Safety of full-dose anticoagulation in a ventilated predominantly black population with COVID-19

INTRODUCTION: Coronavirus disease 2019 (COVID-19) can be associated with coagulopathy and a high incidence of thromboembolic events. These events were associated with worse clinical outcomes, especially in critically ill patients. Our study investigated the safety of full dose anticoagulation (AC), in ventilated, predominantly Black patients with COVID-19 infection. METHODS: This is a retrospective observational study based on a chart review of patients admitted to the University Hospital of Brooklyn in New York City from March 23rd through April 23rd, 2020. Inclusion criteria included age ≥ 18 years, confirmed COVID-19 infection, and need for mechanical ventilation. The variables collected included demographics, comorbidities, laboratory results, type of anticoagulation, and Sepsis- Induced Coagulopathy (SIC) score RESULTS: A total of 48 hospitalized patients met the inclusion criteria. 41 (85.4%) were Black, 26 (54%) were males, 22 (46%) were females, and the average age was 68 years. Average days on mechanical ventilation was 13.6 days. D-Dimer was elevated in all patients, with an average of 5.8 mcg/ml. Almost all patients (47/48) had elevated SIC score, defined as SIC score of 2 or above. AC agent used was Heparin in 13 patients (27.1%), low molecular weight heparin (LMWH) in 12 (25%), direct oral anticoagulants (DOAC) in 8 (16.7%), and multiple AC agents in 15 (31.3%). AC was stopped because of major bleed in 5 patients. Overall mortality was 62.5%. AC discontinuation was not associated with increased overall mortality (Pearson Chi-Square= 0.228;p=0.633) CONCLUSIONS: Our study showed that full dose anticoagulation was administered in high risk ICU patients with COVID-19 infection, and significantly elevated D-Dimer level and SIC score. Most patients received heparin or LMWH, or a combination of heparin products with transition to DOAC. However only 5 patients had a major bleed, that was not a significant contributor to overall mortality. Based on our results, administration of full dose anticoagulation in ventilated predominantly black patients with COVID-19 infection, was overall safe and well tolerated.

Complement c3 a-chain as an indicator of disease severity in COVID-19

INTRODUCTION: As we combat the novel coronavirus SARS-CoV-2, elucidating its immunological pathogenesis is vital for both understanding and treating the disease. A few case studies have suggested that the complement system may play an important role in the course of infection, but its specific role is unclear. Our group has shown that higher circulating levels of the complement C3, particularly C3 α-chain, can be a significant predictor of survival in septic shock patients. We therefore sought to investigate if a similar relationship could be seen in SARS-CoV-2. METHODS: Thirty-six COVID-19 patients were consented for this study. Serial blood samples were collected at different time points from 22 patients not in the ICU and 14 in the ICU at the time of collection. The plasma samples were analyzed using Western Blot for circulating C3 α-chain levels. Clinical data on hematologic, respiratory, renal and coagulation status were collected. The data were analyzed for differences in ICU and Non-ICU patients and for correlations of C3 α-chain levels and clinical parameters. RESULTS: In ICU patients, in mean levels of C3 α-chain had a statistically significant increase from Days 0-5 since admission to Days 16-20 (p = 0.042). C3 α-chain levels were positively correlated with time since admission (R = 0.5401, p = 0.0115). In ICU patients, C3 α-chain levels were negatively correlated with Creatinine levels (R = -0.4515, p<0.05), Neutrophil Percentage (R = -0.5525, p<0.001) and Absolute Count (R = -0.6297, p<0.001) and positively correlated with Lymphocyte Percentage (R= 0.6748, p<0.001). In Non-ICU patients, C3 α-chain levels were negatively correlated with Neutrophil Percentage (R = -0.4929, p<0.05), BUN levels (R = -0.5055, p<0.001), and positively correlated with Lymphocyte Percentage (R = 0.45, p<0.05) and Absolute Count (R = 0.6134, p<0.001) and platelet levels (R = 0.4636, p<0.05). CONCLUSIONS: In summary, levels of circulating C3 α- chain increased with time in ICU patients. C3 α-chain levels negatively correlated with renal injury markers and systemic neutrophil levels. Moreover, C3 α-chain levels positively correlated with circulating lymphocyte levels. These results indicate that native C3 is important in fighting against COVID-19 infection and may be a critical prognostic marker of disease progression.