scispace - formally typeset
Search or ask a question
Posted ContentDOI

Twelve-month specific IgG response to SARS-CoV-2 receptor-binding domain among COVID-19 convalescent plasma donors in Wuhan

TL;DR: Wu et al. as discussed by the authors investigated the duration of humoral immune response in convalescent coronavirus disease 2019 (COVID-19) patients, conducting a 12-month longitudinal study through collecting a total of 1,782 plasma samples from 869 plasma donors in Wuhan, China and test specific antibody responses.
Abstract: To investigate the duration of humoral immune response in convalescent coronavirus disease 2019 (COVID-19) patients, we conduct a 12-month longitudinal study through collecting a total of 1,782 plasma samples from 869 convalescent plasma donors in Wuhan, China and test specific antibody responses The results show that positive rate of IgG antibody against receptor-binding domain of spike protein (RBD-IgG) to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the COVID-19 convalescent plasma donors exceeded 70% for 12 months post diagnosis The level of RBD-IgG decreases with time, with the titer stabilizing at 643% of the initial level by the 9th month Moreover, male plasma donors produce more RBD-IgG than female, and age of the patients positively correlates with the RBD-IgG titer A strong positive correlation between RBD-IgG and neutralizing antibody titers is also identified These results facilitate our understanding of SARS-CoV-2-induced immune memory to promote vaccine and therapy development

Summary (2 min read)

Introduction

  • Since the emergence of coronavirus disease 2019 (COVID- 19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in December 2019, the virus has spread rapidly and globally, leading to a pandemic outbreak.
  • Evaluating the durability of the immune response, especially humoral immune response, induced by SARS-CoV-2 is essential to understand the pathogenesis of SARS-CoV-2 and predict the longevity of its vaccine protection, which further facilitates the urgent development of vaccine or therapeutics 1 .
  • The symptoms of 10 severe COVID-19 patients who received 200 mL of convalescent plasma containing high-titer neutralizing antibody were significantly improved or even completely disappeared within 3-7 days 8 .
  • According to a longitudinal study, though both IgM and IgA antibodies are produced early within one week after symptom onset, IgM reaches the peak at the 10th-12th days but the level subsequently decreases after 18 days, while IgA response persists at a higher level for a longer time period, reaching the peak at the 20th-22nd days 9 .

Results

  • In order to evaluate the stability of RBD-IgG titers in COVID-19 convalescent plasma donors after a long period of time, the authors re-collect the plasma from 237 donors, who present different titer levels of RBD-IgG at the early stage following diagnosis, during the 10th and 11th months after diagnosis.
  • Additionally, the authors analyze the changes of RBD-IgG titers in plasma donors stratified by the initial titers from the early stage to the 10th and 11th months.
  • CC-BY-ND 4.0 International license made available under a (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.

Discussion

  • The overall immunity to SARS-CoV-2, including the durability of immunity against the virus and vaccine-induced protective immunity, has not been fully understood.
  • To investigate the persistence of protective immunity against SARS-CoV-2, the authors have conducted a year-long kinetic analysis on SARS-CoV-2 RBD-IgG response in 1,782 convalescent plasma samples obtained from 869 COVID-19 plasma donors, and assessed the constant influences of patient gender, age, and blood types on RBD-IgG response kinetics.
  • Furthermore, the authors find that although the RBD-IgG titer gradually decreases over time within 12 months, the RBD-IgG titer is stabilized at a GMT of approximately 200 after 9 months following diagnosis.
  • Consistent with previous report 6 , their data show a strong positive correlation between these two types of titers .
  • The acceptable criteria for linearity of the standard curve were: the R 2 value > 0.99; the recovery rate of each standard dilution ≤ 20% of the target value.

Plaque reduction neutralization test (PRNT). Neutralizing titers were defined on

  • The samples were initially 20-fold diluted, and then 4-fold serial dilutions were prepared in maintenance medium.
  • The mixture was added to Vero cell monolayer in 12-well plates and incubated for 1 h.
  • The influences of gender and blood type on RBD-IgG titer were analyzed by twoway ANOVA for inter-group difference, and by a two-tailed nonparametric Mann-Whitney t-test for median difference between groups.
  • 80 are considered as negative, also known as Titers less than 1.

