LitCovid-sentences  

PMC:7200337 / 43904-54099 JSONTXT 11 Projects

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Id Subject Object Predicate Lexical cue
T234 0-16 Sentence denotes B Cell Responses
T235 18-53 Sentence denotes Acute B Cell and Antibody Responses
T236 54-203 Sentence denotes The humoral immune response is critical for the clearance of cytopathic viruses and is a major part of the memory response that prevents reinfection.
T237 204-411 Sentence denotes SARS-CoV-2 elicits a robust B cell response, as evidenced by the rapid and near-universal detection of virus-specific IgM, IgG and IgA, and neutralizing IgG antibodies (nAbs) in the days following infection.
T238 412-520 Sentence denotes The kinetics of the antibody response to SARS-CoV-2 are now reasonably well described (Huang et al., 2020a).
T239 521-890 Sentence denotes Similar to SARS-CoV-1 infection (Hsueh et al., 2004), seroconversion occurs in most COVID-19 patients between 7 and 14 days after the onset of symptoms, and antibody titers persist in the weeks following virus clearance (Figure 4 ) (Haveri et al., 2020, Lou et al., 2020, Okba et al., 2020, Tan et al., 2020b, Wölfel et al., 2020, Wu et al., 2020b, Zhao et al., 2020a).
T240 891-1054 Sentence denotes Antibodies binding the SARS-CoV-2 internal N protein and the external S glycoprotein are commonly detected (Amanat et al., 2020, Ju et al., 2020, To et al., 2020).
T241 1055-1293 Sentence denotes The receptor binding domain (RBD) of the S protein is highly immunogenic, and antibodies binding this domain can be potently neutralizing, blocking virus interactions with the host entry receptor, ACE2 (Ju et al., 2020, Wu et al., 2020b).
T242 1294-1398 Sentence denotes Anti-RBD nAbs are detected in most tested patients (Ju et al., 2020, To et al., 2020, Wu et al., 2020b).
T243 1399-1596 Sentence denotes Although crossreactivity to SARS-CoV-1 S and N proteins and to MERS-CoV S protein was detected in plasma from COVID-19 patients, no crossreactivity was found to the RBD from SARS-CoV-1 or MERS-CoV.
T244 1597-1700 Sentence denotes In addition, plasma from COVID-19 patients did not neutralize SARS-CoV-1 or MERS-CoV (Ju et al., 2020).
T245 1701-1750 Sentence denotes Figure 4 Antibody-Mediated Immunity in SARS-CoV-2
T246 1751-1852 Sentence denotes Virus-specific IgM and IgG are detectable in serum between 7 and 14 days after the onset of symptoms.
T247 1853-1921 Sentence denotes Viral RNA is inversely correlated with neutralizing antibody titers.
T248 1922-2070 Sentence denotes Higher titers have been observed in critically ill patients, but it is unknown whether antibody responses somehow contribute to pulmonary pathology.
T249 2071-2259 Sentence denotes The SARS-CoV-1 humoral response is relatively short lived, and memory B cells may disappear altogether, suggesting that immunity with SARS-CoV-2 may wane 1–2 years after primary infection.
T250 2260-2429 Sentence denotes RBD-specific CD19+IgG+ memory B cells were single-cell sorted from a cohort of eight COVID-19 donors between days 9 and 28 after the onset of symptoms (Ju et al., 2020).
T251 2430-2526 Sentence denotes From their antibody gene sequences, 209 SARS-CoV-2-specific monoclonal antibodies were produced.
T252 2527-2758 Sentence denotes The monoclonal antibodies had a diverse repertoire, relatively low or no somatic mutations, and variable binding reactivity, with dissociation constants reaching 10−8 to 10−9, similar to antibodies isolated during acute infections.
T253 2759-2929 Sentence denotes Two potent neutralizing SARS-CoV-2 RBD-specific monoclonal antibodies were characterized that did not crossreact with the RBD of SARS-CoV-1 or MERS-CoV (Ju et al., 2020).
T254 2930-3078 Sentence denotes Together, these results demonstrate that antibody mediated neutralization is virus specific and likely driven by binding of epitopes within the RBD.
