Effectiveness of Remdesivir Treatment Protocols Among Patients Hospitalized with COVID-19: A Target Trial Emulation.

BACKGROUND: Remdesivir is recommended for certain hospitalized patients with COVID-19. However, these recommendations are based on evidence from small randomized trials, early observational studies, or expert opinion. Further investigation is needed to better inform treatment guidelines with regard to the effectiveness of remdesivir among these patients. METHODS: We emulated a randomized target trial using chargemaster data from 333 US hospitals from 1 May 2020 to 31 December 2021. We compared three treatment protocols: remdesivir within 2 days of hospital admission, no remdesivir within the first 2 days of admission, and no remdesivir ever. We used baseline comorbidities recorded from encounters up to 12 months before admission and identified the use of in-hospital medications, procedures, and oxygen supplementation from charges. We estimated the cumulative incidence of mortality or mechanical ventilation/extracorporeal membrane oxygenation with an inverse probability of censoring weighted estimator. We conducted analyses in the total population as well as in subgroups stratified by level of oxygen supplementation. RESULTS: A total of 274,319 adult patients met the eligibility criteria for the study. Thirty-day in-hospital mortality risk differences for patients adhering to the early remdesivir protocol were -3.1% (95% confidence interval = -3.5%, -2.7%) compared to no early remdesivir and -3.7% (95% confidence interval -4.2%, -3.2%) compared to never remdesivir, with the strongest effect in patients needing high-flow oxygen. For mechanical ventilation/extracorporeal membrane oxygenation, risk differences were minimal. CONCLUSIONS: We estimate that, among hospitalized patients with COVID-19, remdesivir treatment within 2 days of admission reduced 30-day in-hospital mortality, particularly for patients receiving supplemental oxygen on the day of admission.

Association of PTSD With Longitudinal COVID-19 Burden in a Mixed-Serostatus Cohort of Men and Women: Weathering the Storm.

OBJECTIVES: This study of people with HIV (PWH) and those without HIV conducted during the COVID-19 pandemic in the United States in 2020 examines the impact of posttraumatic stress disorder (PTSD) on COVID-19 burden, defined as pandemic-related disruptions. METHODS: Data consisted of survey responses on PTSD among participants (N = 2434) enrolled in the Multicenter AIDS Cohort Study (MACS) and the Women's Interagency HIV (WIHS) cohorts. Unadjusted and adjusted regression models were used to examine the association of PTSD with COVID-19 burden (overall and domain-specific burdens). Quasi-Poisson regression models were used to assess associations with the COVID-19 burden score and 2 domain-specific burdens: (1) changes in resources and (2) interruptions in health care. Analyses was adjusted for age, race/ethnicity, HIV serostatus, current smoking status, number of comorbidities, education, and study regions. RESULTS: Study participants were a median age of 58 (interquartile range, 52-65) years. In both bivariate and multivariable models, PTSD severity was associated with greater overall COVID-19 burden. PTSD severity was associated with the number of resource changes and number of interruptions in medical care. These findings were also consistent across cohorts (MACS/WIHS) and across HIV serostatus, suggesting a greater risk for COVID-19 burden with greater PTSD severity, which remained significant after controlling for covariates. CONCLUSIONS: This study builds on emerging literature demonstrating the impact of mental health on the burden and disruption associated with the COVID-19 pandemic, providing context specific to PWH. The ongoing pandemic requires structural and social interventions to decrease disruption to resources and health resource needs among these vulnerable populations.

Ethnoracial Disparities in SARS-CoV-2 Seroprevalence in a Large Cohort of Individuals in Central North Carolina from April to December 2020.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused millions of deaths around the world within the past 2 years. Transmission within the United States has been heterogeneously distributed by geography and social factors with little data from North Carolina. Here, we describe results from a weekly cross-sectional study of 12,471 unique hospital remnant samples from 19 April to 26 December 2020 collected by four clinical sites within the University of North Carolina Health system, with a majority of samples from urban, outpatient populations in central North Carolina. We employed a Bayesian inference model to calculate SARS-CoV-2 spike protein immunoglobulin prevalence estimates and conditional odds ratios for seropositivity. Furthermore, we analyzed a subset of these seropositive samples for neutralizing antibodies. We observed an increase in seroprevalence from 2.9 (95% confidence interval [CI], 1.8 to 4.5) to 12.8 (95% CI, 10.6 to 15.2) over the course of the study. Latinx individuals had the highest odds ratio of SARS-CoV-2 exposure at 6.56 (95% CI, 4.66 to 9.44). Our findings aid in quantifying the degree of asymmetric SARS-CoV-2 exposure by ethnoracial grouping. We also find that 49% of a subset of seropositive individuals had detectable neutralizing antibodies, which was skewed toward those with recent respiratory infection symptoms. IMPORTANCE PCR-confirmed SARS-CoV-2 cases underestimate true prevalence. Few robust community-level SARS-CoV-2 ethnoracial and overall prevalence estimates have been published for North Carolina in 2020. Mortality has been concentrated among ethnoracial minorities and may result from a high likelihood of SARS-CoV-2 exposure, which we observe was particularly high among Latinx individuals in North Carolina. Additionally, neutralizing antibody titers are a known correlate of protection. Our observation that development of SARS-CoV-2 neutralizing antibodies may be inconsistent and dependent on severity of symptoms makes vaccination a high priority despite prior exposure.

