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: 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
P18 Figure 1The percentage of exacerbations with bacteria detected in sputum by qPCR, according to respiratory virus identified at exacerbation, at a) exacerbation onset (n=30) and at b) two weeks (n=11). HI = H. influenzae, SP = S. pneumoniae, MC = M. catarrhalis. RV = rhinovirus, HCV = human coronaviruses, FluA = influenza A, Other = a combination of the other viral exacerbations[Figure omitted. See PDF]ConclusionsSecondary bacterial outgrowth occurs in COPD exacerbations caused by a range of respiratory viruses suggesting that viral infection results in microbiome dysbiosis. Bacterial qPCR detected several bacteria that were not identified using standard microbiological culture with a high bacterial load and Moraxella detection at two weeks Bacterial overgrowth may explain why some exacerbations show prolonged recovery.
ABSTRACT
Introduction: The use of systemic corticosteroids to suppress SARS-CoV-2-induced lung inflammation is advocated in the treatment of COVID-19 ARDS.1,2 Whilst the evidence for low dose early corticosteroids in COVIDARDS is well established, the effect of larger steroid doses (i.e. short-term 'pulse-dose') is yet to be investigated. Objectives: The objective of this study was to examine the effect of pulse dose steroids on ventilatory parameters such as oxygenation in COVID-19 patients with and without established fibrosis or organising pneumonia (OP). Methods: This was a multi-centre, retrospective observational study performed at four teaching hospitals, with the following inclusion criteria: adult patients requiring invasive mechanical ventilation with confirmed PCR SARS-CoV-2 infection;and received high dose steroids for treatment for COVID-ARDS (defined as dose ≥ 20mg dexamethasone or an equivalent dose of methylprednisolone). This study was carried out as a service evaluation within the National Health Service (NHS) and recorded under the auspices of the clinical audit office at Imperial College HealthcareNHS Trust and Institutional Data Protection Office. Study patients were followed for 14 days or until they were discharged from the ICU and physiological or ventilatory variable data was retrospectively collected from patient records. Results: In total, 92 patients were included: 14 patients 20mg/day dexamethasone;5 patients 50mg/day dexamethasone;16 patients 500mg methylprednisolone;and 57 patients 1000mg methylprednisolone. Our data demonstrate a statistically significant improvement in PaO2/FiO2 (P/F) ratio over time, from baseline to day 14, in those patients who received 1000mg Methylprednisolone (baseline PaO2: 14.47 kPa, Day 3: 17.51 kPa, Day 7: 19.51 kPa, Day 14: 22.87 kPa, p<0.001). Whilst not statistically significant, there was a trend to higher P/F ratios by day 14 in patients who received 500mg Methylprednisolone group. There was no increase in P/F ratios in those patients who received 20mg or 50mg dexamethasone. The increase in P/F ratio was most apparent in those patients who had evidence of fibrosis on CT scan, although some benefit was seen in those patients who did not fibrosis on radiological imaging. Cross sectional random effects models were used to determine the effect of 1000mg methylprednisolone on improvement in P/F ratio and demonstrate that there was an increase of P/F ratio of more than 0.38 kPa per day in those patients that received 1000mg methylprednisolone. The was no significant effect on compliance measures. There was also a trend to more ventilator free days but no difference in mortality in those patients receiving large dose methylprednisolone. Reassuringly, rates of fungal infection and pneumothorax/pneumomediastinum for patients who received steroids, including those with high dose, were equivocal. Conclusion: In this study, we present novel data suggesting that large doses of methylprednisolone may be beneficial in patients with severe COVID-19, late in the disease course when ARDS is well established. This benefit was not demonstrated in patients treated with lesser (but still high) doses of steroids (i.e. 20mg or 50mg of dexamethasone) and suggest that larger pulsed-dose steroids may induce reversibility of the disease process, particularly in those who have developed fibrosis.
