Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 35
Filter
1.
J Clin Invest ; 2021 Jan 11.
Article in English | MEDLINE | ID: covidwho-1112392

ABSTRACT

Characterization of the T cell response in individuals who recover from SARS-CoV-2 infection is critical to understand its contribution to protective immunity. A multiplexed peptide-MHC tetramer approach was used to screen 408 SARS-CoV-2 candidate epitopes for CD8+ T cell recognition in a cross-sectional sample of 30 COVID-19 convalescent individuals. T cells were evaluated using a 28-marker phenotypic panel, and findings were modelled against time from diagnosis, humoral and inflammatory responses. There were 132 SARS-CoV-2-specific CD8+ T cell responses detected across six different HLAs, corresponding to 52 unique epitope reactivities. CD8+ T cell responses were detected in almost all convalescent individuals and were directed against several structural and non-structural target epitopes from the entire SARS-CoV-2 proteome. A unique phenotype for SARS-CoV-2-specific T cells was observed that was distinct from other common virus-specific T cells detected in the same cross-sectional sample and characterized by early differentiation kinetics. Modelling demonstrated a coordinated and dynamic immune response characterized by a decrease in inflammation, increase in neutralizing antibody titer, and differentiation of a specific CD8+ T cell response. Overall, T cells exhibited distinct differentiation into stem-cell and transitional memory states, subsets, which may be key to developing durable protection.

2.
J Clin Invest ; 2021 Feb 23.
Article in English | MEDLINE | ID: covidwho-1097062

ABSTRACT

In recent months genomic characterization of pandemic SARS-CoV-2 isolates identified viral variants that are less susceptible to neutralization by convalescent plasma (CP), vaccine-elicited plasma/sera, or SARS-CoV-2 monoclonal antibodies than earlier SARS-CoV-2 strains. In this Viewpoint, Casadevall et al. argue against the causal association made in some press articles between the emergence of SARS-CoV-2 variants and convalescent plasma use.

3.
Mayo Clinic Proceedings ; 2021.
Article | WHO COVID | ID: covidwho-1087135

ABSTRACT

To determine the effect of COVID-19 convalescent plasma on mortality, we aggregated patient outcome data from 10 randomized clinical trials (RCT), 20 matched-control studies, two dose-response studies, and 96 case-reports or case-series Studies published between January 1, 2020 – January 16, 2021 were identified through a systematic search of online PubMed and MEDLINE databases Random-effects analyses of RCT and matched-control data demonstrated that COVID-19 patients transfused with convalescent plasma exhibited a lower mortality rate compared to patients receiving standard treatments Additional analyses showed that early transfusion (within 3 days of hospital admission) of higher-titer plasma is associated with lower patient mortality These data provide evidence favoring the efficacy of human convalescent plasma as a therapeutic agent in hospitalized COVID-19 patients

4.
Transfusion ; 2021 Feb 14.
Article in English | MEDLINE | ID: covidwho-1081126

ABSTRACT

BACKGROUND: COVID-19 convalescent plasma (CCP) has emerged as a potential treatment for COVID-19. However, efficacy data and recommendations for its use are limited. METHODS: AABB commissioned a panel of experts to develop interim recommendations based on limited data to guide use of this scarce resource. The panel performed a literature review using the search terms "COVID-19," "SARS-CoV-2" and "convalescent plasma." The interim recommendations reflect a consensus of expert opinion. INTERIM RECOMMENDATION 1: When making risk benefit decisions, one should consider the risk of CCP as comparable to standard (SARS-CoV-2 non-immune) plasma. INTERIM RECOMMENDATION 2: CCP is optimally effective when transfused as close to symptom onset as possible. CCP is unlikely to provide benefit for patients with late-stage disease or on mechanical ventilation. INTERIM RECOMMENDATION 3: The effectiveness of CCP is related to the antibody quantity within a unit; high-titer CCP is superior to low-titer CCP. A single high-titer unit should be sufficient for most patients. INTERIM RECOMMENDATION 4: If group B or group AB CCP is unavailable, transfusion of group A or group O CCP with low anti-A/B titer may be acceptable for group B and group AB patients. INTERIM RECOMMENDATION 5: Additional randomized controlled trial (RCT) data are needed to fully assess CCP efficacy and to identify which specific patient populations and unit characteristics might confer the greatest benefit. CONCLUSIONS: These interim recommendations are based on the best-available evidence at the time of writing. Additional data from on-going RCTs will lead to clinical practice guidelines in the future.

