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BackgroundAcetaminophen (APAP = paracetamol) may potentially impact vaccine-associated immune responses as the intake of APAP has been associated with a worse outcome in tumor patients receiving checkpoint inhibitors.[1]Different DMARD regimen have been shown to impair the humoral immune response to mRNA SARS-CoV-2 vaccines in patients with rheumatoid arthritis but the effect of paracetamol has not been explored thus far.ObjectivesTo analyse whether the intake of APAP may interfere with antiviral humoral immune responses following two doses of an anti-SARS-CoV-2 mRNA based vaccine in patients with rheumatoid arthritis (RA) on DMARD therapy.MethodsThe RECOVER trial (Rheumatoid Covid-19 Vaccine Immune Response) was a non-randomised, prospective observational control group trial and enrolled 77 RA patients on DMARD therapy and 21 healthy controls (HC). We performed a posthoc analysis of blood samples taken before the first vaccine dose (T0), two (T1) and three (T2) weeks after the first and second vaccine dose, and at 12 (T3) weeks. APAP intake was measured using ELISA. The antibody response (anti-S) to the receptor binding domain (RBD) within the SARS-CoV-2 S1 protein was measured with the Elecsys Anti-SARS-CoV-2-S (Roche Diagnostics GmbH) test. The neutralizing activity NT50 at week 12 was assessed using an HIV-based pseudovirus neutralization assay against Wuhan-Hu-1.ResultsBaseline characteristics of participants are detailed in Table 1. The immunogenicity analyses were based on 73 RA patients after exclusion of 4 patients with previously unnoticed SARS-CoV-2 infection (positive for anti-nucleoprotein at baseline). APAP was detected in serum samples from 34/73 (25%) RA patients and in 7/21 (33%) HC (least at one timepoint T0, T1 and/or T2). APAP intake in HC did not affect levels of anti-S at any timepoint and all HC developed potent neutralizing activity (NT50 ≥ 250) at week 12. RA patients, who tested positive for APAP at T1, showed comparable anti-S levels at T1, T2 and T3 compared to RA patients not exposed to APAP. The detection of APAP at T2 corresponded to lower anti-S levels at T2 (Figure 1 A, B). The detection of APAP at T2 was associated with a significantly lower SARS-CoV-2 neutralizing activity at week 12 compared to patients without perivaccination APAP exposure (p =0.04) (Figure 1 C).ConclusionA decrease of antiviral humoral immune responses was observed in RA patients (but not in HC) who were exposed to APAP at the time of the second mRNA vaccine dose compared to patients in whom APAP was not detected. Our data suggest that the use of paracetamol within the time period around vaccination may impair vaccine-induced immune responses in patients with an already higher risk for blunted immune responses.Reference[1]Bessede A et al. Ann Oncol 2022;33: 909-915Table 1.Baseline characteristics: RA patients and HC with/without APAP exposureRA APAP – n = 37RA APAP + n = 36p-valueHC APAP – n = 8HC APAP + n = 13p-valueAge (yrs), mean (± SD)62 (13)67 (10)0.07 (NS)45 (12)44 (14)0.90 (NS)Female sex, n (%)24 (65)19 (53)0.29 (NS)2 (25)5 (38)0.53 (NS)Vaccination type/schedulemRNA-1273, n (%)4 (11)8 (22.2)0.19 (NS)0 (0)0 (0)BNT162b2, n (%)33 (89)28 (77.8)0.19 (NS)8 (100)13 (100)RA disease characteristicsACPA ± RF, n (%)17/37 (46)19/36 (53)0.56 (NS)NANANARA disease duration (yrs ± SD)9.2 (9.8)10.2 (8.1)0.67 (NS)NANANADMARD therapycsDMARD-mono, n (%)13/37 (35)9/36 (25)0.35 (NS)NANANAbDMARD-mono/combo, n (%)16/37 (43)16/36 (44)0.92 (NS)NANANAtsDMARDs-mono/combo, n (%)8/37 (22)11/36 (31)0.38 (NS)NANANAPrednisone, n (%)15/37 (41)12/36 (33.3)0.52 (NS)NANANAMean daily dose prednisone (mg ± SD)4.6 ± 1.13.9 ± 2.30.39 (NS)NANANA* APAP = acetaminophenFigure 1.Acknowledgements:NIL.Disclosure of InterestsNone Declared.
