Characterization of SARS-CoV-2-specific antibodies in COVID-19 patients reveals highly potent neutralizing IgA

Zeng, Weihong; Ma, Huan; Ding, Changming; Yu, Yang; Sun, Yong; Huang, Xiaoxue; He, Weihuang; Xiang, Yan; Gao, Yong; Jin, Tengchuan

doi:10.1038/s41392-021-00478-7

Cited by 50 publications

(52 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Next, we explored the sensitivity and specificity for these different antibodies at earlier time points to examine whether our IgA/IgM/IgG combined method is good enough for the diagnosis of COVID-19 patients at the early stage of disease development. We collected 49 serum samples from the First Affiliated Hospital of University of Science and Technology of China, including 34 serum samples from healthy people and 15 serum samples from qPCR-confirmed SARS-CoV-2 patients within 4–10 days post-symptom onset, considered as the early stage of the disease 36 ( Table S4 ). As shown in Figure 5 , with detailed numbers in Table S5 , the corresponding sensitivities of IgA, IgM, and IgG were 93.3% (14/15), 86.7% (13/15), and 66.7% (10/15).…”

Section: Resultsmentioning

confidence: 99%

“…RBD and anti-RBD antibodies (IgA/IgM/IgG) were purified as described previously. 36 Briefly, to make the recombinant SARS-CoV-2 RBD, a leader sequence, a sequence encoding spike protein RBD, and a human IgG1-Fc were fused together. This sequence was cloned into pTT5 vector and then transiently transfected into HEK293F cells through polyethylenimine.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Pulling-Force Spinning Top for Serum Separation Combined with Paper-Based Microfluidic Devices in COVID-19 ELISA Diagnosis

Gong

Wei

et al. 2021

ACS Sens.

Self Cite

View full text Add to dashboard Cite

The spread of Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), resulting in a global pandemic with around four million deaths. Although there are a variety of nucleic acid-based tests for detecting SARS-CoV-2, these methods have a relatively high cost and require expensive supporting equipment. To overcome these limitations and improve the efficiency of SARS-CoV-2 diagnosis, we developed a microfluidic platform that collected serum by a pulling-force spinning top and paper-based microfluidic enzyme-linked immunosorbent assay (ELISA) for quantitative IgA/IgM/IgG measurements in an instrument-free way. We further validated the paper-based microfluidic ELISA analysis of SARS-CoV-2 receptor-binding domain (RBD)-specific IgA/IgM/IgG antibodies from human blood samples as a good measurement with higher sensitivity compared with traditional IgM/IgG detection (99.7% vs 95.6%) for early illness onset patients. In conclusion, we provide an alternative solution for the diagnosis of SARS-CoV-2 in a portable manner by this smart integration of pulling-force spinning top and paper-based microfluidic immunoassay.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Pulling-Force Spinning Top for Serum Separation Combined with Paper-Based Microfluidic Devices in COVID-19 ELISA Diagnosis

Gong

Wei

et al. 2021

ACS Sens.

Self Cite

View full text Add to dashboard Cite

show abstract

“…This supports the importance for screening antibodies in saliva in addition to serum. There is increasing evidence in favor of a key role for IgA in early virus neutralization 24 : (i) early SARS-CoV-2-specific responses are typically dominated by the IgA isotype, (ii) peripheral expansion of IgA-plasmablasts with mucosal-homing shortly after the onset of symptoms and peak during the third week of the disease, and (iii) IgA may contribute to a much larger extent to virus neutralization as compared to IgG 16,25 .…”

Section: Discussionmentioning

confidence: 99%

Multiplex Antibody Analysis of IgM, IgA and IgG to SARS-CoV-2 in Saliva and Serum from Infected Children and their Close Contacts

