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BackgroundPregnancy being immune compromised state, COVID-19 disease poses high risk of premature delivery and threat to fetus. Plasma metabolome regulates immune cellular responses and we aimed to analyze the plasma secretome, metabolome and immune cells in COVID-19 positive pregnant mother and cord blood.MethodsCOVID-19 RT-PCR positive pregnant females (n=112) asymptomatic (n=82), or with mild (n=21) or moderate (n=9) disease and control healthy pregnant (n=10) females were included. Mother’s blood and cord blood (n=80) was analysed for untargeted metabolome profiling and plasma cytokines by high-resolution mass spectrometry (MS) and multiplex cytokine bead array. Immune scan in mothers was done using flow cytometry.ResultsIn asymptomatic SARS-CoV-2 infection, --the amino acid metabolic pathways such as glycine, serine, L-lactate and threonine metabolism was upregulated, riboflavin and tyrosine metabolism, downregulated. In mild to moderate disease, the pyruvate and NAD+metabolism (energy metabolic pathways) were mostly altered. In addition to raised TNF-α, IFN-α, IFN-γ, IL-6 cytokine storm, IL-9 was increased in both mothers and neonates. Pyruvate and NAD+metabolic pathways along with IL-9 and IFN-γ had impact on non-classical monocytes, increased CD4 T cells and B cells but depleted CD8+T cells. Cord blood mimicked the mother’s metabolomic profiles by showing altered valine, leucine, isoleucine, glycine, serine, threonine in asymptomatic and NAD+and riboflavin metabolism in mild and moderate disease subjects.ConclusionsOur results demonstrate a graduated immune-metabolomic interplay in mother and fetus in pregnant females with different degrees of severity of COVID-19 disease. IL-9 and IFN- γ regulated pyruvate, lactate TCA metabolism and riboflavin metabolism with context to disease severity are hall marks of this materno-fetal metabolome.HighlightsSARS-CoV-2 infection alters energy consumption metabolic pathways during pregnancy.Pregnant women with mild to moderate COVID-19 show increased energy demands, and consume stored glucose by upregulating pyruvate and NAD+metabolism.Increased TNF-α and IL-9 in mild COVID-19 disease involve TCA cycle to produce lactate and consume stored glucose by up regulating pyruvate and nicotinamide and nicotinate metabolism.With mild to moderate disease, raised IL-9 and TNF-α, decreased riboflavin pathway, exhaustion of T and B cells cause pathogenesis.Cord blood mimics the metabolic profile of mother’s peripheral blood, SARS- CoV-2 infection reshapes immune-metabolic profiles of mother-infant dyad.Graphical Abstract

This study elucidated the clinical, humoral immune response and genomic analysis of vaccine breakthrough (VBT) infections after ChAdOx1 nCoV-19/Covishield vaccine in healthcare workers (HCWs). Amongst 1858 HCWs, 1639 had received either two doses (1346) or a single dose (293) of ChAdOx1 nCoV-19 vaccine. SARS-CoV-2 IgG antibodies and neutralizing antibodies were measured in the vaccinated group and the development of SARS-CoV-2 infection was monitored.Forty-six RT-PCR positive samples from the 203 positive samples were subjected to whole genome sequencing (WGS). Of the 203 (10.92%) infected HCWs, 21.46% (47/219) were non-vaccinated, which was significantly more than 9.52% (156/1639) who were vaccinated and infection was higher in doctors and nurses. Unvaccinated HCWs had 1.57 times higher risk compared to partially vaccinated HCWs and 2.49 times higher risk than those who were fully vaccinated.The partially vaccinated were at higher risk than the fully vaccinated (RR 1.58). Antibody non-response was seen in 3.44% (4/116), low antibody levels in 15.51% (18/116) and medium levels were found in 81.03% (94/116). Fully vaccinated HCWs had a higher antibody response at day 42 than those who were partially vaccinated (8.96 + 4.00 vs. 7.17 + 3.82). Whole genome sequencing of 46 samples revealed that the Delta variant (B.1.617.2) was predominant (69.5%). HCWs who had received two doses of vaccine showed better protection from mild, moderate, or severe infection, with a higher humoral immune response than those who had received a single dose. The genomic analysis revealed the predominance of the Delta variant (B.1.617.2) in the VBT infections.

Poster session 2, September 22, 2022, 12:30 PM - 1:30 PM Objectives Chronic pulmonary aspergillosis (CPA) is a neglected cause of respiratory disease even in high-TB burden countries like India. It is a term that includes simple aspergilloma, chronic cavitary pulmonary aspergillosis which is the most common variant that presents with formation of lung cavities with or without an aspergilloma or nodules, and chronic fibrosing pulmonary aspergillosis. CPA is a chronic progressive infection that destroys lung tissue in non-immunocompromised patients. So, we studied the prevalence of CPA in liver disease patients with respect to spectrum of infections, fungus isolated, and outcome. Methods A cohort of 2250 liver disease patients with isolation of Aspergillus in respiratory samples, was analyzed retrospectively for the diagnosis of CPA, from June 2018 to June 2020. The demographic characteristics, clinical, radiological, and laboratory objective and subjective variables including age, sex, previous pulmonary conditions, dyspnea score, quality of life, serum albumin, ESR, etc were assessed using Kaplan-Meier curves, log-rank tests, and Cox proportional hazards modeling. In samples of patients, retrospective review of time from likely onset of CPA to referral and cause of death were also investigated. Results CPA was diagnosed in 16% of the patients. Survival was 72%, at 1 year. Increased mortality was associated with chronic obstructive pulmonary disease (hazard ratio 2.57; P = .029), nontuberculous mycobacterial infection (2.04; P Conclusion CPA pulmonary aspergillosis is a common complication and cause of mortality in post-cavitary pulmonary disease. Several factors impact on mortality of CPA, and can be evaluated as tools to assess CPA prognosis. Underlying liver disease is an important predictor of mortality. As there is a rise in azole-resistance, appropriate diagnosis, and antifungal sensitivity testing should be done in all suspected cases. Early diagnosis and treatment can prevent mortality in CPA patients.

