Attenuation of Autoimmune Phenomena in a Patient with Autoimmune Polyglandular Syndrome Type 1

Autoimmune polyglandular syndrome type 1 (APS1) is a progressive life-threatening illness with no known cure. Current treatments involve replacement of the hormone deficiencies that result from autoimmune destruction of multiple endocrine organs. We report on a girl whose disease was progressing rapidly until she began on immunosuppressive agents. A healthy 6-year-old girl with no remarkable medical history presented with new onset hypocalcemic seizures and primary hypoparathyroidism. Howell-Jolly bodies consistent with autoimmune hyposplenism were also noted. Genetic testing revealed compound heterozygosity for 2 disease-associated variants in the autoimmune regulator (AIRE) gene. She later developed elevated liver enzymes, primary adrenal insufficiency, and alopecia totalis. Serologic testing revealed antibodies to 21-hydroxylase, intrinsic factor, and smooth muscle. Hydrocortisone was initiated for adrenal insufficiency. Shortly afterwards, her liver enzymes normalized, and her smooth muscle antibody levels began to decline. Serologic testing performed at age 11 revealed seropositivity for glutamic acid decarboxylase (GAD) antibodies, antinuclear antibodies, and Sjögren syndrome A (SSA) antibodies. At age 12, she was given 2 doses of rituximab. Hair loss rapidly progressed to alopecia totalis and then to alopecia universalis, at which time oral methotrexate treatment was initiated. For the past 7 years while on glucocorticoid and methotrexate treatment, our patient has displayed normalization of 2 antibodies, a lack of progression to additional autoimmune diseases, and experienced reversal of alopecia universalis.

Serologic titers to Leptospira in vaccinated pigs and interpretation for surveillance

Diagnosis and surveillance of pathogenic Leptospira is difficult as organisms may be intermittently shed and in small numbers. Therefore, serologic testing by the microscopic agglutination test (MAT) is the primary screening method for leptospirosis. While a MAT titer ≥1:100 is considered to be a positive result, interpretation is complicated by the use of commercial vaccines in pigs. Most guidelines for interpretation of MAT titers in pigs were published in the 1970’s and 1980’s, prior to the development of the current multivalent vaccines. We evaluated MAT titers in routinely vaccinated healthy research pigs compared to their unvaccinated cohorts. Our study confirmed previous reports that the Pomona serovar elicits minimal antibody response even after a second booster 6 months after initial vaccination. However, MAT titers of ≥1:3,200 were detected as early as 4 weeks post initial vaccination for serovars Bratislava and Icterohaemorrhagiae and remained as high as ≥1:1,600 prior to booster at 24 weeks post vaccination. Our study determined that high levels of MAT titers can occur from vaccination alone and high titers are not necessarily indicative of infection. Therefore, the interpretation of MAT titers as indicators of Leptospira infection should be readdressed.

672. Diagnosis of Rocky Mountain Spotted Fever Using Plasma Metagenomic Next-Generation Sequencing

Background Rocky mountain spotted fever (RMSF), caused by Rickettsia rickettsii, incurs significant morbidity and mortality, especially in children. Early in the course of illness, standard diagnostic tests are of limited sensitivity, and diagnosis is often based on clinical symptoms and local epidemiology. The diagnosis can be missed in areas where RMSF is not endemic, and a delay in initiation of therapy may lead to poor clinical outcomes. Plasma metagenomic next-generation sequencing (mNGS), with turnaround times approaching 48 hours, may be a useful adjunctive tool in the diagnosis of RMSF. Methods We describe four children hospitalized with RMSF between January 1, 2017 to May 15, 2021 at a tertiary children’s hospital in southern California. All had plasma mNGS and rickettsial serologic testing as part of clinical care. Results mNGS detected Rickettsia rickettsii in all 4 patients. Only 2 subjects had positive serologic testing initially and required repeat testing in the convalescent stage to confirm RMSF. The mean turnaround time for mNGS was 2.75 days, which was comparable to serologic testing. Antibiotic therapy was changed in three subjects as a result of the plasma mNGS result. Conclusion Plasma mNGS may be a useful diagnostic modality early in the disease course of RMSF. Disclosures Lauge Farnaes, MD, PhD, Cardea Bio (Advisor or Review Panel member)IDbyDNA (Employee)