Did you find this useful? Give us your feedback

Content maybe subject to copyright    Report

1
Twelve-month specific IgG response to SARS-CoV-2 1
receptor-binding domain among COVID-19 convalescent 2
plasma donors in Wuhan 3
4
Cesheng Li
1,*
, Ding Yu
2,3,*
, Xiao Wu
1
, Hong Liang
2,3
, Zhijun Zhou
1
, Yong Xie
1,3
, Taojing Li
3
, 5
Junzheng Wu
2
, Fengping Lu
1
, Lu Feng
1
, Min Mao
1
, Lianzhen Lin
1
, Huanhuan Guo
1
, Shenglan Yue
1
, 6
Feifei Wang
1
, Yan Peng
1
, Yong Hu
1
, Zejun Wang
4
, Jianhong Yu
1
, Yong Zhang
3
, Jia Lu
4
, Haoran 7
Ning
1
, Huichuan Yang
4
, Daoxing Fu
3
, Yanlin He
1,3
, Dongbo Zhou
3,4
, Tao Du
3
, Kai Duan
4
, Demei 8
Dong
3
, Kun Deng
1
, Xia Zou
1
, Ya Zhang
1
, Rong Zhou
3
, Yang Gao
3
, Xinxin Zhang
6,#
& Xiaoming 9
Yang
4,#
10
11
1
Sinopharm Wuhan Plasma-derived Biotherapies Co., Ltd, 430207 Wuhan, China. 12
2
Chengdu Rongsheng Pharmaceuticals Co., Ltd, 610041 Chengdu, China. 13
3
Beijing Tiantan Biological Products Co., Ltd, 100024 Beijing, China. 14
4
China National Biotec Group Company Limited, 100029 Beijing, China. 15
5
Wuhan Institute of Biological Products Co. Ltd., 430207 Wuhan, China. 16
6
Research Laboratory of Clinical Virology, Ruijin Hospital and Ruijin Hospital North, National Research 17
Center for Translational Medicine, Shanghai Jiao Tong University of Medicine, 200025 Shanghai, China. 18
19
*Equal contributing authors 20
#Jointly supervising authors 21
.CC-BY-ND 4.0 International licensemade available under a
(which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is
The copyright holder for this preprintthis version posted June 3, 2021. ; https://doi.org/10.1101/2021.04.05.437224doi: bioRxiv preprint

2
Abstract 22
To investigate the duration of humoral immune response in convalescent coronavirus 23
disease 2019 (COVID-19) patients, we conduct a 12-month longitudinal study through 24
collecting a total of 1,782 plasma samples from 869 convalescent plasma donors in 25
Wuhan, China and test specific antibody responses. The results show that positive rate 26
of IgG antibody against receptor-binding domain of spike protein (RBD-IgG) to severe 27
acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the COVID-19 28
convalescent plasma donors exceeded 70% for 12 months post diagnosis. The level of 29
RBD-IgG decreases with time, with the titer stabilizing at 64.3% of the initial level by 30
the 9th month. Moreover, male plasma donors produce more RBD-IgG than female, 31
and age of the patients positively correlates with the RBD-IgG titer. A strong positive 32
correlation between RBD-IgG and neutralizing antibody titers is also identified. These 33
results facilitate our understanding of SARS-CoV-2-induced immune memory to 34
promote vaccine and therapy development. 35
36
.CC-BY-ND 4.0 International licensemade available under a
(which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is
The copyright holder for this preprintthis version posted June 3, 2021. ; https://doi.org/10.1101/2021.04.05.437224doi: bioRxiv preprint

