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The present study reports the levels of maternal serum calcium and magnesium from early pregnancy until delivery, along with cord levels, in women who developed preeclampsia (PE) and compares them with those without PE. A total of 324 pregnant women (216 non-PE and 108 PE women) were included in this retrospective case-control study of prospectively collected data nested in an observational cohort study. Maternal blood was collected at 4 time points during pregnancy (V1 = 11-14 weeks, V2 = 18-22 weeks, V3 = 26-28 weeks, and V4 = at delivery) and umbilical cord blood at delivery. Independent t tests were used to compare calcium, magnesium, and their ratio between two groups, and their associations with PE were studied using regression models. Calcium levels were similar between groups at all time points. Magnesium levels were lower (p = 0.021) at V2 in PE group as compared with non-PE group. Maternal calcium and magnesium levels were negatively associated, with blood pressure in early pregnancy. In fully adjusted logistic regression analysis, lower magnesium levels were associated with an increased risk of PE at V2 (OR 0.25 [95% CI 0.07, 0.94] p = 0.04). Lower magnesium in mid-pregnancy was associated with higher risk of PE. These changes were observed before the diagnosis of PE, thereby suggesting that they may have a role in the etiology of PE.

Background Due to waning immunity following primary immunization with Covid-19 vaccines, booster doses may be required. The present study assessed a heterologous booster of SII-NVX-CoV2373 (spike protein vaccine) in adults primed with viral vector and inactivated vaccines. Methods In this Phase 3, observer-blind, randomized, active controlled study, a total of 372 adults primed with ChAdOx1 nCoV-19 (n = 186) or BBV152 (n = 186) at least six months ago, were randomized to receive a booster of SII-NVX-CoV2373 or control vaccine. The control group received homologous booster of ChAdOx1 nCoV-19 or BBV152 depending upon the prime cohort. Anti-S IgG and neutralizing antibodies were assessed at baseline (day 1), day 29, day 91 and day 181 for immunogenicity assessments. Solicited reactions were collected for one week after vaccination. Unsolicited adverse events (AEs) were collected for 28 days while serious adverse events (SAE) and adverse events of special interest (AESI) were reported throughout the six-month study duration. (Identifier: CTRI/2022/04/042017) Results In both the ChAdOx1 nCoV-19 primed group and BBV152 primed group, 186 participants each received the study vaccines. In the ChAdOx1 nCoV-19 Prime cohort, at 28 days after the booster dose, there was a 3.9- to 5.1-fold-rise and 1.9- to 2.8-fold-rise in anti-S IgG and neutralizing antibody titres from the baseline in the SII-NVX-CoV2373 group and the ChAdOx1 nCoV-19 group, respectively. The same responses for the BBV152 prime cohort was 7.4- to 10.4-fold-rise and 1.5- to 2.5-fold-rise in the SII-NVX-CoV2373 group and the BBV152 group, respectively. There was 86.96% (95% CI 78.32, 93.07) to 94.57% (95% CI 87.77, 98.21) and 37.63% (95% CI 27.79, 48.28) to 79.57% (95% CI 69.95, 87.23) anti-S IgG and neutralizing antibody seroresponse (2-fold-rise from baseline) in the SII-NVX-CoV2373 group and ChAdOx1 nCoV-19 group, respectively. The same was 94.51% (95% CI 87.64, 98.19) to 98.90% (95% CI 94.03, 99.97) and 20.43% (95% CI 12.77, 30.05) to 74.19% (95% CI 64.08, 82.71) in the SII-NVX-CoV2373 group and BBV152 group, respectively. No SAE or AESI was caused by the study vaccines. Conclusion SII-NVX-CoV2373 showed a numerically higher boosting effect than homologous boosters in adults primed with ChAdOx1 nCoV-19 and BBV152. The vaccine was also safe and well tolerated.

