An Experience in Laboratory Diagnosis of Fungal Infections in COVID -19 Patients.

Introduction Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has cast a gloom spell on healthcare worldwide, infecting millions of people. Objective The aim of the present study is to determine the prevalence and review the contributing comorbidities and the precipitating factors leading to the emergence of the fungal infections in COVID-19-affected patients. To assess the utility of different laboratory techniques for confirmation of fungal infections. To assess the strengths and limitations of the diagnostic methods. Methods We have studied 252 clinical samples obtained from 121 COVID-positive patients. Results Among the 121 patients clinically diagnosed with fungal infections, 88 had diabetes and were given steroids for treatment ( p -value = 0.001). Ninety-five patients (78.5%) had a positive laboratory diagnosis (either culture positive, potassium hydroxide [KOH]-positive or positive histopathology report). Fungal culture was positive in 75 (61.9%) patients and histopathology report was positive in 62 (51.2%). Histopathology was positive in 7 (5.8%) patients in whom culture and KOH were negative. Conclusion Aggressive treatment methods, administration of immune suppressants, and antibiotics, with an intention to salvage, have made patients susceptible to the benign fungus, causing it to evade the host immunity, thus leading to invasive infections. Applying different laboratory modalities would not only aid in providing fast and valuable information but also help in understanding the pathology which would assist the clinician in selecting the correct treatment for the patient.

Antibiotics With or Without Rifaximin for Acute Hepatic Encephalopathy in Critically Ill Patients With Cirrhosis: A Double-Blind, Randomized Controlled (ARiE) Trial.

INTRODUCTION: Critically ill patients with cirrhosis admitted to the intensive care unit (ICU) are usually on broad-spectrum antibiotics because of suspected infection or as a hospital protocol. It is unclear if additional rifaximin has any synergistic effect with broad-spectrum antibiotics in ICU patients with acute overt hepatic encephalopathy (HE). METHODS: In this double-blind trial, patients with overt HE admitted to ICU were randomized to receive antibiotics (ab) alone or antibiotics with rifaximin (ab + r). Resolution (or 2 grade reduction) of HE, time to resolution of HE, in-hospital mortality, nosocomial infection, and changes in endotoxin levels were compared between the 2 groups. A subgroup analysis of patients with decompensated cirrhosis and acute-on-chronic liver failure was performed. RESULTS: Baseline characteristics and severity scores were similar among both groups (92 in each group). Carbapenems and cephalosporin with beta-lactamase inhibitors were the most commonly used ab. On Kaplan-Meier analysis, 44.6% (41/92; 95% confidence interval [CI], 32-70.5) in ab-only arm and 46.7% (43/92; 95% CI, 33.8-63) in ab + r arm achieved the primary objective ( P = 0.84).Time to achieve the primary objective (3.65 ± 1.82 days and 4.11 ± 2.01 days; P = 0.27) and in-hospital mortality were similar among both groups (62% vs 50%; P = 0.13). Seven percent and 13% in the ab and ab + r groups developed nosocomial infections ( P = 0.21). Endotoxin levels were unaffected by rifaximin. Rifaximin led to lower in-hospital mortality (hazard ratio: 0.39 [95% CI, 0.2-0.76]) in patients with decompensated cirrhosis but not in patients with acute-on-chronic liver failure (hazard ratio: 0.99 [95% CI, 0.6-1.63]) because of reduced nosocomial infections. DISCUSSION: Reversal of overt HE in those on ab was comparable with those on ab + r.

Association of Lower Antispike Antibody Levels with Mortality in ICU Patients with COVID-19 Disease.