Poster session 3, September 23, 2022, 12:30 PM - 1:30 PM Objectives Candida auris (C. auris) infections are associated with misidentification, intrahospital transmission, poor treatment outcomes, and higher mortalities. Prompt detection, earlier initiation of therapy and effective surveillance can curtail C. auris in hospitals. We aimed to study epidemiology, risk factors, and therapeutic management of invasive infections caused by C. auris in patients with hepatobiliary diseases. Methods Single-center, prospective study of patients with suspected invasive fungal infections between January2017-December 2021 in the patients with hepatobiliary diseases. Demographics, comorbidities, and laboratory variables were recorded. The positive yeast cultures were identified by VITEK 2 (Biomerieux, India) and antifungal sensitivity confirmed by Broth microdilution in accordance with CLSI guidelines. The final outcomes considered were mortality within 1 month after diagnosis or discharge of the patient with stable parameters. Results Total of 189 isolates of C. auris from 73 patients, blood 25 (13.2%), abdominal fluids 29 (15.3%), urine 90 (47.6%), respiratory 7 (3.6%), liver abscess 2 (1.05%), pancreatic abscess 1 (0.5%), and wound infections 3 (1.5%). Underlying disease was chronic liver disease 49 (68%), 15 (20%) post liver transplant patients, acute on chronic liver failure 5 (7%), acute liver failure 2 (3%), acute pancreatitis 1 (1.3%), and pancreatic neuroendocrine tumor 1 (1.3%). 18 (25%) patients were discharged, the mortality was 54 (74.04%). Risk factors were MELD 40 (P .04), Child C (P .05), and CTP score above 12. Prior use of steroids (P .02), neutropenia (P .03), prolonged hospital stay (P .029), the use of broad-spectrum antibiotics ˃7 days (P .05) were the risk factors significantly associated with the development of C. auris infections, and higher mortality. Co-morbidities, acute renal failure, diabetes, and hepatitis infection were not significantly associated with mortality. The antifungal resistance: fluconazole 68.42%, voriconazole 14.03%, flucytosine 59.64%, and amphotericin B 28% with no resistance to caspofungin and micafungin. Conclusion Our study depicts the spectrum of invasive infections caused by C. auris, its prevalence, risk factors, and therapeutic options. The presence of risk factors, steroid use, neutropenia, broad-spectrum antibiotic use, and a hospital stay of ˃7 days should prompt toward escalating diagnostic measures for rapid identification of C. auris for early initiation of therapy. Active screening of patients with risk factors can also reduce mortality. The study results also help to guide empiric therapy with echinocandins as azoles and amphotericin B show high resistance in these isolates.

Poster session 3, September 23, 2022, 12:30 PM - 1:30 PM Objective Cryptococcus neoformans is an encapsulated yeast found ubiquitously in the environment, considered important in immunocompromised individuals with HIV. Non-HIV susceptible groups include malignancies, long-term use of corticosteroids, solid organ transplantation, sarcoidosis, immunosuppressive therapy, and cirrhosis. Cryptococcal infections are rising in HIV-negative cirrhotic patients, accounting for 6-21% of the systemic infections. Chronic liver disease (CLD) is a neglected risk factor for fungal infections. To analyze epidemiology, risk factors, and antifungal susceptibility profile of HIV-negative liver disease patients. Material Methods The retrospective study was conducted in tertiary care hepatobiliary center in New Delhi, India from January 2017 to March 2022 after ethical approval. Demographic data, laboratory data, and clinical history of the patients admitted with liver disease and suspected cryptococcal infections were obtained from Hospital records for epidemiology and risk factor analysis. Blood, CSF, serum, urine, and body fluid (Ascitic fluid, peritoneal fluid, pleural fluid, MiniBAL) samples were processed for fungal culture on SDA and SDA with cyclohexamide. Blood and body fluid were also inoculated in an automated blood culture system (BacT/ALERT 3D bioMérieux). Samples were processed for gram stain, India ink, and Cryptococcal antigen. Identification was done by an automated identification system (VITEK 2 compact bioMérieux). The micro-broth dilution method (Sensititre YeastOne colorimetric plate, Thermo Fisher Scientific, MA, United States) was used to determine the susceptibility of all Cryptococcus strains to the six antifungal drugs, fluconazole, 5-fluorocytosine, amphotericin B, itraconazole, posaconazole, and voriconazole. The results were reported as wild-type (WT) or non-wild-type (non-WT) in accordance with the epidemiological cutoff value (ECV) set for Cryptococcus spp. (Espinel-Ingroff et al., 2012a, b; CLSI, 2018). Results We analyzed 30 patients of suspected cryptococcal infection and obtained 40 C. neoformans isolates from different samples from these patients. Out of 40 samples, C neoformans was isolated from blood (25,62.5%), urine (6,15%), ascitic fluid (4,10%), mini-BAL (2,5%), bone marrow (1,2.5%), CSF (1,2.5%), pleural fluid (1,2.5%). All samples were positive for Cryptococcal antigen. India ink positivity was observed in 56%. Alcoholic liver disease was the most common risk predictive factor seen in 30% of patients. Hepatitis B and C-associated with CLD was seen in 20%. Other risk predictive factors were AKI (70%), diabetes mellitus (20%), TB (10%), autoimmune hepatitis (6.6%), autoimmune disease (autoimmune hemolytic anemia, Sjogren syndrome) (6.6%), Sarcoidosis (3.3%), Hepatocellular carcinoma (3.3%), HIV (3.3%). Hepatic encephalopathy was seen in 70% of patients which mimics the symptoms of C. meningitis.7.5% (3/40), 5% (2/40), 2.5% (1/40), 7.5% (3/40), and 2.5% (1/40) of C. neoformans strains were non-WT to fluconazole, 5-fluorocytosine, amphotericin B, posaconazole, and itraconazole, respectively, but all strains were WT to voriconazole. Overall mortality was 66.6%. Conclusion Above study shows that liver diseases are an important risk factor for cryptococcal infection owing to immunosuppressed state, use of steroids, and associated comorbidities like DM, TB, AKI, autoimmune disease, Sarcoidosis, hepatocellular carcinoma. Therefore, it is necessary to investigate and be vigilant about the isolation of Cryptococcus. The use of appropriate antifungals can improve clinical outcomes. As there is increasing resistance to amphotericin B, 5-fluorocytosine, azoles; antifungal susceptibility testing should be done. Cryptococcal antigen detection can be useful in non-CSF samples as well.

