A Prospective Study on Rapidly Declining SARS-CoV-2 IgG Antibodies Within One to Three Months of Testing IgG Positive: Can It Lead to Potential Reinfections?
TL;DR: The findings show that the protective COVID-19 IgG antibodies rapidly decline over one to three months, which is critical for the potential vaccines to generate both protective T- and B-cell immune responses in a sustained manner.
Abstract: Background COVID-19 immunoglobulin G (IgG) antibodies have been considered to provide protective immunity and its immunoassays have been widely used for serosurveillance. In our serosurveillance on an industrial workforce of randomly selected 3296 subjects, COVID-19 IgG antibody positivity was reported in 7.37% (243) subjects. However, when 30 days later, eight of the 243 COVID-19 IgG antibody-positive individuals complained of symptoms suggestive of COVID-19 infection and were confirmed as COVID-19 infection by reverse transcription-polymerase chain reaction (RT-PCR), their COVID-19 IgG antibodies were retested. Seven of the eight previously IgG positive individuals had lost their protective antibodies. Methods Subsequently, a prospective clinical trial was planned by repeating the test for IgG antibodies on the remaining earlier positive 235 individuals at 45-65 days after their initial test. Only 201 of the 235 individuals consented and participated in the non-randomized single-arm observational trial. Results Only 28.36% (57/201) retained their IgG antibodies and 70.15% (141/201) had lost their IgG antibodies. Three cases reported equivocal results on retesting. Conclusions Our findings show that the protective COVID-19 IgG antibodies rapidly decline over one to three months. Further studies are needed with a quantitative assay over a period with neutralizing antibodies to establish if its decay can potentially lead to reinfections. Rapidly decaying protective IgG antibodies would impact herd immunity and vaccine durability. It is critical for the potential vaccines to generate both protective T- and B-cell immune responses in a sustained manner.
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TL;DR: In this paper, the authors evaluate the latest understanding of antibody-mediated immunity to SARS-CoV-2 and to other coronaviruses (SARS CoV, Middle East respiratory syndrome coronavirus, and the four endemic human Coronavirus) in order to predict the consequences of antibody waning on long-term immunity against SARS co-virus.
Abstract: The coronavirus disease 2019 (COVID-19), caused by the novel betacoronavirus severe acute respiratory syndrome 2 (SARS-CoV-2), was declared a pandemic in March 2020. Due to the continuing surge in incidence and mortality globally, determining whether protective, long-term immunity develops after initial infection or vaccination has become critical. In this narrative review, we evaluate the latest understanding of antibody-mediated immunity to SARS-CoV-2 and to other coronaviruses (SARS-CoV, Middle East respiratory syndrome coronavirus and the four endemic human coronaviruses) in order to predict the consequences of antibody waning on long-term immunity against SARS-CoV-2. We summarise their antibody dynamics, including the potential effects of cross-reactivity and antibody waning on vaccination and other public health strategies. At present, based on our comparison with other coronaviruses we estimate that natural antibody-mediated protection for SARS-CoV-2 is likely to last for 1–2 years and therefore, if vaccine-induced antibodies follow a similar course, booster doses may be required. However, other factors such as memory B- and T-cells and new viral strains will also affect the duration of both natural and vaccine-mediated immunity. Overall, antibody titres required for protection are yet to be established and inaccuracies of serological methods may be affecting this. We expect that with standardisation of serological testing and studies with longer follow-up, the implications of antibody waning will become clearer.
41 citations
TL;DR: The COVID-19 vaccination campaign in Italy has started with a huge perplexity about vaccine efficacy, vaccine-borne adverse effects and vaccine clinical trial studies as discussed by the authors, which represent a fundamental topic to be thoroughly addressed in COVID 2019 pandemic.
Abstract: Coronavirus disease 2019 (COVID-19) vaccination campaign in Italy has started with a huge perplexity about vaccine efficacy, vaccine-borne adverse effects and vaccine clinical trial studies. In this commentary I tried to elucidate these issues, which represent a fundamental topic to be thoroughly addressed in COVID-19 pandemic.
16 citations
TL;DR: A review of the latest advances in research and clinical trials, challenges, and perspectives on antibody-based treatments (ABT) as therapies against COVID-19 can be found in this paper.
10 citations
TL;DR: In this article, the sensitivity of three tests applied to 133 individuals with a previous positive PCR result between April and October was assessed. But, little is known on how long rapid tests remain positive after COVID-19 episode, or how much variability exists across different brands and even among batches of the same test.