Short-term binge drinking, marijuana, and recreational drug use trajectories in a prospective cohort of people living with HIV at the start of COVID-19 mitigation efforts in the United States.

BACKGROUND: At the start of the COVID-19 pandemic, HIV experts suggested that an increase in mental health diagnoses and substance use among people living with HIV (PLHIV) may be an unintended consequence of COVID-19 mitigation efforts (e.g., limiting social contact). We evaluated short-term trajectories in binge drinking, marijuana, and recreational drug use in a prospective cohort of PLHIV. METHODS: Data (N = 2121 PLHIV) consist of survey responses on substance use behaviors from two pre-COVID-19 (October 2018-September 2019) and one COVID-19-era (April 2020-September 2020) timepoints within the MACS/WIHS Combined Cohort Study (MWCCS). We conducted group-based trajectory models, triangulated with generalized linear mixed models, to assess changes in binge drinking, daily marijuana use, and recreational drug use at the start of the pandemic. Controlling for age and race/ethnicity, we tested whether trajectories differed by sex and early-pandemic depressive symptoms, loneliness, and social support. RESULTS: Group-based trajectory models yielded two trajectory groups for binge drinking (none vs. any), marijuana (none/infrequent vs. daily), and recreational drug use (none vs. any). Binge drinking and recreational drug use decreased at the beginning of the pandemic. Generalized linear mixed model supported these trends. Consistent with prior research, male sex and having depressive symptoms early pandemic were positively associated with each substance use outcomes. Social support was inversely associated with recreational drug use. CONCLUSIONS: Contrary to hypotheses, problematic substance use behaviors decreased from pre-pandemic to the post-pandemic follow-up in our sample of PLHIV. Ongoing surveillance is needed to assess whether this pattern persists as the pandemic continues.

Exploring Resilience Among Black Women Living With HIV in the Southern United States: Findings From a Qualitative Study.

ABSTRACT: Black women living with HIV (WLWH) face individual and sociostructural challenges. Despite these challenges, many exemplify remarkable levels of resilience and coping. Yet, research on resilience and coping in this population is limited. Twenty Black WLWH in the Southern United States completed semi-structured interviews that explored challenges facing WLWH. We identified six themes related to resilience and coping: self-acceptance, disclosure, self-compassion, social support, will to live, and service. Of these, social support was a driving protective element and an essential component to building and sustaining resilience and coping. Women who experienced positive support often expressed a will to live as well as a desire to support other WLWH. Resilience and social support were characterized by patterns of reciprocity, in that they were mutually sustaining, stabilizing, and strengthening.

Prevalence of COVID-19-Related Social Disruptions and Effects on Psychosocial Health in a Mixed-Serostatus Cohort of Men and Women.

OBJECTIVES: This study describes prevention behavior and psychosocial health among people living with HIV (PLHIV) and HIV-negative people during the early wave of the coronavirus disease 2019 (COVID-19) pandemic in the United States. We assessed differences by HIV status and associations between social disruption and psychosocial health. DESIGN: A cross-sectional telephone/videoconference administered survey of 3411 PLHIV and HIV-negative participants in the Multicenter AIDS Cohort Study/WIHS Combined Cohort Study (MWCCS). METHODS: An instrument combining new and validated measures was developed to assess COVID-19 prevention efforts, social disruptions (loss of employment, childcare, health insurance, and financial supports), experiences of abuse, and psychosocial health. Interviews were performed between April and June 2020. Associations between social disruptions and psychosocial health were explored using multivariable logistic regression, adjusting for sociodemographics and HIV status. RESULTS: Almost all (97.4%) participants reported COVID-19 prevention behavior; 40.1% participants reported social disruptions, and 34.3% reported health care appointment disruption. Men living with HIV were more likely than HIV-negative men to experience social disruptions (40.6% vs. 32.9%; P < 0.01), whereas HIV-negative women were more likely than women with HIV to experience social disruptions (51.1% vs. 39.8%, P < 0.001). Participants who experienced ≥2 social disruptions had significantly higher odds of depression symptoms [aOR = 1.32; 95% confidence interval (CI): 1.12 to 1.56], anxiety (aOR = 1.63; 95% CI: 1.17 to 2.27), and social support dissatisfaction (aOR = 1.81; 95% CI: 1.26 to 2.60). CONCLUSIONS: This study builds on emerging literature demonstrating the psychosocial health impact related to the COVID-19 pandemic by providing context specific to PLHIV. The ongoing pandemic requires structural and social interventions to decrease social disruption and address psychosocial health needs among the most vulnerable populations.