Studies from high-income countries report associations of preeclampsia (PE) with reduced cognitive function and adverse behavioural outcomes in children. We examined these associations in Indian children aged 5-7 years. Children of mothers with PE (n=74) and without PE (non-PE; n=234) were recruited at delivery at Bharati Hospital, Pune, India. The cognitive performance was assessed using 3 core tests from the Kaufman Assessment Battery and additional tests including Verbal fluency, Kohs block design, and Coding A (from Wechsler Intelligence Scale for Children). The parent-reported Strengths and Difficulties Questionnaire (SDQ) was used to assess children’s behavioral characteristics. Scores were compared between children from PE and non-PE groups, and associations analyzed further using regression models, adjusted for potential confounders. After adjusting for age, sex, socio-economic status and maternal education, children of PE mothers had lower Kohs block design scores (adjusted odds ratio per score category 0.57, [95% CI 0.34-0.96] p=0.034; 0.62 [95%CI (0.36, 1.07), p=0.09 on further adjustment for birth weight and gestation) compared to children of mothers without PE. In the SDQ, there was a lower prevalence of abnormal ‘conduct problem’ scores in PE group than non-PE group (OR=0.33, 95% CI 0.13-0.83, p=0.018, in the fully adjusted model); there were no differences for other behavioral domains. This preliminary study in Indian children suggests that fetal exposure to maternal PE may have an adverse impact on visuo-spatial performance but does not adversely affect behavior. Further studies with larger sample sizes are essential to understand effects of maternal PE on cognitive/behavioral outcomes in children.

The human rotavirus vaccine (HRV; Rotarix, GSK) is available as liquid (Liq) and lyophilized (Lyo) formulations, but only Lyo HRV is licensed in India. In this phase III, randomized, open-label trial (NCT02141204), healthy Indian infants aged 6-10 weeks received 2 doses (1 month apart) of either Liq HRV or Lyo HRV. Non-inferiority of Liq HRV compared to Lyo HRV was assessed in terms of geometric mean concentrations (GMCs) of anti-RV immunoglobulin A (IgA), 1-month post-second dose (primary objective). Reactogenicity/safety were also evaluated. Seroconversion was defined as anti-RV IgA antibody concentration ≥20 units [U]/mL in initially seronegative infants (anti-RV IgA antibody concentration

Purpose COVID-19 pandemic remains a serious public health threat worldwide. In view of the limited data on the risk of perinatal transmission of SARS-CoV-2 and transfer of maternal anti-SARS-CoV-2 antibodies, the present study was undertaken. Methods A prospective study including 57 pregnant women with a positive SARS-CoV-2 RNA test (SARS-CoV-2-RNA+) and 59 neonates born to them was conducted at Pune, India. 39 viral RNA negative (SARS-CoV-2-RNA-negative) pregnant women and their 39 neonates were included as controls. Neonatal nasal swab/cord blood samples were subjected to SARS-CoV-2 RNA detection by RT-PCR for investigation of perinatal transmission. Transfer of maternal antibodies was studied using ELISA and PRNT. Results 10/57 SARS-CoV-2-RNA+ mothers were symptomatic. The duration between COVID-19 diagnosis and delivery was ≤ 7 days for 82.4%. Perinatal transmission as evidenced by viral RNA in the neonatal nasal swab/cord blood (CB) was 3.6%. IgG-anti-SARS-CoV-2 positivity was 21.6%. Of the 39 neonates born to SARS-CoV-2-RNA-negative mothers, 20 (51%) and none, respectively, were positive for IgG-anti-SARS-CoV-2 and viral RNA. Preterm deliveries were higher in SARS-CoV-2-RNA+ (18.6%) than SARS-CoV-2 RNA-negative (0/39) mothers (p

Patients with SARS-CoV-2 infection have a wide spectrum of clinical presentations, from asymptomatic infection, to mild illness, to severe disease with recovery or fatal outcome. Immune correlates of protection are not yet clear. To understand the association between presence and titers of neutralizing antibodies (NAb) with recovery, we screened 82 COVID-19 patients classified in mild (n = 56) and severe (n = 26) disease groups on different days post onset of disease and 27 viral RNA–positive asymptomatic contacts examined within 1 week of the identification of index cases. Of 26 patients with severe disease, six died and 20 recovered. Anti-SARS-CoV-2 NAb levels in plasma and serum were measured using a plaque reduction neutralization test with live virus. The proportion of asymptomatic and symptomatic infections was 1:7.8 in males and 1:1 in females, with males predominating the severe disease group (21/26, 80.7%). At the time of presentation, NAb positivity and titers were comparable among groups with asymptomatic and mild infections. Notably, patients with severe disease exhibited higher NAb seropositivity and titers (25 of 26, 96.2%; 866 ± 188) than those in the mild category (39 of 56, 69.6%; 199 ± 50, P < 0.0001) and asymptomatic individuals (21 of 27, 77.8%; 124 ± 28, P = 0.0002). Within first 2 weeks of onset, NAb titers were significantly higher among patients with severe disease than those with mild presentation. Our data suggest that irrespective of fatal outcome, progression to disease severity was associated with induction of early and high levels of NAb. In our patient series, clinical disease, severity and fatality were predominantly seen in males. The role of NAbs in immunopathogenesis or protection needs to be defined.

