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1.
Transplant Direct ; 6(7): e572, 2020 Jul.
Article in English | MEDLINE | ID: covidwho-1794966

ABSTRACT

BACKGROUND: The early effects of coronavirus disease 2019 (COVID-19) on transplantation are dramatic: >75% of kidney and liver programs are either suspended or operating under major restrictions. To resume transplantation, it is important to understand the prevalence of COVID-19 among transplant recipients, donors, and healthcare workers (HCWs) and its associated mortality. METHODS: To investigate this, we studied severe acute respiratory syndrome coronavirus 2 diagnostic test results among patients with end-stage renal disease or kidney transplants from the Johns Hopkins Health System (n = 235), and screening test results from deceased donors from the Southwest Transplant Alliance Organ Procurement Organization (n = 27), and donors, candidates, and HCWs from the National Kidney Registry and Viracor-Eurofins (n = 253) between February 23 and April 15, 2020. RESULTS: We found low rates of COVID-19 among donors and HCWs (0%-1%) who were screened, higher rates of diagnostic tests among patients with end-stage renal disease or kidney transplant (17%-20%), and considerable mortality (7%-13%) among those who tested positive. CONCLUSIONS: These findings suggest the threat of COVID-19 for the transplant population is significant and ongoing data collection and reporting is critical to inform transplant practices during and after the pandemic.

2.
Transplantation ; 105(7): 1405-1422, 2021 07 01.
Article in English | MEDLINE | ID: covidwho-1706459

ABSTRACT

The emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus responsible for the coronavirus disease 2019 (COVID-19) pandemic has raised concerns for programs overseeing donation and transplantation of cells, tissues, and organs (CTO) that this virus might be transmissible by transfusion or transplantation. Transplant recipients are considered particularly vulnerable to pathogens because of immunosuppression, and SARS-CoV-2 is likely to generate complications if contracted. Several signs and symptoms observed in COVID-19 positive patients reflect damage to multiple organs and tissues, raising the possibility of extrapulmonary SARS-CoV-2 infections and risk of transmission. At the beginning of the pandemic, a consensus has emerged not to consider COVID-19 positive patients as potential living or deceased donors, resulting in a global decrease in transplantation procedures. Medical decision-making at the time of organ allocation must consider safely alongside the survival advantages offered by transplantation. To address the risk of transmission by transplantation, this review summarizes the published cases of transplantation of cells or organs from donors infected with SARS-CoV-2 until January 2021 and assesses the current state of knowledge for the detection of this virus in different biologic specimens, cells, tissues, and organs. Evidence collected to date raises the possibility of SARS-CoV-2 infection and replication in some CTO, which makes it impossible to exclude transmission through transplantation. However, most studies focused on evaluating transmission under laboratory conditions with inconsistent findings, rendering the comparison of results difficult. Improved standardization of donors and CTO screening practices, along with a systematic follow-up of transplant recipients could facilitate the assessment of SARS-CoV-2 transmission risk by transplantation.


Subject(s)
COVID-19/transmission , Donor Selection/methods , Hematopoietic Stem Cell Transplantation/adverse effects , Organ Transplantation/adverse effects , Postoperative Complications/etiology , SARS-CoV-2/isolation & purification , COVID-19/diagnosis , COVID-19/prevention & control , COVID-19/virology , Humans , Postoperative Complications/diagnosis , Postoperative Complications/prevention & control , Risk
3.
Vox Sang ; 117(2): 185-192, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1685455

ABSTRACT

BACKGROUND AND OBJECTIVES: Passive immunization using investigational COVID-19 convalescent plasma (CCP) is a promising therapeutic strategy and could improve outcome if transfused early and contain high levels of anti-SARS-CoV-2 antibodies. We report the management of a national CCP collection and distribution program in Israel. MATERIALS AND METHODS: From 1 April 2020 to 15 January 2021, 4020 volunteer donors donated 5221 CCP units and 837 (20.8%) donors donated more than once. Anti-nucleocapsid IgG antibodies were determined using chemiluminescent immunoassay method (Abbott). A statistical model based on repeated IgG tests in sequential donations was created to predict the time of antibody decline below sample/cut-off (S/CO) level of 4.0. RESULTS: Ninety-six percent of CCP donors suffered a mild disease or were asymptomatic. Older donors had higher antibody levels. Higher antibody levels (S/CO ≥4) were detected in 35.2% of the donors. Low positive (S/CO ≥1.4-3.99) were found in 37%, and 27.8% had undetectable antibodies (S/CO ≤1.4). The model predicted decrease antibody thresholds of 0.55%/day since the first CCP donation, providing guidance for the effective timing of future collections from donors with high antibody levels. CONCLUSIONS: An efficient CCP collection and distribution program was achieved, based on performing initial and repeated plasma collections, preferably from donors with higher antibody levels, and only antibody-rich units were supplied for therapeutic use. The inventory met the quantity and quality standards of the authorities, enabled to respond to the growing demand of the medical system and provide a product that may contribute to improve prognosis in patients with COVID-19.


