Ferric carboxymaltose and SARS-CoV-2 vaccination-induced immunogenicity in kidney transplant recipients with iron deficiency: The COVAC-EFFECT randomized controlled trial.

Background: Kidney transplant recipients (KTRs) have an impaired immune response after vaccination against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Iron deficiency (ID) may adversely affect immunity and vaccine efficacy. We aimed to investigate whether ferric carboxymaltose (FCM) treatment improves humoral and cellular responses after SARS-CoV-2 vaccination in iron-deficient KTRs. Methods: We randomly assigned 48 iron-deficient KTRs to intravenous FCM (1-4 doses of 500mg with six-week intervals) or placebo. Co-primary endpoints were SARS-CoV-2-specific anti-Receptor Binding Domain (RBD) Immunoglobulin G (IgG) titers and T-lymphocyte reactivity against SARS-CoV-2 at four weeks after the second vaccination with mRNA-1273 or mRNA-BNT162b2. Results: At four weeks after the second vaccination, patients receiving FCM had higher plasma ferritin and transferrin saturation (P<0.001 vs. placebo) and iron (P=0.02). However, SARS-CoV-2-specific anti-RBD IgG titers (FCM: 66.51 [12.02-517.59] BAU/mL; placebo: 115.97 [68.86-974.67] BAU/mL, P=0.07) and SARS-CoV-2-specific T-lymphocyte activation (FCM: 93.3 [0.85-342.5] IFN-É£ spots per 106 peripheral blood mononuclear cells (PBMCs), placebo: 138.3 [0.0-391.7] IFN-É£ spots per 106 PBMCs, P=0.83) were not significantly different among both arms. After the third vaccination, SARS-CoV-2-specific anti-RBD IgG titers remained similar between treatment groups (P=0.99). Conclusions: Intravenous iron supplementation efficiently restored iron status but did not improve the humoral or cellular immune response against SARS-CoV-2 after three vaccinations.

Ferric Carboxymaltose and SARS-COV-2 Vaccination-Induced Immunogenicity in Kidney Transplant Recipients with Iron Deficiency: The Covac-Effect Randomised, Placebo-Controlled Clinical Trial

BACKGROUND AND AIMS Kidney transplant recipients (KTRs) have a compromised immune response after vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Iron deficiency (ID) impairs B cell proliferation and function, may reduce vaccine efficacy and is highly prevalent among KTRs. We aimed to investigate whether ID correction by ferric carboxymaltose (FCM) treatment improves humoral and cellular responses after SARS-CoV-2 vaccination in iron-deficient KTRs. METHOD In this analysis of an ongoing randomised, double-blind, placebo-controlled clinical trial, iron-deficient KTRs [serum ferritin < 100 μg/L or serum ferritin 100–300 μg/L in combination with transferrin saturation (TSAT) <20%] received up to four doses of 500 mg intravenous FCM or placebo at 6-week intervals (Fig. 1). In the primary intention-to-treat analysis, we determined the effect of ID correction on anti-SARS-CoV-2 IgG titers (ELISA) and T-lymphocyte reactivity against SARS-CoV-2 (ELISPOT) following SARS-CoV-2 vaccination with mRNA-1273 (N = 41) or mRNA-BNT162b2 (N = 5). RESULTS Out of the 46 trial participants (median age 53 (interquartile range 43–65) years, 61% male),  25 were assigned to receive FCM and 21 to receive placebo. FCM treatment efficiently restored iron status:  serum ferritin levels increased from 49 (26–79) μg/L at baseline to 464 (272–621) μg/L at 4 weeks after the second vaccination (P < .001 versus baseline; P < .001 versus placebo group) and TSAT from 21% ± 8% to 34% ± 12% (P < .001 versus baseline; P <.001 versus placebo group), while ID persisted in the placebo group. At 4 weeks after the second vaccination,  anti-SARS-CoV-2 IgG titers tended to be lower in the FCM arm [66.51 (12.02–517.59) BAU/mL; placebo arm:  115.97 (68.86–974.67) BAU/mL,  P = .07,  Fig. 2A]. SARS-CoV-2 specific T-lymphocyte activation did not differ between the study arms [FCM arm:  93.3 (0.85–342.5) IFN-ɣ spots per 106 PBMCs,  placebo arm:  138.3 (0.0–391.7) IFN-ɣ spots per 106 PBMCs,  P = .83,  Fig. 2B]. Anti-SARS-CoV-2 IgG titers and T-lymphocyte reactivity against SARS-CoV-2 significantly correlated with each other (Spearman's rho 0.44,  P = .002), but not with ferritin levels at 4 weeks after the second vaccination (ferritin versus anti-SARS-CoV-2 IgG titer, Spearman's rho –0.15,  P = .33;ferritin versus T-lymphocyte reactivity against SARS-CoV-2, Spearman's rho –0.01,  P = .98). Results were similar in a per-protocol analysis and in sensitivity analyses after the exclusion of individuals with low total IgG levels or mild ID at baseline or patients who received alemtuzumab, anti-thymocyte globulin or high-dose methylprednisolone during the previous 2 years. Separate analyses in subgroups according to immunosuppressive regimen (dual or triple therapy) or vaccine type also yielded highly similar results.  CONCLUSION FCM treatment efficiently restored iron status in KTRs but did not improve the humoral or cellular immune response against SARS-CoV-2 after two vaccinations. (Funded by Dutch Kidney Foundation,  Vifor Fresenius Medical Care Renal Pharma and the Tekke Huizenga Foundation (grant no STHF 2021.01.02);COVAC-EFFECT/EFFECT-KTx ClinicalTrials.gov number,  NCT03769441.)FIGURE 1: Study design.FIGURE 2: Anti-SARS-CoV-2 vaccination response. (A) Anti-SARS-CoV-2 antibody titers before vaccination and four weeks after the first and second vaccination in iron-deficient KTRs who had been treated with FCM or placebo. The dashed horizontal line represents the threshold for IgG seropositivity. (B) SARS-CoV-specific T-lymphocyte response at 4 weeks after the second vaccination in iron-deficient KTRs treated with FCM or placebo. The dashed horizontal line represents the threshold for a positive T-lymphocyte response.

