Waning of SARS-CoV-2 RBD antibodies in longitudinal convalescent plasma samples within 4 months after symptom onset

Perreault, Josée; Tremblay, Tony; Fournier, M; Drouin, Mathieu; Beaudoin-Bussières, Guillaume; Prévost, Jérémie; Lewin, Antoine; Bégin, Philippe; Finzi, Andrés; Bazin, Renée

doi:10.1182/blood.2020008367

Cited by 133 publications

(131 citation statements)

References 29 publications

(27 reference statements)

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“…While our results are only relevant for the first several weeks after infection, experimental evidence suggests that antibody titers are relatively stable for at least a period of 5 months after symptoms onset [ 2 , 3 , 55 ], with only ~3 fold decrease in antibodies levels in ~80–100 days [ 2 , 3 ]. This suggests that antibody production does not halt completely once SARS-CoV-2 viral loads go below the detection limit, which is typical following many viral infections.…”

Section: Discussionmentioning

confidence: 96%

“…While neutralizing antibodies are detected 1–2 weeks after symptom onset, it is less certain whether these antibodies are relevant for clearance of the virus or whether they only protect viral re-exposure. A better understanding of viral antibody interactions is critical to specify the optimal timing for neutralizing antibody treatments which may be more effective according to the stage of infection [ 1 , 2 , 3 , 4 , 5 , 6 , 7 ]. Indeed, recent trials of neutralizing antibody infusions demonstrate antiviral and clinical efficacy though only if dosed early in infection prior to clinical decompensation [ 8 , 9 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

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Endogenously Produced SARS-CoV-2 Specific IgG Antibodies May Have a Limited Impact on Clearing Nasal Shedding of Virus during Primary Infection in Humans

Yang

Jerome

Greninger

et al. 2021

Viruses

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While SARS-CoV-2 specific neutralizing antibodies have been developed for therapeutic purposes, the specific viral triggers that drive the generation of SARS-CoV-2 specific IgG and IgM antibodies remain only partially characterized. Moreover, it is unknown whether endogenously derived antibodies drive viral clearance that might result in mitigation of clinical severity during natural infection. We developed a series of non-linear mathematical models to investigate whether SARS-CoV-2 viral and antibody kinetics are coupled or governed by separate processes. Patients with severe disease had a higher production rate of IgG but not IgM antibodies. Maximal levels of both isotypes were governed by their production rate rather than different saturation levels between people. Our results suggest that an exponential surge in IgG levels occurs approximately 5–10 days after symptom onset with no requirement for continual antigenic stimulation. SARS-CoV-2 specific IgG antibodies appear to have limited to no effect on viral dynamics but may enhance viral clearance late during primary infection resulting from the binding effect of antibody to virus, rather than neutralization. In conclusion, SARS-CoV-2 specific IgG antibodies may play only a limited role in clearing infection from the nasal passages despite providing long-term immunity against infection following vaccination or prior infection.

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Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

Endogenously Produced SARS-CoV-2 Specific IgG Antibodies May Have a Limited Impact on Clearing Nasal Shedding of Virus during Primary Infection in Humans

Yang

Jerome

Greninger

et al. 2021

Viruses

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“…We began by evaluating the presence of RBD-specific IgG, IgM, and IgA antibodies by using a previously published enzyme-linked immunosorbent assay (ELISA) against the SARS-CoV-2 RBD antigen (16). In agreement with recent reports showing the waning of antibody levels in longitudinal convalescent plasma over time (14)(15)(16)(17), we observed that total RBD-specific immunoglobulin (Ig) levels, comprising of IgG, IgM, and IgA, gradually decreased between 6 and 31 weeks after the onset of symptoms ( Figure 1A). However, the percentage of convalescent individuals presenting detectable RBD-specific Ig levels remained stable, with a consistent seropositivity rate above 90% throughout the sampling time frame.…”

Section: Sars-cov-2 Rbd-specific and Spike-specific Antibody Levels Imentioning

confidence: 87%

Longitudinal analysis of humoral immunity against SARS-CoV-2 Spike in convalescent individuals up to 8 months post-symptom onset

