane Library, and medRxiv from inception to October 17 th , 2021. Two reviewers independently extracted the data. The primary efficacy outcome was all-cause mortality. The Cochrane Risk of Bias Tool and GRADE (Grading of Recommendations Assessment, Development and Evaluation) method were used. This study was registered with PROSPERO, CRD42021284861. Of the 8874 studies identified in the initial search, sixteen trials comprising 16 317 patients with Covid-19 were included. In the overall population, the all-cause mortality was 23.8% (2025 of 8524) with convalescent plasma and 24.4% (1903 of 7769) with standard of care (risk ratio (RR) 0.97, 95% CI 0.90-1.04) (high-certainty evidence). All-cause mortality did not differ in the subgroups of noncritically ill (21.7% [1288 of 5929] vs. 22.4% [1320 of 5882]) and critically ill (36.9% [518 of 1404] vs. 36.4% [455 of 1247]) patients with Covid-19. The use of convalescent plasma in patients who tested negative for anti-SARS-CoV-2 antibodies at baseline was not associated with significantly improved survival (RR 0.94, 95% CI 0.87-1.02). In the overall study population, initiation of mechanical ventilation (RR 0.97, 95% CI 0.88-1.07), time to clinical improvement (HR 1.09, 95% CI 0.91-1.30), and time to discharge (HR 0.95, 95% CI 0.89-1.02) were similar between the two groups. In patients with Covid-19, treatment with convalescent plasma, as compared with control, was not associated with lower all-cause mortality or improved disease progression, irrespective of disease severity and baseline antibody status. Systematic Review Registration https://www.crd.york.ac.uk/prospero/ , identifier PROSPERO ( CRD42021284861 ).
... The treatment plan for viral or mixed (viral and bacterial) pneumonia includes antiviral, anticoagulant, anti-inflammatory (Dexamethasone), and antibiotic drugs [11][12][13]. In the clinical forms in which cytokine storm occurs, the treatment plan is supplemented with immunomodulators (Tocilizumab or Anakinra) [14][15][16]. ...
Article
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(1) Background: The antiviral treatment for COVID-19 disease started to be largely used in 2020 and has been found to be efficient, although it is not specific for SARS-CoV-2 virus. There were some concerns that it may produce liver damage or other side effects. (2) Methods: The aim of this study was to observe if antiviral therapy is affecting liver parameters or producing other side-effects in patients hospitalized for COVID-19 disease. The study included a group of patients hospitalized in the internal medicine department of Oradea Municipal Clinical Hospital, Romania, between August 2020–June 2021, diagnosed with SARS-CoV-2 viral infection by RT-PCR method or rapid antigen test. During hospitalization, patients were treated with a Lopinavir/Ritonavir (Kaletra) combination, or with Favipiravir or Remdesivir. In addition to monitoring the evolution of the disease (clinical and biochemical), also hepatic parameters were analyzed at admission, during hospitalization, and at discharge. (3) Results: In the group of studied patients, the mean value of aspartat aminotrensferase did not increase above normal at discharge, alanin aminotransferase increased, but below twice the normal values, and cholestasis registered a statistically insignificant slight increase. (4) Conclusions: In our study, we found that all three antivirals were generally well tolerated and their use did not alter liver function in a significant manner.
... Although convalescent plasma therapy has been considered generally beneficial due to multiple examples, both historical and recent (1,19,20), scientific medical community lacks definitive proof of its efficacy coming from carefully designed randomized clinical trials (2). When such trials were undertaken, they were unable to demonstrate a beneficial effect of plasma over placebo (21). ...
Article
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During the ongoing COVID-19 epidemic many efforts have gone into the investigation of the SARS-CoV-2–specific antibodies as possible therapeutics. Currently, conclusions cannot be drawn due to the lack of standardization in antibody assessments. Here we describe an approach of establishing antibody characterisation in emergent times which would, if followed, enable comparison of results from different studies. The key component is a reliable and reproducible assay of wild-type SARS-CoV-2 neutralisation based on a banking system of its biological components - a challenge virus, cells and an anti-SARS-CoV-2 antibody in-house standard, calibrated to the First WHO International Standard immediately upon its availability. Consequently, all collected serological data were retrospectively expressed in an internationally comparable way. The neutralising antibodies (NAbs) among convalescents ranged from 4 to 2869 IU mL ⁻¹ in a significant positive correlation to the disease severity. Their decline in convalescents was on average 1.4-fold in a one-month period. Heat-inactivation resulted in 2.3-fold decrease of NAb titres in comparison to the native sera, implying significant complement activating properties of SARS-CoV-2 specific antibodies. The monitoring of NAb titres in the sera of immunocompromised COVID-19 patients that lacked their own antibodies evidenced the successful transfusion of antibodies by the COVID-19 convalescent plasma units with NAb titres of 35 IU mL ⁻¹ or higher.
... The presence of virus-specific antibodies has been detected in most of the patients who have successfully eliminated the virus (Ahmad et al., 2020;. The plasma containing antibodies from the recovered patients are thus given to the infected patients who could not mount an adequate humoral response (Luke et al., 2006). This traditional approach is based on the principle that the neutralizing antibodies from the recovered patients will provide a similar and durable response in the infected patients who receive the CPT. ...
Article
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Coronavirus disease 2019 (COVID-19) has overwhelmed the healthcare and economy of the world, with emerging new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) posing an everlasting threat to humanity. While most COVID-19 vaccines provide adequate protective immunological response against the original SARS-CoV-2 variant, there is a pressing need to understand their biological and clinical responses. Recent evidence suggests that some of the new variants of SARS-CoV-2 evade the protection conferred by the existing vaccines, which may impede the ongoing efforts to expedite the vaccination programs worldwide. These concerns have also highlighted the importance of a pan-COVID-19 vaccine, which is currently in the making. Thus, it is imperative to have a better molecular and clinical understanding of the various COVID-19 vaccines and their immunological trajectory against any emerging variant of concerns (VOCs) in particular to break this vicious cycle. Furthermore, other treatment regimens based on cellular therapies and monoclonal antibodies should be explored systematically as an alternative and readily available option considering the possibility of the emergence of more virulent SARS-CoV-2 mutants. In this review, we shed light on the various molecular mechanisms and clinical responses of COVID-19 vaccines. Importantly, we review the recent findings of their long-term immune protection and efficacy against emerging VOCs. Considering that other targeted and effective treatments will complement vaccine therapy, we provide a comprehensive understanding of the role of cell-based therapies, monoclonal antibodies, and immunomodulatory agents as alternative and readily available treatment modalities against any emerging SARS-CoV-2 variant.
... They further found that out of 80 patients, 33 patients transfused convalescent plasma within the 2 weeks of symptom onset showed better outcomes than those transfused later. 1 During the current pandemic (SARS CoV-2), many studies have proven that convalescent plasma can limit viral replication by providing passive neutralising antibodies to SARS CoV-2in the initial viraemia phase and thus mitigate the disease in the absence of definitive therapy. 5 In recovered patients, who are prospective COPLA donors, there are variations in antibody titres and specificities against components of the virus. 6 In this trial, we assessed the safety and efficacy of convalescent plasma transfusion in severe COVID-19 patients using an ordinal scale until 28 days for clinical outcomes. ...
... They further found that out of 80 patients, 33 patients transfused convalescent plasma within the 2 weeks of symptom onset showed better outcomes than those transfused later. 1 During the current pandemic (SARS CoV-2), many studies have proven that convalescent plasma can limit viral replication by providing passive neutralising antibodies to SARS CoV-2in the initial viraemia phase and thus mitigate the disease in the absence of definitive therapy. 5 In recovered patients, who are prospective COPLA donors, there are variations in antibody titres and specificities against components of the virus. 6 In this trial, we assessed the safety and efficacy of convalescent plasma transfusion in severe COVID-19 patients using an ordinal scale until 28 days for clinical outcomes. ...
