For the efficacy of COVID-19 vaccines, emergence of variants accumulating immune-escape mutations remains a major concern. We analyzed the anti-variant (n = 10) neutralization activity of sera from ...COVID-19 patients infected with Wuhan (B.1), Kappa, and Delta variants and COVISHIELD vaccine recipients with (prepositives) or without (prenegatives) prior antibody positivity using V- PLEX ACE2 Neutralization Kit from MSD. MSD and PRNT
correlated well (r = 0.76-0.83, p < 0.0001). Despite the least antibody positivity in Kappa patients, anti-variant neutralizing antibody (Nab) levels in the responders were comparable with Delta patients. Vaccinees sampled at 1 month (PD2-1) and 6 months (PD2-6) post-second dose showed the highest seropositivity and Nab levels against the Wuhan strain. At PD2-1, the responder rate was variant-dependent and 100% respectively in prenegatives and prepositives. Nab levels against B.1.135.1, B.1.620, B.1.1.7+E484K (both groups), AY.2 (prenegatives), and B.1.618 (prepositives) were lower than that of Wuhan. At PD2-6, positivity decreased to 15.6%-68.8% in the prenegatives; 3.5%-10.7% of prepositives turned negative for the same four variants. As against the decline in Nab levels in 9/10 variants (prenegatives), a further reduction was seen against the same four variants in the prepositives. These variants possess immune-evasion-associated mutations in the RBD/S region. In conclusion, our data show that the Nab response of patients to multiple variants depends on the infecting variant. We confirm superiority of hybrid immunity in neutralizing multiple variants. Depending on the infecting variant pre- or postvaccination, immune response to different vaccines in different populations will vary and impact protection against emerging variants. The MSD platform provides an excellent alternative to live virus/pseudovirus neutralization tests.
Abstract
Background
Undernutrition among under five children in India is a major public health problem. Despite India’s growth in the economy, the child mortality rate due to undernutrition is still ...high in both urban and rural areas. Studies that focus on urban slums are scarce. Hence the present study was carried out to assess the prevalence and determinants of undernutrition in children under five in Maharashtra, India.
Methods
A community-based cross-sectional study was conducted in 16 randomly selected clusters in two districts of Maharashtra state, India. Data were collected through house to house survey by interviewing mothers of under five children. Total 2929 mothers and their 3671 under five children were covered. Multivariate logistic regression analysis was carried out to identify the determinants of child nutritional status seperately in urban and rural areas.
Results
The mean age of the children was 2.38 years (±SD 1.36) and mean age of mothers was 24.25 years (± SD 6.37). Overall prevalence of stunting among children under five was 45.9%, wasting was 17.1 and 35.4% children were underweight. Prevalence of wasting, stunting and underweight were more seen in an urban slum than a rural area. In the rural areas exclusive breast feeding (
p
< 0.001) and acute diarrhea (
p
= 0.001) were associated with wasting, children with birth order 2 or less than 2 were associated with stunting and exclusive breast feeding (
p
< 0.05) and low maternal education were associated with underweight. Whereas in the urban slums exclusive breast feeding (
p
< 0.05) was associated with wasting, sex of the child (
p
< 0.05) and type of family (
p
< 0.05) were associated with stunting,and low income of the family (
p
< 0.05) was associated with underweight.
Conclusions
Factors like sex of the child, birth order,exclusive breast feeding,economic status of the family, type of family,acute diarrhea and maternal education have influence on nutritional status of the child. Improvement of maternal education will improve the nutritional status of the child. Strategies are needed to improve the economic status of the community.