In view of the rapidly progressing COVID-19 pandemic, our aim was to isolate and characterize SARS-CoV-2 from Indian patients. SARS-CoV-2 was isolated from nasopharyngeal swabs collected from the two members of a family without any history of (H/O) travel abroad. Both the virus isolates (8003 and 8004) showed CPE on day 3 post-inoculation, viral antigens by immunofluorescence assay and produced distinct, clear and uniform plaques. Infectious virus titers were 5 × 106 and 4 × 106 Pfu/ml by plaque assay and 107.5 and 107 by CPE-based TCID50/ml, respectively. Phylogenetic analysis grouped our isolates with the Italian strains. On comparison with Wuhan strain, 3 unique mutations were identified in nsp3 (A1812D), exonuclease (P1821S) of Orf1ab and spike protein (Q677H) regions, respectively. Both the viruses grouped with Italian strains of SARS-CoV-2 suggesting possible source being the virus imported from Italy. These fully characterized virus isolates will be useful in developing neutralization/virological assays for the evaluation of vaccines/antivirals.

Background & objectives: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) continues to be a devastating pandemic. This study was aimed at performance assessment of SARS-CoV-2 IgM and IgG ELISAs, and investigation of their utility for patient diagnosis and sero-epidemiologic investigations. Methods: Serum/plasma samples from COVID-19 patients or asymptomatic contacts (n=180) and healthy donors (n=90) were tested in parallel using two commercial IgM ELISAs (Erbalisa and Inbios), and four IgG ELISAs (Kavach, Euroimmun, Erbalisa and Inbios) along with an indigenous β-propiolactone inactivated virus-based ELISA (IRSHA-IgG-ELISA). Plaque reduction neutralization test (PRNT) was used as reference test. Results: Among 180 COVID-19 patients, 125 tested positive by PRNT. Inbios-IgM-ELISA showed sensitivity (Se)/specificity (Sp)/positive predictive value (PPV)/negative predictive value (NPV) of 93.6/97.8/98.4/94.4 per cent in relation to PRNT, and performed better than Erbalisa-IgM-ELISA (Se: 48%, Sp: 95.6%, PPV: 95.2%, NPV: 65.2%). During the first week of disease, only 47.4 per cent of the COVID-19 patients tested IgM positive by Inbios-IgM-ELISA, detection improving at two weeks and beyond (~86-100%). Among IgG tests, Inbios-IgG-ELISA ranked first in terms of sensitivity (83.2%), followed by IRSHA (64.8%), Euroimmun (64%), Erbalisa (57.6%) and Kavach (56%) tests. For all IgG tests, sensitivity improved during the third (73.9-95.7%) and fourth week (100%) of illness. The specificity (96.7-100%) and PPV (96.2-100%) of all IgG tests were high; NPV ranged between 71.9 and 87.1 per cent with Inbios-IgG-ELISA scoring highest. Interpretation & conclusions: Our results show that IgM detection by the current, most sensitive ELISAs cannot replace molecular diagnosis, but may aid as a supplement test. The available IgG tests are suitable for serosurveys for the assessment of previous virus exposure.

Objective To assess the epidemiological and clinical characteristics of pediatric inpatients with COVID-19, early in the pandemic. Methods Clinical and laboratory profile and outcomes were studied for children (aged 1 month — 18 years) presenting between 1 April, 2020 and 20 May, 2020 with positive nasopharyngeal swab for SARS-CoV-2 by RT-PCR. Results 50 children (56% male) with median (IQR) age of 6 (2–12) years were included. Majority (56%) were from families belonging to Kuppuswamy upper lower socioeconomic class. 45 (90%) had positive household contact, and 33 (66%) had overcrowding at home. 29 (58%) children were asymptomatic while 20 (40%) had mild symptoms. Fever, cough, and sore throat were the most common symptoms. High C-reactive protein levels were seen in 15 (30%) children. There was no mortality. Conclusion The disease burden appears high in lower socio-economic group with majority having a positive household contact. Milder disease pattern in the pediatric age group is reiterated.