Article
Full-text available
Importance: No proven treatment is available for severely ill COVID-19. Therapeutic use of COVID-19 convalescent plasma (COPLA) is under investigation. Objective: To compare the efficacy of COPLA with standard medical therapy (SMT) alone in severe COVID-19 patients. Design, setting and participants: A multicentric, open-labelled, phase-III randomised controlled trial conducted at two treatment centres with COPLA collected at the third dedicated centre in North-India, the coordinating centre during trial from June 2020 to December 2020. The study population comprised 400 participants in the ratio of 1:1 in each treatment group. Intervention: One group received COPLA with SMT (n=200), and another group received SMT only (n=200). Main outcome measures: Primary outcome was time to clinical improvement measured by a two-point reduction in the ordinal scale. Secondary outcomes included duration of O2 therapy, the proportion of patients on mechanical ventilation at day-7, mortality, SARS-CoV-2 antibody levels, cytokine levels and incidence of adverse events. Results: The median time to a two-point reduction in the ordinal scale in both groups was 9 days (IQR=7-13) (p=0.328). The median duration of O2 therapy was 8 days (IQR=6-12) in COPLA and 10 days (IQR=6-12) in SMT group (p=0.64). The PaO2/FiO2 ratio showed significant improvement at 7 days in COPLA group(p=0.036). There was no difference in mortality till 28 days in both groups (p=0.62). However, if COPLA was given within 3 days of hospital admission, a significant reduction in ordinal scale was observed (p=0.04). Neutralising antibody titres in COPLA group (80 (IQR 80-80)) were higher than SMT group (0 (IQR 0-80)) at 48 hours (p=0.001). COPLA therapy led to a significant reduction in TNF-α levels at 48 hours (p=0.048) and D-dimer at 7 days (p=0.02). Mild allergic reactions were observed in 3 (1.5%) patients in COPLA group. Conclusion and relevance: Convalescent plasma with adequate antibody titres should be transfused in COVID-19 patients along with SMT in the initial 3 days of hospitalisation for better clinical outcomes. Trial registration number: NCT04425915.
... F irst reported in December 2019, 1 the COVID-19 pandemic spread to the US, with an epicenter in New York City (NYC) resulting in 203 000 cases and 18 600 fatalities from March to June 2020. 2 The absence of effective therapies prompted COVID-19 convalescent plasma (CCP) use because of biological plausibility and historical success of convalescent plasma in prior pandemics [3][4][5] and randomized trials for diphtheria 6,7 and Argentine hemorrhagic fever. 8 Although early CCP treatment of hospitalized patients with COVID-19 reduced mortality in matched-control studies, [9][10][11][12] randomized clinical trials have yielded mixed results, reducing mortality in one study 13 but not others, [14][15][16][17][18][19] despite showing signals of efficacy in some subgroups. ...
Article
Full-text available
Importance There is clinical equipoise for COVID-19 convalescent plasma (CCP) use in patients hospitalized with COVID-19. Objective To determine the safety and efficacy of CCP compared with placebo in hospitalized patients with COVID-19 receiving noninvasive supplemental oxygen. Design, Setting, and Participants CONTAIN COVID-19, a randomized, double-blind, placebo-controlled trial of CCP in hospitalized adults with COVID-19, was conducted at 21 US hospitals from April 17, 2020, to March 15, 2021. The trial enrolled 941 participants who were hospitalized for 3 or less days or presented 7 or less days after symptom onset and required noninvasive oxygen supplementation. Interventions A unit of approximately 250 mL of CCP or equivalent volume of placebo (normal saline). Main Outcomes and Measures The primary outcome was participant scores on the 11-point World Health Organization (WHO) Ordinal Scale for Clinical Improvement on day 14 after randomization; the secondary outcome was WHO scores determined on day 28. Subgroups were analyzed with respect to age, baseline WHO score, concomitant medications, symptom duration, CCP SARS-CoV-2 titer, baseline SARS-CoV-2 serostatus, and enrollment quarter. Outcomes were analyzed using a bayesian proportional cumulative odds model. Efficacy of CCP was defined as a cumulative adjusted odds ratio (cOR) less than 1 and a clinically meaningful effect as cOR less than 0.8. Results Of 941 participants randomized (473 to placebo and 468 to CCP), 556 were men (59.1%); median age was 63 years (IQR, 52-73); 373 (39.6%) were Hispanic and 132 (14.0%) were non-Hispanic Black. The cOR for the primary outcome adjusted for site, baseline risk, WHO score, age, sex, and symptom duration was 0.94 (95% credible interval [CrI], 0.75-1.18) with posterior probability (P[cOR<1] = 72%); the cOR for the secondary adjusted outcome was 0.92 (95% CrI, 0.74-1.16; P[cOR<1] = 76%). Exploratory subgroup analyses suggested heterogeneity of treatment effect: at day 28, cORs were 0.72 (95% CrI, 0.46-1.13; P[cOR<1] = 93%) for participants enrolled in April-June 2020 and 0.65 (95% CrI, 0.41 to 1.02; P[cOR<1] = 97%) for those not receiving remdesivir and not receiving corticosteroids at randomization. Median CCP SARS-CoV-2 neutralizing titer used in April to June 2020 was 1:175 (IQR, 76-379). Any adverse events (excluding transfusion reactions) were reported for 39 (8.2%) placebo recipients and 44 (9.4%) CCP recipients (P = .57). Transfusion reactions occurred in 2 (0.4) placebo recipients and 8 (1.7) CCP recipients (P = .06). Conclusions and Relevance In this trial, CCP did not meet the prespecified primary and secondary outcomes for CCP efficacy. However, high-titer CCP may have benefited participants early in the pandemic when remdesivir and corticosteroids were not in use. Trial Registration ClinicalTrials.gov Identifier: NCT04364737
... studies have demonstrated that this method has been used for the remedy of SARS-CoV [7][8][9][10], Ebola [11][12][13][14][15], Influenza A (H5N1) [16], Chikungunya virus [17], H1N1 flu [18,19], H7N9 flu [20], Measles [21], Mumps [22], Human immunodeficiency virus (HIV) [23], MERS-COV [24,25], Pummal virus [26] infections. It has been reported that CPT is a safe option [27,28]. ...
Article
Full-text available
In late 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged, causing a global pandemic called COVID-19. Currently, there is no definitive treatment for this emerging disease. Global efforts resulted in developing multiple platforms of COVID-19 vaccines, but their efficacy in humans should be wholly investigated in the long-term clinical and epidemiological follow-ups. Despite the international efforts, COVID-19 vaccination accompanies challenges, including financial and political obstacles, serious adverse effects (AEs), the impossibility of using vaccines in certain groups of people in the community, and viral evasion due to emerging novel variants of SARS-CoV-2 in many countries. For these reasons, passive immunotherapy has been considered a complementary remedy and a promising way to manage COVID-19. These approaches are based on reduced inflammation due to inhibiting cytokine storm phenomena, immunomodulation, preventing acute respiratory distress syndrome (ARDS), viral neutralization, and decreased viral load. This article highlights passive immunotherapy and immunomodulation approaches in managing and treating COVID-19 patients and discusses relevant clinical trials (CTs).
... Cenci used the blood of a patient who had recovered from measles to successfully protect four children from measles, even as their uninoculated cohabitating siblings became ill [128]. Since then, CPT has been used countless times as a first line of therapy against epidemic and pandemic virus outbreaks including, notably, the Spanish influenza epidemic of 1916-1918 [129], SARS in 2004 [130,131], influenza A H1N1 pandemic of 2009 [132], Ebola in 2014 [133,134], MERS in 2015 [135] and, most recently, COVID-19 [136][137][138][139][140][141][142][143][144][145]. ...
Article
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This is an extensive review on virtually all aspects of antibodies against SARS-CoV-2 and the disease it causes, COVID-19. It contains over 550 references and is completely up to date as of end of February, 2022.
... Convalescent plasma therapy was used in patients with Spanish flu, and a report suggests that its efficacy was demonstrated by an analysis of the patients given the therapy at that time [5]. More than 40 years ago, the therapy was reported to have decreased mortality in a randomized controlled study in patients with Argentine hemorrhagic fever [6]. ...
