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.

The Second- vs First-wave COVID-19: More of the Same or a Lot Worse? A Comparison of Mortality between the Two Waves in Patients Admitted to Intensive Care Units in Nine Hospitals in Western Maharashtra.

BACKGROUND: India, along with the rest of the world, faced the challenging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. The second wave in India lagged behind that in the Western world, due to different timing of seasons. There is scarce data about the differences between the two waves, for intensive care unit (ICU) patients. We present the data of 3,498 patients from 9 ICUs of western Maharashtra. MATERIALS AND METHODS: We collected prospective data of hospitalized, RT-PCR confirmed, coronavirus-2019 (COVID-19) patients, from nine tertiary centers, after institutional ethics committee (IEC) approval. Then, we segregated and analyzed the data of patients admitted to the ICU, for comorbidities, high-resolution computed tomography (HRCT) score, ventilatory support, etc. The primary outcomes were ICU and hospital mortality. We also performed multivariable analysis for predictors of ICU mortality. RESULTS: Overall, there were 3,498 ICU patients. In the first wave, 1,921 patients needed ICU admission, while in the second wave, 1,577 patients. Patients in the second wave had significantly higher ICU (26.1 vs 13.4%, p <0.001) and hospital mortality (29.9 vs 18.2%, p <0.001) and need for ventilatory support of any type. More patients received steroids during the second wave. On multivariable regression, male gender, ICU admission during the second wave, increasing HRCT score, and need for intubation and mechanical ventilation were significant predictors of ICU mortality. CONCLUSION: ICU patients admitted during the two waves were of the similar age, but there were more females, and more patients had comorbidities during the second wave. The ICU and hospital mortality were significantly higher during the second wave. HOW TO CITE THIS ARTICLE: Zirpe KG, Dixit S, Kulkarni AP, Pandit RA, Ranganathan P, Prasad S, et al. The Second- vs First-wave COVID-19: More of the Same or a Lot Worse? A Comparison of Mortality between the Two Waves in Patients Admitted to Intensive Care Units in Nine Hospitals in Western Maharashtra. Indian J Crit Care Med 2021; 25(12):1343-1348.