Poster session 1, September 21, 2022, 12:30 PM - 1:30 PM Objectives Patients with liver disease (LD) are more predisposed to candidemia due to the dysfunctional Kupffer cells which fails to capture the circulating yeasts, thereby causing fungal dissemination. Candidemia is ten times more common among end-stage liver disease patients compared with other LD patients. Compared to those with abdominal candidiasis, ICU admission and mortality are found to be higher in liver transplant recipients (LTRs) with candidemia. Though a majority of Candida infection among LD patients are due to C. albicans, there has been an increasing prevalence of non-albicans isolates. This study was mainly aimed at species differentiation and antifungal susceptibility. Our objective was to study the pattern of Candida isolates from blood among patients with different LD states admitted to tertiary care Liver Hospital. To determine the distribution of Candidemia in patients with different liver disease states. To determine the various species of Candida isolated from blood in patients with liver diseases. To determine the anti-fungal susceptibility pattern of Candida isolates in blood in patients with liver disease. To determine the year-wise changing trends in Candida spp. isolated in blood and its anti-fungal susceptibility pattern in patients with liver disease. Materials and Methods This is a retrospective observational study conducted in the department of Microbiology at Institute of Liver and Biliary Sciences (ILBS), New Delhi. Ethical approval for this study (IEC/2021/84/NA06) was provided by the Institutional ethics committee/Institutional review board. A total of 118 LD patients with candidemia who were admitted to ILBS between January 2017 to December 2020 were included in the study. Clinical details of these patients were collected from the hospital information system. Patients with LD were divided into 4 groups—acute liver failure (ALF), acute on chronic liver failure (ACLF), chronic liver disease (CLD), and post-liver transplantation (Post-LT). Candida speciation as identified by VITEK® 2 (Biomérieux) and also its antifungal susceptibility pattern by broth microdilution. Results The mean age of the 118 LD patients was 48.6 ± 14.9 years [± standard deviation (SD)]. Among them 107 (90.7%) were males and 11 (9.3%) were females. Among the 118 LD patients, 6 (5.1%) were ALF patients, 32 (27.1%) were ACLF patients, 66 (55.9%) were CLD patients and 14 (11.9%) were post-LT patients. The most common Candida species isolated was C. tropicalis (22.9%), followed by C. glabrata (17.8%), C. albicans (16.9%), C. parapsilosis (12.7%), C. auris (8.5%), C. krusei (6.8%) and other Candida species (14.4%). The other Candida species isolated were C. haemulonii, C. kefyr, C. lusitaniae, C.pelliculosa, C. duobushaemulonii, C. lipolytica, and C. rugosa. The sensitivity to fluconazole (55.1%), voriconazole (86.4%), caspofungin (82.2%), micafungin (97.5%), flucytosine (80.5%), amphotericin B (86.4%). Mortality was 66%. Conclusion Our study shows that chronic liver disease, acute liver failure and liver transplantation are important risk factors for invasive candidiasis. There was a rise in the non-albicans Candida, especially C. tropicalis and C. glabrata. There is rising antifungal resistance to azoles and can lead to therapy failure. Hence antifungal sensitivity testing is essential in patients with these neglected risk factors to prevent mortality.

Poster session 3, September 23, 2022, 12:30 PM - 1:30 PM Objectives Liver cirrhosis causes immune dysregulation and increased susceptibility to fungal infections. We studied the epidemiology and risk factors, and compared the rapid diagnostic methods and biomarkers for fungal pneumonia in critically ill cirrhotics. Methods Single-center, prospective cohort study of 100 critically ill cirrhotics with fungal pneumonia between January to September 2021. Comparative analysis was done for culture, realtime PCR and biomarkers, bronchoalveolar lavage and serum Galactomannan, and serum procalcitonin measured on days 1, 3, and 7. The final outcome considered was mortality within 1 month after diagnosis or discharge. Results Aspergillus flavus was the most common species (70/100,70%). Risk factors were, neutropenia (P .03), steroids prior to ICU admission (P .02), prolonged hospitalizations ˃21 days (P .05), and culture positivity was 80%. The culture was not inferior to realtime PCR for the diagnosis of fungal pneumonia. BAL Galactomannan was an early prognostic marker with a median rise above ˃ 3.5 index value. The Median PCT level was higher from day 1in the fungal pneumonia non-survivor group (3.29 vs. 0.8 ng/ml) with higher 30-day mortality (72%). Higher PCT was associated with bacterial co-infection (48%), antibiotic (74%), antifungal therapy, and renal failure and mortality. Conclusion Fungal pneumonia complicates cirrhotics with neutropenia, prolonged hospitalization, and steroids as risk factors. Aspergillus flavus predominate in consensus with Asian epidemiology. Culture methods are reliable and a combination of molecular tests with BAL Galactomannan is useful for rapid diagnosis. Serum PCT is raised in patients with fungal pneumonia and is associated with higher mortality. In our study the baseline PCT at admission to ICU was higher in the non-survivor group, and levels on D3 and D7 were persistently higher. High serum procalcitonin level is an independent prognostic biomarker of mortality risk in fungal pneumonia.

Background A previous community-based severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serosurvey in Delhi in January 2021 reported a seroprevalence of 50.52%. We conducted a repeat serosurvey to obtain a recent estimate of the seroprevalence of IgG SARS-CoV-2 in the general population of Delhi, India. Methods This cross-sectional study was conducted from September 24 to October 14, 2021, in 274 wards of Delhi among 27,811 participants through a multistage sampling technique. Results The crude seroprevalence was 89.5% (95% CI 89.1, 89.8), weight for age and sex was 88% (95% CI 87.6, 88.4), and after adjustment for assay performance was estimated as 97.5% (95% CI 97.0, 98.0). On adjusted analysis, the odds of seroconversion in the participants vaccinated with at least one dose of either COVID-19 vaccine (Covishield/Covaxin) was more than four times compared to the unvaccinated ones (aOR 4.2 (3.8, 4.6)). 86.8% of the seropositive individuals had a SARS-CoV-2 signal/cut-off ≥4.0 although it was significantly lower in the pediatric age group. Post-second wave (August to October 2021), on average there were daily 39 new COVID-19 cases and 0.44 deaths which during Omicron driven the third wave in January to March 2022 increased to daily 4,267 cases and 11.6 deaths. Conclusion A high prevalence of IgG antibodies against SARS-CoV-2 with likely higher antibody titres in the vaccinated compared to the unvaccinated groups with evidence of hybrid immunity in a majority of the population was protective against severe disease during transmission of subsequent omicron variants.