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Patients with inflammatory rheumatic diseases (IRD) have an increased risk for a worse COVID-19 outcome, and impaired immune responses following mRNA COVID-19 vaccines have been observed. In this prospective observational study, we compared the anti-S1 response following vaccination with BNT162b2 and mRNA- 1273 in a large cohort of IRD patients and assessed the effect of different immunomodulatory treatments. Patients from SCQM, the Swiss IRD cohort, who assented to an mRNA COVID-19 vaccine were recruited into the study between 3/2021-9/2021. Participants answered the study questionnaire via the mySCQM patient app and provided self-collected capillary blood samples at baseline, 4, 12, and 24 weeks post second vaccine dose. Samples were tested for IgG antibodies against the S1 domain of the SARS-CoV-2 spike protein using the EUROIMMUN ELISA. We examined differences in antibody titres depending on the vaccine and treatment received, while adjusting for age and history of SARSCoV- 2 infection, by applying mixed effects continuous outcome logistic regression models at each timepoint. Eligible samples were obtained from 564 IRD patients (mean age 53 y (s.d. 12 y), 66% female) with 36% RA, 37%, axSpA, 21% PsA, and 6% UA (undifferentiated arthritis), on no medication (no DMARD & no steroids 15%), csDMARD (9%), TNFi (48%), IL-6/17/23i (14%), JAKi (6%), rituximab (4%), abatacept (3%), and PDE4i (1%) in mono/combination therapy at baseline. 10% of patients had a past SARS-CoV-2 infection, 54% received BNT162b2, 46% mRNA-1273. Independently of the disease, treatment, and history of SARS-CoV- 2 infection, the odds of having higher anti-S1 titres at 4, 12, and 24 weeks post second vaccine dose were, respectively, 3.3, 3.9, and 3.8 times higher with mRNA-1273 compared to BNT162b2 for the average-aged patient of this population (p <0.0001). Moreover, with every year of age, the odds of higher anti-S1 levels increased by 3% to 5% following mRNA-1273 vs BNT162b2 vaccination (p <0.05), indicating an additional benefit for elderly IRD patients. Among monotherapies, rituximab, abatacept, JAKi, and TNFi had the highest odds of reduced anti-S1 responses compared to no medication. Patients on specific combination therapies showed significantly reduced antibody responses compared to respective monotherapies. Our results suggest that in IRD patients, vaccination with mRNA- 1273 vs BNT162b2 results in higher anti-S1 antibody titres, and has an additional benefit in elderly patients.
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Background: Lower seroconversion rates have been reported in patients with rheumatic diseases receiving immunomodulatory therapies following a standard mRNA-based vaccine regimen. Data with regard to immunogenicity and safety of a 3rd vaccine dose in this patient population is limited1. Objectives: We aim to study immunogenicity, vaccine associated side effects and the occurrence of fares in RA patients unresponsive to a standard vaccine regimen eligible for a 3rd vaccine dose. Methods: RA patients who had a low or absent anti-S1 response after 12 (Cohort A) or 24 weeks (Cohort B) following a standard vaccination regimen received a 3rd vaccine dose. Temporary discontinuation of DMARD therapy was recommended. Serum samples were collected before, 2, 12, and 24 weeks after the 3rd vaccine dose. Quantitative measurement of anti-S was performed using the Roche Elecsys Anti-SARS-CoV-2 spike subunit assay. Neutralizing activity (NT50) against Wuhan WT and aasβ-, y-, and ô-variants was assessed by using a HIV-based pseudovirus system. Results: Baseline characteristics are shown in Table 1. 