scholarly journals Evaluation of the IgG antibody response to SARS CoV-2 infection and performance of a lateral flow immunoassay: cross-sectional and longitudinal analysis over 11 months

BMJ Open ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. e048142
Author(s):  
Louise J Robertson ◽  
Julie S Moore ◽  
Kevin Blighe ◽  
Kok Yew Ng ◽  
Nigel Quinn ◽  
...  

ObjectiveTo evaluate the dynamics and longevity of the humoral immune response to SARS-CoV-2 infection and assess the performance of professional use of the UK-RTC AbC-19 Rapid Test lateral flow immunoassay (LFIA) for the target condition of SARS-CoV-2 spike protein IgG antibodies.DesignNationwide serological study.SettingNorthern Ireland, UK, May 2020–February 2021.ParticipantsPlasma samples were collected from a diverse cohort of individuals from the general public (n=279), Northern Ireland healthcare workers (n=195), pre-pandemic blood donations and research studies (n=223) and through a convalescent plasma programme (n=183). Plasma donors (n=101) were followed with sequential samples over 11 months post-symptom onset.Main outcome measuresSARS-CoV-2 antibody levels in plasma samples using Roche Elecsys Anti-SARS-CoV-2 IgG/IgA/IgM, Abbott SARS-CoV-2 IgG and EuroImmun IgG SARS-CoV-2 ELISA immunoassays over time. UK-RTC AbC-19 LFIA sensitivity and specificity, estimated using a three-reference standard system to establish a characterised panel of 330 positive and 488 negative SARS-CoV-2 IgG samples.ResultsWe detected persistence of SARS-CoV-2 IgG antibodies for up to 10 months post-infection, across a minimum of two laboratory immunoassays. On the known positive cohort, the UK-RTC AbC-19 LFIA showed a sensitivity of 97.58% (95.28% to 98.95%) and on known negatives, showed specificity of 99.59% (98.53 % to 99.95%).ConclusionsThrough comprehensive analysis of a cohort of pre-pandemic and pandemic individuals, we show detectable levels of IgG antibodies, lasting over 46 weeks when assessed by EuroImmun ELISA, providing insight to antibody levels at later time points post-infection. We show good laboratory validation performance metrics for the AbC-19 rapid test for SARS-CoV-2 spike protein IgG antibody detection in a laboratory-based setting.

Author(s):  
Louise J. Robertson ◽  
Julie S. Moore ◽  
Kevin Blighe ◽  
Kok Yew Ng ◽  
Nigel Quinn ◽  
...  

AbstractBackgroundThe SARS-CoV-2 pandemic necessitated rapid and global responses across all areas of healthcare, including an unprecedented interest in serological immunoassays to detect antibodies to the virus. The dynamics of the immune response to SARS-CoV-2 is still not well understood and requires further investigation into the longevity of humoral immune response that is evoked due to SARS-CoV-2 infection.MethodsWe measured SARS-CoV-2 antibody levels in plasma samples from 880 people in Northern Ireland using Roche Elecsys Anti-SARS-CoV-2 IgG/IgA/IgM, Abbott SARS-CoV-2 IgG and EuroImmun IgG SARS-CoV-2 ELISA immunoassays to analyse immune dynamics over time. We undertook a laboratory evaluation for the UK-RTC AbC-19 rapid lateral flow immunoassay (LFIA), for the target condition of SARS-CoV-2 Spike protein IgG antibodies using a reference standard system to establish a characterised panel of 330 positive and 488 negative SARS-CoV-2 IgG samples.ResultsWe detected persistence of SARS-CoV-2 IgG up to 140 days (20 weeks) post infection, across all three laboratory-controlled immunoassays. On the known positive cohort, the UK-RTC AbC-19 lateral flow immunoassay showed a sensitivity of 97.58% (95.28%-98.95%) and on known negatives, showed specificity of 99.59% (98.53 %-99.95%).ConclusionsThrough comprehensive analysis of a cohort of pre-pandemic and pandemic individuals, we show detectable levels of IgG antibodies, lasting up to 140 days, providing insight to antibody levels at later time points post infection. We show good laboratory validation performance metrics for the AbC-19 rapid test for SARS-CoV-2 Spike protein IgG antibody detection in a laboratory based setting.


2021 ◽  
Author(s):  
Thomas Akerlund ◽  
Katherina Zakikhany ◽  
Charlotta Lofstrom ◽  
Evelina Lindmark ◽  
Henrik Kallberg ◽  
...  

More knowledge regarding persistence of antibody response to SARS-CoV-2 infections in the general population with mild symptoms is needed. We measured and compared levels of SARS-CoV-2 spike- and nucleocapsid-specific IgG-antibodies in serum samples from 145 laboratory-confirmed COVID-19 cases and 324 non-cases. The IgG-antibody levels against the spike protein in cases were stable over the time-period studied (14 to 256 days), while antibody levels against the nucleocapsid protein decreased over time.