ImportanceNo proven treatment is available for severely ill COVID-19. Therapeutic use of COVID-19 convalescent plasma (COPLA) is under investigation.ObjectiveTo compare the efficacy of COPLA with standard medical therapy (SMT) alone in severe COVID-19 patients.Design, setting and participantsA multicentric, open-labelled, phase-III randomised controlled trial conducted at two treatment centres with COPLA collected at the third dedicated centre in North-India, the coordinating centre during trial from June 2020 to December 2020. The study population comprised 400 participants in the ratio of 1:1 in each treatment group.InterventionOne group received COPLA with SMT (n=200), and another group received SMT only (n=200).Main outcome measuresPrimary outcome was time to clinical improvement measured by a two-point reduction in the ordinal scale. Secondary outcomes included duration of O2therapy, the proportion of patients on mechanical ventilation at day-7, mortality, SARS-CoV-2 antibody levels, cytokine levels and incidence of adverse events.ResultsThe median time to a two-point reduction in the ordinal scale in both groups was 9 days (IQR=7–13) (p=0.328). The median duration of O2therapy was 8 days (IQR=6–12) in COPLA and 10 days (IQR=6–12) in SMT group (p=0.64). The PaO2/FiO2ratio showed significant improvement at 7 days in COPLA group(p=0.036). There was no difference in mortality till 28 days in both groups (p=0.62). However, if COPLA was given within 3 days of hospital admission, a significant reduction in ordinal scale was observed (p=0.04). Neutralising antibody titres in COPLA group (80 (IQR 80–80)) were higher than SMT group (0 (IQR 0–80)) at 48 hours (p=0.001). COPLA therapy led to a significant reduction in TNF-α levels at 48 hours (p=0.048) and D-dimer at 7 days (p=0.02). Mild allergic reactions were observed in 3 (1.5%) patients in COPLA group.Conclusion and relevanceConvalescent plasma with adequate antibody titres should be transfused in COVID-19 patients along with SMT in the initial 3 days of hospitalisation for better clinical outcomes.Trial registration numberNCT04425915.

This study (August-September 2021) estimated the seroprevalence of SARS-CoV-2 neutralizing antibodies in the general population of Delhi and correlated it with their anti-SARS-CoV-2 IgG levels. Samples were selected by simple random sampling method. The neutralizing capacity was estimated by performing a surrogate virus neutralization test (sVNT) (GenScript), Piscataway, NJ, USA. A total of 2233 (87.1%, 95% C.I. 85.7, 88.3) of the 2564 SARS-CoV-2 IgG seropositive samples had detectable SARS-CoV-2 neutralizing antibodies. In samples with S/CO ​≥ ​4.00, the neutralizing antibodies ranged from 94.5% to 100%. The SARS-CoV-2 neutralizing antibody seroprevalence strongly correlated with the S/CO range of IgG SARS-CoV-2 (r ​= ​0.62, p ​= ​0.002).

We conducted this study to estimate seroprevalence of neutralizing antibodies in the general population and to further correlate it with the IgG SARS-CoV-2 IgG levels. This present cross-sectional analysis was conducted as a sequel to a state level community-based seroepidemiological study in Delhi, India. A total of 2564 seropositive samples were selected from 25622 seropositive samples through simple random sampling. Neutralizing capacity was estimated by performing a surrogate virus neutralization test with the sVNT (GenScript) assay. Neutralizing antibody against the SARS-CoV-2 virus was operationally considered as detected when the signal inhibition was ≥30%.A total of 2233 (87.1%, 95% C.I. 85.7, 88.3) of the 2564 SARS-CoV-2 seropositive samples had detectable neutralizing antibodies. On bi-variate analysis but not on adjusted analysis, Covid-19 vaccination showed a statistically significant association with the presence of neutralizing antibodies (p

BackgroundIndia saw a massive surge and emergence of SARS CoV2 variants. We elucidated clinical and humoral immune response and genomic analysis of vaccine breakthrough (VBT) infections after ChAdOx1 nCoV-19 vaccine in healthcare workers (HCWs).MethodsThe study was conducted on 1858 HCWs receiving two doses of ChAdOx1 nCoV-19 vaccine. Serial blood samples were collected to measure SARS CoV2 IgG and neutralizing antibodies. 46 RT-PCR positive samples from VBT infections were subjected to whole genome sequencing (WGS).ResultsInfection was confirmed in 219 (11.79%) HCWs of which 21.46% (47/219) were non-vaccinated, significantly more (p ConclusionsNearly one in ten vaccinated HCWs can get infected, more so with only single dose (13.65%) than two doses (8.62%). Fully vaccinated are better protected with higher humoral immune response. Genomic analysis revealed an alarming rise of Delta variant (B.1.617.2) in VBT infections.

BackgroundThe role of convalescent plasma (COPLA) for the treatment of severely ill Corona Virus Disease-2019 is under investigation. We compared the efficacy and safety of convalescent plasma with fresh frozen plasma (FFP) in severe COVID-19 patients.Methods and findingsThis was an open-label, single-centre phase II RCT on 29 patients with severe COVID-19 from India. One group received COPLA with standard medical care (SMC) (n=14), and another group received FFP with SMC (n=15). A total of 29 patients were randomized in the two treatment groups. Eleven out of 14 (78.5%) patients remained free of ventilation at day seven in the intervention arm while the proportion was 14 out of 15 (93.3 %) in the control arm (p= 0.258). The median reductions in RR per min at 48-hours in COPLA-group and FFP group were -6.5 and -3 respectively [p=0.004] and at day seven were -14.5 and -10 respectively (p=0.008). The median improvements in percentage O2 saturation at 48-hours were 6.5 and 2 respectively [p=0.001] and at day seven were 10 and 7.5 respectively (p=0.026). In the COPLA-group, the median improvement in PaO2/FiO2 was significantly superior to FFP at 48-hours [41.94 and 231.15, p=0.009], and also at day-7 [5.55 and 77.01 pConclusionCOPLA therapy resulted in rapid improvement in respiratory parameters and shortened time to clinical recovery, although no significant reduction in mortality was observed in this pilot trial. We need larger trials to draw conclusive evidence on the use of Convalescent plasma in COVID-19. This trial is registered with ClinicalTrial.gov (identifier: NCT04346446).