Subject(s)
COVID-19 , Blood Donors , COVID-19/therapy , Humans , Immunization, Passive , Israel , SARS-CoV-2
4.
Vox Sang ; 116(7): 766-773, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1573880

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.


Subject(s)
ABO Blood-Group System , COVID-19 , Antibodies, Viral , Antibody Formation , Blood Donors , COVID-19/therapy , COVID-19 Testing , Humans , Immunization, Passive , SARS-CoV-2
5.
Clin Infect Dis ; 73(11): 2073-2082, 2021 12 06.
Article in English | MEDLINE | ID: covidwho-1560084

ABSTRACT

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic poses an urgent need for the development of effective therapies for coronavirus disease 2019 (COVID-19). METHODS: We first tested SARS-CoV-2-specific T-cell (CοV-2-ST) immunity and expansion in unexposed donors, COVID-19-infected individuals (convalescent), asymptomatic polymerase chain reaction (PCR)-positive subjects, vaccinated individuals, non-intensive care unit (ICU) hospitalized patients, and ICU patients who either recovered and were discharged (ICU recovered) or had a prolonged stay and/or died (ICU critical). CoV-2-STs were generated from all types of donors and underwent phenotypic and functional assessment. RESULTS: We demonstrate causal relationship between the expansion of endogenous CoV-2-STs and the disease outcome; insufficient expansion of circulating CoV-2-STs identified hospitalized patients at high risk for an adverse outcome. CoV-2-STs with a similarly functional and non-alloreactive, albeit highly cytotoxic, profile against SARS-CoV-2 could be expanded from both convalescent and vaccinated donors generating clinical-scale, SARS-CoV-2-specific T-cell products with functional activity against both the unmutated virus and its B.1.1.7 and B.1.351 variants. In contrast, critical COVID-19 patient-originating CoV-2-STs failed to expand, recapitulating the in vivo failure of CoV-2-specific T-cell immunity to control the infection. CoV-2-STs generated from asymptomatic PCR-positive individuals presented only weak responses, whereas their counterparts originating from exposed to other seasonal coronaviruses subjects failed to kill the virus, thus disempowering the hypothesis of protective cross-immunity. CONCLUSIONS: Overall, we provide evidence on risk stratification of hospitalized COVID-19 patients and the feasibility of generating powerful CoV-2-ST products from both convalescent and vaccinated donors as an "off-the shelf" T-cell immunotherapy for high-risk patients.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Immunotherapy, Adoptive , T-Lymphocytes
6.
Vox Sang ; 116(9): 946-954, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1462889

ABSTRACT

BACKGROUND AND OBJECTIVES: Access to large pools of healthy adult donors advantageously positions blood component providers to undertake anti-SARS-CoV-2 seroprevalence studies. While numerous seroprevalence reports have been published by blood operators during the COVID-19 pandemic, details on the assay used has not been well documented. The objectives of this study were to evaluate the diversity of assays being used by blood operators and assess how this may affect seroprevalence estimates. MATERIALS AND METHODS: We surveyed 49 blood component providers from 39 countries. Questionnaire included information on the number and identity of assays used, the detected immunoglobulin(s) and target antigen, and performance characteristics (sensitivity, specificity). RESULTS: Thirty-eight of the 49 contacted blood suppliers provided at least partial responses. The results indicate that 19 commercial and five in-house serology assays have been used by surveyed blood operators. The Abbott SARS-CoV-2 IgG assay was the most commonly used kit and utilized by 15 blood suppliers. Two assays did not detect IgG, but detected either IgM/IgA or IgM. 68·2% of assays targeted the spike protein and 50% the nucleocapsid protein, while 18·2% targeted both viral proteins. The sensitivity and specificity of IgG-specific assays ranged from 71·9% to 100% and from 96·2% to 100%, respectively. As of 18 October 2020, the seroprevalence was below 5% in 10 of 14 countries reporting. CONCLUSION: Our results highlight the diversity of assays being used. Analyses comparing blood donor seroprevalence across countries should consider assay characteristics with optimization of signal/cut-off ratios and consistent methodology to adjust for waning antibody.


