scholarly journals Can we predict antibody responses in SARS-CoV-2? A cohort analysis

Author(s):  
Mary Gaeddert ◽  
Philip Kitchen ◽  
Tobias Broger ◽  
Stefan Weber ◽  
Ralf Bartenschlager ◽  
...  

AbstractBackgroundAfter infection with severe acute respiratory syndrome coronavirus (SARS-CoV-2), Immunoglobulin G (IgG) antibodies and virus-specific neutralizing antibodies (nAbs) develop. This study describes antibody responses in a cohort of recovered COVID-19 patients to identify predictors.MethodsWe recruited patients with confirmed SARS-CoV-2 infection from Heidelberg, Germany. Blood samples were collected three weeks after COVID-19 symptoms ended. Participants with high antibody titers were invited for follow-up visits. IgG titers were measured by the Euroimmun Assay, and nAbs titers in a SARS-CoV-2 infection-based assay.Results281 participants were enrolled between April and August 2020 with IgG testing, 145 (51.6%) had nAbs, and 35 (12.5%) had follow-up. The median IgG optical density (OD) ratio was 3.1 (Interquartile range (IQR) 1.6-5.1), and 24.1% (35/145) had a nAb titer>1:80. Higher IgG titers were associated with increased age and more severe disease, and higher nAbs were associated with male gender and CT-value of 25-30 on RT-PCR at diagnosis. The median IgG OD ratio on follow-up was 3.7 (IQR 2.9-5.9), a median increase of 0.5 (IQR −0.3-1.7). Six participants with follow-up nAbs all had titers ≤ 1:80.ConclusionsWhile age and disease severity were correlated with IgG responses, predictive factors for nAbs in convalescent patients remain unclear.

Author(s):  
F. P. Tillmann ◽  
H. Still ◽  
Philipp von Landenberg

Abstract Purpose The predictive value of antibody titers after the first SARS-CoV-2 vaccination and long-term trajectories of antibody titers in hemodialysis patients are unknown. Methods SARS-CoV-2 IgG antibodies and their neutralizing effect six weeks after the first and second vaccination were analysed in 30 hemodialysis patients. IgG titers served to classify participants as responders or non-responders and to calculate sensitivity, specificity, and accuracy. Associations between potential risk factors and post-vaccine non-response were analysed by Mann–Whitney-U test and Chi-Squared test. Long-term follow-up analysis (ANOVA) on the evolution of neutralizing IgG-titers was performed in 24 participants 94 and 135 days after the second immunization. Results IgG antibodies ≥ 1 AU/L (mean 9 ± 20 AU/L) after the first dose were found in 20 patients (66.7%). After the second dose only two participants (6.7%) remained sero-negative and 16.6% showed neutralizing levels below 30%, whereas 25 patients showed IgG antibodies with the high neutralizing activity of 86 ± 18%. Positive IgG antibodies 6 weeks after the first vaccination predicted vaccination effectiveness after two cycles with a specificity of 100%, sensitivity of 76%, and accuracy of 87%. Even low-dose immunosuppressive therapy increased the relative risk for non-response after the first and second dose 1.9 (95% CI 0.8–4.6) and 4.9 (95% CI 1.0–23.8) times, respectively. Over a period of about 4.5 months IgG titers slowly declined by 51% from baseline or by 0.45 AU/mL per day, respectively. Conclusion Two cycles of SARS-CoV-2 vaccination-induced high seroconversion rates comparable to the general population. Immunosuppressive medication is a major risk factor for vaccination non-response. Mounted IgG antibodies showed a high neutralizing capacity as evidence of protective effectiveness. IgG antibodies after the first dose may serve to predict later vaccination outcome. Patients on dialysis display a more rapid decline in antibody titers on long-term follow-up compared to healthy controls.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1383.2-1383
Author(s):  
S. G. Werner ◽  
H. E. Langer ◽  
P. Höhenrieder ◽  
R. Chatelain

