1409. Pulmonary Non-tuberculous Mycobacterium Infection (PNTMI) and COVID-19: Characterization of the National COVID Collaborative Cohort (N3C)

Abstract Background Establishing whether a low-prevalence clinical condition is a risk factor for COVID-19 infection, or serious adverse outcomes, is difficult due to a limited number of patients, and lack of access to patient’s data by researchers. The National COVID Collaborative Cohort (N3C), a centralized national data resource to study COVID-19, provides access to structured clinical data derived from electronic health records. As of June 2021, N3C contains data on 6,193,738 patients (2,090,138 with COVID-19, 33.7%) from 55 participating sites (Figure 1). We describe the characteristics of patients with PNTMI based on COVID-19 infection status. Figure 1 N3C Basic Demographic Data Methods COVID-19 is defined by positive lab result (PCR, antigen, or antibody) or COVID-19 coding diagnosis, as defined by N3C. PNTMI phenotype was built with N3C Data Enclave concept set tool, and ATLAS (https://atlas.ohdsi.org/). We limited analysis to adults (18 years-old or older). We used de-identified data sets stripped of protected health information (PHI). We used N3C Data Enclave analytical tools for exploratory data analysis, and descriptive statistics. Results We identified five hundred and eighty six individuals from 19 sites fulfilling the PNTMI phenotype (9.46 cases per 100,000 people). After our age limit, 555 individuals were included for analysis (Figure 2). 340 were females (61.3%), 447 of white race (80.5%), and 30 were Hispanic (5.4%). Additional descriptive statistics and statistical significance testing are provided (Table 1). The most common concept were "Non-tuberculous mycobacterial pneumonia", and "Pulmonary Mycobacterium avium complex infection". Four sites accounted for more than 50% of identified patients (Figure 2). We identified 24 individuals with COVID-19 (4.32%), and 44 deaths in this cohort (7.9%). Deaths were unrelated to COVID-19 event. Figure 2. Basic demographic data of pulmonary non-tuberculous Mycobacterium infection phenotype in N3C Figure 3. Concepts and data sources of pulmonary non-tuberculous Mycobacterium infection phenotype in N3C Conclusion In N3C, the PNTMI cohort has a lower proportion of COVID-19 infection than the general population, and it was not a cause of mortality. Further analysis to study impact of comorbidities, and differences in race and geographical location are warranted. N3C is a powerful research platform to study the impact of COVID-19 in special populations with low prevalence, and it can be used to study other populations of interest. Disclosures All Authors: No reported disclosures


Pulmonary Non-tuberculous
Background. Establishing whether a low-prevalence clinical condition is a risk factor for COVID-19 infection, or serious adverse outcomes, is difficult due to a limited number of patients, and lack of access to patient's data by researchers. The National COVID Collaborative Cohort (N3C), a centralized national data resource to study , provides access to structured clinical data derived from electronic health records. As of June 2021, N3C contains data on 6,193,738 patients (2,090,33.7%) from 55 participating sites (Figure 1). We describe the characteristics of patients with PNTMI based on COVID-19 infection status.

