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1.
Transfusion Medicine & Hemotherapy ; : 1-6, 2021.
Article in English | Academic Search Complete | ID: covidwho-1533128

ABSTRACT

The pandemic spread of an infectious disease poses a plethora of challenges to society, clinicians, health care providers and regulating authorities. In order to mount a rapid response and to provide hope in a potentially catastrophic situation as the current COVID-19 pandemic, emergency plans, regulations and funding strategies have to be developed on regional, national and international levels. The speed needed to establish rapid response programs is challenged by the dynamics of the spread of the disease, the concurrent and competing development of different and potentially more effective treatment options, and not the least by regulatory uncertainty. Convalescent plasma, that is plasma collected from patients who have recovered from COVID-19 infections, has emerged as one of the first potential treatment options in the absence of drugs or vaccines with proven efficacy against SARS-CoV-2. The societal aspects of convalescent plasma and the public awareness gave an additional boost to the rapid employment of convalescent plasma donation platforms immediately after the SARS-CoV-2 outbreak. At the same time, uncertainty remains as to the efficacy of convalescent plasma. With evidence mostly limited to empirical reports, convalescent plasma has been used for decades for the prophylaxis and treatment of various infectious diseases. Clinical trials have addressed different infectious agents, stages of disease, target groups of patients and yielded sometimes inconclusive results. The aim of this short review is to delineate the regulatory background for the emergency use of convalescent plasma in the USA, in the European Union and in Germany, and the transition to the setting of clinical trials. In addition, we describe observations made in the process of collecting COVID-19 convalescent plasma (herein referred to as CCP), and formulate proposals to further improve the framework for rapid responses in future emergency situations. [ FROM AUTHOR] Copyright of Transfusion Medicine & Hemotherapy is the property of Karger AG and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all Abstracts.)

2.
Transfusion ; 61(11): 3087-3093, 2021 11.
Article in English | MEDLINE | ID: covidwho-1430132

ABSTRACT

BACKGROUND: Convalescent plasma has emerged as a potential specific treatment for coronavirus disease 2019 (COVID-19), since it contains severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies. Several studies are currently investigating the efficacy of convalescent plasma for treatment of COVID-19, with a focus on neutralizing antibodies. However, there is little information on whether convalescent plasma may contain additional immunoregulatory constituents produced by the blood donor during convalescence. Therefore, using a standardized whole blood assay employing synthetic toll-like receptor (TLR) ligands, we have investigated the immunoregulatory capacity of convalescent plasma in direct comparison to ABO-matched allogeneic control plasma. STUDY DESIGN AND METHODS: Whole blood samples from healthy blood donors were collected, and autologous plasma was replaced by convalescent plasma or ABO-matched control plasma. Standardized innate immune triggering and monitoring was performed by adding different TLR ligands (Pam3CsK4 [TLR1/2], HKLM [TLR2], LPS [TLR4], flagellin [TLR5], ssRNA40 [TLR8], imiquimod [TLR7], and FSL-1 [TLR2/6]) and subsequent quantitative analysis of pro- and anti-inflammatory cytokines (IP-10, IL-1ß, TNF-α, MCP-1, IL-6, IL-10, and IFN-γ) by cytometric bead array. Negative controls included unstimulated samples as well as samples spiked with autologous plasma. RESULTS: COVID-19 convalescent plasma (CCP) significantly decreased pro-inflammatory cytokines production triggered by different TLR ligands in healthy donors as compared with healthy control plasma. IL-6, MCP-1, and IFN-γ represented the cytokines that are most frequently downregulated by convalescent plasma. CONCLUSION: Our experiments reveal a potential novel, SARS-CoV-2-independent immunomodulatory activity of CCP, which may be beneficial for COVID-19 patients.


Subject(s)
Antibodies, Neutralizing , Antibodies, Viral , COVID-19/therapy , Convalescence , SARS-CoV-2 , Adolescent , Adult , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , Antibodies, Viral/blood , Antibodies, Viral/immunology , COVID-19/blood , COVID-19/immunology , Female , Humans , Immunization, Passive , Male , Middle Aged , SARS-CoV-2/immunology , SARS-CoV-2/metabolism
3.
Eur J Immunol ; 51(10): 2478-2484, 2021 10.
Article in English | MEDLINE | ID: covidwho-1340251

ABSTRACT

Treatment with convalescent plasma has been shown to be safe in coronavirus disease in 2019 (COVID-19) infection, although efficacy reported in immunocompetent patients varies. Nevertheless, neutralizing antibodies are a key requisite in the fight against viral infections. Patients depleted of antibody-producing B cells, such as those treated with rituximab (anti-CD20) for hematological malignancies, lack a fundamental part of their adaptive immunity. Treatment with convalescent plasma appears to be of general benefit in this particularly vulnerable cohort. We analyzed clinical course and inflammation markers of three B-cell-depleted patients suffering from COVID-19 who were treated with convalescent plasma. In addition, we measured serum antibody levels as well as peripheral blood CD38/HLA-DR-positive T-cells ex vivo and CD137-positive T-cells after in vitro stimulation with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-derived peptides in these patients. We observed that therapy with convalescent plasma was effective in all three patients and analysis of CD137-positive T-cells after stimulation with SARS-CoV-2 peptides showed an increase in peptide-specific T-cells after application of convalescent plasma. In conclusion, we here demonstrate efficacy of convalescent plasma therapy in three B-cell-depleted patients and present data that suggest that while application of convalescent plasma elevates systemic antibody levels only transiently, it may also boost specific T-cell responses.