Background The Corona virus disease 2019 (COVID-19) pandemic caused by SARS -Corona virus-2 (SARS-CoV-2) has been a major concern the world over. Serological surveillance is an important tool to assess the spread of infection in the community. This study attempted to assess the prevalence of antibodies to SARS-CoV-2 among blood donors in Delhi, India during the pre-vaccination period. Methods Seroprevalence of SARS-CoV2-2 IgG antibodies were determined in blood donors reporting to the Department of Transfusion medicine at a tertiary care hepatobiliary center, in India from September to October 2020. The SARS-CoV-2 IgG antibodies against spike subunit 1 protein were measured using the enhanced chemiluminescence method. Results A total of 1066 blood donors were screened. The overall seropositivity for SARS-CoV-2 IgG antibodies was 27.57 % (294/1066). The highest seropositivity was seen in the age group 26−35 years, 46.6 % (137/492), followed by 18−25 years, 28.2 % (83/260), 36−45 years, 19.4 % (57/244), and more than 45 years, 5.8 % (17/70). The seropositivity in the donors who had donated blood previously was 26.1 % (189/723). There was no statistically significant difference amongst seroprevalence in the blood groups, AB blood group (32.6 %, 95 % CI 23.02−43.3), group B (27.2 %, 95 % CI 22.8−32.09 %), group A (27.1 %, 95 % CI 21.8−32.9 %), and group O (27.02 %, 95 % CI 22.3−32.1 %) (p 0.539). Conclusions There was significantly higher seropositivity for SARS-CoV-2 antibodies in the voluntary healthy blood donors indicating community spread and large number of asymptomatic cases in Delhi. Higher seroprevalence in younger adults indicated increased exposure to the virus and lack of COVID appropriate behaviour.

Streptococcus gallolyticus subsp. gallolyticus bacteremia is associated with colorectal malignancies. There is limited data regarding the association of Streptococcus gallolyticus subsp. pasteurianus with malignancies. We aimed to study the pattern of isolation of Streptococcus gallolyticus and analysis of risk factors in patients with hepatobiliary diseases. We also planned to evaluate its association with hepatocellular malignancy.We analyzed clinical and laboratory data of 68 cases of Streptococcus gallolyticus infections (77 isolates) from January 2013 to December 2017. These included blood (58), ascitic fluid (15), bile (2) and pleural fluid (2). We analyzed the risk factors in patients developing malignancy with Streptococcus gallolyticus infections.Amongst the 68 patients studied, eight (11.76%) had confirmed malignancies, hepatocellular carcinoma (HCC) (5), rectal adenocarcinoma (1), pancreatic carcinoma (1) and uterine tumors (1). Simultaneous isolation of S. gallolyticus subsp. pasteurianus from blood and ascitic fluid in eight patients (11.8%, p = .01) was significantly associated with the occurrence of HCC. Streptococcus gallolyticus infection with HCC was associated with younger age (median 55 years), lymphocytosis and elevated gamma-glutamyl transferase (GGT).This study provides a novel insight into the association of Streptococcus gallolyticus subspecies pasteurianus with HCC. The isolation of the organism from blood and ascitic fluid should prompt the clinicians to search for evidence of HCC actively.

There is great variation in cytopenias in cirrhotic patients with same severity and hypersplenism and their causative factors are not clear. Recent studies have highlighted the role of gut microbiome in regulation of constant and emergency hematopoiesis. Broad-spectrum antibiotics can disrupt the homeostatic or adaptive microbiota in cirrhosis, leading to impaired hematopoiesis and a higher susceptibility to infections. We studied all patients with cirrhosis with cytopenia (anemia, leucopenia, and/or thrombocytopenia), admitted in the Institute of Liver & Biliary Sciences, between January 2016 and July 2017, who underwent a bone marrow examination. The effect of the different antimicrobial agents on peripheral blood counts and bone marrow cellularity was assessed. A total of 196 patients’ data was analyzed for this study. Patients on antimicrobials (n=115) had significantly lower hemoglobin (p<0.001), total leucocyte count (p=0.048), and platelet count (p=0.043) compared to patients not on antimicrobials. On unadjusted analysis, significant association with thrombocytopenia existed in beta-lactams (OR = 1.56, 95% CI = 1.06–2.40), quinolones (OR = 1.66, 95% CI = 1.11–2.61), and antifungals (OR = 2.24, 95% CI = 1.96–4.34). Cephalosporins were found to be significantly associated with anemia (OR = 1.91, 95% CI = 1.07–3.41). Patients who received antimicrobials had hypocellular marrow (p<0.001) as compared to nonrecipients of antibiotics. The adjusted analysis showed that quinolones and beta-lactam antibiotics are the drug classes having significant association with thrombocytopenia and alternative class of drug should be explored in these patients to avoid severe thrombocytopenia.

Context: Stenotrophomonas maltophilia is a known nosocomial pathogen which is intrinsically resistant to multiple antibiotics. In India, S. maltophilia infection has only few case reports. Aim: To determine the incidence of S. maltophilia infection from clinical isolates based on the specimen type, antibiotic susceptibility pattern, and impact on outcome. Settings and Design: One-year retrospective study was done at a tertiary liver care center. Methods: Patients with S. maltophilia isolation in clinical samples were selected. Serial levels of serum procalcitonin and total leukocyte count were recorded. Environmental surveillance was done from the wards of S. maltophilia isolation as part of routine practice. Statistical Analysis: Continuous data were compared using Kruskal–Wallis test/Mann–Whitney test. The categorical data were compared by Chi-square/Fisher's exact test, wherever necessary. Besides this, an appropriate analysis like survival was carried out at the time of data analysis. Results: One hundred isolates were obtained from eighty patients of six wards. The greatest number (44/100, 44%) were from the Liver Coma Intensive Care Unit and the lowest (3/100) from the day care. Isolation from the respiratory samples was 1.32% and bloodstream infection 0.6%. Of 100 isolates, 12 (12%) were resistant to both trimethoprim–sulfamethoxazole and levofloxacin. Conclusion: S. maltophilia was effectively isolated from the hospital environment, with two of hand impression and three of water samples' positive. Patients with respiratory infection had most S. maltophilia isolates. Antibiotic susceptibility revealed more resistance than reported in this region.

