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1.
Cell Rep Med ; 3(11): 100811, 2022 Nov 15.
Article in English | MEDLINE | ID: covidwho-2150820

ABSTRACT

Coronavirus disease 2019 (COVID-19) convalescent plasma (CCP), a passive polyclonal antibody therapeutic agent, has had mixed clinical results. Although antibody neutralization is the predominant approach to benchmarking CCP efficacy, CCP may also influence the evolution of the endogenous antibody response. Using systems serology to comprehensively profile severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) functional antibodies of hospitalized people with COVID-19 enrolled in a randomized controlled trial of CCP (ClinicalTrials.gov: NCT04397757), we find that the clinical benefits of CCP are associated with a shift toward reduced inflammatory Spike (S) responses and enhanced nucleocapsid (N) humoral responses. We find that CCP has the greatest clinical benefit in participants with low pre-existing anti-SARS-CoV-2 antibody function and that CCP-induced immunomodulatory Fc glycan profiles and N immunodominant profiles persist for at least 2 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 development of a different class of COVID-19 hyperinflammation-targeting antibody therapeutic agents.


Subject(s)
COVID-19 , Humans , COVID-19/therapy , SARS-CoV-2 , Immunization, Passive/methods , Antibodies, Viral/therapeutic use , Nucleocapsid
2.
Curr Opin Allergy Clin Immunol ; 21(6): 553-558, 2021 12 01.
Article in English | MEDLINE | ID: covidwho-2161180

ABSTRACT

PURPOSE OF REVIEW: To provide an update of the current state of antibody therapy for Severe Acute Respiratory Syndrome Coronavirus 2 infection that has progressed immensely in a very short time period. RECENT FINDINGS: Limited clinical effect of classical passive immunotherapy (plasma therapy, hyperimmune immunoglobulin [IgG] preparations) whereas monoclonal antibody therapy, if initiated early in the disease process, shows promising results. SUMMARY: Although antibody therapy still remains to be fully explored in patients with COVID-19, a combination of IgG monoclonal antibodies against the receptor-binding domain of the spike protein currently appears to provide the best form of antibody therapy, Immunoglobulin A dimers and Immunoglobulin M pentamers also show promising preliminary therapeutic results.


Subject(s)
Antibodies, Monoclonal/therapeutic use , COVID-19/therapy , SARS-CoV-2/immunology , COVID-19/blood , COVID-19/immunology , Clinical Trials as Topic , Humans , Immunization, Passive/methods , Immunoglobulin A/therapeutic use , Immunoglobulin G/therapeutic use , Immunoglobulin M/therapeutic use , Treatment Outcome
3.
Ann Intern Med ; 173(2): JC3, 2020 07 21.
Article in English | MEDLINE | ID: covidwho-2103352

ABSTRACT

SOURCE CITATION: Ye Z, Rochwerg B, Wang Y, et al. Treatment of patients with nonsevere and severe coronavirus disease 2019: an evidence-based guideline. CMAJ. 2020;192:E536-45. 32350002.


Subject(s)
Coronavirus Infections/therapy , Pneumonia, Viral/therapy , Adrenal Cortex Hormones/therapeutic use , Antiviral Agents/therapeutic use , Betacoronavirus , COVID-19 , Coronavirus Infections/immunology , Humans , Immunization, Passive/methods , Pandemics , Plasma , Pneumonia, Viral/immunology , SARS-CoV-2 , Severity of Illness Index
4.
Viruses ; 14(11)2022 Oct 31.
Article in English | MEDLINE | ID: covidwho-2099852