Figure 1
N3C Basic Demographic Data Methods. COVID-19 is defined by positive lab result (PCR, antigen, or antibody) or COVID-19 coding diagnosis, as defined by N3C. PNTMI phenotype was built with N3C Data Enclave concept set tool, and ATLAS (https://atlas.ohdsi.org/). We limited analysis to adults (18 years-old or older). We used de-identified data sets stripped of protected health information (PHI). We used N3C Data Enclave analytical tools for exploratory data analysis, and descriptive statistics.
Results. We identified five hundred and eighty six individuals from 19 sites fulfilling the PNTMI phenotype (9.46 cases per 100,000 people). After our age limit, 555 individuals were included for analysis ( Figure 2). 340 were females (61.3%), 447 of white race (80.5%), and 30 were Hispanic (5.4%). Additional descriptive statistics and statistical significance testing are provided ( Table 1). The most common concept were "Non-tuberculous mycobacterial pneumonia", and "Pulmonary Mycobacterium avium complex infection". Four sites accounted for more than 50% of identified patients ( Figure 2). We identified 24 individuals with COVID-19 (4.32%), and 44 deaths in this cohort (7.9%). Deaths were unrelated to COVID-19 event. Conclusion. In N3C, the PNTMI cohort has a lower proportion of COVID-19 infection than the general population, and it was not a cause of mortality. Further analysis to study impact of comorbidities, and differences in race and geographical location are warranted. N3C is a powerful research platform to study the impact of COVID-19 in special populations with low prevalence, and it can be used to study other populations of interest.
Disclosures. Background. Data on the efficacy and tolerability of latent tuberculosis infection (LTBI) treatment in cancer patients receiving checkpoint inhibitor immunotherapy (CPI) is limited. We sought to assess LTBI therapy and its adverse events and outcomes in patients treated with CPI.
Methods. We performed a retrospective cohort study at MD Anderson Cancer Center of adult patients, between April 2016 and May 2021, who were receiving CPI and were diagnosed with LTBI based on positive T-SPOT TB test. We then compared those patients treated with isoniazid (INH) 5mg/kg daily versus those that did not receive INH therapy.
Results. We identified 35 patients treated with CPI who had a diagnosis of LTBI. Patients were divided into 2 groups: CPI alone (23 patients, 65.7%) and CPI+INH (12 patients, 34.3%). The majority of patients in both groups had renal cell carcinoma (34.3%) and melanoma (17.1%). Nivolumab as monotherapy was the most commonly used CPI agent in both groups (37.1%), whereas nivolumab and ipilimumab combination was mainly used in the CPI group (34.7%) compared to CPI+INH group (8.3%). In the CPI+INH group, 7 patients (58.3%) developed moderate to severe hepatoxicity that led to discontinuation of INH and CPI therapy versus none in the CPI group (p= 0.001). There was no statistically significant difference in the alanine aminotransferase (ALT) at baseline between both groups (p=0.117), whereas the median ALT level was significantly higher during CPI+INH therapy compared to CPI alone (135 U/L vs 24 U/L respectively, p=0.025. Furthermore, immune-related adverse events were reported in a total of 12 of 35 patients (34.2%). None of the patients in either group developed tuberculosis reactivation during a follow up period of up to 1148 days.
Conclusion. Our data suggest that latent tuberculosis reactivation is rare in cancer patients on CPI immunotherapy. Hepatotoxicity remains a concern in this patient population with LTBI treated with CPI and INH. With the widespread use of CPI, close laboratory and clinical monitoring is required to avoid life-threatening drug-induced liver injury and interruption of LTBI therapy and immunotherapy. Further clinical studies are warranted to determine the optimal management of LTBI during CPI therapy.
Disclosures Background. Pretomanid is used in combination with bedaquiline and linezolid (BPaL regimen) in the treatment of multidrug-resistant tuberculosis (MDR-TB). However, the penetration of pretomanid in privileged sites remain unknown. Antimicrobial pharmacokinetic (PK) parameters are traditionally derived from clinical samples (blood and cerebrospinal fluid), which may not accurately represent the intralesional tissue PK, affected by drug properties, vascular supply, barrier permeability, and the microenvironment.
Methods. We developed 18 F-pretomanid (chemically identical to pretomanid) for in vivo multi-compartment PK by positron emission tomography (PET). Dynamic 18 F-pretomanid PET was used to obtain cross species pretomanid concentration-time profiles in animal models of TB (mice and rabbits) to quantify penetration into pulmonary and brain lesions. A subset of animals underwent PET/CT imaging with 18 F-py-albumin and 18 F-FDG to assess vascular supply and inflammation. Postmortem 18 F-pretomanid autoradiography (high-resolution) and mass spectrometry were performed in infected tissues. A mouse model of TB meningitis was used to evaluate the bactericidal activity of the BPaL regimen (Figure 1). (A) A new synthetic approach was developed to obtain radiofluorinated pretomanid (18F-pretomanid), which is chemically identical to pretomanid and therefore