LitCovid-sentences  

PMC:7200337 / 93975-103487 JSONTXT 11 Projects

Annnotations TAB TSV DIC JSON TextAE

Id Subject Object Predicate Lexical cue
T540 0-68 Sentence denotes Neutralizing Antibodies and Convalescent Plasma Therapy for COVID-19
T541 69-274 Sentence denotes While vaccines are being developed to educate a person’s immune system to make their own nAbs against SARS-CoV-2, there is interest in using adoptive transfer of nAbs as a therapeutic approach (Figure 6D).
T542 275-530 Sentence denotes This strategy has already proven to be effective against SARS-CoV-1 (Cao et al., 2010, Ho et al., 2005, ter Meulen et al., 2004, Park et al., 2020, Sui et al., 2004, Zhu et al., 2007) and MERS-CoV (Forni et al., 2015, Jia et al., 2019, Ying et al., 2015).
T543 531-703 Sentence denotes In the case of SARS-CoV-2, these efforts are primarily centered on identifying nAbs made during natural infections or generating nAbs through animal vaccination approaches.
T544 705-740 Sentence denotes nAbs Derived from COVID-19 Patients
T545 741-926 Sentence denotes Patients who have recovered from SARS-CoV-2 infection are one potential source of nAbs (Chen et al., 2020a, Ju et al., 2020, Walls et al., 2020, Wölfel et al., 2020, Yuan et al., 2020).
T546 927-1157 Sentence denotes In an effort to obtain these nAbs, scientists sorted RBD-specific memory B cells and cloned their heavy and light variable regions to express recombinant forms of the corresponding antibodies (Chen et al., 2020a, Ju et al., 2020).
T547 1158-1319 Sentence denotes Four of the antibodies produced in these studies (31B5, 32D4, P2C-2F6, P2C-1F11) showed high neutralizing potential in vitro, and all inhibited ACE2-RBD binding.
T548 1320-1439 Sentence denotes Successful antibody-mediated neutralization of SARS-CoV-2 seemed to be dependent on the inhibition of ACE2/RBD binding.
T549 1440-1634 Sentence denotes However, Chen et al. showed that nearly all antibodies derived from serum of 26 recovered patients bound to S1 and RBD, with only three actually inhibiting ACE2/RBD binding (Chen et al., 2020a).
T550 1635-1872 Sentence denotes Of note, a SARS-CoV-1-derived neutralizing antibody (47D11) (Wang et al., 2020a) and a single-chain antibody against SARS-CoV-2 (n3130) (Wu et al., 2020c) have also been shown to neutralize SARS-CoV-2 without inhibiting ACE2/RBD binding.
T551 1873-1963 Sentence denotes Thus, blocking this interaction may not be a prerequisite for an effective SARS-CoV-2 nAb.
T552 1964-2208 Sentence denotes The generation of a hybridoma producing a monoclonal nAb against SARS-CoV-2 provides the potential for a therapeutic Ab that can be directly administered to patients to block ongoing infection and potentially even as a prophylactic (Figure 6D).
T553 2210-2252 Sentence denotes SARS-CoV-1 nAbs Also Neutralize SARS-CoV-2
T554 2253-2343 Sentence denotes SARS-CoV-1 and SARS-CoV-2 consensus sequences share about 80% identity (Tai et al., 2020).
T555 2344-2513 Sentence denotes Thus, a wide range of SARS-CoV-1 nAbs have been tested for crossreactivity with SARS-CoV-2, as they could help speed up the development of potential COVID-19 treatments.
T556 2514-2639 Sentence denotes In a recent study, antibodies were isolated from the memory B cells of an individual who recovered from SARS-CoV-1 infection.
T557 2640-2793 Sentence denotes While 8 out of 25 isolated antibodies could bind SARS-CoV-2 S protein, one of them (s309; see Table 3 ) also neutralizes SARS-CoV-2 (Pinto et al., 2020).
T558 2794-2929 Sentence denotes The combination of s309 with a weakly neutralizing antibody that could bind another RBD epitope led to enhanced neutralization potency.
T559 2930-3083 Sentence denotes In addition, CR3022 (Table 3) was found to bind SARS-CoV-2 RBD (Tian et al., 2020b), but this antibody did not neutralize SARS-CoV-2 (Yuan et al., 2020).
T560 3084-3298 Sentence denotes Computational simulations identified three amino acids that could be modified on CR3022 to enhance its binding affinity with SARS-CoV-2 RBD (Giron et al., 2020), potentially augmenting its neutralization potential.
