Favipiravir for the treatment of coronavirus disease 2019 pneumonia; a propensity score-matched cohort study.

We retrospectively investigated the clinical outcomes of favipiravir in patients with COVID-19 pneumonia. Patients who between 23 May 2020 and 18 July 2020 received ≥ 24 h of favipiravir were assigned to the favipiravir group, while those who did not formed the non-favipiravir group. The primary outcome was 28-day clinical improvement, defined as two-category improvement from baseline on an 8-point ordinal scale. Propensity scores (PS) for favipiravir therapy were used for 1:1 matching. The unmatched cohort included 1493 patients, of which 51.7% were in the favipiravir group, and 48.3% were not receiving supplemental oxygen at baseline. Significant baseline differences between the two unmatched groups existed, but not between the PS-matched groups (N = 774). After PS-matching, there were no significant differences between the two groups in the proportion with 28-day clinical improvement (93.3% versus 92.8%, P 0.780), or 28-day all-cause mortality (2.1% versus 3.1%, P 0.360). Favipiravir was associated with more viral clearance by day 28 (79.8% versus 64.1%, P < 0.001). Adverse events were common in both groups, but the 93.9% were Grades 1-3. Favipiravir therapy for COVID-19 pneumonia is well tolerated but is not associated with an increased likelihood of clinical improvement or reduced all-cause mortality by 28 days.

Dilemma of Tocilizumab therapy for a patient with critical COVID-19 disease and neutropenia: Case report and review of the literature.

Infection following SARS-Co V-2 leading to COVID-19 disease is associated with significant morbidity and mortality. The clinical entity, COVID-19 cytokine storm syndrome (CSS) is a severe immunological manifestation of the disease associated with ominous consequences. Tocilizumab is interleukin-6 inhibitors that has been shown to hamper the catastrophic outcomes of CCS including the need for mechanical ventilation as well as reduce mortality, but the usage is limited by warnings of reactivation of potential latent infections or immune dysfunctions including severe neutropenia. We describe a case of 39-year-old Nepalese male patient with a background of scleritis maintained on azathioprine and rituximab therapy with normal baseline parameters including complete blood count who presented with acute COVID-19 infection including associated leukopenia as well as severe neutropenia (absolute neutrophil count of 300 cells/µl), then progressed to critical disease culminating into CSS. Based on risks and benefits evaluation, the patient was treated with tocilizumab reinforced with granulocytes-colony stimulating factor (G-CSF, Filgrastim) to full recovery and safe outcome including reversal of neutropenia.

The first consecutive 5000 patients with Coronavirus Disease 2019 from Qatar; a nation-wide cohort study.

BACKGROUND: There are limited data on Coronavirus Disease 2019 (COVID-19) outcomes at a national level, and none after 60 days of follow up. The aim of this study was to describe national, 60-day all-cause mortality associated with COVID-19, and to identify risk factors associated with admission to an intensive care unit (ICU). METHODS: This was a retrospective cohort study including the first consecutive 5000 patients with COVID-19 in Qatar who completed 60 days of follow up by June 17, 2020. The primary outcome was all-cause mortality at 60 days after COVID-19 diagnosis. In addition, we explored risk factors for admission to ICU. RESULTS: Included patients were diagnosed with COVID-19 between February 28 and April 17, 2020. The majority (4436, 88.7%) were males and the median age was 35 years [interquartile range (IQR) 28-43]. By 60 days after COVID-19 diagnosis, 14 patients (0.28%) had died, 10 (0.2%) were still in hospital, and two (0.04%) were still in ICU. Fatal COVID-19 cases had a median age of 59.5 years (IQR 55.8-68), and were mostly males (13, 92.9%). All included pregnant women (26, 0.5%), children (131, 2.6%), and healthcare workers (135, 2.7%) were alive and not hospitalized at the end of follow up. A total of 1424 patients (28.5%) required hospitalization, out of which 108 (7.6%) were admitted to ICU. Most frequent co-morbidities in hospitalized adults were diabetes (23.2%), and hypertension (20.7%). Multivariable logistic regression showed that older age [adjusted odds ratio (aOR) 1.041, 95% confidence interval (CI) 1.022-1.061 per year increase; P < 0.001], male sex (aOR 4.375, 95% CI 1.964-9.744; P < 0.001), diabetes (aOR 1.698, 95% CI 1.050-2.746; P 0.031), chronic kidney disease (aOR 3.590, 95% CI 1.596-8.079, P 0.002), and higher BMI (aOR 1.067, 95% CI 1.027-1.108 per unit increase; P 0.001), were all independently associated with increased risk of ICU admission. CONCLUSIONS: In a relatively younger national cohort with a low co-morbidity burden, COVID-19 was associated with low all-cause mortality. Independent risk factors for ICU admission included older age, male sex, higher BMI, and co-existing diabetes or chronic kidney disease.

Fatal Coronavirus Disease 2019-associated Pulmonary Aspergillosis; A Report of Two Cases and Review of the Literature.

Coronavirus Disease 2019 (COVID-19)-associated pulmonary aspergillosis is an emerging entity. We report two fatal cases of putative COVID-19-associated pulmonary aspergillosis. Both cases were diagnosed on the basis of respiratory tract cultures yielding Aspergillus species and otherwise unexplained clinical and radiological deterioration. Existing published literature on COVID-19-associated pulmonary aspergillosis indicate poor outcomes and high mortality. CAPA should be considered in patients with critical COVID-19 who have unexplained progressive respiratory failure despite optimized supportive care. Diagnostic work-up should be initiated as early as possible and should ideally include fungal cultures, galactomannan detection and Aspergillus PCR on tracheal aspirates or broncho-alveolar lavage fluid. Empiric systemic antifungal therapy may be justified in selected cases, pending diagnostic work up results. Large, multi-center studies are required to further understand the pathogenesis of invasive aspergillosis in COVID-19, and the optimal diagnostic and treatment strategies.

Tocilizumab for the treatment of severe coronavirus disease 2019.

Tocilizumab, an interleukin-6 inhibitor, may ameliorate the inflammatory manifestations associated with severe coronavirus disease 2019 (COVID-19) and thus improve clinical outcomes. This was a retrospective review of patients with laboratory-confirmed severe COVID-19 who received tocilizumab and completed 14 days of follow up. Twenty-five patients were included, median age was 58 years (interquartile range, 50-63) and the majority were males (92%). Co-morbidities included diabetes mellitus (48%), chronic kidney disease (16%), and cardiovascular disease (12%). Fever (92%), cough (84%), and dyspnea (72%) were the commonest presenting symptoms. All patients received at least two concomitant investigational antiviral agents. Median oral temperature was on day 1, 3, and 7 was 38.0°C, 37.3°C (P = .043), and 37.0°C (P = .064), respectively. Corresponding median C-reactive protein was 193 and 7.9 mg/L (P < .0001) and <6 mg/L (P = .0001). Radiological improvement was noted in 44% of patients by day 7% and 68% by day 14. Nine patients (36%) were discharged alive from intensive care unit and three (12%) died. The proportion of patients on invasive ventilation declined from (84%) at the time of tocilizumab initiation to 60% on day 7 (P = .031) and 28% on day 14 (P = .001). The majority (92%) of patients experienced at least one adverse event. However, it is not possible to ascertain which adverse events were directly related to tocilizumab therapy. In patients with severe COVID-19, tocilizumab was associated with dramatic decline in inflammatory markers, radiological improvement and reduced ventilatory support requirements. Given the study's limitations, the results require assessment in adequately powered randomized controlled trials.