5.
J Clin Invest ; 2021 Feb 11.
Article in English | MEDLINE | ID: covidwho-1079151

ABSTRACT

COVID-19 convalescent plasma, particularly plasma with high-titer SARS-CoV-2 (CoV2) antibodies, is one of the leading treatments for individuals with early COVID-19 infection. The functionality of convalescent plasma varies greatly, but the association of antibody epitope specificities with plasma functionality remains uncharacterized. We assessed antibody functionality and reactivities to peptides across the CoV2 and the four endemic human coronavirus (HCoV) genomes in 126 COVID-19 convalescent plasma donations. We found strong correlation between plasma functionality and polyclonal antibody targeting of CoV2 spike protein peptides. Antibody reactivity to many HCoV spike peptides also displayed strong correlation with plasma functionality, including pan-coronavirus cross-reactive epitopes located in a conserved region of the fusion peptide. After accounting for antibody cross-reactivity, we identified an association between greater alphacoronavirus NL63 antibody responses and development of highly neutralizing antibodies to SARS-CoV-2. We also found that plasma preferentially reactive to the CoV2 spike receptor binding domain (RBD), versus the betacoronavirus HKU1 RBD, had higher neutralizing titer. Finally, we developed a two-peptide serosignature that identifies plasma donations with high anti-spike titer, but that suffer from low neutralizing activity. These results suggest that analysis of coronavirus antibody fine specificities may be useful for selecting therapeutic plasma with desired functionalities.

6.
Clinical Microbiology Newsletter ; 43(4):23-32, 2021.
Article | WHO COVID | ID: covidwho-1062296

ABSTRACT

Convalescent plasma has emerged as a promising therapeutic agent for patients with coronavirus disease 2019 (COVID-19), has received emergency use authorization, and is being widely used during the COVID-19 pandemic Passive antibody therapy via plasma or serum has been successfully used to treat infectious diseases for more than a century Passive antibody administration is based on the presumption that convalescent plasma or serum contains therapeutic antibodies that can be passively transferred to the plasma recipient There are numerous examples in which convalescent plasma has been used successfully as post-exposure prophylaxis and treatment of infectious diseases, including previous coronavirus outbreaks In the context of the COVID-19 pandemic, convalescent plasma was demonstrated to be safe and potentially effective among patients infected with COVID-19 This review provides an overview of the historical uses of convalescent plasma therapy, summarizes current evidence for convalescent plasma use for COVID-19, and highlights future antibody therapies

7.
Br J Haematol ; 192(4): 681-682, 2021 02.
Article in English | MEDLINE | ID: covidwho-1057971
8.
N Engl J Med ; 2021 Jan 13.
Article in English | MEDLINE | ID: covidwho-1057739

ABSTRACT

BACKGROUND: Convalescent plasma has been widely used to treat coronavirus disease 2019 (Covid-19) under the presumption that such plasma contains potentially therapeutic antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that can be passively transferred to the plasma recipient. Whether convalescent plasma with high antibody levels rather than low antibody levels is associated with a lower risk of death is unknown. METHODS: In a retrospective study based on a U.S. national registry, we determined the anti-SARS-CoV-2 IgG antibody levels in convalescent plasma used to treat hospitalized adults with Covid-19. The primary outcome was death within 30 days after plasma transfusion. Patients who were enrolled through July 4, 2020, and for whom data on anti-SARS-CoV-2 antibody levels in plasma transfusions and on 30-day mortality were available were included in the analysis. RESULTS: Of the 3082 patients included in this analysis, death within 30 days after plasma transfusion occurred in 115 of 515 patients (22.3%) in the high-titer group, 549 of 2006 patients (27.4%) in the medium-titer group, and 166 of 561 patients (29.6%) in the low-titer group. The association of anti-SARS-CoV-2 antibody levels with the risk of death from Covid-19 was moderated by mechanical ventilation status. A lower risk of death within 30 days in the high-titer group than in the low-titer group was observed among patients who had not received mechanical ventilation before transfusion (relative risk, 0.66; 95% confidence interval [CI], 0.48 to 0.91), and no effect on the risk of death was observed among patients who had received mechanical ventilation (relative risk, 1.02; 95% CI, 0.78 to 1.32). CONCLUSIONS: Among patients hospitalized with Covid-19 who were not receiving mechanical ventilation, transfusion of plasma with higher anti-SARS-CoV-2 IgG antibody levels was associated with a lower risk of death than transfusion of plasma with lower antibody levels. (Funded by the Department of Health and Human Services and others; ClinicalTrials.gov number, NCT04338360.).

