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.

Risk of Severe SARS-CoV-2 Infection in Patients with Autoimmune Rheumatic Diseases in Qatar: A Cohort Matched Study.

BACKGROUND: It remains unclear whether patients with autoimmune rheumatic diseases (ARDs) are at a higher risk of poor outcomes from a SARS-CoV-2 infection. We evaluated whether patients with an ARDs infected with SARS-CoV-2 were at a higher risk of a poorer outcome than those without an ARDs. METHODS: Patients with an ARDs infected with SARS-CoV-2 were matched to control patients without a known ARDs. Matching was performed according to age ( ± 6 years) and sex at a case-to-control ratio of 1:3. Demographic and clinical data were extracted from the databases and were compared between the two groups. Severe SARS-CoV-2 infection was the primary outcome and was defined as the requirement for oxygen therapy support, the need for invasive or noninvasive mechanical ventilation, or the use of glucocorticoids. RESULTS: A total of 141 patients with an ARDs were matched to 398 patients who formed the control group. The mean ages (SD) of the ARDs and non-ARDs groups were 44.4 years (11.4) and 43.4 years (12.2). Women accounted for 58.8% of the ARDs group and 56.3% of the control group (p = 0.59). Demographics and comorbidities were balanced between the groups. ARDs included connective tissue disease in 43 (30.3%) patients, inflammatory arthritis in 92 (65.2%), and other ARDs in 8 (5.7%). ARDs medications included biological/targeted synthetic disease-modifying antirheumatic drugs (b/ts-DMARDs) in 28 (15.6%) patients, conventional synthetic DMARDs in 95 (67.4%), and immunosuppressive antimetabolites in 13 (9.2%). The ARDs group had more respiratory and gastrointestinal symptoms related to SARS-CoV-2 infection than the control group (24.8% and 20.6% vs. 10% and 5.3%, respectively; p <  0.001 for both). Severe SARS-CoV-2 infection was more common in the ARDs group than in the control group (14.9% vs. 5.8%; p <  0.001). CONCLUSIONS: In this single-center matched cohort study, patients with an ARDs experienced more respiratory and gastrointestinal symptoms related to SARS-CoV-2 infection and had more severe infection than those from the control group. Therefore, patients with an ARDs require close observation during the coronavirus disease 2019 pandemic.

Prevalence and clinical significance of antiphospholipid antibodies in patients with coronavirus disease 2019 admitted to intensive care units: a prospective observational study.

Coronavirus disease 2019 (COVID-19) increases the risk of coagulopathy. Although the presence of antiphospholipid antibodies (aPLs) has been proposed as a possible mechanism of COVID-19-induced coagulopathy, its clinical significance remains uncertain. Therefore, this study aimed to evaluate the prevalence and clinical significance of aPLs among critically ill patients with COVID-19. This prospective observational study included 60 patients with COVID-19 admitted to intensive care units (ICU). The study outcomes included prevalence of aPLs, and a primary composite outcome of all-cause mortality and arterial or venous thrombosis between antiphospholipid-positive and antiphospholipid-negative patients during their ICU stay. Multiple logistic regression was used to assess the influence of aPLs on the primary composite outcome of mortality and thrombosis. A total of 60 critically ill patients were enrolled. Among them, 57 (95%) were men, with a mean age of 52.8 ± 12.2 years, and the majority were from Asia (68%). Twenty-two patients (37%) were found be antiphospholipid-positive; 21 of them were positive for lupus anticoagulant, whereas one patient was positive for anti-ß2-glycoprotein IgG/IgM. The composite outcome of mortality and thrombosis during their ICU stay did not differ between antiphospholipid-positive and antiphospholipid-negative patients (4 [18%] vs. 6 [16%], adjusted odds ratio 0.98, 95% confidence interval 0.1-6.7; p value = 0.986). The presence of aPLs does not seem to affect the outcomes of critically ill patients with COVID-19 in terms of all-cause mortality and thrombosis. Therefore, clinicians may not screen critically ill patients with COVID-19 for aPLs unless deemed clinically appropriate.