Trial registration
Trial registration number:
CTRI/2017/12/010881
; Registration date:14/12/2017. Retrospectively registered.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Understanding of the basis for severity and fatal outcome of SARS-CoV-2 infection is of paramount importance for developing therapeutic options and identification of prognostic markers. So far, ...accumulation of neutrophils and increased levels of pro-inflammatory cytokines are associated with disease severity in COVID-19 patients. In this study, we aimed to compare circulatory levels of neutrophil secretory proteins, alpha-defensins (DEFA1), calprotectin (S100A8/A9), and myeloperoxidase (MPO) in COVID-19 patients with different clinical presentations. We studied 19 healthy subjects, 63 COVID-19 patients with mild (n=32) and severe (n=31) disease, 23 asymptomatic individuals identified through contact tracing programme and 23 recovering patients (1-4 months post-disease). At the time of disease presentation, serum levels of DEFA1 were significantly higher in patients with mild (mean230 ± 17, p<0.0001) and severe (mean452 ± 46, p<0.0001) disease respectively in comparison to healthy subjects (mean113 ± 11). S100A8/A9 proteins were significantly higher in COVID-19 patients (p<0.0001) irrespective of disease severity. The levels of DEFA1, S100A8/A9 and MPO reduced to normal in recovering patients and comparable to healthy subjects. Surprisingly, DEFA1 levels were higher in severe than mild patients in first week of onset of disease (p=0.004). Odds-ratio analysis showed that DEFA1 could act as potential biomarker in predicting disease severity (OR=11.34). In addition, levels of DEFA1 and S100A8/A9 were significantly higher in patients with fatal outcome (p=0.004 and p=0.03) respectively. The rise in DEFA1 levels was independent of secondary infections. In conclusion, our data suggest that induction of elevated levels of alpha-defensins and S100A8/A9 is associated with poor disease outcome in COVID-19 patients.
COVID-19 pandemic witnessed rapid development and use of several vaccines. In India, a country-wide immunization was initiated in January 2021. COVISHIELD, the chimpanzee adenoviral-vectored vaccine ...with full-length SARS-COV-2 spike insert and COVAXIN, the whole virus-inactivated vaccines were used. To assess and compare immune response of health-care-workers to COVISHIELD (n=187) and COVAXIN (n=21), blood samples were collected pre-vaccination, 1month post-1/post-2 doses and 6months post-dose-2 and tested for IgG-anti-SARS-CoV-2 (ELISA) and neutralizing (Nab,PRNT50) antibodies. Spike-protein-specific T cells were quantitated by IFN-γ-ELISPOT. In pre-vaccination-antibody-negative COVISHIELD recipients (pre-negatives, n=120), %Nab seroconversion (median, IQR Nab titers) increased from 55.1% (16, 2.5-36.3) post-dose-1 to 95.6% (64.5, 4.5-154.2, p<0.001) post-dose-2 that were independent of age/gender/BMI. Nab response was higher among pre-positives with hybrid immunity at all-time points (p<0.01-0.0001) and independent of age/gender/BMI/Comorbidities. Post-dose-2-seroconversion (50%, p<0.001) and Nab titers (6.75, 2.5-24.8, p<0.001) in COVAXIN-recipients were lower than COVISHIELD. COVAXIN elicited a superior IFN-γ-T cell response as measured by ELISPOT (100%; 1226, 811-1532 spot forming units, SFU/million PBMCs v/s 57.8%; 21.7,1.6-169.2; p<0.001). At 6months, 28.3% (15/53) COVISHIELD and 3/3COVAXIN recipients were Nab-negative. T cell response remained unchanged. During immunization, COVID-19 cases were detected among COVISHIELD (n=4) and COVAXIN (n=2) recipients. At 6months, 9cases were recorded in COVISHIELD-recipients. This first-time, systematic, real-world assessment and long-term follow up revealed generation of higher neutralizing antibody titers by COVISHIELD and stronger T-cell response by COVAXIN. Diminished Nab titers at 6months emphasize early booster. Immunogenicity/efficacy of vaccines will change with the progression of the pandemic needing careful evaluations in the field-settings.
