Metabolic alterations unravel the maternofetal immune responses with disease severity in pregnant women infected with SARS-CoV-2.

Pregnancy being an immune compromised state, coronavirus disease of 2019 (COVID-19) disease poses high risk of premature delivery and threat to fetus. Plasma metabolome regulates immune cellular responses, therefore we aimed to analyze the change in plasma secretome, metabolome, and immune cells with disease severity in COVID-19 positive pregnant females and their cord blood. COVID-19 reverse transcriptase-polymerase chain reaction positive pregnant females (n = 112) with asymptomatic (Asy) (n = 82), mild (n = 21), or moderate (n = 9) disease, healthy pregnant (n = 18), COVID-19 positive nonpregnant females (n = 7) were included. Eighty-two cord blood from COVID-19 positive and seven healthy cord blood were also analyzed. Mother's peripheral blood and cord blood were analyzed for untargeted metabolome profiling and cytokines by using high-resolution mass spectrometry and cytokine bead array. Immune scan was performed only in mothers' blood by flow cytometry. In Asy severe acute respiratory syndrome coronavirus 2 infection, the amino acid metabolic pathways such as glycine, serine, l-lactate, and threonine metabolism were upregulated with downregulation of riboflavin and tyrosine metabolism. However, with mild-to-moderate disease, the pyruvate and nicotinamide adenine dinucleotide (NAD+ ) metabolism were mostly altered. Cord blood mimicked the mother's metabolomic profiles by showing altered valine, leucine, isoleucine, glycine, serine, threonine in Asy and NAD+ , riboflavin metabolism in mild and moderate. Additionally, with disease severity tumor necrosis factor-α, interferon (IFN)-α, IFN-γ, interleukin (IL)-6 cytokine storm, IL-9 was raised in both mothers and neonates. Pyruvate, NAD metabolism and increase in IL-9 and IFN-γ had an impact on nonclassical monocytes, exhausted T and B cells. Our results demonstrated that immune-metabolic interplay in mother and fetus is influenced with increase in IL-9 and IFN-γ regulated pyruvate, lactate tricarboxylic acid, and riboflavin metabolism with context to disease severity.

Comparison of safety and efficacy of convalescent plasma with fresh frozen plasma in severe covid-19 patients.

BACKGROUND: Role of Convalescent plasma (COPLA) to treat severe COVID-19 is under investigation. We compared efficacy and safety of COPLA with fresh frozen plasma (FFP) in severe COVID-19 patients. METHODS: One group received COPLA with standard medical care (n = 14), and another group received random donor FFP, as control with standard medical care (n = 15) in severe COVID-19 disease. RESULTS: The proportion of patients free of ventilation at day seven were 78.5% in COPLA group, and 93.3 % in control group were not significant (p= 0.258). However, improved respiratory rate, O2 saturation, SOFA score, and Ct value were observed in the COPLA group. No serious adverse events were noticed by plasma transfusion in both groups.

A study to evaluate the role of experience in acquisition of the skill of orotracheal intubation in adults.

BACKGROUND AND AIMS: To evaluate the role of experience in acquisition of skill of orotracheal intubation in adults. MATERIAL AND METHODS: A prospective randomized study was conducted on 307 patients of either sex, belonging to ASA grade I and II (aged 18-60 years) posted for surgery under general anaesthesia. The patients were subjected to DL and ETI procedure, which was performed by five different groups of participants. Group 1 consisted of first-year resident of anaesthesiology with experience of less than 10 intubations, group 2 for second-year resident, group 3 for third-year resident, group 4 for senior resident and group 5 for consultant. Ease of mask ventilation, time taken for intubation, number of attempts, success rate, and ease of intubation were assessed for all the groups. RESULTS: Categorical variables were analysed using Chi-square test. For all statistical tests, a P value less than 0.05 was taken as a significant difference. Maximum difficulty in mask ventilation was encountered by group 1 anaesthesiologist, that is, in 69.2% of the patients. Group 1 took maximum time to intubate, that is, 47.98 ± 31.54 sec and least time was taken by group 5 anaesthesiologist (9.55 ± 6.93) sec. First attempt success rate was least in group (80.0%). Group 1 had success rate of 96.9%, whereas rest all groups had 100% success. CONCLUSION: Skill of mask ventilation and intubation and time taken for intubation grossly improves with increasing experience. Minimum of 25 intubation attempts should be required by an anaesthesiologist resident in elective scenario to achieve 100% success rate in our study.

1H NMR Using Metabolic Study in Body Fluids for Diagnosis of Cryptococcal Meningitis in Adults.

Background: Cryptococcal meningitis is considered to affect HIV patients and those with impaired immune systems. Early identification and treatment are the keys to decreasing morbidity and mortality related to CM. Using 1H NMR spectroscopy, a prospective case-control study will assess the metabolic profile of adults' serum, urine, and CSF. Methodology: The present multicentric study was conducted at Lucknow. The study included 150 participants, out of which there were 31 cryptococcal meningitis cases, 34 positive meningitis controls, and the rest, 85, were disease controls. Result: The discriminant function analysis (DFA) of the three biofluids was used to find significant metabolites between the cases and the control group collectively. A group categorization between control group and the cases in serum, urine, and CSF samples was also made possible by the NMR spectral bin-based orthogonal signal correction and principal component analysis score plots of important metabolites produced from DFA. The cases group had a higher proportion of patients with higher CSF protein levels than the positive control group (BM and TM). Acetone was found among urine samples in both control samples, i.e., positive and negative. Conclusion: This is the first study to explore biomarkers in serum, urine, and CSF in addition to radiological features and clinical symptoms. Hence, a quick, non-invasive prognosis and diagnosis of cryptococcal meningitis in adults can be made using clinical and microbiological investigation, as well as metabolomic analysis of urine samples. This study shows that urine can be used as a biofluid to differentiate between Cryptococcus meningitis in adults. However, when compared to the negative control, our sample size was significantly smaller, necessitating further confirmation on a larger sample size.

