Insight into COVID-19 associated liver injury: Mechanisms, evaluation, and clinical implications.

COVID-19 has affected millions worldwide, causing significant morbidity and mortality. While predominantly involving the respiratory tract, SARS-CoV-2 has also caused systemic illnesses involving other sites. Liver injury due to COVID-19 has been variably reported in observational studies. It has been postulated that liver damage may be due to direct damage by the SARS-CoV-2 virus or multifactorial secondary to hepatotoxic therapeutic options, as well as cytokine release syndrome and sepsis-induced multiorgan dysfunction. The approach to a COVID-19 patient with liver injury requires a thorough evaluation of the pattern of hepatocellular injury, along with the presence of underlying chronic liver disease and concurrent medications which may cause drug-induced liver injury. While studies have shown uneventful recovery in the majority of mildly affected patients, severe COVID-19 associated liver injury has been associated with higher mortality, prolonged hospitalization, and greater morbidity in survivors. Furthermore, its impact on long-term outcomes remains to be ascertained as recent studies report an association with metabolic-fatty liver disease. This present review provides insight into the subject by describing the postulated mechanism of liver injury, its impact in the presence of pre-existing liver disease, and its short- and long-term clinical implications.

Clinical characteristics, outcome, and factors associated with mortality of pulmonary mucormycosis: a retrospective single-center study from Pakistan.

Introduction and objective: Pulmonary mucormycosis is a rare but rapidly progressive fatal disease. Limited data exist on the outcomes and factors associated with poor prognosis of pulmonary mucormycosis. The objective of this study was to evaluate clinical characteristics, factors associated with mortality, and outcomes of pulmonary mucormycosis at a tertiary care hospital in Pakistan. Methods: This was a retrospective observational study conducted at a tertiary care hospital in Karachi, Pakistan. Medical records of hospitalized patients diagnosed with proven or probable pulmonary mucormycosis between January 2018 and December 2022 were reviewed. Univariate and regression analyses were performed to identify factors associated with mortality. Results: Fifty-three pulmonary mucormycosis patients (69.8% male) were included, with mean age of 51.19 ± 21.65 years. Diabetes mellitus was the most common comorbidity [n = 26 (49.1%)]. Chronic lung diseases were present in [n = 5 (9.4%)], and [n = 16 (30.2%)] had concurrent coronavirus disease 2019 (COVID-19) pneumonia. The predominant isolated Mucorales were Rhizopus [n = 32 (60.3%)] and Mucor species [n = 9 (17%)]. Main radiological findings included consolidation [n = 39 (73.6%)] and nodules [n = 14 (26.4%)]. Amphotericin B deoxycholate was prescribed in [n = 38 (71.7%)], and [n = 14 (26.4%)] of patients received combined medical and surgical treatment. The median [interquartile range (IQR)] hospital stay was 15.0 (10.0-21.5) days. Intensive care unit (ICU) care was required in [n = 30 (56.6%)] patients, with 26 (49.1%) needing mechanical ventilation. Overall mortality was seen in 29 (54.7%) patients. Significantly higher mortality was found among patients requiring mechanical ventilation 20/29 (69%, p = 0.002). Immunosuppression (p = 0.042), thrombocytopenia (p = 0.004), and mechanical ventilation (p = 0.018) were identified as risk factors for mortality on multivariable analysis. Conclusion: This study provides essential insights into the clinical characteristics, outcomes, and mortality factors associated with pulmonary mucormycosis. The mortality rate was high (54.7%), particularly in patients with immunosuppression, thrombocytopenia, and those who required mechanical ventilation.

Comparison of clinical characteristics and outcomes between COVID-19 pneumonia and H1N1 influenza.