3
Introduction 37
Since the emergence of coronavirus disease 2019 (COVID-19), caused by severe acute 38
respiratory syndrome coronavirus 2 (SARS-CoV-2) in December 2019, the virus has 39
spread rapidly and globally, leading to a pandemic outbreak. As of February 19, 2021, 40
SARS-CoV-2 has infected more than 109 million people worldwide, with the death toll 41
exceeding 2.4 million, and approximately 364,000 newly diagnosed cases are still daily 42
reported (https://covid19.who.int/, accessed February 19, 2021).
43
Several SARS-CoV-2 vaccines have been approved worldwide, but their longevity 44
of immune protection is still uncertain. Evaluating the durability of the immune 45
response, especially humoral immune response, induced by SARS-CoV-2 is essential 46
to understand the pathogenesis of SARS-CoV-2 and predict the longevity of its vaccine 47
protection, which further facilitates the urgent development of vaccine or therapeutics 48
1
. In the patients infected with severe acute respiratory syndrome coronavirus 1 (SARS-49
CoV-1), the specific antibodies against SARS-CoV-1 can last for an average of 2 years, 50
with the positive rate and titer of SARS-CoV-1-specific neutralizing antibodies 51
significantly reduced at the third year. Therefore, SARS patients may become 52
susceptible to the same virus 3 years after recovered from the infection
2
, highlighting 53
the importance of evaluating the durability of the humoral immune response to SARS-54
CoV-2. 55
The antibody responses against SARS-CoV-2 in humans are induced by some 56
viral proteins, including spike glycoprotein (S protein) and nucleocapsid protein, 57
.CC-BY-ND 4.0 International licensemade available under a
(which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is
The copyright holder for this preprintthis version posted June 3, 2021. ; https://doi.org/10.1101/2021.04.05.437224doi: bioRxiv preprint

4
among which S protein can induce neutralizing antibodies that are indispensable for 58
viral neutralization and elimination, through blocking viral binding with host cells
1
. 59
Similar as SARS-CoV-1, SARS-CoV-2 enters host cells via the binding with S protein 60
to angiotensin-converting enzyme 2 (ACE2)
3
, which is expressed on the surface of 61
human alveolar epithelial cells, small intestinal epithelial cells, endothelial cells, and 62
arterial smooth muscle cells
4
. SARS-CoV-2 S protein has an approximate size of 180 63
kDa, consisted of S1 and S2 subunits, the former of which contains ACE2 receptor 64
binding domain (RBD, amino acid residues 331-524)
5
. Anti-RBD IgG (RBD-IgG) 65
titers have been shown to be strongly and positively correlated with virus neutralization 66
6
. Although highly homologous amino acid sequences are shared between the RBD 67
regions of SARS-CoV-2 and SARS-CoV-1, the plasma of convalescent SARS patients 68
or SARS-CoV-1 RBD monoclonal antibodies could not neutralize SARS-CoV-2, 69
indicating the limited cross-neutralization protection between these two viruses
5, 7
. 70
Nevertheless, successful convalescent plasma therapy for COVID-19 patients has been 71
reported: The symptoms of 10 severe COVID-19 patients who received 200 mL of 72
convalescent plasma containing high-titer neutralizing antibody were significantly 73
improved or even completely disappeared within 3-7 days
8
. 74
Furthermore, it has been reported that most COVID-19 patients could produce 75
virus-specific IgM, IgA, and IgG antibodies within a few days after infection
1
. 76
According to a longitudinal study, though both IgM and IgA antibodies are produced 77
early within one week after symptom onset, IgM reaches the peak at the 10th-12th days 78
.CC-BY-ND 4.0 International licensemade available under a
(which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is
The copyright holder for this preprintthis version posted June 3, 2021. ; https://doi.org/10.1101/2021.04.05.437224doi: bioRxiv preprint

