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(which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.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