45/47 patients temporarily discontinued DMARD therapy: Mtx and JAKi were paused one 1 week before/restarted 2 weeks after the 3rd vaccine dose, bDMARDs were paused 2 weeks before/restarted 2 weeks after the 3rd dose. Local pain and/or systemic vaccine associated side effects following the 3rd vaccine dose were reported in 12/17 (71%) in Cohort A, and 10/29 (35%) patients in Cohort B (p = 0.018). Flares were defned as loss of low disease activity (LDA), subsequent to the 3rd vaccine dose and occurred in 17/47 (36%) patients (p = 0.0332) with comparable frequencies in both cohorts (41% Cohort A, 33% Cohort B (NS)). Low or absent anti-S titers were confrmed before the third vaccination (Cohort A: median 19.5 U/ml, IQR 0.47-57;cohort B: median 65.9 U/ml, IQR 22-154) (p = 0.0018). Two weeks after the 3rd dose, a rapid and signifcant increase in anti-S were observed in 12/17 (82%) and 25/28 (89%) patients (Cohort A: median 2500 U/ml, IQR 798-2500;Cohort B: median 2500 U/ml, IQR 2500-2500) (NS). High levels of anti-S were maintained in the majority of patients 55% (11/20) until week 12 in both cohorts (Figure 1). NT50 against Wuhan-WT and other variants was assessed in 21 patients 2 weeks after the 3rd vaccine dose revealing a low or absent NT50 against delta in 38% of patients despite a median anti-S response of 2500 U/ml (IQR 798-2500). 14/21 patients had peak anti-S titres of 2500 U/ml, of those 12/14 developed a strong NT50 response against the delta variant. Conclusion: Our data demonstrate that a 3rd vaccine dose, maybe complimented by temporary discontinuation of DMARD therapy, may lead to a rapid increase in anti-S antibodies when using a homologous vaccine and profound neutralizing activity in the majority of RA patients previously unresponsive to a standard two dose regimen. This seems to be independent of the interval to the previous standard vaccine regimen. As fares occurred in 36% of all patients, the necessity and length of DMARD discontinuation should be explored in more detail to balance between sustained control of disease activity and optimized vaccine induced immune responses.
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Background: Patients on immunomodulatory treatments mount an attenuated immune response following mRNA COVID-19 vaccination, yet longterm studies of vaccine-induced anti-SARS-CoV-2 antibody (Ab) kinetics are missing. Objectives: In this prospective observational study, we mapped the humoral antibody response to mRNA COVID-19 vaccines up to 24 weeks post full vaccination in patients with infammatory rheumatic diseases (IRDs). We aimed to assess differences due to treatment, age, past SARS-CoV-2 infection, and vaccine (BNT162b2 vs. mRNA-1273). Methods: Adult patients from the SCQM cohort who assented to an mRNA COVID-19 vaccine were recruited between 3/21-9/21. Participants answered questionnaires via an app and received kits for the self-collection of capillary blood samples at baseline, 4, 12, and 24 weeks post full vaccination. Samples were tested for IgG Ab against the S1 domain of the SARS-CoV-2 spike protein (anti-S1-IgG) using the EUROIMMUN ELISA. To examine differences in Ab titres arising from the defned parameters, while accounting for inter-assay variability, mixed effects continuous outcome logistic regression models were applied at each timepoint. Results: Samples were obtained from 570 patients: 67% female, mean age 53 y (SD 12 y) with 37% RA, 36% axSpA, 21% PsA, and 6% UA (undifferentiated arthritis), on no medication (no DMARDs & no glucocorticoids;15%), csD-MARDs (10%), TNFi (48%), IL-1/6/17/23i (14%), JAKi (6%), rituximab (RTX;4%), or abatacept (ABA;2%) in mono/combination therapy at the frst vaccination. 10% of patients had a past SARS-CoV-2 infection, 54% received BNT162b2, 46% mRNA-1273. For any Ab threshold, the odds of having a higher Ab titre at 4, 12, and 24 weeks post full vaccination were 3.3-4 times higher with mRNA-1273 compared to BNT162b2 (Table 1, Figure 1). TNFi, JAKi, RTX, and ABA as monotherapy resulted in signifcantly lower Ab levels compared to no medication at almost all timepoints. In combination therapy, TNFi, IL-1/6/17/23i, RTX, and csDMARDs led to consistently lower Ab titres at all timepoints compared to respective monotherapy. Conclusion: Compared to no medication, some immunomodulatory therapies resulted in markedly lower Ab levels at all timepoints. In IRD patients, a past SARS-CoV-2 infection resulted in strikingly increased immunogenicity, as did mRNA-1273 compared to BNT162b2.
