SARS-CoV-2 neutralizing antibody responses are more robust in patients with severe disease

Wang, Pengfei; Liu, Lihong; Nair, Manoj S.; Yin, Michael T.; Luo, Yang; Wang, Qin; Yuan, Ting; Mori, Kanako; Solis, Axel Guzman; Yamashita, Masahiro; Garg, Ankur; Purpura, Lawrence; Laracy, Justin; Yu, Jian; Joshua‐Tor, Leemor; Sodroski, Joseph; Huang, Yaoxing; Ho, David D.

doi:10.1080/22221751.2020.1823890

Cited by 116 publications

(137 citation statements)

References 12 publications

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“…Previous observations suggested that an IgG upsurge for SARS-CoV correlates with a clinical worsening of pneumonia (5). In a pre-print study, SARS-Cov2 neutralizing Ab responses result more robust in 35 patients with severe disease, about 1 month after infection (13). Moreover, in five patients with severe Covid-19, three potent neutralizing antibodies against multiple epitopes on the SARS-Cov2 spike have been detected: one anti-RBD, one other anti-NTD (N-terminal domain) and a third able to bind two separate RBD (9).…”

Section: Discussionmentioning

confidence: 88%

“…f. Therapeutic use of serum Abs from healed subjects (plasma therapy) might have positive effects: recent unofficial data would indicate that a therapy with hyper-immune sera in the initial covid-19 appears to prevent the disease progression, while for patients in advanced severe disease a significant improvement has been noted. This could indicate that Abs might have a favorable effect, but, presumably, only if in high quantities (13), as it occurs in hyper-immune sera therapy. In effect, besides a direct neutralization of viral activities, such as replication, that reduces the viral titer, high Ab amounts might also act leading the Ag/Ab rate closer to the equivalence, that reduce or avoid formation of soluble and fixed ICs.…”

Section: Discussionmentioning

confidence: 99%

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COVID-19 as an Immune Complex Hypersensitivity in Antigen Excess Conditions: Theoretical Pathogenetic Process and Suggestions for Potential Therapeutic Interventions

Manzo¹

2020

Front. Immunol.

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Because of particular properties of SARS-Cov-2, such as an high infection speed, its antigenic nature, evolutionarily unknown to the human immune system, and/or a viral interference on the immune response mechanisms, this virus would determine in the subjects a delayed anomalous (slow and/or low) immune response, ineffective and, finally, self-damaging. The hypothetical pathogenetic process for covid-19 could occur in three phases: a) Viral phase, asymptomatic or weakly symptomatic, with an a-specific innate immune response; b) Immunological phase, intermediately symptomatic, with an anomalous specific immune response (delayed, slow and/or low synthesis of IgM and IgG) in antigen excess conditions, immune complex formation and complement activation with tissue damages; c) Hemo-vascular phase, severely symptomatic, where complement-mediated tissue damages would induce vascular inflammation and systemic alteration of the coagulation homeostasis. This hypothesis is well supported by the immune-histochemical and microscopic demonstration in severe patient lungs of co-localized spike viral proteins, terminal components of the activated complement system (C5b-9 membrane attack complex) and microvascular deposits of small fibrin thrombi. This picture could be aggravated by the involvement of neutrophils and macrophages, releasing additional lytic and inflammatory factors. Thus, covid-19 would arise as a simple viral infection, develop as a diffuse immune complex hypersensitivity and explode as a systemic hemo-vascular pathology. If this hypothesized process would be real, suitable therapeutic interventions might be carried out, able to interfere with or block the critical factors in the various phases.

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Section: Discussionmentioning

confidence: 88%

Section: Discussionmentioning

confidence: 99%

COVID-19 as an Immune Complex Hypersensitivity in Antigen Excess Conditions: Theoretical Pathogenetic Process and Suggestions for Potential Therapeutic Interventions

Manzo¹

2020

Front. Immunol.