Background:PCR (Polymerase Chain Reaction) is generally considered the gold standard for confirming the diagnosis in the early stages of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection. However, in our rheumatology outpatient clinic we observed a significant discrepancy between clinical evidence of COVID-19 and PCR results.Objectives:Aim of this retrospective study was to analyze the significance of PCR and serologic tests in the diagnosis of COVID-19 (Corona Virus Disease 2019) in a cohort of patients with rheumatic diseases.Methods:Between March 2020 and January 2021, 35 patients with a history of established COVID-19 or typical signs and symptoms were identified on the occasion of a routine rheumatology follow-up examination in our institution. Previous diagnostic work-up in external facilities (results of PCR or antibody testing, imaging) was documented. Antibody ELISA-tests (IgG, IgA, IgM, Euroimmun) were performed in patients reporting typical signs and symptoms of COVID-19 in the past.Results:PCR diagnostics had been performed in 15/35 patients (43%), in 13/35 (39%) at the onset of the first symptoms, in 2 subjects only 2 months later. PCR was positive in 7/13 (54%) of those tested early, but negative in the two patients tested later. In 29/35 patients (83%) SARS-CoV-2-ELISA tests were performed on the occasion of the routine rheumatologic examination (interval between first symptoms and testing on average 98 days, median86, range 4-283 days). In two of the initially negative individuals the second PCR was positive. ELISA tests were positive in all patients. SARS-CoV-2 IgM antibodies were positive in only two patients (however 55 and 71 days after disease onset), n=8/29 (28%) IgG only, n=9/29 (31%) IgG and IgA, n=12/29 (41%) IgA only. In these subjects, IgG antibodies did not develop even in the further course. Antibody titers were in part very high, but in part also very low (only just above the normal value), so even low titers were diagnostic obviously. In all patients with negative PCR, ELISA was positive and retrospectively led to confirmation of the diagnosis. Only in 13/35 patients (37%) diagnosis had been made with the onset of the first symptoms or in the course of clinically manifest disease and had led to appropriate quarantine measures and contact tracing by the health authorities. In contrast, in the majority of patients (63%), the diagnosis of COVID-19 infection was only made retrospectively on the occasion of a routine rheumatologic follow-up. However, 5 of these 22 patients (23%) had quarantined themselves during the symptomatic phase. Titer histories were available from 12 patients. The titer became negative in 7 patients, after a mean of 188 days (median 202, min 51, max 296 days), and remained positive in 5 individuals (mean 190 days, median 191, min 122, max 260 days). The change of the titer was independent of disease severity or antirheumatic therapy.Conclusion:The results suggest that the importance of PCR in the diagnosis of COVID-19 may be overestimated. Therefore, antibody testing for SARS-CoV-2 should be performed in cases of clinical suspicion and negative PCR. In antibody diagnostics, special features were observed compared to other viruses, in particular, in some patients only low antibody titers or the absence of seroconversion with lack of development of IgG antibodies. Normalization of antibody titers in some patients supports the recommendation to vaccinate even after expired COVID-19 disease.Disclosure of Interests:None declared


Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 284
Author(s):  
Hulda R. Jonsdottir ◽  
Michel Bielecki ◽  
Denise Siegrist ◽  
Thomas W. Buehrer ◽  
Roland Züst ◽  
...  

Neutralizing antibodies are an important part of the humoral immune response to SARS-CoV-2. It is currently unclear to what extent such antibodies are produced after non-severe disease or asymptomatic infection. We studied a cluster of SARS-CoV-2 infections among a homogeneous population of 332 predominantly male Swiss soldiers and determined the neutralizing antibody response with a serum neutralization assay using a recombinant SARS-CoV-2-GFP. All patients with non-severe COVID-19 showed a swift humoral response within two weeks after the onset of symptoms, which remained stable for the duration of the study. One month after the outbreak, titers in COVID-19 convalescents did not differ from the titers of asymptomatically infected individuals. Furthermore, symptoms of COVID-19 did not correlate with neutralizing antibody titers. Therefore, we conclude that asymptomatic infection can induce the same humoral immunity as non-severe COVID-19 in young adults.


2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
C. Q. Hoang ◽  
H. D. Nguyen ◽  
N. X. Ho ◽  
T. H. T. Vu ◽  
T. T. M. Pham ◽  
...  

