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1.
Lancet Infect Dis ; 22(4): 473-482, 2022 04.
Article in English | MEDLINE | ID: covidwho-1757985

ABSTRACT

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.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibody Formation , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines , Case-Control Studies , Humans , Vaccination
2.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-331051

ABSTRACT

Background: Optimum formulation of Biological Es CORBEVAX vaccine that contains protein sub unit of Receptor Binding Domain (RBD) from the spike protein of SARS-COV-2 formulated with aluminum hydroxide (Al3+) and CpG1018 as adjuvants was selected in phase-1 and 2 studies and proven to be safe, well tolerated and immunogenic in healthy adult population. In the current study, additional data was generated to determine immunogenic superiority of CORBEVAX vaccine over COVISHIELD vaccine and safety in larger and older population. Methods: This is a phase III prospective, single blinded, randomized, active controlled study (CTRI/2021/08/036074) conducted at 18 sites across India in healthy adults aged between 18-80 years. This study has two arms;immunogenicity arm and safety arm. Participants in immunogenicity arm were randomized equally to either CORBEVAX or COVISHIELD vaccination groups to determine the immunogenic superiority. Healthy adults without a history of Covid-19 vaccination or SARS-CoV-2 infection, were enrolled. Findings: The safety profile of CORBEVAX vaccine was comparable to the comparator vaccine COVISHIELD in terms of overall AE rates, related AE rates and medically attended AEs. Majority of reported AEs were mild in nature, and overall CORBEVAX appeared to cause fewer local and systemic adverse reactions/events. Overall, two grade-3 serious AEs (Dengue fever and femur fracture) were reported and they are unrelated to study vaccine. Neutralizing Antibody titers, against both Ancestral and Delta strain, induced post two-dose vaccination regimen were higher in the CORBEVAX arm as compared to COVISHIELD and the analysis of GMT ratios demonstrated immunogenic superiority of CORBEVAX in comparison with COVISHIELD. Both CORBEVAX and COVISHIELD vaccines showed comparable seroconversion post vaccination when assessed against anti-RBD IgG response. The subjects in CORBEVAX cohort also exhibited higher Interferon-gamma secreting PBMCs post stimulation with SARS-COV-2 RBD peptides than the subjects in COVISHIELD cohort. Interpretations: Neutralizing antibody titers induced by CORBEVAX vaccine against Delta and Ancestral strains were protective, indicative of vaccine effectiveness of >90% for prevention of symptomatic infections based on the Correlates of Protection assessment performed during Moderna and Astra-Zeneca vaccine Phase III studies. Safety findings revealed that CORBEVAX vaccine has excellent safety profile when tested in larger and older population.

3.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-330074

ABSTRACT

The underlying factors contributing to the evolution of SARS-CoV-2-specific T cell response during COVID-19 infection remain unidentified. To address this, we characterized innate and adaptive immune responses with metabolomic profiling longitudinally at three different time points (0-4, 7-9, and 14-16 days post-COVID-19 positivity) from young mildly symptomatic active COVID-19 patients who got infected with ancestral virus. We observed the induction of anti-RBD and SARS-CoV-2 neutralizing antibodies together with antigen-specific T cell responses as early as 0-4 days post-infection. T cell responses were largely preserved against the delta and omicron variants as compared to the ancestral strain. We determined innate immune responses at an early (days 0-4 post-COVID-19 positivity) time point of active infection in response to TLR 3/7/8 mediated activation. Interestingly, the innate immune response exhibited by the elevated levels of IL-6, IL-1β, and IL-23 correlated with a robust SARS-CoV-2-specific Th1 response at the later time point (14-16 days post covid positivity). To further understand the association of metabolic pathways induced upon active COVID-19 infection with innate and T cell response, metabolomic profiling was performed. As compared to healthy individuals, COVID-19 patients displayed a distinct metabolic signature with an enrichment of pyroglutamate, itaconate, and azelaic acid, which correlated with the SARS-CoV-2-induced innate and T cells response. Our observations reveal mechanisms and potential interventional approaches that may assist in COVID-19 therapeutics and vaccine adjuvant strategies. One Sentence Summary T cell Immune response against SARS-CoV-2 is driven by a proinflammatory innate immune response and an associated metabolic signature in young adults.