Background: Many risk factors contribute to high morbidity and mortality due to childhood pneumonia. Mostly the risk factors are modifiable and related to behavior. Imparting knowledge to mothers about risk factors, early recognition of danger signs and importance of timely seeking health care is an accepted strategy for control. Aims & Objectives: To assess improvement in knowledge and perceptions about childhood pneumonia, risk factors and hand washing skills among mothers after sequential use of different media. Materials & Methods: This community based, pre and post assessment study was conducted in eight randomly clusters from two districts. Specially field supervisors assessed mothers for their ‘knowledge’, ‘perceptions’ and ‘skills’ about nutrition including breast feeding and malnutrition, indoor pollution, pneumonia and hand washing. Knowledge was assessed pertaining to all four aspects, perception was assessed for first three and skills were assessed only for hand washing. Three rounds of BCC using pictorial booklet, audio-visual film and flash cards consequently were completed, spread over about one year. Marks pertaining knowledge, perceptions about risk factors of childhood pneumonia and hand washing skills etc. were separately measured. Results: A total of 1,321 mothers participated. The mean pre-test marks were 22.31 out of 38 marks which significantly improved and retained to 35.24 after undergoing three BCC rounds. Highly significant improvements, 2.27 times in hand washing skills to 1.15 times for knowledge about indoor air pollution was observed. Conclusions: Consecutive use of different media at appropriate interval spread over a long period certainly yields desired results at diverse places.

Improving health education of the mother by providing community-based interventions is known to help control pneumonia.To determine the effect of behavior change communication (BCC) activities for mothers in reducing the incidence of childhood pneumonia.Open-label cluster randomized controlled trial.Urban slums and villages in two districs of Maharashtra.Under-five children and their mothers from households in the randomly selected 16 clusters out of total 45 clusters, stratified into Pune and Sangli districts and further into rural and urban areas before randomization.Three forms of BCC activities were imparted, viz., interactive sessions of education using pictorial mothers' booklet, screening of a audio-visual film, and virtual hand wash demonstration and use of flashcard. Routine care under the National health program was provided by the Accredited Social Health Activists (ASHA) workers in both the arms.The primary outcome was pneumonia as per the IMNCI criteria assessed during fortnightly visits of the ASHA/anganwadi workers to the houses of under-five children, who received at least one follow-up visit in a period of one year.The incidence of pneumonia in 1993 and 1987 under-five children in the intervention and control arm was 0.80 and 0.48 episodes per child per year, respectively (P=0.03).BCC for mothers is not sufficient to reduce the incidence of childhood pneumonia.

Acute respiratory infections (ARIs) continue to be the most important cause of morbidity and mortality among under-five children. Some demographic and environmental factors are associated with ARIs among under-five children. This study was conducted with the objective to estimate the prevalence of ARIs among under-five children in the rural areas and densely populated urban slum areas in Maharashtra, India and to assess the association of the selected sociodemographic and household environmental factors with ARI. This study was conducted in 16 selected clusters from the rural areas and densely populated urban slum areas of the two districts in Maharashtra, India. Structured and validated proforma was used for collecting the data on the sociodemographic and household environmental risk factors. A total of 3,671 under-five children were surveyed. The prevalence of ARIs for the preceding month was 50.4%. It was higher among the children living in the rural areas (54.2%) compared to the children living in the urban areas (46.7%) (p = 0.01). The prevalence of ARIs was reported to be 51.4 and 49.4% in boys and girls, respectively. In the multivariate analysis, the researchers found that living in rural areas (p = 0.01) and parental smoking (p = 0.04) were significantly associated with the ARIs. An intervention such as reducing parental smoking habits at the household level may reduce ARIs.

