Evaluation of anakinra in the management of patients with COVID-19 infection: A randomized clinical trial.

Background: The global COVID-19 pandemic led to substantial clinical and economic outcomes with catastrophic consequences. While the majority of cases has mild to moderate disease, minority of patients progress into severe disease secondary to the stimulation of the immune response. The hyperinflammatory state contributes towards progression into multi-organ failure which necessitates suppressive therapy with variable outcomes. This study aims to explore the safety and efficacy of anakinra in COVID-19 patients with severe disease leading to cytokine release syndromes. Methods: In this open-label, multi-center, randomized clinical trial, patients with confirmed COVID-19 infection with evidence of respiratory distress and signs of cytokine release syndrome were randomized in 1:1 ratio to receive either standard of care (SOC) or anakinra (100 mg subcutaneously every 12 h for 3 days then 100 mg subcutaneously once daily for 4 days) in addition to SOC. The primary outcome was treatment success at day 14 as defined by the WHO clinical progression score of ≤3. Primary analysis was based upon intention-to-treat population, with value of p of <0.05. Results: Out 327 patients screened for eligibility, 80 patients were recruited for the study. The mean age was 49.9 years (SD = 11.7), with male predominance at 82.5% (n = 66). The primary outcome was not statistically different (87.5% (n = 35) in anakinra group vs. 92.5% (n = 37) in SOC group, p = 0.712; OR = 1.762 (95%CI: 0.39-7.93). The majority of reported adverse events were mild in severity and not related to the study treatment. Elevated aspartate aminotransferase was the only significant adverse event which was not associated with discontinuation of therapy. Conclusion: In patients with severe COVID-19 infection, the addition of anakinra to SOC treatment was safe but was not associated with significant improvement according to the WHO clinical progression scale. Further studies are warranted to explore patients' subgroups characteristics that might benefit from administered therapy. Clinical Trial Registration: Trial registration at ClinicalTrials.gov, identifier: NCT04643678.

Early Predictors of Intensive Care Unit Admission among COVID-19 Patients in Qatar

Background Coronavirus disease (COVID-19) is associated with significant morbidity and mortality. This study aimed to explore the early predictors of intensive care unit (ICU) admission and in-hospital mortality among patients diagnosed with COVID-19. Methods This was a case-control study of adult patients with confirmed COVID-19. Cases were defined as patients admitted to ICU during the period February 29 - May 29, 2020. For each case enrolled, one control was matched by age and gender. Results A total of 1560 patients with confirmed COVID-19 were included. Each group included 780 patients with a predominant male gender (89.7%) and a median age of 49 years (interquartile range = 18). Predictors independently associated with ICU admission were cardiovascular disease (CVD) (adjusted odds ratio (aOR)=1.64, 95% confidence interval (CI): 1.16 - 2.32, p=0.005), diabetes (aOR=1.52, 95% CI: 1.08 - 2.13, p= 0.016), obesity (aOR=1.46, 95% CI: 1.03-2.08, p= 0.034), lymphopenia (aOR=2.69, 95% CI: 1.80-4.02, p< 0.001), high aspartate aminotransferase (AST) (aOR= 2.59, 95% CI: 1.53-4.36, p< 0.001), high ferritin (aOR=1.96, 95% CI: 1.40-2.74, p< 0.001), high C-reactive protein (CRP) (aOR=4.09, 95% CI: 2.81-5.96, p< 0.001), and dyspnea (aOR=2.50, 95% CI: 1.77-3.54, p< 0.001). Similarly, significant predictors of mortality included CVD (aOR=2.16, 95% CI: 1.32- 3.53, p=0.002), diabetes (aOR=1.77, 95% CI: 1.07-2.90, p=0.025), cancer (aOR=4.65, 95% CI: 1.50-14.42, p= 0.008), lymphopenia (aOR=2.34, 95% CI: 1.45-3.78, p= 0.001), and high AST (aOR= 1.89, 95% CI: 1.04-3.43, p=0.036). Risk Factors for ICU admission among patients with COVID-19 (N=1560) Conclusion Having CVD, diabetes, lymphopenia, and increased AST were independent predictors for both ICU admission and in-hospital mortality in patients with COVID-19. In addition, obesity, high ferritin, and CRP levels were associated with increased risk of ICU admission, while cancer was strongly associated with in-hospital mortality. Early identification and monitoring of patients at risk is essential in planning the level of care needed to prevent delay in medical intervention. Disclosures Adel Abou-Ali, PharmD, PhD, Astellas Pharma Global Development, Inc. (Employee)

Avoiding Anchoring Bias in the Times of the Pandemic!