ABSTRACT

Therapeutic blood products including convalescent plasma/serum and immunoglobulins concentrated from convalescent plasma, such as intravenous immunoglobulins or hyperimmune globulins, and monoclonal antibodies are passive immunotherapy options for novel coronavirus disease 2019 (COVID-19). They have been shown to improve the clinical status and biological and radiological parameters in some groups of COVID-19 patients. However, blood products are still potential sources of virus transmission in recipients. The use of pathogen reduction technology (PRT) should increase the safety of the products. The purpose of this study was to determine the impact of solvent/detergents (S/D) procedures on SARS-COV-2 infectivity elimination in the plasma of donors but also on COVID-19 convalescent serum (CCS) capacity to neutralize SARS-COV-2 infectivity. In this investigation, S/D treatment for all experiments was performed at a shortened process time (30 min). We first evaluated the impact of S/D treatments (1% TnBP/1% TritonX-45 and 1% TnBP/1% TritonX-100) on the inactivation of SARS-COV-2 pseudoparticles (SARS-COV-2pp)-spiked human plasma followed by S/D agent removal using a Sep-Pak Plus C18 cartridge. Both treatments were able to completely inactivate SARS-COV-2pp infectivity to an undetectable level. Moreover, the neutralizing activity of CCS against SARS-COV-2pp was preserved after S/D treatments. Our data suggested that viral inactivation methods using such S/D treatments could be useful in the implementation of viral inactivation/elimination processes of therapeutic blood products against SARS-COV-2.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , COVID-19/therapy , Virus Inactivation , Immunization, Passive/methods , Antibodies, Viral , Antibodies, Neutralizing
5.
Medicine (Baltimore) ; 101(31): e29912, 2022 Aug 05.
Article in English | MEDLINE | ID: covidwho-2051697

ABSTRACT

Coronavirus disease 2019 (COVID-19) is a novel acute respiratory infectious disease that can lead to multiple-organ dysfunction in patients with severe disease. However, there is a lack of effective antiviral drugs for COVID-19. Herein, we investigated the efficacy and safety of convalescent plasma (CP) therapy for treating severe COVID-19 in an attempt to explore new therapeutic methods. The clinical data of 3 imported patients with severe COVID-19 who underwent treatment with CP and who were quarantined and treated in a designated COVID-19 hospital from March 2020 to April 2020 were collected and analyzed. The 3 patients, including a 57-year-old male, 65-year-old female, and 59-year-old female, were clinically classified as having severe COVID-19. The main underlying diseases included hypertension, diabetes, sequelae of cerebral infarction, and postoperative thyroid adenoma. The common symptoms included cough, fever, and shortness of breath. All patients received antiviral drugs and other supportive treatments. Additionally, CP treatment was administered. At 48 to 72 hours after the CP transfusion, all 3 of the patients exhibited an improvement and alleviation of symptoms, an elevated arterial oxygen saturation, and decreased C-reactive protein and interleukin-6 levels. The counts of the total lymphocytes and T lymphocytes (CD3+) and their subsets (CD4 + and CD8+) were also obviously increased. Repeated chest computed tomography also revealed obvious absorption of the lesions in the bilateral lungs. Only 1 patient had a mild allergic reaction during the CP infusion, but no severe adverse reactions were observed. The early treatment with CP in patients with severe COVID-19 can rapidly improve the condition of the patients, and CP therapy is generally effective and safe.


Subject(s)
COVID-19 , Aged , Antiviral Agents/therapeutic use , COVID-19/therapy , Female , Humans , Immunization, Passive/methods , Male , Middle Aged , SARS-CoV-2
6.
Sci Rep ; 12(1): 16385, 2022 09 30.
Article in English | MEDLINE | ID: covidwho-2050519

ABSTRACT

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.


Subject(s)
COVID-19 , Adult , COVID-19/therapy , Hospitalization , Humans , Immunization, Passive/methods , SARS-CoV-2 , Treatment Outcome
7.
mBio ; 13(5): e0175122, 2022 10 26.
Article in English | MEDLINE | ID: covidwho-2038241