Author(s):  
Georg Semmler ◽  
Marianna Theresia Traugott ◽  
Marianne Graninger ◽  
Wolfgang Hoepler ◽  
Tamara Seitz ◽  
...  

In this study, we comprehensively analyzed multispecific antibody kinetics of different immunoglobulins in hospitalized patients with acute SARS-CoV-2 infection. Three-hundred-fifty-four blood samples longitudinally obtained from 81 IgG seroconverting CoVID-19 patients were quantified for spike (S)1, S2, and nucleocapsid protein (NCP)- specific IgM, IgA, IgG, and total Ig antibodies using a microarray, eleven different ELISAs/CLIAs, and one rapid test by seven manufacturers. The assays’ specificity was assessed in 130 non-CoVID19 pneumonia patients. Using the microarray, NCP-specific IgA and IgG antibodies continuously displayed higher detection rates during acute CoVID-19 than S1- and S2-specific ones. S1-specific IgG antibodies, however, reached higher peak values. Until the 26th-day post symptom onset, all patients developed IgG responses against S1, S2, and NCP, respectively. Although detection rates by ELISAs/CLIAs generally resembled those of the microarray, corresponding to the target antigen, sensitivities and specificities varied among all tests. Notably, patients with more severe CoVID-19 displayed higher IgG and IgA levels, but this difference was mainly observed with S1-specific immunoassays. In patients with high SARS-CoV-2 levels in the lower respiratory tract, we observed high detection rates of IgG and total Ig immunoassays with a particular rise of S1-specific IgG antibodies when viral concentrations in the tracheal aspirate subsequently declined over time. In summary, our study demonstrates that differences in sensitivity among commercial immunoassays during acute SARS-CoV-2 infection are only partly related to the target antigen. Importantly, our data indicate that NCP-specific IgA and IgG antibodies are detected earlier, while higher S1-specific IgA antibody levels occur in severely ill patients.


2021 ◽  
Vol 9 ◽  
Author(s):  
Julia Schiffner ◽  
Insa Backhaus ◽  
Jens Rimmele ◽  
Sören Schulz ◽  
Till Möhlenkamp ◽  
...  

Characterization of the naturally acquired B and T cell immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is important for the development of public health and vaccination strategies to manage the burden of COVID-19 disease. We conducted a prospective, cross-sectional analysis in COVID-19 recovered patients at various time points over a 10-month period in order to investigate how circulating antibody levels and interferon-gamma (IFN-γ) release by peripheral blood cells change over time following natural infection. From March 2020 till January 2021, we enrolled 412 adults mostly with mild or moderate disease course. At each study visit, subjects donated peripheral blood for testing of anti-SARS-CoV-2 IgG antibodies and IFN-γ release after SARS-CoV-2 S-protein stimulation. Anti-SARS-CoV-2 immunoglobulin G (IgG) antibodies were positive in 316 of 412 (76.7%) and borderline in 31 of 412 (7.5%) patients. Our confirmation assay for the presence of neutralizing antibodies was positive in 215 of 412 (52.2%) and borderline in 88 of 412 (21.4%) patients. Likewise, in 274 of 412 (66.5%) positive IFN-γ release and IgG antibodies were detected. With respect to time after infection, both IgG antibody levels and IFN-γ concentrations decreased by about half within 300 days. Statistically, production of IgG and IFN-γ were closely associated, but on an individual basis, we observed patients with high-antibody titres but low IFN-γ levels and vice versa. Our data suggest that immunological reaction is acquired in most individuals after natural infection with SARS-CoV-2 and is sustained in the majority of patients for at least 10 months after infection after a mild or moderate disease course. Since, so far, no robust marker for protection against COVID-19 exists, we recommend utilizing both, IgG and IFN-γ release for an individual assessment of the immunity status.


Vaccines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1063
Author(s):  
Jürgen Held ◽  
Jan Esse ◽  
Koray Tascilar ◽  
Philipp Steininger ◽  
Kilian Schober ◽  
...  

