Favipiravir in patients hospitalised with COVID-19 (PIONEER trial): a multicentre, open-label, phase 3, randomised controlled trial of early intervention versus standard care.

BACKGROUND: COVID-19 has overwhelmed health services globally. Oral antiviral therapies are licensed worldwide, but indications and efficacy rates vary. We aimed to evaluate the safety and efficacy of oral favipiravir in patients hospitalised with COVID-19. METHODS: We conducted a multicentre, open-label, randomised controlled trial of oral favipiravir in adult patients who were newly admitted to hospital with proven or suspected COVID-19 across five sites in the UK (n=2), Brazil (n=2) and Mexico (n=1). Using a permuted block design, eligible and consenting participants were randomly assigned (1:1) to receive oral favipiravir (1800 mg twice daily for 1 day; 800 mg twice daily for 9 days) plus standard care, or standard care alone. All caregivers and patients were aware of allocation and those analysing data were aware of the treatment groups. The prespecified primary outcome was the time from randomisation to recovery, censored at 28 days, which was assessed using an intention-to-treat approach. Post-hoc analyses were used to assess the efficacy of favipiravir in patients aged younger than 60 years, and in patients aged 60 years and older. The trial was registered with clinicaltrials.gov, NCT04373733. FINDINGS: Between May 5, 2020 and May 26, 2021, we assessed 503 patients for eligibility, of whom 499 were randomly assigned to favipiravir and standard care (n=251) or standard care alone (n=248). There was no significant difference between those who received favipiravir and standard care, relative to those who received standard care alone in time to recovery in the overall study population (hazard ratio [HR] 1·06 [95% CI 0·89-1·27]; n=499; p=0·52). Post-hoc analyses showed a faster rate of recovery in patients younger than 60 years who received favipiravir and standard care versus those who had standard care alone (HR 1·35 [1·06-1·72]; n=247; p=0·01). 36 serious adverse events were observed in 27 (11%) of 251 patients administered favipiravir and standard care, and 33 events were observed in 27 (11%) of 248 patients receiving standard care alone, with infectious, respiratory, and cardiovascular events being the most numerous. There was no significant between-group difference in serious adverse events per patient (p=0·87). INTERPRETATION: Favipiravir does not improve clinical outcomes in all patients admitted to hospital with COVID-19, however, patients younger than 60 years might have a beneficial clinical response. The indiscriminate use of favipiravir globally should be cautioned, and further high-quality studies of antiviral agents, and their potential treatment combinations, are warranted in COVID-19. FUNDING: LifeArc and CW+.

Quality of maternal and newborn care around the time of childbirth in Luxembourg during the COVID-19 pandemic: Results of the IMAgiNE EURO study.

OBJECTIVE: To investigate the quality of maternal and newborn care (QMNC) during childbirth in Luxembourg from women's perspectives. METHODS: Women giving birth in facilities in Luxembourg between March 1, 2020, and July 1, 2021, answered a validated online WHO standards-based questionnaire as part of the multicountry IMAgINE EURO study. Descriptive and multivariate quantile regression analyses were performed. RESULTS: A total of 493 women were included, representing 5.2% of women giving birth in the four maternity hospitals in Luxembourg during the study period. Most quality measures suggested high QMNC, although specific gaps were observed: 13.4% (n = 66) of women reported not being treated with dignity, 9.1% (n = 45) experienced abuse, 42.9% (n = 30) were not asked for consent prior to instrumental vaginal birth, 39.3% (n = 118) could not choose their birth position, 27% (n = 133) did not exclusively breastfeed at discharge (without significant differences over time), 20.5% (n = 101) reported an insufficient number of healthcare professionals, 20% (n = 25) did not receive information on the newborn after cesarean, and 41.2% (n = 203) reported lack of information on newborn danger signs before discharge. Multivariate analyses highlighted higher reported QMNC indexes among women born outside Luxembourg and delivering with a gynecologist, and significantly lower QMNC indexes in women with the highest education levels and those delivering in the hospital offering some private services. CONCLUSIONS: Despite maternal reports suggesting an overall high QMNC in Luxembourg, improvements are needed in specific aspects of care and communication, mostly related to maternal autonomy, respect, and support, but also number and competencies of the health workforce.

Pneumomediastinum in COVID-19: a phenotype of severe COVID-19 pneumonitis? The results of the United Kingdom (POETIC) survey.

BACKGROUND: There is an emerging understanding that coronavirus disease 2019 (COVID-19) is associated with increased incidence of pneumomediastinum. We aimed to determine its incidence among patients hospitalised with COVID-19 in the United Kingdom and describe factors associated with outcome. METHODS: A structured survey of pneumomediastinum and its incidence was conducted from September 2020 to February 2021. United Kingdom-wide participation was solicited via respiratory research networks. Identified patients had SARS-CoV-2 infection and radiologically proven pneumomediastinum. The primary outcomes were to determine incidence of pneumomediastinum in COVID-19 and to investigate risk factors associated with patient mortality. RESULTS: 377 cases of pneumomediastinum in COVID-19 were identified from 58 484 inpatients with COVID-19 at 53 hospitals during the study period, giving an incidence of 0.64%. Overall 120-day mortality in COVID-19 pneumomediastinum was 195/377 (51.7%). Pneumomediastinum in COVID-19 was associated with high rates of mechanical ventilation. 172/377 patients (45.6%) were mechanically ventilated at the point of diagnosis. Mechanical ventilation was the most important predictor of mortality in COVID-19 pneumomediastinum at the time of diagnosis and thereafter (p<0.001) along with increasing age (p<0.01) and diabetes mellitus (p=0.08). Switching patients from continuous positive airways pressure support to oxygen or high flow nasal oxygen after the diagnosis of pneumomediastinum was not associated with difference in mortality. CONCLUSIONS: Pneumomediastinum appears to be a marker of severe COVID-19 pneumonitis. The majority of patients in whom pneumomediastinum was identified had not been mechanically ventilated at the point of diagnosis.

COVID-19, Acute Myocardial Injury, and Infarction.

Severe acute respiratory syndrome coronavirus-2 can affect the cardiovascular system yielding a wide range of complications, including acute myocardial injury. The myocardium can be damaged by direct viral invasion or indirect mechanisms, sustained by systemic inflammation, immune-mediated response, and dysregulation of the renin-angiotensin system. Myocardial injury affects about one-quarter of patients with COVID-19, can manifest even in the absence of previous cardiovascular disease, and is associated to higher mortality rates and long-term sequelae. This review describes the pathophysiological mechanisms of myocardial injury and infarction and discusses the main clinical outcomes and diagnostic challenges associated with myocardial damage during COVID-19.