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Background: Low awareness of BC and its associated risk factors causes delays in diagnosis and impacts survival. It is critical to communicate BC risk to patients in a format that they are easily able to understand. Our study aim was to develop easy-to-follow transmedia prototypes to communicate BC risk and evaluate user preferences, alongside exploring awareness of BC and its risk factors. Methods: Prototypes of transmedia tools for risk communication were developed with multidisciplinary input. A qualitative in-depth online interview study was undertaken using a pre-defined topic guide of BC patients (7), their relatives (6), the general public (6), and health professionals (6). Interviews were analyzed using a thematic approach. Findings: Most participants preferred pictographic representations (frequency format) of lifetime risk and risk factors and storytelling using short animations and comic strips (infographics) for communicating genetic risk and testing: “In a short time, they explained it very well, and I liked it”. Suggestions included minimizing technical terminology, decreasing the delivery speed, “two-way dialogue”, and using local “language for different locations”. There was low awareness of BC, with some understanding of age and hereditary risk factors but limited knowledge of reproductive factors. Interpretation: Our findings support use of multiple context-specific multimedia tools in communicating cancer risk in an easy-to-understand way. The preference for storytelling using animations and infographics is a novel finding and should be more widely explored.

Understanding the quality of immune repertoire triggered during natural infection can provide vital clues that form the basis for development of humoral immune response in some individuals capable of broadly neutralizing pan SARS-CoV-2 variants. We assessed the diversity of neutralizing antibody responses developed in an unvaccinated individual infected with ancestral SARS-CoV-2 by examining the ability of the distinct B cell germline-derived monoclonal antibodies (mAbs) in neutralizing known and currently circulating Omicron variants by pseudovirus and authentic virus neutralization assays. The ability of the antibodies developed post vaccination in neutralizing Omicron variants was compared to that obtained at baseline of the same individual and to those obtained from Omicron breakthrough infected individuals by pseudovirus neutralization assay. Broadly SARS-CoV-2 neutralizing mAbs representing unique B cell lineages with non-overlapping epitope specificities isolated from a single donor varied in their ability to neutralize Omicron variants. Plasma antibodies developed post vaccination from this individual demonstrated neutralization of Omicron BA.1, BA.2 and BA.4 with increased magnitude and found to be comparable with those obtained from other vaccinated individuals who were infected with ancestral SARS-CoV-2. Development of B cell repertoire capable of producing antibodies with distinct affinity and specificities for the antigen immediately after infection capable of eliciting broadly neutralizing antibodies offers highest probability in protecting against evolving SARS-CoV-2 variants.ImportanceDevelopment of robust neutralizing antibodies in SARS-CoV-2 convalescent individuals is known, however varies at population level. We isolated monoclonal antibodies from an individual infected with ancestral SARS-CoV-2 in early 2020 that not only varied in their B cell lineage origin but also varied in their capability and potency to neutralize all the known VOC and currently circulating Omicron variants. This indicated establishment of unique lineages that contributed in forming B cell repertoire in this particular individual immediately following infection giving rise to diverse antibody responses that could compensate each other in providing broadly neutralizing polyclonal antibody response. Individuals who were able to produce such potent polyclonal antibody responses after infection have a higher chance of being protected from evolving SARS-CoV-2 variants.

Objective -To study clinical disease outcomes in both humans and animal models to understand the pathogenicity of omicron compared to delta variant. Methods- In this cross-sectional observational study, clinical outcomes of adults who tested positive at 2 testing centres in Delhi National Capital Region between January 2022 and March 2022 (Omicron infected; N=2998) were compared to a similar geographical cohort (Delta infected; N=3292). Additionally, disease course and outcomes were studied in SARS-CoV2 infected golden Syrian hamster and K-18 humanized ACE2 transgenic mice. Results- Omicron variant infection was associated with milder clinical course [83% (95% CI: 61, 94) reduced risk of severity compared against delta] adjusting for vaccination, age, sex, prior infection and occupational risk. This correlated with lower disease index and viral load scores when comparing omicron with other variants in animal models. Conclusion- Infections caused by the omicron variant is milder compared to delta independent of previous immunity.

