Therapeutic plasma exchange provides native liver survival benefit in children with acute liver failure: A propensity score-matched analysis.

OBJECTIVES: This study aimed to evaluate the safety and efficacy of therapeutic plasma exchange (TPE) in pediatric acute liver failure (PALF). METHODS: All children aged 2-18 years with PALF were included. The intervention cohort included a subset of PALF patients undergoing complete three sessions of TPE, whereas the matching controls were derived by propensity score matching from the patient cohort who did not receive any TPE. Propensity matching was performed based on the international normalized ratio (INR), grade of hepatic encephalopathy (HE), age, bilirubin, and ammonia levels. The primary outcome measure was native liver survival (NLS) in the two arms on day 28. RESULTS: Of the total cohort of 403 patients with PALF, 65 patients who received TPE and 65 propensity-matched controls were included in analysis. The 2 groups were well balanced with comparable baseline parameters. On day 4, patients in the TPE group had significantly lower INR (P = 0.001), lower bilirubin (P = 0.008), and higher mean arterial pressure (MAP) (P = 0.033) than controls. The NLS was 46.15% in the TPE arm and 26.15% in the control arm. The overall survival (OS) was 50.8% in the TPE arm and 35.4% in the control arm. Kaplan-Meier survival analysis showed a significantly higher NLS in patients receiving TPE than controls (P = 0.001). On subgroup analysis, NLS benefit was predominantly seen in hepatitis A-related and indeterminate PALF. CONCLUSION: TPE improved NLS and OS in a propensity-matched cohort of patients with PALF. Patients receiving TPE had lower INR and bilirubin levels and higher MAP on day 4.

Validation of dried blood spot for serological diagnosis of Hepatitis B and C: a multicentric study.

The present study aimed to determine diagnostic performance of dried blood spot (DBS) for the detection of Hepatitis B surface antigen (HBsAg) and Hepatitis C virus antibodies (anti-HCV) using CLIA at 3 different laboratories across India. DBS can serve as a simple and convenient alternative to plasma/serum for HBsAg detection. However for anti-HCV, site-specific validation of the assay is warranted.

A mitochondrial quality control mechanism reverses the phagosome maturation arrest caused by Mycobacterium tuberculosis.

Phagosome maturation arrest (PMA) imposed by Mycobacterium tuberculosis ( Mtb ) is a classic tool that helps Mtb evade macrophage anti-bacterial responses. The exclusion of RAB7, a small GTPase, from Mtb -phagosomes underscores PMA. Here we report an unexpected mechanism that triggers crosstalk between the mitochondrial quality control (MQC) and the phagosome maturation pathways that reverses the PMA. CRISPR-mediated p62/SQSTM1 depletion ( p62 KD ) blocks mitophagy flux without impacting mitochondrial quality. In p62 KD cells, Mtb growth and survival are diminished, mainly through witnessing an increasingly oxidative environment and increased lysosomal targeting. The lysosomal targeting of Mtb is facilitated by enhanced TOM20 + mitochondria-derived vesicles (MDVs) biogenesis, a key MQC mechanism. In p62 KD cells, TOM20 + -MDVs biogenesis is MIRO1/MIRO2-dependent and delivered to lysosomes for degradation in a RAB7-dependent manner. Upon infection in p62 KD cells, TOM20 + -MDVs get extensively targeted to Mtb -phagosomes, inadvertently facilitating RAB7 recruitment, PMA reversal and lysosomal targeting of Mtb . Triggering MQC collapse in p62 KD cells further diminishes Mtb survival signifying cooperation between redox- and lysosome-mediated mechanisms. The MQC-anti-bacterial pathway crosstalk could be exploited for host-directed anti-tuberculosis therapies.

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.

Performance evaluation of NeuMoDx 96 system for hepatitis B and C viral load.

