Lessons learned from the launch and implementation of the COVID-19 contact tracing program in New York City: a qualitative study (preprint)

On June 1, 2020, NYC Health + Hospitals, in partnership with the NYC Department of Health and Mental Hygiene, other city agencies, and a large network of community partners, launched the New York City Test & Trace (T2) COVID-19 response program to identify and isolate cases, reduce transmission through contact tracing, and provide support to residents during isolation or quarantine periods. In this paper, we describe lessons learned with respect to planning and implemention of case notification and contact tracing. Our findings are based on extensive document review and analysis of 74 key informant interviews with T2 leadership and frontline staff, cases, and contacts conducted between January and September 2022. Interviews elicited respondent background, history of program development, program leadership and structure, goals of the program, program evolution, staffing, data systems, elements of community engagement, trust with community, program reach, timeliness, equity, general barriers and challenges, general facilitators and best practices, and recommendations/improvement for the program. Facilitators and barriers revealed in the interviews primarily revolved around hiring and managing staff, data and technology, and quality of interactions with the public. Based on these facilitators and barriers, we identify suggestions to support effective planning and response for future case notification and contact tracing programs, including recommendations for planning during latent periods, case management and data systems, and processes for outreach to cases and contacts.

Racial/Ethnic and Income Disparities in Neighborhood-Level Broadband Access in 766 US Cities, 2017- 2019 (preprint)

Broadband access is an essential social determinant of health, the importance of which has increased due to the ongoing COVID-19 outbreak. Using data from the City Health Dashboard and American Community Survey, we found that in 2017, 30% of urban households in 766 large US cities still had no access to high-speed broadband internet. After controlling for household income, broadband access in majority Black and Hispanic neighborhoods was 10-15% lower than in White or Asian majority neighborhoods. In 2019, lack of broadband access in urban households decreased to 28%, but substantial broadband disparities still persist in these cities.

ACE2-containing defensosomes serve as decoys to inhibit SARS-CoV-2 infection (preprint)

Extracellular vesicles of endosomal origin, exosomes, mediate intercellular communication by transporting substrates with a variety of functions related to tissue homeostasis and disease. Their diagnostic and therapeutic potential has been recognized for diseases such as cancer in which signaling defects are prominent. However, it is unclear to what extent exosomes and their cargo inform the progression of infectious diseases. We recently defined a subset of exosomes termed defensosomes that are mobilized during bacterial infection in a manner dependent on autophagy proteins. Through incorporating protein receptors on their surface, defensosomes mediated host defense by binding and inhibiting pore-forming toxins secreted by bacterial pathogens. Given this capacity to serve as decoys that interfere with surface protein interactions, we investigated the role of defensosomes during infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of COVID-19. Consistent with a protective function, exosomes containing high levels of the viral receptor ACE2 in bronchioalveolar lavage fluid from critically ill COVID-19 patients was associated with reduced ICU and hospitalization times. We found ACE2+ exosomes were induced by SARS-CoV-2 infection and activation of viral sensors in cell culture, which required the autophagy protein ATG16L1, defining these as defensosomes. We further demonstrate that ACE2+ defensosomes directly bind and block viral entry. These findings suggest that defensosomes may contribute to the antiviral response against SARS-CoV-2 and expand our knowledge on the regulation and effects of extracellular vesicles during infection.

Gut microbiome dysbiosis during COVID-19 is associated with increased risk for bacteremia and microbial translocation. (preprint)

The microbial populations in the gut microbiome have recently been associated with COVID-19 disease severity. However, a causal impact of the gut microbiome on COVID-19 patient health has not been established. Here we provide evidence that gut microbiome dysbiosis is associated with translocation of bacteria into the blood during COVID-19, causing life-threatening secondary infections. Antibiotics and other treatments during COVID-19 can potentially confound microbiome associations. We therefore first demonstrate that the gut microbiome is directly affected by SARS-CoV-2 infection in a dose-dependent manner in a mouse model, causally linking viral infection and gut microbiome dysbiosis. Comparison with stool samples collected from 101 COVID-19 patients at two different clinical sites also revealed substantial gut microbiome dysbiosis, paralleling our observations in the animal model. Specifically, we observed blooms of opportunistic pathogenic bacterial genera known to include antimicrobial-resistant species in hospitalized COVID-19 patients. Analysis of blood culture results testing for secondary microbial bloodstream infections with paired microbiome data obtained from these patients suggest that bacteria translocate from the gut into the systemic circulation of COVID-19 patients. These results are consistent with a direct role for gut microbiome dysbiosis in enabling dangerous secondary infections during COVID-19.