Anaplasma phagocytophilum is an emerging, Gram-negative, obligate intracellular pathogen that is transmitted by a tick vector. Human infection ranges from asymptomatic to severe disease that can present with pancytopenia, multiorgan failure, and death. The aim of this systematic review is to analyze case reports and case series reported over the last two decades in peer-reviewed journals indexed in the Medline/PubMed database according to the PRISMA guidelines. We found 110 unique patients from 88 case reports and series. The most common mode of transmission was tick bite (60.9%), followed by blood transfusion (8.2%). Infection was acquired by blood transfusion in nearly half (42%) of the immunocompromised patients. Most patients reported fever (90%), followed by constitutional (59%) and gastrointestinal symptoms (56%). Rash was present in 17% of patients, much higher than in previous studies. Thrombocytopenia was the most common laboratory abnormality (76%) followed by elevated aspartate aminotransferase (AST) (46%). The diagnosis was most commonly established using whole-blood polymerase chain reaction (PCR) in 76% of patients. Coinfection rate was 9.1% and Borrelia burgdorferi was most commonly isolated in seven patients (6.4%). Doxycycline was used to treat 70% of patients but was only used as an empiric treatment in one-third of patients (33.6%). The overall mortality rate was 5.7%, and one patient died from trauma unrelated to HGA. The mortality rates among immunocompetent and immunocompromised patients were 4.2% (n = 4/95) and 18.2% (n = 2/11), respectively. Four of the six patients who died (66.6%) received appropriate antibiotic therapy. Among these, doxycycline was delayed by more than 48 h in two patients.

Strategies to combat COVID-19 include vaccines and Monoclonal Antibody Therapy. While vaccines aim to prevent development of symptoms, Monoclonal Antibody Therapy aims to prevent the progression of mild to severe disease. An increasing number of COVID-19 infections in vaccinated patients raised the question of whether vaccinated and unvaccinated COVID-19 positive patients respond differently to Monoclonal Antibody Therapy. The answer can help prioritize patients if resources are scarce. We performed a retrospective study to evaluate and compare the outcomes and risks for disease progression between vaccinated and unvaccinated COVID-19 patients treated with Monoclonal Antibody Therapy by measuring the number of Emergency Department visits and hospitalizations within 14 days as well as the progression to severe disease, defined through the Intensive Care Unit admissions within 14 days, and death within 28 days from the Monoclonal Antibody infusion. From 3898 included patients, 2009 (51.5%) were unvaccinated at the time of Monoclonal Antibody infusion. Unvaccinated patients had more Emergency Department visits (217 vs. 79, p < 0.0001), hospitalizations (116 vs. 38, p < 0.0001), and progression to severe disease (25 vs. 19, p = 0.016) following treatment with Monoclonal Antibody Therapy. After adjustment for demographics and comorbidities, unvaccinated patients were 2.45 times more likely to seek help in the Emergency Department and 2.70 times more likely to be hospitalized. Our data suggest the added benefit between the COVID-19 vaccine and Monoclonal Antibody Therapy.

Background Clinical trials of monoclonal antibodies therapy (MAB) for COVID-19 demonstrated the risk reduction of COVID related hospitalization and death of any cause if administered within the first 7 days from the symptom onset. The Food and Drug Administration (FDA) issued an emergency use authorization (EUA) for MAB within 10 days from the symptom onset. Our objective was to evaluate how duration of symptoms before MAB affects disease outcome following therapy. Figure 1Duration of Symptoms prior to MAB infusion in Clinical Trials Methods We evaluated a relationship between symptoms duration prior to MAB and disease outcome following treatment by measuring number of emergency department (ED) visits, hospitalizations and ICU admissions within 14 days and number of deaths within 30 days of MAB. Based on the symptom duration, patients were classified in typical (1-7 days) and late group (8-10 days of symptoms). We evaluated outcomes according to the symptom duration using absolute risk reduction and used Chi-squared tests to assess statistical significance using an alpha of p&lt; 0.05. Figure 2Subject Flow Diagram Results From 3898 patients, 3074 (78.9%) were treated within 7 days from the symptom onset. Demographics were similar in both typical and late group. Majority of treated patients in both groups were Non-Hispanic Caucasians suggesting racial and ethnic disparities potentially due to a lack of access to healthcare. All comorbidities were similar or higher in the typical group except for obesity that was more frequent in the late group. Compared with typical, late group had more ED visits (9.22% vs 7.16% p=0.04) and hospitalizations (4.98% vs 3.68%, p=0.08). Absolute risk of progression to severe disease measured through the number of ICU admissions and deaths was low across the groups, and difference was not statistically significant. Adjusted for demographics and comorbidities, patients from the late group were 1.35 times more likely to seek help in the ED and 1.72 times more likely to get hospitalized. Figure 3Demographics and comorbidities for Typical (patients treated within 7 days from the symptom onset) and Late (patients treated 8-10 days from the symptom onset) group. Conclusion Despite FDA EUA allowing for the use of MAB up to 10 days from the symptom’s onset, our real-world findings suggest that patients benefit most when treatment is administered within 7-day from the symptom onset as consistent with clinical trials. Disclosures All Authors: No reported disclosures.

