Consistent Effects of Early Remdesivir on Symptoms and Disease Progression Across At-Risk Outpatient Subgroups: Treatment Effect Heterogeneity in PINETREE Study.

INTRODUCTION: In the PINETREE study, early remdesivir treatment reduced risk of coronavirus disease 2019 (COVID-19)-related hospitalizations or all-cause death versus placebo by 87% by day 28 in high-risk, non-hospitalized patients. Here we report results of assessment of heterogeneity of treatment effect (HTE) of early outpatient remdesivir, focusing on time from symptom onset and number of baseline risk factors (RFs). METHODS: PINETREE was a double-blind, placebo-controlled trial of non-hospitalized patients with COVID-19 who were randomized within 7 days of symptom onset and had ≥ 1 RF for disease progression (age ≥ 60 years, obesity [body mass index ≥ 30], or certain coexisting medical conditions). Patients received remdesivir intravenously (200 mg on day 1 and 100 mg on days 2 and 3) or placebo. RESULTS: In this subgroup analysis, HTE of remdesivir by time from symptom onset at treatment initiation and number of baseline RFs was not detected. Treatment with remdesivir reduced COVID-19-related hospitalizations independent of stratification by time from symptom onset to randomization. Of patients enrolled ≤ 5 days from symptom onset, 1/201 (0.5%) receiving remdesivir and 9/194 (4.6%) receiving placebo were hospitalized (hazard ratio [HR] 0.10; 95% confidence interval [CI] 0.01-0.82). Of those enrolled at > 5 days from symptom onset, 1/78 (1.3%) receiving remdesivir and 6/89 (6.7%) receiving placebo were hospitalized (HR 0.19; 95% CI 0.02-1.61). Remdesivir was also effective in reducing COVID-19-related hospitalizations when stratified by number of baseline RFs for severe disease. Of patients with ≤ 2 RFs, 0/159 (0.0%) receiving remdesivir and 4/164 (2.4%) receiving placebo were hospitalized; of those with ≥ 3 RFs, 2/120 (1.7%) receiving remdesivir and 11/119 (9.2%) receiving placebo were hospitalized (HR 0.16; 95% CI 0.04-0.73). CONCLUSIONS: In the outpatient setting, benefit of remdesivir initiated within 7 days of symptoms appeared to be consistent across patients with RFs. Therefore, it may be reasonable to broadly treat patients with remdesivir regardless of comorbidities. TRIAL REGISTRATION: ClinicalTrials.gov number NCT04501952.

Attenuated humoral responses in HIV after SARS-CoV-2 vaccination linked to B cell defects and altered immune profiles.

We assessed a cohort of people living with human immunodeficiency virus (PLWH) (n = 110) and HIV negative controls (n = 64) after 1, 2 or 3 SARS-CoV-2 vaccine doses. At all timepoints, PLWH had significantly lower neutralizing antibody (nAb) titers than HIV-negative controls. We also observed a delayed development of neutralization in PLWH that was underpinned by a reduced frequency of spike-specific memory B cells (MBCs). Improved neutralization breadth was seen against the Omicron variant (BA.1) after the third vaccine dose in PLWH but lower nAb responses persisted and were associated with global MBC dysfunction. In contrast, SARS-CoV-2 vaccination induced robust T cell responses that cross-recognized variants in PLWH. Strikingly, individuals with low or absent neutralization had detectable functional T cell responses. These PLWH had reduced numbers of circulating T follicular helper cells and an enriched population of CXCR3+CD127+CD8+T cells after two doses of SARS-CoV-2 vaccination.

Ethnic inequalities in mental health and socioeconomic status among older women living with HIV: results from the PRIME Study.

OBJECTIVES: Women living with HIV in the UK are an ethnically diverse group with significant psychosocial challenges. Increasing numbers are reaching older age. We describe psychological and socioeconomic factors among women with HIV in England aged 45-60 and explore associations with ethnicity. METHODS: Analysis of cross-sectional data on 724 women recruited to the PRIME Study. Psychological symptoms were measured using the Patient Health Questionnaire 4 and social isolation with a modified Duke-UNC Functional Social Support Scale. RESULTS: Black African (BA) women were more likely than Black Caribbean or White British (WB) women to have a university education (48.3%, 27.0%, 25.7%, respectively, p<0.001), but were not more likely to be employed (68.4%, 61.4%, 65.2%, p=0.56) and were less likely to have enough money to meet their basic needs (56.4%, 63.0%, 82.9%, p<0.001). BA women were less likely to report being diagnosed with depression than WB women (adjusted odds ratio (aOR) 0.40, p<0.001) but more likely to report current psychological distress (aOR 3.34, p<0.05). CONCLUSIONS: We report high levels of poverty, psychological distress and social isolation in this ethnically diverse group of midlife women with HIV, especially among those who were BA. Despite being more likely to experience psychological distress, BA women were less likely to have been diagnosed with depression suggesting a possible inequity in access to mental health services. Holistic HIV care requires awareness of the psychosocial needs of older women living with HIV, which may be more pronounced in racially minoritised communities, and prompt referral for support including psychology, peer support and advice about benefits.

Risk factors, symptom reporting, healthcare-seeking behaviour and adherence to public health guidance: protocol for Virus Watch, a prospective community cohort study.

INTRODUCTION: The coronavirus (COVID-19) pandemic has caused significant global mortality and impacted lives around the world. Virus Watch aims to provide evidence on which public health approaches are most likely to be effective in reducing transmission and impact of the virus, and will investigate community incidence, symptom profiles and transmission of COVID-19 in relation to population movement and behaviours. METHODS AND ANALYSIS: Virus Watch is a household community cohort study of acute respiratory infections in England and Wales and will run from June 2020 to August 2021. The study aims to recruit 50 000 people, including 12 500 from minority ethnic backgrounds, for an online survey cohort and monthly antibody testing using home fingerprick test kits. Nested within this larger study will be a subcohort of 10 000 individuals, including 3000 people from minority ethnic backgrounds. This cohort of 10 000 people will have full blood serology taken between October 2020 and January 2021 and repeat serology between May 2021 and August 2021. Participants will also post self-administered nasal swabs for PCR assays of SARS-CoV-2 and will follow one of three different PCR testing schedules based on symptoms. ETHICS AND DISSEMINATION: This study has been approved by the Hampstead National Health Service (NHS) Health Research Authority Ethics Committee (ethics approval number 20/HRA/2320). We are monitoring participant queries and using these to refine methodology where necessary, and are providing summaries and policy briefings of our preliminary findings to inform public health action by working through our partnerships with our study advisory group, Public Health England, NHS and government scientific advisory panels.