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1.
Indian Journal of Critical Care Medicine ; 26:S83, 2022.
Article in English | EMBASE | ID: covidwho-2006370

ABSTRACT

Aim and background: The high mortality associated with the thrombotic events in hospitalised COVID-19 patients resulted in the usage of anticoagulants in varying doses. Whether the high-dose anticoagulants have led to better outcomes or higher incidence of clinically significant bleeding events is still debatable. Objectives: To find the incidence of clinically significant bleeding events in moderate to severe COVID-19 patients on therapeutic anticoagulation and the factors influencing these events. Materials and methods: In our retrospective, single-centre, cohort study of 155 critically ill COVID-19 patients we observed the incidence of clinically significant bleeding. Multivariate regression models were used to evaluate the association between anticoagulant regimen, coagulation, and inflammatory markers with the incidence of bleeding and thrombotic events. Results: The incidence of Clinically Relevant Non-Major Bleeding (CRNMB) was 33.5% (26.17-41.46%,) and major bleeding was 9.03% (5.02-14.69%). The anticoagulation intensity at baseline had a very high odds of major bleeding when Enoxaparin and dual antiplatelet therapy were used together (adjusted OR of 434.09 [3.81-49502.95], p < 0.05). At admission, bleeders had a poorer P/F ratio with more patients on invasive ventilation. At the time of bleeding, the bleeders had a higher d-dimer, ferritin, CRP, and procalcitonin. The subhazard ratio (SHR) for death in bleeders was 3.35 (95% CI, 1.97-5.65;p < 0.001). Conclusion: The incidence of bleeding in critically ill COVID-19 patients on therapeutic anticoagulation increases with the severity of the disease as well as with concurrent use of dual antiplatelets. Major bleeding may also contribute to higher mortality.

2.
Indian Journal of Critical Care Medicine ; 26:S82-S83, 2022.
Article in English | EMBASE | ID: covidwho-2006369

ABSTRACT

Aim and background: Efficacy of therapeutic vitamin D3 supplementation for ICU outcomes in severe COVID-19 is sparingly studied. Objective: Effect of single high-dose vitamin D3 supplementation on sequential organ failure assessment (SOFA) score in patients with moderate to severe COVID-19 disease. Materials and methods: A single centre, randomized, doubleblind, placebo-controlled study was carried out among 90 patients with moderate to severe COVID-19 ARDS defined by PaO2/FiO2 <200. Participants received 0.6 million IU vitamin D3 (oral nanoformulation) (intervention) or placebo (equal volume, oral). SOFA score on day-3, -7, -10, and -14 was measured. The primary outcome was a change in day-7 SOFA score from admission. Pre-specified secondary outcomes were day 10 and day-14 SOFA score, change in PaO2/FiO2 ratio, in-hospital all-cause mortality, and inflammatory cytokine levels. Results: A total of 358 patients were screened and 90 patients (45 in each group) were included. 25(OH)D3 levels were 12.0 (10.0-16.0) and 12.7 (12-18) ng/mL (p = 0.059) at study entry;60 (54.40 to 65.59) ng/mL and 3.8 [1.05 to 6.55] at day-3 in the intervention and placebo group, respectively. The SOFA score on day-7 was better in the treatment group [intergroup difference was -2 (95% CI, -3.99 to -0.01, p = 0.009) with effect-size of r = 0.35 (95% CI, 0.09-0.55). The all-cause mortality with intervention was 24.4% compared to 44.4% (p = 0.046) in the control group. A significant improvement in the day-7 PaO2/FiO2 ratio [200.50 (101.01-291.30) and 110.70 (66.20-166.50), p = 0.003;intergroup difference -98.6 (40.70 to 156.49)], a decrease in CRP [-48.63 (-80.78 to -16.48) and 5.4 (-17.62 to 28.42), p = 0.042)], ferritin [-412.3 (-736.29 to -88.31) and 41.5 (-293.68 to 376.68), p = 0.018] was observed in the intervention and placebo groups, respectively. Conclusion: Single high-dose oral cholecalciferol supplementation to increase vitamin D3 >50 ng/mL improves the SOFA score and reduces in-hospital mortality in vitamin-D deficient patients with severe COVID-19.