Abstract: Background Large-scale epidemiological studies of seroprevalence of antibodies against SARS-CoV-2 often rely on point-of-care tests that provide immediate results to participants. Yet, little is known on how long rapid tests remain positive after the COVID-19 episode, or how much variability exists across different brands and even among batches of the same test. Methods In November 2020, we assessed the sensitivity of three tests applied to 133 individuals with a previous positive PCR result between April and October. All subjects provided finger prick blood samples for two batches (A and B) of the Wondfo lateral-flow IgG/IgM test, and dried blood spot samples for the S-UFRJ ELISA test. Results Overall sensitivity levels were 92.5% (95% CI 86.6–96.3), 63.2% (95% CI 54.4–71.4) and 33.8% (95% CI 25.9–42.5) for the S-UFRJ test, Wondfo A and Wondfo B tests, respectively. There was no evidence of a decline in the positivity of S-UFRJ with time since the diagnosis, but the two Wondfo batches showed sharp reductions to as low as 41.9% and 19.4%, respectively, for subjects with a positive PCR in June or earlier. Positive results for batch B of the rapid test were 35% to 54% lower than for batch A at any given month of diagnosis. Interpretation Whereas the ELISA test showed high sensitivity and stability of results over the five months of the study, both batches of the rapid test showed substantial declines, with one of the batches consistently showing lower sensitivity levels than the other. ELISA tests based on dried-blood spots are an inexpensive alternative to rapid lateral-flow tests in large-scale epidemiological studies. Funding The study was funded by the “Todos Pela Saude” initiative, Instituto Serrapilheira, Brazilian Ministry of Health, Brazilian Collective Health Association (ABRASCO) and the JBS S.A. initiative ‘Fazer o Bem Faz Bem’.
8 citations
TL;DR: In this paper, a cross-sectional study was conducted between October 7 and November 30, 2020, in a multi-specialty hospital in Eastern India designated as COVID hospital during this pandemic.
Abstract: Objective We aimed to study the seroprevalence of coronavirus disease 2019 (COVID-19) and sustainability of the immune response in health care workers (HCWs). A cross-sectional study was conducted between October 7 and November 30, 2020, in a multi-specialty hospital in Eastern India designated as COVID hospital during this pandemic. Study participants included 2,110 HCWs, including those who have recovered from COVID infection. Method HCWs were required to complete a questionnaire and give written consent to participate in the study. Their venous blood sample was collected for serum analysis of IgG antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by chemiluminescent immunoassay. Results Positive IgG antibodies were seen in 924 participants with a point prevalence of 43.79%. Slightly higher reactivity was seen in males. History of COVID-19 infection was noted in 10.9%, with the highest antibody response in 81% cases. A maximum of 87.9% reactivity was seen in the first two months, and a significant fall was noted in the fourth month, with reactivity seen in only 50% of the study participants. Conclusion SARS-CoV-2 infection is associated with a variable immune response in the infected population. The declining trend of the antibodies correlates with short-lived protective immunity and the possibility of re-infection. Further studies are needed to explore the probable reasons for varied seroprevalence.
7 citations
References
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TL;DR: A cohort of asymptomatic patients infected with SARS-CoV-2 had significantly lower levels of virus-specific IgG antibodies compared to a cohort of age- and sex-matched symptomatic infected patients.
Abstract: The clinical features and immune responses of asymptomatic individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have not been well described We studied 37 asymptomatic individuals in the Wanzhou District who were diagnosed with RT-PCR-confirmed SARS-CoV-2 infections but without any relevant clinical symptoms in the preceding 14 d and during hospitalization Asymptomatic individuals were admitted to the government-designated Wanzhou People's Hospital for centralized isolation in accordance with policy1 The median duration of viral shedding in the asymptomatic group was 19 d (interquartile range (IQR), 15-26 d) The asymptomatic group had a significantly longer duration of viral shedding than the symptomatic group (log-rank P = 0028) The virus-specific IgG levels in the asymptomatic group (median S/CO, 34; IQR, 16-107) were significantly lower (P = 0005) relative to the symptomatic group (median S/CO, 205; IQR, 58-382) in the acute phase Of asymptomatic individuals, 933% (28/30) and 811% (30/37) had reduction in IgG and neutralizing antibody levels, respectively, during the early convalescent phase, as compared to 968% (30/31) and 622% (23/37) of symptomatic patients Forty percent of asymptomatic individuals became seronegative and 129% of the symptomatic group became negative for IgG in the early convalescent phase In addition, asymptomatic individuals exhibited lower levels of 18 pro- and anti-inflammatory cytokines These data suggest that asymptomatic individuals had a weaker immune response to SARS-CoV-2 infection The reduction in IgG and neutralizing antibody levels in the early convalescent phase might have implications for immunity strategy and serological surveys
2,463 citations
"A Prospective Study on Rapidly Decl..." refers background or result in this paper
...While our findings are similar to the observations of Long QX [6] and Ibarrondo FJ [7], their observations were based on only 37 and 34 participants....
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...9% of symptomatic individuals become seronegative for IgG antibodies in the “early convalescent phase” [6], there are other isolated reports of rapid decay of IgG antibodies in persons with a mild infection [7]....
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TL;DR: Covid-19 Antibodies after Mild Infection Among 34 volunteers who had recovered from mild Covid- 19 illness, antiviral antibodies to the receptor-binding domain of the viral spike protein declined.
Abstract: Covid-19 Antibodies after Mild Infection Among 34 volunteers who had recovered from mild Covid-19 illness, antiviral antibodies to the receptor-binding domain of the viral spike protein declined wi...
