The Characterization of Disease Severity Associated IgG Subclasses Response in COVID-19 Patients

Luo, Huanle; Jia, Tingting; Chen, Jiamin; Zeng, Shike; Qiu, Zengzhao; Wu, Shu; Xu, Li; Lei, Yang; Wang, Xin; Wu, Weihua; Zhang, Renli; Zou, Xuan; Feng, Tiejian; Ding, Ruxia; Zhang, Yue; Chen, Yao-Qing; Sun, Caijun; Wang, Tian; Fang, Shisong; Shu, Yuelong

doi:10.3389/fimmu.2021.632814

Cited by 77 publications

(97 citation statements)

References 54 publications

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“…In this study, using a ow cytometry assay based on the S protein [17], we found that speci c antibody levels were strongly associated with disease severity, in line with other studies [24,29,30]. More speci cally, a few studies have reported an association between IgG1 and IgG3 with severe disease and suggested that potential contributory role of IgG1 and IgG3 in severe disease progression [31][32][33].…”

Section: Discussionsupporting

confidence: 90%

Dynamic Alterations of Anti-S-Protein Igg Subclasses and of Th1/Th2 Responses are Hallmarks of Acute Severe COVID-19 Disease

Goh

Fong

Amrun

et al. 2021

Preprint

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PurposeCOVID-19, caused by Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2), has a wide disease spectrum ranging from asymptomatic to severe. While it is widely accepted that specific humoral immune responses are critical in controlling the infection, the relationship between the humoral immune response and disease severity is currently unclear.MethodsUsing a flow cytometry-based assay to detect specific antibodies against full length S protein, we compared the antibody levels between patients from different severity groups. We also analysed the cytokine profiles of patients from different severity groups by multiplex microbead-based immunoassay.ResultsWe found an association between specific IgM, IgA and IgG against the spike protein and disease severity. By comparing the ratio of Th1 IgG1 and IgG3 to Th2 IgG2 and IgG4, we observed that all severity groups exhibited a ratio that was skewed towards a stronger Th1 response over Th2 response. In addition to the strong Th1 response, patients with severe disease also developed a Th2 response, as exemplified by the smaller ratio of IgG1 and IgG3 over IgG2 and IgG4 and the smaller Th1/Th2 cytokine ratios, compared to patients with mild disease severity. ConclusionThe results suggest that acute severity or disease resolution is associated with a specific immunological phenotype. A smaller skew towards a Th1 response over Th2 response, during infection, may contribute to disease progression, while a greater skew towards a Th1 response over Th2 response may contribute to a better disease outcome. This may suggest potential therapeutic approaches to COVID-19 disease management.

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Section: Discussionsupporting

confidence: 90%

Dynamic Alterations of Anti-S-Protein Igg Subclasses and of Th1/Th2 Responses are Hallmarks of Acute Severe COVID-19 Disease

Goh

Fong

Amrun

et al. 2021

Preprint

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“…IgG1 and IgG3 were the most abundant IgG subclasses produced, but also Spike-specific IgA were released according to the detection of IgA + plasmablasts and memory cells at day 28 and 180, respectively. A similar distribution of IgG subclasses has been previously observed in SARS-CoV-2 infected patients and has been negatively associated with viral load in nasopharyngeal swab (17).…”

Section: Discussionsupporting

confidence: 83%

Evidence of SARS-Cov-2-specific memory B cells six months after vaccination with BNT162b2 mRNA vaccine

Ciabattini

Pastore

Fiorino

et al. 2021

Preprint

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SARS-CoV-2 mRNA vaccines have demonstrated high efficacy and immunogenicity, but limited information is currently available on memory B cells generation and long-term persistence. Here, we investigated Spike-specific memory B cells and humoral responses in 145 subjects, up to six months after the BNT162b2 vaccine (Comirnaty) administration. Spike-specific antibody titers peaked 7 days after the second dose and significant titers and neutralizing activity were still observed after six months, despite a progressive decline over time. Concomitant to antibody reduction, Spike-specific memory B cells, mostly IgG class-switched, increased in blood of vaccinees and persisted six months after vaccination. Following in vitro restimulation, circulating memory B cells reactivated and produced Spike-specific antibodies. A high frequency of Spike-specific IgG+ plasmablasts, identified by computational analysis 7 days after boost, positively correlated with the generation of IgG+ memory B cells at six months. These data demonstrate that mRNA BNT162b2 vaccine elicits strong B cell immunity with Spike-specific memory B cells that still persist six months after vaccination, playing a crucial role for rapid response to SARS-CoV-2 virus encounter.

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“…Interestingly, using the Krammer assay, Stadlbauer et al obtained a sensitivity of 95% and specificity of 100% for IgG [ 10 ]. However, we chose an IgG1-specific secondary due to the prominence of IgG1 as a marker for an effective IgG humoral response against SARS-CoV-2 [ 17 , 18 , 19 , 20 ]. Furthermore, we investigated IgM in parallel to IgG1 at >7 days post symptom onset.…”

Section: Discussionmentioning

confidence: 99%

Dynamic Assay for Profiling Anti-SARS-CoV-2 Antibodies and Their ACE2/Spike RBD Neutralization Capacity

Phelan

Dunne

Conlon

et al. 2021

Viruses

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Serological assays have been widely employed during the coronavirus disease 2019 (COVID-19) pandemic to measure antibody responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and to track seroconversion in populations. However, currently available assays do not allow determination of neutralization capacity within the assay protocol. Furthermore, commercial serology assays have a high buy-in cost that is inaccessible for many research groups. We have replicated the serological enzyme-linked immunosorbent assay for the detection of SARS-CoV-2 antibody isotypes, developed at the Icahn School of Medicine at Mount Sinai, New York. Additionally, we have modified the protocol to include a neutralization assay with only a minor modification to this protocol. We used this assay to screen local COVID-19 patient sera (n = 91) and pre-COVID-19 control sera (n = 103), and obtained approximate parity with approved commercial anti-nucleoprotein-based assays with these sera. Furthermore, data from our neutralization assay closely aligns with that generated using a spike-based pseudovirus infection model when a subset of patient sera was analyzed.

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The Characterization of Disease Severity Associated IgG Subclasses Response in COVID-19 Patients

Cited by 77 publications

References 54 publications

Dynamic Alterations of Anti-S-Protein Igg Subclasses and of Th1/Th2 Responses are Hallmarks of Acute Severe COVID-19 Disease

Dynamic Alterations of Anti-S-Protein Igg Subclasses and of Th1/Th2 Responses are Hallmarks of Acute Severe COVID-19 Disease

Evidence of SARS-Cov-2-specific memory B cells six months after vaccination with BNT162b2 mRNA vaccine

Dynamic Assay for Profiling Anti-SARS-CoV-2 Antibodies and Their ACE2/Spike RBD Neutralization Capacity

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