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Background: Vaccines are highly effective in preventing COVID-19 associated hospitalization and deaths. Strong and persistent immune responses are critical to provide protection for patients with immunomodulatory therapies. Objectives: To assess humoral and cellular immune responses following 2 doses of an anti-SARS-CoV-2 mRNA based vaccine in rheumatoid arthritis (RA). Immune responses in patients treated with csDMARDs, bDMARDs (with the exception of rituximab) and JAK inhibitors were compared to healthy controls (HC) over 24 weeks. In addition, disease activity by CDAI and vaccine-induced side effects were prospectively monitored. Methods: The RECOVER trial (Rheumatoid Covid-19 Vaccine Immune Response) is a non-randomised, prospective observational control group trial and enrolled 77 RA patients on DMARD therapy and 21 HC. Clinical assessment and blood sampling was performed at baseline, 3 weeks after the 1st and 2 weeks after the 2nd vaccine dose and at week 12 and 24 after the 1st. Antibody response to the receptor binding domain (RBD) within the SARS-CoV-2 S1 protein was measured with the Elecsys Anti-SARS-CoV-2-S (Roche Diagnostics GmbH) test. The seroprofling assay ABCORA, which has been suggested as a surrogate for neutralization,1 was used to determine IgG, IgA and IgM responses to RBD, S1, S2 and N. The neutralizing activity NT50 at week 12 was assessed against Wuhan-Hu-1 pseudoviruses (HIV-based). IFN-y ELISpots were applied to detect spike-reactive T cell responses after in vitro stimulation with a spike peptide mix. Results: Baseline characteristics of participants are detailed in Table 1. Vaccination was well tolerated with no differences between RA patients and HC. At baseline, the majority of RA patients were in remission/LDA (57/77, 74%), this proportion decreased to 51% (39/77) after the second vaccine dose (p = 0.005). Treatment adjustments were required in 11/77 patients. The immunogenicity analyses were based on 73 RA patients after exclusion of 4 patients with previously unnoticed SARS-CoV-2 infection (positive for anti-nucleoprotein). In contrast to HC, anti-S titers were lower at all timepoints with signifcantly reduced titers observed in patients on abatacept and JAK inhibitors (Figure 1). Potent neutralizing activity (NT50 ≥ 250)) was detected in all HC at week 12, in contrast to 62% RA patients. NT50 correlated to the results based on the ABCORA assay. Peak anti-S titers (2 weeks after 2nd vaccine) were predictive of NT50 ≥ 250 at week 12 (p < 0.0001). In contrast to marked differences in the humoral immune responses, spike-protein specifc IFN-α secreting T cells were largely unaltered by different DMARD regimen. Conclusion: RA patients, in comparison with HC, revealed a slower kinetic and lower magnitude of humoral immune responses depending on the treatment regimen while T cell responses were largely maintained. Peak anti-S responses two weeks after the second vaccine were able to predict the development of potent neutralizing activity and should therefore be considered to individually tailor vaccination strategies.
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Background: Unravelling autoimmune targets triggered by SARS-CoV-2 infection may provide crucial insights in the physiopathology of the disease and foster the development of potential therapeutic candidate targets and prognostic tools. SARS-CoV-2 autoimmune-mediated inflammation have been reported, but the existence of autoantibodies against apolipoprotein A-1 (anti-apoA-1 IgG) in COVID-19 remains unexplored. Anti-apoA-1 IgGs have emerged as an independent biomarker for cardiovascular disease and mortality in humans with proinflammatory and proatherogenic functions in vivo and in vitro. Purpose:We want to determine i) the degree of homology between SARSCoV-2, apoA-1, and Toll-like receptor-2 (TLR2) epitopes, ii) the association between anti-SARSCoV2 and anti-apoA-1 IgGs, and iii) their relationship to prognosis. Methods: We performed bioinformatics modelling coupled with mimetic peptides engineering, as well as functional and competition assays with antibodies to identify molecular mimicry between SARS-CoV-2, apoA-1 and TLR2 epitopes. Anti-Spike domain 1 (SD1) IgGs, anti-apoA-1 IgGs and against mimic peptides, as well as cytokines were assessed by immunoassays on a case-control (n=101), an intensive care unit (ICU;n=126) with a 28-days follow-up for overall mortality, and a general population cohort (n=663) with available samples in the pre and post-pandemic period. Results: Linear sequence homologies and antibodies cross-reactivity between apoA-1, TLR2, and Spike epitopes were identified. Overall, antiapoA-1 IgG levels were higher in COVID-19 patients or anti-SARS-CoV-2 seropositive individuals than in healthy donors or anti-SARS-CoV-2 seronegative individuals (p<0.0001). Significant and similar associations were noted between anti-apoA-1, anti-SARS-CoV-2 IgG, cytokines, and lipid profile. In ICU patients, anti-SARS-CoV-2 and anti-apoA-1 seroconversion rates displayed similar 7-days kinetics, reaching 82% for anti-apoA-1 seropositivity. C-statistics (CS) indicated that baseline anti-Spike/TLR2 mimic-peptide IgGs displayed a significant prognostic accuracy for overall mortality at 28 days (CS: 0.64;p=0.02). In the general population, SARSCoV-2 exposure increased baseline anti-apoA-1 IgG levels. Conclusions: COVID-19 induces a marked humoral response against the major protein of high-density lipoproteins. As a correlate of poorer prognosis in other clinical settings, such autoimmunity signatures may relate to long-term COVID-19 prognosis assessment and warrant further scrutiny in the current COVID-19 pandemic.