ABSTRACT

COVID-19 convalescent plasma (CCP) was an early and widely adopted putative therapy for severe COVID-19. Results from randomized control trials and observational studies have failed to demonstrate a clear therapeutic role for CCP for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Underlying these inconclusive findings is a broad heterogeneity in the concentrations of neutralizing antibodies (nAbs) between different CCP donors. We conducted this study to evaluate the effectiveness and safety of nAb titer-defined CCP in adults admitted to an academic referral hospital. Patients positive by a SARS-CoV-2 nucleic acid amplification test and with symptoms for <10 days were eligible. Participants received either CCP with nAb titers of >1:640 (high-titer group) or ≥1:160 to 1:640 (standard-titer group) in addition to standard of care treatments. The primary clinical outcome was time to hospital discharge, with mortality and respiratory support evaluated as secondary outcomes. Adverse events were contrasted by CCP titer. Between 28 August and 4 December 2020, 316 participants were screened, and 55 received CCP, with 14 and 41 receiving high- versus standard-titer CCP, respectively. Time to hospital discharge was shorter among participants receiving high- versus standard-titer CCP, accounting for death as a competing event (hazard ratio, 1.94; 95% confidence interval [CI], 1.05 to 3.58; Gray's P = 0.02). Severe adverse events (SAEs) (≥grade 3) occurred in 4 (29%) and 23 (56%) of participants receiving the high versus standard titer, respectively, by day 28 (risk ratio, 0.51; 95% CI, 0.21 to 1.22; Fisher's P = 0.12). There were no observed treatment-related AEs. (This study has been registered at ClinicalTrials.gov under registration no. NCT04524507). IMPORTANCE In this study, in a high-risk population of patients admitted for COVID-19, we found an earlier time to hospital discharge among participants receiving CCP with nAb titers of >1:640 compared with participants receiving CCP with a lower nAb titer and no CCP-related AEs. The significance of our research is in identifying a dose response of CCP and clinical outcomes based on nAb titer. Although limited by a small study size, these findings support further study of high-nAb-titer CCP defined as >1:640 in the treatment of COVID-19.


Subject(s)
COVID-19 , SARS-CoV-2 , Adult , Humans , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/therapy , Immunization, Passive/methods
8.
Int J Environ Res Public Health ; 19(17)2022 Aug 25.
Article in English | MEDLINE | ID: covidwho-2006005

ABSTRACT

This study investigated the efficacy and safety of convalescent plasma (CP) transfusion against the coronavirus disease 2019 (COVID-19) via a systematic review and meta-analysis of randomized controlled trials (RCTs). A total of 5467 articles obtained from electronic databases were assessed; however, only 34 RCTs were eligible after manually screening and eliminating unnecessary studies. The beneficial effect was addressed by assessing the risk ratio (RR) and standardized mean differences (SMDs) of the meta-analysis. It was demonstrated that CP therapy is not effective in improving clinical outcomes, including reducing mortality with an RR of 0.88 [0.76; 1.03] (I2 = 68% and p = 0.10) and length of hospitalization with SMD of -0.47 [-0.95; 0.00] (I2 = 99% and p = 0.05). Subgroup analysis provided strong evidence that CP transfusion does not significantly reduce all-cause mortality compared to standard of care (SOC) with an RR of 1.01 [0.99; 1.03] (I2 = 70% and p = 0.33). In addition, CP was found to be safe for and well-tolerated by COVID-19 patients as was the SOC in healthcare settings. Overall, the results suggest that CP should not be applied outside of randomized trials because of less benefit in improving clinical outcomes for COVID-19 treatment.


Subject(s)
COVID-19 , COVID-19/drug therapy , COVID-19/therapy , Humans , Immunization, Passive/methods , Randomized Controlled Trials as Topic
9.
Ann Intern Med ; 175(9): 1310-1321, 2022 09.
Article in English | MEDLINE | ID: covidwho-1994458

ABSTRACT

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.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/therapy , Hospitalization , Humans , Immunization, Passive/methods
10.
PLoS One ; 17(8): e0273223, 2022.
Article in English | MEDLINE | ID: covidwho-1993521