Subject(s)
Antibodies, Viral/blood , B-Lymphocytes/immunology , COVID-19/therapy , T-Lymphocytes/immunology , Adolescent , Aged , Antibodies, Neutralizing/blood , B-Lymphocytes/cytology , Humans , Immunity, Cellular/immunology , Immunization, Passive/methods , Lymphocyte Count , Lymphocyte Depletion , Lymphoma, B-Cell/drug therapy , Lymphoma, Mantle-Cell/drug therapy , Male , Middle Aged , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Rituximab/adverse effects , SARS-CoV-2/immunology , Treatment Outcome , Tumor Necrosis Factor Receptor Superfamily, Member 9/metabolism
4.
Cells ; 9(12)2020 12 12.
Article in English | MEDLINE | ID: covidwho-971834

ABSTRACT

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) leads to an adaptive immune response in the host and the formation of anti-SARS-CoV-2 specific antibodies. While IgG responses against SARS-CoV-2 have been characterized quite well, less is known about IgA. IgA2 activates immune cells and induces inflammation and neutrophil extracellular trap (NET) formation which may contribute to organ injury and fatal outcome in SARS-CoV-2-infected patients. SARS-CoV-2 spike protein specific antibody levels were measured in plasma samples of 15 noninfected controls and 82 SARS-CoV-2-infected patients with no or mild symptoms, moderate symptoms (hospitalization) or severe disease (intensive care unit, ICU). Antibody levels were compared to levels of C-reactive protein (CRP) and circulating extracellular DNA (ecDNA) as markers for general inflammation and NET formation, respectively. While levels of SARS-CoV-2-specific IgG were similar in all patient groups, IgA2 antibodies were restricted to severe disease and showed the strongest discrimination between nonfatal and fatal outcome in patients with severe SARS-CoV-2 infection. While anti-SARS-CoV-2 IgG and IgA2 levels correlated with CRP levels in severely diseased patients, only anti-SARS-CoV-2 IgA2 correlated with ecDNA. These data suggest that the formation of anti-SARS-CoV-2 IgA2 during SARS-CoV-2 infection is a marker for more severe disease related to NET formation and poor outcome.


Subject(s)
Antibodies, Viral/blood , COVID-19/immunology , Extracellular Traps/immunology , Immunoglobulin A/blood , Spike Glycoprotein, Coronavirus/immunology , Adult , Aged , Aged, 80 and over , Biomarkers/blood , C-Reactive Protein/immunology , COVID-19/epidemiology , Case-Control Studies , Cell-Free Nucleic Acids/blood , Female , Humans , Male , Middle Aged , SARS-CoV-2 , Severity of Illness Index , Young Adult
5.
Transfusion ; 61(2): 368-374, 2021 02.
Article in English | MEDLINE | ID: covidwho-894804

ABSTRACT

BACKGROUND: The frequency of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNAemia in blood donors is uncertain. Thus, assays for SARS-CoV-2 RNA detection in blood, validated on commercially available polymerase chain reaction (PCR) systems, are required to allow a good comparability of data. STUDY DESIGN AND METHODS: The cobas SARS-CoV-2 dual-target reverse transcriptase PCR (RT-PCR) assay, licensed for respiratory swab SARS-CoV-2 RNA testing, was validated for detection of viral RNA in blood. For the validation panel, SARS-CoV-2-positive plasma samples were prepared by spiking SARS-CoV-2-positive respiratory specimens in negative human plasma. The 95% limit of detection (LOD95) was determined by probit analysis. For clinical validation, coronavirus disease 2019 (COVID-19) convalescent plasma (CCP) donors and patients with COVID-19 with a severe disease course treated in an intensive care unit (ICU) were included. RESULTS: The validation of the SARS-CoV-2 RT-PCR assay for blood demonstrated high sensitivity and specificity and intra- and inter-assay precision and efficiency. The LOD95 for SARS-CoV-2 RNA was 5.0 genome copies/mL (95% confidence interval [CI], 3.3-12 copies/mL) for target 1 and 4.3 genome copies/mL (95% CI, 2.9-10 copies/mL) for target 2. In a cohort of 39 CCP donors with 66 CCP donations no SARS-CoV-2 RNA in plasma was detected. Screening of 25 blood samples of 19 ICU patients with COVID-19 showed six positive results for SARS-CoV-2 RNA in at least one target of the assay. CONCLUSION: The SARS-CoV-2 RNA assay, only licensed for respiratory swabs, performed on a PCR system for high-throughput testing, showed a good assay performance for blood testing.


Subject(s)
COVID-19/diagnosis , COVID-19/therapy , SARS-CoV-2/pathogenicity , Aged , Aged, 80 and over , Blood Donors , Female , Humans , Immunization, Passive , Male , Middle Aged , RNA, Viral/genetics , Reverse Transcriptase Polymerase Chain Reaction , SARS-CoV-2/genetics
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