5
but the level subsequently decreases after 18 days, while IgA response persists at a 79
higher level for a longer time period, reaching the peak at the 20th-22nd days
9
. On the 80
contrary, the level of IgG antibody keeps increasing for 3 weeks after symptom onset, 81
declines after 8 weeks, while remains detectable over 8 months
1, 10, 11
. However, the 82
antibody response and neutralizing activity in COVID-19 convalescent patients up to 83
12 months are still unclear. For preventing and controlling SARS-CoV-2, as well as the 84
vaccine development, the duration of functional neutralizing antibody response after 85
individual infection with SARS-CoV-2 and the protective immunity for reinfection are 86
necessary to be investigated by a long-term study. 87
Therefore, we aim to investigate the RBD-IgG response of convalescent COVID-88
19 patients for up to 12 months. In this study, a total of 1,782 convalescent plasma 89
samples from 869 COVID-19 convalescent plasma donors are tested for the presence 90
and titers of RBD-IgG, which is proved to be positively associated with neutralizing 91
antibody titers. In addition, influences of other factors (gender, age, and blood type) on 92
the kinetics of RBD-IgG responses are analyzed. Our finding is critical for assessing 93
the durability of the protective immunity induced by COVID-19 vaccines and 94
predicting the future trend of COVID-19 pandemic. 95
96
.CC-BY-ND 4.0 International licensemade available under a
(which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is
The copyright holder for this preprintthis version posted June 3, 2021. ; https://doi.org/10.1101/2021.04.05.437224doi: bioRxiv preprint

Citations
More filters
Journal ArticleDOI
14 Jun 2021-Nature
TL;DR: In the absence of vaccination, antibody reactivity to the receptor binding domain (RBD) of SARS-CoV-2, neutralizing activity and the number of RBD-specific memory B cells remain relatively stable between 6 and 12 months after infection.
Abstract: More than one year after its inception, the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains difficult to control despite the availability of several working vaccines. Progress in controlling the pandemic is slowed by the emergence of variants that appear to be more transmissible and more resistant to antibodies1,2. Here we report on a cohort of 63 individuals who have recovered from COVID-19 assessed at 1.3, 6.2 and 12 months after SARS-CoV-2 infection, 41% of whom also received mRNA vaccines3,4. In the absence of vaccination, antibody reactivity to the receptor binding domain (RBD) of SARS-CoV-2, neutralizing activity and the number of RBD-specific memory B cells remain relatively stable between 6 and 12 months after infection. Vaccination increases all components of the humoral response and, as expected, results in serum neutralizing activities against variants of concern similar to or greater than the neutralizing activity against the original Wuhan Hu-1 strain achieved by vaccination of naive individuals2,5–8. The mechanism underlying these broad-based responses involves ongoing antibody somatic mutation, memory B cell clonal turnover and development of monoclonal antibodies that are exceptionally resistant to SARS-CoV-2 RBD mutations, including those found in the variants of concern4,9. In addition, B cell clones expressing broad and potent antibodies are selectively retained in the repertoire over time and expand markedly after vaccination. The data suggest that immunity in convalescent individuals will be very long lasting and that convalescent individuals who receive available mRNA vaccines will produce antibodies and memory B cells that should be protective against circulating SARS-CoV-2 variants. Antibodies against SARS-CoV-2 continue to evolve 6 to 12 months after infection in patients who have recovered from COVID-19, increasing in potency and breadth with time.

505 citations

Journal ArticleDOI
TL;DR: The understanding of immune memory for 1 year to SARS‐CoV‐2 infection and vaccines already supersedes that of any other acute infectious disease.
Abstract: Immunological memory is the basis of protective immunity provided by vaccines and previous infections. Immunological memory can develop from multiple branches of the adaptive immune system, including CD4 T cells, CD8 T cells, B cells, and long‐lasting antibody responses. Extraordinary progress has been made in understanding memory to SARS‐CoV‐2 infection and COVID‐19 vaccines, addressing development; quantitative and qualitative features of different cellular and anatomical compartments; and durability of each cellular component and antibodies. Given the sophistication of the measurements; the size of the human studies; the use of longitudinal samples and cross‐sectional studies; and head‐to‐head comparisons between infection and vaccines or between multiple vaccines, the understanding of immune memory for 1 year to SARS‐CoV‐2 infection and vaccines already supersedes that of any other acute infectious disease. This knowledge may help inform public policies regarding COVID‐19 and COVID‐19 vaccines, as well as the scientific development of future vaccines against SARS‐CoV‐2 and other diseases.