BACKGROUND: Hepatitis B virus (HBV) and hepatitis C virus (HCV) viral load (VL) estimation is essential for the management of both HBV and HCV infections. Due to a longer turnaround time for VL estimation, many patients drop out from the cascade of care. To achieve the global goals of reducing morbidity and mortality due to HBV/HCV and moving towards their elimination by 2030, molecular diagnostic platforms with faster and random (i.e. single sample) access are needed. AIM: To evaluate the performance of the recently launched NeuMoDx 96 random access system with the conventional COBAS®AmpliPrep/COBAS TaqMan system for HBV and HCV VL estimation. METHODS: Archived once-thawed plasma samples were retrieved and tested on both platforms. Correlation between the assays was determined by linear regression and Bland-Altman analysis. The study included samples from 186 patients, 99 for HBV of which 49 were true infected HBV cases (hepatitis B surface antigen, anti-hepatitis B core antibody, and HBV DNA-positive) and 87 for HCV assay in which 39 were true positives for HCV infection (anti-HCV and HCV RNA-positive). RESULTS: The median VL detected by NeuMoDx for HBV was 2.9 (interquartile range [IQR]: 2.0-4.3) log10 IU/mL and by COBAS it was 3.70 (IQR: 2.28-4.56) log10 IU/mL, with excellent correlation (R2 = 0.98). In HCV, the median VL detected by NeuMoDx was 4.9 (IQR: 4.2-5.4) log10 IU/mL and by COBAS it was 5.10 (IQR: 4.07-5.80) log10 IU/mL with good correlation (R2 = 0.96). CONCLUSION: The overall concordance between both the systems was 100% for both HBV and HCV VL estimation. Moreover, no genotype-specific bias for HBV/HCV VL quantification was seen in both the systems. Our findings reveal that NeuMoDx HBV and HCV quantitative assays have shown overall good clinical performance and provide faster results with 100% sensitivity and specificity compared to the COBAS AmpliPrep/COBAS TaqMan system.

Large volume plasmapheresis using a single-use immunoadsorption column: A cost-effective approach for desensitization in ABO-incompatible liver transplant.

INTRODUCTION: Liver transplant is a life-saving treatment, but due to the limited availability of suitable liver donors, ABO-incompatible liver transplants (ABOi-LT) are conducted to increase the availability of liver donors. Perioperative desensitization for ABOi-LT is an established strategy to circumvent the risk of graft rejection. A single prolonged session can be performed to achieve the desired titers to avoid using multiple immunoadsorption (IA) columns or off-label reuse of single-use columns. This study retrospectively assessed the effectiveness of a single prolonged plasmapheresis session using IA as a desensitization strategy in live donor liver transplant (LDLT). MATERIALS AND METHODS: This retrospective observational study conducted at a center for liver diseases in North India on six ABOi-LDLT patients who underwent single prolonged IA sessions in the perioperative period from January 2018 to June 2021. RESULTS: Median baseline titer in patients was 320 (64, 1024). The median plasma volume adsorbed was 7.5 volumes (4, 8) per procedure, with a mean procedure time of 600 min (310-753). The reduction in titer ranged from 4 log to 7 log reduction per procedure. Two patients developed transient hypotension during the procedure, which was managed successfully. The median duration of pre-transplant hospital stay was 1.5 days (1, 3). CONCLUSION: Desensitization therapy helps overcome the ABO barrier and decreases the waiting period before a transplant when ABO identical donors are unavailable. A single prolonged IA session reduces the cost of additional IA columns and hospital stay, thus making it a cost-effective approach to desensitization.

Delayed adverse reactions in whole blood donors: Importance of active surveillance in identifying the missing gaps in the donor safety.

Background & objectives: The information available regarding delayed adverse donor reactions (D-ADRs) is limited. Proactive follow up of donors for delayed reactions is not done routinely. This study was undertaken to analyze frequency and type of D-ADRs in whole blood donors as also the contributory factors. Methods: In this prospective observational study, all eligible whole blood donors were contacted telephonically twice (24 h and 2 wks after donation) and asked about general health and ADR specific questions. The International Society of Blood Transfusion standard guidelines were used to categorize ADRs. Results: The ADR data of 3514 donors were analyzed in the study. D-ADRs were more common as compared to immediate delayed adverse donor reactions (I-ADRs) (13.7 vs. 2.9%, P<0.001). The most common D-ADRs were bruises (4.98%), fatigue or generalized weakness (4.24%) and sore arms (2.25%). D-ADRs were more common in first time donors as compared to the repeat blood donors (16.1 vs. 12.5%, P=0.002). Females were more prone to D-ADRs (17 vs. 13.6%). Localized D-ADRs were more frequent as compared to systemic D-ADRs (P<0.001). Repeat donors had a lower incidence of systemic D-ADRs (4.11% vs. 7.37%, P<0.001). Interpretation & conclusions: D-ADRs were more common than I-ADRs with a different profile. First time, female and young donors were more prone to D-ADRs. These categories need special care at the time of blood donation. Active follow up of blood donors should be done from time to time to strengthen donor safety.