Background: In low- and middle-income country (LMIC) healthcare facilities, gaps in infection prevention and control (IPC) practices increase risk of healthcare-associated infections (HAIs) and mortality among hospitalized neonates. Method: In this quasi-experimental study, we implemented the Comprehensive Unit-based Safety Program (CUSP) to improve adherence to evidence-based IPC practices in neonatal intensive care units (NICUs) in 4 tertiary-care facilities in Pune, India. CUSP is a validated strategy to empower staff to improve unit-level patient safety. Baseline safety culture was measured using the Hospital Survey on Patient Safety Culture (HSOPS). Baseline IPC assessments using the Infection Control Assessment Tool (ICAT) were completed to describe existing IPC practices to identify focus areas, the first of which was hand hygiene (HH). Sites received training in CUSP methodology and formed multidisciplinary CUSP teams, which met monthly and were supported by monthly coaching calls. Staff safety assessments (SSAs) guided selection of multimodal interventions. HH compliance was measured by direct observation using trained external observers. The primary outcome was HH compliance, evaluated monthly during the implementation and maintenance phases. Secondary outcomes included CUSP meeting frequency and HH compliance by healthcare worker (HCW) role. Result: In March 2018, 144 HCWs and administrators participated in CUSP training. Site meetings occurred monthly. During the implementation phase (June 2018–January 2019), HH monitoring commenced, sites formed their teams, completed the SSA, and selected interventions to improve HH based on the WHO’s IPC multimodal improvement strategy: (1) system change; (2) training and education; (3) monitoring and feedback; (4) reminders and communication; and (5) a culture of safety (Fig. 1). During the maintenance phase (February–September 2019), HH was monitored monthly and sites adapted interventions as needed. HH compliance improved from 58% to 70% at participant sites from implementation to maintenance phases (Fig. 2), with an odds ratio (OR) of 1.66 (95% CI, 1.50–1.84; P < .001). HH compliance improved across all HCW roles: (1) physician compliance improved from 55% to 67% (OR, 1.69; 95% CI, 1.42–2.01; P < .001); (2) nurse compliance from 61% to 73% (OR, 1.68; 95% CI, 1.46–1.93; P < .001); and (3) other HCW compliance from 52% to 62% (OR, 1.48; 95% CI, 1.10–1.99; P = .010). Conclusion: CUSP was successfully adapted by 4 diverse tertiary-care NICUs in Pune, India, and it resulted in increased HH compliance at all sites. This multimodal strategy is a promising framework for LMIC healthcare facilities to sustainably address IPC gaps and reduce HAI and mortality in neonates.Funding: NoneDisclosures: Aaron Milstone, Johns Hopkins University, BD (consulting)

Background Preeclampsia is a major cause of maternal, fetal and neonatal morbidity and mortality, particularly in developing countries. Considering the burden of preeclampsia and its associated complications, it is important to understand the underlying risk factors and mechanisms involved in its etiology. There is considerable interest in the potential for dietary long chain polyunsaturated fatty acids (LCPUFA) as a therapeutic intervention to prevent preeclampsia, as they are involved in angiogenesis, oxidative stress, and inflammatory pathways. Methods The REVAMP study (Research Exploring Various Aspects and Mechanisms in Preeclampsia) follows a cohort of pregnant women from early pregnancy until delivery to examine longitudinally the associations of maternal LCPUFA with clinical outcome in preeclampsia. A multisite centre for advanced research was established and pregnant women coming to Bharati hospital and Gupte hospital, Pune, India for their first antenatal visit are recruited and followed up at 11–14 weeks, 18–22 weeks, 26–28 weeks, and at delivery. Their personal, obstetric, clinical, and family history are recorded. Anthropometric measures (height, weight), food frequency questionnaire (FFQ), physical activity, socioeconomic status, fetal ultrasonography, and color Doppler measures are recorded at different time points across gestation. Maternal blood at all time points, cord blood, and placenta at delivery are collected, processed and stored at − 80 °C. The children’s anthropometry is assessed serially up to the age of 2 years, when their neurodevelopmental scores will be assessed. Discussion This study will help in early identification of pregnant women who are at risk of developing preeclampsia. The prospective design of the study for the first time will establish the role of LCPUFA in understanding the underlying biochemical and molecular mechanisms involved in preeclampsia and their association with developmental programming in children.

Respiratory syncytial virus (RSV) causes significant infant mortality worldwide and a vaccine may be available soon. This study determined age-stratified anti-RSV antibody positivity (enzyme-linked immunosorbent assay [ELISA]) at Pune, India (cord blood-85 years). Antibody positivity declined from 100% at birth to 71.3% (3 months), and 0.7% (6 months). A significant rise was noted at 15 months (16%), 16 to 24 months (64.5%) and 4 years (95.2%) with concomitant IgM-anti-RSV positivity indicative of recent infection. Antibody decline was higher in infants born preterm than full-term. Across subsequent age groups including the elderly, antibody positivity was similar and comparable, suggestive of repeated exposure to the virus. Early protection/vaccination is essential for the infant population.

