ABSTRACT
Background: Oral anti-viral therapies are licensed worldwide in COVID-19 but indications and efficacy rates vary. Aims and Objectives: To evaluate the safety and efficacy of oral favipiravir in patients hospitalised with COVID-19. Method(s): We conducted a multi-centre, open-label, randomised controlled trial of oral favipiravir in patients newly hospitalised with COVID-19, in five centres worldwide. 500 participants were randomised 1:1 to receive oral favipiravir (1800 mg twice daily (BD) for one-day;800 mg BD for nine-days) plus standard care (SC), or SC alone. NCT: 04373733. Result(s): Recruitment was performed between May 2020 and May 2021, with 251 patients randomised to favipiravir and 249 to SC. There was no difference in time to recovery in all patients (HR 1 06;95% CI 0 89-1 27;n=499;p=0.52). A faster rate of recovery was observed in patients receiving favipiravir under the age of 60 years (HR 1 35;95% CI 1 06-1 72;n=247, p=0 01). A 66 % improvement in mechanical ventilation free survival was evident in patients under 60-years of age (HR 0 34;95% CI 0 13-0 85;n=247, p=0 02). A non-significant 26 % reduction in mortality was observed in patients receiving favipiravir (favipiravir: 26;SC: 34;p=0 24). No significant differences were observed in serious adverse events (SAE) between arms (favipiravir: 36 in 27 patients;SC: 33 in 27 patients). Conclusion(s): Orally administered favipiravir has a beneficial effect on recovery, and mechanical ventilation freesurvival in patients under 60-years of age, hospitalised with COVID-19. Wider evaluation of anti-viral medications and their potential treatment combinations is warranted in patients with COVID-19.
ABSTRACT
Background: Airway inflammation post COVID-19 is a possible cause for persistent breathlessness. Aim(s): We sought to evaluate the role of fractional exhaled nitric oxide (FeNO) measurements in this cohort. Methodology: We report FeNO results in patients undergoing lung function testing as part of the PHENOTYPE study (NCT 04459351). Result(s): 83 patients had FeNO performed between January and Nov 2021. Of the patients admitted to hospital (n=78), the median time to testing from discharge was 96 days (IQR 90-115). Median FeNO results for the whole cohort was 20 ppb (16-29). 24/83 (29%) had a FeNO in the intermediate range [median 33 (IQR 28-45)], and 5/83 (6%), FeNO >50 ppb. Chi squared testing revealed no relationship between patient-reported breathlessness (p=0.12) or cough (p=0.45) and FeNO >=25ppb. 52 patients underwent repeat lung function and FeNO testing at a median of 363 (355-370) days post discharge. 26/52 (50%) of individuals had a FeNO>=25 ppb, with a median 35 (28-42): 10/52 (19%) deteriorated from normal to intermediate range and 2/52 from intermediate to high range as compared to initial values. 7/52 (13%) of FeNO results that were abnormal at the first visit, normalized with no additional treatment. Again, no association was found between breathlessness (p=0.48) or cough (p=0.73) at the second visit and a FeNO result >=25ppb. None of the patients with a FeNO >= 25 had a prior diagnosis of asthma. Conclusion(s): The clinical relevance of an intermediate or high FeNO in this cohort is unclear. However, this preliminary work highlights that in a significant proportion of patients, the FeNO is not normal even at 1 year post discharge. The trajectory of these changes and in particular, development of small airways disease are important to study.
ABSTRACT
Background: Small airway disease (SAD) can occur following viral infection, but the prevalence of this in individuals recovering post SARS-COV2 infection is not known. Aim(s): We sought to assess the prevalence of SAD in patients 1 year post hospital discharge for COVID-19. Method(s): A subset of patients recruited to the PHENOTYPE study (NCT 04459351) underwent forced oscillometry assessment (THORASYS). We assessed the fall in resistance from 5 to 20 Hz (R5-R20) as a marker of peripheral airway dysfunction. A value of >0.07kPa/L/s was used as a cut off definition for small airways dysfunction. All patients had lung function testing and a clinical assessment of symptoms within a median of 7.5 (IQR 4-15) days and median of 7 (IQR 4-11) days, respectively, of small airways testing. Result(s): 40 patients were enrolled between November 2021 and January 2022, at a median of 371 days (IQR 359- 380) post hospital discharge. 31/40 (78%) were male with a median age of 63 (IQR 51-72). The median length of hospital stay was 6.5 days (IQR 4-12). 11/40 patients had required non-invasive ventilation and 29/40 oxygen therapy alone. 11/40 (28%) of patients had evidence of SAD. Self-reported breathlessness (p=0.75) and cough (p=0.50) at 1 year were not increased in SAD. Similarly, there was no association between SAD and ventilatory status (p=0.98), FENO>=25 (p=0.63) or FENO> 50 (p=0.86) at 3 months or FENO >=25 (p=0.87) or FENO>50 (p=0.29) at 1 year. Conclusion(s): Small airways disease is present in patients recovering post COVID-19 but the risk factors for developing this is unclear. Longitudinal studies are required to assess the trajectory and long term impact of small airways pathology.
