ABSTRACT
Background Patients with hematologic malignancy have a higher risk of death from COVID-19 compared to the general population. A blunted immune response from both the underlying disease and applied treatment may contribute to development of more severe forms of COVID-19, absence of seroconversion, prolonged viral shedding, and might also impair humoral vaccine response. Factors influencing efficacy of SARS-CoV-2 vaccines in this patient population are still insufficiently explored. Methods We prospectively enrolled 143 patients with malignant or non-malignant hematologic diseases from University Hospital Centre Zagreb vaccinated between January and June 2021 with either mRNA-1273 (Moderna), BNT162b2 mRNA (Pfizer-BioNTech), or ChAdOx1 nCoV-19 (Oxford-AstraZeneca) vaccines. A qualitative assay against SARS-CoV-2 nucleocapsid antigen was used to detect prior infection;these patients (n=23) were excluded from the final analysis. Humoral response following vaccination was monitored using serological immunoassay registered for quantitative measurement of serum anti-SARS-CoV-2 RDB-spike protein antibodies. Both electrochemiluminescent assays performed by Cobas e801 analyzer (Roche Diagnostics, Mannheim, Germany) detect total antibodies (including IgG). Response was recorded after the first and second doses. A positive response was defined as > 0.8 U/mL. Upper and lower limits of quantification were 0,4 U/mL and 250 U/mL respectively. We reviewed patient records for demographics, underlying hematological diseases, current treatment, the total number of lines of therapy received, IgG levels, application of anti-CD20 monoclonal antibodies (mAbs) and corticosteroids in the last 6 months before vaccination, and subsequent SARS-CoV-2 infection. Inter-group comparisons were performed with Mann-Whitney U, χ 2, or Fisher's exact test as appropriate. ROC curve analysis was used to find optimized cut-off values of numerical variables regarding response to the second dose. P values <0.05 were considered statistically significant. MedCalc statistical software v 20.008 was used for all analyses. Results We evaluated a total of 120 patients who received at least one dose. Patient characteristics are summarized in Table 1. The majority received the Pfizer-BioNTech vaccine (66.7%), followed by Oxford-AstraZeneca (24.2%) and Moderna (9.2%). Data on humoral response after the first dose was available in 66 patients, among whom 20 (33%) achieved response with median specific IgG levels 6.1 U/mL. Response after the second dose was available in 90 patients;58 (64.4%) achieved response with median specific IgG levels 250 U/mL. The second dose significantly improved response both in terms of achieved response (P=0.031) and specific IgG levels (P<0.001). There were no significant differences in response or specific IgG levels regarding the type of the vaccine (P>0.05). Lower response rates after the second dose were achieved in patients aged >67 years (P<0.001;response in 32.4% vs. 83.9%), with specific diagnosis (P=0.002, driven by response in patients with non-Hodgkin's lymphoma (NHL;response in 29.2% NHL vs. 77.3% non-NHL) and chronic myeloid leukemia (CML;100% response in CML vs. 61.4% non-CML)), those receiving active treatment (50% vs. 88%;P<0.001), no prior hematopoietic stem cell transplantation (HSCT;51% vs. 93%;P<0.001) and prior anti-CD20 mAbs therapy (4% vs. 85%;P<0.001). Corticosteroid therapy (>120 mg prednisone equivalent dose) did not influence the response significantly (response in 88.9% vs. 42.1%;P=0.056), and neither did steroid type. Four (3,3%) patients tested positive for SARS-CoV-2 after vaccination, 2 of which had no humoral response, and 2 had received only one dose. Three patients required in-hospital treatment and oxygen supplementation. Conclusions Patients with hematologic diseases have lower serological response rates to SARS-CoV-2 vaccines than those previously reported in clinical trials. Our results also suggest they benefit from receiving both doses with no significant difference between vaccine types. Those in active treatment, no prior HSCT, diagnosed with NHL, and receiving anti-CD20 mAb seem more likely to be seronegative after receiving both doses. However, the present study did not examine potential confounding effects between these factors and these findings should be elaborated further in larger patient cohorts. [Formula presented] Disclosures: Aurer: Novartis: Consultancy, Honoraria;Janssen: Consultancy, Honoraria;Swixx/BMS: Honoraria;sanofi genzyme: Consultancy, Honoraria;Teva/Pilva: Honoraria;Abbvie: Consultancy, Honoraria;Eusapharma: Consultancy, Honoraria;Amgen: Consultancy, Honoraria;takeda: Consultancy, Honoraria. Durakovic: Takeda, Novartis, Genyzme: Honoraria.
ABSTRACT
Aim To evaluate three fully automated serological assays in terms of reactivity to SARS-CoV-2 immunoglobulin G (IgG) and perform SARS-CoV-2 IgG antibody testing among asymptomatic health care workers (HCW) at the University Hospital Center Zagreb. Methods Three IgG serological assays (Abbott SARS-CoV-2 IgG, Elecsys Anti-SARS-CoV-2, and MAGLUMI 2019-nCoV IgG) were initially evaluated by analyzing 42 samples from confirmed COVID-19-recovered patients and 48 negative individuals. A total of 1678 HCW (similar to 30% of all hospital employees) were screened for SARS-CoV-2 IgG with the Abbott assay, run on Abbott Architect i2000SR. The samples exceeding the predefined cut-off (1.4 S/C) were reanalyzed with the Elecsys, MAGLUMI, and VIDAS SARS-COV-2 IgG assays. Results Initially, the MAGLUMI 2019-nCoV IgG produced 26.2% false negatives and the Elecsys Anti-SARS-CoV-2 produced one false positive. Among 1678 HCW, the Abbott assay showed only 10 (0.6%) positive results, with mostly mildly elevated signals. Nine of these samples were nonreactive when they were retested with the Elecsys, MAGLUMI, and VIDAS assays. As for the one remaining sample, it was positive when tested with the Elecsys assay, while the other two assays yielded negative results. Conclusions SARS-CoV-2 IgG seroprevalence among asymptomatic HCW in our hospital setting was low, with different assays indicating a different number of positive samples. One of the assays yielded a large false negative rate. These findings can be attributed to differences in assay formulation but also to heterogeneity and diverse reactivity of antibodies against SARS-CoV-2 antigens.