ABSTRACT
We investigated Favipiravir (FPV) efficacy in mild cases of COVID-19 without pneumonia and its effects towards viral clearance, clinical condition, and risk of COVID-19 pneumonia development. PCR-confirmed SARS-CoV-2-infected patients without pneumonia were enrolled (2:1) within 10 days of symptomatic onset into FPV and control arms. The former received 1800 mg FPV twice-daily (BID) on Day 1 and 800 mg BID 5-14 days thereafter until negative viral detection, while the latter received supportive care only. The primary endpoint was time to clinical improvement, which was defined by a reduced National Early Warning Score (NEWS) or score of <1. 62 patients (41 female) comprised the FPV arm (median age: 32 years, median BMI: 22 kg/m2) and 31 patients (19 female) comprised the control arm (median age: 28 years, median BMI: 22 kg/m2). The median time to sustained clinical improvement by NEWS was 2 vs 14 days for FPV and control arms respectively (adjusted hazard ratio (aHR) of 2.77, 95% CI 1.57-4.88, P <0.001). The FPV arm also had significantly higher likelihoods of clinical improvement within 14 days after enrolment by NEWS (79% vs 32% respectively, P <0.001), particularly female patients (aOR 6.35, 95% CI 1.49-27.07, P <0.001). 8 (12.9%) and 7 (22.6%) patients in FPV and control arms developed mild pneumonia at a median (range) 6.5 (1-13) and 7 (1-13) days after treatment, respectively (P = 0.316); all recovered well without complications. We can conclude that early treatment of FPV in symptomatic COVID-19 patients without pneumonia was associated with faster clinical improvement.
Subject(s)
Pneumonia , Severe Acute Respiratory Syndrome , COVID-19ABSTRACT
We assessed the pharmacokinetics of favipiravir (FPV) in adults with symptomatic SARS-CoV-2 infection without pneumonia in Thailand. FPV dosing was 1800 mg twice-daily on day 1, then 800 mg twice-daily for 14 days. Eight subjects (7 female), median (range) age 39 (19-53) years and BMI 27.9 (18.0-33.6) were included. Inter-subject variability was high but all achieved minimum plasma concentrations (Cmin) above EC50 (9.7 mg/L). FPV was well tolerated; 1 subject stopped prematurely due to rash.
Subject(s)
COVID-19 , Exanthema , PneumoniaABSTRACT
Background The unprecedented public health impact of the COVID-19 pandemic has motivated a rapid search for potential therapeutics, with some key successes. However, the potential impact of different treatments, and consequently research and procurement priorities, have not been clear. Methods and Findings We develop a mathematical model of SARS-CoV-2 transmission, COVID-19 disease and clinical care to explore the potential public-health impact of a range of different potential therapeutics, under a range of different scenarios varying: i) healthcare capacity, ii) epidemic trajectories; and iii) drug efficacy in the absence of supportive care. In each case, the outcome of interest was the number of COVID-19 deaths averted in scenarios with the therapeutic compared to scenarios without. We find the impact of drugs like dexamethasone (which are delivered to the most critically-ill in hospital and whose therapeutic benefit is expected to depend on the availability of supportive care such as oxygen and mechanical ventilation) is likely to be limited in settings where healthcare capacity is lowest or where uncontrolled epidemics result in hospitals being overwhelmed. As such, it may avert 22% of deaths in high-income countries but only 8% in low-income countries (assuming R=1.35). Therapeutics for different patient populations (those not in hospital, early in the course of infection) and types of benefit (reducing disease severity or infectiousness, preventing hospitalisation) could have much greater benefits, particularly in resource-poor settings facing large epidemics. Conclusions There is a global asymmetry in who is likely to benefit from advances in the treatment of COVID-19 to date, which have been focussed on hospitalised-patients and predicated on an assumption of adequate access to supportive care. Therapeutics that can feasibly be delivered to those earlier in the course of infection that reduce the need for healthcare or reduce infectiousness could have significant impact, and research into their efficacy and means of delivery should be a priority.