374. Need to Improve Minority Representation through COVID-19 Community Research Partnership

Background Minorities are often unrepresented in research, which limits equity in healthcare advances. The racial and ethnic disparities in outcomes of individuals infected with COVID-19 highlight the importance of inclusivity in research to improve public health measures. Methods We performed a descriptive analysis of the racial and ethnic distribution of children enrolled in our COVID-19 Community Research Partnership (CRP) study, a syndromic and serological surveillance study of children aged 2 – 17 years receiving care at three healthcare systems spanning North and South Carolina. Syndromic surveillance involved daily symptom reporting using a web-based monitoring application. Participants consenting to serological surveillance were mailed at-home tests sampling finger prick capillary blood. In-person and electronic recruitment efforts were conducted in English and Spanish. At one of the study sites, we compared the racial/ethnic distribution of enrolled children to the racial/ethnic distribution of all children who received care at the same site during the same timeframe. We compared the racial/ethnic distribution of participants who ultimately submitted samples for serological testing compared to those who consented to serologic testing. Results At total of1630 children were enrolled from April 2, 2021 – June 8, 2021. Most children were > 5 years old, 50.2% were female, and 88.5% were from mostly urban counties (Table 1). Of enrolled children, 4.2% were Hispanic, 8.2% were black, and 81.6% were white (Table 2). Among 135,355 unique children who received care at the institution during the same time, 12.4% were Hispanic, 23.0% were black, and 63.1% were white. Of 1552 participants who consented to serologic testing, 4.4% were Hispanic, 8.1% were black, and 81.8% were white (Table 3). To date, 242 children submitted serologic samples; 4.1% were Hispanic, 5.0% were black, and 85.5% were white. Table 1. Characteristics of enrolled children in COVID-19 surveillance study Table 2. Racial and Ethnic distribution of children enrolled in the study compared to target population Table 3. Racial and ethnic distribution of children who participated in serology testing Conclusion Despite efforts to recruit a diverse group of children, the proportion of minorities enrolled in our COVID-19 surveillance study underrepresents the targeted population. Ongoing efforts will work to identify barriers and facilitators to research participation among minority families. Disclosures Amina Ahmed, MD, Nothing to disclose

Limited diagnostic utility of SARS-CoV-2 serologic testing in symptomatic PCR negative patients

Background Guidelines from the CDC and the IDSA suggest the use of serologic testing to support the diagnosis of COVID-19 in individuals with high clinical suspicion that repeatedly test negative by diagnostic methods. Given that variability in specimen type, collection technique, and time from symptoms all reduce the sensitivity of molecular methods for SARS-CoV-2. The routine use of serology to diagnose and manage patients with symptoms concerning COVID-19 is tempting, despite limited studies in the literature supporting this approach. Here, we assessed the utility of serology testing for diagnosing SARs-CoV-2 in symptomatic, PCR-negative patients. Methods Remnant EDTA plasma specimens were obtained from 393 patients with clinical suspicion for COVID-19 and a negative SARs-COV-2 RNA test by the nasopharyngeal swab. The specimens were analyzed for SARs-CoV-2 IgG on an Abbott Architect i2000 (Abbott diagnostic). Patient information and symptoms adjudication were obtained from patient electronic health records. Results 14 of 393 patients were positive for antibodies to SARS-CoV-2 (seropositivity rate of 3.6%), 6 of which were from patients with previous RT-PCR-confirmed COVID-19 infection. Among patients without previously diagnosed COVID-19, the seropositivity rate in symptomatic patients was 1.2% (2/171), in patients with altered mental status was 4.3% (2/46), and in asymptomatic patients with no known previous COVID-19 diagnoses was 2.6% (4/170). The seropositivity rate among symptomatic patients presenting ≥ 14 days after symptom onset was 0% (0/67), 7-13 days was 5% (1/20), and for patients < 7 days, was 2.1% (1/47). Among the 4 patients with AMS that were serologically positive, 2 were previously diagnosed by PCR. Conclusion There is a low diagnostic utility of SARS-COV-2 serological testing for identifying novel cases of acute SARS-CoV-2 infections in the ED after a negative PCR test.

COVID-19 symptoms, patient contacts, PCR-positivity and seropositivity among healthcare personnel in a Maryland healthcare system

In a large system-wide healthcare personnel (HCP) testing experience using SARS-CoV-2 PCR and serologic testing early in the COVID-19 pandemic, we did not find increased infection risk related to COVID-19 patient contact. Our findings support workplace policies for HCP protection and underscore the role of community exposure and asymptomatic infection.