Article
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Background: Coronavirus disease 2019 is a global public health concern. As of December 2020, the therapeutic agents approved for coronavirus disease 2019 in Japan were limited to two drugs: remdesivir, an antiviral drug, granted a Special Approval for Emergency on 7 May 2020, and dexamethasone, which has an anti-inflammatory effect. The aim of this study is to evaluate the efficacy of convalescent plasma collected from donors who recovered from coronavirus disease 2019. Methods: This is an open-label, randomized controlled trial comprising two groups: a convalescent plasma and a standard-of-care group. Plasma administered to patients with coronavirus disease 2019 randomized in the convalescent plasma group of this trial will be plasma that has been collected and stored in an associated study. Patients with a diagnosis of mild coronavirus disease 2019 will be included in this trial. The efficacy of convalescent plasma transfusion will be evaluated by comparing the convalescent plasma group to the standard-of-care group (without convalescent plasma transfusion) with respect to changes in the viral load and other measures. The primary endpoint will be time-weighted average changes in the SARS-CoV-2 virus load in nasopharyngeal swabs from day 0 to days 3 and 5. It is hypothesized that the intervention should result in a decrease in the viral load in the convalescent plasma group until day 5. This endpoint has been used as a change in viral load has and been used as an index of therapeutic effect in several previous studies. Discussion: The proposed trial has the potential to prevent patients with mild COVID-19 from developing a more severe illness. Several RCTs of convalescent plasma therapy have already been conducted in countries outside of Japan, but no conclusion has been reached with respect to the efficacy of convalescent plasma therapy, which is likely in part because of the heterogeneity of the types of target patients, interventions, and endpoints among trials. Actually, previous clinical trials on plasma therapy have shown inconsistent efficacy and are sometimes ineffective in COVID-19 patients with severe disease, which is due to unmeasured neutralizing antibody titer in the COVID-19 convalescent plasma. To improve this issue, in this study, we measure neutralizing activity of convalescent plasma before administration and provide the plasma with high neutralizing activity to the subjects. It is hoped that this study will further evidence to support the role of convalescent plasma therapy in COVID-19.
... NABs are transferred into recently infected patients with SARS-CoV-2, which helps in combating viral multiplication [21][22][23]. CPT has been employed in various viral outbreaks, namely SARS, MERS, Ebola, and H1N1 influenza [24][25][26][27][28]. Although the CPT was tested during the SARS, MERS, and Ebola epidemics, but there were no randomized control trials to back up its effectiveness. ...
Article
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Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has resulted in a catastrophic pandemic and severely impacted people’s livelihoods worldwide. In addition, the emergence of SARS-CoV-2 variants has posed a severe threat to humankind. Due to the dearth of therapeutic options during the commencement of the pandemic, convalescent plasma therapy (CPT) played a significant part in the management of patients with severe form of COVID-19. Several recent studies have proposed various protective effects of CPT, such as antiviral, anti-inflammatory, antithrombotic, and immunomodulatory actions, curtailing the devastating consequences of the SARS-CoV-2 infection. On the contrary, several clinical studies have raised some serious concerns about the effectiveness and reliability of CPT in the management of patients with COVID-19. The protective effects of CPT in severely ill patients are yet to be proved. Moreover, the emergence of SARS-CoV-2 variants has raised concerns about the effectiveness of CPT against COVID-19. Therefore, to establish concrete evidence of the efficacy of CPT and adjudicate its inclusion in the management of COVID-19, an updated review of present literature is required, which could help in the development of an efficient therapeutic regimen to treat COVID-19 amid the emergence of new viral variants.
... Convalescent plasma is a passive antibody therapy that has been used successfully to treat respiratory illnesses during previous epidemics. 2,3 Given early reports of mortality secondary to COVID-19 in the United States during the early phases of the pandemic and the lack of effective treatment to combat the disease, patients in Arkansas were treated with CCP via the Food and Drug Administration (FDA) emergency Investigational New Drug (eIND) mechanism. Patients began receiving 2 units of CCP starting in April 2020. ...
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Importance Many therapies are used to treat COVID-19, the disease caused by the virus SARS-CoV-2, including convalescent plasma. The clinical utility of using 2 units of convalescent plasma for COVID-19 hospitalized patients is not fully understood. Objective Many therapies are used to treat COVID-19, the disease caused by the virus SARS-CoV-2, including convalescent plasma. The clinical utility of using 2 units of convalescent plasma for COVID-19 hospitalized patients is not fully understood. Our study aims to determine the safety and efficacy of treating hospitalized COVID-19 patients with 2 units of COVID-19 convalescent plasma (CCP). Method This was a retrospective study of Arkansas patients treated with CCP using the (US) Food and Drug Administration (FDA) emergency Investigational New Drug (eIND) mechanism from April 9, 2020, through August 9, 2020. It was a multicenter, statewide study in a low-resource setting, which are areas that lack funding for healthcare cost coverage on various levels including individual, family, or social. Adult patients (n = 165, volunteer sample) in Arkansas who were hospitalized with severe or life-threatening acute COVID-19 disease as defined by the FDA criteria were transfused with 2 units of CCP (250 mL/unit) using the FDA eIND mechanism. The primary outcome was 7- and 30-day mortality after the second unit of CCP. Results Unadjusted mortality was 12.1% at 7 days and 23.0% at 30 days. The unadjusted mortality was reduced to 7.7% if the first CCP unit was transfused on the date of diagnosis, 8.7% if transfused within 3 days of diagnosis, and 32.0% if transfused at or after 4 or more days of diagnosis. The risk of death was higher in patients that received low, negative, or missing titer CCP units in comparison to those that received higher titer units. Conclusion The provision of 2 units of CCP was associated with a reduction in mortality in patients treated with high titer units within 3 days of COVID-19 diagnosis. Given the results, CCP is a viable, low-cost therapy in resource-constrained states and countries.
... In the present study, we extended the observations by groups, including Chan et al. and Haagmans et al., and demonstrated that hn-plasmas reduced the severity of lung lesions in SARS-CoV-2-exposed Syrian hamsters even when such plasmas were given to the animals 24 h after the inoculation compared to those receiving a nonneutralizing (control) plasma or moderately neutralizing plasmas (mn-plasmas) as assessed with micro-CT-captured images (Fig. S2 in the supplemental material and Fig. 3) and the presence of SARS-CoV-2infected cells in the lung (Fig. 4 and Fig. S3 and S4). In fact, there is a growing body of literature that convalescent plasma therapy is not beneficial when started in the late stage of the disease (44), and early transfusion (within 3 days of hospital administration) of hn-plasma represents the optimal use for the highest efficacy of the treatment (45). Moreover, hn-plasmas induced a significant reduction of viral titers in the lungs of SARS-CoV-2-exposed Syrian hamsters compared to those receiving control plasma or mn-plasmas (Fig. 5a). ...