IntroductionExisting risk assessment tools to identify children at risk of hospitalised pneumonia-related mortality have shown suboptimal discriminatory value during external validation. Our objective was to derive and validate a novel risk assessment tool to identify children aged 2–59 months at risk of hospitalised pneumonia-related mortality across various settings.MethodsWe used primary, baseline, patient-level data from 11 studies, including children evaluated for pneumonia in 20 low-income and middle-income countries. Patients with complete data were included in a logistic regression model to assess the association of candidate variables with the outcome hospitalised pneumonia-related mortality. Adjusted log coefficients were calculated for each candidate variable and assigned weighted points to derive the Pneumonia Research Partnership to Assess WHO Recommendations (PREPARE) risk assessment tool. We used bootstrapped selection with 200 repetitions to internally validate the PREPARE risk assessment tool.ResultsA total of 27 388 children were included in the analysis (mean age 14.0 months, pneumonia-related case fatality ratio 3.1%). The PREPARE risk assessment tool included patient age, sex, weight-for-age z-score, body temperature, respiratory rate, unconsciousness or decreased level of consciousness, convulsions, cyanosis and hypoxaemia at baseline. The PREPARE risk assessment tool had good discriminatory value when internally validated (area under the curve 0.83, 95% CI 0.81 to 0.84).ConclusionsThe PREPARE risk assessment tool had good discriminatory ability for identifying children at risk of hospitalised pneumonia-related mortality in a large, geographically diverse dataset. After external validation, this tool may be implemented in various settings to identify children at risk of hospitalised pneumonia-related mortality.

The establishment and maintenance of pregnancy in humans proceed through a continuous change of biochemical and biophysical processes. It requires a constant interaction between the fetus and the maternal system. The present prospective study aims to elucidate changes in salivary proteome from the early to middle stages of term pregnancy, and establishing an expressional trajectory for modulated proteins. To date, a comprehensive characterization of the longitudinal salivary proteome in pregnancy has not been performed and it is our immediate interest. In the discovery phase, maternal saliva (N = 20) at 6–13, 18–21, and 26–29 weeks of gestation was analyzed using level-free proteomics (SWATH-MS) approach. The expression levels of 65 proteins were found to change significantly with gestational age and distributed into two distinct clusters with a unique expression trajectory. The results revealed that altered proteins are involved in maternal immune modulation, metabolism, and host defense mechanism. Further, verification of 12 proteins was employed using targeted mass spectrometry (MRM-MS) in a separate subset of saliva (N = 14). The MRM results of 12 selected proteins confirmed a similar expression pattern as in SWATH-MS analysis. Overall, the results not only demonstrate the longitudinal maternal saliva proteome for the first time but also set the groundwork for comparative analysis between term birth and adverse pregnancy outcomes.

The trillions of microorganisms residing in the human body display varying degrees of compositional and functional diversities within and between individuals and contribute significantly to host physiology and susceptibility to disease. Microbial species present in the vaginal milieu of reproductive age women showed a large personal component and varies widely in different ethnic groups at the taxonomic, genomic, and functional levels. Lactobacillus iners, L. crispatus, L. gasseri, L. jensenii, and L. johnsonii are most frequently detected bacterial species in the vaginal milieu of reproductive age women. However, we currently lack (i) an understanding of the baseline vaginal microbiota of reproductive age Indian women, (ii) the extent of taxonomic and functional variations of vaginal microbiota between individuals and (iii) the genomic repertoires of the dominant vaginal microbiota associated with the Indian subjects. In our study, we analyzed the metagenome of high vaginal swab (HVS) samples collected from 40 pregnant Indian women enrolled in the GARBH-Ini cohort. Composition and abundance of bacterial species was characterized by pyrosequencing 16S rRNA gene. We identified 3067 OTUs with ≥ 10 reads from four different bacterial phyla. Several species of lactobacilli were clustered into three community state types (CSTs). L. iners, L. crispatus, L. gasseri, and L. jensenii are the most frequently detected Lactobacillus species in the vaginal environment of Indian women. Other than Lactobacillus, several species of Halomonas were also identified in the vaginal environment of most of the women sampled. To gain genomic and functional insights, we isolated several Lactobacillus species from the HVS samples and explored their whole genome sequences by shotgun sequencing. We analyzed the genome of dominant Lactobacillus species, L. iners, L. crispatus, L. gasseri, and L. paragesseri to represent the CSTs and identify functions that may influence the composition of complex vaginal microbial ecology. This study reports for the first time the vaginal microbial ecology of Indian women and genomic insights into L. iners, L. crispatus, L. gasseri, and L. paragesseri commonly found in the genital tract of reproductive age women.

