Longitudinal observation and decline of neutralizing antibody responses in the three months following SARS-CoV-2 infection in humans
Antibody responses to SARS-CoV-2 can be detected in most infected individuals 10–15 d after the onset of COVID-19 symptoms. However, due to the recent emergence of SARS-CoV-2 in the human population, it is not known how long antibody responses will be maintained or whether they will provide protecti...
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| Published in | Nature microbiology Vol. 5; no. 12; pp. 1598 - 1607 |
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| Main Authors | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
London
Nature Publishing Group UK
01.12.2020
Nature Publishing Group |
| Subjects | |
| Online Access | Get full text |
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| Abstract | Antibody responses to SARS-CoV-2 can be detected in most infected individuals 10–15 d after the onset of COVID-19 symptoms. However, due to the recent emergence of SARS-CoV-2 in the human population, it is not known how long antibody responses will be maintained or whether they will provide protection from reinfection. Using sequential serum samples collected up to 94 d post onset of symptoms (POS) from 65 individuals with real-time quantitative PCR-confirmed SARS-CoV-2 infection, we show seroconversion (immunoglobulin (Ig)M, IgA, IgG) in >95% of cases and neutralizing antibody responses when sampled beyond 8 d POS. We show that the kinetics of the neutralizing antibody response is typical of an acute viral infection, with declining neutralizing antibody titres observed after an initial peak, and that the magnitude of this peak is dependent on disease severity. Although some individuals with high peak infective dose (ID
50
> 10,000) maintained neutralizing antibody titres >1,000 at >60 d POS, some with lower peak ID
50
had neutralizing antibody titres approaching baseline within the follow-up period. A similar decline in neutralizing antibody titres was observed in a cohort of 31 seropositive healthcare workers. The present study has important implications when considering widespread serological testing and antibody protection against reinfection with SARS-CoV-2, and may suggest that vaccine boosters are required to provide long-lasting protection.
Neutralizing antibody responses of patients infected with SARS-CoV-2 peak at 3–4 weeks post onset of symptoms, then decline to low levels over the course of 3 months in some individuals. |
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| AbstractList | Antibody responses to SARS-CoV-2 can be detected in most infected individuals 10–15 d after the onset of COVID-19 symptoms. However, due to the recent emergence of SARS-CoV-2 in the human population, it is not known how long antibody responses will be maintained or whether they will provide protection from reinfection. Using sequential serum samples collected up to 94 d post onset of symptoms (POS) from 65 individuals with real-time quantitative PCR-confirmed SARS-CoV-2 infection, we show seroconversion (immunoglobulin (Ig)M, IgA, IgG) in >95% of cases and neutralizing antibody responses when sampled beyond 8 d POS. We show that the kinetics of the neutralizing antibody response is typical of an acute viral infection, with declining neutralizing antibody titres observed after an initial peak, and that the magnitude of this peak is dependent on disease severity. Although some individuals with high peak infective dose (ID50 > 10,000) maintained neutralizing antibody titres >1,000 at >60 d POS, some with lower peak ID50 had neutralizing antibody titres approaching baseline within the follow-up period. A similar decline in neutralizing antibody titres was observed in a cohort of 31 seropositive healthcare workers. The present study has important implications when considering widespread serological testing and antibody protection against reinfection with SARS-CoV-2, and may suggest that vaccine boosters are required to provide