ABSTRACT

BACKGROUND: Although frequently used in the early pandemic, data on the effectiveness of COVID-19 convalescent plasma (CCP) remain mixed. We investigated the effectiveness and safety of CCP in hospitalized COVID-19 patients in real-world practices during the first two waves of the pandemic in a multi-hospital healthcare system in Texas. METHODS AND FINDINGS: Among 11,322 hospitalized patients with confirmed COVID-19 infection from July 1, 2020 to April 15, 2021, we included patients who received CCP and matched them with those who did not receive CCP within ±2 days of the transfusion date across sites within strata of sex, age groups, days and use of dexamethasone from hospital admission to the match date, and oxygen requirements 4-12 hours prior to the match date. Cox proportional hazards model estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for effectiveness outcomes in a propensity score 1:1 matched cohort. Pre-defined safety outcomes were described. We included 1,245 patients each in the CCP treated and untreated groups. Oxygen support was required by 93% of patients at the baseline. The pre-defined primary effectiveness outcome of 28-day in-hospital all-cause mortality (HR = 0.85; 95%CI: 0.66,1.10) were similar between treatment groups. Sensitivity and stratified analyses found similar null results. CCP-treated patients were less likely to be discharged alive (HR = 0.82; 95%CI: 0.74, 0.91), and more likely to receive mechanical ventilation (HR = 1.48; 95%CI: 1.12, 1.96). Safety outcomes were rare and similar between treatment groups. CONCLUSION: The findings in this large, matched cohort of patients hospitalized with COVID-19 and mostly requiring oxygen support at the time of treatment, do not support a clinical benefit in 28-day in-hospital all-cause mortality for CCP. Future studies should assess the potential benefits with specifically high-titer units in perhaps certain subgroups of patients (e.g. those with early disease or immunocompromised).


Subject(s)
COVID-19 , COVID-19/therapy , Cohort Studies , Humans , Immunization, Passive/methods , Oxygen , SARS-CoV-2 , Treatment Outcome
11.
Immunotherapy ; 14(14): 1133-1147, 2022 10.
Article in English | MEDLINE | ID: covidwho-1963293

ABSTRACT

Background: The authors describe the developmental process of intravenous anti-COVID-19 hyperimmune immunoglobulin from anti-SARS-CoV-2 neutralizing antibody-containing plasma. Furthermore, the authors investigated its safety and protective activity in animal models. Materials & methods: The manufacturing process included standard ethanol fractionation, chromatographic purification steps and virus removal or inactivation. Results: The authors produced pure and safe immunoglobulin for intravenous administration, with 98.1 ± 6.5 mg/ml protein content, of which 97.6 ± 0.7% was IgG. The concentration factor of SARS-CoV-2 neutralizing antibodies was 9.4 ± 1.4-times. Safety studies in animals showed no signs of acute/chronic toxicity or allergenic or thrombogenic properties. Intravenous anti-COVID-19 hyperimmune immunoglobulin protected immunosuppressed hamsters against SARS-Cov-2. Conclusion: The obtained results can allow the start of clinical trials to study the safety and efficacy in healthy adults.


An intravenous immunoglobulin with a high concentration of SARS-CoV-2-neutralizing antibodies was prepared from COVID-19 convalescent plasma, which could be utilized as a passive immunization tool in regard to COVID-19 treatment. The manufacturing process employed conforms to commonly held business standards within the intravenous immunoglobulin industry and includes plasma ethanol fractionation following chromatographic purification and special virus removal or inactivation steps. The results of the preclinical in vitro and in vivo experiments demonstrate that the immunoglobulin produced in this study is pure and safe enough to be considered for intravenous applications. The SARS-CoV-2 neutralizing antibody concentration was found to have increased 9.4 ± 1.4-times compared with human plasma. The anti-COVID-19 hyperimmune immunoglobulin showed no signs of toxicity and did not cause any blood clot formations when administered to rabbits. Furthermore, the anti-COVID-19 hyperimmune immunoglobulin was demonstrated to protect immunosuppressed hamsters against SARS-CoV-2.


Subject(s)
COVID-19 , SARS-CoV-2 , Administration, Intravenous , Antibodies, Neutralizing/therapeutic use , Antibodies, Viral/therapeutic use , COVID-19/therapy , Humans , Immunization, Passive/methods , Immunoglobulins, Intravenous/therapeutic use
12.
Turk J Med Sci ; 52(3): 554-564, 2022 06.
Article in English | MEDLINE | ID: covidwho-1918427