T255 3080-3094 Sentence denotes B Cell Memory:
T256 3095-3119 Sentence denotes Development and Lifespan
T257 3120-3262 Sentence denotes The B cell response to a virus serves not only to protect from the initial challenge, but also to offer extended immunity against reinfection.
T258 3263-3428 Sentence denotes Following resolution of an infection, plasma cells formed during the acute and convalescent phases continue to secrete antibodies, giving rise to serological memory.
T259 3429-3537 Sentence denotes Memory B cells that are also formed during the primary infection constitute the second arm of B cell memory.
T260 3538-3635 Sentence denotes Memory B cells can quickly respond to a reinfection by generating new high-affinity plasma cells.
T261 3636-3737 Sentence denotes Long-term protection is achieved through the induction of long-lived plasma cells and memory B cells.
T262 3738-3833 Sentence denotes There is great interest in understanding the lifespan of B cell memory responses to SARS-CoV-2.
T263 3834-3987 Sentence denotes Protection from reinfection has direct medical and social consequences as the world works to develop vaccination strategies and resume normal activities.
T264 3988-4229 Sentence denotes In COVID-19 patients, evidence of near-universal seroconversion and the lack of substantial descriptions of reinfection point to a robust antibody response, which, along with the T cell memory response, would offer protection to reinfection.
T265 4230-4588 Sentence denotes Indeed, a case study of a single patient described induction of CD38HiCD27Hi antibody-secreting cells (ASCs), concomitant with an increase in circulating follicular T helper cells (Tfh) cells (Thevarajan et al., 2020), and a scRNA-seq study of PBMCs from critically ill and recently recovered individuals revealed a plasma cell population (Guo et al., 2020).
T266 4589-4712 Sentence denotes In addition, IgG memory cells specific to the RBD have been identified in the blood of COVID-19 patients (Ju et al., 2020).
T267 4713-4969 Sentence denotes Consistent with the development of immunity after COVID-19 infection, a recent study of SARS-CoV-2 infection in rhesus macaques found that two macaques that had resolved the primary infection were resistant to reinfection 28 days later (Bao et al., 2020b).
T268 4970-5145 Sentence denotes Due to the timing of this outbreak, it is not yet possible to know the nature and extent of long-term memory responses, but lessons may again be learned from other human CoVs.
T269 5146-5362 Sentence denotes In the case of the human CoV 229E, specific IgG and nAbs are rapidly induced but wane in some individuals around a year after infection, with some residual protection to reinfection (Callow et al., 1990, Reed, 1984).
T270 5363-5645 Sentence denotes The lifespan of the humoral response following SARS-CoV-1 infection is also relatively short, with the initial specific IgG and nAb response to SARS-CoV-1 diminishing 2–3 years after infection and nearly undetectable in up to 25% of individuals (Cao et al., 2007, Liu et al., 2006).
T271 5646-5902 Sentence denotes A long-term study following 34 SARS-CoV-1-infected healthcare workers over a 13-year period also found that virus-specific IgG declined after several years, but the authors observed detectable virus-specific IgG 12 years after infection (Guo et al., 2020).
T272 5903-6032 Sentence denotes In the case of MERS-CoV, antibodies were detected in six of seven volunteers tested 3 years after infection (Payne et al., 2016).
T273 6033-6225 Sentence denotes IgG specific to SARS-CoV-2 trimeric spike protein was detectable in serum up to 60 days after symptom onset, but IgG titers began decreasing by 8 weeks post symptom onset (Adams et al., 2020).
T274 6226-6312 Sentence denotes Long-term protection from reinfection may also be mediated by reactive memory B cells.
T275 6313-6556 Sentence denotes A study that analyzed SARS-CoV-1 S protein-specific IgG memory cells at 2, 4, 6, and 8 months post infection found that S-specific IgG memory B cells decreased progressively about 90% from 2 to 8 months after infection (Traggiai et al., 2004).
T276 6557-6722 Sentence denotes A further retrospective study of 23 individuals found no evidence of circulating SARS-CoV-1-specific IgG+ memory B cells 6 years after infection (Tang et al., 2011).