long-lasting protection.Neutralizing antibody responses of patients infected with SARS-CoV-2 peak at 3–4 weeks post onset of symptoms, then decline to low levels over the course of 3 months in some individuals. Antibody responses to SARS-CoV-2 can be detected in most infected individuals 10-15 d after the onset of COVID-19 symptoms. However, due to the recent emergence of SARS-CoV-2 in the human population, it is not known how long antibody responses will be maintained or whether they will provide protection from reinfection. Using sequential serum samples collected up to 94 d post onset of symptoms (POS) from 65 individuals with real-time quantitative PCR-confirmed SARS-CoV-2 infection, we show seroconversion (immunoglobulin (Ig)M, IgA, IgG) in >95% of cases and neutralizing antibody responses when sampled beyond 8 d POS. We show that the kinetics of the neutralizing antibody response is typical of an acute viral infection, with declining neutralizing antibody titres observed after an initial peak, and that the magnitude of this peak is dependent on disease severity. Although some individuals with high peak infective dose (ID > 10,000) maintained neutralizing antibody titres >1,000 at >60 d POS, some with lower peak ID had neutralizing antibody titres approaching baseline within the follow-up period. A similar decline in neutralizing antibody titres was observed in a cohort of 31 seropositive healthcare workers. The present study has important implications when considering widespread serological testing and antibody protection against reinfection with SARS-CoV-2, and may suggest that vaccine boosters are required to provide long-lasting protection. Antibody responses to SARS-CoV-2 can be detected in most infected individuals 10-15 d after the onset of COVID-19 symptoms. However, due to the recent emergence of SARS-CoV-2 in the human population, it is not known how long antibody responses will be maintained or whether they will provide protection from reinfection. Using sequential serum samples collected up to 94 d post onset of symptoms (POS) from 65 individuals with real-time quantitative PCR-confirmed SARS-CoV-2 infection, we show seroconversion (immunoglobulin (Ig)M, IgA, IgG) in >95% of cases and neutralizing antibody responses when sampled beyond 8 d POS. We show that the kinetics of the neutralizing antibody response is typical of an acute viral infection, with declining neutralizing antibody titres observed after an initial peak, and that the magnitude of this peak is dependent on disease severity. Although some individuals with high peak infective dose (ID50 > 10,000) maintained neutralizing antibody titres >1,000 at >60 d POS, some with lower peak ID50 had neutralizing antibody titres approaching baseline within the follow-up period. A similar decline in neutralizing antibody titres was observed in a cohort of 31 seropositive healthcare workers. The present study has important implications when considering widespread serological testing and antibody protection against reinfection with SARS-CoV-2, and may suggest that vaccine boosters are required to provide long-lasting protection.Antibody responses to SARS-CoV-2 can be detected in most infected individuals 10-15 d after the onset of COVID-19 symptoms. However, due to the recent emergence of SARS-CoV-2 in the human population, it is not known how long antibody responses will be maintained or whether they will provide protection from reinfection. Using sequential serum samples collected up to 94 d post onset of symptoms (POS) from 65 individuals with real-time quantitative PCR-confirmed SARS-CoV-2 infection, we show seroconversion (immunoglobulin (Ig)M, IgA, IgG) in >95% of cases and neutralizing antibody responses when sampled beyond 8 d POS. We show that the kinetics of the neutralizing antibody response is typical of an acute viral infection, with declining neutralizing antibody titres observed after an initial peak, and that the magnitude of this peak is dependent on disease severity. Although some individuals