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“…Clinical and demographic correlates of the neutralising antibody response are described in Table 3. Neutralising antibody responses correlated with disease severity in all studies in which this association was tested [7,43,49,108,117,126,127,[135][136][137]. Importantly, the few studies that investigated asymptomatic cases found those individuals were considerably less likely to develop detectable serum neutralising antibody responses than cases with symptoms.…”

Section: Protective Immunitymentioning

confidence: 97%

“…Antibody titre • Ten studies reported a higher titre of neutralising antibodies in more clinically severe cases [7,43,49,108,126,127,[134][135][136][137]. • One study reported undetectable neutralising activity in plasma from a majority of asymptomatic cases [126].…”

Section: Clinical Disease Severitymentioning

confidence: 99%

Antibody response to SARS-CoV-2 infection in humans: A systematic review

et al. 2020

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Background Progress in characterising the humoral immune response to Severe Acute Respiratory Syndrome 2 (SARS-CoV-2) has been rapid but areas of uncertainty persist. Assessment of the full range of evidence generated to date to understand the characteristics of the antibody response, its dynamics over time, its determinants and the immunity it confers will have a range of clinical and policy implications for this novel pathogen. This review comprehensively evaluated evidence describing the antibody response to SARS-CoV-2 published from 01/01/2020-26/06/2020. Methods Systematic review. Keyword-structured searches were carried out in MEDLINE, Embase and COVID-19 Primer. Articles were independently screened on title, abstract and full text by two researchers, with arbitration of disagreements. Data were double-extracted into a pre-designed template, and studies critically appraised using a modified version of the Public Health Ontario Meta-tool for Quality Appraisal of Public Health Evidence (MetaQAT) tool, with resolution of disagreements by consensus. Findings were narratively synthesised. Results 150 papers were included. Most studies (113 or 75%) were observational in design, were based wholly or primarily on data from hospitalised patients (108, 72%) and had important methodological limitations. Few considered mild or asymptomatic infection. Antibody dynamics were well described in the acute phase, up to around three months from disease onset, but the picture regarding correlates of the antibody response was inconsistent. IgM was consistently detected before IgG in included studies, peaking at weeks two to five and declining over a further three to five weeks post-symptom onset depending on the patient group; IgG peaked around weeks three to seven post-symptom onset then plateaued, generally persisting for at least eight weeks. Neutralising antibodies were detectable within seven to 15 days following disease onset, with levels increasing until days 14–22 before levelling and then decreasing, but titres were lower in those with asymptomatic or clinically mild disease. Specific and potent neutralising antibodies have been isolated from convalescent plasma. Cross-reactivity but limited cross-neutralisation with other human coronaviridae was reported. Evidence for protective immunity in vivo was limited to small, short-term animal studies, showing promising initial results in the immediate recovery phase. Conclusions Literature on antibody responses to SARS-CoV-2 is of variable quality with considerable heterogeneity of methods, study participants, outcomes measured and assays used. Although acute phase antibody dynamics are well described, longer-term patterns are much less well evidenced. Comprehensive assessment of the role of demographic characteristics and disease severity on antibody responses is needed. Initial findings of low neutralising antibody titres and possible waning of titres over time may have implications for sero-surveillance and disease control policy, although further evidence is needed. The detection of potent neutralising antibodies in convalescent plasma is important in the context of development of therapeutics and vaccines. Due to limitations with the existing evidence base, large, cross-national cohort studies using appropriate statistical analysis and standardised serological assays and clinical classifications should be prioritised.

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“…Wang et al further reported that mean antibody neutralization titers against SARS-CoV-2 live virus were ~ sevenfold higher in the sicker patients and that patients with severe COVID-19 had more robust binding antibodies to both the N protein and S trimer (Wang P et al 2020 ). Even though antibodies against the SARS-CoV-2 N protein do not provide protective immunity against infection (Gralinski and Menachery 2020 ), specific antibodies against the S protein do (Gao et al 2020 ).…”

Section: Serological Characteristics Of Covid-19 Patientsmentioning

confidence: 99%

Human Monoclonal Antibodies: On the Menu of Targeted Therapeutics Against COVID-19

et al. 2020

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SARS-CoV-2 neutralizing antibody responses are more robust in patients with severe disease

Cited by 116 publications

References 12 publications

COVID-19 as an Immune Complex Hypersensitivity in Antigen Excess Conditions: Theoretical Pathogenetic Process and Suggestions for Potential Therapeutic Interventions

COVID-19 as an Immune Complex Hypersensitivity in Antigen Excess Conditions: Theoretical Pathogenetic Process and Suggestions for Potential Therapeutic Interventions

Antibody response to SARS-CoV-2 infection in humans: A systematic review

Human Monoclonal Antibodies: On the Menu of Targeted Therapeutics Against COVID-19

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