Subject(s)
COVID-19 , SARS-CoV-2 , Adult , Antibodies, Viral , Humans , Pandemics , Sensitivity and Specificity , Seroepidemiologic Studies , Surveys and Questionnaires
7.
Transfusion ; 61(1): 17-23, 2021 01.
Article in English | MEDLINE | ID: covidwho-1388418

ABSTRACT

BACKGROUND: The transfer of passive immunity with convalescent plasma is a promising strategy for treatment and prevention of COVID-19, but donors with a history of nonsevere disease are serologically heterogenous. The relationship between SARS-Cov-2 antigen-binding activity and neutralization activity in this population of donors has not been defined. STUDY DESIGN AND METHODS: Convalescent plasma units from 47 individuals with a history of nonsevere COVID-19 were assessed for antigen-binding activity of using three clinical diagnostic serology assays (Beckman, DiaSorin, and Roche) with different SARS-CoV-2 targets. These results were compared with functional neutralization activity using a fluorescent reporter strain of SARS-CoV-2 in a microwell assay. RESULTS: Positive correlations of varying strength (Spearman r = 0.37-0.52) between antigen binding and viral neutralization were identified. Donors age 48 to 75 years had the highest neutralization activity. Units in the highest tertile of binding activity for each assay were enriched (75%-82%) for those with the highest levels of neutralization. CONCLUSION: The strength of the relationship between antigen-binding activity and neutralization varies depending on the clinical assay used. Units in the highest tertile of binding activity for each assay are predominantly comprised of those with the greatest neutralization activity.


Subject(s)
SARS-CoV-2/immunology , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/immunology , COVID-19/therapy , COVID-19 Serological Testing , Enzyme-Linked Immunosorbent Assay , Humans , Immunization, Passive , Immunoglobulin G/immunology , SARS-CoV-2/pathogenicity , Serologic Tests
10.
Nat Immunol ; 22(5): 620-626, 2021 05.
Article in English | MEDLINE | ID: covidwho-1387432

ABSTRACT

The immune response to SARS-CoV-2 is critical in controlling disease, but there is concern that waning immunity may predispose to reinfection. We analyzed the magnitude and phenotype of the SARS-CoV-2-specific T cell response in 100 donors at 6 months following infection. T cell responses were present by ELISPOT and/or intracellular cytokine staining analysis in all donors and characterized by predominant CD4+ T cell responses with strong interleukin (IL)-2 cytokine expression. Median T cell responses were 50% higher in donors who had experienced a symptomatic infection, indicating that the severity of primary infection establishes a 'set point' for cellular immunity. T cell responses to spike and nucleoprotein/membrane proteins were correlated with peak antibody levels. Furthermore, higher levels of nucleoprotein-specific T cells were associated with preservation of nucleoprotein-specific antibody level although no such correlation was observed in relation to spike-specific responses. In conclusion, our data are reassuring that functional SARS-CoV-2-specific T cell responses are retained at 6 months following infection.


Subject(s)
Antigens, Viral/immunology , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , COVID-19/immunology , Immunity, Cellular , SARS-CoV-2/immunology , Adult , Aged , Antibodies, Viral/blood , CD4-Positive T-Lymphocytes/metabolism , CD4-Positive T-Lymphocytes/virology , CD8-Positive T-Lymphocytes/metabolism , CD8-Positive T-Lymphocytes/virology , COVID-19/blood , COVID-19/virology , Female , Host-Pathogen Interactions , Humans , Interleukin-2/blood , Male , Middle Aged , Phenotype , SARS-CoV-2/pathogenicity , Time Factors , Young Adult
11.
Clin Infect Dis ; 73(Suppl 2): S154-S162, 2021 07 30.
Article in English | MEDLINE | ID: covidwho-1334204

