Combined Use of ECMO, Prone Positioning, and APRV in the Management of Severe COVID-19 Patients.

Background: Severe COVID-19-associated Acute Respiratory Distress Syndrome (ARDS) may warrant extracorporeal membrane oxygenation (ECMO). We evaluated the safety and physiologic changes in oxygenation and hemodynamic profile during ECMO, prone positioning, and the two modalities combined in patients receiving veno-venous (VV) ECMO. Methods: Cohort study of consecutive adult patients with COVID-19-associated ARDS requiring VV-ECMO, classified into three groups: ECMO support only; Prone positioning only; and Prone positioning during ECMO. We collected hemodynamic, respiratory and ventilation variables as follows: pre-treatment, 1, 6, and 24 h post-treatment, and documented treatment-related complications. On-treatment variables were compared with pre-treatment using one-sample paired t-test with Bonferroni correction. Results: Fourteen patients (mean age 48.1 [SD 9.3] years, male [100%]) received VV-ECMO. Of those, 10 patients had data during prone positioning alone and seven had data while proned on ECMO. While on ECMO, patients had improvement in oxygen saturation, PaO2/FiO2 ratio, and minute ventilation up to 24 h post-treatment. Vasopressor requirements increased with ECMO at 1 h and 24 h post-treatment. Prone positioning was not associated with clinically significant hemodynamic or respiratory changes, either alone or during ECMO support. All patients sustained deep tissue injuries, but only those on the face or chest were related to prone positioning. Three patients required cannula replacement. In-hospital mortality was 43%. Conclusions: VV-ECMO and prone positioning in patients with COVID-19 ARDS was overall well-tolerated; however, physiologic improvements were marginal, and patients sustained deep tissue injuries. Although this was a selected population with high mortality, our data call into question the benefits of these management modalities in this severe COVID-19 population.

Treatments Associated with Lower Mortality among Critically Ill COVID-19 Patients: A Retrospective Cohort Study.

BACKGROUND: Mortality in critically ill COVID-19 patients remains high. Although randomized controlled trials must continue to definitively evaluate treatments, further hypothesis-generating efforts to identify candidate treatments are required. This study's hypothesis was that certain treatments are associated with lower COVID-19 mortality. METHODS: This was a 1-yr retrospective cohort study involving all COVID-19 patients admitted to intensive care units in six hospitals affiliated with Yale New Haven Health System from February 13, 2020, to March 4, 2021. The exposures were any COVID-19-related pharmacologic and organ support treatments. The outcome was in-hospital mortality. RESULTS: This study analyzed 2,070 patients after excluding 23 patients who died within 24 h after intensive care unit admission and 3 patients who remained hospitalized on the last day of data censoring. The in-hospital mortality was 29% (593 of 2,070). Of 23 treatments analyzed, apixaban (hazard ratio, 0.42; 95% CI, 0.363 to 0.48; corrected CI, 0.336 to 0.52) and aspirin (hazard ratio, 0.72; 95% CI, 0.60 to 0.87; corrected CI, 0.54 to 0.96) were associated with lower mortality based on the multivariable analysis with multiple testing correction. Propensity score-matching analysis showed an association between apixaban treatment and lower mortality (with vs. without apixaban, 27% [96 of 360] vs. 37% [133 of 360]; hazard ratio, 0.48; 95% CI, 0.337 to 0.69) and an association between aspirin treatment and lower mortality (with vs. without aspirin, 26% [121 of 473] vs. 30% [140 of 473]; hazard ratio, 0.57; 95% CI, 0.41 to 0.78). Enoxaparin showed similar associations based on the multivariable analysis (hazard ratio, 0.82; 95% CI, 0.69 to 0.97; corrected CI, 0.61 to 1.05) and propensity score-matching analysis (with vs. without enoxaparin, 25% [87 of 347] vs. 34% [117 of 347]; hazard ratio, 0.53; 95% CI, 0.367 to 0.77). CONCLUSIONS: Consistent with the known hypercoagulability in severe COVID-19, the use of apixaban, enoxaparin, or aspirin was independently associated with lower mortality in critically ill COVID-19 patients.

Early but not late convalescent plasma is associated with better survival in moderate-to-severe COVID-19.

BACKGROUND: Limited therapeutic options exist for coronavirus disease 2019 (COVID-19). COVID-19 convalescent plasma (CCP) is a potential therapeutic, but there is limited data for patients with moderate-to-severe disease. RESEARCH QUESTION: What are outcomes associated with administration of CCP in patients with moderate-to-severe COVID-19 infection? STUDY DESIGN AND METHODS: We conducted a propensity score-matched analysis of patients with moderate-to-severe COVID-19. The primary endpoints were in-hospital mortality. Secondary endpoints were number of days alive and ventilator-free at 30 days; length of hospital stay; and change in WHO scores from CCP administration (or index date) to discharge. Of 151 patients who received CCP, 132 had complete follow-up data. Patients were transfused after a median of 6 hospital days; thus, we investigated the effect of convalescent plasma before and after this timepoint with 77 early (within 6 days) and 55 late (after 6 days) recipients. Among 3,217 inpatients who did not receive CCP, 2,551 were available for matching. RESULTS: Early CCP recipients, of whom 31 (40%) were on mechanical ventilation, had lower 14-day (15% vs 23%) and 30-day (38% vs 49%) mortality compared to a matched unexposed cohort, with nearly 50% lower likelihood of in-hospital mortality (HR 0.52, [95% CI 0.28-0.96]; P = 0.036). Early plasma recipients had more days alive and ventilator-free at 30 days (+3.3 days, [95% CI 0.2 to 6.3 days]; P = 0.04) and improved WHO scores at 7 days (-0.8, [95% CI: -1.2 to -0.4]; P = 0.0003) and hospital discharge (-0.9, [95% CI: -1.5 to -0.3]; P = 0.004) compared to the matched unexposed cohort. No clinical differences were observed in late plasma recipients. INTERPRETATION: Early administration of CCP improves outcomes in patients with moderate-to-severe COVID-19, while improvement was not observed with late CCP administration. The importance of timing of administration should be addressed in specifically designed trials.

COVID-19 mortality risk for older men and women.

BACKGROUND: Case-fatality from COVID-19 has been reported to be relatively high in patients age 65 years or older. We sought to determine the age-specific rates of COVID-19 mortality at the population level. METHODS: We obtained information regarding the total number of COVID-19 reported deaths for six consecutive weeks beginning at the 50th recorded death, among 16 countries that reported a relatively high number of COVID-19 cases as of April 12, 2020. We performed an ecological study to model COVID-19 mortality rates per week by age group (54 years or younger, 55-64 years, and 65 years or older) and sex using a Poisson mixed effects regression model. RESULTS: Over the six-week period of data, there were 178,568 COVID-19 deaths from a total population of approximately 2.4 billion people. Age and sex were associated with COVID-19 mortality. Compared with individuals ages 54 years or younger, the incident rate ratio (IRR) was 8.1, indicating that the mortality rate of COVID-19 was 8.1 times higher (95%CI = 7.7, 8.5) among those 55 to 64 years, and more than 62 times higher (IRR = 62.1; 95%CI = 59.7, 64.7) among those ages 65 or older. Mortality rates from COVID-19 were 77% higher in men than in women (IRR = 1.77, 95%CI = 1.74, 1.79). CONCLUSIONS: In the 16 countries examined, persons age 65 years or older had strikingly higher COVID-19 mortality rates compared to younger individuals, and men had a higher risk of COVID-19 death than women.