Evaluating the Association of Clinical Characteristics With Neutralizing Antibody Levels in Patients Who Have Recovered From Mild COVID-19 in Shanghai, China

Wu, Fan; Liu, Mei; Wang, Aojie; Lu, Lu; Wang, Qimin; Gu, Cheng; Chen, Jun; Wu, Yang; Xia, Shuai; Ling, Yun; Zhang, Yuling; Xun, Jingna; Zhang, Rong; Xie, Youhua; Jiang, Shibo; Zhu, Tongyu; Lu, Hongzhou; Wen, Yumei; Huang, Jinghe

doi:10.1001/jamainternmed.2020.4616

Cited by 217 publications

(219 citation statements)

References 18 publications

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“…It was reported that stronger antibody response was associated with delayed viral clearance and increased disease severity in patients of COVID-19 30 . We also reported that NAb titers were higher in elderly patients of COVID-19, who tend to have worse outcomes, while a few patients recovered without generating detectable NAbs 18 Figure 9). We found that amino acid substitutions F342L and E516A on RBD allowed the virus escape from the neutralization by 7F3 without reducing binding affinity to antibody.…”

Section: Discussionmentioning

confidence: 57%

“…17 [13][14][15][16][17][18][19][20][21][22][23] days, P < 0.0001, Figure 1I and 1J). These results indicated that ADE is more likely to develop in elderly patients with severe and critical condition, longer hospital stays and disease duration, suggesting a possible association of ADE with disease severity in COVID-19 patients.…”

Section: Ade Is More Likely To Develop In Elderly Patients With Severmentioning

confidence: 99%

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Antibody-dependent enhancement (ADE) of SARS-CoV-2 infection in recovered COVID-19 patients: studies based on cellular and structural biology analysis

Yan

Liu

et al. 2020

Preprint

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Antibody-dependent enhancement (ADE) has been reported in several virus infections including dengue fever virus, severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronavirus infection. To study whether ADE is involved in COVID-19 infections, in vitro pseudotyped SARS-CoV-2 entry into Raji cells, K562 cells, and primary B cells mediated by plasma from recovered COVID-19 patients were employed as models. The enhancement of SARS-CoV-2 entry into cells was more commonly detected in plasma from severely-affected elderly patients with high titers of SARS-CoV-2 spike protein-specific antibodies. Cellular entry was mediated via the engagement of FcγRII receptor through virus-cell membrane fusion, but not by endocytosis. Peptide array scanning analyses showed that antibodies which promote SARS-CoV-2 infection targeted the variable regions of the RBD domain. To further characterize the association between the spike-specific antibody and ADE, an RBD-specific monoclonal antibody (7F3) was isolated from a recovered patient, which potently inhibited SARS-Cov-2 infection of ACE-2 expressing cells and also mediated ADE in Raji cells. Site-directed mutagenesis the spike RBD domain reduced the neutralization activity of 7F3, but did not abolish its binding to the RBD domain. Structural analysis using cryo-electron microscopy (Cryo-EM) revealed that 7F3 binds to spike proteins at a shift-angled pattern with one up and two down RBDs, resulting in partial overlapping with the receptor binding motif (RBM), while a neutralizing monoclonal antibody that lacked ADE activity binds to spike proteins with three up RBDs, resulting in complete overlapping with RBM. Our results revealed that ADE mediated by SARS-CoV-2 spike-specific antibodies could result from binding to the receptor in slightly different pattern from antibodies mediating neutralizations. Studies on ADE using antibodies from recovered patients via cell biology and structural biology technology could be of use for developing novel therapeutic and preventive measures for control of COVID-19 infection.

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Section: Discussionmentioning

confidence: 57%

Section: Ade Is More Likely To Develop In Elderly Patients With Severmentioning

confidence: 99%

Antibody-dependent enhancement (ADE) of SARS-CoV-2 infection in recovered COVID-19 patients: studies based on cellular and structural biology analysis

Yan

Liu

et al. 2020

Preprint

Self Cite

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“…In both humans and animals, such cross-reactivity was suspected to be due to non-neutralizing anti-S antibody again likely relating to a conserved region [33]. Crossneutralization was however uncommon, but conceivably there could be other reasons for any such non-specificity [34][35][36]. Among humans, S-specific antibody dominates and may correlate better with neutralization [34,35,37].…”

Section: Provisional Acceptance Of What Constitutes Immunitymentioning

confidence: 99%

“…Crossneutralization was however uncommon, but conceivably there could be other reasons for any such non-specificity [34][35][36]. Among humans, S-specific antibody dominates and may correlate better with neutralization [34,35,37]. Furthermore, the correlation between antibodies for different antigens (e.g., S and N proteins) may not be as initially conceived [35,38].…”

Section: Provisional Acceptance Of What Constitutes Immunitymentioning

confidence: 99%

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A Minimalist Strategy Towards Temporarily Defining Protection for COVID-19

Cimolai

2020

SN Compr. Clin. Med.

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Until either efficacious therapy or vaccination for COVID-19 is achieved, there will be a need to regain world economic stability while yet controlling the pandemic with current approaches. For those infected thus far, there is a prevailing perspective that devising recognition for protective immunity will progressively allow segments of society to return to some functionality more than is existing. At this time, the best correlates with protection from natural coronavirus infections are systemic neutralizing antibody and mucosal IgA. Serum neutralizing antibody more easily fulfills the latter requisite, but current live virus methods for neutralization prevent large-scale application. It is conceivable that the exposure of previously infected individuals can allow for the definition of protective thresholds of neutralizing antibody. Thereafter, many other antibody assays will be able to screen for surrogate protection after correlations with protective neutralizing antibody are made. Specificity of common antibody tests would benefit from confirmatory blocking systems or confirmatory immunoblotting fingerprints with well-defined antigen(s). The opportunity for the scientific community to make these assessments is evident in the current context of the COVID-19 epidemic given the large numbers of infected individuals worldwide. Such information will also be vital to guide vaccine development and/or immunotherapy.

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Neutralizing Antibodies Against SARS-CoV-2—Important Questions, Unclear Answers

Katz

2020

JAMA Intern Med

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Evaluating the Association of Clinical Characteristics With Neutralizing Antibody Levels in Patients Who Have Recovered From Mild COVID-19 in Shanghai, China

Cited by 217 publications

References 18 publications

Antibody-dependent enhancement (ADE) of SARS-CoV-2 infection in recovered COVID-19 patients: studies based on cellular and structural biology analysis

Antibody-dependent enhancement (ADE) of SARS-CoV-2 infection in recovered COVID-19 patients: studies based on cellular and structural biology analysis

A Minimalist Strategy Towards Temporarily Defining Protection for COVID-19

Neutralizing Antibodies Against SARS-CoV-2—Important Questions, Unclear Answers

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