907 citations
"A Prospective Study on Rapidly Decl..." refers background or result in this paper
...While our findings are similar to the observations of Long QX [6] and Ibarrondo FJ [7], their observations were based on only 37 and 34 participants....
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...Given the fact that the majority of COVID-9 infections are mild, our findings show that rapidly decaying protective IgG antibodies would impact herd immunity and vaccine durability [7]....
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...9% of symptomatic individuals become seronegative for IgG antibodies in the “early convalescent phase” [6], there are other isolated reports of rapid decay of IgG antibodies in persons with a mild infection [7]....
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TL;DR: An overview of the experimental and clinical data obtained from recent SARS-CoV-2 vaccines trials are provided, and certain potential safety issues that require consideration when developing vaccines are highlighted.
Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging virus that is highly pathogenic and has caused the recent worldwide pandemic officially named coronavirus disease (COVID-19). Currently, considerable efforts have been put into developing effective and safe drugs and vaccines against SARS-CoV-2. Vaccines, such as inactivated vaccines, nucleic acid-based vaccines, and vector vaccines, have already entered clinical trials. In this review, we provide an overview of the experimental and clinical data obtained from recent SARS-CoV-2 vaccines trials, and highlight certain potential safety issues that require consideration when developing vaccines. Furthermore, we summarize several strategies utilized in the development of vaccines against other infectious viruses, such as severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), with the aim of aiding in the design of effective therapeutic approaches against SARS-CoV-2.
408 citations
"A Prospective Study on Rapidly Decl..." refers background in this paper
...This would not only impact our current understanding on monitoring the potential vaccine recipients, but it would also make it critical for the potential vaccines to generate both “protective T- and Bcell immune responses” in a sustained manner [13]....
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TL;DR: A brief summary of the performance of a number of serologic assays reported in the literature is provided, comment on what the authors do and do not know regarding their immune response to SARS-CoV-2, and number of scenarios for which serologic testing will play a role during their global response to this pandemic are provided.
Abstract: The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) brought with it rapid development of both molecular and serologic assays for identification of COVID-19 infections. While Food and Drug Administration (FDA) emergency use authorization (EUA) is required for clinical application of SARS-CoV-2 molecular tests, submission for EUA is currently a voluntary process for manufacturers of serologic assays. The absence of FDA oversight of serologic tests is concerning given that the commercially available serologic assays are highly variable, differing in their format, the antibody class detected, the targeted antigen, and the acceptable specimen types. An added complication is the lack of a clear understanding for how such assays should be utilized and what the reported results ultimately indicate or, perhaps more importantly, what they do not indicate. Here, we provide a brief summary of the performance of a number of serologic assays reported in the literature, comment on what we do and do not know regarding our immune response to SARS-CoV-2, and provide a number of scenarios for which serologic testing will play a role during our global response to this pandemic.
281 citations
"A Prospective Study on Rapidly Decl..." refers background in this paper
...Besides, in the absence of neutralizing antibody tests, semi-quantitative assays of SARS‐CoV‐2 IgG antibody may only indicate prior exposure to the SARS‐CoV‐2 infection and “does not equate to protective immunity” [10]....
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...Standard plaque reduction neutralization tests (PRNTs) or the currently investigational neutralizing impact on pseudotyped vesicular stomatitis virus (VSV) expressing different SARS-CoV-2 surface antigens would be needed to establish humoral immunity [10]....
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...Given the wide variability in the incidence of asymptomatic infection ranging from 4%80% [10], it could potentially identify the actual number of infected in a defined population....
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TL;DR: Focusing on IgG antibodies, it is demonstrated the performance of two enzyme‐linked immunosorbent assay (ELISA) assays (Euroimmun SARS‐CoV‐2 IgG and Vircell COVID‐19 ELISA IgG) in comparison to one lateral flow assay and two in‐house developed assays.
Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serological assays are urgently needed for rapid diagnosis, contact tracing, and for epidemiological studies. So far, there is limited data on how commercially available tests perform with real patient samples, and if positive tested samples show neutralizing abilities. Focusing on IgG antibodies, we demonstrate the performance of two enzyme-linked immunosorbent assay (ELISA) assays (Euroimmun SARS-CoV-2 IgG and Vircell COVID-19 ELISA IgG) in comparison to one lateral flow assay (FaStep COVID-19 IgG/IgM Rapid Test Device) and two in-house developed assays (immunofluorescence assay [IFA] and plaque reduction neutralization test [PRNT]). We tested follow up serum/plasma samples of individuals polymerase chain reaction-diagnosed with COVID-19. Most of the SARS-CoV-2 samples were from individuals with moderate to the severe clinical course, who required an in-patient hospital stay. For all examined assays, the sensitivity ranged from 58.8 to 76.5% for the early phase of infection (days 5-9) and from 93.8% to 100% for the later period (days 10-18).
123 citations
"A Prospective Study on Rapidly Decl..." refers background in this paper
...However, recent studies have expressed doubts on the longevity and the “protective immunity” provided by the SARS‐CoV‐2 IgG antibodies [5]....
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