Article
Despite various attempts to treat SARS-CoV-2-infected patients with COVID-19-convalescent plasmas, neither appropriate approach nor clinical utility has been established. We examined the efficacy of administration of highly-neutralizing COVID-19-convalescent plasma ( hn -plasmas) and such plasma-derived IgG administration using the Syrian hamster COVID-19 model. Two hn -plasmas, which were in the best 1% of 340 neutralizing-activity-determined convalescent plasma samples, were intraperitoneally administered to SARS-CoV-2-infected hamsters, resulting in significant reduction of viral titers in lungs by up to 32-fold as compared to the viral titers in hamsters receiving control non-neutralizing plasma, while with two moderately neutralizing plasmas ( mn -plasmas) administered, viral titer reduction was by up to 6-fold. IgG fractions purified from the two hn -plasmas also reduced viral titers in lungs than those from the two mn -plasmas. The severity of lung lesions seen in hamsters receiving hn -plasmas was minimal to moderate as assessed using micro-computerized tomography, which histological examination confirmed. Western blotting revealed that all four COVID-19-convalescent-plasmas variably contained antibodies against SARS-CoV-2 components including the receptor-binding domain and S1 domain. The present data strongly suggest that administering potent-neutralizing-activity-confirmed COVID-19-convalescent plasmas would be efficacious in treating patients with COVID-19. Importance Convalescent plasmas obtained from patients, who recovered from a specific infection, have been used as agents to treat other patients infected with the very pathogen. To treat using convalescent plasmas, despite that more than 10 randomized-controlled-clinical-trials have been conducted and more than 100 studies are currently ongoing, the effects of convalescent plasma against COVID-19 remained uncertain. On the other hand, certain COVID-19 vaccines have been shown to reduce the clinical COVID-19 onset by 94-95%, for which the elicited SARS-CoV-2-neutralizing antibodies are apparently directly responsible. Here, we demonstrate that highly-neutralizing-effect-confirmed convalescent plasmas significantly reduce the viral titers in the lung of SARS-CoV-2-infected Syrian hamsters and block the development of virally-induced lung lesions. The present data provide a proof-of-concept that the presence of highly-neutralizing antibody in COVID-19-convalescent plasmas is directly responsible for the reduction of viral replication and support the use of highly-neutralizing antibody-containing plasmas in COVID-19 therapy with convalescent plasmas.
... The results showed that convalescent plasma therapy in addition to standard treatment, compared with standard treatment alone, did not result in a significant improvement in time to clinical improvement within 28 days. Of note, it is known that other treatments, including antiviral drugs, steroids, and intravenous immunoglobulin, have the possibility to affect the relationship between convalescent plasma and antibody level (Luke et al., 2006). Thus, it is controversial whether it is worthwhile to examine the safety and efficacy of convalescent plasma intervention against SARS-CoV-2 infection in further randomized clinical trials. ...
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Since the outbreak of corona virus disease 2019 (COVID-19) in Wuhan (China) in December 2019, the epidemic has rapidly spread to many countries around the world, posing a huge threat to global public health. In response to the pandemic, a number of clinical studies have been initiated to evaluate the effect of various treatments against COVID-19, combining medical strategies and clinical trial data from around the globe. Herein, we summarize the clinical evaluation about the drugs mentioned in this review for COVID-19 treatment. This review discusses the recent data regarding the efficacy of various treatments in COVID-19 patients, to control and prevent the outbreak.
... Treatment with CP dates back to the end of the 19th century, in treatment of diphtheria and tetanus patients [87] and over the past decades, CP transfusion has proved its specificity and effectiveness as a potential treatment in patients with MERS-CoV [88], H1N15 [89], SARS-CoV [90][91][92] and cancer therapy which could help ameliorate survival rates in patients whose condition deteriorated even with conventional treatment. Previous studies of SARS and severe influenza recommended transfusion of CP as early as possible because the production of endogenous IgM and IgG antibodies summitted at 2 w and 4 w after infection, respectively [93]. To employ convalescent serum administration for COVID-19 the following six conditions must be met: (i) availability of donors (ii) blood banking facilities (iii) availability of assays to detect virus in serum and to estimate viral neutralization; (iv) virology lab facilities (v) randomized clinical trials (vi) regulatory compliance, comprising institutional review board approval, which might vary depending on location [94]. ...
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In December 2019, Wuhan City, Hubei Province, China, first reported pneumonia like symptoms with unknown aetiology caused by a novel coronavirus. The novel coronavirus was renamed as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) by Coronaviridae Study Group of the International Committee on Taxonomy of Viruses and the disease was termed as Coronavirus Disease 2019 (COVID-19). As of 19 August, 2022, the infection has reached above 220 countries, areas or territories with a total of 591 683 619 confirmed cases and 6 443 306 deaths, as published by the World Health Organization (WHO). SARS-CoV-2 is strongly contagious as it has R0, 2.2-2.6, in comparison to SARS-CoV (<1) and Middle East respiratory syndrome coronavirus (MERS-CoV) (1.4-2.5), respectively. SARS-CoV-2 might become less virulent than the SARS-CoV and MERS-CoV, with the currently analyzed mortality of COVID-19 is 3.4%. The original SARS-CoV-2 has undergone “virus evolution” with the occurrence of numerous variants such as Alpha, Beta, Gamma and Delta etc. Recently, the circulating variant of concern is Omicron subvariants. Currently, real-time reverse transcription–polymerase chain reaction-based detection of the viral genome (RNA) is the gold standard for diagnosis of SARS-CoV-2 infection. At present, Remdesivir (RDV) and Baricitinib drugs as well as vaccines Pfizer-BioNTech and Moderna have been approved for the treatment of COVID-19 by Food and Drug Administration (FDA). In this review, we summarized the existing state of knowledge on approved antiviral therapy, combination therapy, blood-derived therapeutics and immunomodulators to treat COVID-19 pandemic.
... 4 The practice of using blood products from recovered patients as a therapeutic agent was way back in the late 1800s. CPT has been effectively used since the Spanish influenza pandemic in 1915-1917, 5 severe acute respiratory syndrome (SARS) in 2003, 6 influenza A (H1N1) in 2009, 7 avian influenza A (H5N1), 8 and even in viral hemorrhagic fever-like Ebola. 3 The CPT seems to be a promising option, with some early promising results on the improvement of clinical symptoms and reduction in mortality. ...
Article
In the absence of a definitive therapy during this ongoing unprecedented crisis, coronavirus disease-2019 (COVID-19) pandemic, convalescent plasma transfusion (CPT) has shown some promising results. This review summarizes the existing evidence of the efficacy of CPT in COVID-19 patients based upon scientific publications to date. We have included only the randomized controlled trials (RCTs) through an extensive screening of electronic databases up to July 31, 2021. In 19 RCTs, with a total of 16,476 COVID-19 patients we found low-quality evidence of significant reduction in mortality (odds ratio (OR) = 0.80; 95% confidence interval (CI): 0.66-0.96, I2 = 40%), better clinical outcome when applied <7 days (OR = 2.13, 95% CI 1.28-3.53, I2 = 0%), and improved viral clearance (OR = 2.6, 95% CI: 1.3-5.45, I2 = 74%). Meta-regression analysis found that as a covariate, intubation on admission (p = 0.007) had a significant impact. However, there was any significant reduction neither in duration for clinical improvement (MD = -0.79, 95% CI: -2.76-1.18, I2 = 98%), nor in total period of hospital stay (MD = 0.02, 95% CI: -0.75-0.78, I2 = 81%). Early application of CPT is still relevant in reducing morbidity and mortality in critically ill patients and is too early to write it off as a potential therapeutic modality for COVID-19 patients. How to cite this article: Sarkar S, Khanna P, Singh AK. Convalescent -Plasma-A Light at the End of the Tunnel: A Systematic Review and Meta-analysis of Randomized Controlled Trials. Indian J Crit Care Med 2021;25(11):1292-1300.
... The number of deaths from COVID-19 in the United States (US) had surpassed 500,000 by February 11, 2021 (1), less than a year after the first case of novel coronavirus (SARS-CoV-2) was confirmed in the US, demonstrating the urgent need to find safe and effective treatment options. Convalescent plasma, rich in antibodies from recently recovered patients, was used successfully in the 1918 influenza pandemic (2), SARS-1 (3), and Ebola (4) epidemics. Recognizing that a vaccine would not be widely available for several months to a year, and facing a paucity of treatment options, the US Federal Government, in collaboration with the Mayo Clinic and the national blood banking community, developed the Expanded Access Program (EAP) for COVID-19 convalescent plasma as a national registry to provide access to this potentially lifesaving treatment, examine the safety, and as much as possible, the efficacy of convalescent plasma treatment in hospitalized patients. ...
