Adding colchicine to tocilizumab in hospitalized patients with severe COVID-19 pneumonia: An open-label randomized controlled trial.

INTRODUCTION: Colchicine acts upstream in the cytokines cascade by inhibiting the nod-like receptor protein 3 (NLRP3) inflammasome while interleukin 6 (IL-6) receptor antagonists, such as tocilizumab, block the end result of the cytokines cascade. Hence, adding colchicine to tocilizumab with the aim of blocking the early and end products of the cytokines cascade, might reduce the risk of developing cytokine storm. METHODS AND ANALYSIS: We aim to conduct an open-label randomized controlled trial to evaluate the efficacy and safety of adding colchicine to tocilizumab among patients with severe COVID-19 pneumonia to reduce the rate of invasive mechanical ventilation and mortality. We will include patients with severe COVID-19 pneumonia who received tocilizumab according to our local guidelines. Enrolled patients will be then randomized in 1:1 to colchicine versus no colchicine. Patients will be followed up for 30 days. The primary outcome is the rate of invasive mechanical ventilation and will be determined using Cox proportional hazard model. DISCUSSION: Given colchicine's ease of use, low cost, good safety profile, and having different anti-inflammatory mechanism of action than other IL-6 blockade, colchicine might serve as a potential anti-inflammatory agent among patients with severe COVID-19 pneumonia. This study will provide valuable insights on the use of colchicine in severe COVID-19 when added to IL-6 antagonists. ETHICS AND DISSEMINATION: The Medical Research Center and Institutional Review Board at Hamad Medical Corporation in Qatar approved the study protocol (MRC-01-21-299). Results of the analysis will be submitted for publication in a peer-reviewed journal.

Case Report: Prolonged Viral Shedding in Six COVID-19 Patients.

COVID-19 has surfaced as a multi-organ disease predominantly affecting the respiratory system. Detection of the viral RNA through reverse transcriptase-PCR (RT-PCR) from a nasopharyngeal or throat sample is the preferred method of diagnosis. Recent evidence has suggested that COVID-19 patients can shed the SARS-CoV-2 for several weeks. Herein, we report six cases of COVID-19 who had persistently positive SARS-CoV-2 on repeat RT-PCR testing reaching up to 9 weeks. The spectrum of cases described ranges from asymptomatic infection to severe COVID-19 pneumonia. A full understanding of the virus's transmission dynamics needs further research. Prolonged viral shedding currently has unclear implications on the management and isolation decisions-the role of the cycle threshold (Ct) value in guiding therapeutic decisions is yet to be clarified. More data on the relationship between Ct values and viral cultivation are needed, especially in patients with prolonged viral shedding, to understand the virus's viability and infectivity.

Proposed Scoring System for Evaluating Clinico-radiological Severity of COVID- 19 using Plain Chest X- ray (CXR) changes (CO X-RADS): Preliminary results.

BACKGROUND: Plain chest radiograph (CXR), although less sensitive than chest CT, is usually the first-line imaging modality used for patients with symptomatic SARS-CoV-2 infection. The relation between radiological changes in CXR and clinical severity of the disease in symptomatic patients with COVID 19 has not been fully studied and there is no scoring system for the severity of the lung involvement, using the plain CXR. AIM OF THE STUDY: Current COVID-19 radiological literature is dominated by CT and a detailed description CXR appearances in relation to the disease time course is lacking. We propose an easy scoring system (CO X-RADS) to describe the severity of chest involvement in symptomatic COVID 19 patients using CXR and to correlate the radiological changes with the clinical severity of the disease. PATIENTS AND METHODS: The clinical manifestations and CXR findings were recorded in 500 symptomatic COVID-19 positive patients who were admitted to Hamad Medical Corporation (HMC) COVID-19 designated facility Center from January to June 2020. The severity and outcome of the disease included: intensive care unit admission, need for oxygen therapy, mechanical ventilation. and mortality rate. RESULTS: Most of our symptomatic patients (86.8%) had mild and moderate clinical manifestations. The remaining 13.2% had severe manifestations, including: fever, persistent dry cough, shortness of breath, dyspnea, abdominal and generalized body pains. Based on our radiological scoring system (0 to 10) patients were distributed according to their CXR findings into different categories and according to our suggested (CO X-RADS) severity system into five categories (0 to IV). Patients with mild clinical manifestations showed low scoring in CXR (score 0 up to 4) and they represented 72% of our patients. Patients with moderately severe clinical manifestations showed mainly GGO (scoring 5 and 6) and represented about 14.8% of patients. Patients presented with severe clinical manifestations had obvious lung consolidations at the time of presentation with CXR scoring system ≥ 7 and represented about 13.2% of patients. CONCLUSION: We proposed a simple CXR reporting scoring system (CO X-RADS) to categorize COVID-19 patients according to their radiological severity. This radiological score was correlated well with the clinical severity score of patients. We encourage other centers to test this scoring system in correlation with the clinical status of patients.

