Prone position versus usual care in hypoxemic COVID-19 patients in medical wards: a randomised controlled trial.

BACKGROUND: Benefit of early awake prone positioning for COVID-19 patients hospitalised in medical wards and who need oxygen therapy remains to be demonstrated. The question was considered at the time of COVID-19 pandemic to avoid overloading the intensive care units. We aimed to determine whether prone position plus usual care could reduce the rate of non-invasive ventilation (NIV) or intubation or death as compared to usual care alone. METHODS: In this multicentre randomised clinical trial, 268 patients were randomly assigned to awake prone position plus usual care (N = 135) or usual care alone (N = 132). The primary outcome was the proportion of patients who underwent NIV or intubation or died within 28 days. Main secondary outcomes included the rates of NIV, of intubation or death, within 28 days. RESULTS: Median time spent each day in the prone position within 72 h of randomisation was 90 min (IQR 30-133). The proportion of NIV or intubation or death within 28 days was 14.1% (19/135) in the prone position group and 12.9% (17/132) in the usual care group [odds ratio adjusted for stratification (aOR) 0.43; 95% confidence interval (CI) 0.14-1.35]. The probability of intubation, or intubation or death (secondary outcomes) was lower in the prone position group than in the usual care group (aOR 0.11; 95% CI 0.01-0.89 and aOR 0.09; 95% CI 0.01-0.76, respectively) in the whole study population and in the prespecified subgroup of patients with SpO2 ≥ 95% on inclusion (aOR 0.11; 95% CI 0.01-0.90, and aOR 0.09; 95% CI 0.03-0.27, respectively). CONCLUSIONS: Awake prone position plus usual care in COVID-19 patients in medical wards did not decrease the composite outcome of need for NIV or intubation or death. Trial registration ClinicalTrials.gov Identifier: NCT04363463 . Registered 27 April 2020.

Does awake prone positioning prevent the use of mechanical respiratory support or death in COVID-19 patients on standard oxygen therapy hospitalised in general wards? A multicentre randomised controlled trial: the PROVID-19 protocol.

INTRODUCTION: COVID-19 is responsible of severe hypoxaemia and acute respiratory distress syndrome (ARDS). Prone positioning improves oxygenation and survival in sedated mechanically patients with ARDS not related to COVID-19. Awake prone positioning is a simple and safe technique which improves oxygenation in non-intubated COVID-19 patients. We hypothesised that early prone positioning in COVID-19 patients breathing spontaneously in medical wards could decrease the rates of intubation or need for noninvasive ventilation or death. METHODS AND ANALYSIS: PROVID-19 is an investigator-initiated, prospective, multicentre randomised, controlled, superiority trial comparing awake prone positioning to standard of care in hypoxaemic COVID-19 patients in 20 medical wards in France and Monaco. Patients are randomised to receive either awake prone position plus usual care or usual care alone with stratification on centres, body mass index and severity of hypoxaemia.The study objective is to compare the rate of treatment failure defined as a composite endpoint comprising the need for non-invasive ventilation (at two pressure levels) or for intubation or death, between the intervention group (awake prone position plus usual care) and the usual care (usual care alone) group at 28 days. ETHICS AND DISSEMINATION: The protocol and amendments have been approved by the ethics committees (Comité de protection des personnes Ouest VI, France, no 1279 HPS2 and Comité Consultatif d'Ethique en matière de Recherche Biomédicale, Monaco, no 2020.8894 AP/jv), and patients are included after written informed consent. The results will be submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04363463.

Efficacy and safety of anakinra in adults presenting deteriorating respiratory symptoms from COVID-19: A randomized controlled trial.

OBJECTIVE: We aimed to investigate whether anakinra, an interleukin-1receptor inhibitor, could improve outcome in moderate COVID-19 patients. METHODS: In this controlled, open-label trial, we enrolled adults with COVID-19 requiring oxygen. We randomly assigned patients to receive intravenous anakinra plus optimized standard of care (oSOC) vs. oSOC alone. The primary outcome was treatment success at day 14 defined as patient alive and not requiring mechanical ventilation or extracorporeal membrane oxygenation. RESULTS: Between 27th April and 6th October 2020, we enrolled 71 patients (240 patients planned to been enrolled): 37 were assigned to the anakinra group and 34 to oSOC group. The study ended prematurely by recommendation of the data and safety monitoring board due to safety concerns. On day 14, the proportion of treatment success was significantly lower in the anakinra group 70% (n = 26) vs. 91% (n = 31) in the oSOC group: risk difference-21 percentage points (95% CI, -39 to -2), odds ratio 0.23 (95% CI, 0.06 to 0.91), p = 0.027. After a 28-day follow-up, 9 patients in the anakinra group and 3 in the oSOC group had died. Overall survival at day 28 was 75% (95% CI, 62% to 91%) in the anakinra group versus 91% (95% CI, 82% to 100%) (p = 0.06) in the oSOC group. Serious adverse events occurred in 19 (51%) patients in the anakinra group and 18 (53%) in the oSOC group (p = 0·89). CONCLUSION: This trial did not show efficacy of anakinra in patients with COVID-19. Furthermore, contrary to our hypothesis, we found that anakinra was inferior to oSOC in patients with moderate COVID-19 pneumonia.

Seroprevalence of anti-SARS-CoV-2 antibodies after the first wave of the COVID-19 pandemic in a vulnerable population in France: a cross-sectional study.

OBJECTIVES: We aimed to assess the level of prior SARS-CoV-2 infection in socially deprived neighbourhoods after the first wave of the pandemic, and to identify factors associated with seropositivity. DESIGN: A cross-sectional study. SETTING: Three socially deprived neighbourhoods of the city of Perpignan, in the south of France, where large settled Roma communities live. PARTICIPANTS: People aged 6 years old or over, living in the study area. 700 people were included in the study using two-stage stratified sampling design. INTERVENTIONS: The study included a questionnaire and SARS-CoV-2 antibody testing by the Roche Elecsys immunoassay between 29 June and 17 July 2020. PRIMARY AND SECONDARY OUTCOME MEASURES: SARS-CoV-2 antibody seroprevalence was estimated from weighted data. Associated factors and reported symptoms were investigated using univariable and multivariable logistic regressions. RESULTS: The seroprevalence of anti-SARS-CoV-2 antibodies was 35.4% (95% CI 30.2% to 41.0%). People aged 15-64 years old had increased odds of being seropositive than those aged 65 years or over. Obese people had higher odds of being seropositive (adjusted OR (aOR)=2.0, 95% CI 1.1 to 3.8). The odds of being seropositive were higher in households with clinical COVID-19 cases (one case: aOR=2.5, 95% CI 1.3 to 5.0; several cases: aOR=6.9, 95% CI 3.1 to 15.2). In the neighbourhood with the highest measured seroprevalence, people living in a dwelling with one to two rooms had higher odds of being seropositive than those living in a four-room house (aOR=2.8, 95% CI 1.2 to 6.3). Working during the lockdown was associated with lower odds of being seropositive (aOR=0.2, 95% CI 0.03 to 1.0). CONCLUSION: Transmission of SARS-COV-2 in this vulnerable population was very high during the COVID-19 pandemic's first wave. Our results highlight the need to strengthen and adapt preventive measures taking into account all social determinants of health, especially housing conditions.