9.
Vox Sang ; 2021 Jan 25.
Article in English | MEDLINE | ID: covidwho-1045664

ABSTRACT

BACKGROUND AND OBJECTIVES: ABO blood group may affect risk of SARS-CoV-2 infection and/or severity of COVID-19. We sought to determine whether IgG, IgA and neutralizing antibody (nAb) to SARS-CoV-2 vary by ABO blood group. MATERIALS AND METHODS: Among eligible convalescent plasma donors, ABO blood group was determined via agglutination of reagent A1 and B cells, IgA and IgG were quantified using the Euroimmun anti-SARS-CoV-2 ELISA, and nAb titres were quantified using a microneutralization assay. Differences in titre distribution were examined by ABO blood group using non-parametric Kruskal-Wallis tests. Adjusted prevalence ratios (aPR) of high nAb titre (≥1:160) were estimated by blood group using multivariable modified Poisson regression models that adjusted for age, sex, hospitalization status and time since SARS-CoV-2 diagnosis. RESULTS: Of the 202 potential donors, 65 (32%) were blood group A, 39 (19%) were group B, 13 (6%) were group AB, and 85 (42%) were group O. Distribution of nAb titres significantly differed by ABO blood group, whereas there were no significant differences in anti-spike IgA or anti-spike IgG titres by ABO blood group. There were significantly more individuals with high nAb titre (≥1:160) among those with blood group B, compared with group O (aPR = 1·9 [95%CI = 1·1-3·3], P = 0·029). Fewer individuals had a high nAb titre among those with blood group A, compared with group B (aPR = 0·6 [95%CI = 0·4-1·0], P = 0·053). CONCLUSION: Eligible CCP donors with blood group B may have relatively higher neutralizing antibody titres. Additional studies evaluating ABO blood groups and antibody titres that incorporate COVID-19 severity are needed.

11.
J Infect Dis ; 222(12): 1974-1984, 2020 11 13.
Article in English | MEDLINE | ID: covidwho-1024104

ABSTRACT

BACKGROUND: Convalescent plasma therapy is a leading treatment for conferring temporary immunity to COVID-19-susceptible individuals or for use as post-exposure prophylaxis. However, not all recovered patients develop adequate antibody titers for donation and the relationship between avidity and neutralizing titers is currently not well understood. METHODS: SARS-CoV-2 anti-spike and anti-nucleocapsid IgG titers and avidity were measured in a longitudinal cohort of COVID-19 hospitalized patients (n = 16 individuals) and a cross-sectional sample of convalescent plasma donors (n = 130). Epidemiologic correlates of avidity were examined in donors by linear regression. The association of avidity and a high neutralizing titer (NT) were also assessed in donors using modified Poisson regression. RESULTS: Antibody avidity increased over duration of infection and remained elevated. In convalescent plasma donors, higher levels of anti-spike avidity were associated with older age, male sex, and hospitalization. Higher NTs had a stronger positive correlation with anti-spike IgG avidity (Spearman ρ = 0.386; P < .001) than with anti-nucleocapsid IgG avidity (Spearman ρ = 0.211; P = .026). Increasing levels of anti-spike IgG avidity were associated with high NT (≥160) (adjusted prevalence ratio = 1.58 [95% confidence interval = 1.19-2.12]), independent of age, sex, and hospitalization. CONCLUSIONS: SARS-CoV-2 antibody avidity correlated with duration of infection and higher neutralizing titers, suggesting a potential alternative screening parameter for identifying optimal convalescent plasma donors.