Background Despite advances in microbiologic techniques, for patients with complex infections it often remains a challenge to identify the causative infectious pathogen. Traditional cultures (Cx) may fail to grow microorganisms due to inadequate sampling, prior antibiotic use, or the inherent insensitivity of culture methods for fastidious pathogens. Molecular tests allow for the detection of microbial nucleic acids directly from clinical specimens and do not require the presence of viable organisms for identification. Universal polymerase chain reaction testing (UPCR) is offered though the University of Washington Department of Laboratory Medicine and Pathology as a metagenomic approach using broad-range PCR primers followed by sequencing to hypothetically identify any pathogen present. The testing is composed of 3 separate tests for bacterial (BUPCR), fungal (FUPCR), and acid-fast (AFUPCR) organisms. The utility of UPCR has not been formally evaluated. Our objective is to describe the diagnostic utility of UPCR by comparing Cx and UPCR results, and their impact on management. Figure 1:Introduction - Types of Universal PCR Testing Methods We retrospectively collected data on UPCR and culture results and changes in antimicrobial therapy based on UPCR results for all patients with at least 1 UPCR test done during the 2-year study period. Results 367 UPCR tests were performed over 24 months on 155 patients. From 367 tests, 119 were FUPCR, 111 AFUPCR, and 137 BUPCR. 32/155 (20.6%) patients had positive UPCR. 25/32 were BUPCR and 7/32 were FUPCR. No AFUPCR was positive. In 8/155 (5.2%) patients management was changed based on UPCR results: Positive UPCR results directed treatment in 5 patients: 4 patients had positive UPCR and negative culture, and 1 had both UPCR and Cx positive but for different organisms. In all 5 therapy was changed in favor of UPCR result. All 5 tests were BUPCR.Negative UPCR led to antimicrobial discontinuation in 3 patients. 11/155 (7.1%) patients had negative UPCR and positive Cx, 10 of which were BUPCR and 1 AFUPCR. These results did not change management. Figure 2:Results – Type of Tissue and Test ResultsFigure 3:Results – Universal PCR Test Type and ResultsFigure 4:Results - Summary Conclusion Based on the real-world experience, UPCR results have limited impact on antimicrobial management in our institution. Further studies may try to identify clinical scenarios where UPCR may be of better clinical utility. Disclosures All Authors: No reported disclosures.

Background Strategies to combat COVID include vaccines and Monoclonal Antibody Therapy (MAB). While vaccines aim to prevent symptom development, MAB aims to prevent progression of mild symptoms to severe. Increasing numbers of COVID infections in vaccinated patients raised the question of whether vaccinated and unvaccinated patients respond differently to MAB. Methods We performed a retrospective review of the medical charts to evaluate responses of MAB in vaccinated and unvaccinated COVID patients by measuring the number of emergency department (ED) visits, hospitalizations, and ICU admissions within 14 days and the 30-day mortality following MAB. We evaluated outcomes according to vaccination status using absolute risk reduction and used Chi-squared tests to assess statistical significance using an alpha of p&lt; 0.05. We used multivariable generalized linear models with a log link and binomial distribution to estimate adjusted relative risk and 95% confidence intervals. Figure 1:Subject Flow Diagram Results Based on the inclusion criteria, we found 4,128 patients from which 230 had missing vaccination information or dose. From 3898 included patients, 296 (7.59%) visited the ED, 154 (3.95%) were hospitalized, and 25 (0.64%) were in ICU within 14 days of infusion. 12 patients (0.31%) died within 30 days. 2009 (51.5%) were unvaccinated at the time of infusion. Demographics were similar in both groups except that most of the patients in both groups were Non-Hispanic Caucasians, raising the question of racial and ethnic disparities. All comorbidities except pregnancy were predominant in the vaccinated group. Unvaccinated patients were more likely to receive MAB after 7 days of symptoms and in the ER, suggesting that they may have had more severe disease at the time of infusion, despite having less comorbidities. Unvaccinated patients had more ED visits (11.2% vs 4.3%, p&lt; 0.0001), hospitalizations (6.2% vs 2.1%, p&lt; 0.0001), and deaths (1.1% vs 0.3%, p=0.005) following infusion. Adjusted for demographics and comorbidities, unvaccinated patients were 2.41 times more likely to seek help in the ED and 2.73 times to be hospitalized. Figure 2:Patient Demographics and ComorbiditiesFigure 3:Comparison of Outcomes by Vaccination StatusFigure 4:Relative Risk by Vaccination Status Model 1 – Unadjusted Model 2 – Adjusted for financial class, infusion location, patient sex, patient age, patient race, and time to infusion Model 3 – Model 2 Variables + Comorbidity Count Model 4 – Model 2 + Specific Comorbidities (diabetes, cancer, immunosuppression, BMI, chronic kidney disease, cardiovascular disease, lung disease, neurological disorders, and smoking) Conclusion Our data confirms that immunization plays a key role in reducing COVID-related morbidity and mortality. It also supports MAB efficiency from clinical trials. Figure 5:Future Actions Disclosures All Authors: No reported disclosures.