Introduction: India is the second country with the highest Coronavirus Disease-2019 (COVID-19) case burden in the world. In India, Maharashtra state has the highest number of cases. Aim: To study the ...clinico-epidemiological profile of COVID-19 patients admitted in a COVID-19 designated tertiary care centre in Pune, Maharashtra, India. Materials and Methods: The authors retrospectively investigated epidemiological, demographic, clinical, laboratory, radiological and treatment data of 413 Real Time-Polymerase Chain Reaction (RT-PCR) confirmed COVID-19 patients from 14thApril 2020 to 30th June 2020. The data was analysed using the Mann-Whitney U test for continuous variables with non-normal distribution. Also, the multivariate logistic regression was used for analysis. Results: Among the 413 laboratory confirmed COVID-19 patients, 249 (60.29 %) were males, majority {87 (21.07%)} of the patients belonged to the age group of 51-60 years. The most common co-morbid condition found was diabetes mellitus {102 (24.69%)}. The most common symptoms were fever {185 (44.79%)} and cough {146 (35.35%)} followed by breathlessness {134 (32.45%)}. History of close contact with a confirmed COVID-19 case was present in 205 (49.64%) patients. The mean time from the onset of symptoms to hospital admission was 3.75 (SD±2.64) days. There was a strong association between increasing age and the need for intensive care. Total 63 (80.77%) out of 78 patients above 60 years of age had abnormal Chest X-Ray (CXR) findings during hospitalisation. Furthermore, the maximum number of deaths i.e., 31 patients (58.49%, n=53) occurred in the age group of more than 60 years of age. Conclusion: The findings suggest that increased value of serum Lactate Dehydrogenase (LDH) and Urea can be used as predictors for mortality rate. Patients aged more than 60 years are more prone for severe disease with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pneumonia and this subset of patients requires urgent medical attention.
Birth weight and post-natal growth are important predictors of adult health. Preeclampsia (PE) is associated with low birth weight and may have long term effects on the health of the children. The ...current study aims to compare anthropometry and blood pressure between children of mothers with and without PE in an Indian cohort.
We studied children born to women with (PE; n = 211) and without preeclampsia (non-PE; n = 470) at Bharati Hospital, Pune, India. Anthropometry and blood pressure were measured in children at 3-7 years of age. Weight and height Z-scores were calculated using the WHO 2006 growth reference. Independent t-tests were used to compare means between the two groups, and associations between preeclampsia and child outcomes were analyzed using multiple linear regression, adjusting for potential confounders.
Weight and height Z-scores (p = 0.04 and 0.008), and subscapular skinfold thickness (p = 0.03) were higher among children of PE compared with children of non-PE mothers. Systolic blood pressure was also higher in children of PE mothers (1.70 mmHg 95% CI 0.05, 2.90 p = 0.006). BMI and diastolic blood pressure did not differ between groups. In regression models adjusted for newborn weight and gestational age, current age and sex, and maternal height, BMI and socio-economic status, children of PE mothers had higher weight Z-score (0.27 SD 95%CI 0.06, 0.48 p = 0.01), height Z-score (0.28 SD 95%CI 0.09, 0.47 p = 0.005), and subscapular skinfold thickness (0.38 mm 95%CI 0.00, 0.76 p = 0.049). A trend for higher systolic blood pressure (1.59 mmHg 95%CI -0.02, 3.20 p = 0.053) in the children was also observed in the adjusted model. The difference in systolic blood pressure was attenuated after adjusting further for the child's weight and height (1.09 mmHg 95%CI -0.48, 2.67 p = 0.17). There was no evidence of differences in effects between boys and girls.
Children of PE mothers were taller and heavier, and had higher systolic blood pressure, partly explained by their increased body size, than children of non-PE mothers. In utero exposure to preeclampsia may increase the risk of future cardiovascular disease.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Thrombocytopenia is the most notable phenomenon in dengue. Activation status of platelets and interaction of platelets with endothelium contribute towards dengue disease pathogenesis. Platelets are ...the major cell types known to release extracellular vesicles, especially exosomes in circulation. However, the role of platelet derived exosomes (PLT-EXOs) in endothelial dysfunction during dengue infection remains unknown.