Background: Though vaccines have been reported as highly efficacious in preventing severe COVID-19 disease, there is emerging data of severe infections, albeit a small number, in vaccinated individuals. We have conducted a retrospective observational study to assess the clinical characteristics, immunological response, and disease outcomes among the vaccinated and unvaccinated patients admitted to the ICU with severe COVID-19 disease. Methods: Study Design and Participants. We conducted a retrospective observational study in COVID ICU of a tertiary care hospital. Data were collected from the month of 1 April 2021 to 31 November 2021. All adult patients admitted to the ICU having severe COVID-19 disease were included in the study. Data were collected from the medical records database which included demographics, a clinical course in the ICU, laboratory and radiological parameters, and disease outcomes. In a subset of patients, cell-mediated immunity and S1S2-neutralising antibody assessment was done. Results: A total of 419 patients with severe COVID-19 were included in the study. Of the 419 patients, 90 (21.5%) were vaccinated, and 329 (78.5%) were unvaccinated. There was a significantly higher mortality in unvaccinated severe COVID 19 patients as compared to vaccinated severe COVID patients (46.2% vs 34.4%; P < 0.0455). The neutralizing antibody titre was significantly higher in survivors as compared to nonsurvivors (2139.8, SE ± 713.3 vs 471, SE ± 154.4); P < 0.026. Conclusion: Our study suggests the association of lower neutralizing antibody levels with mortality in ICU patients admitted with COVID-19 breakthrough infections.

Heterologous Booster Dose with CORBEVAX following Primary Vaccination with COVISHIELD Enhances Protection against SARS-CoV-2.

Despite effective vaccination programs, waning immunity in the vaccinated populations and the emergence of variants of concern posed a risk of breakthrough infections. A booster dose was demonstrated to provide substantially increased protection against symptomatic disease and hospitalization. We aimed to evaluate immune memory and the efficacy of reducing the rate of SARS-CoV-2 infection post heterologous booster with CORBEVAX after primary vaccination with two doses of COVISHIELD. SARS-CoV-2 S1/S2 spike IgG and RBD-specific antibody responses were elicited with both booster vaccines, with a greater response in individuals receiving heterologous booster. T and B memory responses were increased with booster dose, whereas B memory needed a longer duration to develop in individuals who received a homologous booster (90 days) in comparison to a heterologous booster (30 days). RBD-specific B memory and antibody-secreting (non-memory) B lymphocytes were enhanced with both boosters; however, the duration of response was longer with the heterologous booster compared to the homologous, indicating greater protection with the heterologous booster. The rate of infection 14 days after administration of the heterologous booster was comparatively lower than that of the homologous booster, with the symptoms being much less or asymptomatic.

Poor immune response to coronavirus disease vaccines in decompensated cirrhosis patients and liver transplant recipients.

BACKGROUND AND AIMS: Recent studies have reported poor humoral immune response to mRNA vaccines in patients with chronic liver disease (CLD). However, the immunogenicity of ChAdOx1 (vector-based) and BBV152 (inactivated virus) vaccines in patients with CLD and liver transplant recipients (LTRs) is unknown. Therefore, we aimed to assess the immunogenicity of ChAdOx1 and BBV152 vaccines in patients with CLD (including cirrhosis patients) and LTRs. METHODS: In this single-center prospective study, consecutive completely vaccinated (ChAdOx1 or BBV152) non-cirrhosis CLD patients, those with cirrhosis, and LTRs were compared with matched healthy controls for anti-spike antibody and cellular response. RESULTS: Sixty healthy individuals, 50 NCCLD patients, 63 compensated and 50 decompensated cirrhosis, and 17 LTRs were included. The proportion of non-responders was similar among the healthy control (8 %), non-cirrhosis CLD (16 %), and compensated cirrhosis groups (17.5 %;p = 0.3). However, a higher proportion of patients with decompensated cirrhosis (34 %) and LTRs (59 %) were non-responders than the healthy controls (p = 0.001). Cluster of differentiation (CD) 4-effector cells were lower in patients with non-cirrhosis CLD and compensated cirrhosis. CD4-naïve, CD4-effector, B, and B-memory cells were lower in the decompensated cirrhosis group. Although the central memory cells were higher in the decompensated cirrhosis group, they could not differentiate into effector cells. CD4- and CD8-naïve cells were higher in the marrow in the LTRs, while the CD4-effector memory cells and CD4- and CD8-effector cells were lower in the LTRs. Furthermore, B cells were more deficient in the LTRs, suggesting poor antibody response. CONCLUSION: Patients with decompensated cirrhosis and LTRs demonstrated suboptimal humoral and cellular immune responses against recombinant and inactivated COVID-19 vaccines.