A lyophilized bovine-human rotavirus reassortant pentavalent vaccine (BRV-PV, Rotasiil®) was licensed in 2016. A liquid formulation of this vaccine (LBRV-PV, Rotasiil - Liquid) was subsequently developed and was tested for non-inferiority to Rotasiil® and for lot-to-lot consistency.This Phase II/III, open label, randomized study was conducted at seven sites across India from November 2017 to June 2018. Participants were randomized into four arms; Lots A, B, and C of LBRV-PV and Rotasiil® in 1:1:1:1 ratio. Three doses of study vaccines were given at 6, 10, and 14 weeks of age. Blood samples were collected four weeks after the third dose to assess rotavirus IgA antibody levels. Non-inferiority of LBRV-PV to Rotasiil was proven if the lower limit two-sided 95% confidence interval (CI) of geometric mean concentration (GMC) ratio was at least 0.5. Lot-to-lot consistency was proven if 95% CI of the GMC ratios of three lots were between 0.5 and 2. Solicited reactions were collected by using diary cards.Of the 1500 randomized infants, 1436 infants completed the study. The IgA GMC ratio of LBRV-PV to Rotasiil® was 1.19 (95% CI 0.96, 1.48). The corresponding IgA seropositivity rates were 60.41% (57.41, 63.35) and 52.75% (47.48, 57.97). The IgA GMC ratios among the three LBRV-PV lots were: Lot A versus Lot B: 1.34 (1.03, 1.75); Lot A versus Lot C: 1.22 (0.93, 1.60); and Lot B versus Lot C: 0.91 (0.69, 1.19). The 95% CIs for the GMC ratios were between 0.69 and 1.75. The incidence of solicited reactions was comparable across the four arms. Only one serious adverse event of gastroenteritis event in the Rotasiil® group was causally related.The immunological non-inferiority of LBRV-PV against Rotasiil® as well as lot-to-lot consistency of LBRV-PV was demonstrated. LBRV-PV had safety profile similar to Rotasiil®.Clinical Trials.Gov [NCT03474055] and Clinical Trial Registry of India [CTRI/2017/10/010104].

A quadrivalent split-virion inactivated influenza vaccine (IIV4; Fluzone® Quadrivalent, Sanofi Pasteur) has been available in the US since 2013 for individuals aged ≥ 6 months. Here, we describe the results of an open-label, multicenter trial (WHO Universal Trial Number U1111-1143–8370) evaluating the immunogenicity and safety of IIV4 in Indian children aged 6–35 months and 3–8 years, adolescents aged 9–17 years, and adults aged ≥ 18 years (n = 100 per group). Post-vaccination hemagglutination inhibition titers for all strains in all age groups were ≥ 8 fold higher than at baseline (range, 8–51). At least 70% of participants in all age groups seroconverted or had a significant increase in titer for each strain. The most common solicited reactions were injection-site pain and tenderness, plus fever in participants 6–23 months and myalgia in older children and adolescents. All injection-site reactions and most systemic reactions were grade 1 or 2 and resolved within 3 days. Only three vaccine-related unsolicited adverse events were reported, all of which were grade 1 or 2 and transient. No immediate adverse events, adverse events leading to study discontinuation, adverse events of special interest, or serious adverse events were reported. This study showed that IIV4 was well tolerated and highly immunogenic in all age groups. This adds important data on the safety, tolerability, and immunogenicity of influenza vaccines in India.

Background Immunization of children with vaccines against Measles, Mumps, Rubella, and Varicella (MMRV) is practiced globally with varied recommendations. In India, measles vaccine is administered alone or as MMR at 9 months age. Varicella vaccine is not routinely used. Immunization age is a function of disappearance of maternal antibodies and natural exposure of the children to the pathogens. In view of the measles-WHO-initiative, we aimed to assess if the current immunization age for measles is still valid. In addition, the kinetics of IgG and IgM antibodies against rubella, mumps and varicella viruses was also examined. Methods This cross-sectional study was conducted at a tertiary care hospital in Pune, India. A total of 600 children, 150 each in 6-month/9-month (no vaccination) and 12-month/15-month (minimum 4 weeks post-measles-vaccine) cohorts were included. History of these infections and birth status (term/preterm) was recorded. All serum samples were screened for IgG-anti-MMRV-antibodies while IgG-positives were tested for specific IgM antibodies (ELISA). Results At 6-months, the prevalence of MMRV antibodies was 4.7%, 2.7%, 10.7%, 5.3% respectively depicting disappearance of maternal antibodies in majority of the children. Birth status did not influence antibody positivity. Despite vaccination at ∼9-months, >25% children were still susceptible to measles virus at the age of 12/15-months. The ratio of clinical:subclinical infections was 4:10 (measles) and 12:1 (varicella). All the mumps/rubella IgM positives (1 and 2 respectively) represented subclinical infections. Conclusion Demonstration of early disappearance of maternal antibodies against MMRV viruses leading to the risk of these infections at an early age emphasize need for early immunization of Indian children. Suboptimal response to measles vaccine needs to be seriously addressed especially in view of the WHO’s initiative for measles eradication.