Background. Scarce information exists about immunity to hand, foot, and mouth disease (HFMD) among household contacts of index cases in Vietnam and what that means for reducing ongoing HFMD transmission in the community. Methods. We analyzed neutralizing antibodies (NT) and the incidence of enterovirus (EVs) infection among household contacts of index cases in a province where HFMD remains endemic. Throat swab and 2 mL blood samples from household contacts were collected at enrollment, during and after 2 weeks follow-up. Results. The incidence of EV-A71 infection among household contacts was 40/84 (47.6%, 95% Cl: 36.9-58.3%), compared with 106/336 (31.5%, 95% Cl: 26.6-36.5%) for CV-A6 and 36/107 (33.6%, 95% Cl: 24.7-42.6%) for CV-A16. The incidence of CV-A6 infection was fairly constant across ages; in contrast, CV-A71 and CV-A16 had some variation across ages. At baseline, higher geometric mean titer (GMT) of EV-A71, CV-A6, and CV-A16 antibody titers was found for 25-34-year groups (range 216.3 to 305.0) compared to the other age groups. There was a statistically significant difference in GMT values of CV-A6 and CV-A16 between those who had an infection or did not have infection among households with an index case of these serotypes. Conclusions. Our results indicated that adults were becoming infected with HFMD and could be contributing to the transmission. There is, therefore, a need for considering the household setting as an additional target for intervention programs for HFMD.


2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
F. Castiglione ◽  
F. Mantile ◽  
P. De Berardinis ◽  
A. Prisco

The immune system is able to respond more vigorously to the second contact with a given antigen than to the first contact. Vaccination protocols generally include at least two doses, in order to obtain high antibody titers. We want to analyze the relation between the time elapsed from the first dose (priming) and the second dose (boost) on the antibody titers. In this paper, we couplein vivoexperiments with computer simulations to assess the effect of delaying the second injection. We observe that an interval of several weeks between the prime and the boost is necessary to obtain optimal antibody responses.


2004 ◽  
Vol 53 (5) ◽  
pp. 435-438 ◽  
Author(s):  
Weijun Chen ◽  
Zuyuan Xu ◽  
Jingsong Mu ◽  
Ling Yang ◽  
Haixue Gan ◽  
...  

To understand the time-course of viraemia and antibody responses to severe acute respiratory syndrome-associated coronavirus (SARS-CoV), RT-PCR and ELISA were used to assay 376 blood samples from 135 SARS patients at various stages of the illness, including samples from patients who were in their early convalescent phase. The results showed that IgM antibodies decreased and became undetectable 11 weeks into the recovery phase. IgG antibodies, however, remained detectable for a period beyond 11 weeks and were found in 100 % of patients in the early convalescent phase. SARS-CoV viraemia mainly appeared 1 week after the onset of illness and then decreased over a period of 1 month, becoming undetectable in the blood samples of the convalescent patients. At the peak of viraemia, viral RNA was detectable in 75 % of blood samples from patients who were clinically diagnosed with SARS 1 or 2 weeks before the test.


2021 ◽  
Author(s):  
Naranjargal J. Dashdorj ◽  
Oliver F. Wirz ◽  
Katharina Roeltgen ◽  
Emily Haraguchi ◽  
Anthony S. Buzzanco ◽  
...  

Different vaccines for SARS-CoV-2 are approved in various countries, but few direct comparisons of the antibody responses they stimulate have been reported. We collected plasma specimens in July 2021 from 196 Mongolian participants fully vaccinated with one of four Covid vaccines: Pfizer/BioNTech, AstraZeneca, Sputnik V and Sinopharm. Functional antibody testing with a panel of nine SARS-CoV-2 viral variant RBD proteins reveal marked differences in the vaccine responses, with low antibody levels and RBD-ACE2 blocking activity stimulated by the Sinopharm and Sputnik V vaccines in comparison to the AstraZeneca or Pfizer/BioNTech vaccines. The Alpha variant caused 97% of infections in Mongolia in June and early July 2021. Individuals who recover from SARS-CoV-2 infection after vaccination achieve high antibody titers in most cases. These data suggest that public health interventions such as vaccine boosting, potentially with more potent vaccine types, may be needed to control the COVID-19 pandemic in Mongolia and worldwide.


2021 ◽  
Author(s):  
Tomoko Hamaya ◽  
Shingo Hatakeyama ◽  
Tohru Yoneyama ◽  
Yuki Tobisawa ◽  
Hirotake Kodama ◽  
...  