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Treatment of patients with COVID-19 using convalescent plasma from recently recovered patients has been shown to be safe, but the time course of change in clinical status following plasma transfusion in relation to baseline disease severity has not yet been described. We analyzed short, descriptive daily reports of patient status in 7,180 hospitalized recipients of COVID-19 convalescent plasma in the Mayo Clinic Expanded Access Program. We assessed, from the day following transfusion, whether the patient was categorized by his or her physician as better, worse or unchanged compared to the day before, and whether, on the reporting day, the patient received mechanical ventilation, was in the ICU, had died or had been discharged. Most patients improved following transfusion, but clinical improvement was most notable in mild to moderately ill patients. Patients classified as severely ill upon enrollment improved, but not as rapidly, while patients classified as critically ill/end-stage and patients on ventilators showed worsening of disease status even after treatment with convalescent plasma. Patients age 80 and over showed little or no clinical improvement following transfusion. Clinical status at the time of convalescent plasma treatment and age appear to be the primary factors in determining the therapeutic effectiveness of COVID-19 convalescent plasma among hospitalized patients.
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Transfer of convalescent plasma (CP) had been proposed early during the SARS-CoV-2 pandemic as an accessible therapy, yet trial results worldwide have been mixed, potentially due to the heterogeneous nature of CP. Here we perform deep profiling of SARS-CoV-2-specific antibody titer, Fc-receptor binding, and Fc-mediated functional assays in CP units, as well as in plasma from hospitalized COVID-19 patients before and after CP administration. The profiling results show that, although all recipients exhibit expanded SARS-CoV-2-specific humoral immune responses, CP units contain more functional antibodies than recipient plasma. Meanwhile, CP functional profiles influence the evolution of recipient humoral immunity in conjuncture with the recipient’s pre-existing SARS-CoV2-specific antibody titers: CP-derived SARS-CoV-2 nucleocapsid-specific antibody functions are associated with muted humoral immune evolution in patients with high titer anti-spike IgG. Our data thus provide insights into the unexpected impact of CP-derived functional anti-spike and anti-nucleocapsid antibodies on the evolution of SARS-CoV-2-specific response following severe infection. Convalescent plasma (CP) has been trialed as a therapy for SARS-CoV-2 symptoms, but its heterogenous nature precludes uniform outcomes. Here the authors perform deep profiling of CP, as well as plasma of CP recipients before and after transfer, to find CP-mediated, spike/nucleocapsid-focused modulations of humoral responses in the recipient.
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Introduction: Transfusion systems worldwide have had to face many challenges against the emergence or the re-emergence of numerous infectious diseases. Some of those viruses have posed significant impacts on blood transfusion activities. Several scientific and transfusion experts consider the current COVID-19 pandemic to present a potential risk of reducing and compromising the supply of blood products. Blood establishments had to activate their emergency plans and to propose appropriate response measures. Method: It is an international review where we used key terms search strategy to identify necessary information about: (i) the impact of some previous emergent viruses on the availability and the safety of blood products and (ii) the impact of the current COVID-19 pandemic on the blood transfusion activities worldwide. Additionally, we presented the impact of the COVID-19 pandemic on the Moroccan transfusion system activities and the measures established by the Moroccan National Centre of Blood Transfusion and Hematology (MNCBTH) to ensure management of this health crisis on the availability and the safety of blood products in Morocco.Results: Viruses like Zika, Influenza A (H1N1), Chikungunya, SARS-CoV, MERS-CoV, and Ebola have been of great concern in terms of virulence, modes of transmission, and impact on blood transfusion activities. The COVID-19 pandemic has impacted the availability of blood products in blood establishments worldwide. In Morocco, the COVID-19 pandemic affected blood collections and caused a significant decrease in the number of blood donors nationally. Data provided from all regional blood transfusion centers and blood banks in Morocco show that the total number of blood donations made in 2020 was 297,841 blood donations nationally compared to 334,510 blood donations made in 2019, with a decrease of 36,669 blood donations. The number of labile blood products (LBP) produced in 2020 was 455,805 units compared to 695,974 units produced in 2019, which corresponds to a reduction of 57,654 units. The number of LBP delivered in 2020 is 455,805 units against 451,736 delivered in 2019, with an increase of 4069 units. The pandemic impacted other activities of the blood transfusion system in Morocco like continuing education programs, meeting activities, technical missions, and the Moroccan plasma removal for the fractionation. Conclusion: The COVID-19 pandemic has had a significant impact on blood transfusion activities worldwide. The MNCBTH has expressed continued adaptability to ensure proper management of the impact of the COVID-19 pandemic on the availability and safety of blood products in Morocco.
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Humans infected with SARS-CoV-2 may develop COVID-19, which manifests across a wide spectrum of clinical severity ranging from mild upper respiratory tract illnesses to diffuse viral pneumonia, causing acute respiratory failure. Many therapies have been tested for their efficacy in treating COVID-19. Controversy surrounds convalescent plasma transfusions as an effective treatment for COVID-19. This study discusses the efficacy of this treatment on COVID-19 patients. Electronic medical record data were collected from patients diagnosed with COVID-19, from November 2020 to August 2021, in the Galilee Medical Center’s COVID-19 departments. Epidemiological, clinical, laboratory and imaging variables were analyzed. Multivariate stepwise regression and discriminant analyses were used to identify and validate the correlation between convalescent treatment and either death or time to negative PCR and hospitalization length. The study population included 270 patients, 100 of them treated with convalescent plasma. The results show that convalescent plasma therapy significantly prevented mortality in moderate patients, reduced hospitalization length and time to negative PCR. Additionally, high BMI, elderly age, high CRP and 4C-scores correlated with the severity and mortality of COVID-19 patients. Convalescent plasma also significantly reduced inflammatory markers, especially in moderate COVID-19 patients. In non-critical hospitalized patients, convalescent plasma therapy reduces morbidity and mortality in moderate COVID-19 patients and hospitalization length. Identifying patients who could benefit from this treatment could reduce the risk of death and shorten their hospitalization stay.
Article
Background Despite extensive vaccination, the quantity of patients infected with the SARS-CoV-2 virus and its variants continues to grow worldwide. Treating patients with a severe course of COVID-19 is a difficult challenge. One of the generally accepted and specific therapy methods is the use of plasma rich in anti-SARS-CoV-2 antibodies. On the other hand, assessing the antibodies level depending on the time after infection allows for vaccine-decision. Methods the study marked the level of anti-SARS-CoV-2 IgG antibodies in 351 COVID-19 convalescent residents of one geographical region in Poland. The study group included blood donors. The studies were cross-sectional and extended to a questionnaire to determine infection severity. The data was compiled statistically. The study considered epidemiological factors, the time from the end of the infection, and infection severity. Findings The fastest increase of the antibodies level was observed up to 59 days after COVID-19, and it was statistically significantly higher among men. Higher levels of antibodies were found among people above the average age in both men and women. It was an increase in the level of antibodies since the onset of the disease in men, while in women, it decreased. The antibodies level was also found to depend on the severity of the course of COVID-19 infection. Conclusions The optimal group of plasma donors in the studied geographical region is men and women above 39 y.o. after more severe infection. The titer of antibodies increases with time from the disease. This article is protected by copyright. All rights reserved.
Chapter
The ongoing outbreak of coronavirus-19 (COVID-19) has quickly become a daunting challenge to global health. The ultraviolet radiations (UVR) A wavebands fall in the region of 320-400 nm of the solar spectrum and comprise about 95% of overall ultraviolet (UVs) approaching the biosphere. The UVA is extensively used in phototherapy systems, as a disinfectant, and in various skin-related conditions. This chapter aimed to address the reduction of coronavirus replication by direct application of phototherapy (UVA) in lungs and modulation of nitric oxide (NO) in skin cells following UVA exposures. This NO influx inside the bloodstream to deliver into the lungs endothelial cells where it goes to incur cytoprotection to alveolar lung cells. Moreover, it is also proposed for direct application of therapeutic doses of UVA light inside the lungs. It uses a fiberoptic adapter to modulate the production of NO in lung endothelial cells, which will diffuse into the bronchi and lungs to leave bronchodilatory and vasodilatory effects. How NO reduces inflammatory burst and reactive oxygen species (ROS) in the lungs' alveolar cells is also discussed. Moreover, it is also proposed that UVA radiation application should be limited to physiological doses and applied every 4-8 h, with at least 24 h of therapy before reassessment. The treating physician should determine discontinuation of this direct UVA treatment into the lungs following observation of the patient's condition and the safety and efficacy of the treatment. This study will highlight and emphasize the importance of utilizing UVA radiation to control this epidemic.