The characteristics of immune memory established in response to inactivated SARS-CoV-2 vaccines remains unclear. We determined the magnitude, quality and persistence of cellular and humoral memory responses up to 6 months after vaccination with BBV152/Covaxin. Here, we show that the quantity of vaccine-induced spike- and nucleoprotein-antibodies is comparable to that following natural infection and the antibodies are detectable up to 6 months. The RBD-specific antibodies decline in the range of 3 to 10-fold against the SARS-CoV-2 variants in the order of alpha (B.1.1.7) > delta (B.1.617.2) > beta (B.1.351), with no observed impact of gamma (P.1) and kappa (B.1.617.1) variant. We found that the vaccine induces memory B cells, similar to natural infection, which are impacted by virus variants in the same order as antibodies. The vaccine further induced antigen-specific functionally potent multi-cytokine expressing CD4+ T cells in ∼85% of the subjects, targeting spike and nucleoprotein of SARS-CoV-2. Marginal ∼1.3 fold-reduction was observed in vaccine-induced CD4+ T cells against the beta variant, with no significant impact of the alpha and the delta variants. The antigen-specific CD4+ T cells were populated in the central memory compartment and persisted up to 6 months of vaccination. Importantly the vaccine generated Tfh cells that are endowed with B cell help potential, similar to the Tfh cells induced after natural infection. Altogether, these findings establish that the inactivated virus vaccine BBV152 induces robust immune memory to SARS-CoV-2 and variants of concern, which persist for at least 6 months after vaccination. This study provides insight into the attributes of BBV152-elicited immune memory, and has implication for future vaccine development, guidance for use of inactivated virus vaccine, and booster immunization.

Summary Background SARS-CoV-2 variants of concern (VOCs) have threatened COVID-19 vaccine effectiveness. We aimed to assess the effectiveness of the ChAdOx1 nCoV-19 vaccine, predominantly against the delta (B.1.617.2) variant, in addition to the cellular immune response to vaccination. Methods We did a test-negative, case-control study at two medical research centres in Faridabad, India. All individuals who had a positive RT-PCR test for SARS-CoV-2 infection between April 1, 2021, and May 31, 2021, were included as cases and individuals who had a negative RT-PCR test were included as controls after matching with cases on calendar week of RT-PCR test. The primary outcome was effectiveness of complete vaccination with the ChAdOx1 nCoV-19 vaccine against laboratory-confirmed SARS-CoV-2 infection. The secondary outcomes were effectiveness of a single dose against SARS-CoV-2 infection and effectiveness of a single dose and complete vaccination against moderate-to-severe disease among infected individuals. Additionally, we tested in-vitro live-virus neutralisation and T-cell immune responses to the spike protein of the wild-type SARS-CoV-2 and VOCs among healthy (anti-nucleocapsid antibody negative) recipients of the ChAdOx1 nCoV-19 vaccine. Findings Of 2379 cases of confirmed SARS-CoV-2 infection, 85 (3·6%) were fully vaccinated compared with 168 (8·5%) of 1981 controls (adjusted OR [aOR] 0·37 [95% CI 0·28–0·48]), giving a vaccine effectiveness against SARS-CoV-2 infection of 63·1% (95% CI 51·5–72·1). 157 (6·4%) of 2451 of cases and 181 (9·1%) of 1994) controls had received a single dose of the ChAdOx1 nCoV-19 vaccine (aOR 0·54 [95% CI 0·42–0·68]), thus vaccine effectiveness of a single dose against SARS-CoV-2 infection was 46·2% (95% CI 31·6–57·7). One of 84 cases with moderate-to-severe COVID-19 was fully vaccinated compared with 84 of 2295 cases with mild COVID-19 (aOR 0·19 [95% CI 0·01–0·90]), giving a vaccine effectiveness of complete vaccination against moderate-to-severe disease of 81·5% (95% CI 9·9–99·0). The effectiveness of a single dose against moderate-to-severe disease was 79·2% (95% CI 46·1–94·0); four of 87 individuals with moderate-to-severe COVID-19 had received a single dose compared with 153 of 2364 participants with mild disease (aOR 0·20 [95% CI 0·06–0·54]). Among 49 healthy, fully vaccinated individuals, neutralising antibody responses were lower against the alpha (B.1.1.7; geometric mean titre 244·7 [95% CI 151·8–394·4]), beta (B.1.351; 97·6 [61·2–155·8]), kappa (B.1.617.1; 112·8 [72·7–175·0]), and delta (88·4 [61·2–127·8]) variants than against wild-type SARS-CoV-2 (599·4 [376·9–953·2]). However, the antigen-specific CD4 and CD8 T-cell responses were conserved against both the delta variant and wild-type SARS-CoV-2. Interpretation The ChAdOx1 nCoV-19 vaccine remained effective against moderate-to-severe COVID-19, even during a surge that was dominated by the highly transmissible delta variant of SARS-CoV-2. Spike-specific T-cell responses were maintained against the delta variant. Such cellular immune protection might compensate for waning humoral immunity. Funding Department of Biotechnology India, Council of Scientific and Industrial Research India, and Fondation Botnar.