T561 3299-3363 Sentence denotes Table 3 Strategies to Isolate SARS-CoV-2 Neutralizing Antibodies
T562 3364-3459 Sentence denotes Ab Source Clone Target Type of Antibody Neutralization Inhibition of ACE2/RBD Binding Reference
T563 3460-3547 Sentence denotes Derived from COVID-19 patients 31B532D4 RBD human monoclonal yes yes Chen et al., 2020a
T564 3548-3608 Sentence denotes P2C-2F6P2C-1F11 RBD human monoclonal yes yes Ju et al., 2020
T565 3609-3733 Sentence denotes Derived from SARS-CoV-1 patients CR3022 RBD human monoclonal no no Tian et al., 2020b, Yuan et al., 2020, Giron et al., 2020
T566 3734-3785 Sentence denotes S309 RBD human monoclonal yes no Pinto et al., 2020
T567 3786-3895 Sentence denotes Derived from SARS-CoV-1 or MERS-CoV-1 animal models R325R302R007 S1 rabbit monoclonal yes no Sun et al., 2020
T568 3896-4019 Sentence denotes 47D11 S1 recombinant human monoclonal (derived from hybridomas of immunized transgenic H2L2 mice) yes no Wang et al., 2020a
T569 4020-4094 Sentence denotes VHH-72-Fc S Fc-fusion derived from camelids VHH yes yes Wrapp et al., 2020
T570 4095-4170 Sentence denotes S polyclonal mouse antibodies yes N/A Walls et al., 2020, Yuan et al., 2020
T571 4171-4247 Sentence denotes Other ACE2-Fc RBD ACE2-Fc fusion yes N/A Lei et al., 2020a, Li et al., 2020d
T572 4248-4298 Sentence denotes RBD-Fc ACE2 RBD-Fc fusion yes N/A Li et al., 2020d
T573 4299-4397 Sentence denotes N3130 S1 human monoclonal single domain antibody isolated by phage display yes no Wu et al., 2020c
T574 4398-4473 Sentence denotes IVIg N/A polyclonal human IVIg N/A N/A Díez et al., 2020, Shao et al., 2020
T575 4474-4527 Sentence denotes F(ab′)2 RBD horse polyclonal yes N/A Pan et al., 2020
T576 4528-4546 Sentence denotes N/A, not assessed.
T577 4548-4573 Sentence denotes nAbs Derived from Animals
T578 4574-4657 Sentence denotes Animal models represent another tool to generate nAbs against SARS-CoV-2 (Table 3).
T579 4658-4864 Sentence denotes In one study, the authors developed a protocol to synthetize human nanobodies, smaller antibodies that only contain a variable heavy (VH) chain as first described in camelids (Wu et al., 2020c) (Figure 6D).
T580 4865-5073 Sentence denotes Another antibody isolated from camelids immunized with SARS-CoV-1 and MERS-CoV S proteins then fused to a human Fc fragment showed neutralization potential against SARS-CoV-2 (VHH-72-Fc) (Wrapp et al., 2020).
T581 5074-5258 Sentence denotes Genetically modified mice with humanized antibody genes can also be used to generate therapeutic monoclonal antibodies, as successfully experimented against Ebola virus (Levine, 2019).
T582 5259-5567 Sentence denotes Similar studies are now focused on the use of SARS-CoV-2 or derivatives to generate highly effective nAb in animal models, which can be directly given to infected patients, and efforts are already underway with estimates of clinical trials of pooled antibody cocktails beginning in early summer by Regeneron.
T583 5568-5753 Sentence denotes Finally, another approach to nAb development is to fuse ACE2 protein and the Fc part of antibodies, as they would bind RBD and potentially be crossreactive among other CoVs (Figure 6D).
T584 5754-5896 Sentence denotes Indeed, an ACE2-Fc (Lei et al., 2020a) and an RBD-Fc (Li et al., 2020d) have been shown to neutralize both SARS-CoV-1 and SARS-CoV-2 in vitro.
T585 5898-5925 Sentence denotes Convalescent Plasma Therapy
T586 5926-6131 Sentence denotes Although recombinant nAbs could provide an effective treatment, they will require a significant time investment to develop, test, and bring production to scale before becoming widely available to patients.
T587 6132-6308 Sentence denotes A faster strategy consists of transferring convalescent plasma (CP) from previously infected individuals that have developed high titer nAbs that target SARS-CoV-2 (Figure 6D).