T277 6723-6856 Sentence denotes This is in contrast to the memory T cell response, which was robustly detected based on induced IFN-γ production (Tang et al., 2011).
T278 6857-7051 Sentence denotes Studies of common CoVs SARS-CoV-1 and MERS-CoV indicate that virus-specific antibody responses wane over time and, in the case of common CoVs, result in only partial protection from reinfection.
T279 7052-7239 Sentence denotes These data suggest that immunity to SARS-CoV-2 may diminish following a primary infection, and further studies will be required to determine the degree of long-term protection (Figure 4).
T280 7241-7277 Sentence denotes Consequences of the B Cell Response:
T281 7278-7307 Sentence denotes Protection versus Enhancement
T282 7308-7587 Sentence denotes Several studies have demonstrated that high virus-specific antibody titers to SARS-CoV-2 are correlated with greater neutralization of virus in vitro and are inversely correlated with viral load in patients (Figure 4) (Okba et al., 2020, Wölfel et al., 2020, Zhao et al., 2020a).
T283 7588-7929 Sentence denotes Despite these indications of a successful neutralizing response in the majority of individuals, higher titers are also associated with more severe clinical cases (Li et al., 2020b, Okba et al., 2020, Zhao et al., 2020a, Zhou et al., 2020a), suggesting that a robust antibody response alone is insufficient to avoid severe disease (Figure 4).
T284 7930-8135 Sentence denotes This was also observed in the previous SARS-CoV-1 epidemic, where neutralizing titers were found to be significantly higher in deceased patients compared to patients who had recovered (Zhang et al., 2006).
T285 8136-8292 Sentence denotes This has led to concerns that antibody responses to these viruses may contribute to pulmonary pathology via antibody-dependent enhancement (ADE) (Figure 4).
T286 8293-8551 Sentence denotes This phenomenon is observed when non-neutralizing virus-specific IgG facilitate entry of virus particles into Fc-receptor (FcR) expressing cells, particularly macrophages and monocytes, leading to inflammatory activation of these cells (Taylor et al., 2015).
T287 8552-8752 Sentence denotes A study in SARS-CoV-1-infected rhesus macaques found that anti-S IgG contributed to severe acute lung injury (ALI) and massive accumulation of monocytes and macrophages in the lung (Liu et al., 2019).
T288 8753-8921 Sentence denotes Furthermore, serum containing anti-S Ig from SARS-CoV-1 patients enhanced the infection of SARS-CoV-1 in human monocyte-derived macrophages in vitro (Yip et al., 2014).
T289 8922-9029 Sentence denotes ADE was also reported with a monoclonal antibody isolated from a patient with MERS-CoV (Wan et al., 2020c).
T290 9030-9267 Sentence denotes Somewhat reassuringly, there was no evidence of ADE mediated by sera from rats vaccinated with SARS-CoV-2 RBD in vitro (Quinlan et al., 2020) nor in macaques immunized with an inactivated SARS-CoV-2 vaccine candidate (Gao et al., 2020c).
T291 9268-9415 Sentence denotes As of now, there is no evidence that naturally developed antibodies toward SARS-CoV-2 contribute to the pathological features observed in COVID-19.
T292 9416-9542 Sentence denotes However, this possibility should be considered when it comes to experimental design and development of therapeutic strategies.
T293 9543-9677 Sentence denotes Importantly, in all of the descriptions of ADE as it relates to CoV, the FcR was necessary to trigger the antibody-mediated pathology.
T294 9678-9937 Sentence denotes High-dose intravenous immunoglobulin (IVIg), which may blunt ADE, has been trialed in COVID-19 patients (Cao et al., 2020b, Shao et al., 2020), but further studies are needed to determine the extent to which IVIg is safe or beneficial in SARS-CoV-2 infection.
T295 9938-10195 Sentence denotes Vaccine trials will need to consider the possibility of antibody-driven pathology upon antigen rechallenge; strategies using F(ab) fragments or engineered Fc monoclonal antibodies may prove particularly beneficial in this setting (Amanat and Krammer, 2020).