ABSTRACT

BACKGROUND: Convalescent plasma (CP) might be an additional treatment modality in COVID-19. The aim of this study was to compare CP-related clinical characteristics and perinatal outcomes in pregnant women with mild or moderate-severe COVID-19. METHODS: This prospective cohort study included 36 pregnant women (12 mild and 24 moderate-severe), who underwent CP therapy. The CP obtained from recently recovered donors was transfused to patients together with maximum supportive care and antiviral agents. The groups were then compared in respect of clinical characteristics, laboratory parameters, obstetric complications, and neonatal outcomes. RESULTS: Significant differences were determined between the groups in respect of systemic corticosteroids in COVID-19 treatment (41.7%, 87.5%, p = 0.004), oxygen (O2) support (0%, 91.7%, p < 0.001), chest imaging (41.7%, 58.3%, p = 0.02), intensive care unit admission (0%, 20.8%, p = 0.03) and length of hospitalization (5.5 versus 9.5 days, p < 0.001). The O2 saturation levels before and after administration of CP were significantly lower in the moderate-severe COVID-19 group (p < 0.05). The O2 therapy time before and after administration of CP and total O2 therapy time were significantly lower in the mild COVID-19 group (p < 0.05). Platelet, plateletcrit and lymphocyte counts were significantly higher in both the mild and moderate-severe COVID-19 groups after treatment compared to the pretreatment values (p < 0.05). DISCUSSION: Although data on the results of CP treatment in pregnant women are somewhat limited, it has been suggested that early CP treatment may be associated with improvements in laboratory and ventilatory parameters in pregnant women with mild and moderate-severe COVID-19. Nevertheless, there is a need for further, randomized controlled studies on this subject with the inclusion of greater numbers of patients.


Subject(s)
COVID-19 , Pregnancy Complications, Infectious , Female , Humans , Infant, Newborn , Pregnancy , COVID-19/therapy , Immunization, Passive/methods , Pandemics , Pregnancy Complications, Infectious/epidemiology , Pregnancy Complications, Infectious/therapy , Prospective Studies , SARS-CoV-2
13.
Viruses ; 14(7)2022 Jun 30.
Article in English | MEDLINE | ID: covidwho-1917789

ABSTRACT

COVID-19 convalescent plasma (CCP) has been the only specific anti-viral therapy against SARS-CoV-2 available for more than one year. Following the negative results from most randomized controlled trials on its efficacy in COVID-19 hospitalized patients and the availability of anti-spike monoclonal antibodies (mAbs), the use of CCP has subsequently rapidly faded. However, the continuous appearance of new variants of concern (VOCs), most of which escape mAbs and vaccine-elicited neutralizing antibodies (nAbs), has renewed the interest towards CCP, at least in seronegative immunocompetent patients, and in immunocompromised patients not able to mount a protective immune response. We report here the experience of a single Italian hospital in collecting and transfusing CCP in immunocompromised patients hospitalized for severe COVID-19 between October 2021 and March 2022. During this 6-month period, we collected CCP from 32 vaccinated and convalescent regular blood donors, and infused high nAb-titer CCP units (titered against the specific VOC affecting the recipient) to 21 hospitalized patients with severe COVID-19, all of them seronegative at the time of CCP transfusion. Patients' median age was 66 years (IQR 50-74 years) and approximately half of them (47.6%, 10/21) were immunocompromised. Two patients were rescued after previous failure of mAbs. No adverse reactions following CCP transfusion were recorded. A 28-day mortality rate of 14.3 percent (3/21) was reported, with age, advanced disease stage and late CCP transfusion associated with a worse outcome. This real-life experience also supports the use of CCP in seronegative hospitalized COVID-19 patients during the Delta and Omicron waves.


Subject(s)
COVID-19 , SARS-CoV-2 , Aged , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/therapy , Humans , Immunization, Passive/methods
14.
Front Immunol ; 13: 821721, 2022.
Article in English | MEDLINE | ID: covidwho-1902983

ABSTRACT

Many studies already reported on the association between patient characteristics on the severity of COVID-19 disease outcome, but the relation with SARS-CoV-2 antibody levels is less clear. To investigate this in more detail, we performed a retrospective observational study in which we used the IgG antibody response from 11,118 longitudinal antibody measurements of 2,082 unique COVID convalescent plasma donors. COVID-19 symptoms and donor characteristics were obtained by a questionnaire. Antibody responses were modelled using a linear mixed-effects model. Our study confirms that the SARS-CoV-2 antibody response is associated with patient characteristics like body mass index and age. Antibody decay was faster in male than in female donors (average half-life of 62 versus 72 days). Most interestingly, we also found that three symptoms (headache, anosmia, nasal cold) were associated with lower peak IgG, while six other symptoms (dry cough, fatigue, diarrhoea, fever, dyspnoea, muscle weakness) were associated with higher IgG concentrations.