Childhood vaccination plays critical role in protecting infants from several dreaded diseases. Of the global 15 million preterm (PT) infants with compromised immune system born annually, India contributes to >3.5 million. Generation of adequate vaccine-induced immune response needs to be ensured of their protection. Immune response of Indian PT (n = 113) and full-term (FT, n = 80) infants to pentavalent vaccine administered as per the national recommendation was studied. Antibody titers against component antigens of pentavalent vaccine, immune cells profiling (T and B cells, monocytes and dendritic cells) and plasma cytokines were determined pre- and post-vaccination. Additionally, cell-mediated recall immune responses to pentavalent antigens were evaluated after short time antigenic exposure to infant PBMCs. Irrespective of gestational age (GA), all the infants developed adequate antibody response against tetanus, diphtheria, and protective but lower antibody levels for Haemophilus influenzae type-b and hepatitis B in preterm infants. Lower (~74%) protective antibody response to pertussis was independent of gestational age. PT-infants exhibited lower frequencies of CD4 T cells/dendritic cells/monocytes, increased plasma IL-10 levels and lower proliferation of central and effector memory T cells than in term-infants. Proliferative central memory response of FT-infants without anti-pertussis antibodies suggests protection from subsequent infection. Responder/non-responder PT-infants lacked immunological memory and could be infected with Bordetella. For hepatitis B, the recall response was gestational age-dependent and antibody status-independent. Humoral/cellular immune responses of PT-infants were dependent on the type of the immunogen. Preterm infants born before 32 weeks of gestation may need an extra dose of pentavalent vaccine for long lived robust immune response.

For the assessment of vaccine-induced immune response and to understand the role of antibodies in neutralization, it is necessary to assess dynamics of various antibodies in patients with different clinical manifestations. This study aims to quantitate circulating levels of IgA/IgG and IgG subtypes induced at different days postonset of symptoms, in severe and nonsevere patients. For this, serum or plasma samples (n = 146) collected from 79 COVID-19 patients were used. Indirect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) specific IgA, IgG, and IgG subtype specific enzyme-linked immunosorbent assays (ELISAs) were performed. Antibody titers between severe and nonsevere patients were compared at different times postonset of clinical symptoms. Titers in ELISA were compared to neutralizing antibody (Nab) titers determined by plaque reduction neutralization test (PRNT). Over 75% patients were positive for IgA/IgG antibodies in the first week. The ELISA titers did not differ during the first week; however, severe disease exhibited raised titers thereafter. Nab titers correlated with the ELISA titers in mild presentation but not in severe disease. IgA and IgG1 antibodies correlated stronger with Nabs. The findings highlighted that IgA together with IgG play an important in SARS-CoV-2 neutralization. These results will prove useful in assessing efficacy of vaccines and understanding disease pathogenesis.

Introduction Infection with SARS‐CoV‐2 leads to a spectrum of symptoms. Understanding the basis for severity remains crucial for better management and therapy development. So far, older age, associated‐comorbidities, and IL‐6 have been associated with severity/mortality. Materials and Methodology As a primary step, we analyzed the frequency and functional profile of innate immune cells (NK cells/dendritic cells/monocytes) and adaptive immunity‐driving lymphocytes (B cells/T cells/follicular T helper cells) by flow cytometry. Sixty cases of SARS CoV‐2 infection (25 severe, 35 mild) and ten healthy subjects without SARS CoV‐2 IgG were included. Disease‐duration based analysis of immune profile was explored for early events differentiating the two disease forms. Neutralizing antibody titers were determined by PRNT. Results and Conclusion Disease severity was found to be associated with impaired maturation of mDCs and hyperactivation of NK, follicular T helper cells, and CD8 T cells. Lower IL‐21 receptor expression on memory B cells indicated an imbalance in IL‐21/IL‐21 R ratio. Lower BCMA positive plasmablast cells in severe cases did suggest a probable absence of long‐term humoral immunity. Multivariate analysis revealed a progressive association of PD‐1+CD4 T cells with PRNT50 titers. Thus, in addition to identifying probable prognostic markers for severity, our study emphasizes the definite need for in‐depth viral antigen‐specific functional analyses in a larger patient cohort and with multiple sampling., Understanding pathogenesis of severity in current SARS‐CoV2 pandemic is of prime importance. Another concern is the recent observations (including ours) of early, higher neutralizing antibody titers in severe disease. India is reporting >80,000/day for several weeks now. Identification of prognostic markers for severity may help identifying “extra‐care‐needed” patients. As a first step, this flow‐cytometry based study was planned to understand (1) differences in immunologic modulations in patients with mild and severe disease (2) if we can identify early events associated with severity (3) prognostic markers for severity (4) association of functionality of immune cells with higher antibody titers in severe disease.

