A multi-mechanism approach reduces length of stay in the ICU for severe COVID-19 patients

Abstract

Purpose: COVID-19 pandemic has multifaceted presentations with rising evidence of immune-mediated mechanisms underplay. We sought to explore the outcomes of severe COVID-19 patients treated with a multi-mechanism approach (MMA) in addition to standard-of-care (SC) versus patients who only received SC treatment.

Materials and methods: Data were collected retrospectively for patients admitted to the intensive care unit (ICU). This observational cohort study was performed at five institutions, 3 in the United States and 2 in Honduras. Patients were stratified for MMA vs. SC treatment during ICU stay. MMA treatment consists of widely available medications started immediately upon hospitalization. These interventions target immunomodulation, anticoagulation, viral suppression, and oxygenation. Primary outcomes included in-hospital mortality and length of stay (LOS) for the index hospitalization and were measured using logistic regression.

Results: Of 86 patients admitted, 65 (76%) who had severe COVID-19 were included in the study; 30 (46%) patients were in SC group, compared with 35 (54%) patients treated with MMA group. Twelve (40%) patients in the SC group died, compared with 5 (14%) in the MMA group (p-value = 0.01, Chi squared test). After adjustment for gender, age, treatment group, Q-SOFA score, the MMA group had a mean length of stay 8.15 days, when compared with SC group with 13.55 days. ICU length of stay was reduced by a mean of 5.4 days (adjusted for a mean age of 54 years, p-value 0.03) and up to 9 days (unadjusted for mean age), with no significant reduction in overall adjusted mortality rate, where the strongest predictor of mortality was the use of mechanical ventilation.

Conclusion: The finding that MMA decreases the average ICU length of stay by 5.4 days and up to 9 days in older patients suggests that implementation of this treatment protocol could allow a healthcare system to manage 60% more COVID-19 patients with the same number of ICU beds.

Fig 1. Days following COVID-19 clinical phases.

*A2: double anti-inflammatory, AC: anticoagulation. MMA used in the hospital phases of COVID-19, illustrating timing is essential.

Fig 2. Multi-mechanism Approach (MMA).

Includes widely available medications thought to target early immunomodulation, anticoagulation, and viral suppression to prevent catastrophic cytokine release syndrome and potential progression to respiratory failure, shock, and multi-organ dysfunction.

Fig 3. Overview of participants includes in the MMA cohort.

Fig 4. Notched box plot, showing the difference in median LOS in ICU and scatterplot accounting age in y-axis.

*Visual indicator of the significant differences in median in LOS in ICU, the lower panel plots age and treatment were the only predictor variables.

Fig 5. Delta LOS in ICU.

*Based on the optimized model, which considers treatment and age as predictors of LOS, showing greater benefit in reducing LOS in older patients (up to 9 days).