Role of awake prone positioning in patients with moderate-to-severe COVID-19: an experience from a developing country.

There is limited evidence on the efficacy of awake prone positioning (PP) in non-ventilated patients with COVID-19 who have hypoxemia. We, therefore, aim to describe our experience with the use of early proning in awake, non-intubated patients with confirmed COVID-19. In our retrospective observational study, 23 patients with confirmed positive PCR test results for Severe Acute respiratory Syndrome Coronavirus-2 (SARS-CoV-2) and hypoxemia that required oxygen therapy with or without non-invasive ventilation were treated with PP. Patients were classified into mild, moderate and severe COVID-19 disease. There were no targeted number of hours for proning per day and patients were kept in prone position according to their tolerance. The primary outcome measure was the avoidance of intubation and secondary outcomes were in-hospital mortality, length of hospital stays and complications related to PP. The mean (standard deviation) age of our cohort was 54.5 (11.7) years, and the majority were males (21/23, 91.3%). Sixty-one per cent (14/23) of the patients were suffering from severe disease and 82.6% (19/23) had bilateral lung involvement with interstitial infiltrates. Majority of the patients were prone positioned for a median of 6 days (IQR 4 - 8). Only one patient required transfer to ICU for mechanical ventilation and subsequently died due to severe ARDS. All 22 patients showed progressive improvement in oxygen requirement and PF ratio, mostly after 3-5 days of proning. The mean length of hospital stay was 12 days. All patients, except one, were discharged in stable conditions, on room air or on a minimal oxygen requirement of 1-2 liters. No major complication of PP was recorded. Awake prone positioning is a valuable and safe therapeutic adjunct that can be applied in patients with moderate-to-severe COVID-19. It can also be included in the home-based management protocols of COVID-19 to improve patient outcomes and mitigate the burden on health care facilities.

Title: SARS-CoV-2 Induced Coagulopathy and Potential Role of Anticoagulation: Scoping Review of Literature (preprint)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can vary on a spectrum of asymptomatic disease, to rarer manifestations like hypercoagulability especially among elderly, patients admitted in the intensive care unit (ICU) and those with preexisting comorbidities. The exact mechanism behind this phenomenon is unexplored; however studies have shown an association with elevated cytokines and severe inflammatory response which encompasses this disease. Hypercoagulability can be limited to the lungs, or present as systemic manifestations of arterial and venous thrombosis leading to mortal outcomes. Thus, careful evaluation of risk factors should be performed by physicians and treatment with anticoagulants should be modified accordingly. All COVID-19 in-patients should receive thromboprophylactic therapy. The dosage increases with increase in severity of the disease and in high risk patients. D-dimer levels and SIC score aid in identifying high risk patients and predicting outcome. This article highlights the pathophysiology behind hypercoagulability and discusses therapeutic modalities to combat this mortal consequence of SARS-CoV-2.

Treatment of ARDS and hyperinflammation in COVID-19 with IL-6 antagonist Tocilizumab: a tertiary care experience from Pakistan (preprint)

Cytokine release syndrome in COVID-19 is characterized by hyperinflammation which manifests as ARDS, multi-organ failure, and high inflammatory parameters. Tocilizumab, an IL-6 antagonist has been used in COVID-19 acute respiratory distress syndrome (ARDS) with conflicting results from different parts of the world. We conducted a retrospective descriptive study from Feb 2020 to May 2020 on COVID-19 patients with ARDS and hyperinflammation characterized by raised CRP and/or ferritin. A total of 244 patients with COVID-19 were admitted out of which 107 had ARDS. Thirty patients had both ARDS and hyperinflammation and received tocilizumab. The mean age was 62.5 years (SD: 13.5) and the majority were male (83%). The mean CRP pre-treatment was 217.5 mg/L and post 48 to 72 hours of tocilizumab treatment was 98.5 mg/L. Twenty-one patients (70%) also received concomitant intravenous methylprednisolone. Of the 30 patients, 7 died and 20 recovered. Ten patients required intensive care unit admission and nine developed nosocomial infections. COVID-19 associated aspergillosis was diagnosed in three patients post tocilizumab treatment. Mortality was significantly higher in patients who developed a nosocomial infection and who required intermittent positive pressure ventilation (IPPV). Our study is the first to describe the treatment outcomes with tocilizumab from a low-middle income country. The availability and cost of tocilizumab in our region which makes it imperative to understand its potential for use in our setting. Our study supports the use of tocilizumab in a select patient population with COVID-19 and recommends monitoring of nosocomial infections and opportunistic infections.

Transcriptomic profiling of disease severity in patients with COVID-19 reveals role of blood clotting and vasculature related genes (preprint)

COVID-19 caused by SARS-CoV-2 manifests as a range of symptoms. Understanding the molecular mechanisms responsible for immuno-pathogenesis of disease is important for treatment and management of COVID-19. We examined host transcriptomes in moderate and severe COVID-19 cases with a view to identifying pathways that affect its progression. RNA extracted from whole blood of COVID-19 cases was analysed by microarray analysis. Moderate and severe cases were compared with healthy controls and differentially regulated genes (DEGs) categorized into cellular pathways. DEGs in COVID-19 cases were mostly related to host immune activation and cytokine signaling, pathogen uptake, host defenses, blood and vasculature genes, and SARS-CoV-2- and other virus- affected pathways. The DEGs in these pathways were increased in severe compared with moderate cases. In a severe COVID-19 patient with an unfavourable outcome we observed dysregulation of genes in platelet homeostasis and cardiac conduction and fibrin clotting with disease progression.