In this study, we recruited 28 healthy subjects and 69 dengue patients categorized as WS- (n=31), WS+ (n=29) and SD (n=9). Platelets were isolated from platelet rich plasma of dengue patients and their activation was assessed by flow cytometry. PLT-EXOs were isolated by ultracentrifugation method. Western blot analyses were performed to characterize the exosomes. Exosome uptake experiment was carried out to see the internalization of exosomes inside endothelial cells (HUVECs). To observe the effect of exosomes on endothelial cells, exosomes were added on HUVECs and expression of adherens and tight junctional proteins were examined by immunofluorescence assay and western blot. Expression levels of vascular injury markers were measured in the culture supernatants of Exosome-HUVEC coculture and sera of dengue patients by MSD-multiplex assay.
As compared to healthy subjects, CD41/CD61 expression was significantly reduced (p<0.0001) and CD62p expression was significantly increased (p<0.0001) on platelets in dengue patients. PLT-EXOs isolated from the dengue patients showed higher expression of CD63 and CD9 proteins than the healthy subjects. With
immunofluorescence assays, we illustrated the internalization of PLT-EXOs by the HUVECs and observed disruption of endothelial cell monolayer integrity in the presence of PLT-EXOs from WS+ and SD patients. Furthermore, the significant reduction in the expressions of ZO-2, VE-Cadherin and CD31 in endothelial cells following exposure to PLT-EXOs from the dengue patients provide direct evidence of PLT-EXOs mediated vascular permeability. PLT-EXOs stimulated the release of inflammatory markers CRP, SAA, sVCAM-1 and sICAM-1 in the supernatants of HUVEC cells. Importantly, significantly higher levels of CRP, sVCAM-1 and sICAM-1 in the sera of severe than mild dengue patients (p<0.0001) suggest their role in disease severity.
In summary, our data suggest that PLT-EXOs promote vascular leakage via release of proinflammatory mediators and compromise vascular barrier integrity in dengue patients.
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
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
. 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.
Pneumonia is responsible for high morbidity and mortality amongst children under five year of age. India accounts for one-third of the total WHO South East Asia burden of under-five mortality. There ...is a paucity of epidemiological studies indicating the true burden of pneumonia. Identification of the risk factors associated with pneumonia will help to effectively plan and implement the preventive measures for its reduction.
It was a descriptive cross-sectional study conducted in 16 randomly selected clusters in two districts of Maharashtra state, India. All mothers of under-five children in the selected clusters were included. A validated pretested interview schedule was filled by trained field supervisors through the house to house visits.WHO definition was used to define and classify clinical pneumonia. Height and weight of children were taken as per standard guidelines. Quality checks for data collection were done by the site investigators and critical and noncritical fields in the questionnaire were monitored during data entry. For continuous variables mean and SD were calculated. Chi-square test was applied to determine the association between the variables. Level of significance was considered at 0.05.
There were 3671 under five-year children, 2929 mothers in 10,929 households.Unclean fuel usage was found in 15.1% of households. Mean birth weight was 2.6 kg (SD;0.61). Exclusive breastfeeding till 6 months of age was practiced by 46% of mothers. Reported incidence of ARI was 0.49 per child per month and the reported incidence of pneumonia was 0.075 per child per year. It was not associated with any of the housing environment factors (p > 0.05) but was found to be associated with partial immunization (p < 0.05). Poor practices related to child feeding, hand hygiene and poor knowledge related to signs and symptoms of pneumonia amongst mother were found.
Very low incidence of pneumonia was observed in Pune and Sangli districts of Maharashtra. Partial immunization emerged as a most important risk factor. Reasons for low incidence and lack of association of pneumonia with known risk factors may be a better literacy rate among mothers and better immunization coverage.
Registration number of the trial- CTRI/2017/12/010881 ; date of registration-14/12/2017.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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 × 10
6
and 4 × 10
6
Pfu/ml by plaque assay and 10
7.5
and 10
7
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.
PDF
