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Persistent while declined neutralizing antibody responses in the convalescents of COVID-19 across clinical spectrum during the 16 months follow up

TL;DR: In this paper, the authors investigated the kinetics of neutralizing antibody response in COVID-19 convalescents and found that neutralization antibody responses could last at least 480 days despite of the obvious decline of neutralization activity, while the up to 50% undetectable neutralizing activity in the asymptomatic infections is of great concern.
Abstract: Elucidation the kinetics of neutralizing antibody response in the coronavirus disease 2019 (COVID-19) convalescents is crucial for the future control of the COVID-19 pandemic and vaccination strategies. Here we tested 411 sequential plasma samples collected up to 480 days post symptoms onset (d.a.o) from 214 convalescents of COVID-19 across clinical spectrum without re-exposure history after recovery and vaccination of SARS-CoV-2, using authentic SARS-CoV-2 microneutralization (MN) assays. COVID-19 convalescents free of re-exposure and vaccination could maintain relatively stable anti-RBD IgG and MN titers during 400∼480 d.a.o after the peak at around 120 d.a.o and the subsequent decrease. Undetectable neutralizing activity started to occur in mild and asymptomatic infections during 330 to 480 d.a.o with an overall rate of 14.29% and up to 50% for the asymptomatic infections. Significant decline in MN titers was found in 91.67% COVID-19 convalescents with ≥ 50% decrease in MN titers when comparing the available peak and current MN titers (≥ 300 d.a.o). Antibody-dependent immunity could also provide protection against most of circulating variants after one year, while significantly decreased neutralizing activities against the Beta, Delta and Lambda variants were found in most of individuals. In summary, our results indicated that neutralizing antibody responses could last at least 480 days in most COVID-19 convalescents despite of the obvious decline of neutralizing activity, while the up to 50% undetectable neutralizing activity in the asymptomatic infections is of great concern.

Summary (4 min read)

Introduction

  • Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was the seventh member of coronaviruses that has been found to infect human beings in late December, 2019, in Wuhan, China 1, 2 .
  • Notably, asymptomatic infections account for up to 40% of all the SARS-CoV-2 infections, and silent transmission during the pre-symptomatic and asymptomatic stages are responsible for more than 50% of the overall attack rate in COVID-19 outbreaks [3] [4] [5] [6] .
  • The two coronavirus that cause severe disease in human beings including SARS-CoV and Middle East Respiratory Syndrome coronavirus (MERS-CoV) induce stronger and more durable antibody responses up to 3 years 8, [10] [11] [12] [13] [14] .
  • Limitations of existing studies included either limited number of cohort, or short duration of follow up, enzyme-linked immunosorbent assay or.

Disease severity classification was evaluated according to China National Health Commission Guidelines for Diagnosis and Treatment of SARS-CoV-2 infection

  • In brief, laboratory confirmed patients with fever, respiratory manifestations and radiological findings indicative of pneumonia were considered moderate cases.
  • Laboratory confirmed patients who met any of the following were considered to have severe COVID-19: 1) respiratory distress (respiration rate ≥ 30/min; 2) resting oxygen saturation ≤ 93%, or 3) arterial oxygen partial pressure (PaO2) / fraction of inspired oxygen (FiO2) ≤ 300 mmHg (1 mmHg = 0.133 kPa).
  • Laboratory confirmed patients who had any of the following were considered critically ill: 1) respiratory failure requiring mechanical ventilation, 2) shock, or 3) failure of other organs requiring intensive care unit (ICU).

Cell lines and viruses

  • African green monkey kidney Vero cell (ATCC, CCL-81) were obtained from ATCC, and 293 cells stably expressing ACE-2 (293-ACE-2) were obtained from .
  • Both cell lines were maintained in Dulbecco's minimal essential medium (DMEM) supplemented with 10% fetal bovine serum (FBS) and penicillin (100U/ml)-streptomycin (100mg/ml) .
  • The 50% tissue culture infectious dose (TCID50) assay was done to measure the titre of the viral stock as previously described 36, 37 .
  • In brief, Vero cells in 96-well plates were grown to 90% confluence and infected with 10-fold serial dilutions of the viral stock for 1 h at 37°C.

