The significance of antiglobulin (Coombs) test reactivity in patients with COVID-19.

Previous case reports have described patients with COVID-19-associated autoimmune hemolytic anemia (AIHA), and cold agglutinin disease (CAD) which is characterized by a positive direct antiglobulin (DAT) or "Coombs" test, yet the mechanism is not well understood. To investigate the significance of Coombs test reactivity among COVID-19 patients, we conducted a retrospective study on hospitalized COVID-19 patients treated at NMC Royal Hospital between 15 April and 30 May 2020. There were 27 (20%) patients in the Coombs-positive group and 108 (80%) in the Coombs-negative group. The cold agglutinin titer was examined in 22 patients due to symptoms suggestive of cold agglutinin disease, and all tested negative. We demonstrated a significant association with reactive Coombs test results in univariate analysis through clinical findings such as ICU admission rate, the severity of COVID-19, and several laboratory findings such as CRP, D-dimer, and hemoglobin levels lactate dehydrogenase, and RDW-CV. However, only hemoglobin levels and disease severity had a statistically significant association in multivariate analysis. A possible explanation of COVID-19-associated positive Coombs is cytokine storm-induced hyperinflammation, complement system activation, alterations of RBCs, binding of SARS-CoV-2 proteins to hemoglobin or its metabolites, and autoantibody production. Coombs-positive patients were tested for hemolysis using indirect bilirubin, consumed haptoglobin, and/or peripheral smear that ruled out any evidence of hemolysis. Understanding this etiology sheds new light on RBC involvement as a pathophysiological target for SARS-CoV-2 by interfering with their function; consequently, therapies capable of restoring RBC function, such as erythrocytapheresis, could be repurposed for the treatment of worsening severe and critical COVID-19.

Treatment Outcomes of Tocilizumab in Critically-Ill COVID-19 Patients, Single-Centre Retrospective Study.

(1) Background: Severe COVID-19 outcomes are associated with cytokine release syndrome, characterized by the release of several immune modulators, including Interleukin-6 (IL-6). Tocilizumab (TCZ) is an IL-6 receptor antagonist used to treat rheumatic arthritis. The study aimed to evaluate the efficacy and safety of TCZ against COVID-19. (2) Methods: This was a retrospective study including 49 severe COVID-19 patients who received TCZ therapy in NMC Royal Hospital, UAE. (3) Results: Before Tocilizumab administration, the median temperature was 37.0 (IQR 36.0-39.6), and after day seven, the median reduced to 36.5 (IQR 35.8-37.9), p > 0.001. Thirty (61.2%) patients were admitted to the ICU, of which, eight (16.3%) were on WHO scale 4, sixteen (32.6%) on scale 5, and six (20.0%) on scale 6. TCZ reduced inflammatory markers over time, including CRP, D-Dimer, Ferritin, and Fibrinogen. By the end of week seven, 14 patients died (28.6%) while 35 (71.4%) improved and were discharged. (4) Conclusions: The study showed limited improvements in COVID-19 outcomes with TCZ therapy and highlighted the importance of D-Dimer monitoring for possible risk of thrombosis. Additionally, it could be recommended to upgrade the anti-coagulation dose to therapeutic levels once TCZ therapy is decided upon.

Reduced ADAMTS13 Activity in Correlation with Pathophysiology, Severity, and Outcome of COVID-19: A Retrospective Observational Study.

BACKGROUND: Low ADAMTS13 activity has been suggested to be an interplaying factor in the pathogenesis of COVID-19, considering that it is a thromboinflammatory disease with high risk of microthrombosis. OBJECTIVES: The study aimed to explore the correlation between ADAMTS13 activity and the pathophysiological pathway of COVID-19. METHODS: We carried out a retrospective observational study of 87 patients with COVID-19 in NMC Royal Hospital, Abu Dhabi, UAE. ADAMTS13 activity was measured and compared with patients' characteristics and clinical outcomes. RESULTS: Low ADAMTS13 activity was associated with pneumonia (p = 0.007), severity of COVID-19 (p <0.001), and mechanical ventilation rates (p = 0.018). Death was more frequently observed among patients (5 patients) with low ADAMTS13 activity compared with normal activity (1 patient), as well as inflammatory markers. Decreased ADAMTS13 activity increased with the risk of pneumonia, severity of COVID-19, need for mechanical ventilation, and use of anticoagulants ([OR = 4.75, 95% CI 1.54-18.02, p = 0.011], [OR = 6.50, 95% CI 2.57-17.74; p <0.001], [OR = 4.10, 95% CI 1.29-15.82; p = 0.024], [OR = 8.00, 95% CI 3.13-22.16; p <0.001], respectively). The low ADAMTS13 activity group had a slightly longer time to viral clearance than the normal ADAMTS13 activity group, but it was not statistically significant (20 days, 95% CI 16-27 days vs 17 days, 95% CI 13-22 days; p = 0.08; Log rank = 3.1). CONCLUSIONS: Low ADAMTS13 activity has been linked to pneumonia, COVID-19 severity, use of anticoagulants, and need for mechanical ventilation but not to mortality. We propose rADAMTS13 as a novel treatment for severe COVID-19.