Inhaled budesonide in the treatment of early COVID-19 (STOIC): a phase 2, open-label, randomised controlled trial.

BACKGROUND: Multiple early reports of patients admitted to hospital with COVID-19 showed that patients with chronic respiratory disease were significantly under-represented in these cohorts. We hypothesised that the widespread use of inhaled glucocorticoids among these patients was responsible for this finding, and tested if inhaled glucocorticoids would be an effective treatment for early COVID-19. METHODS: We performed an open-label, parallel-group, phase 2, randomised controlled trial (Steroids in COVID-19; STOIC) of inhaled budesonide, compared with usual care, in adults within 7 days of the onset of mild COVID-19 symptoms. The trial was done in the community in Oxfordshire, UK. Participants were randomly assigned to inhaled budsonide or usual care stratified for age (≤40 years or >40 years), sex (male or female), and number of comorbidities (≤1 and ≥2). Randomisation was done using random sequence generation in block randomisation in a 1:1 ratio. Budesonide dry powder was delivered using a turbohaler at a dose of 400 µg per actuation. Participants were asked to take two inhalations twice a day until symptom resolution. The primary endpoint was COVID-19-related urgent care visit, including emergency department assessment or hospitalisation, analysed for both the per-protocol and intention-to-treat (ITT) populations. The secondary outcomes were self-reported clinical recovery (symptom resolution), viral symptoms measured using the Common Cold Questionnare (CCQ) and the InFLUenza Patient Reported Outcome Questionnaire (FLUPro), body temperature, blood oxygen saturations, and SARS-CoV-2 viral load. The trial was stopped early after independent statistical review concluded that study outcome would not change with further participant enrolment. This trial is registered with ClinicalTrials.gov, NCT04416399. FINDINGS: From July 16 to Dec 9, 2020, 167 participants were recruited and assessed for eligibility. 21 did not meet eligibility criteria and were excluded. 146 participants were randomly assigned-73 to usual care and 73 to budesonide. For the per-protocol population (n=139), the primary outcome occurred in ten (14%) of 70 participants in the usual care group and one (1%) of 69 participants in the budesonide group (difference in proportions 0·131, 95% CI 0·043 to 0·218; p=0·004). For the ITT population, the primary outcome occurred in 11 (15%) participants in the usual care group and two (3%) participants in the budesonide group (difference in proportions 0·123, 95% CI 0·033 to 0·213; p=0·009). The number needed to treat with inhaled budesonide to reduce COVID-19 deterioration was eight. Clinical recovery was 1 day shorter in the budesonide group compared with the usual care group (median 7 days [95% CI 6 to 9] in the budesonide group vs 8 days [7 to 11] in the usual care group; log-rank test p=0·007). The mean proportion of days with a fever in the first 14 days was lower in the budesonide group (2%, SD 6) than the usual care group (8%, SD 18; Wilcoxon test p=0·051) and the proportion of participants with at least 1 day of fever was lower in the budesonide group when compared with the usual care group. As-needed antipyretic medication was required for fewer proportion of days in the budesonide group compared with the usual care group (27% [IQR 0-50] vs 50% [15-71]; p=0·025) Fewer participants randomly assigned to budesonide had persistent symptoms at days 14 and 28 compared with participants receiving usual care (difference in proportions 0·204, 95% CI 0·075 to 0·334; p=0·003). The mean total score change in the CCQ and FLUPro over 14 days was significantly better in the budesonide group compared with the usual care group (CCQ mean difference -0·12, 95% CI -0·21 to -0·02 [p=0·016]; FLUPro mean difference -0·10, 95% CI -0·21 to -0·00 [p=0·044]). Blood oxygen saturations and SARS-CoV-2 load, measured by cycle threshold, were not different between the groups. Budesonide was safe, with only five (7%) participants reporting self-limiting adverse events. INTERPRETATION: Early administration of inhaled budesonide reduced the likelihood of needing urgent medical care and reduced time to recovery after early COVID-19. FUNDING: National Institute for Health Research Biomedical Research Centre and AstraZeneca.

The perfect storm: Disruptions to institutional delivery care arising from the COVID-19 pandemic in Nepal.

