LitCovid-sentences  

PMC:7546122 / 900-15609 JSONTXT 10 Projects

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Id Subject Object Predicate Lexical cue
T8 0-197 Sentence denotes Intravenous immunoglobulins (IVIG) are produced from thousands of pooled plasma donations, and thus contain a wide variety of antibodies the donors have generated against infectious disease agents.
T9 198-308 Sentence denotes IVIG can therefore protect people with immune deficiencies against circulating bacterial and viral infections.
T10 309-519 Sentence denotes When a new pathogen emerges, antibodies to the new agent only become detectable in IVIG preparations after a certain proportion of plasma donors have contracted the infection and successfully recovered from it.
T11 520-719 Sentence denotes An even higher number of convalescent plasma donors is needed to result in neutralizing antibody (nAb) levels high enough for the resulting IVIG to afford protection against the new infectious agent.
T12 720-1013 Sentence denotes After the arrival of West Nile virus (WNV) in the United States, for example, it took several years before the prevalence of WNV nAbs reached approximately 0.5% in the plasma donor community, at which point they became detectable in IVIG lots produced from plasma donated in the United States.
T13 1014-1107 Sentence denotes Thereafter, a significant proportion of IVIG lots even reached in vivo protective levels [1].
T14 1108-1287 Sentence denotes Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spread around the globe at unprecedented speed, infecting millions of people within the first 6 months of circulation.
T15 1288-1408 Sentence denotes The virus belongs to the Coronaviridae family of viruses, which contains several species of importance for human health.
T16 1409-1912 Sentence denotes The human coronaviruses (HCoVs) 229E, NL63, OC43, and HKU1 are in circulation as seasonal respiratory viruses that mostly cause self-limiting and mild infections but which can also lead to pneumonia and bronchiolitis [2–4], whereas the Middle East respiratory syndrome coronavirus (MERS-CoV) caused a prolonged outbreak mainly limited to the Arabian Peninsula, and the SARS-CoV and SARS-CoV-2 viruses have established global transmissions chains—the latter 3 associated with significant human mortality.
T17 1913-2133 Sentence denotes Due to the widespread and long-term circulation of HCoVs, and the pooling of plasma from thousands of donors for every lot, IVIGs contain significant levels of HCoV nAb levels, as was shown for example for HCoV-NL63 [5].
T18 2134-2255 Sentence denotes Whether these HCoV antibodies cross-react with, or even neutralize, the related SARS-CoV-2 has not been fully elucidated.
T19 2256-2522 Sentence denotes To date, antibody binding assays have shown some cross-reactivity between different HCoVs and SARS-CoV-2; however, functional and therefore clinically more relevant virus neutralization assays have shown no or only very low levels of cross-reactive antibodies [6–8].
T20 2523-2805 Sentence denotes The question is of significant clinical relevance, as SARS-CoV-2 cross-neutralizing antibodies in IVIGs, if they were present, might afford some protection to people with immune deficiencies and may even represent a treatment option for coronavirus disease 2019 (COVID-19) patients.
T21 2806-3072 Sentence denotes The current study tested a representative number of IVIG lots for nAbs against SARS-CoV-2 and the longer-circulating HCoV-229E, to establish clarity about cross-neutralization of the pandemic virus by antibodies induced by earlier circulating seasonal coronaviruses.
T22 3073-3211 Sentence denotes In addition, results from the ongoing monitoring of the plasma donor community for the development of SARS-COV-2 antibodies are presented.
T23 3213-3220 Sentence denotes METHODS
T24 3222-3239 Sentence denotes IVIG Preparations
T25 3240-3352 Sentence denotes A total of 54 IVIG lots fractionated from plasma collected prior to the circulation of SARS-CoV-2 were analyzed.
T26 3353-3657 Sentence denotes The IVIG lots were manufactured from plasma either donated by plasmapheresis (source) or recovered from whole-blood donations (recovered), in the United States (Gammagard Liquid; Baxter Healthcare Corp.; n = 30) or central Europe, that is Austria, Germany, and Czech Republic (KIOVIG; Baxter AG; n = 24).
T27 3658-3792 Sentence denotes These 54 IVIG lots were tested in 2 independent experiments for nAbs (1 European lot was in a single assay due to volume constraints).
T28 3794-3814 Sentence denotes Human Plasma Samples
T29 3815-3904 Sentence denotes Two prepandemic plasma donations were collected in April and May 2019 by BioLife Austria.
T30 3905-4063 Sentence denotes Human plasma pool samples were generated by the combination of 6 individual donations obtained in the same week at Austrian plasma donation centers (BioLife).