Background: Existing scores to identify children at risk of hospitalized pneumonia-related mortality lack broad external validation. Our objective was to externally validate three such risk scores. Methods: We applied the Respiratory Index of Severity in Children (RISC) for HIV-negative children, the RISC-Malawi, and the Pneumonia Etiology Research for Child Health (PERCH) scores to hospitalized children in the Pneumonia REsearch Partnerships to Assess WHO REcommendations (PREPARE) data set. The PREPARE data set includes pooled data from 41 studies on pediatric pneumonia from across the world. We calculated test characteristics and the area under the curve (AUC) for each of these clinical prediction rules. Results: The RISC score for HIV-negative children was applied to 3574 children 0-24 months and demonstrated poor discriminatory ability (AUC = 0.66, 95% confidence interval (CI) = 0.58-0.73) in the identification of children at risk of hospitalized pneumonia-related mortality. The RISC-Malawi score had fair discriminatory value (AUC = 0.75, 95% CI = 0.74-0.77) among 17 864 children 2-59 months. The PERCH score was applied to 732 children 1-59 months and also demonstrated poor discriminatory value (AUC = 0.55, 95% CI = 0.37-0.73). Conclusions: In a large external application of the RISC, RISC-Malawi, and PERCH scores, a substantial number of children were misclassified for their risk of hospitalized pneumonia-related mortality. Although pneumonia risk scores have performed well among the cohorts in which they were derived, their performance diminished when externally applied. A generalizable risk assessment tool with higher sensitivity and specificity to identify children at risk of hospitalized pneumonia-related mortality may be needed. Such a generalizable risk assessment tool would need context-specific validation prior to implementation in that setting. publishedVersion

BackgroundThe prevalence of preterm birth (PTB) is high in lower and middle-income countries (LMIC) such as India. In LMIC, since a large proportion seeks antenatal care for the first time beyond 14-weeks of pregnancy, accurate estimation of gestational age (GA) using measures derived from ultrasonography scans in the second and third trimesters is of paramount importance. Different models have been developed globally to estimate GA, and currently, LMIC uses Hadlock’s formula derived from data based on a North American cohort. This study aimed to develop a population-specific model using data from GARBH-Ini, a multidimensional and ongoing pregnancy cohort established in a district hospital in North India for studying PTB.MethodsData obtained by longitudinal ultrasonography across all trimesters of pregnancy was used to develop and validate GA models for second and third trimesters. The first trimester GA estimated by ultrasonography was considered the Gold Standard. The second and third trimester GA model named, Garbhini-GA2 is a multivariate random forest model using five ultrasonographic parameters routinely measured during this period. Garbhini-GA2 model was compared to Hadlock and INTERGROWTH-21st models in the TEST set by estimating root-mean-squared error, bias and PTB rate.FindingsGarbhini-GA2 reduced the GA estimation error by 23-45% compared to the published models. Furthermore, the PTB rate estimated using Garbhini-GA2 was more accurate when compared to published formulae that overestimated the rate by 1·5-2·0 times.InterpretationThe Garbhini-GA2 model developed is the first of its kind developed solely using Indian population data. The higher accuracy of GA estimation by Garbhini-GA2 emphasises the need to apply population-specific GA formulae to improve antenatal care and better PTB rate estimates.FundingCentre for Integrative Biology and Systems Medicine, IIT Madras; Department of Biotechnology, Government of India; Grand Challenges India, BIRAC.Panel: Research in ContextEvidence before this studyThe appropriate delivery of antenatal care and accurate delivery date estimation is heavily dependent on accurate pregnancy dating. Unlike GA estimation using crown-rump length in the first trimester, dating using foetal biometry during the second and third trimesters is prone to inaccuracies. This is a public health concern, particularly in low and middle-income countries like India, where nearly 40% of pregnant women seek their first antenatal care beyond 14 weeks of gestation. The dating formulae used in LMIC were developed using foetal biometry data from the Caucasian population, and these formulae are prone to be erroneous when used in ethnically different populations.Added value of this studyThis study developed a dating model, the Garbhini-GA2 model for second and third trimesters of pregnancy using multiple candidate biometric predictors measured in a North Indian population. When evaluated internally, this model outperformed the currently used dating models by reducing the errors in the estimation of gestational age by 25-40%. Further, Garbhini-GA2 estimated a PTB rate similar to that estimated by the Gold Standard in our population, while the published formulae overestimated the PTB rates.Implications of all the available evidenceOur Garbhini-GA2 model, after due validations in independent cohorts across the Southeast Asian regions, has the potential to be quickly translated for clinical use across the region. A precise dating will benefit obstetricians and neonatologists to plan antenatal and neonatal care more exactly. From an epidemiologist standpoint, using the Garbhini-GA2 dating formulae will improve the precision of the estimates of pregnancy outcomes that heavily depend on gestational age, such as preterm birth, small for gestational age and stillbirth in our population. Additionally, our dating models will improve phenotyping by reducing the risk of misclassification between outcomes for mechanistic and biomarker research.