Viral entry inhibition assay with SARS-CoV-2 pseudotyped virus

  • Firefly luciferase activity was measured using Bright-Light TM Luciferase Assay System and a VARIOSKAN LUX Multi-Mode plate reader according to the manufacture's protocols.
  • Measurements were performed in triplicate and relative luciferase units (RLU) were then converted into neutralization percentages.

Authentic SARS-CoV-2 microneutralization (MN) assays

  • Authentic SARS-CoV-2 microneutralization assays were performed as the authors described previously 23, 24, 40 .
  • Briefly, plasma samples were heat-inactivated at 56 °C for 30 min to remove complement activity and then serially diluted in 2-folds with DMEM supplemented with 2% FBS from 1:10 to 1:5120.
  • Diluted plasma samples were then mixed with 100 TCID50 of SARS-CoV-2 and incubated at 37°C for 1 hour.
  • The mixture was added to Vero cells and incubated at 37°C and 5% CO2 for another 96 hours.
  • Then cytopathic effect was evaluated and recorded using microscopy.

Enzyme-linked immunosorbent assay (ELISA)

  • RBD and nucleocapsid (N) specific binding immunoglobulin G (IgG) antibodies were measured according to the manufacture's protocols .
  • All plasma samples were heat inactivated at 56 °C for 30 min before use.
  • The copyright holder for this this version posted September 26, 2021.
  • Wells were then washed with PBS-T (PBS with 0.05% Tween-20), and secondary antibody was added and incubated for 1 h at room temperature.
  • After 15 minutes, the reaction was stopped with a 2M H2SO4 solution and then the absorbance was measured at 450 nm.

Statistical analysis

  • U test was used to compare the antibody levels and MN titers between two groups.
  • The Spearman rank correlation coefficient was used for linear correlation analysis between the antibody levels and MN titers.
  • All statistical tests were calculated using SPSS 20.0 for Windows (IBM).
  • P value less than 0.05 was considered statistically significant.
  • The kinetics of anti-RBD IgG and MN titers during follow-up were calculated by the LOESS (locally estimated scatterplot smoothing) curve fitting polynomial regression using R software.

Baseline characteristics of the cohort

  • A total of 214 laboratory confirmed COVID-19 patients with 51 individuals in severe group, 134 individuals in mild group and 29 individuals in asymptomatic group were included in this study for the analysis of antibody response.
  • This cohort was 46.73% male with an average age of 48 years (range 2-79) (Table 1 ), and patients in severe group were significantly older than mild and asymptomatic groups.
  • The body mass index (BMI) in severe group was significantly higher than the asymptomatic group.
  • The median days of interval between onset to qPCR negative for SARS-CoV-2 was 21, and longer duration of viral shedding was found in severe and mild groups, compared with asymptomatic group.
  • The complete blood count for each patient either on the date of hospital admission or at the earliest time-point showed that expression levels of D-dimer, CRP, IL-6, PCT and LDH were significantly higher in severe and mild groups, while percentage of lymphocyte (LYM), ALB and CD4 count were significantly lower in severe group.

Persistent neutralizing antibody response in COVID-19 convalescents

  • Notably, these individuals were mainly from the mild and asymptomatic groups, and the rate of individuals with undetectable neutralizing activity reached 50% .
  • Meanwhile, the distribution of MN titers obtained during 180 to 480 d.a.o showed that individuals with MN titers ≥ 160 decreased rapidly while proportion of MN titers ranging from negative to 80 increased rapidly along with time, indicating the decline of neutralizing activity in COVID-19 convalescents.
  • Combining IgG response and MN titer measurements, higher coincidence rate of 93.19% were found between anti-RBD IgG and MN tiers than that for anti-RBD IgG and MN tiers , and also the significant correlations between MN titers and levels of anti-RBD IgG, especially the severe and mild groups .

Comparison of neutralizing antibody response among COVID-19 patients across clinical spectrum

  • To determine whether disease severity impacts neutralizing antibody responses in COVID-19 patients, the authors firstly compared the differences of antibody development within 28 d.a.o among the severe, mild and asymptomatic groups .
  • For the asymptomatic patients, is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint.
  • The copyright holder for this this version posted September 26, 2021.
  • Significant differences were found for the current anti-RBD IgG levels among the three groups, with the highest in severe group and the lowest in asymptomatic group .