89 citations

Journal ArticleDOI
TL;DR: Investigation of the durability and functionality of the humoral and T-cell response to the original SARS-CoV-2 strain and variants in recovered patients 12 months after infection found neutralising antibodies remained stable 6 and 12 years after initial infection in most individuals younger than 60 years.

40 citations

Posted ContentDOI
02 Jun 2021-bioRxiv
TL;DR: In the absence of vaccination antibody reactivity to the receptor binding domain (RBD) of SARS-CoV-2, neutralizing activity and the number of RBD-specific memory B cells remain relatively stable from 6 to 12 months as discussed by the authors.
Abstract: Over one year after its inception, the coronavirus disease-2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) remains difficult to control despite the availability of several excellent vaccines. Progress in controlling the pandemic is slowed by the emergence of variants that appear to be more transmissible and more resistant to antibodies 1,2 . Here we report on a cohort of 63 COVID-19-convalescent individuals assessed at 1.3, 6.2 and 12 months after infection, 41% of whom also received mRNA vaccines 3,4 . In the absence of vaccination antibody reactivity to the receptor binding domain (RBD) of SARS-CoV-2, neutralizing activity and the number of RBD-specific memory B cells remain relatively stable from 6 to 12 months. Vaccination increases all components of the humoral response, and as expected, results in serum neutralizing activities against variants of concern that are comparable to or greater than neutralizing activity against the original Wuhan Hu-1 achieved by vaccination of naive individuals 2,5-8 . The mechanism underlying these broad-based responses involves ongoing antibody somatic mutation, memory B cell clonal turnover, and development of monoclonal antibodies that are exceptionally resistant to SARS-CoV-2 RBD mutations, including those found in variants of concern 4,9 . In addition, B cell clones expressing broad and potent antibodies are selectively retained in the repertoire over time and expand dramatically after vaccination. The data suggest that immunity in convalescent individuals will be very long lasting and that convalescent individuals who receive available mRNA vaccines will produce antibodies and memory B cells that should be protective against circulating SARS-CoV-2 variants.

27 citations

References
More filters
Journal ArticleDOI
03 Feb 2020-Nature
TL;DR: Identification and characterization of a new coronavirus (2019-nCoV), which caused an epidemic of acute respiratory syndrome in humans in Wuhan, China, and it is shown that this virus belongs to the species of SARSr-CoV, indicates that the virus is related to a bat coronav virus.
Abstract: Since the outbreak of severe acute respiratory syndrome (SARS) 18 years ago, a large number of SARS-related coronaviruses (SARSr-CoVs) have been discovered in their natural reservoir host, bats1–4. Previous studies have shown that some bat SARSr-CoVs have the potential to infect humans5–7. Here we report the identification and characterization of a new coronavirus (2019-nCoV), which caused an epidemic of acute respiratory syndrome in humans in Wuhan, China. The epidemic, which started on 12 December 2019, had caused 2,794 laboratory-confirmed infections including 80 deaths by 26 January 2020. Full-length genome sequences were obtained from five patients at an early stage of the outbreak. The sequences are almost identical and share 79.6% sequence identity to SARS-CoV. Furthermore, we show that 2019-nCoV is 96% identical at the whole-genome level to a bat coronavirus. Pairwise protein sequence analysis of seven conserved non-structural proteins domains show that this virus belongs to the species of SARSr-CoV. In addition, 2019-nCoV virus isolated from the bronchoalveolar lavage fluid of a critically ill patient could be neutralized by sera from several patients. Notably, we confirmed that 2019-nCoV uses the same cell entry receptor—angiotensin converting enzyme II (ACE2)—as SARS-CoV. Characterization of full-length genome sequences from patients infected with a new coronavirus (2019-nCoV) shows that the sequences are nearly identical and indicates that the virus is related to a bat coronavirus.