BACKGROUND: The COVID-19 pandemic has led to system-wide disruption of health services globally. We assessed the effect of the pandemic on the disruption of institutional delivery care in Nepal. METHODS: We conducted a prospective cohort study among 52 356 women in nine hospitals to assess the disruption of institutional delivery care during the pandemic (comparing March to August in 2019 with the same months in 2020). We also conducted a nested follow up cohort study with 2022 women during the pandemic to assess their provision and experience of respectful care. We used linear regression models to assess the association between provision and experience of care with volume of hospital births and women's residence in a COVID-19 hotspot area. RESULTS: The mean institutional births during the pandemic across the nine hospitals was 24 563, an average decrease of 11.6% (P < 0.0001) in comparison to the same time-period in 2019. The institutional birth in high-medium volume hospitals declined on average by 20.8% (P < 0.0001) during the pandemic, whereas in low-volume hospital institutional birth increased on average by 7.9% (P = 0.001). Maternity services halted for a mean of 4.3 days during the pandemic and there was a redeployment staff to COVID-19 dedicated care. Respectful provision of care was better in hospitals with low-volume birth (ß = 0.446, P < 0.0001) in comparison to high-medium-volume hospitals. There was a positive association between women's residence in a COVID-19 hotspot area and respectful experience of care (ß = 0.076, P = 0.001). CONCLUSIONS: The COVID-19 pandemic has had differential effects on maternity services with changes varying by the volume of births per hospital with smaller volume facilities doing better. More research is needed to investigate the effects of the pandemic on where women give birth and their provision and experience of respectful maternity care to inform a "building-back-better" approach in post-pandemic period.

Mental Distress and Human Rights Violations During COVID-19: A Rapid Review of the Evidence Informing Rights, Mental Health Needs, and Public Policy Around Vulnerable Populations.

Background: COVID-19 prevention and mitigation efforts were abrupt and challenging for most countries with the protracted lockdown straining socioeconomic activities. Marginalized groups and individuals are particularly vulnerable to adverse effects of the pandemic such as human rights abuses and violations which can lead to psychological distress. In this review, we focus on mental distress and disturbances that have emanated due to human rights restrictions and violations amidst the pandemic. We underscore how mental health is both directly impacted by the force of pandemic and by prevention and mitigation structures put in place to combat the disease. Methods: We conducted a review of relevant studies examining human rights violations in COVID-19 response, with a focus on vulnerable populations, and its association with mental health and psychological well-being. We searched PubMed and Embase databases for studies between December 2019 to July 2020. Three reviewers evaluated the eligibility criteria and extracted data. Results: Twenty-four studies were included in the systematic inquiry reporting on distress due to human rights violations. Unanimously, the studies found vulnerable populations to be at a high risk for mental distress. Limited mobility rights disproportionately harmed psychiatric patients, low-income individuals, and minorities who were at higher risk for self-harm and worsening mental health. Healthcare workers suffered negative mental health consequences due to stigma and lack of personal protective equipment and stigma. Other vulnerable groups such as the elderly, children, and refugees also experienced negative consequences. Conclusions: This review emphasizes the need to uphold human rights and address long term mental health needs of populations that have suffered disproportionately during the pandemic. Countries can embed a proactive psychosocial response to medical management as well as in existing prevention strategies. International human rights guidelines are useful in this direction but an emphasis should be placed on strengthening rights informed psychosocial response with specific strategies to enhance mental health in the long-term. We underscore that various fundamental human rights are interdependent and therefore undermining one leads to a poor impact on the others. We strongly recommend global efforts toward focusing both on minimizing fatalities, protecting human rights, and promoting long term mental well-being.

Improving Hospital Oxygen Systems for COVID-19 in Low-Resource Settings: Lessons From the Field.

Oxygen therapy is an essential medicine and core component of effective hospital systems. However, many hospitals in low- and middle-income countries lack reliable oxygen access-a deficiency highlighted and exacerbated by the coronavirus disease (COVID-19) pandemic. Oxygen access can be challenged by equipment that is low quality and poorly maintained, lack of clinical and technical training and protocols, and deficiencies in local infrastructure and policy environment. We share learnings from 2 decades of oxygen systems work with hospitals in Africa and the Asia-Pacific regions, highlighting practical actions that hospitals can take to immediately expand oxygen access. These include strategies to: (1) improve pulse oximetry and oxygen use, (2) support biomedical engineers to optimize existing oxygen supplies, and (3) expand on existing oxygen systems with robust equipment and smart design. We make all our resources freely available for use and local adaptation.