Developing Treatment Guidelines During a Pandemic Health Crisis: Lessons Learned From COVID-19.

The development of the National Institutes of Health (NIH) COVID-19 Treatment Guidelines began in March 2020 in response to a request from the White House Coronavirus Task Force. Within 4 days of the request, the NIH COVID-19 Treatment Guidelines Panel was established and the first meeting took place (virtually-as did subsequent meetings). The Panel comprises 57 individuals representing 6 governmental agencies, 11 professional societies, and 33 medical centers, plus 2 community members, who have worked together to create and frequently update the guidelines on the basis of evidence from the most recent clinical studies available. The initial version of the guidelines was completed within 2 weeks and posted online on 21 April 2020. Initially, sparse evidence was available to guide COVID-19 treatment recommendations. However, treatment data rapidly accrued based on results from clinical studies that used various study designs and evaluated different therapeutic agents and approaches. Data have continued to evolve at a rapid pace, leading to 24 revisions and updates of the guidelines in the first year. This process has provided important lessons for responding to an unprecedented public health emergency: Providers and stakeholders are eager to access credible, current treatment guidelines; governmental agencies, professional societies, and health care leaders can work together effectively and expeditiously; panelists from various disciplines, including biostatistics, are important for quickly developing well-informed recommendations; well-powered randomized clinical trials continue to provide the most compelling evidence to guide treatment recommendations; treatment recommendations need to be developed in a confidential setting free from external pressures; development of a user-friendly, web-based format for communicating with health care providers requires substantial administrative support; and frequent updates are necessary as clinical evidence rapidly emerges.

Toward Understanding COVID-19 Recovery: National Institutes of Health Workshop on Postacute COVID-19.

Over the past year, the SARS-CoV-2 pandemic has swept the globe, resulting in an enormous worldwide burden of infection and mortality. However, the additional toll resulting from long-term consequences of the pandemic has yet to be tallied. Heterogeneous disease manifestations and syndromes are now recognized among some persons after their initial recovery from SARS-CoV-2 infection, representing in the broadest sense a failure to return to a baseline state of health after acute SARS-CoV-2 infection. On 3 to 4 December 2020, the National Institute of Allergy and Infectious Diseases, in collaboration with other Institutes and Centers of the National Institutes of Health, convened a virtual workshop to summarize existing knowledge on postacute COVID-19 and to identify key knowledge gaps regarding this condition.

Call to action: how can the US Ending the HIV Epidemic initiative succeed?

With more than 1·2 million people living with HIV in the USA, a complex epidemic across the large and diverse country, and a fragmented health-care system marked by widening health disparities, the US HIV epidemic requires sustained scientific and public health attention. The epidemic has been stubbornly persistent; high incidence densities have been sustained over decades and the epidemic is increasingly concentrated among racial, ethnic, and sexual and gender minority communities. This fact remains true despite extraordinary scientific advances in prevention, treatment, and care-advances that have been led, to a substantial degree, by US-supported science and researchers. In this watershed year of 2021 and in the face of the COVID-19 pandemic, it is clear that the USA will not meet the stated goals of the National HIV/AIDS Strategy, particularly those goals relating to reductions in new infections, decreases in morbidity, and reductions in HIV stigma. The six papers in the Lancet Series on HIV in the USA have each examined the underlying causes of these challenges and laid out paths forward for an invigorated, sustained, and more equitable response to the US HIV epidemic than has been seen to date. The sciences of HIV surveillance, prevention, treatment, and implementation all suggest that the visionary goals of the Ending the HIV Epidemic initiative in the USA might be achievable. However, fundamental barriers and challenges need to be addressed and the research effort sustained if we are to succeed.