ABSTRACT
Case Report A 25 year old woman, G3P2 at 23w6d presented to the Emergency Department for one week of progressive cough and shortness of breath. Patient was febrile, tachypnic, with oxygen desaturation to 88% with minimal exertion. Chest radiograph showed bilateral airspace disease consistent with viral pneumonia. The Patient was diagnosed with covid- 19 and admitted for acute hypoxic respiratory failure secondary and started on dexamethasone and remdesivir. The patient subsequently had escalating oxygen requirements and was stepped up to the ICU on BIPAP on hospital day two. Her oxygen requirements gradually improved, and she was stepped down to the floor on day 8 of admission on highflow nasal cannula. The following day, the patient was noted to have oxygen saturation of 97% on room air with a disposable finger probe applied to the forehead. Placement of the finger probe on the forehead is an uncommon practice reserved for use when unable to obtain adequate wave-form on the finger. A separate evaluation that day using a disposable finger probe on the finger revealed markedly different oxygen saturation in the low 90's. Confirmatory ABG showed pH 7.46, pCO2 31, O2 48, and HCO3 22. After determining hypoxemia, we placed disposable finger probes on both the finger and forehead at the same time using two separate machines. The probe on the forehead showed an spO2 consistently 10% higher than the reading on the finger. The probe connectors were switched and continued to show a 10% higher reading on the probe attached to the forehead. Discussion Given the hypoxemia confirmed on ABG, we concluded that the disposable finger probe used on the forehead provided a falsely elevated spO2 reading. One small study comparing disposable finger probes on the finger vs the forehead showed a discrepancy of >5% in over half of the patients. Critical management decisions are made based on the spO2, and inaccurate readings pose significant risk to the patient. Use of disposable finger probes on the forehead should be avoided.
ABSTRACT
The COVID-19 pandemic has caused millions of deaths and devastated communities across the globe. Vaccines will play a key role in bringing the pandemic under control, with successful clinical trials, authorizations and roll-out having now occurred in several countries. However, large-scale manufacturing of such vaccines remains a bottleneck to delivering doses to billions of people at risk of infection, as well as producing new versions of the vaccines that target variants. Here we discuss the current status of manufacturing, focusing on the adenovirus-vectored vaccine developed by the University of Oxford and how the process for manufacturing it was developed. © 2021 The Authors. Published by Portland Press Limited. All Rights Reserved.
ABSTRACT
INTRODUCTION: Public health measures to reduce the transmission of COVID-19 have required various changes in life-style, including loss or risk to employment and social isolation. We wished to assess how these measured effected 30-45 year old smokers at risk of COPD participating in the BLF Early COPD cohort study METHODS: At enrolment, participants were aged 30-45 years, tobacco smokers with >10 pack-year smoking history, FEV1=>80% predicted and a BMI < 35kg/m2. Participants were seen face-to-face in clinic pre-COVID. During lock-down, they were posted questionnaires and contacted by telephone. The last clinic visit took place on the 12 March 2020, remote visits took place between 16 April and 28 Sep. 260 individuals at six sites (25 Belfast, 38 Birmingham, 25 Edinburgh, 101 London, 27 Manchester and 44 Nottingham) were asked about smoking habits. The MRC chronic bronchitis questionnaire, COPD Assessment test (CAT), Leicester cough questionnaire, Hospital Anxiety and Depression questionnaire were completed in writing by the participant and returned by post or photographed and returned by email. At enrolment, the post-BD FEV1 was 3.81 (SD 0.8) litres, 101% (11) of GLI predicted. Comparisons were made by paired t-tests and chi-squared tests. RESULTS: Level of anxiety increased from 6.74 (SD 4.4) to 7.37 (SD 4.7, n=233;p=0.010) during lock-down;depression scores increased from 4.30 (3.9) to 5.14 (SD 4.1;n=233;p<0.001). Anxiety increased in 78/233 and depression in 89/233 participants by 2 or more units, 2 units is considered the minimally important (MCID) in bronchiectasis, COPD and ILD (Wynne, 2020) Figure 1 shows that during lock-down, the proportion of participants not smoking increased from 31/259 (12.0%) to 62/259 (23.9%;p<0.001). In those who continued to smoke, cigarettes per day (p=0.59) and rolling tobacco consumption (g/week) (p=0.92) were unchanged. Participants reported less chronic bronchitis defined as “do you bring up phlegm like this on most days (or nights) as much as three months each year”, fell from 83/260 (31.9%) participants to 74/259 (28.6%;p<0.001). CAT scores fell from 10.5 (SD 6.4) to 9.6 (SD 6.3;n=233;p=0.007) and total cough score improved from 18.7 (SD 2.7) to 19.1 (2.6;n=204;p=0.007). CONCLUSIONS: Despite increased anxiety and depression, participants quit smoking and those that continued to smoke, did not smoke more. Respiratory symptoms of chronic bronchitis, cough and CAT scores improved. REFERENCES:Wynne SC, et al. Chron Respir Dis. 2020 Jan-Dec;17:1479973120933292. doi: 10.1177/1479973120933292. .