with high peak infective dose (ID50 > 10,000) maintained neutralizing antibody titres >1,000 at >60 d POS, some with lower peak ID50 had neutralizing antibody titres approaching baseline within the follow-up period. A similar decline in neutralizing antibody titres was observed in a cohort of 31 seropositive healthcare workers. The present study has important implications when considering widespread serological testing and antibody protection against reinfection with SARS-CoV-2, and may suggest that vaccine boosters are required to provide long-lasting protection. Antibody responses to SARS-CoV-2 can be detected in most infected individuals 10–15 d after the onset of COVID-19 symptoms. However, due to the recent emergence of SARS-CoV-2 in the human population, it is not known how long antibody responses will be maintained or whether they will provide protection from reinfection. Using sequential serum samples collected up to 94 d post onset of symptoms (POS) from 65 individuals with real-time quantitative PCR-confirmed SARS-CoV-2 infection, we show seroconversion (immunoglobulin (Ig)M, IgA, IgG) in >95% of cases and neutralizing antibody responses when sampled beyond 8 d POS. We show that the kinetics of the neutralizing antibody response is typical of an acute viral infection, with declining neutralizing antibody titres observed after an initial peak, and that the magnitude of this peak is dependent on disease severity. Although some individuals with high peak infective dose (ID 50 > 10,000) maintained neutralizing antibody titres >1,000 at >60 d POS, some with lower peak ID 50 had neutralizing antibody titres approaching baseline within the follow-up period. A similar decline in neutralizing antibody titres was observed in a cohort of 31 seropositive healthcare workers. The present study has important implications when considering widespread serological testing and antibody protection against reinfection with SARS-CoV-2, and may suggest that vaccine boosters are required to provide long-lasting protection. Neutralizing antibody responses of patients infected with SARS-CoV-2 peak at 3–4 weeks post onset of symptoms, then decline to low levels over the course of 3 months in some individuals. |
| Author | Martinez-Nunez, Rocio Edgeworth, Jonathan D. Graham, Carl MacMahon, Eithne Martinez, Lauren Douthwaite, Sam Patel, Amita Nebbia, Gaia Signell, Adrian W. Stokes, Brielle Izquierdo-Barras, Alba Snell, Luke B. Green, Adrian O’Connell, Lorcan Wilson, Harry D. Galao, Rui Pedro Doores, Katie J. Kerridge, Claire Batra, Rahul Betancor, Gilberto Merrick, Blair Acors, Sam Lista, Maria Jose O’Byrne, Aoife Seow, Jeffrey Jimenez-Guardeño, Jose M. Honey, Johanna Winstone, Helena Tan, Mark Kia Ik Hemmings, Oliver Arbane, Gill Neil, Stuart J. D. Kouphou, Neophytos Pickering, Suzanne Temperton, Nigel Malim, Michael H. Huettner, Isabella Bisnauthsing, Karen Shankar-Hari, Manu Moore, Amelia O’Hara, Geraldine Steel, Kathryn J. A. |
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| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/33106674$$D View this record in MEDLINE/PubMed |
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Med. 217, https://doi.org/10.1084/jem.20201181 (2020). Seydoux, E. et al. Analysis of a SARS-CoV-2-infected individual reveals development of potent neutralizing antibodies with limited somatic mutation. Immunityhttps://doi.org/10.1016/j.immuni.2020.06.001 (2020). Brouwer, P. J. M. et al. Potent neutralizing antibodies from COVID-19 patients define multiple targets of vulnerability. Sciencehttps://doi.org/10.1126/science.abc5902 (2020). Laing, A. G. et al. A dynamic COVID-19 immune signature includes associations with poor prognosis. Nat. Med. https://doi.org/10.1038/s41591-020-1038-6 (2020). Thompson, C. et al. Neutralising antibodies to SARS coronavirus 2 in Scottish blood donors—a pilot study of the value of serology to determine population exposure. Preprint at medRxivhttps://doi.org/10.1101/2020.04.13.20060467 (2020). PrevostJCross-sectional