ABSTRACT

BACKGROUND: Although the risk of exposure to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is higher for frontline healthcare workers, not all personnel have similar risks. Determining infection rate is difficult due to the limits on testing and the high rate of asymptomatic individuals. Detection of antibodies against SARS-CoV-2 may be useful for determining prior exposure to the virus and assessing mitigation strategies, such as isolation, masks, and other protective equipment. METHODS: An online assessment that included demographic, clinical, and exposure information and a blood sample was collected from 20 614 participants out of ~43 000 total employees at Beaumont Health, which includes 8 hospitals distributed across the Detroit metropolitan area in southeast Michigan. The presence of anti-SARS-CoV-2 IgG was determined using the EUROIMMUN assay. RESULTS: A total of 1818 (8.8%) participants were seropositive between April 13 and May 28, 2020. Among the seropositive individuals, 44% reported that they were asymptomatic during the month prior to blood collection. Healthcare roles such as phlebotomy, respiratory therapy, and nursing/nursing support exhibited significantly higher seropositivity. Among participants reporting direct exposure to a Coronavirus Disease 2019 (COVID-19) positive individual, those wearing an N95/PAPR mask had a significantly lower seropositivity rate (10.2%) compared to surgical/other masks (13.1%) or no mask (17.5%). CONCLUSIONS: Direct contact with COVID-19 patients increased the likelihood of seropositivity among employees but study participants who wore a mask during COVID-19 exposures were less likely to be seropositive. Additionally, a large proportion of seropositive employees self-reported as asymptomatic. (Funded by Beaumont Health and by major donors through the Beaumont Health Foundation). CLINICALTRIALS.GOV NUMBER: NCT04349202.


Subject(s)
COVID-19 , Antibodies, Viral , Health Personnel , Humans , Michigan , SARS-CoV-2
12.
Eur J Intern Med ; 89: 87-96, 2021 07.
Article in English | MEDLINE | ID: covidwho-1313078

ABSTRACT

Elucidating the characteristics of human immune response against SARS-CoV-2 is of high priority and relevant for determining vaccine strategies. We report the results of a follow-up evaluation of anti-SARS-CoV-2 antibodies in 148 convalescent plasma donors who participated in a phase 2 study at a median of 8.3 months (range 6.8-10.5 months) post first symptom onset. Monitoring responses over time, we found contraction of antibody responses for all four antigens tested, with Spike antibodies showing higher persistence than Nucleocapsid antibodies. A piecewise linear random-effects multivariate regression analysis showed a bi-phasic antibody decay with a more pronounced decrease during the first 6 months post symptoms onset by analysis of two intervals. Interestingly, antibodies to Spike showed better longevity whereas their neutralization ability contracted faster. As a result, neutralizing antibodies were detected in only 76% of patients at the last time point. In a multivariate analysis, older age and hospitalization were independently associated with higher Spike, Spike-RBD, Nucleocapsid, N-RBD antibodies and neutralizing antibody levels. Results on persistence and neutralizing ability of anti-SARS-CoV-2 antibodies, especially against Spike and Spike-RBD, should be considered in the design of future vaccination strategies.


Subject(s)
COVID-19 , SARS-CoV-2 , Aged , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/therapy , Humans , Immunization, Passive , Kinetics , Spike Glycoprotein, Coronavirus
13.
Curr Treat Options Cardiovasc Med ; 23(5): 28, 2021.
Article in English | MEDLINE | ID: covidwho-1298597

ABSTRACT

PURPOSE OF REVIEW: With increasing survival of patients with stage D heart failure, the demand for heart transplantation has increased. The supply of donor hearts remains relatively limited. Strategies have been investigated and new technologies have been developed to expand the current donor pool. These new approaches will be discussed herein. RECENT FINDINGS: Donor hearts are often considered "marginal" due to risk factors such as older age, size mismatch with the intended recipient, prolonged ischemic time, presence of left ventricular hypertrophy, and hepatitis B/C infection. We reviewed recent data regarding the use of donor hearts with these risk factors and suggest ways to safely liberalize current donor heart acceptance criteria. New technologies such as temperature-controlled transport systems and ex vivo cardiac perfusion methods have also demonstrated promising short-term and intermediate outcomes as compared with routine cold storage, by promoting heart preservation and enabling heart procurement from remote sites with shorter cold ischemic time. Recent use of hearts from donation after circulatory death donors has demonstrated comparable outcomes to conventional donation after brain death, which can further expand the current donor pool. SUMMARY: Careful selection of "marginal" donor hearts, use of ex vivo cardiac perfusion, and acceptance of hearts after circulatory death may expand our current cardiac donor pool with comparable outcomes to conventional donor selection and preparation methods.