Soluble factors and suppressive monocytes can predict early development of sepsis in acute-on-chronic liver failure.

Patients with acute-on-chronic liver failure (ACLF) have a high probability of developing systemic inflammation and sepsis due to immune dysregulation. Fifty-nine patients with ACLF (12 without and 19 with systemic inflammation, and 28 with sepsis) were serially monitored for clinical and immunological changes at baseline, 6 hours, 24 hours, day 3, and day 7 following hospitalization. Ten healthy controls were also included. At all time points, soluble plasma factors and monocyte functions were studied. Patients with ACLF and systemic inflammation showed higher interleukin (IL)-6, vascular endothelial growth factor-a, monocyte chemoattractant protein 1, and macrophage inflammatory protein 1ß than patients with no systemic inflammation. Patients with ACLF with sepsis had raised (p < 0.001) levels of IL-1Ra, IL-18, and triggering receptor expressed on myeloid cells 1 (TREM1) compared to patients with ACLF-systemic inflammation. Five of the 19 (26.3%) patients with systemic inflammation developed sepsis within 48-72 hours with a rapid rise in plasma levels of IL-1Ra (1203-35,000 pg/ml), IL-18 (48-114 pg/ml), and TREM1 (1273-4865 pg/ml). Monocytes of patients with ACLF with systemic inflammation and sepsis showed reduced human leukocyte antigen-DR but increased programmed death ligand 1 (PD-L1) and T-cell immunoglobulin and mucin domain-containing protein 3 (TIM3) (p < 0.04) expression with increased ETosis by monocytes at baseline and until day 7. Conclusion: High and rising levels of plasma IL-1Ra, IL-18, TREM1 soluble factors, and increased suppressive monocytes (PDL1+ve , TIM3+ve ) at baseline can stratify patients with ACLF at high risk of developing sepsis within 48-72 hours of hospitalization.

Sustained expression of inflammatory monocytes and activated T cells in COVID-19 patients and recovered convalescent plasma donors.

INTRODUCTION: Intense monocyte activation and infiltration into the target tissues are the main mechanisms of lung injury in severe acute respiratory syndrome coronavirus 2 infection. A reduction in the degree and nature of such cellular responses is expected following recovery. We aimed to investigate the immune responses in moderate coronavirus disease 2019 (COVID-19) patients and recovered patients. METHODS: Moderate COVID-19 patients (n = 34) at Lok Nayak Hospital, New Delhi, and COVID-19 recovered patients (n = 15) from the mild disease who were considered for convalescent plasma (COPLA) donation at the Institute of Liver and Biliary Sciences, New Delhi and healthy individuals (n = 10), were recruited. We have assessed 21 plasma cytokines using cytokine bead array, performed proteomics on serum proteins, and analyzed immune cells using a detailed multicolor flow cytometry. RESULTS: A significant increase in inflammatory markers such as macrophage inflammatory protein (MIP)1-α, monocyte chemotactic protein-1, macrophage migration inhibitory factor, vascular endothelial growth factor-A, and Leptin was observed in the moderate patients. Nonsurvivors additionally showed increased interleukin (IL)-6 levels. Consistently, the proteomics analysis showed the signatures of cytokine production and interferon-γ response, and increased level of acute-phase protein SAA1 in the serum of COVID-19 patients. Despite the sustained expression of MIPs, the recovered COPLA donors showed a surge in MCSF and IL-18 levels. Both the groups had increased CCR2, CX3CR1 positive monocytes, low CD8+ T cells, A proliferation-inducing ligand, and B-cell activating factor receptor+ B cells compared with healthy subjects. CONCLUSIONS: Patients who have recovered and considered for COPLA donations still have compromised immunity with sustained expression of inflammatory monocytes and activated T cells.

Assessment of metabolic syndrome in HIV-infected individuals.

BACKGROUND: Metabolic syndrome (MS) is a cluster of risk factors for cardiovascular disease and Type 2 diabetes mellitus. OBJECTIVES: The aim is to assess the prevalence of MS in HIV patients receiving highly active antiretroviral therapy (HAART) and to compare it with treatment naïve HIV patients. METHODS: Cross-sectional study carried out in a teaching hospital in North India. A total of 116 HIV positive patients who were on HAART and those who were treatment naïve were included in the study. Adult Treatment Panel III (ATP III) and International Diabetes Foundation (IDF) definitions were used to define MS. Clinical and laboratory investigations were performed as per requirement and then analyzed using SPSS software. RESULTS: A high prevalence of MS was observed in HIV positive patients (ATP III - 19.8% and IDF - 25.9%). The prevalence of MS was higher in the anti-retroviral therapy (ART) group (ATP III - 33.3% and IDF - 36.4%) than ART-naïve group (ATP III - 2% and IDF - 12%). CONCLUSIONS: A sincere effort should always be made to detect MS in patients on HAART, especially in Indian subcontinent where there is a genetic predisposition to cardiovascular risk.