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Background: Vaccination against anti SARS-CoV-2 is recommended in patients with rheumatic diseases, but limited data are available in patients on immunosuppressive therapy. The objective of this study is to analyse magnitude and kinetics of mRNA vaccine induced anti-S1 titers in patients with rheumatoid arthritis (RA) on DMARD therapy and healthy controls (HC). Methods: 77 RA patients and 21 HC were eligible for vaccination according to federal guidelines and were enrolled in the prospective RECOVER trial (Rheumatoid Covid-19 Vaccine Immune Response) between 10th January and March 15th 2021. Vaccination itself was not part of the study. The anti-SARS-CoV-2 vaccines mRNA-1273 and BNT162b2 were applied according to the manufacturers' recommendations. All patients continued their DMARD therapy. Serum samples were obtained before the first vaccine, 3 weeks after the first, 2 weeks after the second vaccine and after 12 weeks. Quantitative antibody testing was performed using the Roche Elecsys® Anti-SARS-CoV-2 S1 assay that measures antibodies to the S1 protein (range 0.4-2500 U/l) and nucleoprotein to exclude subclinical SARS-CoV-2 infection. A threshold level of anti-S1 that correlates to neutralization has been proposed at 133 U/l.1. More recently, even lower cut-off levels (>15 U/l) have been suggested. 2 Results: At present, 43/77 patients reached the 12 week timepoint after the first vaccine dose. 4/77 patients with antibodies to nucleoprotein at baseline were excluded from the analysis. Median titers of anti-S1 antibodies were significantly lower in RA patients at all time points. 3 weeks after the first vaccine dose, 9/21 HC but only 1/73 RA patients developed anti-S1 titers exceeding 133 U/l (p = 0.0001) or 15 U/l (19/21 HC versus 11/73 RA patients). Two weeks after the second vaccine, the proportion of RA patients with anti-S1 titers exceeding 133 u/l was still significantly lower than in HC (75.3% versus 100%, p = 0.01). Of note, RA patients on abatacept (n = 9) or JAK inhibitors (n = 19) achieved both threshold levels significantly less frequently compared to patients on csDMARDs and/or anti-cytokine directed biologics. Conclusions: The development of anti-S1 titers after vaccination with mRNA vaccines against SARS-CoV-2 in patients with RA is overall slower and results in lower antibody titers in comparison to healthy controls.
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Background and Aims: Unravelling autoimmune targets triggered by SARS-CoV-2 infection may provide crucial insights in the physiopathology of the disease and foster the development of potential therapeutic candidate targets and prognostic tools. We want to determine whether SARS-CoV-2 exposure could trigger a humoral response against apolipoprotein A-1 (anti-apoA-1 IgG) through molecular mimicry and assess its relationship to patient prognosis. Methods: Anti-Spike domain 1 (SD1) IgGs, anti-apoA-1 IgGs and against mimic peptides, as well as cytokines were assessed by immunoassays on a case-control (n=101), an intensive care unit (ICU;n=126) with a 28-days follow-up, and a general population cohort (n=663) with available samples in the pre and post-pandemic period. Results: Linear sequence homologies and antibodies cross-reactivity between apoA-1, TLR2, and Spike epitopes were identified. Overall, anti-apoA-1 IgG levels were higher in COVID-19 patients or anti-SARS-CoV-2 seropositive individuals than in healthy donors or anti-SARS-CoV-2 seronegative individuals (p<0.0001). Significant and similar associations were noted between anti-apoA-1, anti-SARS-CoV-2 IgG, cytokines, and lipid profile. In ICU patients, anti-SARS-CoV-2 and anti-apoA-1 seroconversion rates displayed similar 7-days kinetics, reaching 82% for anti-apoA-1 seropositivity. C-statistics (CS) indicated that anti-Spike/TLR2 mimic-peptide IgGs displayed a significant prognostic accuracy for overall mortality at 28 days (CS: 0.64;p=0.02). In the general population, SARS-CoV-2 exposure increased baseline anti-apoA-1 IgG levels. Conclusions: COVID-19 induces a marked humoral response against the major protein of high-density lipoproteins. As a correlate of poorer prognosis in other clinical settings, such autoimmunity signatures may relate to long-term COVID-19 prognosis assessment and warrant further scrutiny in the current COVID-19 pandemic.
