Background In solid organ transplant (SOT) recipients, the primary vaccination series against COVID-19 is three doses followed by boosters. We determined whether a fourth dose booster induced Omicron BA.4/5 neutralizing antibodies and T-cells in a large multicenter cohort study. Methods Serum was collected 4-6 weeks post third and fourth dose of mRNA vaccine in 222 SOT recipients. Neutralizing antibodies (nAb) were measured using a pseudovirus neutralization assay targeting the Omicron BA.4/5 spike protein. A subset underwent T-cell testing. Results Median age of the cohort was 63 years (IQR 50-68) with 61.7% men. BA.4/5 nAb detection increased from 26.6%(59/222) post third dose to 53.6%(119/222) post fourth dose (p<0.0001). In patients with breakthrough infection prior to fourth dose (n=27), nAb were detected in 77.8% and median nAb titers were significantly higher compared to those with four vaccine doses alone (p<0.0001). Factors associated with a low BA.4/5 neutralization response after fourth dose were older age (OR 0.96, 95%CI 0.94-0.99), mycophenolate use (OR 0.39, 95%CI 0.20-0.77) and prednisone use (OR 0.34, 95%CI 0.18-0.63), and vaccine type (OR 0.72, 95%CI 0.51-0.99) while breakthrough infection prior to fourth dose (OR 3.6, 95%CI 1.3-9.9) was associated with a greater nAb response. Polyfunctional BA.4/5-specific CD4+ T-cells significantly increased after four doses and were identified in 76.9% of patients at a median frequency of 213 per 106 cells (IQR 98-650). Conclusion In summary, a booster significantly increases BA.4/5-specific neutralization and polyfunctional CD4+ T-cell responses, suggesting protection from severe disease even with new Omicron variants. However, SOT recipients that are older, on mycophenolate and prednisone need further preventative strategies.
Increased‐risk donor (IRD) organs make up a significant proportion of the deceased organ donor pool but may be declined by patients on the waiting list for various reasons. We conducted a survey of patients awaiting a liver transplant to determine the factors leading to the acceptance of an IRD organ as well as what strategies could increase the rate of acceptance. Adult liver transplant candidates who were outpatients completed a survey of 51 questions on a 5‐point Likert scale with categories related to demographics, knowledge of IRDs, and likelihood of acceptance. A total of 150 transplant candidates completed the survey (age 19‐80 years). Male patients constituted 67.3%. Many patients (58.7%) had postsecondary education. Only 23.3% of patients had a potential living donor, and 58/144 (40.3%) were not optimistic about receiving an organ in the next 3 months. The overall IRD organ acceptance rate was 41.1%, whereas 26.2% said they would decline an IRD organ. Women were more likely to accept an IRD organ (54.3% versus 34.7%; P = 0.02). Those who had a college education or higher tended to have lower IRD organ acceptability (28.3% versus 47.4%; P = 0.07). Acceptability also increased as the specified transmission risk of human immunodeficiency virus or hepatitis C virus decreased (P < 0.001). Patients were also more likely to accept an IRD organ if they were educated on the benefits of IRD organs (eg, knowledge that an IRD organ was of better quality increased overall acceptance from 41.1% to 63.3%; P < 0.001). Our survey provides insight into liver transplant candidates who would benefit from greater education on IRD organs. Strategies targeting specific educational points are likely to increase acceptability.
Background In North America, both mRNA vaccines, Pfizer-BioNTech BNT162b2, and Moderna mRNA-1273, each utilizing a two-dose regimen, have started to be administered to individuals. Methods We evaluated the quantitative serologic antibody response following administration of either a single dose or both doses of an mRNA SARS-CoV-2 vaccine in a cohort of 98 participants (88 healthcare workers [HCW] and 10 solid organ transplant [SOT] recipients). Antibody levels were compared across three immunoassays: Elecsys Anti-SARS-CoV-2 S (Roche Diagnostics), SARS-CoV-2 TrimericS IgG (DiaSorin), and SARS-CoV-2 IgG II Quant (Abbott). Results Among HCW, sensitivity ranged from 100% (Roche), 99% (Abbott) and 98% (DiaSorin). The SARS-CoV-2 IgG II Quant and SARS-CoV-2 TrimericS IgG assays showed good agreement with a Pearson correlation coefficient of R = 0.95. Pearson correlation coefficients of R = 0.82 and 0.83 were obtained for Elecsys Anti-SARS-CoV-2 S vs SARS-CoV-2 TrimericS IgG followed by SARS-CoV-2 IgG II Quant vs Elecsys Anti-SARS-CoV-2 S, respectively. Significant differences in antibody levels between HCW and SOT recipients were observed. A decrease in antibody levels from time of vaccine administration to blood draw was evident. Among those with a second dose, an increase in antibody levels with increased time between administration of the first and second dose was observed. Conclusions The absolute values generated from each of the assay platforms are not interchangeable. Antibody levels differed with increased time between vaccine administration and with increased time between administration of the first and second dose. Further, significant differences in antibody levels between HCW and SOT recipients were observed.
Health care workers (HCWs) are at higher risk for SARS-CoV-2 infection and may play a role in transmitting the infection to vulnerable patients and members of the community. This is particularly worrisome in the context of asymptomatic infection. We performed a cross-sectional study looking at asymptomatic SARS-CoV-2 infection in HCWs. We screened asymptomatic HCWs for SARS-CoV-2 via PCR. Complementary viral genome sequencing was performed on positive swab specimens. A seroprevalence analysis was also performed using multiple assays. Asymptomatic health care worker cohorts had a combined swab positivity rate of 29/5776 (0.50%, 95%CI 0.32–0.75) relative to a comparative cohort of symptomatic HCWs, where 54/1597 (3.4%) tested positive for SARS-CoV-2 (ratio of symptomatic to asymptomatic 6.8:1). SARS-CoV-2 seroprevalence among 996 asymptomatic HCWs with no prior known exposure to SARS-CoV-2 was 1.4–3.4%, depending on assay. A novel in-house Coronavirus protein microarray showed differing SARS-CoV-2 protein reactivities and helped define likely true positives vs. suspected false positives. Our study demonstrates the utility of routine screening of asymptomatic HCWs, which may help to identify a significant proportion of infections.
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