T31 4064-4336 Sentence denotes The pools were assembled from donations collected in week 13 (last week of March; n = 40), week 14 (n = 80), week 15 (n = 80), week 16 (n = 80), week 20 (n = 100), week 24 (n = 80), and week 28 (first week of July; n = 100) of 2020, that is during the SARS-CoV-2 pandemic.
T32 4337-4563 Sentence denotes Cumulative incidence of COVID-19 was calculated from data provided by the Austrian Federal Ministry for Social Affairs, Health, Care and Consumer Protection (www.sozialministerium.at) and Statistics Austria (www.statistik.at).
T33 4565-4612 Sentence denotes Detection of SARS-CoV-2 Neutralizing Antibodies
T34 4613-4853 Sentence denotes SARS-CoV-2 nAb titers were determined in IVIG and human plasma samples that were used undiluted, or prediluted with cell culture medium 1:4, 1:5, 1:10, or 1:20 depending on sample amount available, and then serially diluted in 2-fold steps.
T35 4854-5042 Sentence denotes Equal volumes of sample dilutions were mixed with virus stock at 103.0 tissue culture infectious doses 50% per milliliter (TCID50/mL) SARS-CoV-2 (strain BavPat1/2020, kindly provided by C.
T36 5043-5057 Sentence denotes Drosten and V.
T37 5058-5175 Sentence denotes Corman, Charité Berlin, Germany) and incubated for 150 minutes ± 15 minutes, before titration on Vero cells (Cat. no.
T38 5176-5300 Sentence denotes 84113001, European Collection of Authenticated Cell Cultures, Porton Down, Salisbury, UK) in 8-fold replicates per dilution.
T39 5301-5381 Sentence denotes The virus-induced cytopathic effect was determined after 5–7 days of incubation.
T40 5382-5585 Sentence denotes The reciprocal sample dilution resulting in 50% virus neutralization (NT50) was determined using the Spearman-Kärber formula, and the calculated neutralization titer for 50% of the wells reported as 1:X.
T41 5586-5765 Sentence denotes The detection limits were as follows: <1:0.8 for undiluted, <1:3.1 for 1:4 prediluted, <1:3.9 for 1:5 prediluted, <1:7.7 for 1:10 prediluted, and <1:15.4 for 1:20 prediluted IVIG.
T42 5766-6017 Sentence denotes The neutralization assay (µNT) included several validity criteria, that is confirmatory titration of input virus infectivity, cell viability, and neutralization testing of an internal reference standard, all of which had to comply with defined ranges.
T43 6019-6065 Sentence denotes Detection of HCoV-229E Neutralizing Antibodies
T44 6066-6301 Sentence denotes The neutralization assay for HCoV-229E antibodies is essentially identical to the SARS-CoV-2, where samples were used undiluted or prediluted, then serially diluted in 2-fold steps and mixed 1:2 with 103.0 TCID50/mL HCoV-229E (Cat. no.
T45 6302-6415 Sentence denotes VR-740, American Type Culture Collection [ATCC], Rockville, MD), incubated, and titrated on MRC-5 cells (Cat. no.
T46 6416-6446 Sentence denotes CCL-171, ATCC, Rockville, MD).
T47 6447-6527 Sentence denotes The virus-induced cytopathic effect was determined after 7–9 days of incubation.
T48 6529-6560 Sentence denotes Graphs and Statistical Analysis
T49 6561-6673 Sentence denotes Graphical illustration and statistical analysis (paired t tests) were done using GraphPad Prism v8.1.1 software.
T50 6675-6682 Sentence denotes RESULTS
T51 6683-7016 Sentence denotes The validity, specificity, and reliability of the SARS-CoV-2 neutralization assay used in the current study were demonstrated by the analysis of 100 convalescent plasma donations from polymerase chain reaction (PCR)-confirmed SARS-CoV-2 cases [9] and was the basis for the correlation of function against diverse binding assays [10].
T52 7017-7212 Sentence denotes As controls, 2 plasma samples collected before the emergence of SARS-CoV-2 did not contain SARS-CoV-2 nAbs, as expected, but neutralized HCoV-229E with NT50 values of 1:43 and 1:26, respectively.
T53 7214-7229 Sentence denotes Testing of IVIG
T54 7230-7454 Sentence denotes SARS-CoV-2 nAb titers were below the limit of detection for all 54 IVIG lots tested, irrespective of geographic origin of the plasma (Europe vs United States) and plasma collection modality (recovered vs source) (Figure 1A).
T55 7455-7464 Sentence denotes Figure 1.