Immune predictors of hepatitis B surface antigen seroconversion in patients with hepatitis B reactivation.

BACKGROUND: Hepatitis B surface antigen (HBsAg) seroconversion is sometimes observed in hepatitis B reactivation (rHBV), probably due to immune resetting and differentiation. AIMS: To investigate sequential immune differentiation and abrogation of tolerance in patients with rHBV who achieved HBsAg seroconversion. METHODS: We included 19 patients with chronic hepatitis B (CHBV; HBV DNA log103-8 ), 67 with rHBV (raised ALT [>5XULN], HBV DNAlog104-8 ) and 10 healthy controls. Immune differentiation, tolerance and functional status of CD4, CD8, T regulatory cells (Tregs), B cells and follicular T helper (Tfh) cells were assessed at baseline and 24 weeks. RESULTS: At 24 weeks, 81% rHBV (n = 67) lost HBV DNA and HBeAg (41%), and 12 (19%) lost HBsAg and made anti-HBs titers >10 IU/ml. rHBV patients had higher Th1/17, TEM , Tfh, Tfh1/17, plasma and ATM B cells, and lower Tregs, Th2, Th17 and TEMRA expression. rHBV showed lower PD1, TIM3, LAG3, SLAM and TOX compared to CHBV. There was a significant increase in CD8, CD8EM, Tfh, Tfh1/17 and plasma B cells in seroconverters than non-seroconverters. At 24 weeks, we also observed increased plasma B cell frequency in seroconverters. While non-seroconverters showed higher expression of PD1, TIM3, LAG3, SLAM and TOX on CD4/CD8 T cells, blockade of PD1, TIM3, LAG3 and CTLA4 significantly enhanced IFN-γ, TNF-α, IL-4 and IL-21 expression on CD4/CD8 and Tfh cells in non-seroconverters. CONCLUSIONS: Non-seroconverters have increased inhibitory markers on CD4/CD8 T cells. There is a critical play of CD8, Tfh and B cells and subsets in seroclearance, along with checkpoint molecules as a potential therapy for non-seroconverters in HBV infection.

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.

An Exploratory Study of the Differences in Attitudes and Motives Regarding COVID-19 Plasma Donation.

Background: Understanding the attitude and motives and differences between voluntary and replacement blood donation is the key to the sustainable availability of this precious resource. This study aimed to assess the attitude and motives for convalescent plasma (CP) donation in the recovered COVID-19 plasma donors and further understand the differences between voluntary and replacement donation. Materials and Methods: This prospective cross-sectional survey-based study was conducted among500 COVID-19 recovered blood donors who visited for CP donation at a tertiary care super-speciality centre in northern India. Data were collected using a structured questionnaire based on donor attitude, motives, and belief, which was validated by the experts of Psychiatry, Transfusion Medicine, and Epidemiology and was administered by the online medium. Results: The study's findings depicted that voluntary plasma donors were previously regular blood donors (36.8%) compared to replacement plasma donors (26.4%). Almost all voluntary donors (99.5%) showed altruistic reasons to donate plasma and expressed that donating plasma is a good way to save a life, and it was more than for replacement plasma donors (p=0.004). The motives of most voluntary plasma donors were to contribute to society, and they believed that donating plasma is a good way, while it was not the case for most replacement plasma donors (p=0.02). Voluntary donors were more eagerly willing to donate plasma to help COVID sufferers (40.9%) when compared to replacement donors (33.2%) (p=0.037). Conclusion: Most voluntary plasma donors were regular whole blood donors and were keen to contribute to society. Convalescent plasma donation during this time of grief and loss was considered a moral responsibility by voluntary donors. The impact of media was more highly perceived in voluntary plasma donors when compared to replacement donors.

Rotational thromboelastometry-guided blood component use in cirrhotic children undergoing invasive procedures: Randomized controlled trial.