Abstract We aimed to evaluate the rate of anti–SARS-CoV-2 IgG seropositivity and investigated factors associated with seropositivity after the second SARS-CoV-2 mRNA vaccination in kidney transplant (KT) recipients. This retrospective study conducted between June 2021 and November 2021 included 106 KT recipients and 127 healthy controls who received the second dose of the BNT162b2 mRNA vaccine at least seven days before the measurement of antibody titers. The titers of immunoglobulin G (IgG) antibodies against the receptor-binding domain of SARS-CoV-2 spike (S) protein were determined. Seropositivity was defined as an anti–SARS-CoV-2 IgG level of ≥15 units/mL, which was considered as the presence of sufficient neutralizing antibodies. The median ages and the seroprevalence rates of the healthy controls and KT recipients were 68 and 56 years and 98% and 22%, respectively. Univariate logistic regression analysis revealed that age >53 years, rituximab use, mycophenolate mofetil use, and KT vintage <7 years were negatively associated with anti–SARS-CoV-2 IgG seropositivity in KT recipients. Humoral response after the second BNT162b2 mRNA vaccine was greatly hindered by immunosuppression therapy in KT recipients. Older age, rituximab use, mycophenolate mofetil use, and KT vintage may play key roles in seroconversion.


2021 ◽  
Author(s):  
Sabrina E Racine-Brzostek ◽  
Jim Yee ◽  
Ashley Sukhu ◽  
Yuqing Qiu ◽  
Sophie Rand ◽  
...  

Longitudinal studies are needed to evaluate the SARS-CoV-2 mRNA vaccine antibody response under real-world conditions. This longitudinal study investigated the quantity and quality of SARS-CoV-2 antibody response in 846 specimens from 350 subjects: comparing BNT162b2-vaccinated individuals (19 previously diagnosed with COVID-19 [RecoVax]; 49 never been diagnosed [NaiveVax]) to 122 hospitalized unvaccinated (HospNoVax) and 160 outpatient unvaccinated (OutPtNoVax) COVID-19 patients. NaiveVax experienced a delay in generating SARS-CoV-2 total antibody levels (TAb) and neutralizing antibodies (SNAb) after the 1st vaccine dose (D1), but a rapid increase in antibody levels was observed after the 2nd dose (D2). However, these never reached the robust levels observed in RecoVax. In fact, NaiveVax TAb and SNAb levels decreased 4-weeks post-D2 (p=0.003;p<0.001). For the most part, RecoVax TAb persisted throughout this study, after reaching maximal levels 2-weeks post-D2; but SNAb decreased significantly ~6-months post-D1 (p=0.002). Although NaiveVax avidity lagged behind that of RecoVax for most of the follow-up periods, NaiveVax did reach similar avidity by ~6-months post-D1. These data suggest that one vaccine dose elicits maximal antibody response in RecoVax and may be sufficient. Also, despite decreasing levels in TAb and SNAb overtime, long-term avidity maybe a measure worth evaluating and possibly correlating to vaccine efficacy.


BMC Medicine ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Ioannis P. Trougakos ◽  
Evangelos Terpos ◽  
Christina Zirou ◽  
Aimilia D. Sklirou ◽  
Filia Apostolakou ◽  
...  

Abstract Background Coronavirus SARS-CoV-2, the causative agent of COVID-19, has caused a still evolving global pandemic. Given the worldwide vaccination campaign, the understanding of the vaccine-induced versus COVID-19-induced immunity will contribute to adjusting vaccine dosing strategies and speeding-up vaccination efforts. Methods Anti-spike-RBD IgGs and neutralizing antibodies (NAbs) titers were measured in BNT162b2 mRNA vaccinated participants (n = 250); we also investigated humoral and cellular immune responses in vaccinated individuals (n = 21) of this cohort 5 months post-vaccination and assayed NAbs levels in COVID-19 hospitalized patients (n = 60) with moderate or severe disease, as well as in COVID-19 recovered patients (n = 34). Results We found that one (boosting) dose of the BNT162b2 vaccine triggers robust immune (i.e., anti-spike-RBD IgGs and NAbs) responses in COVID-19 convalescent healthy recipients, while naïve recipients require both priming and boosting shots to acquire high antibody titers. Severe COVID-19 triggers an earlier and more intense (versus moderate disease) immune response in hospitalized patients; in all cases, however, antibody titers remain at high levels in COVID-19 recovered patients. Although virus infection promotes an earlier and more intense, versus priming vaccination, immune response, boosting vaccination induces antibody titers significantly higher and likely more durable versus COVID-19. In support, high anti-spike-RBD IgGs/NAbs titers along with spike (vaccine encoded antigen) specific T cell clones were found in the serum and peripheral blood mononuclear cells, respectively, of vaccinated individuals 5 months post-vaccination. Conclusions These findings support vaccination efficacy, also suggesting that vaccination likely offers more protection than natural infection. Graphical abstract


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