Dynamic change of neutralizing antibody response in COVID-19 convalescents

  • Generally, both the anti-RBD IgG and MN titers reached the peak at around 120 days post illness onset/laboratory confirmation, and then decreased slowly and maintained relatively stable after 400 days post illness onset/laboratory confirmation .
  • When comparing among the three groups, the results showed that it took longer (about 150 days) for the severe group to reach the peak anti-RBD IgG and MN titers than the mild (about 120 days) and asymptomatic (about 80 days) groups .
  • The copyright holder for this this version posted September 26, 2021.
  • Similar pattern was found for the MN titers .

Neutralizing activity against the circulating variants of SARS-CoV-2 after one year

  • To test whether individuals recovered from SARS-CoV-2 infection early in the pandemic could provide protection against the circulating variants after at least one year, the authors tested the neutralizing activity using pseudotyped SARS-CoV-2 variants of Alpha, Beta, Gamma, Delta and Lambda .
  • The information of the tested fourteen plasma samples was shown in Table S1 .
  • These samples contain samples from COVID-19 convalescents across clinical spectrum, with follow up days varied from 377 to 477 and the MN titers varied from 10 to 320.
  • Meanwhile, significantly lower inhibition rates against Beta, Delta and Lambda variants were also found in all the five individuals.

Discussion

  • Detectable levels of neutralizing antibodies against SARS-CoV-2 have been shown to maintain positive at least 300 d.a.o for most individuals 29 , and most studies supported that neutralizing antibody response started to decline shortly after infection, especially the mild and asymptomatic cases 14, 23, [25] [26] [27] [28] [29] .
  • Individuals with undetectable neutralizing activity were found between 331 and 480 d.a.o with an overall rate of 14.29% .
  • The copyright holder for this this version posted September 26, 2021.
  • In such case, neutralizing antibody response was sufficient to provide enough protection against reinfection even and severe infection at 480 d.a.o for most individuals according to their study.
  • In their study, all the individuals of the cohort did not receive vaccination of SARS-CoV-2 before the last follow-up, while about 40 individual started to receive vaccination of inactivated SARS-CoV-2 vaccine, and the specific antibody response of these individuals merits further investigation.

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Persistent while declined neutralizing antibody responses in the convalescents of1
COVID-19 across clinical spectrum during the 16 months follow up
2
3
Yang Yang
1
†, Minghui Yang
1
†, Yun Peng
1
†, Yanhua Liang
1
†, Jinli Wei
1
, Li Xing
1
,
4
Liping Guo
1
, Xiaohe Li
1
, Jie Li
1
, Jun Wang
1
, Mianhuan Li
1
, Zhixiang Xu
1
, Mingxia
5
Zhang
1
, Fuxiang Wang
1
, Yi Shi
2
, Jing Yuan
1
*, Yingxia Liu
1
*
6
7
1
Shenzhen Key Laboratory of Pathogen and Immunity, National Clinical Research
8
Center for infectious disease, State Key Discipline of Infectious Disease, Shenzhen
9
Third People's Hospital, Second Hospital Affiliated to Southern University of Science
10
and Technology, Shenzhen, China
11
2
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of
12
Microbiology, Chinese Academy of Sciences, Beijing, China
13
14
†Contributed equally.
15
*Contributed equally.
16
17
Correspondence to: Dr Liu, email: yingxialiu@hotmail.com; Dr Yuan, email:
18
13500054798@139.com;
19
20
Word count: 3499.
21
. CC-BY-NC-ND 4.0 International licenseIt is made available under a
perpetuity.
is the author/funder, who has granted medRxiv a license to display the preprint in(which was not certified by peer review)preprint
The copyright holder for thisthis version posted September 26, 2021. ; https://doi.org/10.1101/2021.09.18.21263550doi: medRxiv preprint
NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice.