3.
Journal of Clinical and Experimental Hepatology ; 12:S30, 2022.
Article in English | EMBASE | ID: covidwho-1996318

ABSTRACT

Background and Aim: Hepatic encephalopathy (HE) in acute-on-chronic liver failure (ACLF) is associated with significant morbidity and mortality. There is limited evidence regarding HE management in patients with ACLF. We conducted a prospective, randomized controlled clinical trial to study the efficacy of intravenous branched chain amino acids (IV-BCAA) with lactulose versus lactulose alone for improvement in HE at 24h, day 3 & day 7. Duration of ICU stay and survival at days 7 and 28 was compared. Methods: CANONIC ACLF patients with HE grades>=2 were randomized into two groups - experimental arm (IV-BCAA - 500mL/day for 3 days + Lactulose;n=39) and comparator arm (Lactulose alone;n=37). Six patients developed COVID-19 after randomization & were excluded (4-experimental arm & 2-comparator arm). HE Grade was assessed by West Haven Classification and Hepatic Encephalopathy Scoring Algorithm (HESA). ACLF severity was determined by CLIF-C ACLF and MELD scores. All patients received standard of care. Results: Both groups were similar in baseline characteristics including grade of HE (2.85 ± 0.75 vs 2.82 ± 0.66;P = 0.864) and CLIF-C ACLF score (54.19 ± 5.55 vs 54.79 ± 5.74;P = 0.655). Overall survival was 40% at 28 days (48.5% vs 31.4%;P=0.143). Significant improvement in HESA score by 1 grade at 24h was seen in 14 patients (40%) in BCAA arm and 6 patients (17.14%) in control group (P=0.034) which translated to shorter ICU stay in the BCAA arm. Median change in HESA score at 24h was significantly more in BCAA arm than control arm (P=0.006), however, this was not sustained at day 3 or 7. Ammonia levels did not correlate with HE grade (Spearman correlation coefficient (-0.0843;P=0.295). Conclusion: Intravenous BCAA leads to early but ill-sustained improvement in grade of HE and reduced ICU stay in ACLF.

4.
Critical Care ; 26(SUPPL 1), 2022.
Article in English | EMBASE | ID: covidwho-1793849

ABSTRACT

Introduction: The cause of respiratory distress by the novel corona virus is an acute hyper inflammatory “cytokine storm”. Besides glucocorticoids, tocilizumab, a recombinant monoclonal antibody, directed against the IL-6 receptor, has been used as a treatment modality with variable results [1]. Factors affecting poor response to tocilizumab remain unrecognized. We report a model to predict worse outcomes among patients with severe COVID-19 pneumonia treated with tocilizumab. Methods: In this retrospective study, patients with severe COVID 19 pneumonia admitted to the intensive care unit of our hospital who received Inj. tocilizumab besides the standard treatment between July 2020 to July 2021, were included. Electronic records of such patients were accessed and demographic, biochemical and outcome measures were recorded. Patients were divided into survivor cohort and mortality cohort. To predict mortality as an outcome, a multivariate logistic regression model was constructed. Results: Total of 101 patients were included, 71 in survival cohort and 30 in mortality cohort. Lactate dehydrogenase (LDH), neutrophil to lymphocyte ratio (NL ratio), creatine kinase myocardial band (CKMB) and partial pressure of oxygen to fraction of inspired oxygen ratio (PFR) on day of drug administration differed significantly among the two cohorts after correction for multiple comparison. However, on multivariable logistic regression analysis, a model incorporating LDH, NL ratio, pro-brain natriuretic peptide levels (ProBNP) and PFR best predicted mortality (Fig. 1). A nomogram was also created to estimate probability of mortality using the model parameters. Conclusions: LDH, ProBNP, NL ratio and PFR at Tocilizumab administration are independently associated with mortality. A model incorporating the combination of these parameters at admission can predict mortality among patients with severe COVID-19 pneumonia with good accuracy. (Figure Presented).