BACKGROUND & AIMS: This randomized controlled trial (RCT) was conducted with the aim to evaluate the efficacy and safety of using ROTEM-based transfusion strategy in cirrhotic children undergoing invasive procedures. METHODS: This was an open-label, RCT which included (i) children under 18 years of age with liver cirrhosis; (ii) INR between 1.5 and 2.5; and/or (iii) platelet count between 20 × 109 /L and 50 × 109 /L (for procedures other than liver biopsy) and between 40 × 109 /L and 60 × 109 /L (for liver biopsy); and (iv) listed for invasive procedures. Stratified randomization was done for children undergoing liver biopsies. Patients randomized to the ROTEM and conventional groups received blood component transfusion using predefined criteria. RESULTS: A total of 423 invasive procedures were screened for inclusion of which 60 were randomized (30 in each group with comparable baseline parameters). The volume of total blood components, fresh frozen plasma (FFP) and platelets transfused was significantly lower in ROTEM as compared to conventional group. Only 46.7% of children in ROTEM group received a blood component compared to 100% in conventional group (p < .001). The requirement of FFP (ROTEM: 43.3%, Conventional: 83.3%, p = .001) was significantly lower in the patients receiving ROTEM-guided transfusions. There was no difference in procedure-related bleed and transfusion-related complications between the two groups. ROTEM was cost-effective (p = .002) despite the additional cost of the test. CONCLUSION: ROTEM-based transfusion strategies result in lower blood component transfusion in cirrhotic children undergoing invasive procedures without an increase in risk of procedure-related bleed. ROTEM-guided transfusion strategy is cost-effective.

Bioenergetic Failure Drives Functional Exhaustion of Monocytes in Acute-on-Chronic Liver Failure.

Objective: The monocyte-macrophage system is central to the host's innate immune defense and in resolving injury. It is reported to be dysfunctional in acute-on-chronic liver failure (ACLF). The disease-associated alterations in ACLF monocytes are not fully understood. We investigated the mechanism of monocytes' functional exhaustion and the role of umbilical cord mesenchymal stem cells (ucMSCs) in re-energizing monocytes in ACLF. Design: Monocytes were isolated from the peripheral blood of ACLF patients (n = 34) and matched healthy controls (n = 7) and patients with compensated cirrhosis (n = 7); phagocytic function, oxidative burst, and bioenergetics were analyzed. In the ACLF mouse model, ucMSCs were infused intravenously, and animals were sacrificed at 24 h and day 11 to assess changes in monocyte function, liver injury, and regeneration. Results: Patients with ACLF (alcohol 64%) compared with healthy controls and those with compensated cirrhosis had an increased number of peripheral blood monocytes (p < 0.0001) which displayed significant defects in phagocytic (p < 0.0001) and oxidative burst capacity (p < 0.0001). ACLF patients also showed a significant increase in the number of liver macrophages as compared with healthy controls (p < 0.001). Bioenergetic analysis showed markedly reduced oxidative phosphorylation (p < 0.0001) and glycolysis (p < 0.001) in ACLF monocytes. Patients with monocytes having maximum mitochondrial respiration of <37.9 pmol/min [AUC = 0.822, hazard ratio (HR) = 4.5] and baseline glycolysis of ≤42.7 mpH/min (AUC = 0.901, HR = 9.1) showed increased 28-day mortality (p < 0.001). Co-culturing ACLF monocytes with ucMSC showed improved mitochondrial respiration (p < 0.01) and phagocytosis (p < 0.0001). Furthermore, ucMSC therapy increased monocyte energy (p < 0.01) and phagocytosis (p < 0.001), reduced hepatic injury, and enhanced hepatocyte regeneration in ACLF animals. Conclusion: Bioenergetic failure drives the functional exhaustion of monocytes in ACLF. ucMSCs resuscitate monocyte energy and prevent its exhaustion. Restoring monocyte function can ameliorate hepatic injury and promote liver regeneration in the animal model of ACLF.

Secretome of senescent hepatoma cells modulate immune cell fate by macrophage polarization and neutrophil extracellular traps formation.

