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?

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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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Clinical and immunological assessment of asymptomatic SARS-CoV-2 infections

Quan-Xin Long, Xiao-Jun Tang, Qiu-Lin Shi … (2020)

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 = 0.028). The virus-specific IgG levels in the asymptomatic group (median S/CO, 3.4; IQR, 1.6-10.7) were significantly lower (P = 0.005) relative to the symptomatic group (median S/CO, 20.5; IQR, 5.8-38.2) in the acute phase. Of asymptomatic individuals, 93.3% (28/30) and 81.1% (30/37) had reduction in IgG and neutralizing antibody levels, respectively, during the early convalescent phase, as compared to 96.8% (30/31) and 62.2% (23/37) of symptomatic patients. Forty percent of asymptomatic individuals became seronegative and 12.9% 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.

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Rapid Decay of Anti–SARS-CoV-2 Antibodies in Persons with Mild Covid-19

F. Ibarrondo, Jennifer A. Fulcher, David Goodman-Meza … (2020)

To the Editor: A recent article suggested the rapid decay of anti–SARS-CoV-2 IgG in early infection, 1 but the rate was not described in detail. We evaluated persons who had recovered from Covid-19 and referred themselves to our institution for observational research. Written informed consent was obtained from all the participants, with approval by the institutional review board. Blood samples were analyzed by enzyme-linked immunosorbent assay (ELISA) to detect anti–SARS-CoV-2 spike receptor-binding domain IgG. 2 The ELISA was further modified to precisely quantify serum anti–receptor-binding domain activity in terms of equivalence to the concentration of a control anti–receptor-binding domain monoclonal IgG (CR3022, Creative Biolabs). Infection had been confirmed by polymerase-chain-reaction assay in 30 of the 34 participants. The other 4 participants had had symptoms compatible with Covid-19 and had cohabitated with persons who were known to have Covid-19 but were not tested because of mild illness and the limited availability of testing. Most of the participants had mild illness; 2 received low-flow supplemental oxygen and leronlimab (a CCR5 antagonist), but they did not receive remdesivir. There were 20 women and 14 men. The mean age was 43 years (range, 21 to 68) (see the Supplementary Appendix, available with the full text of this letter at NEJM.org). A total of 31 of the 34 participants had two serial measurements of IgG levels, and the remaining 3 participants had three serial measurements. The first measurement was obtained at a mean of 37 days after the onset of symptoms (range, 18 to 65), and the last measurement was obtained at a mean of 86 days after the onset of symptoms (range, 44 to 119). The initial mean IgG level was 3.48 log10 ng per milliliter (range, 2.52 to 4.41). On the basis of a linear regression model that included the participants’ age and sex, the days from symptom onset to the first measurement, and the first log10 antibody level, the estimated mean change (slope) was −0.0083 log10 ng per milliliter per day (range, −0.0352 to 0.0062), which corresponds to a half-life of approximately 36 days over the observation period (Figure 1A). The 95% confidence interval for the slope was −0.0115 to −0.0050 log10 ng per milliliter per day (half-life, 26 to 60 days) (Figure 1B). The protective role of antibodies against SARS-CoV-2 is unknown, but these antibodies are usually a reasonable correlate of antiviral immunity, and anti–receptor-binding domain antibody levels correspond to plasma viral neutralizing activity. Given that early antibody decay after acute viral antigenic exposure is approximately exponential, 3 we found antibody loss that was quicker than that reported for SARS-CoV-1, 4,5 and our findings were more consistent with those of Long et al. 1 Our findings raise concern that humoral immunity against SARS-CoV-2 may not be long lasting in persons with mild illness, who compose the majority of persons with Covid-19. It is difficult to extrapolate beyond our observation period of approximately 90 days because it is likely that the decay will decelerate. 3 Still, the results call for caution regarding antibody-based “immunity passports,” herd immunity, and perhaps vaccine durability, especially in light of short-lived immunity against common human coronaviruses. Further studies will be needed to define a quantitative protection threshold and rate of decline of antiviral antibodies beyond 90 days.

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A systematic review of SARS-CoV-2 vaccine candidates

Yetian Dong, Tong Dai, Yujun Wei … (2020)

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.

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Author and article information

Journal

Journal ID (nlm-ta): Cureus

Journal ID (iso-abbrev): Cureus

Journal ID (issn): 2168-8184

Title: Cureus

Publisher: Cureus (Palo Alto (CA) )

ISSN (Electronic): 2168-8184

Publication date (Electronic, pub): 2 December 2020

Publication date (Electronic, collection): December 2020

Volume: 12

Issue: 12

Electronic Location Identifier: e11845

Affiliations

[1 ] Anaesthesiology, Tata Main Hospital, Jamshedpur, IND

[2 ] Medical Services, Tata Main Hospital, Jamshedpur, IND

[3 ] Pathology, Tata Main Hospital, Jamshedpur, IND

[4 ] Microbiology, Tata Main Hospital, Jamshedpur, IND

Author notes

Deb Sanjay Nag debsanjay@ 123456gmail.com

Article

DOI: 10.7759/cureus.11845

PMC ID: 7714733

PubMed ID: 33282604

SO-VID: abb7ac12-7c24-4c66-8add-ce73c6c4d614

License:

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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?

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Novel Coronavirus Disease COVID-19

Most cited references 15

Clinical and immunological assessment of asymptomatic SARS-CoV-2 infections

Rapid Decay of Anti–SARS-CoV-2 Antibodies in Persons with Mild Covid-19

A systematic review of SARS-CoV-2 vaccine candidates

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