Objectives: Convalescent plasma (CP) as a passive source of neutralizing antibodies and immunomodulators is a century-old therapeutic option used for the management of viral diseases. We investigated its effectiveness for the treatment of COVID-19. Design: Open-label, parallel-arm, phase II, multicentre, randomized controlled trial. Setting: Thirty-nine public and private hospitals across India. Participants: Hospitalized, moderately ill confirmed COVID-19 patients (PaO2/FiO2: 200-300 or respiratory rate > 24/min and SpO2 ≤ 93% on room air). Intervention: Participants were randomized to either control (best standard of care (BSC)) or intervention (CP + BSC) arm. Two doses of 200 mL CP was transfused 24 hours apart in the intervention arm. Main Outcome Measure: Composite of progression to severe disease (PaO2/FiO2<100) or all-cause mortality at 28 days post-enrolment. Results: Between 22 nd April to 14 th July 2020, 464 participants were enrolled; 235 and 229 in intervention and control arm, respectively. Composite primary outcome was achieved in 44 (18.7%) participants in the intervention arm and 41 (17.9%) in the control arm [aOR: 1.09; 95% CI: 0.67, 1.77]. Mortality was documented in 34 (13.6%) and 31 (14.6%) participants in intervention and control arm, respectively [aOR) 1.06 95% CI: -0.61 to 1.83]. Interpretation: CP was not associated with reduction in mortality or progression to severe COVID-19. This trial has high generalizability and approximates real-life setting of CP therapy in settings with limited laboratory capacity. A priori measurement of neutralizing antibody titres in donors and participants may further clarify the role of CP in management of COVID-19.

PurposeUlinastatin, a serine protease inhibitor, inhibits several pro-inflammatory proteases and decreases inflammatory cytokine levels and mortality in experimental sepsis. We studied the effect of ulinastatin on 28-day all-cause mortality in a double-blind trial in patients with severe sepsis in seven Indian hospitals.MethodsPatients with sepsis were randomized within 48 h of onset of one or more organ failures to receive intravenous administration of ulinastatin (200,000 IU) or placebo 12 hourly for 5 days.ResultsOf 122 randomized subjects, 114 completed the study (55 receiving ulinastatin, 59 receiving placebo). At baseline, the mean APACHE II score was 13.4 (SD = 4.4), 48 (42 %) patients were receiving mechanical ventilation, 58 (51 %) were on vasopressors, and 35 % had multiple organ failure. In the modified intention-to-treat analysis (patients receiving six or more doses of study drugs), 28-day all-cause mortality was 7.3 % with ulinastatin (4 deaths) versus 20.3 % (12 deaths) with placebo (p = 0.045). On multivariate analysis too, treatment with ulinastatin (odds ratio 0.26, 95 % CI 0.07–0.95; p = 0.042) independently decreased 28-day all-cause mortality. However, the mortality difference did not reach statistical significance in the intention-to-treat analysis [10.2 % (6/59 deaths) with ulinastatin versus 20.6 % (13/63 deaths) in the placebo group; p = 0.11]. The ulinastatin group had lower incidence of new-onset organ failure (10 vs. 26 patients, p = 0.003), more ventilator-free days (mean ± SD 19.4 ± 10.6 days vs. 10.2 ± 12.5 days, p = 0.019), and shorter hospital stay (11.8 ± 7.1 days vs. 24.2 ± 7.2 days, p < 0.001).ConclusionsIn this pilot study, intravenous administration of ulinastatin reduced mortality in patients with severe sepsis in the modified intention-to-treat analysis, but not in the intention-to-treat analysis.Electronic supplementary materialThe online version of this article (doi:10.1007/s00134-014-3278-8) contains supplementary material, which is available to authorized users.

Background:A pregnant woman is usually young and in good health until she suffers from some acute injury. Her prognosis will hopefully be better if she receives timely intensive care.Materials and Methods:The aims of this study were to study the indications of medical intensive care unit (MICU) transfers for critically ill pregnant and postpartum females, biochemical and hematological profile, organ failure, ICU interventions, outcome of mother/fetus, APACHE II score and its correlation with mortality.Study Design and Setting:It is a prospective observational study, carried out in the MICU of a tertiary care teaching hospital over a period of 18 months. One hundred and twenty-two pregnant and postpartum females (up to 42 days after delivery) were studied.Results and Conclusion:Maternal age >30 years was associated with high mortality (68.2%). Majority of the females were admitted in the third trimester (50 patients) and postpartum period (41 patients), and mortality was highest in the postpartum period (39%). Increasing parity and gravida was associated with significantly high mortality (59.5%). Acute viral hepatitis E (45 patients) was most common indication for MICU transfer, followed by malaria and pregnancy-induced hypertension. The mortality rate was 30.3%. The most common cause of death was acute viral hepatitis E (24 patients), with hepatic failure (53 patients) being the most common organ failure. Majority of the females (88 patients) were ANC registered. Low Glasgow coma score and high APACHE II score on admission were associated with significantly high mortality (85.2%). Prompt treatment with oseltamivir in H1N1 infection was associated with good maternal and fetal outcomes.