12.
Med ; 1(1):66-77, 2020.
Article | WHO COVID | ID: covidwho-988791

ABSTRACT

Summary Antibody-based therapy for infectious diseases predates modern antibiotics and, in the absence of other therapeutic options, was deployed early in the SARS-CoV-2 pandemic through COVID-19 convalescent plasma (CCP) administration Although most studies have demonstrated signals of efficacy for CCP, definitive assessment has proved difficult under pandemic conditions, with rapid changes in disease incidence and the knowledge base complicating the design and implementation of randomized controlled trials Nevertheless, evidence from a variety of studies demonstrates that CCP is as safe as ordinary plasma and strongly suggests that it can reduce mortality if given early and with sufficient antibody content

13.
JAMA Intern Med ; 2020 Nov 24.
Article in English | MEDLINE | ID: covidwho-972800
14.
J Clin Invest ; 130(10): 5112-5114, 2020 10 01.
Article in English | MEDLINE | ID: covidwho-965886

ABSTRACT

Most patients with COVID-19 lack antibody to SARS-CoV-2 in the first 10 days of illness while the virus drives disease pathogenesis. SARS-CoV-2 antibody deficiency in the setting of a tissue viral burden suggests that using an antibody as a therapeutic agent would augment the antiviral immune response. In this issue of the JCI, Wang and collaborators describe the kinetics of viral load and the antibody responses of 23 individuals with COVID-19 experiencing mild and severe disease. The researchers found that (a) individuals with mild and severe disease produced neutralizing IgG to SARS-CoV-2 10 days after disease onset, (b) SARS-CoV-2 persisted longer in those with severe disease, and (c) there was cross-reactivity between antibodies to SARS-CoV-1 and SARS-CoV-2, but only antibodies from patients with COVID-19 neutralized SARS-CoV-2. These observations provide important information on the serological response to SARS-CoV-2 of hospitalized patients with COVID-19 that can inform the use of convalescent plasma therapy.


Subject(s)
Coronavirus Infections , Pandemics , Pneumonia, Viral , Severe Acute Respiratory Syndrome , Antibodies, Viral , Antibody Formation , Betacoronavirus , Coronavirus Infections/therapy , Humans , Immunization, Passive , Kinetics , Viral Load
16.
Proc Natl Acad Sci U S A ; 117(48): 30009-30011, 2020 12 01.
Article in English | MEDLINE | ID: covidwho-920653
17.
J Virol ; 2020 Nov 03.
Article in English | MEDLINE | ID: covidwho-910218

ABSTRACT

The paper "Middle East respiratory syndrome coronavirus Gene 5 modulates pathogenesis in mice" by Gutierrez-Alvarez et al., in this issue of the Journal of Virology (1), demonstrates that the MERS-CoV accessory protein, Gene 5, also known as ORF5, plays a major role in MERS-CoV pathogenesis.….

18.
J Clin Microbiol ; 2020 Nov 02.
Article in English | MEDLINE | ID: covidwho-901257

ABSTRACT

Accurate serological assays to detect antibodies to SARS-CoV-2 are needed to characterize the epidemiology of SARS-CoV-2 infection and identify potential candidates for COVID-19 convalescent plasma (CCP) donation. This study compared the performance of commercial enzyme immunoassays (EIAs) to detect IgG or total antibodies to SARS-CoV-2 and neutralizing antibodies (nAb). The diagnostic accuracy of five commercially available EIAs (Abbott, Euroimmun, EDI, ImmunoDiagnostics, and Roche) to detect IgG or total antibodies to SARS-CoV-2 was evaluated from cross-sectional samples of potential CCP donors that had prior molecular confirmation of SARS-CoV-2 infection (n=214) and pre-pandemic emergency department patients without SARS-CoV-2 infection (n=1,099). Of the 214 potential CCP donors, all were sampled >14 days since symptom onset and only a minority had been hospitalized due to COVID-19 (n=16 [7.5%]); 140 potential CCP donors were tested by all five EIAs and a microneutralization assay. When performed according to the manufacturers' protocol to detect IgG or total antibodies to SARS-CoV-2, the sensitivity of each EIA ranged from 76.4% to 93.9%, and the specificity of each EIA ranged from 87.0% to 99.6%. Using a nAb titer cutoff of ≥160 as the reference positive test (n=140 CCP donors), the empirical area under receiver operating curve of each EIA ranged from 0.66 (Roche) to 0.90 (Euroimmun). Commercial EIAs with high diagnostic accuracy to detect SARS-CoV-2 antibodies did not necessarily have high diagnostic accuracy to detect high nAbs. Some but not all commercial EIAs may be useful in the identification of individuals with high nAbs in convalescent individuals.