T56 7466-7570 Sentence denotes Coronavirus neutralizing antibody titers in IVIG lots (n = 54) against (A) SARS-CoV-2 and (B) HCoV-229E.
T57 7571-7737 Sentence denotes The IVIG lots were manufactured from plasma either donated by plasmapheresis (S), or recovered from whole blood donations (R), in the United States or central Europe.
T58 7738-7877 Sentence denotes Each dot represents the mean of 2 independent experiments, except in (B) from 1 EU-R IVIG lot the titer of a single determination is shown.
T59 7878-7923 Sentence denotes The lines represent the median in each group.
T60 7924-7983 Sentence denotes Paired t tests were used for determination of significance.
T61 7984-8212 Sentence denotes Abbreviation: EU, Europe; HCoV, human coronavirus; IVIG, intravenous immunoglobulin; LOD, limit of detection; µNT50, 50% neutralization titer; R, recovered; S, source; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.
T62 8213-8338 Sentence denotes In contrast, HCoV-229E nAb titers between 1:43 and 1:196 (mean = 1:98) were measured for the 54 IVIG lots tested (Figure 1B).
T63 8339-8529 Sentence denotes IVIG lots produced from recovered plasma contained significantly higher levels of nAb to HCoV-229E as compared to IVIG lots produced from source plasma, independent of the geographic origin.
T64 8530-8700 Sentence denotes A significant, although quantitatively minor, difference was also found between IVIG lots manufactured from source plasma collected in either the United States or Europe.
T65 8702-8725 Sentence denotes Testing of Human Plasma
T66 8726-8876 Sentence denotes To evaluate the potential development of SARS-CoV-2 antibodies in the plasma donor community, samples of plasma pools of 6 donations each were tested.
T67 8877-9011 Sentence denotes The use of pools enabled testing of a high amount of plasma donations for SARS-CoV-2 nAbs with the biosafety level-3 functional assay.
T68 9012-9185 Sentence denotes As the mean SARS-CoV-2 µNT50 of plasma donations is rather high (approximately 1:230 [9]) even the nAbs of only 1 positive sample within a pool are detectable in this assay.
T69 9186-9470 Sentence denotes Testing a total of 560 plasma pools of 6 donations each, in total reflective of 3360 plasma donations, from week 13 (ie, last week of March) until week 28 (ie, first week of July) 2020 revealed that most of these pools had SARS-CoV-2 µNT titers below the limit of detection (Table 1).
T70 9471-9546 Sentence denotes The first pool with detectable nAbs to SARS-CoV-2 was collected in week 14.
T71 9547-9609 Sentence denotes Further positive pools were found in weeks 15, 16, 24, and 28.
T72 9610-9822 Sentence denotes Up to 7% of the tested pools showed nAbs to SARS-CoV-2, which indicates that up to 1.17% of the plasma donors were positive for SARS-CoV-2 nAbs at a cumulative incidence of COVID-19 in Austria of 0.21% (Table 1).
T73 9823-9831 Sentence denotes Table 1.
T74 9833-9890 Sentence denotes SARS-CoV-2 Neutralizing Antibodies in Tested Plasma Pools
T75 9891-9903 Sentence denotes Week in 2020
T76 9904-9941 Sentence denotes Parameter 13 14 15 16 20 24 28
T77 9942-9997 Sentence denotes Plasma pools ≥LOD, % 0.0 1.3 1.3 6.3 0.0 5.0 7.0
T78 9998-10041 Sentence denotes µNT50 of plasma pool titers ≥LOD, 1:X n.a.
T79 10043-10073 Sentence denotes 37 5 6, 18, 26, 34, 87 n.a.
T80 10075-10112 Sentence denotes 7, 10, 20, 22 4, 7, 8, 9, 12, 18, 24
T81 10113-10172 Sentence denotes Number of plasma pools tested 40 80 80 80 100 80 100
T82 10173-10266 Sentence denotes SARS-CoV-2 nAb positive plasma donors in Austria, % 0.00 0.21 0.21 1.04 0.00 0.83 1.17
T83 10267-10353 Sentence denotes Cumulative COVID-19 incidence in Austria, %a 0.10 0.14 0.16 0.17 0.18 0.19 0.21
T84 10354-10622 Sentence denotes Abbreviations: µNT50, neutralization titer for 50% of the wells; COVID-19, coronavirus disease 2019; LOD, limit of detection; n.a., not applicable; nAb, neutralizing antibody; PCR, polymerase chain reaction; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.