Subject(s)
Age Factors , COVID-19/immunology , COVID-19/therapy , SARS-CoV-2/physiology , Adult , Antibodies, Viral/blood , Antibody Formation , Blood Donors , Body Mass Index , COVID-19/epidemiology , COVID-19/physiopathology , Convalescence , Female , Humans , Immunization, Passive/methods , Immunoglobulin G/blood , Male , Middle Aged , Netherlands/epidemiology , Retrospective Studies
15.
Trials ; 23(1): 527, 2022 Jun 22.
Article in English | MEDLINE | ID: covidwho-1902404

ABSTRACT

BACKGROUND: The 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. METHODS: During 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. RESULTS: Ninety-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. CONCLUSIONS: Our 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.


Subject(s)
COVID-19 , Pandemics , COVID-19/therapy , Clinical Trials as Topic , Humans , Immunization, Passive/methods , Research , SARS-CoV-2
16.
Transfus Apher Sci ; 61(3): 103355, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1900220

ABSTRACT

Coronavirus disease 2019 (COVID-19) convalescent plasma (CovCP) infusions have been widely used for the treatment of hospitalized patients with COVID-19. The aims of this narrative review were to analyze the safety and efficacy of CovCP infusions in the overall population and in immunocompromised patients with COVID-19 and to identify the lessons learned concerning the use of convalescent plasma (CP) to fill treatment gaps for emerging viruses. Systematic searches (PubMed, Scopus, and COVID-19 Research) were conducted to identify peer-reviewed articles and pre-prints published between March 1, 2020 and May 1, 2021 on the use of CovCP for the treatment of patients with COVID-19. From 261 retrieved articles, 37 articles reporting robust controlled studies in the overall population of patients with COVID-19 and 9 articles in immunocompromised patients with COVID-19 were selected. While CovCP infusions are well tolerated in both populations, they do not seem to improve clinical outcomes in critically-ill patients with COVID-19 and no conclusion could be drawn concerning their potential benefits in immunocompromised patients with COVID-19. To be better prepared for future epidemics/pandemics and to evaluate potential benefits of CP treatment, only CP units with high neutralizing antibodies (NAbs) titers should be infused in patients with low NAb titers, patient eligibility criteria should be based on the disease pathophysiology, and measured clinical outcomes and methods should be comparable across studies. Even if CovCP infusions did not improve clinical outcomes in patients with COVID-19, NAb-containing CP infusions remain a safe, widely available and potentially beneficial treatment option for future epidemics/pandemics.


Subject(s)
COVID-19 , COVID-19/therapy , Humans , Immunization, Passive/methods , Immunocompromised Host , Pandemics , SARS-CoV-2
17.
Transfus Apher Sci ; 61(4): 103487, 2022 Aug.
Article in English | MEDLINE | ID: covidwho-1886108

ABSTRACT

When the COVID-19 pandemic hit, blood transfusion services worldwide started collection of convalescent plasma as early as possible, as exemplified by the response in Norway. There were challenges related to donor selection, donor safety, testing for relevant antibodies and indications for and dosing of the convalescent plasma. As more knowledge became available, the product quality was more standardised. Multiple case reports, observational studies and some randomized studies were published during the pandemic, as well as laboratory studies reporting different approaches to antibody testing. The results were conflicting and the importance of convalescent plasma was disputed. Even though there has been strong international collaboration with involvement of many key organisations, we may better prepare for the next pandemic. An even stronger, more formalised collaboration between these organisations could provide more clear evidence of the importance of convalescent plasma, based on the principles of passive immunisation.


Subject(s)
COVID-19 , Pandemics , COVID-19/therapy , Humans , Immunization, Passive/methods , SARS-CoV-2
18.
J Clin Immunol ; 42(2): 232-239, 2022 02.
Article in English | MEDLINE | ID: covidwho-1838372

ABSTRACT

PURPOSE: To 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. METHODS: Sera 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. RESULTS: IFN-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. CONCLUSIONS: IFN-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.