mRNA vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), such as BNT162b2 (Comirnaty®), have proven to be highly immunogenic and efficient but also show marked reactogenicity, leading to adverse effects (AEs). Here, we analyzed whether the severity of AEs predicts the antibody response against the SARS-CoV-2 spike protein. Healthcare workers without prior SARS-CoV-2 infection, who received a prime-boost vaccination with BNT162b2, completed a standardized electronic questionnaire on the duration and severity of AEs. Serum specimens were collected two to four weeks after the boost vaccination and tested with the COVID-19 ELISA IgG (Vircell-IgG), the LIAISON® SARS-CoV-2 S1/S2 IgG CLIA (DiaSorin-IgG) and the iFlash-2019-nCoV NAb surrogate neutralization assay (Yhlo-NAb). A penalized linear regression model fitted by machine learning was used to correlate AEs with antibody levels. Eighty subjects were enrolled in the study. Systemic, but not local, AEs occurred more frequently after the boost vaccination. Elevated SARS-CoV-2 IgG antibody levels were measured in 92.5% of subjects with Vircell-IgG and in all subjects with DiaSorin-IgG and Yhlo-NAb. Gender, age and BMI showed no association with the antibody levels or with the AEs. The linear regression model identified headache, malaise and nausea as AEs with the greatest variable importance for higher antibody levels (Vircell-IgG and DiaSorin-IgG). However, the model performance for predicting antibody levels from AEs was very low for Vircell-IgG (squared correlation coefficient r2 = 0.04) and DiaSorin-IgG (r2 = 0.06). AEs did not predict the surrogate neutralization (Yhlo-NAb) results. In conclusion, AEs correlate only weakly with the SARS-CoV-2 spike protein antibody levels after COVID-19 vaccination with BNT162b2 mRNA.


Author(s):  
Niko Kohmer ◽  
Sandra Westhaus ◽  
Cornelia Rühl ◽  
Sandra Ciesek ◽  
Holger F. Rabenau

AbstractAs the current SARS-CoV-2 pandemic continues, serological assays are urgently needed for rapid diagnosis, contact tracing and for epidemiological studies. So far, there is little data on how commercially available tests perform with real patient samples and if detected IgG antibodies provide protective immunity. Focusing on IgG antibodies, we demonstrate the performance of two ELISA assays (Euroimmun SARS-CoV-2 IgG & Vircell COVID-19 ELISA IgG) in comparison to one lateral flow assay ((LFA) 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 PCR-diagnosed with COVID-19. Most of the SARS-CoV-2 samples were from individuals with moderate to 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) after PCR-diagnosed with COVID-19. With exception of one sample, all positive tested samples in the analysed cohort, using the commercially available assays examined (including the in-house developed IFA), demonstrated neutralizing (protective) properties in the PRNT, indicating a potential protective immunity to SARS-CoV-2. Regarding specificity, there was evidence that samples of endemic coronavirus (HCoV-OC43, HCoV-229E) and Epstein Barr virus (EBV) infected individuals cross-reacted in the ELISA assays and IFA, in one case generating a false positive result (may giving a false sense of security). This need to be further investigated.


2021 ◽  
Vol 8 (25) ◽  
pp. 2216-2221
Author(s):  
Kiranmayi Bogarapu ◽  
Aruna P

BACKGROUND Coronavirus disease - 19 (COVID-19) is an infectious disease caused by a newly discovered coronavirus, severe acute respiratory syndrome coronavirus 2 (SARSCoV-2). Anti-SARS-CoV-2 IgM and IgG antibodies can be detected in almost all patients of COVID-19. We sought to evaluate the antibody responses in COVID19 patients and also analyse their potential role in disease prognostication. METHODS All consecutive COVID-19 patients, between ages 20 - 65 years, encountered between April and July 2020 were included and compared to age-matched controls. Severity of the SARS-CoV-2 infection was categorized as none, mild and severe, based on the presence of symptoms, oxygen saturation and need for respiratory support. Serum levels of IgM and IgG antibody assays were obtained, using chemiluminescence immunoassay, after the 2nd week of presentation (range 14 - 60 days). Antibody titres above 10 AU/ml were taken as elevated. RESULTS Of 50 eligible patients, majority (40/50, 80 %) had mild symptoms and oxygen saturations above 94 %. Of the remainder, 10 % (5/50) had severe infection with need for either high flow nasal cannula oxygen or mechanical ventilation while the remainder (10 %; 5/50) were asymptomatic. IgM and IgG seroconversion were noted in almost all COVID-19 patients (46/50, 92 %) compared to healthy controls. While elevated IgG antibody levels were noted in 76 % (38/50), combined elevation of IgM and IgG antibodies is seen in 16 % (8/50) of patients. Seroconversion was markedly profound in patients with severe infection than those with mild infection. Also, greater seroconversion was noted after 21 days of testing compared to 14th day, especially for IgG. CONCLUSIONS Antibody seroconversion to SARS-CoV-2 occurred in majority of patients with COVID-19, with most salient increase in the IgG antibody levels. Antibody titres correlated directly to the disease severity, suggestive of the potential value of antibodies not only in diagnosis but also in prognostication. KEYWORDS COVID-19, Chemiluminescence Immunoassay, Invasive Mechanical Ventilation, High Flow Nasal Oxygen


2003 ◽  
Vol 10 (6) ◽  
pp. 1043-1050 ◽  
Author(s):  
Ketil Moen ◽  
Johan G. Brun ◽  
Tor Magne Madland ◽  
Turid Tynning ◽  
Roland Jonsson