evaluation of humoral responses against SARS-CoV-2 SpikeCell Rep. Med.2020110012610.1016/j.xcrm.2020.100126 WangMAntibody dynamics of 2009 influenza A (H1N1) virus in infected patients and vaccinated people in ChinaPLoS ONE20116e168091:CAS:528:DC%2BC3MXitlyjt74%3D10.1371/journal.pone.0016809 van Doremalen, N. et al. ChAdOx1 nCoV-19 vaccine prevents SARS-CoV-2 pneumonia in rhesus macaques. Naturehttps://doi.org/10.1038/s41586-020-2608-y (2020). IyerASPersistence and decay of human antibody responses to the receptor binding domain of SARS-CoV-2 spike protein in COVID-19 patients.Sci. Immunol.20205eabe036710.1126/sciimmunol.abe0367 Rodda, L. B. et al. Functional SARS-CoV-2-specific immune memory persists after mild COVID-19. Preprint at medRxivhttps://doi.org/10.1101/2020.08.11.20171843 (2020). Lee, W. T. et al. Neutralizing antibody responses in COVID-19 convalescent sera. Preprint at medRxivhttps://doi.org/10.1101/2020.07.10.20150557 (2020). Gao, Q. et al. Rapid development of an inactivated vaccine candidate for SARS-CoV-2. Sciencehttps://doi.org/10.1126/science.abc1932 (2020). OkbaNMASevere acute respiratory syndrome coronavirus 2-specific antibody responses in coronavirus disease patientsEmerg. Infect. Dis.2020261478148810.3201/eid2607.200841 Cao, Y. et al. Potent neutralizing antibodies against SARS-CoV-2 identified by high-throughput single-cell sequencing of convalescent patients’ B cells. Cellhttps://doi.org/10.1016/j.cell.2020.05.025 (2020). IshoBPersistence of serum and saliva antibody responses to SARS-CoV-2 spike antigens in COVID-19 patientsSci. Immunol.20205eabe551133033173 Corbett, K. S. et al. Evaluation of the mRNA-1273 vaccine against SARS-CoV-2 in nonhuman primates. N. Engl. J. Med.https://doi.org/10.1056/NEJMoa2024671 (2020). GorseGJDonovanMMPatelGBAntibodies to coronaviruses are higher in older compared with younger adults and binding antibodies are more sensitive than neutralizing antibodies in identifying coronavirus-associated illnessesJ. Med. Virol2020925125171:CAS:528:DC%2BB3cXltFems7k%3D10.1002/jmv.25715 LongQXClinical and immunological assessment of asymptomatic SARS-CoV-2 infectionsNat. Med202026120012041:CAS:528:DC%2BB3cXhtF2qtbrM10.1038/s41591-020-0965-6 IwasakiAYangYThe potential danger of suboptimal antibody responses in COVID-19Nat. Rev. Immunol2020203393411:CAS:528:DC%2BB3cXns1CisL0%3D10.1038/s41577-020-0321-6 Edridge, A. W. D. et al. Seasonal coronavirus protective immunity is short-lasting. Nat. Med.https://doi.org/10.1038/s41591-020-1083-1 (2020). Rogers, T. F. et al. Isolation of potent SARS-CoV-2 neutralizing antibodies and protection from disease in a small animal model. Sciencehttps://doi.org/10.1126/science.abc7520 (2020). Wu, F. et al. Evaluating the association of clinical characteristics with neutralizing antibody levels in patients who have recovered from mild COVID-19 in Shanghai, China. JAMA Intern. Med. https://doi.org/10.1001/jamainternmed.2020.4616 (2020). Crawford, K. H. D. et al. Dynamics of neutralizing antibody titers in the months after SARS-CoV-2 infection. J. Infect. Dis.https://doi.org/10.1093/infdis/jiaa618 (2020). Shi, R. et al. A human neutralizing antibody targets the receptor binding site of SARS-CoV-2. Naturehttps://doi.org/10.1038/s41586-020-2381-y (2020). LeeNAnti-SARS-CoV IgG response in relation to disease severity of severe acute respiratory syndromeJ. Clin. Virol2006351791841:CAS:528:DC%2BD28XjvVKhtA%3D%3D10.1016/j.jcv.2005.07.005 Wajnberg, A. et al. SARS-CoV-2 infection induces robust, neutralizing antibody responses that are stable for at least three months. Preprint at medRxivhttps://doi.org/10.1101/2020.07.14.20151126 (2020). 813_CR20 813_CR21 813_CR26 813_CR27 813_CR28 PG Choe (813_CR24) 2017; 23 813_CR29 eKM Petersen (813_CR43) 2020; 20 813_CR11 NMA Okba (813_CR5) 2020; 26 813_CR12 813_CR51 813_CR52 813_CR10 813_CR54 M Wang (813_CR22) 2011; 6 QX Long (813_CR3) 2020; 26 J Prevost (813_CR7) 2020; 1 813_CR15 813_CR17 813_CR18 813_CR9 GJ Gorse (813_CR2) 2020; 92 813_CR8 AS Iyer (813_CR35) 2020; 5 813_CR4 813_CR50 813_CR44 813_CR45 813_CR46 813_CR47 813_CR40 813_CR41 813_CR42 813_CR1 IJ Amanna (813_CR23) 2007; 357 813_CR48 G Beaudoin-Bussières (813_CR36) 2020; 11 QX Long (813_CR13) 2020; 26 B Isho (813_CR37) 2020; 5 H Mo (813_CR16) 2006; 11 S Pickering (813_CR6) 2020; 16 813_CR34 T Sekine (813_CR53) 2020; 183 813_CR30 813_CR31 K Grehan (813_CR25) 2015; 2 813_CR38 813_CR39 A Iwasaki (813_CR33) 2020; 20 N Lee (813_CR32) 2006; 35 KA Callow (813_CR14) 1990; 105 WC Cao (813_CR19) 2007; 357 TRF Smith (813_CR49) 2020; 11 |