Subject(s)
Autoantibodies/immunology , COVID-19/immunology , COVID-19/therapy , Interferon alpha-2/immunology , Plasma/immunology , Adult , Aged , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Antiviral Agents/immunology , Blood Component Transfusion/methods , Critical Illness , Female , Humans , Immunization, Passive/methods , Immunoglobulin G/immunology , Male , Middle Aged , SARS-CoV-2/immunology
19.
J Assoc Physicians India ; 70(4): 11-12, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1801680

ABSTRACT

Convalescent plasma therapy, a classic adaptive immunotherapy used in the treatment of SARS, MERS, and 2009 H1N1 pandemic with acceptable efficacy and safety in the past. Convalescent plasma therapy was taken into consideration in management of COVID 19 disease during the initial days of pandemic but was withdrawn later due to its doubtful beneficial role. This study aims to explore the beneficial role of convalescent plasma and to determine whether convalescent plasma therapy holds a second chance in treating SARS COV-2. MATERIAL: This cross-sectional observational study includes 82 cases of moderate to severely ill COVID 19 patients who received convalescent plasma therapy and 41 controls who didn't. Regular monitoring of TLC, P/F ratio, N/L ratio inflammatory markers, respiratory rate, oxygen saturation, ABG and radiological imaging was done for comparative analysis. OBSERVATION: In case group 39 patients (47.56%) were on oxygen mask, 17 patients (20.73%) on NIV, 9 Patients on NRM (10.97%), 16 patients (19.51%) on room air, 1(1.21%) on HFNC initially. After 7th day of convalescent plasma therapy 49 patients (59.75%) were on room air which suggests significant improvement in mode of ventilation in case group as compared to control group. Mean respiratory rate in case group was 30.46 CPM initially and 24.7 CPM on day 7th of plasma therapy which is statistically significant. CONCLUSION: Plasma therapy is effective if given in early stage of disease and convalescent plasma donors having adequate antibody titre.


Subject(s)
COVID-19 , Influenza A Virus, H1N1 Subtype , COVID-19/therapy , Cross-Sectional Studies , Humans , Immunization, Passive/adverse effects , Immunization, Passive/methods
20.
Transfus Med ; 32(4): 327-337, 2022 Aug.
Article in English | MEDLINE | ID: covidwho-1794553

ABSTRACT

BACKGROUND: Convalescent plasma containing high levels of SARS-CoV-2 antibodies has been studied as a possible treatment for COVID-19. Better understanding of predictors of high antibody levels is needed for improving supply of high-quality therapeutic plasma. AIMS: We have evaluated demographic and clinical factors associated with the probability of a convalescent plasma donor having high SARS-CoV-2 IgG antibody levels. METHODS: A total of 29,585 convalescent plasma donors employed during the first and second waves of the COVID-19 pandemic in England were included in this study. All had been tested for SARS-CoV-2 IgG antibodies by EUROimmun ELISA. A multivariable logistic regression model was used to quantify the association of the demographic and clinical factors with high (EUROimmun S/Co>6.0) SARS-CoV-2 IgG antibody level. RESULTS: Most of the donors were male (23,024; 78%), with white ethnic background (24,598;83%) and had not been tested for SARS-CoV-2 (15,266; 52%).Overall, less than 20% of convalescent plasma donors with confirmed or suspected SARS-CoV-2 infection harboured high SARS-CoV-2 antibody levels (n = 4,978). We found that older male donors who had been hospitalised with COVID-19 were most likely to harbour high levels of antibodies. White donors were less likely to have high SARS-CoV-2 antibody levels than donors with Asian orblack ethnic backgrounds residing in affluent areas likely reflecting ethnic inequality previously associated with SARS-CoV-2 infection. DISCUSSION: In a time of great uncertainty, and predicted new waves associated with newly emerging SARS-CoV-2 variants, these results will help us to target future convalescent plasma collections.


Subject(s)
COVID-19 , Coronavirus Infections , Pneumonia, Viral , Antibodies, Neutralizing , Antibodies, Viral , Betacoronavirus , COVID-19/epidemiology , COVID-19/therapy , Coronavirus Infections/epidemiology , Coronavirus Infections/therapy , Demography , Female , Humans , Immunization, Passive/methods , Immunoglobulin G , Male , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/therapy , SARS-CoV-2
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