Clinical Outcome of Eosinophilia in Patients with COVID-19: A Controlled Study.

BACKGROUND: Eosinophils can be considered as multifunctional leukocytes that contribute to various physiological and pathological processes depending on their location and activation status. There are emerging eosinophil-related considerations concerning COVID-19. Variable eosinophil counts have been reported during COVID-19. Whether these changes are related to the primary disease process or due to immunomodulation induced by the treatment has not yet been elucidated. AIM OF THE STUDY: To describe changes in the differential leukocyte counts including eosinophils, in a cohort of symptomatic patients with confirmed COVID-19 and to correlate these changes, if any, with the severity of the disease. PATIENTS AND METHODS: We recorded the clinical data, lab findings, including inflammatory markers and leukocyte and differential count, course of the disease and severity score in 314 confirmed symptomatic cases of COVID-19. RESULTS: Laboratory tests revealed that 28.7 % (n =86) had mild eosinophilia (eosinophil count > 500 <1,500/µL). Thirty-four patients (11.3%) had elevated absolute neutrophil count (ANC) (>8,000/µL), and 7 (2.3%) had decreased ANC (< 1,500/µl). Seven patients (2.3%) had lymphopenia (<1,000/µL) and 4 (4.67%) had lymphocytosis (> 4,000/µL). C-reactive protein (CRP) was elevated in 83 patients (27.6%). Chest X-Ray changes included: increased broncho vascular markings (38%), ground-glass opacity (GGO) pneumonitis (19.3%), lobar consolidation (5%), bronchopneumonia (8.3%), nodular opacity (1%), acute respiratory distress syndrome (ARDS) (2.3%), pleural effusion (1.0%) and other atypical findings (6.6%). Patients with eosinophilia had significantly lower CRP, and lower % of GGO, lobar and bronchopneumonia and ARDS in their chest images compared to patients without eosinophilia (p: <0.05). They also had a lower requirement for a hospital stay, ICU admission, mechanical ventilation, and oxygen supplementation versus patients without eosinophilia (p: <0.05). The eosinophils count was correlated negatively with the duration of ICU admission, mechanical ventilation, and oxygen supplementation and with CRP level (r: - 0.34, -0.32, -0.61 and - 0.39, respectively) (p: < 0.01). CONCLUSIONS: Our study reports a relatively high prevalence of eosinophilia in symptomatic COVID-19 positive patients. Patients with eosinophilia had a lower level of CRP, milder clinical course and better disease outcomes compared to those without eosinophilia. Our findings indicated a protective role of eosinophils in mitigating the severity of inflammatory diseases through an inhibitory mechanism, as evidenced by lower CRP. This protective role of eosinophils needs to be validated by further prospective studies.

A Case of COVID-19 in a Patient with Asymptomatic Hemoglobin D Thalassemia and Glucose-6-Phosphate Dehydrogenase Deficiency.

BACKGROUND Beta-hemoglobinopathies and glucose-6-phosphate dehydrogenase (G6PD) deficiency are genetic disorders that cause hemolytic anemia when exposed to oxidative stress. Their co-existence is, however, not proven to enhance the severity of anemia. CASE REPORT We report the case of a young man with no known co-morbidities, who came with fever and cough and was diagnosed with COVID-19 pneumonia. He was found to have hemoglobin D thalassemia and G6PD deficiency during further evaluation. Hydroxychloroquine therapy started initially, was discontinued after 3 doses once the G6PD deficiency was diagnosed. His hospital course showed a mild drop in hemoglobin with evidence of hemolysis on peripheral smear. However, the hemoglobin improved without any need for transfusion. CONCLUSIONS Hydroxychloroquine therapy can induce hemolytic crises in patients with underlying G6PD deficiency or hemoglobinopathies and should be avoided or closely monitored. Immediate intervention to stop hydroxychloroquine after 3 doses saved our patient from a major hemolytic crisis. The significance of this case report is that it is the first report that outlines the clinic course of COVID-19 pneumonia in a patient with underlying hemoglobin D disease and G6PD deficiency.