BackgroundDNA methylation (DNAm) may play an important role in birth outcomes.Material and MethodsGenome wide DNAm was analysed in peripheral blood DNA of women at multiple time points during gestation. A novel empirical method was used to identify CpG sites with high temporal variance in methylation associating with preterm birth.ResultsHigh variability at 1296 CpG sites from the promoter regions of 1197 genes significantly associated with PTB. These genes belonged to pathways involved in signalling by platelet derived growth factor, platelet homeostasis, collagen degradation, extracellular matrix and circadian clock.ConclusionsThe findings provide novel information which might help in development of predictive biomarkers of preterm birth outcome.

BACKGROUND "Kangaroo mother care," a type of newborn care involving skin-to-skin contact with the mother or other caregiver, reduces mortality in infants with low birth weight (

Clinical and epidemiological characteristics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are now widely available, but there are few data regarding longitudinal serology in large cohorts, particularly those from low-income and middle-income countries. We established an ongoing prospective cohort of 3,840 SARS-CoV-2-positive individuals according to RT-PCR in the Delhi-National Capital Region of India to document clinical and immunological characteristics during illness and convalescence. The immunoglobulin G (IgG) responses to the receptor binding domain (RBD) and nucleocapsid were assessed at 0 to 7 days, 10 to 28 days, and 6 to 10 weeks after infection. The clinical predictors of seroconversion were identified by multivariable regression analysis. The seroconversion rates during the postinfection windows of 0 to 7 days, 10 to 28 days, and 6 to 10 weeks were 46%, 84.7%, and 85.3%, respectively (N = 743). The proportion with a serological response increased with the severity of coronavirus disease 2019 (COVID-19). All participants with severe disease, 89.6% with mild to moderate infection, and 77.3% of asymptomatic participants had IgG antibodies to the RBD antigen. The threshold values for the nasopharyngeal viral RNA RT-PCR of a subset of asymptomatic and symptomatic seroconverters were comparable (P = 0.48) to those of nonseroconverters (P = 0.16) (N = 169). This is the first report of longitudinal humoral immune responses to SARS-CoV-2 over a period of 10 weeks in South Asia. The low seropositivity of asymptomatic participants and differences between assays highlight the importance of contextualizing the understanding of population serosurveys.

BackgroundDevelopment of methods to detect risk of preterm birth in pregnant women can result in reduction in occurrence of preterm birth. Our objective was to undertake a longitudinal study to investigate the association of telomere length shortening in peripheral blood DNA of women during pregnancy with preterm birth.MethodsTelomere length reduction in peripheral blood DNA was measured at two time points by Real Time PCR in pregnant women enrolled in a large prospective cohort (GARBH-Ini) in Gurugram, India. Out of 248 women who participated in this study, 60 mothers delivered preterm while 188 mothers delivered at term. ResultsTelomere length was found to be significantly reduced in preterm birth delivering mothers compared to those who delivered at term at less than 20 weeks (p=0.02) and at 26-28 weeks (p=0.84 x 10-15) of pregnancy. Predictive modelling by binary logistic regression analysis revealed that reduction of telomere length (T/S ratio) at 26-28 weeks was found to be significantly (p=7.7181 x 10-06) associated with enhanced risk of preterm birth. A mean odds ratio of 8.4 was found for association of T/S ratio with preterm birth outcome. There was no significant difference in maternal age between the mothers who delivered preterm and those who delivered at term. ConclusionsOur preliminary results indicate that telomere length reduction in maternal peripheral blood DNA might be a potential indicator of risk of preterm delivery.

Clinical and epidemiological characteristics of SARS-CoV-2 infection are now widely available, but there are few data on longitudinal serology in large cohorts, particularly from low-and middle-income countries. We established an ongoing prospective cohort of 3840 SARS-CoV-2 RT-PCR positive individuals in the Delhi-National Capital Region of India, to document clinical and immunological characteristics during illness and convalescence. The IgG responses to the receptor binding domain (RBD) and nucleocapsid were assessed at 0-7, 10-28 days and 6-10 weeks after infection. The clinical predictors of seroconversion were identified by multivariable regression analysis. The seroconversion rates in the post-infection windows of 0–7 days, 10–28 days and 6–10 weeks were 46%, 84.7% and 85.3% respectively (n=782). The proportion with a serological response increased with severity of COVID-19 disease. All participants with severe disease, 89.6% with mild to moderate infection and 77.3% of asymptomatic participants had IgG antibodies to the RBD antigen. The threshold values in the nasopharyngeal viral RNA RT-PCR in a subset of asymptomatic and symptomatic seroconverters were comparable (p value: 0.48), with similar results among non-seroconverters (p value: 0.16) (n=169). This is the first report of longitudinal humoral immune responses to SARS-CoV-2 infection over a period of ten weeks from South Asia. The low seropositivity in asymptomatic participants and differences between assays highlight the importance of contextualizing the understanding of population serosurveys.SummaryWe measured anti-SARS-CoV-2 RBD and NC protein IgG in a multi-hospital-based prospective cohort from northern India up to ten weeks post-infection. The lower seroconversion rate among asymptomatic RT-PCR positive participants has public health significance particularly for interpreting community seroprevalence estimates.