COVID-19 has a broad spectrum of clinical presentations, including central nervous system manifestations that are not uncommon. The high pretest probability of COVID-19 in pandemic can lead to anchoring. We present a patient of COVID-19 pneumonia who presented with dyspnea and acute confusional state. His initial workup was suggestive of tuberculous meningoencephalitis with lymphocytic pleocytosis, high protein in CSF analysis, and suspicious MRI findings, which was later confirmed with a positive CSF culture. To the best of our knowledge, it is the first such case. Anchoring to the diagnosis of COVID-19 may deter clinicians from considering other concurrent diagnoses and a poor outcome consequently.

Case Report: Development of Miliary Pulmonary Tuberculosis in a Patient with Peritoneal Tuberculosis after COVID-19 Upper Respiratory Tract Infection.

We report a 29-year-old patient who presented with coronavirus disease 2019 (COVID-19) upper respiratory tract infection in addition to clinical, laboratory, and radiological findings highly suggestive of peritoneal tuberculosis (TB) without pulmonary involvement. Two weeks after the resolution of COVID-19 infection, he presented with shortness of breath and oxygen desaturation requiring intubation and admission to the intensive care unit. The workup confirmed miliary pulmonary TB. The patient subsequently improved on antitubercular treatment. We discuss the possible contribution of COVID-19 infection to the rapid progression of TB infection to involve the lung in a miliary pattern, and how the coexistence of the two diseases might have led to a worse outcome.

COVID-19-Associated Bronchiectasis and Its Impact on Prognosis.

Coronavirus disease 2019 (COVID-19), which initially emerged in Wuhan, China, has rapidly swept around the world, causing grave morbidity and mortality. It manifests with several symptoms, on a spectrum from asymptomatic to severe illness and death. Many typical imaging features of this disease are described, such as bilateral multi-lobar ground-glass opacities (GGO) or consolidations with a predominantly peripheral distribution. COVID-19-associated bronchiectasis is an atypical finding, and it is not a commonly described sequel of the disease. Here, we present a previously healthy middle-aged man who developed progressive bronchiectasis evident on serial chest CT scans with superimposed bacterial infection following COVID-19 pneumonia. The patient's complicated hospital course of superimposed bacterial infection in the setting of presumed bronchiectasis secondary to COVID-19 is alleged to have contributed to his prolonged hospital stay, with difficulty in weaning off mechanical ventilation. Clinicians should have high suspicion and awareness of such a debilitating complication, as further follow-up and management might be warranted.

Non-ST Segment Elevation Myocardial Infarction in a Patient with COVID-19.

Coronavirus disease 2019 (COVID-19) is associated with a wide spectrum of cardiovascular (CV) manifestations. Primary cardiac manifestations of COVID-19 disease include acute coronary syndrome (ACS), myocarditis, and arrhythmias. Secondary cardiac involvement is usually due to a systemic inflammatory syndrome and can manifest as acute myocardial injury/biomarker elevation and/or heart failure (congestive heart failure). Elevated cardiac biomarkers indicate an unfavorable prognosis. Health-care systems of the world are rapidly learning more about the manifestations of COVID-19 on the CV system, as well as the strategies for the management of infected patients with CV disease. There is still a paucity of literature on the management of non-ST-segment elevation ACSs in the current literature. Herein, we report the case of a 53-year-old male patient, who presented with severe COVID-19 pneumonia deteriorating into adult respiratory distress syndrome requiring mechanical ventilation. The patient had a history of coronary artery disease. During the course of treatment, he developed sudden cardiac arrest with diffuse ST-segment depression, which was treated by percutaneous coronary intervention to the left anterior descending artery. The patient had a favorable outcome with excellent recovery from the disease.

Case Report: COVID-19-Related Pneumothorax-Case Series Highlighting a Significant Complication.

COVID-19 is a recent outbreak in China and rapidly spread worldwide. Lung consolidation is the most common radiologic finding of COVID-19 pneumonia. Pneumothorax has been rarely reported as a complication of severe COVID-19 pneumonia. Early recognition and management are detrimental to the outcome. We here report three cases of SARS-CoV-2 infection complicated by pneumothorax. In addition, we present a brief literature review.

COVID-19 and Plasmodium vivax malaria co-infection.

The ongoing outbreak of COVID-19 poses an unprecedented global health challenge. With its variety of clinical manifestations including, but not limited to, fever, cough, diarrhea, vomiting, headache, myalgia and fatigue, it may be challenging to distinguish COVID-19 from a spectrum of diseases with similar presentations, such as malaria, especially in endemic areas. Risk of concomitant infections also remains a concern owing to overburdening of healthcare services and possible scarcity of resources. We present the first reported case of confirmed COVID and malaria co-infection. In this case, we emphasize the need for vigilance from frontline clinicians for timely diagnosis and appropriate clinical management of potential co-infections in the COVID era.

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.