Presence of dysfunctional senescent hepatocytes is a hallmark feature of liver cirrhosis which finally culminates in liver cancer. We now report the presence of senescent hepatocytes (p21 and p53 positive) in the vicinity of infiltrated immune cells in hepatocellular carcinoma tissue specimens by immunohistochemistry. Hence, we evaluated in vitro, the relevance of senescent hepatoma cells in altering the fate of monocytes and neutrophils by assaying for macrophage polarization and extracellular trap (NETs) formation, respectively. Premature senescence was induced in hepatoma cells (HepG2 and Huh7 cells) by treating cells with doxorubicin. Senescent hepatoma cells showed strong inflammatory phenotype with induced expression of cytokines (IL1ß, IL6, IL8 and IL13) as evaluated by flow cytometry. The senescent secretome from hepatoma cells when incubated with healthy monocytes caused it to differentiate predominantly towards M2 fate (CD80low CD86low CD163high CD206high) when analysed by flow cytometry. This was corroborated by the finding in clinical samples where human hepatocellular carcinoma harbouring senescent hepatocytes showed presence of M2 macrophages, while M1 macrophages were predominant in non-tumorous region. Additionally, the senescent secretome from Huh7 cells enhanced the NETs formation, while HepG2 secretome had an inhibitory effect. In conclusion, the "pro-inflammatory" senescent secretome drives non-inflammatory type M2 macrophage polarization and modulated neutrophil traps which in turn can influence the tumor microenvironment.

Efficacy of convalescent plasma therapy in the patient with COVID-19: a randomised control trial (COPLA-II trial).

IMPORTANCE: No proven treatment is available for severely ill COVID-19. Therapeutic use of COVID-19 convalescent plasma (COPLA) is under investigation. OBJECTIVE: To compare the efficacy of COPLA with standard medical therapy (SMT) alone in severe COVID-19 patients. DESIGN, SETTING AND PARTICIPANTS: A 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. INTERVENTION: One group received COPLA with SMT (n=200), and another group received SMT only (n=200). MAIN OUTCOME MEASURES: Primary outcome was time to clinical improvement measured by a two-point reduction in the ordinal scale. Secondary outcomes included duration of O2 therapy, the proportion of patients on mechanical ventilation at day-7, mortality, SARS-CoV-2 antibody levels, cytokine levels and incidence of adverse events. RESULTS: The 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 O2 therapy was 8 days (IQR=6-12) in COPLA and 10 days (IQR=6-12) in SMT group (p=0.64). The PaO2/FiO2 ratio 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 RELEVANCE: Convalescent 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 NUMBER: NCT04425915.

Standard-Volume Plasma Exchange Improves Outcomes in Patients With Acute Liver Failure: A Randomized Controlled Trial.

BACKGROUND: High volume plasma-exchange (HVPE) improves survival in patients with acute liver failure (ALF), but apprehension regarding volume overload and worsening of cerebral edema remain. METHODS: In an open-label randomized controlled trial, 40 consecutive patients of ALF were randomized 1:1 to either standard medical treatment (SMT) or SMT with standard-volume plasma-exchange (SVPE). SVPE was performed using centrifugal apheresis [target volume of 1.5 to 2.0 plasma volumes per session] until desired response was achieved. Cerebral edema was assessed by brain imaging. Results were analyzed in an intention-to-treat analysis. Primary outcome was 21-day transplant-free survival. The levels of cytokines, damage-associated molecular patterns (DAMPs) and endotoxins were analyzed at baseline and day 5. RESULTS: ALF patients [aged 31.5 ± 12.2 years, 60% male, 78% viral, 83% hyperacute, 70% with SIRS were included. At day 5, SVPE [mean sessions 2.15 ± 1.42, median plasma volume replaced 5.049 L] compared to SMT alone, resulted in higher lactate clearance (p = .02), amelioration of SIRS (84% vs. 26%; P = .02), reduction in ammonia levels [(221.5 ± 96.9) vs.(439 ± 385.6) µg/dl, P = .02) and SOFA scores [9.9(±3.3) vs. 14.6(±4.8); P = .001]. There were no treatment related deaths. SVPE was associated with a higher 21-day transplant free-survival [75% vs. 45%; P = .04, HR 0.30, 95%CI 0.01-0.88]. A significant decrease in levels of pro-inflammatory cytokines and an increase in anti-inflammatory cytokines along with a decrease in endotoxin and DAMPs was seen with SVPE. CONCLUSION: In ALF patients with cerebral edema, SVPE is safe and effective and improves survival possibly by a reduction in cytokine storm and ammonia. CLINICALTRIAL: gov (identifier: NCT02718079).

SARS-Coronavirus-2 seroprevalence in asymptomatic healthy blood donors: Indicator of community spread.

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.