ABSTRACT The objective of the present study was to investigate immunoglobulin G (IgG) and IgA antibody immune responses to Porphyromonas gingivalis, Prevotella intermedia, Bacteroides forsythus, and Candida albicans in the sera of patients with rheumatoid arthritis (RA), the synovial fluid (SF) of patients with RA (RA-SF samples), and the SF of patients without RA (non-RA-SF samples). An enzyme-linked immunosorbent assay was used to determine IgG and IgA antibody levels in 116 serum samples from patients with RA, 52 RA-SF samples, and 43 non-RA-SF samples; and these were compared with those in SF samples from 9 patients with osteoarthritis (OA-SF samples) and the blood from 100 donors (the control [CTR] group). Higher levels of IgG antibodies against B. forsythus (P < 0.0001) and P. intermedia (P < 0.0001) were found in non-RA-SF samples than in OA-SF samples, and higher levels of IgG antibodies against B. forsythus (P = 0.003) and P. intermedia (P = 0.024) were found in RA-SF samples than in OA-SF samples. Significantly higher levels of IgA antibodies against B. forsythus were demonstrated in both RA-SF and non-RA-SF samples than in OA-SF samples. When corrected for total Ig levels, levels of IgG antibody against B. forsythus were elevated in RA-SF and non-RA-SF samples compared to those in OA-SF samples. Lower levels of Ig antibodies against B. forsythus were found in the sera of patients with RA than in the plasma of the CTR group for both IgG (P = 0.003) and IgA (P < 0.0001). When corrected for total Ig levels, the levels of IgG and IgA antibodies against B. forsythus were still found to be lower in the sera from patients with RA than in the plasma of the CTR group (P < 0.0001). The levels of antibodies against P. gingivalis and C. albicans in the sera and SF of RA and non-RA patients were comparable to those found in the respective controls. The levels of IgG and IgA antibodies against B. forsythus were elevated in SF from patients with RA and non-RA-SF samples compared to those in OA-SF samples. Significantly lower levels of IgG and IgA antibodies against B. forsythus were found in the sera of patients with RA than in the plasma of the CTR group. This indicates the presence of an active antibody response in synovial tissue and illustrates a potential connection between periodontal and joint diseases.


2021 ◽  
Author(s):  
Jia Wei ◽  
Koen B. Pouwels ◽  
Nicole Stoesser ◽  
Philippa C. Matthews ◽  
Ian Diamond ◽  
...  

We investigated anti-spike IgG antibody responses following second doses of ChAdOx1 or BNT162b2 SARS-CoV-2 vaccines in the UK general population. In 186,527 individuals, we found significant boosting of anti-spike IgG by second doses of both vaccines in all ages and using different dosing intervals, including the 3-week interval for BNT162b2. After second vaccination, BNT162b2 generated higher peak levels than ChAdOX1. Antibody levels declined faster at older ages than younger ages with BNT162b2, but were similar across ages with ChAdOX1. With both vaccines, prior infection significantly increased antibody peak level and half-life. Protection was estimated to last for 0.5-1 year after ChAdOx1 and >1 year after BNT162b2, but could be reduced against emerging variants. Reducing the dosing interval to 8 weeks for both vaccines or further to 3 weeks for BNT162b2 may help increase short-term protection against the Delta variant. A third booster dose may be needed, prioritised to more vulnerable people.


2021 ◽  
Author(s):  
Masaaki Takeuchi ◽  
Yukie Higa ◽  
Akina Esaki ◽  
Yosuke Nabeshima ◽  
Akemi Nakazono

Adverse reactions are more common after the second injection of messenger RNA vaccines such as Pfizer/BioNTech's BNT162b2. We hypothesized that the degree and severity of reactogenicity after the second injection reflects the magnitude of antibody production against the SARS CoV-2 virus spike protein (spike IgG). Blood samples were obtained from 67 healthy Japanese healthcare workers three weeks after the first injection and two weeks after the second injection of the BNT162b2 vaccine to measure spike IgG levels. Using questionnaires, we calculated an adverse event (AE) score (0-11) for each participant. The geometric mean of spike IgG titers increased from 1,047 antibody units (AU/mL) (95% CI: 855±1282 AU/mL) after the first injection to 17,378 AU/mL (14,622±20,663 AU/mL) after the second injection. The median AE score increased from 2 to 5. Spike IgG levels after the second injection were negatively correlated with age and positively correlated with spike IgG after the first injection. AE scores after the second injection were not significantly associated with log-transformed spike IgG after the second injection, when adjusted for age, sex, and log-transformed spike IgG after the first injection. Although the sample size was relatively small, reactogenicity after the second injection may not accurately reflect antibody production.


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