The first consensus report of the working party of the Asian Pacific Association for the Study of the Liver (APASL) set up in 2004 on acute-on-chronic liver failure (ACLF) was published in 2009. With international groups volunteering to join, the “APASL ACLF Research Consortium (AARC)” was formed in 2012, which continued to collect prospective ACLF patient data. Based on the prospective data analysis of nearly 1400 patients, the AARC consensus was published in 2014. In the past nearly four-and-a-half years, the AARC database has been enriched to about 5200 cases by major hepatology centers across Asia. The data published during the interim period were carefully analyzed and areas of contention and new developments in the field of ACLF were prioritized in a systematic manner. The AARC database was also approached for answering some of the issues where published data were limited, such as liver failure grading, its impact on the ‘Golden Therapeutic Window’, extrahepatic organ dysfunction and failure, development of sepsis, distinctive features of acute decompensation from ACLF and pediatric ACLF and the issues were analyzed. These initiatives concluded in a two-day meeting in October 2018 at New Delhi with finalization of the new AARC consensus. Only those statements, which were based on evidence using the Grade System and were unanimously recommended, were accepted. Finalized statements were again circulated to all the experts and subsequently presented at the AARC investigators meeting at the AASLD in November 2018. The suggestions from the experts were used to revise and finalize the consensus. After detailed deliberations and data analysis, the original definition of ACLF was found to withstand the test of time and be able to identify a homogenous group of patients presenting with liver failure. New management options including the algorithms for the management of coagulation disorders, renal replacement therapy, sepsis, variceal bleed, antivirals and criteria for liver transplantation for ACLF patients were proposed. The final consensus statements along with the relevant background information and areas requiring future studies are presented here., Article Highlights Updated on the basis of AARC data of >3300 cases enrolled into AARC registry prospectivelyACLF is distinct form Acute Decompensation of cirrhosisNewer sections on DILI-ACLF, AIH-ACLF, PVT/HVOTO–ACLFReversibility of Chronic Liver Disease in ACLFPortal and systemic hemodynamics and their relevance in ACLFAcute Portal Hypertension and Variceal progression in ACLFAARC score as a guide for treatment strategies in ACLFACLF in Children-first consensus on pediatric ACLF

Background and Aims Endothelial injury and dysfunction play a detrimental role in the pathogenesis of infections. Endothelium-related molecules have been reported as potential biomarkers for early diagnosis and/or prognosis of infections. The prognostic value of these biomarkers in patients with liver cirrhosis and infections however remain elusive. Methods In this study, we investigated the performance of key soluble endothelial injury biomarkers, including intercellular adhesion molecule 1 (ICAM1), von Willebrand Factor (vWF) antigen, vascular endothelial growth factor receptor 1 (vegfr1), angiopoietin 1 and 2 (Ang1, 2) as mortality predictors in liver cirrhosis patients with severe covid-19 or bacterial sepsis. Results A total of 66 hospitalized patients [admitted in covid-19 ward or liver intensive care unit (ICU)] were included. 22 patients had covid-19 alone while 20 patients had cirrhosis plus covid-19. 24 patients had liver cirrhosis plus bacterial sepsis. Among cirrhosis patients, most common aetiology was alcohol. ICAM1 was increased (p=0.003) while vegfr1 (p, Graphical abstract

Introduction: The prevalence of nosocomial infection by Elizabethkingia meningoseptica (E. meningoseptica) has increased. It has been found to be associated with outbreaks of neonatal, adult and device related infections with mortality rates as high as 50%. Conventional empirical antibiotics against Gram-Negative Bacteria (GNB) are not effective against E. meningoseptica and interpretive Minimum Inhibitory Concentration (MIC) breakpoints are not available yet, making the treatment tricky. Hence, early detection is essential to prevent morbidity and mortality associated with E. meningoseptica. Aim: To know the incidence, clinical profile, associated risk factors and antibiotic susceptibility of E. meningoseptica isolates from suspected patients. Materials and Methods: This prospective study was done on patients admitted from January 2017-December 2018 to a tertiary care Hepatobilliary center in India. Clinical details, demographic details, associated risk factors and antibiotic sensitivity pattern of E. meningoseptica isolates obtained from various clinical samples during the study period were analysed. Analysis was done using SPSS software version 22. The categorical data was represented in frequency (%) and continuous data in mean. Results: A total of 32 isolates from 20 patients were included. Out of the 20 patients, 15 (75%) were males with a mean age of 43.05 years (range, 2-71 years). E. meningoseptica was most frequently isolated from respiratory samples (87.5%). Risk factors were chronic liver disease (75%), diabetes mellitus (50%), prolonged hospital admission (55%), prior ICU stay (100%), invasive procedures like insertion of Central Venous Catheter (CVC) (100%), need for life supports like prolonged ventilation (70%) and haemodialysis (55%). Minocycline was the most susceptible drug with 100% sensitivity followed by cotrimoxazole (65.6%). Conclusion: Patients with E. meningoseptica infection have significant morbidity and mortality. Hence awareness about the organism, active surveillance and investigation for the source of the organism will help in implementation of appropriate infection control measures and prevent outbreaks or recurrence.