Subject(s)
COVID-19ABSTRACT
Background: The unprecedented public health impact of the COVID-19 pandemic has motivated a rapid search for potential therapeutics, with some key successes. However, the potential impact of current and proposed treatments, and consequently research and procurement priorities, have not been clear. Methods: First, we used a model of SARS-CoV-2 transmission, COVID-19 disease and clinical care pathways to explore the potential impact of dexamethasone - the main treatment currently for hospitalised COVID-19 patients - under scenarios varying: i) healthcare capacity, ii) epidemic trajectories; and iii) the efficacy of dexamethasone in the absence of supportive care. We then fit the model to the observed epidemic trajectory to-date in 165 countries and analysed the potential future impact of dexamethasone in different countries, regions, and country-income strata. Finally, we constructed hypothetical profiles of novel therapeutics based on current trials, and compared the potential impact of each under different circumstances. In each case, the outcome of interest was the number of COVID-19 deaths averted in scenarios with the therapeutic compared to scenarios without. Findings: We find the potential benefit dexamethasone is severely limited in settings where healthcare capacity is lowest or where uncontrolled epidemics result in hospitals being overwhelmed. As such, it may avert 22% of deaths in high-income countries but only 8% in low-income countries (assuming R=1.35). However, therapeutics for different patient populations (in particular, those not in hospital and early in the course of infection) and types of benefit (in particular, reducing disease severity or infectiousness) could have much greater benefits. Such therapeutics would have particular value in resource-poor settings facing large epidemics, even if the efficacy or achievable coverage of such therapeutics is lower in comparison to other types. Interpretation: People in low-income countries will benefit the least from advances in the treatment of COVID-19 to date, which have focussed on hospitalised-patients with adequate access to supportive care. Therapeutics that can feasibly be delivered to those earlier in the course of infection that reduce the need for healthcare or reduce infectiousness could have much greater impact. Such therapeutics may be feasible and research into their efficacy and means of delivery should be a priority. Funding: None to declare. Declaration of Interest: None to declare.
Subject(s)
COVID-19ABSTRACT
BackgroundClinical spectrum of COVID-19 has been unclear, especially with regard to the presence of pneumonia. We aimed to present clinical course of all laboratory-confirmed adult COVID-19 patients and to identify potential predicting factors of pneumonia. MethodsWe conducted a retrospective study among adult patients with confirmed COVID-19 who were hospitalized at Bamrasnaradura Infectious Diseases Institute, Thailand, regardless of their disease severity, between January 8 and April 16, 2020. We described the full picture of COVID-19, defined definite outcomes and evaluated factors associated with pneumonia. ResultsOne-hundred-and-ninety-three patients were included. The median (IQR) age was 37.0 (29.0-53.0) years, and 58.5% were male. Of whom, 189 (97.9%) recovered and 4 (2.1%) died. More than half (56%) of the patients were mild, 22% were moderate, 14% were severe, and 3% were critically ill. Asymptomatic infection was found in 5%. The overall incidence of pneumonia was 39%. Bilateral was more prevalent than unilateral pneumonia (65% vs. 35%). Increasing age (OR 2.60 for every 10-year increase from 30 years old; 95% CI, 1.68 to 3.97; p<0.001), obesity (OR 9.17; 95% CI, 2.11 to 39.89; p=0.003), and higher temperature at presentation (OR 4.66 per one-degree Celsius increase from 37.2 degree Celsius; 95% CI, 2.32 to 9.34; p<0.001) were potential predicting factors of COVID-19 pneumonia. Severe cases had a longer viral RNA shedding duration than the non-severe cases. The longest observed duration of viral RNA shedding was 45 days. ConclusionAcross different disease severities, most patients with COVID-19 in Thailand had a good prognosis. COVID-19 pneumonia was found in one-third of the hospitalized patients. Potential predicting factors included old age, obesity, fever at presentation.