What makes (hydroxy)chloroquine ineffective against COVID-19: insights from cell biology.

Since chloroquine (CQ) and hydroxychloroquine (HCQ) can inhibit the invasion and proliferation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in cultured cells, the repurposing of these antimalarial drugs was considered a promising strategy for treatment and prevention of coronavirus disease (COVID-19). However, despite promising preliminary findings, many clinical trials showed neither significant therapeutic nor prophylactic benefits of CQ and HCQ against COVID-19. Here, we aim to answer the question of why these drugs are not effective against the disease by examining the cellular working mechanisms of CQ and HCQ in prevention of SARS-CoV-2 infections.

Dynamical system of the growth of COVID-19 with controller.

Recently, various studied were presented to describe the population dynamic of covid-19. In this effort, we aim to introduce a different vitalization of the growth by using a controller term. Our method is based on the concept of conformable calculus, which involves this term. We investigate a system of coupled differential equations, which contains the dynamics of the diffusion among infected and asymptomatic characters. Strong control is considered due to the social separation. The result is consequently associated with a macroscopic law for the population. This dynamic system is useful to recognize the behavior of the growth rate of the infection and to confirm if its control is correctly functioning. A unique solution is studied under self-mapping properties. The periodicity of the solution is examined by using integral control and the optimal control is discussed in the sequel.

Solvability and stability of a fractional dynamical system of the growth of COVID-19 with approximate solution by fractional Chebyshev polynomials.

Lately, many studies were offered to introduce the population dynamics of COVID-19. In this investigation, we extend different physical conditions of the growth by employing fractional calculus. We study a system of coupled differential equations, which describes the dynamics of the infection spreading between infected and asymptomatic styles. The healthy population properties are measured due to the social meeting. The result is associated with a macroscopic law for the population. This dynamic system is appropriate to describe the performance of growth rate of the infection and to verify if its control is appropriately employed. A unique solution, under self-mapping possessions, is investigated. Approximate solutions are presented by utilizing fractional integral of Chebyshev polynomials. Our methodology is based on the Atangana-Baleanu calculus, which provides various activity results in the simulation. We tested the suggested system by using live data. We found positive action in the graphs.