T85 10623-10752 Sentence denotes aSARS-CoV-2 PCR-positive individuals per 100 000 population in Austria are described as cumulative COVID-19 incidence in percent.
T86 10754-10764 Sentence denotes DISCUSSION
T87 10765-10913 Sentence denotes Our analysis of IVIG lots revealed high nAb titers to HCoV-229E (Figure 1B), which confirmed the presence of functionally intact nAbs in these lots.
T88 10914-11121 Sentence denotes It is interesting to note that in IVIG lots produced from recovered plasma significantly higher titers to HCoV-229E were found compared to IVIG lots produced from source plasma, independent of plasma origin.
T89 11122-11182 Sentence denotes Recovered plasma is usually obtained from older donors [11].
T90 11183-11315 Sentence denotes A trend towards increasing probability of HCoV-229E infections with age has been detected in the Scottish [3] and US [4] population.
T91 11316-11463 Sentence denotes Furthermore, higher HCoV-229E–specific nAb titers were found in older study participants (60–85 years) compared to younger ones (21–40 years) [12].
T92 11464-11722 Sentence denotes Thus, a higher infection rate with HCoV-229E in older people and consequently the generation of neutralizing HCoV-229E–specific antibodies in the older plasma donors would explain the higher HCoV-229E titers found in IVIG lots produced from recovered plasma.
T93 11723-11918 Sentence denotes Low levels of cross-neutralizing Abs have earlier been demonstrated between specific pairs of coronaviruses, specifically between SARS-CoV-2 sera and SARS-CoV [6] and SARS-CoV sera and MERS [13].
T94 11919-12099 Sentence denotes In clear contrast, testing the same lots of IVIG that were shown to contain high HCoV-229E nAb titers with a highly specific SARS-CoV-2 µNT did not detect SARS-CoV-2–specific nAbs.
T95 12100-12310 Sentence denotes These results are entirely consistent with the absence of SARS-CoV-2 antibodies in the plasma used for production of these IVIG lots, as this plasma was donated well before the start of the SARS-CoV-2 pandemic.
T96 12311-12718 Sentence denotes The current study, as well as an earlier study that tested 21 IVIG lots (9 Gamunex C, 10 Gammagard Liquid, 2 other) with a SARS-CoV-2-specific enzyme-linked immunosorbent assay (ELISA; receptor-binding domain or spike protein) that was shown to correlate well with a neutralization test [14] revealed the absence of cross-reactive antibodies against SARS-CoV-2 in IVIG lots produced from prepandemic plasma.
T97 12719-12822 Sentence denotes Currently available IVIGs can therefore not be expected to afford protection from SARS-CoV-2 infection.
T98 12823-13098 Sentence denotes Nevertheless, several clinical trials currently investigate IVIG at high dosage in the treatment of COVID-19 patients (clinicaltrials.gov), with the expected benefit attributable to the anti-inflammatory and immunomodulatory capacity of IVIG, rather than an antiviral effect.
T99 13099-13398 Sentence denotes With increasing numbers of human infections, including in the plasma donor community, it is interesting to follow the development of antibodies against SARS-CoV-2 in plasma donations and, after the several months production cycle time between plasma donation and IVIG lot release, also in IVIG lots.
T100 13399-13459 Sentence denotes A longitudinal study on this topic is currently in progress.
T101 13460-13591 Sentence denotes In this context it is noteworthy that the mean nAb titers induced by WNV [1] and SARS-CoV-2 [9] infection are of similar magnitude.
T102 13592-13770 Sentence denotes After the emergence of WNV in the United States, nAb titers became detectable in IVIGs after approximately 0.5% of the population had contracted and recovered from the infection.
T103 13771-13892 Sentence denotes In Austria, testing of plasma pool samples indicated that up to 1.17% of plasma donors were positive for SARS-CoV-2 nAbs.
T104 13893-14236 Sentence denotes Based on the current number of reported SARS-CoV-2 infections in the United States (approximately 4.3 million per 30 July 2020; www.cdc.gov), and an estimated rate of >40% asymptomatic infections [15], more than 7.2 million people in the United States could have been infected already, that is 2.2% of the approximately 330 million population.
T105 14237-14405 Sentence denotes Based on these facts, the detection of SARS-CoV-2 nAbs in IVIG lots produced from US plasma, the major source for fractionation, is expected within the next few months.
T106 14406-14709 Sentence denotes Another, more immediately available possibility for the treatment of COVID-19 is production of a hyper-IVIG from the plasma of COVID-19 convalescent donors (CoVIg-19), and developmental work is currently under way through a large alliance of plasma stakeholders (https://www.covig-19plasmaalliance.org).