SARS-CoV-2 antibody detection assays are crucial for gathering seroepidemiological information and monitoring the sustainability of antibody response against the virus. The SARS-CoV-2 Spike protein’s receptor-binding domain (RBD) is a very specific target for anti-SARS-CoV-2 antibodies detection. Moreover, many neutralizing antibodies are mapped to this domain, linking antibody response to RBD with neutralizing potential. Detection of IgG antibodies, rather than IgM or total antibodies, against RBD is likely to play a larger role in understanding antibody-mediated protection and vaccine response. Here we describe a rapid and stable RBD-based IgG ELISA test obtained through extensive optimization of the assay components and conditions. The test showed a specificity of 99.79% (95% CI: 98.82–99.99%) in a panel of pre-pandemic samples (n = 470) from different groups, i.e., pregnancy, fever, HCV, HBV, and autoantibodies positive. Test sensitivity was evaluated using sera from SARS-CoV-2 RT-PCR positive individuals (n = 312) and found to be 53.33% (95% CI: 37.87–68.34%), 80.47% (95% CI: 72.53–86.94%), and 88.24% (95% CI: 82.05–92.88%) in panel 1 (days 0–13), panel 2 (days 14–20) and panel 3 (days 21–27), respectively. Higher sensitivity was achieved in symptomatic individuals and reached 92.14% (95% CI: 86.38–96.01%) for panel 3. Our test, with a shorter runtime, showed higher sensitivity than parallelly tested commercial ELISAs for SARS-CoV-2-IgG, i.e., Euroimmun and Zydus, even when equivocal results in the commercial ELISAs were considered positive. None of the tests, which are using different antigens, could detect anti-SARS-CoV-2 IgGs in 10.5% RT-PCR positive individuals by the fourth week, suggesting the lack of IgG response.

Additional file 1. Supplementary information.

Sepsis, an important and preventable cause of death in the newborn, is associated with high out of pocket hospitalization costs for the parents/guardians. The government of Nepal’s Free Newborn Care (FNC) service that covers hospitalization costs has set a maximum limit of Nepalese rupees (NPR) 8000 i.e. USD 73.5, the basis of which is unclear. We aimed to estimate the costs of treatment in neonates and young infants fulfilling clinical criteria for sepsis, defined as clinical severe infection (CSI) to identify determinants of increased cost. This study assessed costs for treatment of 206 infants 3–59 days old, enrolled in a clinical trial, and admitted to the Kanti Children’s Hospital in Nepal through June 2017 to December 2018. Total costs were derived as the sum of direct costs for bed charges, investigations, and medicines and indirect costs calculated by using work time loss of parents. We estimated treatment costs for CSI, the proportion exceeding NPR 8000 and performed multivariable linear regression to identify determinants of high cost. Of the 206 infants, 138 (67%) were neonates (3–28 days). The median (IQR) direct costs for treatment of CSI in neonates and young infants (29–59 days) were USD 111.7 (69.8–155.5) and 65.17 (43.4–98.5) respectively. The direct costs exceeded NPR 8000 (USD 73.5) in 69% of neonates with CSI. Age

ObjectivesConvalescent plasma (CP) as a passive source of neutralizing antibodies and immunomodulators is a century-old therapeutic option used for the management of viral diseases. We investigated its effectiveness for the treatment of COVID-19.DesignOpen-label, parallel-arm, phase II, multicentre, randomized controlled trial.SettingThirty-nine public and private hospitals across India.ParticipantsHospitalized, moderately ill confirmed COVID-19 patients (PaO2/FiO2: 200-300 or respiratory rate > 24/min and SpO2 ≤ 93% on room air).InterventionParticipants were randomized to either control (best standard of care (BSC)) or intervention (CP + BSC) arm. Two doses of 200 mL CP was transfused 24 hours apart in the intervention arm.Main Outcome MeasureComposite of progression to severe disease (PaO2/FiO2< 100) or all-cause mortality at 28 days post-enrolment.ResultsBetween 22ndApril to 14thJuly 2020, 464 participants were enrolled; 235 and 229 in intervention and control arm, respectively. Composite primary outcome was achieved in 44 (18.7%) participants in the intervention arm and 41 (17.9%) in the control arm [aOR: 1.09; 95% CI: 0.67, 1.77]. Mortality was documented in 34 (13.6%) and 31 (14.6%) participants in intervention and control arm, respectively [aOR) 1.06 95% CI: −0.61 to 1.83].InterpretationCP was not associated with reduction in mortality or progression to severe COVID-19. This trial has high generalizability and approximates real-life setting of CP therapy in settings with limited laboratory capacity. A priori measurement of neutralizing antibody titres in donors and participants may further clarify the role of CP in management of COVID-19.Trial registrationThe trial was registered with Clinical Trial Registry of India (CTRI); CTRI/2020/04/024775.

