ABSTRACT
Purpose: Emerging SARS-CoV-2 variants may be associated with a higher risk of breakthrough infections compared to wild-type (WT) virus in kidney transplant recipients (KTRs). The purpose of this study was to evaluate antiviral immune responses against WT and Delta (B.1.617.2) variant of SARS-CoV-2 after 3 doses of SARS-CoV-2 mRNA vaccines in KTRs. Method(s): We conducted a multicenter prospective cohort study of adult KTRs who received 3 doses of BNT162b2 or mRNA-1273. Blood samples were collected from KTRs before and 4 weeks after the 3rd vaccine dose. Sera from pre-pandemic healthy controls (HCs) and pre-pandemic kidney transplant control patients (KCs) were used for comparison. A Luminex-based multiplex assay was used to measure anti-spike antibodies for the WT, Alpha, Beta, Gamma and Delta variants of SARSCoV- 2. A surrogate virus neutralization test was used to assess neutralization against the WT and Delta variant. Patients were also monitored for rejection using several non-invasive biomarkers. Result(s): 54 KTRs were enrolled in the study. The median age was 63, 44% were female and the median time post-transplantation was 42 months. 94% received BNT162b2 vaccine. After the 3rd vaccine dose, there was a significant increase in anti-spike antibody MFIs against the WT, Alpha, Beta, Gamma and Delta variants (Fig. 1A, p<0.0001 for all). For comparison, all pre-pandemic HCs and KCs had a negative result for anti-spike antibody levels (Fig. 1B). Prior to the 3rd vaccine dose, 29% of KTRs had anti-spike antibodies against the WT compared to only 2% against the Delta variant (Fig. 1C, p=0.0001). After the 3rd vaccine dose, 67% of KTRs had anti-spike antibodies against the WT compared to 25% against the Delta variant (p<0.0001, Fig. 1D). Differences between WT and other variants are shown in Figure 1C-D. After the 3rd vaccine dose, there was a 2.1-fold and 2.5-fold increase in the percentage of KTRs with neutralizing responses against the WT and Delta variant respectively (p<0.0001 for both). There was no significant change in serum creatinine, proteinuria, or donor-derived cell-free DNA levels after vaccination. No episodes of rejection occurred during follow-up. Conclusion(s): Two doses of SARS-CoV-2 mRNA vaccines in KTRs are associated with minimal anti-spike antibody response directed against the Delta variant of SARS-CoV-2. After the third dose, a quarter of KTRs developed anti-spike antibodies directed against the Delta variant of SARS-CoV-2.
ABSTRACT
Background: There is limited data on the safety and efficacy of SARS-CoV-2 mRNA vaccines in kidney transplant recipients (KTRs). Methods: We conducted a prospective, multi-center study of 58 adult KTRs receiving mRNA-BNT162b2 or mRNA-1273 vaccines to assess vaccine safety and efficacy. Primary outcome was biopsy-proven rejection within 3 months of vaccination. Secondary outcomes included adverse events, serum creatinine, proteinuria, donor-derived cell-free DNA (ddcfDNA) levels, and antibody and cellular immunity generation against SARSCoV-2. Results: Median age was 62 with 41% females. Median time post-transplantation was 48 months. Only one patient (2%) developed acute cellular rejection though patient had been recently converted to belatacept. There were no severe adverse events or deaths during follow-up. Two patients (3%) developed SARS-CoV-2 infection, one of whom required hospitalization. There was no significant change in serum creatinine, proteinuria or ddcfDNA during the study. Following vaccination, 36%, 25% and 20% of KTRs developed anti-spike, anti-S1 and anti-RBD antibodies. KTRs on mycophenolate-based and steroid-maintenance regimens were less likely to develop an anti-spike antibody response. 100% of KTRs with anti-spike and anti-RBD antibodies had a neutralizing response, compared to 44% in KTRs with anti-spike but without anti-RBD antibodies (RR 2.25, 95% CI 1.08-4.67). There was a significant increase in IFN-gamma spots per 106 PBMCs incubated with S1 peptides following vaccination (p=0.0143). Conclusions: SARS-CoV-2 vaccination in KTRs was safe and associated with the generation of cellular immune response and in a third of patients with anti-spike antibody response. The degree of protection gained by these responses needs to be evaluated in future studies.
ABSTRACT
This work aims to demonstrate that three medium sized cities-Araguaína (TO), Imperatriz (MA) and Marabá (PA), located in the Legal Amazon, suffered a significant impact from the pandemic due to the spread of the virus following the flow of capital in the country. This impact was probably due to the characteristics of economic development linked to the production of commodities, which interconnect them with large national and international producing centers and consumers, independently of their capitals. To demonstrate the dynamics of dissemination, the occurrences of Acute Respiratory Syndrome for the three states (TO, MA and PA) as well as confirmed cases of COVID-19 were quantitatively analyzed for the cities studied and their respective capitals. The data made available by the Oswaldo Cruz Foundation and the Epidemiological Bulletins released by the State Health Secretariats and City Halls were collected. As a result, it was observed that the disease growth rates are higher in three cities, as they behave in a similar fashion with respect to the pandemic and differentiate to each other by the incidence of COVID-19 in their respective cities. It is argued that in a post-COVID-19 period, the characteristics of interconnection between the three cities must be valued, through public policies that promote the development of the region with a focus on reorganizing the city for its people. © 2020, Universidade de Taubate. All rights reserved.