Understanding the Potential Impact of Different Drug Properties on Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Transmission and Disease Burden: A Modelling Analysis.

BACKGROUND: The public health impact of the coronavirus disease 2019 (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: Using a mathematical model of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission, COVID-19 disease and clinical care, we explore the public-health impact of different potential therapeutics, under a range of scenarios varying healthcare capacity, epidemic trajectories; and drug efficacy in the absence of supportive care. RESULTS: The impact of drugs like dexamethasone (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 hospitalization) could have much greater benefits, particularly in resource-poor settings facing large epidemics. CONCLUSIONS: Advances in the treatment of COVID-19 to date have been focused on hospitalized-patients and predicated on an assumption of adequate access to supportive care. Therapeutics delivered 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.

Early treatment of Favipiravir in COVID-19 patients without pneumonia: a multicentre, open-labelled, randomized control study.

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 only supportive care. The primary endpoint was time to clinical improvement, defined by a National Early Warning Score (NEWS) 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 and 14 days for FPV and control arms, respectively (adjusted hazard ratio (aHR) of 2.77, 95% CI 1.57-4.88, P < .001). The FPV arm also had significantly higher likelihoods of clinical improvement within 14 days after enrolment by NEWS (79% vs. 32% respectively, P < .001). 8 (12.9%) and 7 (22.6%) patients in FPV and control arms developed mild pneumonia at a median (range) of 6.5 (1-13) and 7 (1-13) days after treatment, respectively (P = .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.Trial registration: Thai Clinical Trials Registry identifier: TCTR20200514001.

Nasopharyngeal SARS-CoV-2 Viral Load Response among COVID-19 Patients Receiving Favipiravir.

We retrospectively studied nasopharyngeal severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) viral load in coronavirus disease 2019 (COVID-19) patients who were hospitalized between January 13 and April 1, 2020. Quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) was conducted using primers and probes targeting the ORF1ab and N genes. All patients were classified in the following groups: Group 1: received favipiravir + chloroquine or hydroxychloroquine + lopinavir/ritonavir or darunavir/ritonavir for 5-10 days, Group 2: received chloroquine or hydroxychloroquine + lopinavir/ritonavir or darunavir/ritonavir for 5-10 days, and Group 3: no antiviral medication. Among the 115 patients, 38 (33%), 54 (47%), and 23 (20%) were in Groups 1, 2, and 3, respectively. The median (IQR) baseline viral loads on day 0 of Groups 1, 2, and 3 were 7.2 (6.0-8.1), 6.9 (5.8-7.8), and 6.9 (5.8-7.6) log10 copies/mL, respectively. The reductions of mean viral loads on day 3 from baseline were 2.41, 1.38, and 2.19 log10 copies/mL in the corresponding groups (P < 0.05). There were no differences in the reduction of mean viral loads from baseline among the three groups on days 5 and 10 (P > 0.05). Multiple logistic regression analysis showed that receiving favipiravir was associated with nasopharyngeal viral load reduction at three days (P = 0.001). Significant nasopharyngeal SARS-CoV-2 viral load reduction was achieved in COVID-19 patients who received a favipiravir-containing regimen.

Clinical course and potential predictive factors for pneumonia of adult patients with Coronavirus Disease 2019 (COVID-19): A retrospective observational analysis of 193 confirmed cases in Thailand.

Clinical spectrum of Coronavirus Disease 2019 (COVID-19) remains unclear, especially with regard to the presence of pneumonia. We aimed to describe the clinical course and final outcomes of adult patients with laboratory-confirmed COVID-19 in the full spectrum of disease severity. We also aimed to identify potential predictive factors for COVID-19 pneumonia. We conducted a retrospective study among adult patients with laboratory-confirmed COVID-19 who were hospitalized at Bamrasnaradura Infectious Diseases Institute, Thailand, between January 8 and April 16, 2020. One-hundred-and-ninety-three patients were included. The median (IQR) age was 37.0 (29.0-53.0) years, and 58.5% were male. The median (IQR) incubation period was 5.5 (3.0-8.0) days. More than half (56%) of the patients were mild disease severity, 22% were moderate, 14% were severe, and 3% were critical. Asymptomatic infection was found in 5%. The final clinical outcomes in 189 (97.9%) were recovered and 4 (2.1%) were deceased. The incidence of pneumonia was 39%. The median (IQR) time from onset of illness to pneumonia detection was 7.0 (5.0-9.0) days. Bilateral pneumonia was more prevalent than unilateral pneumonia. In multivariable logistic regression, increasing age (OR 2.55 per 10-year increase from 30 years old; 95% CI, 1.67-3.90; p<0.001), obesity (OR 8.74; 95%CI, 2.06-37.18; p = 0.003), and higher temperature at presentation (OR 4.59 per 1°C increase from 37.2°C; 95% CI, 2.30-9.17; p<0.001) were potential predictive factors for COVID-19 pneumonia. Across the spectrum of disease severities, most patients with COVID-19 in our cohort had good final clinical outcomes. COVID-19 pneumonia was found in one-third of them. Older age, obesity, and higher fever at presentation were independent predictors of COVID-19 pneumonia.

Potential dual dengue and SARS-CoV-2 infection in Thailand: A case study.

Coronavirus disease 2019 (Covid-19) has non-specific clinical and laboratory characteristics that might be similar to other viral infection including dengue. Two Covid-19 cases with 'false-positive' dengue serology have been reported in Singapore but no public health consequence was described. We describe a Thai patient with an initial diagnosis of dengue fever who was later confirmed to also infect with SARSCoV-2. The Covid-19 infection appeared to spread to one family member and one healthcare worker.