19.
J Clin Invest ; 130(9): 4791-4797, 2020 09 01.
Article in English | MEDLINE | ID: covidwho-840726

ABSTRACT

BACKGROUNDConvalescent plasma is the only antibody-based therapy currently available for patients with coronavirus disease 2019 (COVID-19). It has robust historical precedence and sound biological plausibility. Although promising, convalescent plasma has not yet been shown to be safe as a treatment for COVID-19.METHODSThus, we analyzed key safety metrics after transfusion of ABO-compatible human COVID-19 convalescent plasma in 5000 hospitalized adults with severe or life-threatening COVID-19, with 66% in the intensive care unit, as part of the US FDA expanded access program for COVID-19 convalescent plasma.RESULTSThe incidence of all serious adverse events (SAEs), including mortality rate (0.3%), in the first 4 hours after transfusion was <1%. Of the 36 reported SAEs, there were 25 reported incidences of related SAEs, including mortality (n = 4), transfusion-associated circulatory overload (n = 7), transfusion-related acute lung injury (n = 11), and severe allergic transfusion reactions (n = 3). However, only 2 of 36 SAEs were judged as definitely related to the convalescent plasma transfusion by the treating physician. The 7-day mortality rate was 14.9%.CONCLUSIONGiven the deadly nature of COVID-19 and the large population of critically ill patients included in these analyses, the mortality rate does not appear excessive. These early indicators suggest that transfusion of convalescent plasma is safe in hospitalized patients with COVID-19.TRIAL REGISTRATIONClinicalTrials.gov NCT04338360.FUNDINGMayo Clinic, Biomedical Advanced Research and Development Authority (75A50120C00096), National Center for Advancing Translational Sciences (UL1TR002377), National Heart, Lung, and Blood Institute (5R35HL139854 and R01 HL059842), National Institute of Diabetes and Digestive and Kidney Diseases (5T32DK07352), Natural Sciences and Engineering Research Council of Canada (PDF-532926-2019), National Institute of Allergy and Infectious Disease (R21 AI145356, R21 AI152318, and AI152078), Schwab Charitable Fund, United Health Group, National Basketball Association, Millennium Pharmaceuticals, and Octapharma USA Inc.


Subject(s)
Betacoronavirus , Coronavirus Infections/therapy , Pneumonia, Viral/therapy , Adolescent , Adult , Aged , Aged, 80 and over , Compassionate Use Trials , Coronavirus Infections/epidemiology , Coronavirus Infections/mortality , Female , Humans , Immunization, Passive/adverse effects , Immunization, Passive/mortality , Male , Middle Aged , Pandemics , Pneumonia, Viral/epidemiology , Safety , Transfusion Reaction/epidemiology , Transfusion Reaction/etiology , Transfusion-Related Acute Lung Injury/epidemiology , Transfusion-Related Acute Lung Injury/etiology , United States/epidemiology , United States Food and Drug Administration , Young Adult
20.
Journal of Clinical Investigation ; 130(2):553-555, 2020.
Article | WHO COVID | ID: covidwho-823375

ABSTRACT

Climate change will bring major changes to the epidemiology of infectious diseases through changes in microbial and vector geographic range Human defenses against microbial diseases rely on advanced immunity that includes innate and adaptive arms and endothermy, which creates a thermal restriction zone for many microbes Given that microbes can adapt to higher temperatures, there is concern that global warming will select for microbes with higher heat tolerance that can defeat our endothermy defenses and bring new infectious disease Here, Casadevall discusses the strong possibility that new, previously unknown infectious diseases will emerge from warmer climates as microbes adapt to higher global temperatures that can defeat our endothermy thermal barrier

SELECTION OF CITATIONS
SEARCH DETAIL