5.
Journal of Association of Physicians of India ; 70(1):28-32, 2022.
Article in English | Scopus | ID: covidwho-1728241

ABSTRACT

Background: Although hydroxychloroquine (HCQ) lacks benefit in patients with moderate-to-severe COVID-19, its role in asymptomatic and mildly symptomatic disease needs better elucidation. Methods: This multi-centre cohort study included asymptomatic and mildly symptomatic, RT-PCR confirmed COVID-19 cases between 30 March and 20 May, 2020. Patients were categorized into two groups (HCQ-treated and untreated) based on exposure to HCQ. Dose of HCQ used was 400 mg twice daily (day one) followed by once daily for seven days. HCQ-untreated patients were managed supportively without any active antiviral or immunomodulatory therapy. Nasopharyngeal SARS-CoV-2 clearance by RT-PCR (primary outcome) was compared between HCQ-treated and untreated patients using Kaplan-Meier analysis and Cox proportional-hazards regression. Clinical efficacy and safety profile of HCQ were assessed (secondary outcomes). Results:162 patients [84 (51·9%) males;mean age 38·2 (15·2) years] were included. Forty-four (27·2%) patients had mild disease, rest 118 (72·8%) were asymptomatic. Seventy-five (46·3%) patients received HCQ. Median time to virological negativity was lesser in HCQ-treated (13 days) versus untreated patients (15 days) (log-rank<0·001) in both asymptomatic and mildly symptomatic patients. Treatment with HCQ was the only independent predictor of virological negativity (hazard-ratio=2·24;adjusted p-value<0·001). Two (5·4%) mildly symptomatic patients progressed to severe disease within 24 hours (two doses) of HCQ initiation, compared to none in the HCQ-untreated group. Five HCQ-treated patients developed minor gastrointestinal side effects, not requiring drug discontinuation. Conclusion: HCQ reduced the time to virologic negativity (by 2 days) in asymptomatic and mildly symptomatic COVID-19, without any serious adverse events. However, no obvious clinical benefit was noted. © 2022 Journal of Association of Physicians of India. All rights reserved.

6.
Placenta ; 101: 13-29, 2020 11.
Article in English | MEDLINE | ID: covidwho-725549

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus, was first identified after a cluster of cases in Wuhan, China in December 2019. Whether vertical transmission or placental pathology might occur following maternal infection during pregnancy remains unknown. This review aimed to summarise all studies that examined the placenta or neonates following infection with SARS-CoV-2, or closely related highly pathogenic coronavirus (SARS-CoV-1, or the Middle East respiratory syndrome coronavirus (MERS-CoV)). Structured literature searches found 50 studies that met the inclusion criteria. Twenty studies reported placental histopathology findings in third trimester placentas following maternal SARS-CoV-2 infection. Using the Amsterdam Consensus criteria to categorise the histopathology results, evidence of both fetal vascular malperfusion (35.3% of cases; 95% Confidence Interval (CI) 27.7-43.0%) and maternal vascular malperfusion (46% of cases; 95% CI 38.0-54.0%) were reported, along with evidence of inflammation in the placentas (villitis 8.7% cases, intervillositis 5.3% of cases, chorioamnionitis 6% of cases). The placental pathologies observed in SARS-CoV-2 were consistent with findings following maternal SARS-CoV-1 infection. Of those tested, a minority of neonates (2%) and placental samples tested positive for SARS-CoV-2 infection (21%). Limited conclusions can be drawn about the effect of maternal SARS-CoV-2 infection on placental pathology as most lack control groups and the majority of reports followed third trimester infection. Collaboration to maximise the number of samples examined will increase the reliability and generalisability of findings. A better understanding of the association between maternal SARS-CoV-2 infection and placental pathology will inform maternity care during the coronavirus pandemic.


Subject(s)
Betacoronavirus/pathogenicity , Coronavirus Infections/pathology , Infectious Disease Transmission, Vertical , Placenta/pathology , Pneumonia, Viral/pathology , Pregnancy Complications, Infectious/pathology , Betacoronavirus/physiology , COVID-19 , Coronavirus Infections/epidemiology , Coronavirus Infections/physiopathology , Coronavirus Infections/transmission , Female , Humans , Infant, Newborn , Pandemics , Placenta/blood supply , Placenta/virology , Placental Circulation/physiology , Pneumonia, Viral/epidemiology , Pneumonia, Viral/physiopathology , Pneumonia, Viral/transmission , Pregnancy , Pregnancy Complications, Infectious/epidemiology , Pregnancy Complications, Infectious/physiopathology , Pregnancy Complications, Infectious/virology , SARS Virus/pathogenicity , SARS Virus/physiology , SARS-CoV-2
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