4.
EBioMedicine ; 78: 103938, 2022 Mar 15.
Article in English | MEDLINE | ID: covidwho-1739674

ABSTRACT

BACKGROUND: Rapid spread of the omicron SARS-CoV-2 variant despite extensive vaccination suggests immune escape. The neutralising ability of different vaccines alone or with natural SARS-CoV-2 infection against omicron is not well-known. METHODS: In this cross-sectional study, we tested the ability of vaccine and natural infection induced antibodies to neutralise omicron variant in a live virus neutralisation assay in four groups of individuals: (i) ChAdOx1 nCoV-19 vaccination, (ii) ChAdOx1 nCoV-19 vaccination plus prior SARS-CoV-2 infection, (iii) vaccination with inactivated virus vaccine (BBV152), and (iv) BBV152 vaccination plus prior SARS-CoV-2 infection. Primary outcome was fold-change in virus neutralisation titre against omicron compared with ancestral virus. FINDINGS: We included 80 subjects. The geometric mean titre (GMT) of the 50% focus reduction neutralisation test (FRNT50) was 380·4 (95% CI: 221·1, 654·7) against the ancestral virus with BBV152 vaccination and 379·3 (95% CI: 185·6, 775·2) with ChAdOx1 nCov-19 vaccination alone. GMT for vaccination plus infection groups were 806·1 (95% CI: 478·5, 1357·8) and 1526·2 (95% CI: 853·2, 2730·0), respectively. Against omicron variant, only 5 out of 20 in both BBV152 and ChAdOx1 nCoV-19 vaccine only groups, 6 out of 20 in BBV152 plus prior SARS-CoV-2 infection group, and 9 out of 20 in ChAdOx1 nCoV-19 plus prior SARS-CoV-2 infection group exhibited neutralisation titres above the lower limit of quantification (1:20) suggesting better neutralisation with prior infection. A reduction of 26·6 and 25·7 fold in FRNT50 titres against Omicron compared to ancestral SARS-CoV-2 strain was observed for individuals without prior SARS-CoV-2 infection vaccinated with BBV152 and ChAdOx1 nCoV-19, respectively. The corresponding reduction was 57·1 and 58·1 fold, respectively, for vaccinated individuals with prior infection. The 50% neutralisation titre against omicron demonstrated moderate correlation with serum anti-RBD IgG levels [Spearman r: 0·58 (0·41, 0·71)]. INTERPRETATION: Significant reduction in the neutralising ability of both vaccine-induced and vaccine plus infection-induced antibodies was observed for omicron variant which might explain immune escape. FUNDING: Department of Biotechnology, India; Bill & Melinda Gates Foundation, USA.

5.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-329364

ABSTRACT

Importance Both vaccination and natural infection lead to immunity and may augment mutual immune response against SARS-CoV-2. There is a need for an evidence-driven booster vaccination policy depending on durability of immune response. Objective To determine the durability of humoral immune response with varying age, vaccine type, duration, and previous natural infection at least six months after complete vaccination with ChAdOx1 nCov-19 or BBV152. Design Cross-sectional observational study conducted between November 2021 and January 2022. Setting Participants were drawn from a DBT COVID-19 Research Consortium cohort in Delhi National Capital Region, India. Participants We included 2003 individuals who had completed six months after complete vaccination: (i) vaccination with ChAdOx1 nCoV-19 and aged 18-59 years, (ii) vaccination with ChAdOx1 nCoV-19 and aged ≥60 years (iii) vaccination with BBV152 and aged 18-59 years (iv) vaccination with BBV152 and aged ≥60 years (v) vaccination with either vaccine plus SARS-CoV-2 infection referred as those having hybrid immunity. A group of 94 unvaccinated individuals was also included for comparison. Exposure Age, vaccination type, prior SARS-CoV-2 infection and duration from vaccination/infection. Main Outcome(s) and Measure(s) Humoral immune response determined by anti-RBD IgG concentrations and the presence of anti-nucleocapsid IgG. Results The serum anti-RBD IgG antibodies were detected (cut-off 24 BAU/ml) in 85% participants with a median titer of 163 (IQR 73, 403) BAU/ml. In the hybrid immunity group, 97.6% [295 (IQR 128, 687) BAU/mL] tested positive for anti-RBD IgG compared to 81.3% [139 (IQR 62, 326) BAU/ml] of only vaccinated participants [χ2 test: p <0.001]. The median anti-RBD IgG titers were higher in the ChAdOx1 nCoV-19 versus BBV152 groups. The median anti-RBD IgG titer in the anti-nucleocapsid positive participants [326 (IQR 132, 739) BAU/ml] was significantly higher than in those without anti-nucleocapsid antibodies [131 (IQR 58, 288) BAU/ml;p <0.001]. The IgG anti-RBD antibodies was present in 85% of participants beyond a median of 8 months after complete vaccination. Conclusions and Relevance Considering the wide seropositivity rates due to natural SARS-CoV-2 infection, recommendation for boosters should take into account past infections in the population. Key points Question What is the extent of waning of humoral immune response in various groups of vaccinated individuals at least six months after complete vaccination with ChAdOx1 nCov-19 or BBV152 with or without prior natural infection? Findings Cross-sectional observational study demonstrates persistence of anti-RBD IgG in 85% of participants even beyond a median of 8 months after complete vaccination. The antibody concentrations were significantly higher in those with hybrid immunity. Meaning Humoral immunity may last longer due to heterologous antigenic exposure following vaccination and natural infection emphasizing the need for contextualizing the booster policy.