Anand

Prévost

Nayrac

et al. 2021

Preprint

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Functional and lasting immune responses to the novel coronavirus (SARS-CoV-2) are currently under intense investigation as antibody titers in plasma have been shown to decline during convalescence. Since the absence of antibodies does not equate to absence of immune memory, we sought to determine the presence of SARS-CoV-2-specific memory B cells in COVID-19 convalescent patients. In this study, we report on the evolution of the overall humoral immune responses on 101 blood samples obtained from 32 COVID-19 convalescent patients between 16 and 233 days post-symptom onset. Our observations indicate that anti-Spike and anti-RBD IgM in plasma decay rapidly, whereas the reduction of IgG is less prominent. Neutralizing activity in convalescent plasma declines rapidly compared to Fc-effector functions. Concomitantly, the frequencies of RBD-specific IgM+ B cells wane significantly when compared to RBD-specific IgG+ B cells, which increase over time, and the number of IgG+ memory B cells which remain stable thereafter for up to 8 months after symptoms onset. With the recent approval of highly effective vaccines for COVID-19, data on the persistence of immune responses are of central importance. Even though overall circulating SARS-CoV-2 Spike-specific antibodies contract over time during convalescence, we demonstrate that RBD-specific B cells increase and persist up to 8 months post symptom onset. We also observe modest increases in RBD-specific IgG+ memory B cells and importantly, detectable IgG and sustained Fc-effector activity in plasma over the 8-month period. Our results add to the current understanding of immune memory following SARS-CoV-2 infection, which is critical for the prevention of secondary infections, vaccine efficacy and herd immunity against COVID-19.

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“…This difference may be due to the fact that infected individuals may not have comparable antigen loads and uniform antibody responses over the time of the disease, as suggested by a study conducted on asymptomatic and symptomatic cases [6]. Interestingly, the kinetics of the humoral response was recently described in symptomatic (non-severe) and convalescent COVID-19 individuals and revealed that antibody levels against the receptor binding domain (RBD) of SARS-CoV-2 decline over time [7][8][9][10]. Despite these findings, long-term antibody responses remain to be fully characterized, particularly in hospitalized patients, and for instance, for those transferred to ICU and with very poor prognosis.…”

Section: Introductionmentioning

confidence: 99%

Serological Surveillance of COVID-19 Hospitalized Patients in Réunion Island (France) Revealed that Specific Immunoglobulin G Are Rapidly Vanishing in Severe Cases

Dobi

Seteyen

Rakoto

et al. 2020

JCM

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Humoral immunity is critically important to control COVID-19. Long-term antibody responses remain to be fully characterized in hospitalized patients who have a high risk of death. We compared specific Immunoglobulin responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) between two groups, intensive care unit (ICU) and non-ICU hospitalized patients over several weeks. Plasma specific IgG, IgM, and IgA levels were assessed using a commercial ELISA and compared to an in-house cell-based ELISA. Among the patients analyzed (mean (SD) of age, 64.4 (15.9) years, 19.2% female), 12 (46.2%) were hospitalized in ICU. IgG levels increased in non-ICU cases from the second to the eighth week after symptom onset. By contrast, IgG response was blunted in ICU patients over the same period. ICU patients with hematological malignancies had very weak or even undetectable IgG levels. While both groups had comparable levels of specific IgM antibodies, we found much lower levels of specific IgA in ICU versus non-ICU patients. In conclusion, COVID-19 ICU patients may be at risk of reinfection as their specific IgG response is declining in a matter of weeks. Antibody neutralizing assays and studies on specific cellular immunity will have to be performed.

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Waning of SARS-CoV-2 RBD antibodies in longitudinal convalescent plasma samples within 4 months after symptom onset

Abstract: Perreault and colleagues examined antibody titers in sequential samples from serum donors recovering from COVID-19 and demonstrated that antibody titers fall over 3-4 months. These results have important implications for convalescent serum collection and seroprevalence studies.

Cited by 133 publications

References 29 publications

Endogenously Produced SARS-CoV-2 Specific IgG Antibodies May Have a Limited Impact on Clearing Nasal Shedding of Virus during Primary Infection in Humans

Endogenously Produced SARS-CoV-2 Specific IgG Antibodies May Have a Limited Impact on Clearing Nasal Shedding of Virus during Primary Infection in Humans

Longitudinal analysis of humoral immunity against SARS-CoV-2 Spike in convalescent individuals up to 8 months post-symptom onset

Serological Surveillance of COVID-19 Hospitalized Patients in Réunion Island (France) Revealed that Specific Immunoglobulin G Are Rapidly Vanishing in Severe Cases

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