Background and Aims:Critical illness may complicate any pregnancy. Timely intensive care management of critically ill obstetric patients has better outcomes than expected from the initial severity of illness. The aim was to study the indications of transfer of post-cesarean section patients to post-anesthesia intensive care unit (PACU). (PACU transfer indicated that the patient required intensive care).Materials and Methods:This was a prospective observational study carried out in the PACU of a tertiary care teaching public hospital over a period of 2 years. Sixty-one postoperative lower segment cesarean section (LSCS) females admitted consecutively in PACU were studied. The study included obstetric PACU utilization rate, intensive care unit interventions, outcome of mother, Acute Physiology and Chronic Health Evaluation (APACHE II) score, and its correlation with mortality.Results:Postanesthesia intensive care unit admission rate was 2.8% and obstetric PACU utilization rate was 3.22%. Of 61 patients, four had expired. Obstetric indications (67.2%) were the most common cause of admission to PACU. Among the obstetric indications hemorrhage (36.1%) was found to be a statistically significant indication for PACU admission followed by hypertensive disorder of pregnancy (29.5%). Cardiovascular disease (16.4%) was the most common nonobstetric indication for PACU transfer and was associated with high mortality. The observed mortality was 6.557%, which was lower than predicted mortality by APACHE II Score.Conclusion:Obstetric hemorrhage, hypertensive disorders of pregnancy and cardiovascular diseases are the leading causes of PACU admission in post LSCS patients. Prompt provision of intensive care to critically ill obstetric patients can lead to a significant drop in maternal morbidity and mortality.

Background To be universally applicable in treatment of severe COVID-19, novel therapies, especially those with little toxicity and low cost, are urgently needed. We report here the use of one such therapeutic combination involving two commonly used nutraceuticals, namely resveratrol and copper in patients with this disease. This study was prompted by pre-clinical reports that sepsis-related cytokine storm and fatality in mice can be prevented by oral administration of small quantities of resveratrol and copper. Since cytokine storm and sepsis are major causes of death in severe COVID-19, we retrospectively analyzed outcomes of patients with this condition who had received resveratrol and copper. Methods & Findings Our analysis comprised of 230 patients with severe COVID-19 requiring inhaled oxygen who were admitted in a single tertiary care hospital in Mumbai between April 1 and May 13 2020. Thirty of these patients received, in addition to standard care, resveratrol and copper at doses of 5.6 mg and 560 ng, respectively, orally, once every 6 hours, until discharge or death. These doses were based on our pre-clinical studies, and were nearly 50 times and 2000 times less, respectively, than those recommended as health supplements. A multivariable-adjusted analysis was used to model the outcome of death in these patients and evaluate factors associated with this event. A binary logistic regression analysis was used, with age, sex, presence of comorbidities and receipt of resveratrol-copper as covariates. Data were updated as of May 30 2020. The number of deaths in resveratrol-copper and standard care only groups were 7/30 (23.3%, 95% CI 8.1%-38.4%) and 89/200 (44.5%, 95% CI 37.6%-51.3%), respectively. In multivariable analysis, age >50 years [odds ratio (OR) 2.558, 95% CI 1.454-4.302, P=0.0011] and female sex (OR 1.939, 95% CI 1.079-3.482, P=0.0267) were significantly associated, while presence of co-morbidities was not significantly associated (OR 0.713, 95% CI 0.405-1.256, P=0.2421) with death. There was a trend towards reduction in death in patients receiving resveratrol-copper (OR 0.413, 95% CI 0.164-1.039, P= 0.0604). Conclusions We provide preliminary results of a novel approach to the treatment of severe COVID-19 using a combination of small amounts of commonly used nutraceuticals, which is non-toxic and inexpensive, and therefore could be widely accessible globally. The nearly two-fold reduction in mortality with resveratrol-copper observed in our study needs to be confirmed in a randomized controlled trial.