14.
Transfusion ; 61(9): 2677-2687, 2021 09.
Article in English | MEDLINE | ID: covidwho-1268131

ABSTRACT

BACKGROUND: Antibody response duration following severe acute respiratory syndrome coronavirus 2 infection tends to be variable and depends on severity of disease and method of detection. STUDY DESIGN AND METHODS: COVID-19 convalescent plasma from 18 donors was collected longitudinally for a maximum of 63-129 days following resolution of symptoms. All the samples were initially screened by the Ortho total Ig test to confirm positivity and subsequently tested with seven additional direct sandwich or indirect binding assays (Ortho, Roche, Abbott, Broad Institute) directed against a variety of antigen targets (S1, receptor binding domain, and nucleocapsid [NC]), along with two neutralization assays (Broad Institute live virus PRNT and Vitalant Research Institute [VRI] Pseudovirus reporter viral particle neutralization [RVPN]). RESULTS: The direct detection assays (Ortho total Ig total and Roche total Ig) showed increasing levels of antibodies over the time period, in contrast to the indirect IgG assays that showed a decline. Neutralization assays also demonstrated declining responses; the VRI RVPN pseudovirus had a greater rate of decline than the Broad PRNT live virus assay. DISCUSSION: These data show that in addition to variable individual responses and associations with disease severity, the detection assay chosen contributes to the heterogeneous results in antibody stability over time. Depending on the scope of the research, one assay may be preferable over another. For serosurveillance studies, direct, double Ag-sandwich assays appear to be the best choice due to their stability; in particular, algorithms that include both S1- and NC-based assays can help reduce the rate of false-positivity and discriminate between natural infection and vaccine-derived seroreactivity.


Subject(s)
Antibodies, Viral/immunology , Blood Donors , COVID-19/epidemiology , COVID-19/immunology , SARS-CoV-2/immunology , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , Antibodies, Viral/blood , COVID-19/blood , COVID-19/diagnosis , Host-Pathogen Interactions/immunology , Humans , Immunoglobulin G/blood , Immunoglobulin G/immunology , Seroepidemiologic Studies , Serologic Tests/methods , Serologic Tests/standards , Severity of Illness Index
15.
Clin Biochem ; 95: 77-80, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1265657

ABSTRACT

INTRODUCTION: Commercially available serological assays for SARS-CoV-2 detect antibodies to either the nucleocapsid or spike protein. Here we compare the performance of the Beckman-Coulter SARS-CoV-2 spike IgG assay to that of the Abbott SARS-CoV-2 nucleocapsid IgG and Roche Anti-SARS-CoV-2 nucleocapsid total antibody assays. In addition, we document the trend in nucleocapsid and spike antibodies in sequential samples collected from convalescent plasma donors. METHODS: Plasma or serum samples from 20 individual SARS-CoV-2 RT-PCR-positive inpatients (n = 172), 20 individual convalescent donors with a previous RT-PCR-confirmed SARS-CoV-2 infection (n = 20), were deemed positive SARS-CoV-2 samples. RT-PCR-negative inpatients (n = 24), and 109 pre-SARS-CoV-2 samples were determined to be SARS-CoV-2 negative. Samples were assayed by the Abbott, Roche, and Beckman assays. RESULTS: All three assays demonstrated 100% specificity. Abbott, Beckman, and Roche platforms had sensitivities of 98%, 93%, and 90% respectively, with the difference in sensitivity attributed primarily to samples from immunocompromised patients. After the exclusion of samples immunocompromised patients, all assays exhibited ≥ 95% sensitivity. In sequential samples collected from the same individuals, the Roche nucleocapsid antibody assay demonstrated continually increasing signal intensity, with maximal values observed at the last time point examined. In contrast, the Beckman spike IgG antibody signal peaked between 14 and 28 days post positive SARS-CoV-2 PCR and steadily declined in subsequent samples. Subsequent collections 51-200 days (median of 139 days) post positive SARS-CoV-2 RT-PCR from five inpatients and five convalescent donors revealed that spike and nucleocapsid antibodies remained detectable for several months after confirmed infection. CONCLUSIONS: The three assays are sensitive and specific for SARS-CoV-2 antibodies. Nucleocapsid and spike antibodies were detectable for up to 200 days post-positive SARS-CoV-2 PCR but demonstrated markedly different trends in signal intensity.


