Ventilatory ratio with proning in COVID-19 ards patients: A new tool for an old strategy

INTRODUCTION: Prone positioning is a cornerstone therapy in COVID-19 associated severe Acute Respiratory Distress Syndrome (ARDS). Ventilatory ratio (VR) calculates dead space ventilation, which is independently associated with an increased risk of mortality in ARDS patients. However, no studies so far have demonstrated the changes in VR with proning in such patients. We evaluated VR as a new tool to predict survival in prone positioned COVID -19 ARDS patients. METHODS: This retrospective study included 24 COVID-19 positive ARDS patients admitted to SUNY Downstate Medical Center ICU between April 4, 2020 to May 15, 2020, who had PaO2/FiO2 (PF) ratio < 150, and were proned. Data points of total number of proning days, PaCO2, PF ratio, and VR, were collected before proning, on day 1, and on the last day of proning, along with the mortality data. Statistical analysis was performed in R using student t-test and linear regression. RESULTS: Of the 24 patients included, 80% were male. The median age of the patients was 68 years. With proning, the PF ratio increased by a mean of 0.32 (IQR 0.04,0.54 p<0.01) on day 1 and 0.592 (IQR 0.17,0.91 p<0.001) on last day of proning. VR decreased by a mean of -0.156 (IQR -0.837,+0.09 p=0.15) on day 1 and -0.388 (IQR -0.725,- 0.056 p= 0.15) on last day of proning. PaCO2 is predictive of VR before proning (adjusted R2 =0.69, p<0.001), and on last day of proning (adjusted R2 =0.5, p<0.001). The length of proning had no relationship with change in VR or PF ratio at any time point. VR of < 2 before proning was predictive of overall survival (p < 0.05) with an average survival of 25 days vs 9.8 days for VR > 2. The mortality rate for all patients included was 80% (20/24). CONCLUSIONS: COVID -19 ARDS patients demonstrate impaired ventilation and hypoxemia. Commonly used PF ratio, in proning protocols, has limited prognostic value but deadspace fraction is a powerful predictor of mortality in ARDS. Proning improved PF ratio and VR, however, the latter did not reach statistical significance. PF ratio was not predictive of length of survival, however, VR > 2 before proning is a significant predictor for overall mortality. Hence, VR can function as a new bedside predictive tool with proning in COVID-19 ARDS patients.

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.