| References_xml | – reference: SekineTRobust T cell immunity in convalescent individuals with asymptomatic or mild COVID-19Cell Press20201831581681:CAS:528:DC%2BB3cXhvFKjs7jE – reference: Ju, B. et al. Human neutralizing antibodies elicited by SARS-CoV-2 infection. Naturehttps://doi.org/10.1038/s41586-020-2380-z (2020). – reference: IwasakiAYangYThe potential danger of suboptimal antibody responses in COVID-19Nat. Rev. Immunol2020203393411:CAS:528:DC%2BB3cXns1CisL0%3D10.1038/s41577-020-0321-6 – reference: Amanat, F. et al. A serological assay to detect SARS-CoV-2 seroconversion in humans. Nat. Med. https://doi.org/10.1038/s41591-020-0913-5(2020). – reference: LeeNAnti-SARS-CoV IgG response in relation to disease severity of severe acute respiratory syndromeJ. Clin. Virol2006351791841:CAS:528:DC%2BD28XjvVKhtA%3D%3D10.1016/j.jcv.2005.07.005 – reference: Beaudoin-BussièresGDecline of humoral responses against SARS-CoV-2 Spike in convalescent individualsmBio202011e025902010.1128/mBio.02590-20 – reference: MoHLongitudinal profile of antibodies against SARS-coronavirus in SARS patients and their clinical significanceRespirology200611495310.1111/j.1440-1843.2006.00783.x – reference: PrevostJCross-sectional evaluation of humoral responses against SARS-CoV-2 SpikeCell Rep. Med.2020110012610.1016/j.xcrm.2020.100126 – reference: Kellam, P. & Barclay, W. The dynamics of humoral immune responses following SARS-CoV-2 infection and the potential for reinfection. J. Gen. Virol. https://doi.org/10.1099/jgv.0.001439 (2020). – reference: GorseGJDonovanMMPatelGBAntibodies to coronaviruses are higher in older compared with younger adults and binding antibodies are more sensitive than neutralizing antibodies in identifying coronavirus-associated illnessesJ. Med. Virol2020925125171:CAS:528:DC%2BB3cXltFems7k%3D10.1002/jmv.25715 – reference: Deng, W. et al. Primary exposure to SARS-CoV-2 protects against reinfection in rhesus macaques. Sciencehttps://doi.org/10.1126/science.abc5343 (2020). – reference: IshoBPersistence of serum and saliva antibody responses to SARS-CoV-2 spike antigens in COVID-19 patientsSci. Immunol.20205eabe551133033173 – reference: Thompson, C. et al. Neutralising antibodies to SARS coronavirus 2 in Scottish blood donors—a pilot study of the value of serology to determine population exposure. Preprint at medRxivhttps://doi.org/10.1101/2020.04.13.20060467 (2020). – reference: AmannaIJCarlsonNESlifkaMKDuration of humoral immunity to common viral and vaccine antigensN. Engl. J. Med.2007357190319151:CAS:528:DC%2BD2sXht1ymtbjI10.1056/NEJMoa066092 – reference: Moore, J. P. & Klasse, P. J. SARS-CoV-2 vaccines: ‘Warp Speed’ needs mind melds not warped minds. J. Virol. https://doi.org/10.1128/JVI.01083-20 (2020). – reference: CaoWCLiuWZhangPHZhangFRichardusJHDisappearance of antibodies to SARS-associated coronavirus after recoveryN. Engl. J. Med2007357116211631:CAS:528:DC%2BD2sXhtVGqu7nN10.1056/NEJMc070348 – reference: PeterseneKMComparing SARS-CoV-2 with SARS-CoV and influenza pandemicsLancet Infect.202020e238e2441:CAS:528:DC%2BB3cXhtlegu7rE10.1016/S1473-3099(20)30484-9 – reference: Rogers, T. F. et al. Isolation of potent SARS-CoV-2 neutralizing antibodies and protection from disease in a small animal model. Sciencehttps://doi.org/10.1126/science.abc7520 (2020). – reference: Carter, M. J. et al. Peripheral immunophenotypes in children with multisystem inflammatory syndrome associated with SARS-CoV-2 infection. Nat. Med.https://doi.org/10.1038/s41591-020-1054-6 (2020). – reference: Shi, R. et al. A human neutralizing antibody targets the receptor binding site of SARS-CoV-2. Naturehttps://doi.org/10.1038/s41586-020-2381-y (2020). – reference: Seydoux, E. et al. Analysis of a SARS-CoV-2-infected individual reveals development of potent neutralizing antibodies with limited somatic mutation. Immunityhttps://doi.org/10.1016/j.immuni.2020.06.001 (2020). – reference: Wang, K. et al. Longitudinal dynamics of the neutralizing antibody response to SARS-CoV-2 infection. Clin. Infect. Dis.https://doi.org/10.1093/cid/ciaa1143 (2020). – reference: Wajnberg, A. et al. SARS-CoV-2 infection induces robust, neutralizing antibody responses that are stable for at least three months. Preprint at medRxivhttps://doi.org/10.1101/2020.07.14.20151126 (2020). – reference: Wu, F. et al. Evaluating the association of clinical characteristics with neutralizing antibody levels in patients who have recovered from mild COVID-19 in Shanghai, China. JAMA Intern. Med. https://doi.org/10.1001/jamainternmed.2020.4616 (2020). – reference: GrehanKFerraraFTempertonNAn optimised method for the production of MERS-CoV spike expressing viral pseudotypesMethodsX201523793841:STN:280:DC%2BC28rgsVektQ%3D%3D10.1016/j.mex.2015.09.003 – reference: Luchsinger, L. L. et al. Serological assays estimate highly variable SARS-CoV-2 neutralizing antibody activity in recovered COVID19 patients. J. Clin. Microbiol. https://doi.org/10.1128/JCM.02005-20 (2020). – reference: OkbaNMASevere acute respiratory syndrome coronavirus 2-specific antibody responses in coronavirus disease patientsEmerg. Infect. Dis.2020261478148810.3201/eid2607.200841 – reference: IyerASPersistence and decay of human antibody responses to the receptor binding domain of SARS-CoV-2 spike protein in COVID-19 patients.Sci. Immunol.20205eabe036710.1126/sciimmunol.abe0367 – reference: ChoePGMERS-CoV antibody responses 1 year after symptom onset, South Korea, 2015Emerg. Infect. Dis.201723107910841:CAS:528:DC%2BC1cXhvFGjt7nI10.3201/eid2307.170310 – reference: WangMAntibody dynamics of 2009 influenza A (H1N1) virus in infected patients and vaccinated people in ChinaPLoS ONE20116e168091:CAS:528:DC%2BC3MXitlyjt74%3D10.1371/journal.pone.0016809 – reference: Keech, C. et al. Phase 1–2 trial of a SARS-CoV-2 recombinant spike protein nanoparticle vaccine. N. Engl. J. Med. https://doi.org/10.1056/NEJMoa2026920 (2020). – reference: Crawford, K. H. D. et al. Dynamics of neutralizing antibody titers in the months after SARS-CoV-2 infection. J. Infect. Dis.https://doi.org/10.1093/infdis/jiaa618 (2020). – reference: Sterlin, D. et al. IgA dominates the early neutralizing antibody response to SARS-CoV-2. Preprint at medRxivhttps://doi.org/10.1101/2020.06.10.20126532 (2020). – reference: Lee, W. T. et al. Neutralizing antibody responses in COVID-19 convalescent sera. Preprint at medRxivhttps://doi.org/10.1101/2020.07.10.20150557 (2020). – reference: LongQXClinical and immunological assessment of asymptomatic SARS-CoV-2 infectionsNat. Med202026120012041:CAS:528:DC%2BB3cXhtF2qtbrM10.1038/s41591-020-0965-6 – reference: Edridge, A. W. D. et al. Seasonal coronavirus protective immunity is short-lasting. Nat. Med.https://doi.org/10.1038/s41591-020-1083-1 (2020). – reference: Schmidt, F. et al. Measuring SARS-CoV-2 neutralizing antibody activity using pseudotyped and chimeric viruses. J. Exp. Med. 217, https://doi.org/10.1084/jem.20201181 (2020). – reference: Jackson, L. A. et al. An mRNA vaccine against SARS-CoV-2—preliminary report. N. Engl. J. Med.https://doi.org/10.1056/NEJMoa2022483 (2020). – reference: Rodda, L. B. et al. Functional SARS-CoV-2-specific immune memory persists after mild COVID-19. Preprint at medRxivhttps://doi.org/10.1101/2020.08.11.20171843 (2020). – reference: van Doremalen, N. et al. 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| Title | Longitudinal observation and decline of neutralizing antibody responses in the three months following SARS-CoV-2 infection in humans |
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