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Objectives and background Convalescent plasma (CP) has been used worldwide to contrast SARS-CoV-2 infection. Since April 2020, it has also been used in the treatment of patients with COVID-19 in the Veneto region (Italy), along with all the other available drugs and therapeutic tools. Here we report data analysis and clinical results in 1,517 COVID-19 inpatients treated with CP containing high-titre neutralizing anti-SARS-CoV-2 antibodies (CCP). Mortality after 30 days of hospitalization has been considered primary outcome, by comparing patients treated with CCP vs all COVID-19 patients admitted to hospitals of the Veneto region in a one-year period (from April 2020 to April 2021). Patients and methods Adult inpatients with a severe form of COVID-19 have been enrolled, with at least one of the following inclusion criteria: 1) tachypnea with respiratory rate (RR) ≥ 30 breaths/min; 2) oxygen saturation (SpO2) ≤ 93% at rest and in room air; 3) partial pressure of oxygen (PaO2)/fraction of inspired oxygen (FiO2) ≤ 200 mmHg, 4) radiological picture and/or chest CT scan showing signs of interstitial disease and/or rapid progression of lung involvement. Patients received a maximum of three therapeutic fractions (TFs) of CCP with a neutralizing antibody titre of ≥ 1:160, administered over a period of 3-5 days. If TFs of CCP with titre ≥ 1:160 were unavailable, 2 with antibody titre of ≥ 1:80 have been administered. Results Of the 1,517 patients treated with CCP, 209 deceased at the 30-day follow-up (14%). Death was significantly associated with an older age (p<0.001), a longer time of hospitalization before CCP infusion (p<0.001), a greater number of inclusion criteria (p<0.001) and associated comorbidities (p<0.001). Conditions significantly associated with an increased frequency of death were PaO2/FiO2 ≤ 200 (p<0.001) and tachypnea with RR>30 (p<0.05) at entry, concurrent arterial hypertension (p<0.001), cardiovascular disease (p<0.001), chronic kidney disease (p<0.001), dyslipidemia (p<0.05) and cancer (p<0.05). Moreover, factors leading to an unfavorable prognosis were a life-threatening disease (p<0.001), admission to Intensive Care Unit (p<0.001), high flow oxygen therapy or mechanical ventilation (p<0.05) and a chest X-ray showing consolidation area (p<0.001). By analyzing the regional report of hospitalized patients, a comparison of mortality by age group, with respect to our series of patients treated with CCP, has been made. Mortality was altogether lower in patients treated with CCP (14% v. 25%), especially in the group of the elderly patients (23% vs 40%,), with a strong significance (p<0.001). As regards the safety of CCP administration, 16 adverse events were recorded out of a total of 3,937 transfused TFs (0,4%). Conclusions To overcome the difficulties of setting up a randomized controlled study in an emergency period, a data collection from a large series of patients with severe COVID-19 admitted to CCP therapy with well-defined inclusion criteria has been implemented in the Veneto region. Our results have shown that in patients with severe COVID-19 early treatment with CCP might contribute to a favourable outcome, with a reduced mortality, in absence of relevant adverse events.
Article
As the coronavirus disease (COVID-19) pandemic led to a global health crisis, there were limited treatment options and no prophylactic therapies for those exposed to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Convalescent plasma is quick to implement, potentially provides benefits, and has a good safety profile. The therapeutic potential of COVID-19 convalescent plasma (CCP) is likely mediated by antibodies through direct viral neutralization and Fc-dependent functions such as a phagocytosis, complement activation, and antibody-dependent cellular cytotoxicity. In the United States, CCP became one of the most common treatments with over half million units transfused despite limited efficacy data. More than a dozen randomized trials now demonstrate that CCP does not provide benefit for those with moderate to severe disease. However, similar to other passive antibody therapies, CCP is beneficial for early disease, when provided to elderly outpatients within 72 hours after symptom onset. Only high-titer CCP should be transfused. CCP should also be considered for immunosuppressed COVID-19 patients. CCP collected in proximity, by time and location, to the patient may be more beneficial due to SARS-CoV-2 variants. Additional randomized trial data are still accruing and should be incorporated with other trial data to optimize CCP indications.
Article
Background The aim of this study was to analyze clinical features and short-term mortality in hemodialysis (HD) patients infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) omicron BA.2.2.1 variant. Methods In a retrospective single-center case series, 102 consecutive hospitalized HD patients infected with the coronavirus omicron variant were assessed at Pudong Hospital in Shanghai, China, from April 6 to April 18, 2022; the final date of follow-up was May 16, 2022. Clinical, laboratory, chest CT, and treatment data were collected and analyzed. The association between these factors and all-cause mortality was studied using univariate and multivariate analyses. The relationship between lymphocyte count and short-term mortality was based on receiver operating characteristic (ROC) curve analysis. Kaplan–Meier analysis was used to assess overall survival. Results In total, 102 patients were included in this study. The patients were divided into two groups: HD patients with pneumonia (N = 46) and without pneumonia (N = 56). Of the 102 patients, 12 (11.8%) died. Multivariate regression analysis revealed that all-cause mortality was correlated with lymphocyte counts and type B natriuretic peptide (BNP), C-reactive protein (CRP), and D-dimer levels (P < 0.05). The cut-off value of lymphocyte counts was 0.61 × 10⁹/L for all-cause mortality. The overall survival rate was significantly different between HD patients with and without pneumonia (P < 0.05). Conclusions Lymphocyte counts are important for the prediction of short-term mortality in HD patients with SARS-CoV-2 infection. HD patients with lung involvement have poorer survival rates than those without lung involvement.
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Introduction South America is one of the regions most affected by the COVID-19 pandemic. Specific and affordable treatments are needed to treat SARS-CoV-2 infection. Evidence regarding the use of convalescent plasma in COVID-19 patients is still limited. We compared the safety and efficacy of COVID-19-convalescent plasma administration as a complement to standard treatment in the early management of patients with moderate SARS-CoV-2 infection. Methods We carried out a random double blinded, placebo-controlled trial that compared standard treatment plus convalescent plasma (CP) or plus non-convalescent plasma in the management of COVID-19 patients. The main outcome was survival and secondary endpoints included: length of hospitalisation (LOH), days from treatment to discharge, time to clinical improvement or death within a 28-day period, and adverse reactions to treatment. Results Administration of CP with antibodies against SARS-CoV-2 did not affect patient survival, RR = 1.003, 95% CI (0.3938, 2.555). These results led to terminate the RCT prematurely. However, early treatment of COVID-19 patients with CP tended to decrease the LOH while the delay in CP treatment was associated with longer hospitalisation. In addition, delay in CP treatment negatively affected the recovery of the respiratory rate. Conclusion Use of CP for the treatment of COVID-19 patients is safe and its early use can decrease the LOH and improve respiratory function. Early administration of antibody-rich CP could contribute to decrease the negative impact of COVID-19 pandemic in patients with impaired immune response.
Article
In this short narrative, we highlight some of our experiences leading the US Convalescent Plasma Program at the beginning of the pandemic in the spring and summer of 2020. This includes a brief summary of how the program emerged and high‐level lessons we learned. We also share our impressions about and why convalescent plasma was used at scale in the United States, early in the pandemic and share ideas that might inform the use of convalescent plasma in future outbreaks of novel infectious diseases.