Introduction: Infections are common in cirrhosis and is the leading cause of progression of liver failure and increased mortality. Non-specific findings on radiology prompt a need for a diagnostic armamentarium targeting both typical as well as atypical pathogens. With the advent of molecular diagnostic techniques, an early diagnosis and timely initiation of therapy prevents the injudicious use of antibiotics. Aim: To determine the utility of real time multiplex Polymerase Chain Reaction (PCR) as a diagnostic aid in identification of atypical bacterial respiratory pathogens in cirrhotic patients. Materials and Methods: The observational study was conducted at Tertiary Hepatobiliary Centre, Institute of Liver and Biliary Sciences Hospital, New Delhi, India, from April to September 2018. Bronchoalveolar Lavage (BAL)/mini-BAL samples were collected from 88 suspected cases of pneumonia for routine laboratory work-up as per clinician request. The lower respiratory tract samples were subjected to semi-quantitative culture and PCR. Results were analysed on the basis of aetiological categorisation of liver diseases, radiological and microbiological findings. Results: Among 88 samples, nine were positive either by culture or PCR. PCR analysis revealed three positive samples. A sample positive for Legionella species on PCR showed growth of A. flavus in culture. Another sample was positive for both Legionella species and S. aureus on PCR. The third sample was positive for S. aureus on PCR and on culture grew Methicillin Sensitive S. aureus (MSSA). Conclusion: Liver disease is a risk factor for development of Legionella and other atypical pathogens. Therefore, it becomes important to actively look for such pathogens during the workup of a patient with clinical suspicion of pneumonia. Thus, early diagnosis help in limiting the use of indiscriminate antimicrobials, and timely initiation of targeted antimicrobials. Use of molecular techniques like PCR help in identifying the atypical pathogens which are neglected and thus determines the course of treatment.

Methicillin-resistant Staphylococcus aureus (MRSA) is an important cause of infection, both in hospitalised patients with significant healthcare exposure and in patients without healthcare risk factors. Community-acquired methicillin-resistant S. aureus (CA-MRSA) are known for their rapid community transmission and propensity to cause aggressive skin and soft tissue infections and community-acquired pneumonia. The distinction between the healthcare-associated (HA)-MRSA and CA-MRSA is gradually fading owing to the acquisition of multiple virulence factors and genetic elements. The movement of CA-MRSA strains into the nosocomial setting limits the utility of using clinical risk factors alone to designate community or HA status. Identification of unique genetic characteristics and genotyping are valuable tools for MRSA epidemiological studies. Although the optimum pharmacotherapy for CA-MRSA infections has not been determined, many CA-MRSA strains remain broadly susceptible to several non-β-lactam antibacterial agents. This review aimed at illuminating the characteristic features of CA-MRSA, virulence factors, changing clinical settings and molecular epidemiology, insurgence into the hospital settings and therapy with drug resistance.

Hookworm infestations, endemic in India, are a common cause of iron deficiency anemia. Hemosuccus pancreaticus, a rare clinical condition, is due to passage of blood into the pancreatic duct possibly through a route between an aneurysm of an artery close to the pancreas and/or pancreatic duct, leading to gastrointestinal (GI) bleeding. Portal hypertensive upper GI bleed is also known since long. We report a case of a 38-year-old male with a history of alcoholism who was being investigated for GI bleeding who had concomitant hookworm infestation, hemosuccus pancreaticus as well as portal hypertension. To the best of our knowledge, this is the first report of common occurrence of hemosuccus pancreaticus and portal hypertension with hookworm infection. This case signifies the importance of infectious causes of GI bleeding to be considered even in cases where anatomic malformations or pathophysiological alterations are predominant.

Infections are the leading cause of morbidity and mortality in liver transplant (LT) recipients. We studied timeline, spectrum of infection, system involved, and antimicrobial resistance in 64 patients undergoing live donor LT with 6-month follow-up. Of 64 patients, 38 (59.5%) patients had 103 infectious episodes, 10 patients had single infectious episode and 28 patients had two or more infectious episodes. 96 (93.2%) were bacterial and Candida infections were in 7 (6.8%). Early phase had 30 (29.1%) episodes; intermediate phase 25 (24.2%) and late phase 48 (46.6%). Mortality was 11/64 (17.1%). Knowledge of timeline, aetiological agent and antimicrobial resistance is useful to guide empirical therapy and infection prevention.

Introduction: There is paucity of data regarding mycobacterial infections in liver diseases. Guidelines do not exist for diagnosis, monitoring of patients and modification of the treatment. Aim: Our aim was to elucidate demographic characteristics, profile of mycobacterial infection and comparison of diagnostic methods in liver diseases. Materials and Methods: We studied liver disease patients from January 2012 to December 2016, screened for Tuberculosis (TB) if having fever, cough for >2 weeks, haemoptysis, unexplained weight loss, increasing ascites, unresponsive to diuretics, unexplained bowel symptoms, radiological lesions and past or family history of TB. TB diagnosed if there is: (i) histological caseating granulomas; (ii) smear Acid Fast Bacilli; (AFB) positivity; (iii) growth on Mycobacterial Growth Indicator Tube (MGIT) culture; or (iv) positive quantitative polymerase chain reaction for Mycobacterium tuberculosis (MTB qPCR). Mycobacteria other than tuberculosis (MOTT) were identified by negative MPT64 assay. Results: Of the 118/816 positive samples, 31/260 (11.92%) were pulmonary and 87/556 (15.65%) were extra-pulmonary TB (EPTB). There was a male preponderance (66.1%), median age 53 years in pulmonary and 37 years in EPTB. Thirty two samples (27.11%) were smear positive, low in EPTB 13/87 (14.9%) as compared to 19/31 (61.2%) pulmonary. MGIT was positive in 108/118 (91.52%) and 97/118 (82.2%) were MTB qPCR positive. MTB was isolated from all pulmonary samples and 72/87 (82.75%) of EPTB. MOTT was identified in 15/118(12.71%). Sensitivity and specificity of MTB qPCR was 90.3% and 100% respectively in pulmonary and 76.6% and 97.9% respectively in EPTB. Conclusion: There is predominance of smear negative, EPTB and MOTT in liver diseases. MGIT culture and TB PCR have additive advantage over either test alone. MOTT should be ruled out in all cases as treatment varies. High index of suspicion and good screening methods are needed to identify TB and MOTT owing to similar presentation and anti-tubercular drug toxicity issues.

