Neutralizing activity and 3-month durability of tixagevimab and cilgavimab prophylaxis against Omicron sublineages in transplant recipients.

Neutralizing antibody (nAb) responses are attenuated in solid organ transplant recipients (SOTRs) despite severe acute respiratory syndrome-coronavirus-2 vaccination. Preexposure prophylaxis (PrEP) with the antibody combination tixagevimab and cilgavimab (T+C) might augment immunoprotection, yet in vitro activity and durability against Omicron sublineages BA.4/5 in fully vaccinated SOTRs have not been delineated. Vaccinated SOTRs, who received 300 + 300 mg T+C (ie, full dose), within a prospective observational cohort submitted pre and postinjection samples between January 31, 2022, and July 6, 2022. The peak live virus nAb was measured against Omicron sublineages (BA.1, BA.2, BA.2.12.1, and BA.4), and surrogate neutralization (percent inhibition of angiotensin-converting enzyme 2 receptor binding to full length spike, validated vs live virus) was measured out to 3 months against sublineages, including BA.4/5. With live virus testing, the proportion of SOTRs with any nAb increased against BA.2 (47%-100%; P < .01), BA.2.12.1 (27%-80%; P < .01), and BA.4 (27%-93%; P < .01), but not against BA.1 (40%-33%; P = .6). The proportion of SOTRs with surrogate neutralizing inhibition against BA.5, however, fell to 15% by 3 months. Two participants developed mild severe acute respiratory syndrome-coronavirus-2 infection during follow-up. The majority of fully vaccinated SOTRs receiving T+C PrEP achieved BA.4/5 neutralization, yet nAb activity commonly waned by 3 months postinjection. It is critical to assess the optimal dose and interval of T+C PrEP to maximize protection in a changing variant climate.

Omicron BA.1 and BA.2 Neutralizing Activity Following Pre-Exposure Prophylaxis with Tixagevimab plus Cilgavimab in Vaccinated Solid Organ Transplant Recipients.

Neutralizing antibody responses are attenuated in many solid organ transplant recipients (SOTRs) despite SARS-CoV-2 vaccination. Pre-exposure prophylaxis (PrEP) with the monoclonal antibody combination Tixagevimab and Cilgavimab (T+C) might augment immunoprotection, yet activity against Omicron sublineages in vaccinated SOTRs is unknown. Vaccinated SOTRs who received 300+300mg T+C (either single dose or two 150+150mg doses) within a prospective observational cohort submitted pre- and post-injection samples between 1/10/2022-4/4/2022. Binding antibody (anti-receptor binding domain [RBD], Roche) and surrogate neutralization (%ACE2 inhibition; ≥20% connoting neutralizing inhibition, Meso Scale Discovery) were measured against variants including Omicron sublineages BA.1 and BA.2. Data were analyzed using the Wilcoxon matched-pairs signed-rank test and McNemar's test. Among 61 participants, median (IQR) anti-RBD increased from 424 (IQR <0.8-2322.5) to 3394.5 (IQR 1403.9-7002.5) U/ml post T+C (p<0.001). The proportion demonstrating vaccine strain neutralizing inhibition increased from 46% to 100% post-T+C (p<0.001). BA.1 neutralization was low and did not increase (8% to 16% of participants post-T+C, p=0.06). In contrast, BA.2 neutralization increased from 7% to 72% of participants post-T+C (p<0.001). T+C increased anti-RBD levels, yet BA.1 neutralizing activity was minimal. Encouragingly, BA.2 neutralization was augmented and in the current variant climate T+C PrEP may serve as a useful complement to vaccination in high-risk SOTRs.

Heterologous Ad.26.COV2.S versus homologous BNT162b2/mRNA-1273 as a third dose in solid organ transplant recipients seronegative after two-dose mRNA vaccination.

Heterologous vaccination ("mixing platforms") for the third (D3) dose of SARS-CoV-2 vaccine is a potential strategy to improve antibody responses in solid organ transplant recipients (SOTRs), but data are mixed regarding potential differential immunogenicity. We assessed for differences in immunogenicity and tolerability of homologous (BNT162b2 or mRNA-1273; D3-mRNA) versus heterologous (Ad.26.COV2.S; D3-JJ) D3 among 377 SARS-CoV-2-infection naïve SOTRs who remained seronegative after two mRNA vaccines. We measured anti-spike titers and used weighted Poisson regression to evaluate seroconversion and development of high-titers, comparing D3-JJ to D3-mRNA, at 1-, 3-, and 6 month post-D3. 1-month post-D3, seroconversion (63% vs. 52%, p = .3) and development of high-titers (29% vs. 25%, p = .7) were comparable between D3-JJ and D3-mRNA recipients. 3 month post-D3, D3-JJ recipients were 1.4-fold more likely to seroconvert (80% vs. 57%, weighted incidence-rate-ratio: wIRR = 1.10 1.401.77 , p = .006) but not more likely to develop high-titers (27% vs. 22%, wIRR = 0.44 0.921.93 , p = .8). 6 month post-D3, D3-JJ recipients were 1.41-fold more likely to seroconvert (88% vs. 59%, wIRR = 1.04 1.411.93 , p = .029) and 2.63-fold more likely to develop high-titers (59% vs. 21%, wIRR = 1.38 2.635.00 , p = .003). There was no differential signal in alloimmune events or reactogenicity between platforms. SOTRs without antibody response after two mRNA vaccines may derive benefit from heterologous Ad.26.COV2.S D3.