Nucleic acid real-time PCR test has become the main diagnostic tool for SARS‐CoV‐2 infection, and there are also drawbacks to these real-time PCR test kits. Additionally, it has reported high false-negative rates. A reliable and rapid test method is urgently required to briskly detect antibody response in a large number of infected patients and ensure prompt care for patients. Therefore, we report here a Luminex bead based multiplexed immunoassay to serologically diagnose the SARS-CoV2 infection and detect IgM and IgG response in COVID-19 patients. The technology can provide sensitive and specific detection using a low amount of serum samples in high-throughput screening platforms.

BackgroundDifferent formulae have been developed globally to estimate gestational age (GA) by ultrasonography in the first trimester of pregnancy. In this study, we develop an Indian population-specific dating formula and compare its performance with published formulae. Finally, we evaluate the implications of the choice of dating method on preterm birth (PTB) rate. This study’s data was from GARBH-Ini, an ongoing pregnancy cohort of North Indian women to study PTB.MethodsComparisons between ultrasonography-Hadlock and last menstrual period (LMP) based dating methods were made by studying the distribution of their differences by Bland-Altman analysis. Using data-driven approaches, we removed data outliers more efficiently than by applying clinical parameters. We applied advanced machine learning algorithms to identify relevant features for GA estimation and developed an Indian population-specific formula (Garbhini-GA1) for the first trimester. PTB rates of Garbhini-GA1 and other formulae were compared by estimating sensitivity and accuracy.ResultsPerformance of Garbhini-GA1 formula, a non-linear function of crown-rump length (CRL), was equivalent to published formulae for estimation of first trimester GA (LoA, - 0.46,0.96 weeks). We found that CRL was the most crucial parameter in estimating GA and no other clinical or socioeconomic covariates contributed to GA estimation. The estimated PTB rate across all the formulae including LMP ranged 11.27 – 16.50% with Garbhini-GA1 estimating the least rate with highest sensitivity and accuracy. While the LMP-based method overestimated GA by three days compared to USG-Hadlock formula; at an individual level, these methods had less than 50% agreement in the classification of PTB.ConclusionsAn accurate estimation of GA is crucial for the management of PTB. Garbhini-GA1, the first such formula developed in an Indian setting, estimates PTB rates with higher accuracy, especially when compared to commonly used Hadlock formula. Our results reinforce the need to develop population-specific gestational age formulae.

BackgroundBacterial infections account for a significant proportion of neonatal and infant mortality globally. We aimed to identify predictors of death in infants with probable serious bacterial infection (PSBI) defined as signs/symptoms of possible serious bacterial infection along with baseline C-reactive protein (CRP) ≥12 mg/l.MethodsWe did a secondary analysis using the data collected from 700 infants with PSBI who participated in a randomized controlled trial in India in which zinc or placebo was given in addition to the standard antibiotics. Logistic regression was used to estimate the associations between relevant variables and death within 21 days.ResultsThose infants who were fed cow's milk or formula before the illness episode had 3.7-fold (95% confidence interval (CI) 1.5-9.3) and 5.3-fold (95% CI 2.0-13.6) higher odds of death, respectively. Lethargy (odds ratio (OR) 2.4, 95% CI 1.1-5.4) and CRP (OR 1.9, 95% CI 1.1-3.3) were also independent predictors of death. In the model including only clinical features, female gender (OR 2.25, 95% CI 1.0-5.0), abdominal distention (3.7, 95% CI 1.1-12.3), and bulging fontanelle (5.8, 95% CI 1.1-30.5) were also independent predictors for death.ConclusionFormula or cow milk feeding prior to the illness, lethargy at the time of presentation, and high serum CRP levels predicted death in infants with PSBI.

Objective To evaluate the effect of zinc as an adjuvant therapy in radiologically confirmed pneumonia in children 2-24 months of age. Patients and methods We analyzed data of 212 children with pneumonia for whom chest X-ray films were available at enrollment and at least two radiologists agreed on the diagnosis of pneumonia. We compared the time to recovery in the two groups (n = 121, zinc group and n = 91, placebo group) using a Cox proportional hazards regression model. Results Time to recovery was similar in both groups [median interquartile range: zinc, 84 h (64, 140 h); placebo, 85 h (65, 140 h)]. The absolute risk reduction for treatment failure was 5.2% (95% confidence interval: -4.8, 15.1) with zinc supplementation. Conclusion There was no significant beneficial effect of zinc on the duration of recovery or risk of treatment failure in children with radiologically confirmed pneumonia.

