Ulinastatin Add-on to Standard of Care in Critically Ill COVID-19 Patients: A Multicenter, Retrospective Study

Aim: To assess the impact on 30-day mortality with ulinastatin (ULI) used as add-on to standard of care (SOC) compared to SOC alone in coronavirus disease (COVID-19) patients requiring admission to the intensive care unit (ICU). Materials and methods: In this multicentric, retrospective study, we collected data on clinical, laboratory, and outcome parameters in patients with COVID-19. Thirty-day mortality outcome was compared among patients treated with SOC alone and ULI used as add-on to SOC. Odds ratio (OR) and 95% confidence intervals (CI) were determined to identify the predictors of 30-day mortality. Results: Ninety-four patients were identified and enrolled in both groups with comparable baseline parameters. On univariate analysis, 30-day mortality was significantly lower in ULI plus SOC group than SOC alone group (36.2 vs 51.1%, OR 0.54, 95% CI 0.30–0.97, p = 0.040). The effect on mortality was more pronounced in patients who did not require intubation (10.9 vs 34.0%, OR 0.24, 95% CI 0.09–0.66, p = 0.006) and with early administration (within 72 hours of admission) of ULI (30.7 vs 57.9%, OR 0.32, 95% CI 0.11–0.91, p = 0.032). On multivariate analysis, only intubation predicted mortality (adjusted OR 10.13, 95% CI 3.77–27.25, p<0.0001) and the effect of ULI on survival was not significant (adjusted OR 0.58, 95% CI 0.22–1.52, p = 0.270). Conclusion: Given the limited options for COVID-19 patients treated in ICU, early administration of ULI may be helpful, especially in patients not requiring intubation to improve the outcomes. Further, a large, randomized study is warranted to confirm these findings.

Retrospective Cohort Observational Study to compare the Effect of Mycobacterium w along with Standard of Care vs Standard of Care alone in critically ill COVID-19 Patients

Background: COVID-19 has created enormous health crisis in India due to limited available treatments. Majority of the physicians use sepsis as a prototype to understand the pathophysiology of COVID-19 as there are similarities. Heat-killed Mycobacterium w (Mw) (Inj. Mw®) is a known immunomodulator, which is approved for the treatment of gram-negative sepsis. This observational study was aimed to evaluate the role of Mw along with standard of care (SOC) in critically ill COVID-19 patients. Methods: Total 448 patients’ data (intervention group: 298 in Mw plus SOC vs 150 in SOC alone) with reverse transcriptase-polymerase chain reaction (RT-PCR) confirmed critically ill COVID-19 patients who were admitted at five tertiary care centers were evaluated. They were observed for changes in laboratory [C-reactive protein (CRP), D-dimer, ferritin, lactate dehydrogenase (LDH), and interleukin-6 (IL-6)] parameters, hospital stay, intensive care unit (ICU) stay, and discharge status after giving 0.3 mL intradermal Mw for 3 consecutive days along with SOC during hospitalization. Standard of care included injectable steroids, remdesivir, and heparin. Data were analyzed using STATA 14.2 (StataCorp., College Station, Texas, USA). Results: In baseline characteristics, Mw plus SOC arm had more critically ill patients as seen by higher high-resolution computed tomography (HRCT) score, higher lab values [CRP, ferritin, D-dimer, LDH, creatinine, alanine aminotransferase (ALT)], and more oxygen requirement as compared to SOC alone. Mycobacterium w arm had significantly higher mortality rate in ICU and hospital. Both hospital stay and ICU stay were longer in Mw arm. However, subgroup analysis found that early initiation of Mw (<3 days vs >3 days) was associated with significantly lesser odds of mortality and lesser odds of intubation requirement. Early initiation of Mw (<3 days vs >3 days) also resulted in significantly lesser duration of stay in the ICU along with reduction of CRP, D-dimer, and LDH. Moreover, further analysis of early initiation of Mw (<3 days vs control) resulted in significant reduction in lab values (procalcitonin, CRP, ferritin, LDH, and D-dimer). Conclusion: Mw when added to SOC was found to associate with significantly increased risk of mortality and increased length of hospital stay. However, time since admission to administration of Mw was a significant predictor of in-ICU deaths in multivariate analysis. Early initiation of Mw (<3 days) was observed to be a protective factor against ICU deaths from the multivariate logistic regression model. However, large randomized controlled trials are required to support the same.