Subject(s)
Antibodies, Viral/blood , COVID-19 Serological Testing/methods , COVID-19/blood , Nucleocapsid/blood , SARS-CoV-2/metabolism , Antibodies, Viral/immunology , COVID-19/diagnosis , COVID-19/immunology , Humans , Immunoassay/methods , Longitudinal Studies , Nucleocapsid/immunology , SARS-CoV-2/isolation & purification
16.
Orv Hetil ; 162(23): 890-896, 2021 06 06.
Article in Hungarian | MEDLINE | ID: covidwho-1259268

ABSTRACT

Összefoglaló. Bevezetés: A SARS-CoV-2-világjárvány terjedése drasztikus változásokat okozott a mindennapi betegellátásban, amelyek érintették a szervadományozás és -átültetés területét is, így csökkent az élo és az elhunyt donorokból történo donációk és transzplantációk száma világszerte. Az esetszám csökkenése mellett a transzplantált és egyben immunszupprimált betegek védelme érdekében további biztonsági intézkedéseket kellett bevezetni. Módszer: A vizsgálat célja a COVID-19-járvány hazai donációs és transzplantációs aktivitásra gyakorolt hatásának kimutatása volt 2020-ban, a megelozo évvel történo összehasonlításban. A magyar eredményeket összehasonlítottuk elsosorban az Eurotransplant, illetve az Európai Unió tagállamainak adataival is. Eredmények: A lakosságszámra súlyozott, regisztrált COVID-19-fertozöttség és -halálozás tekintetében nem igazoltunk 2020-ban kiemelkedo eltérést itthon az Eurotransplant-tagállamokhoz képest. A hazai szervdonációs potenciál nem csökkent a vizsgált idoszakban, ugyanakkor 38,33%-kal csökkent az agyhalott szervdonorok száma Magyarországon, míg az Eurotransplantban átlagosan 8,64%-kal és 23 adatközlo európai országban 17,55%-kal. Az elhunytból történt szervátültetések száma 29,27%-kal csökkent, különösen a szív- és a májátültetések esetén. A külföldrol kapott szervek száma 21,13%-kal és aránya 12,34%-kal emelkedett. Az élo donoros veseátültetések száma nem változott. 2020-ban 25%-kal kevesebb új beteget regisztráltak, mint 2019-ben, és a várólista-mortalitás 28%-kal növekedett az elozo évhez képest, kifejezetten a veseátültetésre várók között. Következtetés: A hazai szervátültetési program biztonságos: donoreredetu SARS-CoV-2-átvitel nem történt hazánkban. A szervdonációs potenciál és a COVID-19-járvány mellett a szervdonációs és -transzplantációs aktivitás jelentosen csökkent Magyarországon 2020. márciustól az év végéig. A legtöbb európai országban átmeneti és kisebb mértéku szervdonációs csökkenést regisztráltak. A szervátültetések száma nem csökkent olyan mértékben, mint a donorszám, mert az Eurotransplantból több donorszerv érkezett hazánkba, mint amennyit külföldre küldtünk. Orv Hetil. 2021; 162(23): 890-896. INTRODUCTION: The spread of the SARS-CoV-2 pandemic has resulted in drastic changes in day-to-day patient care, which has also affected the field of organ donation and transplantation, thus reducing the number of donations and transplants from living and deceased donors worldwide. In addition to the reduction in the number of cases, additional safety measures had to be introduced to protect transplanted and implicatively immunosuppressed patients. METHOD: The aim of the study was to demonstrate the impact of the COVID-19 epidemic on domestic donation and transplantation activity in 2020, compared to the previous year. We also compared the Hungarian results with the data of the Eurotransplant and the European Union member states. RESULTS: In terms of population-weighted, registered COVID-19 infection and mortality, we did not find a significant difference in Hungary in 2020 compared to the Eurotransplant member states. The national organ donation potential did not diminish in the period under review, however, the number of brain-dead organ donors decreased by 38.33% in Hungary, while in the Eurotransplant it did by 8.64% on average and in 23 reporting European countries by 17.55%. The number of organ transplants from the deceased decreased by 29.27%, especially regarding heart and liver transplants. Both the number and the proportion of organs received from abroad increased by 21.13% and 12.34%, respectively. The number of living donor kidney transplants did not change. In 2020, 25% fewer new patients were registered than in 2019 and the mortality on waiting list increased by 28% compared to the previous year, especially among those waiting for a kidney transplant. CONCLUSION: The national organ transplantation program is safe: donor-derived SARS-CoV-2 transmission did not occur in Hungary. In addition to the organ donation potential and the COVID-19 pandemic, organ donation and transplantation activity decreased significantly in Hungary from March 2020 until the end of the year. Transient and smaller reductions in organ donation rates have been reported in most European countries. The number of organ transplants did not decrease as much as the number of donors, because more donor organs arrived in Hungary from the Eurotransplant than we sent abroad. Orv Hetil. 2021; 162(23): 890-896.