16,857 citations

Journal ArticleDOI
TL;DR: ACE2 is abundantly present in humans in the epithelia of the lung and small intestine, which might provide possible routes of entry for the SARS‐CoV.
Abstract: Severe acute respiratory syndrome (SARS) is an acute infectious disease that spreads mainly via the respiratory route. A distinct coronavirus (SARS-CoV) has been identified as the aetiological agent of SARS. Recently, a metallopeptidase named angiotensin-converting enzyme 2 (ACE2) has been identified as the functional receptor for SARS-CoV. Although ACE2 mRNA is known to be present in virtually all organs, its protein expression is largely unknown. Since identifying the possible route of infection has major implications for understanding the pathogenesis and future treatment strategies for SARS, the present study investigated the localization of ACE2 protein in various human organs (oral and nasal mucosa, nasopharynx, lung, stomach, small intestine, colon, skin, lymph nodes, thymus, bone marrow, spleen, liver, kidney, and brain). The most remarkable finding was the surface expression of ACE2 protein on lung alveolar epithelial cells and enterocytes of the small intestine. Furthermore, ACE2 was present in arterial and venous endothelial cells and arterial smooth muscle cells in all organs studied. In conclusion, ACE2 is abundantly present in humans in the epithelia of the lung and small intestine, which might provide possible routes of entry for the SARS-CoV. This epithelial expression, together with the presence of ACE2 in vascular endothelium, also provides a first step in understanding the pathogenesis of the main SARS disease manifestations.

4,714 citations

Journal ArticleDOI
TL;DR: In this article, the authors describe the long-term health consequences of patients with COVID-19 who have been discharged from hospital and investigate the associated risk factors, in particular disease severity.

2,933 citations

01 Jan 1987
TL;DR: A longitudinal study of service delivery within MRI services at Auckland University for patients, researchers and referring practitioners has been carried out since 2006 as mentioned in this paper, with a focus on the effects of service provision on patient satisfaction.
Abstract: A longitudinal study (since 2006) looking at the effects of service delivery within MRI services at Auckland University for patients, researchers and referring practitioners

2,922 citations

Journal ArticleDOI
TL;DR: It is shown that the SARS-CoV-2 spike protein is less stable than that of SARS -CoV, and limited cross-neutralization activities between SARS and COVID-19 patients’ sera showlimited cross- neutralization activities, suggesting that recovery from one infection might not protect against the other.
Abstract: Since 2002, beta coronaviruses (CoV) have caused three zoonotic outbreaks, SARS-CoV in 2002-2003, MERS-CoV in 2012, and the newly emerged SARS-CoV-2 in late 2019. However, little is currently known about the biology of SARS-CoV-2. Here, using SARS-CoV-2 S protein pseudovirus system, we confirm that human angiotensin converting enzyme 2 (hACE2) is the receptor for SARS-CoV-2, find that SARS-CoV-2 enters 293/hACE2 cells mainly through endocytosis, that PIKfyve, TPC2, and cathepsin L are critical for entry, and that SARS-CoV-2 S protein is less stable than SARS-CoV S. Polyclonal anti-SARS S1 antibodies T62 inhibit entry of SARS-CoV S but not SARS-CoV-2 S pseudovirions. Further studies using recovered SARS and COVID-19 patients' sera show limited cross-neutralization, suggesting that recovery from one infection might not protect against the other. Our results present potential targets for development of drugs and vaccines for SARS-CoV-2.

2,622 citations

Related Papers (5)
Frequently Asked Questions (1)
Q1. What are the contributions in "Twelve-month specific igg response to sars-cov-2 receptor-binding domain among covid-19 convalescent plasma donors in wuhan" ?

Wu et al. this paper reported a twelve-month specific IgG response to SARS-CoV-2 1 receptor-binding domain among COVID-19 convalescent 2 plasma donors in Wuhan.