Abstract22
Elucidation the kinetics of neutralizing antibody response in the coronavirus disease
23
2019 (COVID-19) convalescents is crucial for the future control of the COVID-19
24
pandemic and vaccination strategies. Here we tested 411 sequential plasma samples
25
collected up to 480 days post symptoms onset (d.a.o) from 214 convalescents of
26
COVID-19 across clinical spectrum without re-exposure history after recovery and
27
vaccination of SARS-CoV-2, using authentic SARS-CoV-2 microneutralization (MN)
28
assays. COVID-19 convalescents free of re-exposure and vaccination could maintain
29
relatively stable anti-RBD IgG and MN titers during 400~480 d.a.o after the peak at
30
around 120 d.a.o and the subsequent decrease. Undetectable neutralizing activity
31
started to occur in mild and asymptomatic infections during 330 to 480 d.a.o with an
32
overall rate of 14.29% and up to 50% for the asymptomatic infections. Significant
33
decline in MN titers was found in 91.67% COVID-19 convalescents with 50%
34
decrease in MN titers when comparing the available peak and current MN titers (≥
35
300 d.a.o). Antibody-dependent immunity could also provide protection against most
36
of circulating variants after one year, while significantly decreased neutralizing
37
activities against the Beta, Delta and Lambda variants were found in most of
38
individuals. In summary, our results indicated that neutralizing antibody responses
39
could last at least 480 days in most COVID-19 convalescents despite of the obvious
40
decline of neutralizing activity, while the up to 50% undetectable neutralizing activity
41
in the asymptomatic infections is of great concern.
42
43
. CC-BY-NC-ND 4.0 International licenseIt is made available under a
perpetuity.
is the author/funder, who has granted medRxiv a license to display the preprint in(which was not certified by peer review)preprint
The copyright holder for thisthis version posted September 26, 2021. ; https://doi.org/10.1101/2021.09.18.21263550doi: medRxiv preprint

Introduction44
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was the seventh
45
member of coronaviruses that has been found to infect human beings in late
46
December, 2019, in Wuhan, China
1,2
. The pandemic of SARS-CoV-2 is ongoing and
47
has caused over 209 million human infections with over 4.4 million fatal cases
48
worldwide until now (https://covid19.who.int/). Notably, asymptomatic infections
49
account for up to 40% of all the SARS-CoV-2 infections, and silent transmission
50
during the pre-symptomatic and asymptomatic stages are responsible for more than
51
50% of the overall attack rate in COVID-19 outbreaks
3-6
. Therefore,
52
antibody-mediated protective immunity induced either by natural infection or
53
vaccination is of great importance for the control of COVID-19 pandemic.
54
Neutralizing antibodies (NAbs) rapidly rise after infection and maintained for
55
years to decades by long-lived plasma and memory B cells in most acute viral
56
infections, playing vital roles in the viral clearance and protection against viral
57
diseases
7
. Studies have shown that the antibody response induced by coronavirus in
58
human beings tends to wane over time, and varies among types of coronaviruses and
59
the severity of the disease
8
. Seasonal human coronaviruses including HCoV-229E,
60
HCoVOC43, HCoV-NL63, and HCoV-HKU1 induce short-lasting antibody response,
61
and reinfection with the same seasonal coronavirus occurred frequently at 12 months
62
after infection
9
. However, the two coronavirus that cause severe disease in human
63
beings including SARS-CoV and Middle East Respiratory Syndrome coronavirus
64
(MERS-CoV) induce stronger and more durable antibody responses up to 3 years
8,10-14
.
65
Recent data from animal models, therapeutic use of neutralizing monoclonal66
antibodies and convalescent plasma suggest the critical role of neutralizing antibody67
in controlling SARS-CoV-2 infection and reinfection
15-22
, while a key question yet to68
. CC-BY-NC-ND 4.0 International licenseIt is made available under a
perpetuity.
is the author/funder, who has granted medRxiv a license to display the preprint in(which was not certified by peer review)preprint
The copyright holder for thisthis version posted September 26, 2021. ; https://doi.org/10.1101/2021.09.18.21263550doi: medRxiv preprint

