Biology ■ SARS-CoV-2 is single-stranded RNA, enveloped virus that likely spread to humans from a zoonotic source, possibly bats or pangolins 1. ■ It is believed to spread from person to person via respiratory droplet nuclei 2. ■ Other routes of infection (e.g. contact, enteric) are possible as the virus can persist on surfaces and is shed in feces, but it is unclear if these are significant means of spread. 2,3 ■ There is evidence of transmission by asymptomatic individuals 4. ■ The virus binds to the ACE2 receptor on type II pneumocytes. However, the role of Angiotensin Converting Enzyme Inhibitors and Angiotensin Receptor Blockers (ARBs) as treatments or risk factors for disease is unclear 5. ■ The reported incubation time is 3-12 days with a median duration of viral shedding of 20 days 6,7. ■ There is evidence that the virus changes over time. There may be multiple strains of SARS-CoV-2 in circulation 8. Dyspnea 20-40% URI symptoms 15% GI symptoms (nausea, vomiting, diarrhea) 10% Diagnosis and Management of COVID-19 Disease SARS-CoV-2 is a novel coronavirus that was identified in late 2019 as the causative agent of COVID-19 (aka coronavirus disease 2019). On March 11, 2020, the World Health Organization (WHO) declared the worldwide outbreak of COVID-19 a pandemic. This document summarizes the most recent knowledge regarding the biology, epidemiology, diagnosis, and management of COVID-19.

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Background Healthcare-associated transmission of nontuberculous mycobacteria (NTM) among people with cystic fibrosis (pwCF) has been reported and is of increasing concern. No standardized epidemiologic investigation tool has been published for healthcare-associated NTM outbreak investigations. This report describes the design of an ongoing observational study to standardize the approach to NTM outbreak investigation among pwCF. Methods This is a parallel multi-site study of pwCF within a single Center who have respiratory NTM isolates identified as being highly-similar. Participants have a history of positive airway cultures for NTM, receive care within a single Center, and have been identified as part of a possible outbreak based on genomic analysis of NTM isolates. Participants are enrolled in the study over a 3-year period. Primary endpoints are identification of a shared healthcare-associated encounter(s) among patients in a Center and identification of environmental isolates that are genetically highly-similar to respiratory isolates recovered from pwCF. Secondary endpoints include characterization of potential transmission modes and settings, as well as incidence and prevalence of healthcare-associated environmental NTM species/subspecies by geographical region. Discussion We hypothesize that genetically highly-similar strains of NTM among pwCF cared for at the same Center may arise from healthcare sources including patient-to-patient transmission and/or acquisition from environmental sources. This novel study design will establish a standardized, evidence-based epidemiologic investigation tool for healthcare-associated NTM outbreak investigation within CF Care Centers, will broaden the scope of independent outbreak investigations and demonstrate the frequency and nature of healthcare-associated NTM transmission in CF Care Centers nationwide. Furthermore, it will provide valuable insights into modeling risk factors associated with healthcare-associated NTM transmission and better inform future infection prevention and control guidelines. This study will systematically characterize clinically-relevant NTM isolates of CF healthcare environmental dust and water biofilms and set the stage to describe the most common environmental sources within the healthcare setting harboring clinically-relevant NTM isolates. Trial registration ClinicalTrials.gov NCT04024423. Date of registry July 18, 2019.

Rationale Outbreaks of nontuberculous mycobacteria (NTM) among people with cystic fibrosis (pwCF) have been reported at CF centers with conflicting conclusions. The occurrence of NTM at the UVMC (University of Vermont Medical Center) adult CF program was investigated. Objectives Use the HALT NTM (Healthcare-associated Links in Transmission of NTM) toolkit to investigate the healthcare-associated transmission and/or acquisition of NTM among pwCF having genetically similar NTM isolates. Methods Whole genome sequencing of NTM isolates from 23 pwCF was conducted to identify genetically similar NTM isolate clusters (30 or fewer single-nucleotide polymorphism differences). The epidemiological investigation, comparison of respiratory and healthcare environmental isolates, and home residence watershed mapping were analyzed. Results Whole genome sequencing analysis revealed two clusters of NTM isolates ( Mycobacterium avium and M. intracellulare ssp. chimaera ) among pwCF. The epidemiologic investigation demonstrated opportunities for healthcare-associated transmission within both clusters. Healthcare environmental M. avium isolates revealed no genetic similarity to respiratory isolates. However, M. intracellulare ssp. chimaera respiratory isolates revealed greater genetic similarity to a hospital water biofilm isolate than to each other. Neither cluster had all subjects residing in the same watershed. Conclusions This study suggests the healthcare-associated transmission of M. avium among pwCF is unlikely at UVMC but supports the healthcare-associated environmental acquisition of M. intracellulare ssp. chimaera . The presence of genetically similar isolates alone is insufficient to confirm healthcare-associated transmission and/or acquisition. The HALT NTM toolkit standardizes outbreak investigation with genetic analysis, epidemiologic investigation, healthcare environmental sampling, and home of residence watershed identification to test the frequency and nature of healthcare-associated NTM transmission among pwCF.

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