Background: ChAdOx1 nCoV-19 Corona Virus Vaccine (Recombinant) (SII-ChAdOx1 nCoV-19), manufactured in India at Serum Institute of India Pvt Ltd (SIIPL) after technology transfer from AstraZeneca, was evaluated in this phase 2/3 immunobridging study. Methods: This observer-blind study randomised participants 3:1 to SII-ChAdOx1 nCoV-19 or AZD1222 (ChAdOx1 nCoV-19) (immunogenicity/reactogenicity cohort) and 3:1 to SII-ChAdOx1 nCoV-19 or placebo (safety cohort). Two doses of vaccine (5 × 10¹⁰ viral particles) or placebo were given at 4-week intervals (+2-week window). Primary objectives were to demonstrate non-inferiority of SII-ChAdOx1 nCoV-19 to AZD1222 in terms of geometric mean titre (GMT) ratio of anti-SARS-CoV-2 spike immunoglobulin G (IgG) antibodies 28 days after second dose (defined as lower 95% CI >0·67) and to determine the incidence of serious adverse events (SAEs) causally related to SII-ChAdOx1 nCoV-19. Anti-spike IgG response was assessed using a validated multiplexed electrochemiluminescence-based immunoassay. Safety follow-up continued until 6 months after first dose. Findings: Between August 25 and October 31, 2020, n=1601 participants were enrolled: n=401 to the immunogenicity/reactogenicity cohort and n=1200 to the safety cohort. After two doses of SII-ChAdOx1 nCoV-19 or AZD1222, seroconversion rates for anti-spike IgG antibodies were 98·0% and 98·9%, respectively, with anti-spike IgG GMTs of 30 245·6 AU/mL (95% CI 26 794·0–34 141·8) and 28 558·3 AU/mL (23 479·3–34 735·8); SII-ChAdOx1 nCoV-19 was non-inferior to AZD1222 (GMT ratio 0·98; 95% CI 0·79–1·23). SAEs were reported in 15/1200 (1·3%, 95% CI 0·7–2·1), 2/300 (0·7%, 0·1–2·4) and 2/100 (2·0%, 0·2–7·0) participants who received SII-ChAdOx1 nCoV-19, placebo and AZD1222, respectively; none were causally related. SARS-CoV-2 infections were observed in 1·9% (n=22), 3·4% (n=10) and 2·0% (n=2) of the SII-ChAdOx1 nCoV-19, placebo and AZD1222 groups, respectively; none were severe. Interpretation: SII-ChAdOx1 nCoV-19 has a non-inferior immune response compared to AZD1222 and an acceptable safety/reactogenicity profile. Trial Registration: This study was registered with number CTRI/2020/08/027170 Funding: SIIPL, Indian Council of Medical Research, AstraZeneca. Declaration of Interest: PSK, CB, AD, MG, US, DK, and BG are employees of SIIPL. JV and EJK are employees of AstraZeneca. All other authors declare no competing interests. Ethical Approval: The study was approved by the Drugs Controller General of India (DCGI) and the ethics committees of each study site.

Background: Being a long-term preventive measure, COVID-19 vaccines are used in global populations. In India, country-wide immunization drive was initiated in January 2021. Methods: To assess immune response of health-care-workers to COVISHIELD(n=187) and COVAXIN(n=21), blood samples collected pre-vaccination and 1month-post-1/post-2 dose, administered 28days apart, were tested for IgG-anti-SARS-CoV-2 (ELISA) and neutralizing (Nab, PRNT50) antibodies. Spike protein-specific T cells were quantitated by IFN-γ ELISPOT and Flow-cytometry-based Intra-cellular-secretion (ICS) for IFN-γ/IL2. Findings: Among pre-vaccination-antibody negative (pre-negatives, n=120) and positive (pre-positives, n=67) COVISHIELD recipients, %Nab seroconversion and median (IQR) Nab titers were 55.1%/95.6% and 16(IQR 2.5-36.3)/(64.5, IQR 34.5-154.2, p