Dobaño

Alonso

Vidal

et al. 2021

Preprint

View full text Add to dashboard Cite

COVID-19 affects children to a lesser extent than adults but they can still get infected and transmit SARS-CoV-2 to their contacts. Field deployable non-invasive sensitive diagnostic techniques are needed to evaluate the infectivity dynamics of the coronavirus in pediatric populations and guide public health interventions. We evaluated the utility of high-throughput Luminex-based assays applied to saliva samples to quantify IgM, IgA and IgG antibodies against five SARS-CoV-2 spike (S) and nucleocapsid (N) antigens in the context of a contacts and infectivity longitudinal study. We compared the antibody levels obtained in saliva versus serum/plasma samples from a group of children and adults tested weekly by RT-PCR over 35 days and diagnosed as positive (n=58), and a group of children and adults who consistently tested negative over the follow up period (n=61), in the Summer of 2020 in Barcelona, Spain. Antibody levels in saliva samples from individuals with confirmed RT-PCR diagnosis of SARS-CoV-2 infection were significantly higher than in negative individuals and correlated with those measured in sera/plasmas. Higher levels of anti-S IgG were found in asymptomatic individuals that could indicate protection against disease in infected individuals. Higher anti-S IgG and IgM levels in serum/plasma and saliva, respectively, in infected children compared to infected adults could also be related to stronger clinical immunity in them. Among infected children, males had higher levels of saliva IgG to N and RBD than females. Despite overall correlation, individual clustering analysis suggested that responses that may not be detected in blood could be patent in saliva, and vice versa, and therefore that both measurements are complementary. In addition to serum/plasma, measurement of SARS-CoV-2-specific saliva antibodies should be considered as a complementary non-invasive assay to better estimate the percentage of individuals who have experienced coronavirus infection. Saliva antibody detection could allow determining COVID-19 prevalence in pediatric populations, alternative to bleeding or nasal swab, and serological diagnosis following vaccination.

show abstract

“…Chemiluminescence-based kits to detect SARS-CoV-2-specific IgA, IgM, and IgG antibodies were developed by Kangrun Biotech (Guangzhou, China), in which the receptor-binding domain of the spike protein was coated onto magnetic particles to capture SARS-CoV-2-specific IgA, IgM, and IgG in patient samples [ 46 ]. Secondary acridinium-conjugated antibodies were used for detecting IgA, IgM, and IgG.…”

Section: Methodsmentioning

confidence: 99%

“…The detected chemiluminescent signals were calculated as relative light units (RLU) (over background signal, the cut-off RLU value for anti-RBD IgA, IgM, and IgG was 32,189, 17,538, and 9971, respectively). These kits have been validated in a large set of serum samples and showed high sensitivities and specificities [ 45 , 46 ]. Serum samples were collected via the centrifugation of whole blood in test tubes at 1000× g for 15 min at room temperature.…”

Section: Methodsmentioning

confidence: 99%

The Potential Role of an Aberrant Mucosal Immune Response to SARS-CoV-2 in the Pathogenesis of IgA Nephropathy

Zhang

Guo

et al. 2021

Pathogens

Self Cite

View full text Add to dashboard Cite

The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global concern. Immunoglobin A (IgA) contributes to virus neutralization at the early stage of infection. Longitudinal studies are needed to assess whether SARS-CoV-2-specific IgA production persists for a longer time in patients recovered from severe COVID-19 and its lasting symptoms that can have disabling consequences should also be alerted to susceptible hosts. Here, we tracked the anti-SARS-CoV-2 spike protein receptor-binding domain (RBD) antibody levels in a cohort of 88 COVID-19 patients. We found that 52.3% of the patients produced more anti-SARS-CoV-2 RBD IgA than IgG or IgM, and the levels of IgA remained stable during 4–41 days of infection. One of these IgA-dominant COVID-19 patients, concurrently with IgA nephropathy (IgAN), presented with elevated serum creatinine and worse proteinuria during the infection, which continued until seven months post-infection. The serum levels of anti-SARS-CoV-2 RBD and total IgA were higher in this patient than in healthy controls. Changes in the composition of the intestinal microbiota, increased IgA highly coated bacteria, and elevated concentration of the proinflammatory cytokine IL-18 were indicative of potential involvement of intestinal dysbiosis and inflammation to the systemic IgA level and, consequently, the disease progression. Collectively, our work highlighted the potential adverse effect of the mucosal immune response to SARS-CoV-2 infection, and that additional care should be taken with COVID-19 patients presenting with chronic diseases such as IgAN.

show abstract

Characterization of SARS-CoV-2-specific antibodies in COVID-19 patients reveals highly potent neutralizing IgA

Cited by 50 publications

References 5 publications

Pulling-Force Spinning Top for Serum Separation Combined with Paper-Based Microfluidic Devices in COVID-19 ELISA Diagnosis

Pulling-Force Spinning Top for Serum Separation Combined with Paper-Based Microfluidic Devices in COVID-19 ELISA Diagnosis

Multiplex Antibody Analysis of IgM, IgA and IgG to SARS-CoV-2 in Saliva and Serum from Infected Children and their Close Contacts

The Potential Role of an Aberrant Mucosal Immune Response to SARS-CoV-2 in the Pathogenesis of IgA Nephropathy

Contact Info

Product

Resources

About