Subject(s)
COVID-19 , Organ Transplantation , Tissue and Organ Procurement , Europe , Humans , Hungary , Pandemics , SARS-CoV-2
17.
J Clin Invest ; 131(10)2021 05 17.
Article in English | MEDLINE | ID: covidwho-1255762

ABSTRACT

BACKGROUNDRecent studies have reported T cell immunity to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in unexposed donors, possibly due to crossrecognition by T cells specific for common cold coronaviruses (CCCs). True T cell crossreactivity, defined as the recognition by a single TCR of more than one distinct peptide-MHC ligand, has never been shown in the context of SARS-CoV-2.METHODSWe used the viral functional expansion of specific T cells (ViraFEST) platform to identify T cell responses crossreactive for the spike (S) glycoproteins of SARS-CoV-2 and CCCs at the T cell receptor (TCR) clonotype level in convalescent COVID-19 patients (CCPs) and SARS-CoV-2-unexposed donors. Confirmation of SARS-CoV-2/CCC crossreactivity and assessments of functional avidity were performed using a TCR cloning and transfection system.RESULTSMemory CD4+ T cell clonotypes that crossrecognized the S proteins of SARS-CoV-2 and at least one other CCC were detected in 65% of CCPs and unexposed donors. Several of these TCRs were shared among multiple donors. Crossreactive T cells demonstrated significantly impaired SARS-CoV-2-specific proliferation in vitro relative to monospecific CD4+ T cells, which was consistent with lower functional avidity of their TCRs for SARS-CoV-2 relative to CCC.CONCLUSIONSOur data confirm, for what we believe is the first time, the existence of unique memory CD4+ T cell clonotypes crossrecognizing SARS-CoV-2 and CCCs. The lower avidity of crossreactive TCRs for SARS-CoV-2 may be the result of antigenic imprinting, such that preexisting CCC-specific memory T cells have reduced expansive capacity upon SARS-CoV-2 infection. Further studies are needed to determine how these crossreactive T cell responses affect clinical outcomes in COVID-19 patients.FUNDINGNIH funding (U54CA260492, P30CA006973, P41EB028239, R01AI153349, R01AI145435-A1, R21AI149760, and U19A1088791) was provided by the National Institute of Allergy and Infectious Diseases, the National Cancer Institute, and the National Institute of Biomedical Imaging and Bioengineering. The Bloomberg~Kimmel Institute for Cancer Immunotherapy, The Johns Hopkins University Provost, and The Bill and Melinda Gates Foundation provided funding for this study.


Subject(s)
CD4-Positive T-Lymphocytes/immunology , COVID-19/immunology , Epitopes, T-Lymphocyte/immunology , Immunologic Memory , Receptors, Antigen, T-Cell/immunology , SARS-CoV-2/immunology , Adult , Aged , Cross Reactions , Female , Humans , Jurkat Cells , Male , Middle Aged
18.
Sci Immunol ; 6(59)2021 05 25.
Article in English | MEDLINE | ID: covidwho-1243688

ABSTRACT

The emergence of SARS-CoV-2 variants harboring mutations in the spike (S) protein has raised concern about potential immune escape. Here, we studied humoral and cellular immune responses to wild type SARS-CoV-2 and the B.1.1.7 and B.1.351 variants of concern in a cohort of 121 BNT162b2 mRNA-vaccinated health care workers (HCW). Twenty-three HCW recovered from mild COVID-19 disease and exhibited a recall response with high levels of SARS-CoV-2-specific functional antibodies and virus-specific T cells after a single vaccination. Specific immune responses were also detected in seronegative HCW after one vaccination, but a second dose was required to reach high levels of functional antibodies and cellular immune responses in all individuals. Vaccination-induced antibodies cross-neutralized the variants B.1.1.7 and B.1.351, but the neutralizing capacity and Fc-mediated functionality against B.1.351 was consistently 2- to 4-fold lower than to the homologous virus. In addition, peripheral blood mononuclear cells were stimulated with peptide pools spanning the mutated S regions of B.1.1.7 and B.1.351 to detect cross-reactivity of SARS-CoV-2-specific T cells with variants. Importantly, we observed no differences in CD4+ T-cell activation in response to variant antigens, indicating that the B.1.1.7 and B.1.351 S proteins do not escape T-cell-mediated immunity elicited by the wild type S protein. In conclusion, this study shows that some variants can partially escape humoral immunity induced by SARS-CoV-2 infection or BNT162b2 vaccination, but S-specific CD4+ T-cell activation is not affected by the mutations in the B.1.1.7 and B.1.351 variants.