be addressed is whether COVID-19 convalescents could maintain long-lasting69
antibody mediated protective immunity. Studies have set out to investigate the
70
dynamic change and longevity of both binding and neutralizing antibody response in
71
COVID-19 convalescents
14,23-31
, and the results in a very recent study indicated that
72
neutralizing antibody response in COVID-19 convalescents could maintain up to 300
73
days after symptoms onset (d.a.o) accompanied by waning of neutralizing antibody
74
titers
29-31
.
75
Limitations of existing studies included either limited number of cohort, or short
76
duration of follow up, enzyme-linked immunosorbent assay (ELISA) or
77
pseudoparticle neutralization based detection of neutralizing antibody response.
78
Moreover, possible re-exposure to SARS-CoV-2 in the pandemic area of COVID-19
79
could significantly influence the dynamics and longevity of NAb titers in COVID-19
80
convalescents. Owing to the highly efficient control of the COVID-19 endemic in
81
China, cohort in China offers ideal model to evaluate the natural dynamics and
82
longevity of neutralizing antibody responses after SARS-CoV-2 infection. In this
83
study, we investigated the dynamics and longevity of NAb titers up to 480 d.a.o from
84
214 convalescents of COVID-19 across clinical spectrum without any further
85
exposure history after recovery and vaccination of SARS-CoV-2, using authentic
86
virus based microneutralization assay, and tested the neutralizing activity against the
87
circulating variants utilizing SARS-CoV-2 pseudotype neutralization assays.
88
89
. CC-BY-NC-ND 4.0 International licenseIt is made available under a
perpetuity.
is the author/funder, who has granted medRxiv a license to display the preprint in(which was not certified by peer review)preprint
The copyright holder for thisthis version posted September 26, 2021. ; https://doi.org/10.1101/2021.09.18.21263550doi: medRxiv preprint

Materials and Methods90
Patient information and sample collection
91
Subjects presented in this study were laboratory confirmed COVID-19 patients using
92
quantitative real-time PCR (Mabsky Biotech Co.) and admitted to our hospital during
93
January 11 to April 18, 2020 (N=214). These individuals were further divided into
94
severe (including critically ill and severe cases), mild (including mild and moderate
95
patients) and asymptomatic group based on disease severity categorized according to
96
the China National Health Commission Guidelines for Diagnosis and Treatment of
97
SARS-CoV-2 infection. Clinical information and laboratory result were collected at
98
the earliest time-point after hospital admission. Blood samples were collected from
99
the enrolled patients during hospitalization and follow-up. Individuals with any
100
further exposure history after discharge or vaccination of SARS-CoV-2 were ruled out
101
during follow-up. The study protocol was approved by the Ethics Committees of
102
Shenzhen Third People’s Hospital (2020-010). Written informed consents were
103
obtained from all patients. The study was conducted in accordance with the
104
International Conference on Harmonisation Guidelines for Good Clinical Practice and
105
the Declaration of Helsinki and institutional ethics guidelines.
106
Disease severity classification
107
Disease severity classification was evaluated according to China National Health
108
Commission Guidelines for Diagnosis and Treatment of SARS-CoV-2 infection
109
(seventh version) as previously reported
32,33
. In brief, laboratory confirmed patients
110
with fever, respiratory manifestations and radiological findings indicative of
111
pneumonia were considered moderate cases. Laboratory confirmed patients who met112
any of the following were considered to have severe COVID-19: 1) respiratory113
distress (respiration rate 30/min; 2) resting oxygen saturation 93%, or 3) arterial114
. CC-BY-NC-ND 4.0 International licenseIt is made available under a
perpetuity.
is the author/funder, who has granted medRxiv a license to display the preprint in(which was not certified by peer review)preprint
The copyright holder for thisthis version posted September 26, 2021. ; https://doi.org/10.1101/2021.09.18.21263550doi: medRxiv preprint

References
More filters
Journal ArticleDOI
TL;DR: Human airway epithelial cells were used to isolate a novel coronavirus, named 2019-nCoV, which formed a clade within the subgenus sarbecovirus, Orthocoronavirinae subfamily, which is the seventh member of the family of coronaviruses that infect humans.
Abstract: In December 2019, a cluster of patients with pneumonia of unknown cause was linked to a seafood wholesale market in Wuhan, China. A previously unknown betacoronavirus was discovered through the use of unbiased sequencing in samples from patients with pneumonia. Human airway epithelial cells were used to isolate a novel coronavirus, named 2019-nCoV, which formed a clade within the subgenus sarbecovirus, Orthocoronavirinae subfamily. Different from both MERS-CoV and SARS-CoV, 2019-nCoV is the seventh member of the family of coronaviruses that infect humans. Enhanced surveillance and further investigation are ongoing. (Funded by the National Key Research and Development Program of China and the National Major Project for Control and Prevention of Infectious Disease in China.).