Effect of glycemic index and carbohydrate intake on kidney function in healthy adults.

BACKGROUND: Replacing carbohydrate with protein acutely increases glomerular filtration rate (GFR) but is associated with faster, long-term kidney disease progression. The effects of carbohydrate type (i.e. glycemic index, GI) on kidney function are unknown. METHODS: We conducted an ancillary study of a randomized, crossover feeding trial in overweight/obese adults without diabetes or kidney disease (N = 163). Participants were fed each of four healthy, DASH-like diets for 5 weeks, separated by 2-week washout periods. Weight was kept constant. The four diets were: high GI (GI ≥65) with high %carb (58 % kcal) (reference diet), low GI (≤45) with low %carb (40 % kcal), low GI with high %carb; and high GI with low %carb. Plasma was collected at baseline and after each feeding period. Study outcomes were cystatin C, ß2-microglobulin (ß2M), and estimated GFR based on cystatin C (eGFRcys). RESULTS: Mean (SD) age was 52 (11) years; 52 % were women; 50 % were black. At baseline, mean (SD) cystatin C, ß2M, and eGFRcys were 0.8 (0.1) mg/L, 1.9 (0.4) mg/L, and 104 (16) mL/min/1.73 m(2). Compared to the high GI/high %carb diet, reducing GI, %carb, or both increased eGFRcys by 1.9 mL/min/1.73 m(2) (95 % CI: 1.1, 2.7; P < 0.001), 3.0 mL/min/1.73 m(2) (1.9, 4.0; P < 0.001), and 4.5 mL/min/1.73 m(2) (3.5, 5.4; P < 0.001), respectively. Increases in eGFRcys from reducing GI were significantly associated with increases in eGFRcys from reducing %carb (P < 0.001). Results for cystatin C and ß2M reflected eGFRcys. CONCLUSIONS: Reducing GI increased GFR. Reducing %carb by increasing calories from protein and fat, also increased GFR. Future studies on GI should examine the long-term effects of this increase in GFR on kidney injury markers and clinical outcomes. TRIAL REGISTRATION: Clinical Trials.gov, number: NCT00608049 (first registered January 23, 2008).

Effects of a behavioral intervention that emphasizes spices and herbs on adherence to recommended sodium intake: results of the SPICE randomized clinical trial.

BACKGROUND: For decades, dietary sodium intake in the United States has remained high, and few studies have examined strategies for maintaining recommended intakes. OBJECTIVE: We examined the effects of a behavioral intervention, which emphasized spices and herbs, on the maintenance of sodium intake at the recommended intake of 1500 mg/d in individuals to whom the US Dietary Guidelines for Americans apply. DESIGN: We conducted a 2-phase study that included adults ≥18 y of age for whom Dietary Guidelines for Americans recommends 1500 mg Na/d. The study was conducted in Baltimore, Maryland, from 2012 to 2014. In phase 1, 55 individuals consumed a low-sodium diet for 4 wk. Participants were provided all foods, snacks, and calorie-containing drinks. In phase 2, 40 participants from phase 1 were randomly assigned to either a behavioral intervention to reduce sodium intake (n = 20) or a self-directed control group (n = 20) for 20 wk. The primary study outcome was the change in mean 24-h urinary sodium excretion during phase 2. Linear regression analyses were used to determine intervention effects on urinary sodium excretion. RESULTS: Participant characteristics were as follows: women: 65%; African American: 88%; hypertension: 63%; diabetes: 18%; mean age: 61 y; and mean body mass index (in kg/m(2)): 30. At the end of phase 2, mean 24-h sodium excretion was lower in the behavioral intervention than in the self-directed group (mean difference: -956.8 mg/d; 95% CI: -1538.7, -374.9 mg/d) after sodium intake at screening was controlled for (P = 0.002). These findings persisted in sensitivity analyses that excluded potentially incomplete urine collections [Mage's equation mean difference: -1090 mg/d (P = 0.001); Joosens' equation mean difference: -796 mg/d (P = 0.04)]. CONCLUSIONS: A multifactorial behavioral intervention emphasizing spices and herbs significantly reduced sodium intake. Because of the ubiquity of sodium in the US food supply, multilevel strategies addressing individual behaviors and the food supply are needed to improve adherence to recommendations. This trial was registered at clinicaltrials.gov as NCT01615159.