T588 6309-6594 Sentence denotes Despite the current lack of appropriately controlled trials, CP therapy has been previously used and shown to be beneficial in several infectious diseases, such as the 1918 influenza pandemic (Luke et al., 2006), H1N1 influenza (Hung et al., 2011), and SARS-CoV-1 (Arabi et al., 2016).
T589 6595-6812 Sentence denotes Thanks to the development of serological tests (Amanat et al., 2020, Cai et al., 2020, Xiang et al., 2020b, Zhang et al., 2020d), recovered COVID-19 patients can be screened to select plasma with high antibody titers.
T590 6813-7081 Sentence denotes Some studies and case reports on CP therapy for COVID-19 have evaluated the safety and the potential effectiveness of CP therapy in patients with severe disease (Ahn et al., 2020, Duan et al., 2020, Pei et al., 2020, Shen et al., 2020, Zhang et al., 2020b) (Table 4 ).
T591 7082-7244 Sentence denotes These studies were neither controlled nor randomized, but they suggest that CP therapy is safe and can have a beneficial effect on the clinical course of disease.
T592 7245-7344 Sentence denotes Further controlled trials are needed to determine the optimal timing and indication for CP therapy.
T593 7345-7524 Sentence denotes CP therapy has also been proposed for prophylactic use in at-risk individuals, such as those with underlying health conditions or health care workers exposed to COVID-19 patients.
T594 7525-7607 Sentence denotes The FDA has approved the use of CP to treat critically ill patients (Tanne, 2020).
T595 7608-7876 Sentence denotes Determining when to administer the CP is also of great importance, as a study in SARS-CoV-1 patients showed that CP was much more efficient when given to patients before day 14 day of illness (Cheng et al., 2005b), as previously shown in influenza (Luke et al., 2006).
T596 7877-7974 Sentence denotes This study also showed that CP therapy was more efficient in PCR-positive, seronegative patients.
T597 7975-8071 Sentence denotes The amount of plasma and number of transfusions needed requires further investigation (Table 4).
T598 8072-8148 Sentence denotes Table 4 Clinical Studies of Convalescent Plasma Therapy in COVID-19 Patients
T599 8149-8210 Sentence denotes Patient Characteristics Start of CP Therapy Results Reference
T600 8211-8366 Sentence denotes 5 severe patients (30–70 yo) between 10 and 22 days after hospital admission body temperature normalized within 3 days in 4 of 5 patients Shen et al., 2020
T601 8367-8387 Sentence denotes clinical improvement
T602 8388-8449 Sentence denotes viral loads became negative within 12 days of the transfusion
T603 8450-8470 Sentence denotes nAb titers increased
T604 8471-8578 Sentence denotes 10 severe patients (34–78 yo) median 16.5 dpo disappearance of clinical symptoms after 3d Duan et al., 2020
T605 8579-8596 Sentence denotes chest CT improved
T606 8597-8661 Sentence denotes elevation of lymphocyte counts in patients with lymphocytopenia.
T607 8662-8694 Sentence denotes increase in SaO2 in all patients
T608 8695-8741 Sentence denotes resolution of SARS-CoV-2 viremia in 7 patients
T609 8742-8796 Sentence denotes increase in neutralizing antibody titers in 5 patients
T610 8797-8943 Sentence denotes 4 critical patients (31–73 yo) at degradation of symptoms,between 11 and 19 days after hospital admission clinical improvement Zhang et al., 2020b
T611 8944-8962 Sentence denotes reduced viral load
T612 8963-8980 Sentence denotes chest CT improved
T613 8981-9093 Sentence denotes 1 moderate patient, 2 critical patients 12 dpo, 27 dpo viral detection negative 4 days after CP Pei et al., 2020
T614 9094-9128 Sentence denotes clinical improvement of 2 patients
T615 9129-9215 Sentence denotes 2 severe patients (67 and 71 yo) 7 dpo or 22 dpo clinical improvement Ahn et al., 2020
T616 9216-9234 Sentence denotes reduced viral load
T617 9235-9252 Sentence denotes chest CT improved
T618 9253-9301 Sentence denotes yo, years old; dpo, days post onset of symptoms.
T619 9302-9428 Sentence denotes Overall, CP therapy seems to be associated with improved outcomes and appears to be safe, but RCTs are needed to confirm this.
T620 9429-9512 Sentence denotes Several clinical trials are currently in progress worldwide (Belhadi et al., 2020).