INTRODUCTION: The COVID-19 pandemic has been likened to the 2009 H1N1 influenza pandemic. We aim to study the similarities and differences between patients hospitalized with COVID-19 and H1N1 influenza in order to provide better care to patients, particularly during the co-circulation of Influenza A Subtype H1N1 and SARS-CoV-2. MATERIAL AND METHODS: A retrospective cohort study was conducted in order to compare clinical characteristics, complications, and outcomes of hospitalized patients with PCR-confirmed H1N1 influenza pneumonia and COVID-19 at a tertiary care center in Karachi, Pakistan. RESULTS: A total of 115 patients hospitalized with COVID-19 were compared with 55 patients with H1N1 Influenza A pneumonia. Median age was similar in both COVID-19 patients (54 years) and in patients with H1N1 influenza (59 years), but there was male predominance in COVID-19 patients (OR = 2.95; 95% CI: 1.12-7.79). Patients with COVID-19 pneumonia were 1.34 (95% CI: 1.14-1.62) times more likely to have a greater duration of illness prior to presentation compared to H1N1 influenza patients. COVID-19 patients were 4.59 times (95% CI: 1.32-15.94) more likely to be admitted to a general ward compared to H1N1 pneumonia patients. Moreover, patients with COVID-19 were 7.62 times (95% CI: 2.42-24.00) more likely to be treated with systemic steroids compared to patients with H1N1 pneumonia. The rate of nosocomial infections as well as mortality was similar in both H1N1 and COVID-19 pneumonia. CONCLUSION: Our study found a male predominance and longer duration of illness in hospitalized patients with COVID-19 compared to H1N1 influenza patients but no difference in outcomes with either infection.

Clinical characteristics and outcomes of COVID-19: Experience at a major tertiary care center in Pakistan.

INTRODUCTION: Limited data exist on clinical characteristics and outcomes of hospitalized COVID-19 patients in low-middle income countries. We aimed to describe the clinical spectrum and outcomes of hospitalized COVID-19 patients at a tertiary-care center in Karachi, Pakistan. METHODOLOGY: We conducted an observational study of adult COVID-19 patients hospitalized between February-June 2020. Patients with a discharge diagnosis of COVID-19 and PCR positivity were included. We created logistic regression models to understand association of clinical characteristics with illness severity and in-hospital mortality. RESULTS: The study population comprised 445 patients [67% males, median age 53 (IQR 40-64) years]. Majority of patients (N = 268; 60%) had ≥ 1 co-morbid [37.5% hypertension, 36.4% diabetes]. In-hospital mortality was 13%. Age ≥ 60 (aOR] =1.92; 95 %CI = 1.23-3.03), shortness of breath (aOR=4.43; 95% CI=2.73-7.22), CRP ≥150mg/L (aOR:1.77; 95% CI=1.09-2.85), LDH ≥ 500 I.U/L (aOR:1.98; 95% CI=1.25-3.16), Neutrophil-to-Lymphocyte ratio (NLR) ≥5 (aOR:2.80; 95%CI = 1.77-4.42) and increase in serum creatinine (aOR:1.32; 95%CI=1.07-1.61) were independently associated with disease severity. Septic shock (aOR: 13.27; 95% CI=3.78-46.65), age ≥ 60 (aOR: 3.26; 95% CI=1.07-9.89), Ferritin ≥ 1500ng/ml (aOR: 3.78; 95% CI=1.21-11.8), NLR ≥ 5 (aOR: 4.04; 95% CI=1.14-14.35) and acute kidney injury (aOR: 5.52; 95% CI=1.78-17.06) were independent predictors of in-hospital mortality. CONCLUSIONS: We found multiple predictors to be independently associated with in-hospital mortality, except diabetes and gender. Compared to reports from other countries, the in-hospital mortality among COVID-19 patients was lower, despite a high burden of co-morbidities. Further research is required to explore reasons behind this dichotomy.

An antibiotic stewardship program in a surgical ICU of a resource-limited country: financial impact with improved clinical outcomes.