Subject(s)
Antibodies, Viral/immunology , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , COVID-19/immunology , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , COVID-19 Vaccines/immunology , Cell Line , Cross Reactions/immunology , Humans , Immunologic Memory/immunology , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics , Vaccination
19.
Cornea ; 40(8): 1018-1023, 2021 08 01.
Article in English | MEDLINE | ID: covidwho-1240937

ABSTRACT

PURPOSE: The purpose of this study was to assess the impact of COVID-19 guidelines for corneal donor tissue screening and the utility of routine postmortem COVID-19 testing of donors intended for surgical use at a single eye bank. METHODS: A retrospective analysis of referrals to and eligible donors from an eye bank between March 1, 2020, and June 30, 2020, was performed, with the same time period in 2019 as a control. Referrals who were not procured because of Eye Bank Association of America COVID-19 guidelines and eye bank-specific restrictions were noted. The results of 1 month of routine postmortem testing performed by the eye bank were examined. Analysis of variance tests were performed to assess the change between donors from 2019 to 2020. RESULTS: There was a significant reduction in both the number of total referrals to the eye bank (P = 0.044) and donors eligible for surgical transplantation (P = 0.031). Eye Bank Association of America COVID-19 guidelines reduced the number of referrals over this period by 4% to 14%. Of the 266 surgically eligible donors who received postmortem COVID-19 testing in June by the eye bank, 13 resulted positive (4.9%). CONCLUSIONS: Despite a reduction in referrals and eligible corneal transplant donors at a single eye bank, there was a surplus of surgically suitable corneal tissue during the first wave of the COVID-19 pandemic. Eye banks should consider routine postmortem COVID-19 testing to identify asymptomatic infected donors although the risk of transmission of COVID-19 from infected donors is unknown.


Subject(s)
COVID-19/epidemiology , Cornea , Eye Banks/statistics & numerical data , Keratoplasty, Penetrating/statistics & numerical data , SARS-CoV-2 , Tissue Donors/supply & distribution , Tissue and Organ Procurement/standards , Adolescent , Adult , Aged , COVID-19 Nucleic Acid Testing , Corneal Diseases/surgery , Eye Banks/standards , Humans , Middle Aged , Practice Guidelines as Topic , Retrospective Studies
20.
Cell ; 184(13): 3452-3466.e18, 2021 06 24.
Article in English | MEDLINE | ID: covidwho-1240207

ABSTRACT

Antibodies against the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein prevent SARS-CoV-2 infection. However, the effects of antibodies against other spike protein domains are largely unknown. Here, we screened a series of anti-spike monoclonal antibodies from coronavirus disease 2019 (COVID-19) patients and found that some of antibodies against the N-terminal domain (NTD) induced the open conformation of RBD and thus enhanced the binding capacity of the spike protein to ACE2 and infectivity of SARS-CoV-2. Mutational analysis revealed that all of the infectivity-enhancing antibodies recognized a specific site on the NTD. Structural analysis demonstrated that all infectivity-enhancing antibodies bound to NTD in a similar manner. The antibodies against this infectivity-enhancing site were detected at high levels in severe patients. Moreover, we identified antibodies against the infectivity-enhancing site in uninfected donors, albeit at a lower frequency. These findings demonstrate that not only neutralizing antibodies but also enhancing antibodies are produced during SARS-CoV-2 infection.


Subject(s)
Antibodies, Monoclonal/immunology , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Animals , COVID-19/immunology , Cell Line , Chlorocebus aethiops , HEK293 Cells , Humans , Protein Binding/immunology , Protein Domains/immunology , Spike Glycoprotein, Coronavirus/genetics , Vero Cells
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