Background & objectives: Healthcare associated infections (HAIs) increase the length of stay in the hospital and consequently costs as reported from studies done in developed countries. The current study was undertaken to evaluate the impact of HAIs on length of stay and costs of health care in children admitted to Paediatric Intensive Care Unit (PICU) of a tertiary care hospital in north India.Methods: This prospective study was done in the seven bedded PICU of a large multi-specialty tertiary care hospital in New Delhi, India. A total of 20 children with HAI (cases) and 35 children without HAI (controls), admitted to the PICU during the study period (January 2012 to June 2012), were matched for gender, age, and average severity of illness score. Each patient's length of stay was obtained prospectively. Costs of healthcare were estimated according to traditional and time driven activity based costing methods approach. Results: The median extra length of PICU stay for children with HAI (cases), compared with children with no HAI (controls), was seven days (IQR 3-16). The mean total costs of patients with and without HAI were ' 2,04,787 (US$ 3,413) and ' 56,587 (US$ 943), respectively and the mean difference in the total cost between cases and controls was ' 1,48,200 (95% CI 55,716 to 2,40,685, p

Memory T and B lymphocyte numbers are thought to be regulated by recent and cumulative microbial exposures. We report here that memory-phenotype lymphocyte frequencies in B, CD4 and CD8 T-cells in 3-monthly serial bleeds from healthy young adult humans were relatively stable over a 1-year period, while recently activated -B and -CD4 T cell frequencies were not, suggesting that recent environmental exposures affected steady state levels of recently activated but not of memory lymphocyte subsets. Frequencies of memory B and CD4 T cells were not correlated, suggesting that variation in them was unlikely to be determined by cumulative antigenic exposures. Immunophenotyping of adult siblings showed high concordance in memory, but not of recently activated lymphocyte subsets, suggesting genetic regulation of memory lymphocyte frequencies. To explore this possibility further, we screened effector memory (EM)-phenotype T cell frequencies in common independent inbred mice strains. Using two pairs from these strains that differed predominantly in either CD4EM and/or CD8EM frequencies, we constructed bi-parental bone marrow chimeras in F1 recipient mice, and found that memory T cell frequencies in recipient mice were determined by donor genotypes. Together, these data suggest cell-autonomous determination of memory T niche size, and suggest mechanisms maintaining immune variability.

Background An estimated 2.7 of the 5.9 million deaths in children under 5 years of age occur in the neonatal period. Severe infections contribute to almost a quarter of these deaths. Mortality due to severe infections in developing country settings is substantial despite antibiotic therapy. Effective interventions that can be added to standard therapy for severe infections are required to reduce case fatality. Methods/Design This is a double-blind randomized placebo-controlled parallel group superiority trial to investigate the effect of zinc administered orally as an adjunct to standard therapy to infants aged 3 days up to 2 months (59 days) hospitalized with clinical severe infection, that will be undertaken in seven hospitals in Delhi, India and Kathmandu, Nepal. In a 1:1 ratio, we will randomly assign young infants to receive 10 mg of elemental zinc or placebo orally in addition to the standard therapy for a total of 14 days. The primary outcomes hospital case fatality, which is death due to any cause and at any time after enrolment while hospitalized for the illness episode, and extended case fatality, which encompasses the period until 12 weeks after enrolment. Discussion A previous study showed a beneficial effect of zinc in reducing the risk of treatment failure, as well as a non-significant effect on case fatality. This study was not powered to detect an effect on case fatality, which this current study is. If the results are consistent with this earlier trial, we would have provided strong evidence for recommending zinc as an adjunct to standard therapy for clinical severe infection in young infants. Trial registration Universal Trial Number: U1111-1187-6479, Clinical Trials Registry – India: CTRI/2017/02/007966 : Registered on February 27, 2017.

To explore the natural microbial community of any ecosystems by high-resolution molecular approaches including next generation sequencing, it is extremely important to develop a sensitive and reproducible DNA extraction method that facilitate isolation of microbial DNA of sufficient purity and quantity from culturable and uncultured microbial species living in that environment. Proper lysis of heterogeneous community microbial cells without damaging their genomes is a major challenge. In this study, we have developed an improved method for extraction of community DNA from different environmental and human origin samples. We introduced a combination of physical, chemical and mechanical lysis methods for proper lysis of microbial inhabitants. The community microbial DNA was precipitated by using salt and organic solvent. Both the quality and quantity of isolated DNA was compared with the existing methodologies and the supremacy of our method was confirmed. Maximum recovery of genomic DNA in the absence of substantial amount of impurities made the method convenient for nucleic acid extraction. The nucleic acids obtained using this method are suitable for different downstream applications. This improved method has been named as the THSTI method to depict the Institute where the method was developed.