21,455 citations

Journal ArticleDOI
TL;DR: The serial respiratory viral load of SARS-CoV-2 in posterior oropharyngeal saliva samples from patients with COVID-19, and serum antibody responses from patients infected with severe acute respiratory syndrome coronavirus 2 are ascertained.
Abstract: Summary Background Coronavirus disease 2019 (COVID-19) causes severe community and nosocomial outbreaks. Comprehensive data for serial respiratory viral load and serum antibody responses from patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are not yet available. Nasopharyngeal and throat swabs are usually obtained for serial viral load monitoring of respiratory infections but gathering these specimens can cause discomfort for patients and put health-care workers at risk. We aimed to ascertain the serial respiratory viral load of SARS-CoV-2 in posterior oropharyngeal (deep throat) saliva samples from patients with COVID-19, and serum antibody responses. Methods We did a cohort study at two hospitals in Hong Kong. We included patients with laboratory-confirmed COVID-19. We obtained samples of blood, urine, posterior oropharyngeal saliva, and rectal swabs. Serial viral load was ascertained by reverse transcriptase quantitative PCR (RT-qPCR). Antibody levels against the SARS-CoV-2 internal nucleoprotein (NP) and surface spike protein receptor binding domain (RBD) were measured using EIA. Whole-genome sequencing was done to identify possible mutations arising during infection. Findings Between Jan 22, 2020, and Feb 12, 2020, 30 patients were screened for inclusion, of whom 23 were included (median age 62 years [range 37–75]). The median viral load in posterior oropharyngeal saliva or other respiratory specimens at presentation was 5·2 log10 copies per mL (IQR 4·1–7·0). Salivary viral load was highest during the first week after symptom onset and subsequently declined with time (slope −0·15, 95% CI −0·19 to −0·11; R2=0·71). In one patient, viral RNA was detected 25 days after symptom onset. Older age was correlated with higher viral load (Spearman's ρ=0·48, 95% CI 0·074–0·75; p=0·020). For 16 patients with serum samples available 14 days or longer after symptom onset, rates of seropositivity were 94% for anti-NP IgG (n=15), 88% for anti-NP IgM (n=14), 100% for anti-RBD IgG (n=16), and 94% for anti-RBD IgM (n=15). Anti-SARS-CoV-2-NP or anti-SARS-CoV-2-RBD IgG levels correlated with virus neutralisation titre (R2>0·9). No genome mutations were detected on serial samples. Interpretation Posterior oropharyngeal saliva samples are a non-invasive specimen more acceptable to patients and health-care workers. Unlike severe acute respiratory syndrome, patients with COVID-19 had the highest viral load near presentation, which could account for the fast-spreading nature of this epidemic. This finding emphasises the importance of stringent infection control and early use of potent antiviral agents, alone or in combination, for high-risk individuals. Serological assay can complement RT-qPCR for diagnosis. Funding Richard and Carol Yu, May Tam Mak Mei Yin, The Shaw Foundation Hong Kong, Michael Tong, Marina Lee, Government Consultancy Service, and Sanming Project of Medicine.

2,778 citations

Journal ArticleDOI
TL;DR: It is shown that neutralization level is highly predictive of immune protection, and an evidence-based model of SARS-CoV-2 immune protection that will assist in developing vaccine strategies to control the future trajectory of the pandemic is provided.
Abstract: Predictive models of immune protection from COVID-19 are urgently needed to identify correlates of protection to assist in the future deployment of vaccines. To address this, we analyzed the relationship between in vitro neutralization levels and the observed protection from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection using data from seven current vaccines and from convalescent cohorts. We estimated the neutralization level for 50% protection against detectable SARS-CoV-2 infection to be 20.2% of the mean convalescent level (95% confidence interval (CI) = 14.4–28.4%). The estimated neutralization level required for 50% protection from severe infection was significantly lower (3% of the mean convalescent level; 95% CI = 0.7–13%, P = 0.0004). Modeling of the decay of the neutralization titer over the first 250 d after immunization predicts that a significant loss in protection from SARS-CoV-2 infection will occur, although protection from severe disease should be largely retained. Neutralization titers against some SARS-CoV-2 variants of concern are reduced compared with the vaccine strain, and our model predicts the relationship between neutralization and efficacy against viral variants. Here, we show that neutralization level is highly predictive of immune protection, and provide an evidence-based model of SARS-CoV-2 immune protection that will assist in developing vaccine strategies to control the future trajectory of the pandemic. Estimates of the levels of neutralizing antibodies necessary for protection against symptomatic SARS-CoV-2 or severe COVID-19 are a fraction of the mean level in convalescent serum and will be useful in guiding vaccine rollouts.

2,705 citations

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