Primary Norfloxacin Prophylaxis for APASL-Defined Acute-on-Chronic Liver Failure: A Placebo-Controlled Double-Blind Randomized Trial.

INTRODUCTION: This study aimed to evaluate the role of prophylactic norfloxacin in preventing bacterial infections and its effect on transplant-free survival (TFS) in patients with acute-on-chronic liver failure (ACLF) identified by the Asian Pacific Association for the Study of the Liver criteria. METHODS: Patients with ACLF included in the study were randomly assigned to receive oral norfloxacin 400 mg or matched placebo once daily for 30 days. The incidence of bacterial infections at days 30 and 90 was the primary outcome, whereas TFS at days 30 and 90 was the secondary outcome. RESULTS: A total of 143 patients were included (72 in the norfloxacin and 71 in the placebo groups). Baseline demographics, biochemical variables, and severity scores were similar between the 2 groups. On Kaplan-Meier analysis, the incidence of bacterial infections at day 30 was 18.1% (95% confidence interval [CI], 10-28.9) and 33.8% (95% CI, 23-46) (P = 0.03); and the incidence of bacterial infections at day 90 was 46% (95% CI, 34-58) and 62% (95% CI, 49.67-73.23) in the norfloxacin and placebo groups, respectively (P = 0.02). On Kaplan-Meier analysis, TFS at day 30 was 77.8% (95% CI, 66.43-86.73) and 64.8% (95% CI, 52.54-75.75) in the norfloxacin and placebo groups, respectively (P = 0.084). Similarly, TFS at day 90 was 58.3% (95% CI, 46.11-69.84) and 43.7% (95% CI, 31.91-55.95), respectively (P = 0.058). Thirty percent of infections were caused by multidrug-resistant organisms. More patients developed concomitant candiduria in the norfloxacin group (25%) than in the placebo group (2.63%). DISCUSSION: Primary norfloxacin prophylaxis effectively prevents bacterial infections in patients with ACLF.

To assess the efficacy of safety measures adopted during endoscopy in the Corona Virus Disease-19 era for health care professionals-A single-centre tertiary care hospital experience.

BACKGROUND AND OBJECTIVES: During Corona Virus Disease-19 (COVID-19) pandemic, it has been estimated that approximately 10% of health care professionals (HCPs) have been diagnosed contacting  COVID-19. Aerosol-generating procedures have led to change in safety practices among HCPs. We thus evaluated the efficacy of the endoscopic safety measures among HCPs posted in the endoscopy unit. METHODS: In this retrospective analysis, all endoscopic procedures performed over a period of 4 months, from 1 April to 31 July 2020 were included. We noted indications and number of COVID-positive procedures as well as comprehensive screening of HCPs posted in our endoscopy unit. The aim of the study was to evaluate the incidence and outcome of COVID-19 among HCPs. RESULTS: Three thousand four hundred and sixty procedures were included in the analysis. Indications were divided as urgent (n = 190, 5.49%), semi-urgent (n = 553, 16%) and non-urgent group (n = 2717, 78.52%). Thirty-four procedures (0.98%) were done on diagnosed COVID-19 patients. The most common indications were gastrointestinal bleed (n = 12/34, 35.30%) followed by biliary sepsis (n = 9/34, 26.5%). Among the HCPs, the incidence of symptomatic COVID-19 was 6.58% (n = 5/76). All HCPs recovered with excellent outcomes. A comprehensive screening showed 7.90% (n = 6/76) HCPs having Immunoglobulin G (IgG) antibody in their sera. CONCLUSION: Addition of safety measures in endoscopy leads to low risk of transmission among HCPs.