ABSTRACT
Background. There are few real-world data on the use of remdesivir (RDV) looking at timing of initiation in relation to symptom onset and severity of presenting disease. Methods. We conducted multi-country retrospective study of clinical practice and use of RDV in COVID-19 patients. De-identified medical records data were entered into an e-CRF. Primary endpoints were all-cause mortality at day 28 and hospitalization duration. We assessed time from symptom onset to RDV start and re-admission. We included adults with PCR-confirmed symptomatic COVID-19 who were hospitalized after Aug 31, 2020 and received at least 1 dose of RDV. Descriptive analyses were conducted. Kaplan-Meier methods were used to calculate the mortality rate, LogRank test to compare groups defined by severity of disease. Competing risk regression with discharge and death as competing events was used to estimate duration of hospitalization, and Gray's test to compare the groups. Results. 448 patients in 5 countries (12 sites) were included. Demographics are summarized (table) by 3 disease severity groups at baseline: no supplemental oxygen (NSO), low flow oxygen ≤6 L/min (LFO), and high-flow oxygen > 6L/min (HFO). No demographic differences were found between groups except for the higher percentage of cancer/chemotherapy patients in NSO group. Corticosteroids use was HFO 73.6%, LFO 62.7%, NSO 58.0%. Mortality rate was significantly lower in NSO, and LFO groups compared with HFO (6.2%, 10.2%, 23.6%, respectively;Fig1). Median duration of hospitalization was 9 (95%CI 8-10), 9 (8-9), 13 (10-15) days, respectively (Fig2). Median time from first symptom to RDV start was 7 days in all 3 groups. Patients started RDV on day 1 of hospitalization in HFO and LFO and day 2 on NSO groups. And received a 5 day course (median). Readmission within 28-days of discharge was < 5% and similar across all 3 groups. Conclusion. In this real-world cohort of COVID-19 positive hospitalized patients, RDV use was consistent across countries. RDV was started within a median of 7 days from symptom within 2 days of admission and given for a median of 5 days. Higher mortality rate and duration of hospitalization was seen in the HFO group and similar rates seen in the LFO and NSO groups. Readmission was consistently low across all 3 groups.
ABSTRACT
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has resulted in an unprecedented shutdown in social and economic activity, with the cultural sector particularly severely affected. Restrictions on musical performances have arisen from a perception that there is a significantly higher risk of aerosol production from singing than speaking, based upon high-profile examples of clusters of COVID-19 following choral rehearsals. However, comparing aerosol generation from different types of vocalization, including singing, across a range of volumes is a rapidly evolving area of research. Here, we measured aerosols from singing, speaking and breathing from a large cohort of 25 professional singers in a range of musical genres in a zero-background environment, allowing unequivocal attribution of aerosol production to specific vocalizations. We do not assess the relative volumes at which people speak and sing. However, both showed steep increases in mass concentration with increase in loudness (spanning a factor of 20–30 across the dynamic range measured, p < 0.001). At the quietest volume (50 to 60 dBA), neither singing (p = 0.19) nor speaking (p = 0.20) were significantly different to breathing. At the loudest volume (90 to 100 dBA), a statistically significant difference (p < 0.001) was observed between singing and speaking, but with singing only generating a factor of between 1.5 and 3.4 more aerosol mass. Guidelines for musical performances should be based on the loudness and duration of the vocalization, the number of participants and the environment in which the activity occurs, rather than the type of vocalization. Mitigations such as the use of amplification and increased attention to ventilation should be employed where practicable. Copyright © 2021 American Association for Aerosol Research. © 2021 American Association for Aerosol Research.