Earlier studies demonstrated immunological response to Alternaria alternata in patients with eosinophil-related fungal rhinosinusitis (FRS). However, Aspergillus flavus rather than A. alternata is predominantly isolated from such patients in Asia. We compared immunological response to A. flavus and A. alternata in our patients with eosinophil related FRS. Total immunoglobulin E, absolute eosinophil count (AEC), cytokine response, and in vitro eosinophil degranulation in the presence of A. flavus/A. alternata were compared among patients with eosinophil-related FRS, non-eosinophilic rhinosinusitis (NECRS), and healthy individuals. Eosinophil-related FRS patients were subgrouped into: Group A - presence of mucin with fungus in tissues and positive immediate hypersensitivity; group B - presence of mucin with fungus in biopsies and no immediate hypersensitivity; and group C - presence of mucin without fungi and hypersensitivity. A. flavus was the predominant (89%) isolate. Significantly higher major basic protein (MBP) was induced by A. flavus in Group A (279.15 ± 32.29 ng/2.5 × 10(5) cells) compared to Group B (254.9 ± 17.14 ng), Group C (238.33 ± 17.56 ng), NECRS (56.96 ± 10.97 ng), and normal subjects (28.73 ± 7.04 ng). A. alternata - eosinophil interaction failed to induce detectable MBP. AEC and serum cytokines, interleukin (IL)- 2, IL-4, IL-5, IL-10, tumor necrosis factor α, and interferon-γ were significantly higher (P < 0.001) in eosinophil-related FRS compared to NECRS and control. Thus a mixed Th1 and Th2 cytokine response was observed in eosinophil-related FRS. In conclusion, immune response in eosinophil-related FRS depends on locally inciting fungi rather than A. alternata in all instances, and the categorization of this group appears to be arbitrary.

A 15 year old girl presented to the emergency with complaints of foreign body sensation in eyes. Multiple translucent larvae were observed on the conjunctivae. A nasal cavity search also revealed similar larvae localised near the opening of nasolacrimal duct in the inferior meatus. They were identified as Oestrus ovis, which can affect humans causing cavitary myiasis, affecting eyes and rarely nose. In addition, presence of Pthirus pubis was also found in the nasal cavity. Pthirus pubis infestation has been reported from pubic hairs, axillary hairs, eyelashes, moustache and beard but never from the nasal cavity. This is a very rare case of concomitant ophthalmic and nasal myiasis along with pubic louse infestation of nasal cavity.

Improvement in CD4 counts in children with human immunodeficiency virus (HIV) has been reported with some infections. We present an 11-year-old HIV-infected boy who developed acute myeloid leukemia that showed spontaneous remission along with improvement in CD4 counts with documented Demodex mite infestation. The child presented with fever without localization during course of illness, and developed crusted lesion at angle of mouth. Direct microscopy of skin biopsy revealed Demodex mite infestation. The child was continued on highly active antiretroviral treatment along with single dose of ivermectin and local application of permethrin. The crusted lesion improved within a weeks’ time. His CD4 counts improved from baseline of 534/μL to 1674/μL over a period of 4 weeks.

Mucormycoses are opportunistic fungal infections with a high mortality rate. Rhizopus oryzae is the most common agent implicated in human infections. Although R. homothallicus has been previously reported to be a cause of pulmonary mucormycosis, it is the first time that we are reporting as a causative agent of rhino-orbital and cutaneous mucormycosis.

Background Liver cirrhosis causes immune dysregulation and increased susceptibility to fungal infections. We studiede risk factors, molecular epidemiology and compared the rapid diagnostic methods and biomarkers for fungal pneumonia in critically ill cirrhotics Methods Single-center, prospective cohort study of 50 critically ill cirrhotics with fungal pneumonia between January and September 2017. Comparative analysis of culture, real-time PCR and biomarkers; Bronchoalveolar lavage and serum galactomannan, serum procalcitonin were measured by ELISA and chemiluminescence assay on Days 1, 3, 7. Final outcome were mortality within 1 month after diagnosis or discharge. Genotyping of clinical and air sampling Aspergillus isolates was done Results Aspergillus flavus was most common species (34/50, 68%). Risk factors were, neutropenia (P 0.03), steroids prior to ICU admission (P 0.02), prolonged hospitalizations >21 days (P 0.05). Culture positivity was 80%. Culture was not inferior to real-time PCR for diagnosis of fungal pneumonia. BAL Galactomannan was early prognostic marker with median rise above >1 index value on Day 1. Median PCT level was higher from Day 1 in the fungal pneumonia nonsurvivor group (3.29 vs. 0.8 ng/mL) with higher 30-day mortality (72%). Higher PCT was associated with bacterial co-infection (48%), antibiotic(74%) and antifungal therapy and renal failure and mortality. Cinical isolates from patients matched those recovered from air in two clusters. Conclusion Fungal pneumonia complicates cirrhotics with neutropenia, prolonged hospitalization and steroids as risk factors. Aspergillus species predominate as in Asian epidemiology. Culture methods are reliable and combination of molecular test with BAL galactomannan is useful for rapid diagnosis. SerumPCT is raised in patients with fungal pneumonia and associated with higher mortality. In our study the baseline PCT at admission to ICU was higher in nonsurvivor group, levels on D3 and D7 were persistantly higher. High serum procalcitonin level is an independent prognostic biomarker of mortality risk in fungal pneumonia. Genetic relatedness of clinical and environmental sample necessitates infection control measures to prevent invasive aspergillosis in high-risk patients. Disclosures All authors: No reported disclosures.

Increasing demand for energy in recent years has seen a rise in development of alternative energy sources. Wind being one of the most abundant and easily available sources is an excellent alternative to conventional energy sources. Vertical Axis Wind Turbines (VAWT's) are of two type's viz. Darrieus (lift based) and Savonius (drag based). The problem associated with Darrieus is the lack of self-starting while the Savonius has a low efficiency. In order to overcome these flaws, an innovative design has been created by incorporating both the types into one single unique structure not tested before. In this design, the Darrieus blades are helically twisted to get even torque distribution. The Savonius blades are of half drum type and at the center of the assembly. This unique design allows the use Savonius as a method of self-starting the wind turbine which the Darrieus cannot achieve on its own. There are 3 Darrieus blades placed circumferentially and 2 Savonius couples attached perpendicular to each other along the shaft. The cross-section of the Darrieus blades is of NACA-4415. The objective is to eliminate the need for external motors for self-starting purposes and study the performance of the model. The testing of the model was carried out for different wind velocities. Initially the Darrieus and Savonius blades were tested independently and then the new model which combines the two designs was tested.