Chapter
The Coronavirus 2 relentless discriminating Respiratory Syndrome, the source of coronavirus syndrome (COVID-19), has sparked a universal fitness catastrophe. So far, there is no such thing as approved prophylaxis solutions for the ones who were revealed to neither SARS-CoV-2 nor therapies for individuals who have acquired COVID-19. Impervious, i.e., “convalescent” plasma relates toward plasma obtained as of persons, subsequent infection decree, and antibody production. Flaccid supervision of antibodies throughout Convalescent plasma transfusion can happen to provide Just for the short term policy on behalf of giving instantaneous resistance headed for liable Participants. In COVID-19 convalescent plasma was also used epidemic; It is limited in China records advise scientific detriment, together with radiological motion, viral load diminution, and enhanced endurance. Internationally, blood centers have a robust infrastructure for storing and building a catalog of convalescent plasma to congregate increasing stipulate.KeywordsSARS-COV-2COVID-19Convalescent plasma therapyCOV-MERSConvalescent plasma
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Establishing the optimal treatment for COVID-19 patients remains challenging. Specifically, immunocompromised and pre-diseased patients are at high risk for severe disease course and face limited therapeutic options. Convalescent plasma (CP) has been considered as therapeutic approach, but reliable data are lacking, especially for high-risk patients. We performed a retrospective analysis of 55 hospitalized COVID-19 patients from University Hospital Duesseldorf (UKD) at high risk for disease progression, in a substantial proportion due to immunosuppression from cancer, solid organ transplantation, autoimmune disease, dialysis. A matched-pairs analysis (1:4) was performed with 220 patients from the Lean European Open Survey on SARS-CoV-2-infected Patients (LEOSS) who were treated or not treated with CP. Both cohorts had high mortality (UKD 41.8%, LEOSS 34.1%). A matched-pairs analysis showed no significant effect on mortality. CP administration before the formation of pulmonary infiltrates showed the lowest mortality in both cohorts (10%), whereas mortality in the complicated phase was 27.8%. CP administration during the critical phase revealed the highest mortality: UKD 60.9%, LEOSS 48.3%. In our cohort of COVID-19 patients with severe comorbidities CP did not significantly reduce mortality in a retrospective matched-pairs analysis. However, our data supports the concept that a reduction in mortality is achievable by early CP administration.
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SARS-CoV-2, the coronavirus disease-2019 (COVID-19), and the cause of the pandemic is extremely contagious among people and has spread around the world. Antivirals, immunomodulators, and other medications, such as antibiotics, stem cells, and plasma therapy, have all been utilized in the treatment of COVID-19. To better understand the clinical efficacy of these agents and to aid in the selection of effective COVID-19 therapies in various countries, this study reviewed the effectiveness of the various pharmacologic agents that have been used for COVID-19 therapy globally by summarizing the clinical outcomes that have been obtained from the clinical trials published on each drug related to COVID-19 infection. The Food and Drug Administration (FDA) has authorized the use of remdesivir, paxlovid, molnupiravir, baricitinib, tixagevimab–cilgavimab, and bebtelovimab for the management of COVID-19. On the other hand, most research advises against using chloroquine and hydroxychloroquine to treat COVID-19 patients because they are not beneficial. Although the FDA has given emergency use authorization for some monoclonal antibodies, including bamlanivimab, etesevimab, casirivimab, and imdevimab for managing COVID-19, they are not currently approved for use because the Omicron variant has significantly reduced their in vitro susceptibility. In this study, we also included a wide range of alternative therapy strategies that effectively treat COVID-19 patients, although further randomized studies are necessary to support and assess their applicability.
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Passive immunotherapy with convalescent plasma may be the only available agent during the early phases of a pandemic. Here, we report safety and efficacy of high-titer convalescent plasma for COVID-19 pneumonia. Double-blinded randomized multicenter placebo-controlled trial of adult patients hospitalized with COVID-19 pneumonia. The intervention was COVID-19 convalescent plasma and placebo was saline allocated 2:1. The primary outcome was clinical status 14 days after the intervention evaluated on a clinical ordinal scale. The trial was registered at ClinicalTrials.Gov, NCT04345289, 14/04/2020. The CCAP-2 trial was terminated prematurely due to futility. Of 147 patients randomized, we included 144 patients in the modified intention-to-treat population. The ordinal clinical status 14 days post-intervention was comparable between treatment groups (odds ratio (OR) 1.41, 95% confidence interval (CI) 0.72–2.09). Results were consistent when evaluating clinical progression on an individual level 14 days after intervention (OR 1.09; 95% CI 0.46–1.73). No significant differences in length of hospital stay, admission to ICU, frequency of severe adverse events or all-cause mortality during follow-up were found between the intervention and the placebo group. Infusion of convalescent plasma did not influence clinical progression, survival or length of hospitalization in patients with COVID-19 pneumonia.
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Background: Convalescent plasma administration in severe and critically-ill COVID-19 patients have been proven to not provide improvement in patients' outcome, yet it is still widely used in countries with limited resources due to its high availability and safety. This study aims to investigate its effects on ICU mortality, ICU length of stay (LoS), and improvement of oxygen support requirements. Methods: Data of all severe and critically-ill patients in our COVID-19 ICU was collected retrospectively between May and November 2020. We dichotomized the variables and compared outcome data of 48 patients, who received convalescent plasma to 131 patients, receiving standard of care. Data were analyzed using multiple logistic regression to make prediction models of mortality, length of stay, and oxygen support device requirement. Result: Overall mortality rate in our COVID-19 ICU was 55.3%, with a median overall length of stay of 8 (4-11) days. Less patients that received convalescent plasma presented with the need for mechanical ventilation on ICU admission (p < 0.001), but with comparable PaO2 to FiO2 (P/F) ratio (p=0.95). Factors that confounded mortality were obesity (aOR = 14.1; 95% CI (1.25, 166.7); p=0.032), mechanical ventilation (aOR = 333; 95% CI (4.5,1,000); p < 0.001), higher neutrophil-to-lymphocyte ratio (NLR) (aOR = 7.32; 95% CI (1.82, 29.4); p=0.005), and lower P/F ratio (aOR = 7.70; 95% CI (2.04, 29.4); p=0.003). ICU LoS was longer in patients, who had prior history of hypertension (aOR = 2.14; 95% CI (1.05, 4.35); p=0.036) and received convalescent plasma (aOR = 3.88; 95% CI (1.77, 8.05); p < 0.001). Deceased patients, who received convalescent plasma, stayed longer in the ICU with a mean length of stay of 12.87 ± 5.7 days versus 8.13 ± 4.8 days with a significant difference (U = 434; p < 0.000). The chance of improved oxygen support requirements was lower in obese patients (aOR = 9.18; 95%CI (2.0, 42.1); p < 0.004), mechanically ventilated patients (aOR = 13.15; 95% CI (3.75, 46.09); p < 0.001), patients with higher NLR (aOR = 2.5; 95% CI (1.07, 5.85); p=0.034), and lower P/F ratio (aOR = 2.76; 95% CI (1.1, 6.91); p=0.031). Conclusion: The length of stay of patients in the convalescent plasma group was significantly longer than the control group. There was no effect of convalescent plasma in ICU mortality and no improvement was observed in terms of oxygen support requirements.
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Background: The COVID-19 convalescent plasma (CCP) has been tried as a therapy in moderate COVID-19 pneumonia. Donation of CCP requires motivation from recovered patients. This study evaluated the response of such recovered health care workers (HCWs) when they were motivated for CCP donation. Methods: An interview-based survey was carried out with recovered HCWs as study participants between August 2020 and November 2020. A qualified social worker explained the details of CCP donation over a mobile call; he clarified all their doubts and motivated them for the plasma donation. Their responses were recorded as "interested" or "not interested" followed by analysis. Results: We tried to call 624 recovered HCWs, but could not reach 213, and the final group available for the study was 411 participants. Of these 411, 186 were deferred. Finally, we analyzed a total of 225 responses. Eventually, 105 out of 225 HCWs (47%) were interested; there were no significant differences in responses among males and females and between different age groups (<.001) and the "doctors" designation category (P = .01) had a maximum number of "interested" responses. In multivariate logistic regression, only the "interested" responses of the doctors were significantly higher after adjusting the confounding effect of the "graduate and above" educational qualification category. Conclusion: This study found that nearly half of the eligible HCWs were interested in CCP donation. The educational qualification and designation among the recovered HCWs had an impact on CCP donation interest. The doctors were more interested in CCP donation compared to others.