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OBJECTIVES: To evaluate longitudinally the persistence of humoral immunity for up to 6 months in a cohort of hospital employees with mild coronavirus disease 2019 (COVID-19). METHODS: We measured anti-RBD (receptor binding domain of viral spike protein), anti-N (viral nucleoprotein) and neutralizing antibodies at 1, 3 and 6 months after mostly mild COVID-19 in 200 hospital workers using commercial ELISAs and a surrogate virus neutralization assay. RESULTS: Antibodies specific for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) persisted in all participants for up to 6 months. Anti-RBD geometric mean concentrations (GMCs) progressively increased between months 1 (74.2 U/mL, 95%CI: 62.7-87.8), 3 (103.2 U/mL, 95%CI: 87.9-121.2;p < 0.001), and 6 (123.3 U/mL, 95%CI: 103.4-147.0;p < 0.001) in the whole cohort. Anti-N antibodies were detectable in >97% at all times. Neutralizing antibodies were detectable in 99.5% of participants (195/196) at 6 months post infection. Their GMC progressively decreased between months 1 (20.1 AU/mL, 95%CI: 16.9-24.0), 3 (15.2 AU/mL, 95%CI: 13.2-17.6;p < 0.001) and 6 (9.4 AU/mL, 95%CI: 7.7-11.4;p < 0.001). RBD-ACE2-inhibiting antibody titres and anti-RBD antibody concentrations strongly correlated at each timepoint (all r > 0.86, p < 0.001). Disease severity was associated with higher initial anti-RBD and RBD-ACE2-inhibiting antibody titres, but not with their kinetics. CONCLUSIONS: Neutralizing antibodies persisted at 6 months in almost all participants, indicating more durability than initially feared. Anti-RBD antibodies persisted better and even increased over time, possibly related to the preferential detection of progressively higher-affinity antibodies.
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OBJECTIVES: To validate the diagnostic accuracy of a Euroimmun SARS-CoV-2 IgG and IgA immunoassay for COVID-19. METHODS: In this unmatched (1:2) case-control validation study, we used sera of 181 laboratory-confirmed SARS-CoV-2 cases and 326 controls collected before SARS-CoV-2 emergence. Diagnostic accuracy of the immunoassay was assessed against a whole spike protein-based recombinant immunofluorescence assay (rIFA) by receiver operating characteristic (ROC) analyses. Discrepant cases between ELISA and rIFA were further tested by pseudo-neutralization assay. RESULTS: COVID-19 patients were more likely to be male and older than controls, and 50.3% were hospitalized. ROC curve analyses indicated that IgG and IgA had high diagnostic accuracies with AUCs of 0.990 (95% Confidence Interval [95%CI]: 0.983-0.996) and 0.978 (95%CI: 0.967-0.989), respectively. IgG assays outperformed IgA assays (p=0.01). Taking an assessed 15% inter-assay imprecision into account, an optimized IgG ratio cut-off > 2.5 displayed a 100% specificity (95%CI: 99-100) and a 100% positive predictive value (95%CI: 96-100). A 0.8 cut-off displayed a 94% sensitivity (95%CI: 88-97) and a 97% negative predictive value (95%CI: 95-99). Substituting the upper threshold for the manufacturer's, improved assay performance, leaving 8.9% of IgG ratios indeterminate between 0.8-2.5. CONCLUSIONS: The Euroimmun assay displays a nearly optimal diagnostic accuracy using IgG against SARS-CoV-2 in patient samples, with no obvious gains from IgA serology. The optimized cut-offs are fit for rule-in and rule-out purposes, allowing determination of whether individuals in our study population have been exposed to SARS-CoV-2 or not. IgG serology should however not be considered as a surrogate of protection at this stage.