BACKGROUND: Antibiotic resistance (ABX-R) is alarming in lower/middle-income countries (LMICs). Nonadherence to antibiotic guidelines and inappropriate prescribing are significant contributing factors to ABX-R. This study determined the clinical and economic impacts of antibiotic stewardship program (ASP) in surgical intensive care units (SICU) of LMIC. METHOD: We conducted this pre and post-test analysis in adult SICU of Aga Khan University Hospital, Pakistan, and compared pre-ASP (September-December 2017) and post-ASP data (April-July 2018). January-March 2018 as an implementation/training phase, for designing standard operating procedures and training the team. We enrolled all the patients admitted to adult SICU and prescribed any antibiotic. ASP-team daily reviewed antibiotics prescription for its appropriateness. Through prospective-audit and feedback-mechanism changes were made and recorded. Outcome measures included antibiotic defined daily dose (DDDs)/1000 patient-days, prescription appropriateness, antibiotic duration, readmission, mortality, and cost-effectiveness. RESULT: 123 and 125 patients were enrolled in pre-ASP and post-ASP periods. DDDs/1000 patient-days of all the antibiotics reduced in the post-ASP period, ceftriaxone, cefazolin, metronidazole, piperacillin/tazobactam, and vancomycin showed statistically significant (p < 0.01) reduction. The duration of all antibiotics use reduced significantly (p < 0.01). Length of SICU stays, mortality, and readmission reduced in the post-ASP period. ID-pharmacist interventions and source-control-documentation were observed in 62% and 50% cases respectively. Guidelines adherence improved significantly (p < 0.01). Net cost saving is 6360US$ yearly, mainly through reduced antibiotics consumption, around US$ 18,000 (PKR 2.8 million) yearly. CONCLUSION: ASP implementation with supplemental efforts can improve the appropriateness of antibiotic prescriptions and the optimum duration of use. The approach is cost-effective mainly due to the reduced cost of antibiotics with rational use. Better source-control-documentation may further minimize the ABX-R in SICU.

Cerebral phaeohyphomycosis due to Rhinocladiella mackenziei in an immunocompetent patient: A case report and review of literature.

BACKGROUND AND PURPOSE: Rhinocladiella mackenziei is a neurotropic fungus, which can cause devastating intracerebral infections with up to 100% fatality rate. It is difficult to isolate this fungus in laboratory as it grows slowly and requires diagnostic skills. CASE REPORT: A 42-year-old Pakistani man presented with headache, facial numbness, progressive upper limb weakness, and dysarthria. Magnetic resonance imaging of the brain showed a space-occupying lesion in the basal ganglia region. The patient underwent supratentorial craniotomy for biopsy and excision. Histopathology of the specimen revealed granulomatous inflammation with abscess formation. Periodic acid- Schiff special stains highlighted the presence of numerous septate fungal hyphae. The results revealed the growth of dematiaceous fungi, which were morphologically classified as R. mackenziei. The patient is currently stable and is being on amphotericin and posaconazole, along with neurorehabilitation therapy. CONCLUSION: Rhinocladiella mackenziei brain abscess is a devastating infection with significant mortality. This condition should be suspected in patients with brain abscess from high endemic areas.

Tocilizumab for COVID-19 Acute Respiratory Distress Syndrome: Outcomes Assessment Using the WHO Ordinal Scale.

Introduction Cytokine release syndrome in COVID-19 is characterized by hyperinflammation, which manifests as acute respiratory distress syndrome (ARDS), multiorgan failure, and high inflammatory parameters. Tocilizumab, an interleukin 6 (IL-6) antagonist has been used in COVID-19 ARDS with conflicting results from different parts of the world. Objective To study the treatment outcomes with tocilizumab in patients with COVID-19 ARDS and hyperinflammation using the World Health Organization (WHO) COVID-19 ordinal scale. Methods An observational study was conducted from Feb 2020 to May 2020 on COVID-19 ARDS patients with hyperinflammation. Results A total of 244 patients with COVID-19 were admitted, out of which 107 had ARDS. Thirty patients had both ARDS and hyperinflammation and received tocilizumab. The mean age was 62.5 years (SD: 13.5) and the majority were male (83%). The mean CRP pre-treatment was 217.5 mg/L and post 48 to 72 hours of tocilizumab treatment was 98.5 mg/L. Twenty-one patients (70%) also received concomitant intravenous (IV) methylprednisolone. Of the 30 patients, seven died and 20 recovered. Ten patients required intensive care unit admission and nine developed nosocomial infections. COVID-19-associated aspergillosis was diagnosed in three patients post tocilizumab treatment. Mortality was significantly higher in patients who developed a nosocomial infection and who required intermittent positive pressure ventilation (IPPV). Post-treatment, clinical improvement was observed in patients who had a median score of 5 on the WHO ordinal scale. Conclusion Our study supports the use of tocilizumab in COVID-19 ARDS patients with a pre-treatment median WHO ordinal severity score of 5 and recommends the monitoring of nosocomial infections and opportunistic infections.