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Description: Coronavirus disease 2019 convalescent plasma (CCP) has emerged as a potential treatment of COVID-19. However, meta-analysis data and recommendations are limited. The Association for the Advancement of Blood and Biotherapies (AABB) developed clinical practice guidelines for the appropriate use of CCP. Methods: These guidelines are based on 2 living systematic reviews of randomized controlled trials (RCTs) evaluating CCP from 1 January 2019 to 26 January 2022. There were 33 RCTs assessing 21 916 participants. The results were summarized using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) method. An expert panel reviewed the data using the GRADE framework to formulate recommendations. Recommendation 1 (outpatient): The AABB suggests CCP transfusion in addition to the usual standard of care for outpatients with COVID-19 who are at high risk for disease progression (weak recommendation, moderate-certainty evidence). Recommendation 2 (inpatient): The AABB recommends against CCP transfusion for unselected hospitalized persons with moderate or severe disease (strong recommendation, high-certainty evidence). This recommendation does not apply to immunosuppressed patients or those who lack antibodies against SARS-CoV-2. Recommendation 3 (inpatient): The AABB suggests CCP transfusion in addition to the usual standard of care for hospitalized patients with COVID-19 who do not have SARS-CoV-2 antibodies detected at admission (weak recommendation, low-certainty evidence). Recommendation 4 (inpatient): The AABB suggests CCP transfusion in addition to the usual standard of care for hospitalized patients with COVID-19 and preexisting immunosuppression (weak recommendation, low-certainty evidence). Recommendation 5 (prophylaxis): The AABB suggests against prophylactic CCP transfusion for uninfected persons with close contact exposure to a person with COVID-19 (weak recommendation, low-certainty evidence). Good clinical practice statement: CCP is most effective when transfused with high neutralizing titers to infected patients early after symptom onset.
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Faced with an evolving pandemic and a lack of clarity of the role of convalescent plasma for patients with COVID‐19, the CONCOR‐1 trial was launched. In 14 months the trial was designed, launched, completed, and submitted for publication. In total, 72 sites in three countries served by four blood suppliers randomised 940 patients. Many enablers facilitated the trial including: three study principal investigators to distribute the trial workload, diverse steering committee members, an international data safety monitoring committee, multiple statisticians and methodologists, virtual meeting platforms, REDCap data platform, pausing of non‐COVID‐19 trials, rapid approval pathways for institutional review boards and regulators, centralised institutional review boards in many locations, restriction of use of convalescent plasma to trial participants and the incredible dedication by research personnel. In future pandemics, we need to be prepared for rapid launch of trials. The protocols, consent forms, data collection tools, and procedures need to be in draft form ready for use at all times. We were well‐prepared for blood shortages but should have anticipated the need to conduct trials with convalescent plasma. In this short article, we detail our lessons learned to inform researchers faced with the next pandemic pathogen.
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Introduction The role of plasma therapy in the management of the COVID-19, pandemic has been speculated. However, in view of the varied response regarding its effectiveness from various multicenter studies, there is a need to conduct more singlecenter population-specific studies. We, thus, aimed to assess the role of convalescent plasma therapy in COVID-19 patient management in a single -center. Methods This retrospective study was conducted using records of all COVID-19 patients who received plasma therapy over a period of 6 months in a dedicated COVID-19 hospital in Delhi. Information pertaining to transfusion, disease severity, associated comorbidities, the treatment given and patient outcome were recorded. Data was analyzed using SPSSv23. Results Of the141 patients who received plasma therapy, 62% were discharged after treatment. Mortality was found to be significantly higher in patients >60 years of age (p< 0.001), those with severe COVID-19 infection (p < 0.05) and pre-existing renal disease (p < 0.05). The admission-transfusion interval was significantly correlated to mortality and was a sensitive parameter for predicting outcome at cut off value of <5 days (p <0.001). There was no significant association of mortality with patient blood group, plasma antibody levels or donor hemoglobin levels. Conclusions We report improvement and recovery in a large number of patients who received convalescent plasma within the first 5 days of hospitalization with moderate to severe disease. Further research to compare dosage and administration protocols to delineate role of CCP in survival of COVID-19 patients is needed before it is prematurely shelved.
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Coronavirus disease 2019 (COVID-19), caused by the Severe Acute Respiratory Syndrome Coronavirus type 2 (SARS-CoV-2), is the largest pandemic in modern history with very high infection rates and considerable mortality. The disease, which emerged in China's Wuhan province, had its first reported case on December 29, 2019, and spread rapidly worldwide. On March 11, 2020, the World Health Organization (WHO) declared the COVID-19 outbreak a pandemic and global health emergency. Since the outbreak, efforts to develop COVID-19 vaccines, engineer new drugs, and evaluate existing ones for drug repurposing have been intensively undertaken to find ways to control this pandemic. COVID-19 therapeutic strategies aim to impair molecular pathways involved in the virus entrance and replication or interfere in the patients' overreaction and immunopathology. Moreover, nanotechnology could be an approach to boost the activity of new drugs. Several COVID-19 vaccine candidates have received emergency-use or full authorization in one or more countries, and others are being developed and tested. This review assesses the different strategies currently proposed to control COVID-19 and the issues or limitations imposed on some approaches by the human and viral genetic variability.
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Convalescent plasma therapy is an important treatment method for patients with severe coronavirus disease (COVID-19). This study was conducted to confirm the safety of this therapy. We conducted an open-label clinical trial to administer convalescent plasma transfusion in a small Japanese cohort. Blood was collected from the recovered COVID-19 patients with high anti-severe acute respiratory syndrome coronavirus 2 (anti-SARS-CoV-2) spike IgG titer and high neutralizing activity and stored in the National Center for Global Health and Medicine Hospital until use. Convalescent plasma was administered to COVID-19 patients who required supplemental oxygen within 3 days of hospitalization. Convalescent plasma was administered to 11 patients with moderate to severe COVID-19. One patient experienced an adverse event, such as redness of the skin around the intravenous injection site within 3 hours after transfusion. Ten patients (91%) showed clinical improvement within 28 days, and one patient died of causes unrelated to plasma therapy. The data suggest that patients with COVID-19 examined in the present study received convalescent plasma without having any significant adverse effects. We plan to conduct a randomized controlled trial to examine the clinical effectiveness of convalescent plasma transfusion in a large Japanese COVID-19 cohort.
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Background Coronavirus disease 2019 (COVID-19) causes life-threatening pneumonia. Convalescent plasma therapy (CPT) is expected to be the effective COVID-19 treatment for passive immunity. The high neutralizing antibodies titer of CPT is needed to prove the benefit in early developed severe COVID-19. Objective This case–control study evaluated transfusion efficacy and adverse events with high-titer (≥ 1:320) COVID-19 convalescent plasma compared with standard care alone in severe COVID-19 pneumonia. Results Among 107 severe COVID-19 patients, 55 received CPT plus standard care, and 52 received standard care alone. All-cause mortality was 15.3% in the CPT group compared with 85.4% in the standard care group (p < 0.001). Univariate and multivariate analyses revealed reduced mortality with CPT (HR 0.14; 95% CI 0.07–0.31; p < 0.001 and HR 0.26; 95% CI 0.08–0.79; p = 0.018, respectively). CPT resulted in decreased use of mechanical ventilation, duration of supplemental oxygen, and high-flow oxygen requirement. Clinical and radiological outcomes improved. Conclusions Immediate high neutralizing antibody titer CPT is safe and reduces mortality in early developed severe COVID-19 patients. The benefit of CPT in the early course of illness is challenging and requires additional study. Trial registration Thai clinical trials registry (TCTR) no. 20220101003.
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