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Background: COVID-19 is a new pandemic, and its impact by HIV status is unknown. National reporting does not include gender identity; therefore, data are absent on the impact of COVID-19 on transgender people, including those with HIV. Baseline data from the American Cohort to Study HIV Acquisition Among Transgender Women in High Risk Areas (LITE) Study provide an opportunity to examine pre-COVID factors that may increase vulnerability to COVID-19-related harms among transgender women., Setting: Atlanta, Baltimore, Boston, Miami, New York City, Washington, DC., Methods: Baseline data from LITE were analyzed for demographic, psychosocial, and material factors that may affect vulnerability to COVID-related harms., Results: The 1020 participants had high rates of poverty, unemployment, food insecurity, homelessness, and sex work. Transgender women with HIV (n = 273) were older, more likely to be Black, had lower educational attainment, and were more likely to experience material hardship. Mental and behavioral health symptoms were common and did not differ by HIV status. Barriers to health care included being mistreated, provider discomfort serving transgender women, and past negative experiences; as well as material hardships, such as cost and transportation. However, most reported access to material and social support-demonstrating resilience., Conclusions: Transgender women with HIV may be particularly vulnerable to pandemic harms. Mitigating this harm would benefit everyone, given the highly infectious nature of this coronavirus. Collecting gender identity in COVID-19 data is crucial to inform an effective public health response. Transgender-led organizations' response to this crisis serve as an important model for effective community-led interventions.