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American Journal of Transplantation ; 22(Supplement 3):381, 2022.
Article in English | EMBASE | ID: covidwho-2063378


Purpose: mRNA SARS-CoV-2 vaccines are highly efficacious in the general population but have shown a diminished response in immunosuppressed adolescent kidney allograft recipients. We investigated immunological parameters that could be associated with a blunted antibody response. We also analyzed whether a third vaccine dose could improve the antibody response. Method(s): Adolescent kidney transplant recipients who received mRNA SARSCoV- 2 vaccine had SARS-CoV-2 spike protein antibody levels measured 4-8 weeks after their second vaccine dose and again after the third vaccine dose. Immunological labs including lymphocyte subsets, immunoglobulin levels, and vaccine titers and immunosuppressive medication dosing were evaluated prior to vaccination. Patients were compared in groups of vaccine responders vs non-responders via a Mann-Whitney U test. The impact of mycophenolate mofetil dosage on immune parameters was analyzed via a linear regression model. Result(s): 14 of 27 (52%) vaccinated pts had a positive spike antibody level. There was no significant difference in immunoglobulin levels, T-cell populations, or vaccine titers. There was a trend toward negative spike antibodies with higher doses of mycophenolate mofetil, MMF, at 91 mg/m2/day median difference (p=0.06). All four patients receiving azathioprine instead of MMF developed spike antibodies. Non-responders had lower hemoglobin levels (beta=-1.30, p=0.009) and lower platelet count (beta=-56.00, p=0.057). MCV levels were normal in both groups. Non-responders showed a trend toward increased naive B-cell percentage (beta= 12.50, p=0.11) and decreased total memory B-cell percentage (beta=-12.54, p=0.080). Increasing MMF dosage was associated with an increase in naive B-cell percentage (beta=0.016, p=0.0032) decrease in total memory B-cell percentage (beta=-0.016, p=0.0034), and decreased in IgG level (beta=-0.35, p=0.012). Of the 13 patients that did not develop spike antibodies after the second vaccine dose, 9 pts (69%) developed antibodies after the third dose. In total, 23/27 (85%) patients vaccinated developed spiked antibodies. Conclusion(s): Disruption in B-cell population could be due to immunosuppression with MMF. Non-responders showed trends toward high MMF dosage, increased naive B-cell percentage, and decreased total memory B-cell percentage. Increasing MMF dosage was associated with all trends as well as decreased IgG levels. Decreased hemoglobin levels and normal MCV supports that anemia could be due to bone marrow suppression caused by MMF. Altered B-cell populations and MMF therapy are a potential biomarker for reduced efficacy of SARS-CoV-2 vaccine in adolescent kidney allograft recipients. Interestingly, a third vaccine dose can overcome the immunosuppressive effects and improve vaccine efficacy.

Journal of Clinical Immunology ; 42(SUPPL 1):S91-S92, 2022.
Article in English | Web of Science | ID: covidwho-1848920
Annals of Allergy, Asthma and Immunology ; 127(5):S13, 2021.
Article in English | EMBASE | ID: covidwho-1748295


Introduction -Currently, IgE blood testing requires phlebotomy that can be painful and leads to a delay in accurate diagnosis of allergies. An opportunity exists for in-office point-of-care (POC) testing to quantify patient IgE from a low-volume fingerstick blood sample. A system has been developed that performs up to 20 tests for whole protein and components in approximately 30 minutes by Kenota Health. Methods - Preliminary platform performance validation is required and Total IgE quantification (fingerstick) has been used to compare the system against a commonly used lab method (phlebotomy). 59 subjects & 10 contrived samples were tested for Total IgE on both systems. Whole blood, and plasma were analyzed using the POC and ImmunoCAP systems, respectively. The IgE measurements were compared using a Passing-Bablok regression analysis. Results - The 59 subjects were between 14-65 years old (a young population has been used successfully, but due to COVID lockdown, fewer younger subjects were available). The IgE ranged from 1 kU/L to 3500 kU/L. The Log of the IgE measurements were plotted against each other to evaluate the POC system accuracy, precision and fit. The systems aligned very well with the slope (1.015) and y-intercept (0.923) being within the Confidence interval of the data. The r2 value for the fit was 0.98. Conclusions - The data confirms that the Kenota POC system demonstrates substantially equivalent performance to ImmunoCAP. This conclusion sets the stage for a future with specific IgE quantification (whole allergen and component testing) in allergists’ offices used to guide rapid and convenient patient diagnosis. [Formula presented]

Annals of Allergy Asthma & Immunology ; 127(5):S7-S8, 2021.
Article in English | Web of Science | ID: covidwho-1529391
Open Forum Infectious Diseases ; 7(SUPPL 1):S295-S296, 2020.
Article in English | EMBASE | ID: covidwho-1185818


Background: Smell loss has been recognized as an important, and potentially early, sign of COVID-19. However, to date smell loss has only been assessed in retrospective, COVID+ cohorts, and largely through self-report. The objective of this study was to implement a daily standardized behavioral test of smell sensitivity in healthcare workers (HCW) to capture changes in smell sensitivity over time and to assess whether these changes occur prior to positive COVID test. Methods: The study enrolled 500 high-risk COVID-negative HCW during the COVID-19 epidemic in Connecticut, beginning March 28, 2020 (80% F, mean age 38, 58% nurses). Initially, HCW received a daily symptom questionnaire with parosmia screening questions. On April 23 we introduced the “Jiffy”, a daily at-home psychophysical test of smell sensitivity, where olfactory stimuli are sampled and rated for perceived intensity. SARS-CoV-2 infection was tested every three days by PCR of nasopharyngeal swabs or saliva Results: Of the first 500 enrolled HCW, 376 HCW (75%) completed the Jiffy 4528 times (mean 12 times/HCW). 17/500 HCW (3.4%) had a COVID+ test, of which 9/17 (53%) reported smell loss through the Jiffy or the daily symptom survey. 6/9 (67%) reported smell loss that preceded or was concurrent with a COVID+ test. 8/17 COVID+ HCW completed the Jiffy, with 5/8 (63%) reporting reductions in smell versus 42/368 (11%) COVID- HCW (OR=13, 95% CI: 2.4-85, p=.001). COVID+ HCW rated their greatest reduction in smell sensitivity as slight (40%) and severe (60%), versus slight (88%) and moderate (12%) in COVID- HCW. 16/17 COVID+ HCW completed a daily symptom survey (mean 14 times/HCW), with 8/16 (50%) ever reporting parosmia versus 90/466 (19%) of COVID- HCW (OR=4.2, 95% CI: 1.3-13, p=.007). Overall, parosmia was the first reported symptom in 3/13 (23%) COVID+ HCW who reported symptoms. Conclusion: We conducted a prospective study of smell testing in a population at high risk for COVID-19 using two parallel approaches. Our results demonstrate the feasibility of at-home smell testing for assessing parosmia during COVID-19, in some cases even prior to a positive PCR result. Given the urgent need for widespread, lowcost, non-invasive testing for COVID-19, we are now developing an easy-to-use app to distribute this survey more widely to high-risk populations. (Table Presented).