6.
EuropePMC;
Preprint in English | EuropePMC | ID: ppcovidwho-327520

ABSTRACT

ABSTRACT Most adults in India have received at least one dose of COVID-19 vaccine and also been infected naturally during the pandemic. As immunization of individuals continues under this situation where the virus has attained endemicity, we assessed whether this hybrid immunity is further boosted by a single dose of BBV152, an inactivated SARS-CoV-2 vaccine, and, if these antibodies can neutralize SARS-CoV-2 delta and omicron variants. We found that natural infection during the second wave in 2021 led to generation of neutralizing antibodies against other lineages of SARS-CoV-2 including the omicron variant, albeit at a significantly lower level for the latter. A single dose of BBV152 boosted antibody titers against the delta and the omicron variants but the antibody levels remained low for the omicron variant. Boosting of antibodies showed negative correlation with baseline neutralizing antibody titers suggesting anergy of the immune system in individuals with high levels of antibodies.

7.
EuropePMC;
Preprint in English | EuropePMC | ID: ppcovidwho-327236

ABSTRACT

SARS-CoV-2 variants are emerging at frequent intervals with an ability to transmit faster and evade the immune responses. Most of Indian adults have received one or two doses of vaccination and, have also been infected naturally during the first and second waves. However, whether or not this hybrid immunity is protective against the emerging variants has not been determined. We found that a single dose of ChAdOx1 nCoV-19 vaccine in individuals with prior history of COVID-19 infection induced high levels of neutralizing antibodies which associated with protection from infection. Natural infection during the delta variant surge generated neutralizing antibodies against other lineages including the omicron variant. However, most of the subjects had undetectable levels of antibodies to neutralize omicron variant in the follow-up samples collected after six months suggesting that a large majority of people in India are at risk of infection by omicron variant due to waning antibody titers.

8.
Blood Cells Mol Dis ; 94: 102653, 2022 05.
Article in English | MEDLINE | ID: covidwho-1676413

ABSTRACT

Abnormal coagulation dynamics, including disseminated intravascular coagulopathy, pulmonary embolism, venous thromboembolism and risk of thrombosis are often associated with the severity of COVID-19. However, very little is known about the contribution of platelets in above pathogenesis. In order to decipher the pathophysiology of thrombophilia in COVID-19, we recruited severely ill patients from ICU, based on the above symptoms and higher D-dimer levels, and compared these parameters with their asymptomatic counterparts. Elevated levels of platelet-derived microparticles and platelet-leukocyte aggregates suggested the hyperactivation of platelets in ICU patients. Strikingly, platelet transcriptome analysis showed a greater association of IL-6 and TNF signalling pathways in ICU patients along with higher plasma levels of IL-6 and TNFα. In addition, upregulation of pathways like blood coagulation and hemostasis, as well as inflammation coexisted in platelets of these patients. Further, the increment of necrotic pathway and ROS-metabolic processes in platelets was suggestive of its procoagulant phenotype in ICU patients. This study suggests that higher plasma IL-6 and TNFα may trigger platelet activation and coagulation, and in turn aggravate thrombosis and hypercoagulation in severe COVID-19 patients. Therefore, the elevated IL-6 and TNFα, may serve as potential risk factors for platelet activation and thrombophilia in these patients.


Subject(s)
COVID-19 , Cell-Derived Microparticles , Thrombophilia , Blood Platelets/metabolism , COVID-19/complications , Cell-Derived Microparticles/metabolism , Cytokines/metabolism , Humans , SARS-CoV-2 , Thrombophilia/complications , Up-Regulation
9.
Am J Obstet Gynecol ; 2021 Dec 20.
Article in English | MEDLINE | ID: covidwho-1653985

ABSTRACT

BACKGROUND: Among nonpregnant individuals, diabetes mellitus and high body mass index increase the risk of COVID-19 and its severity. OBJECTIVE: This study aimed to determine whether diabetes mellitus and high body mass index are risk factors for COVID-19 in pregnancy and whether gestational diabetes mellitus is associated with COVID-19 diagnosis. STUDY DESIGN: INTERCOVID was a multinational study conducted between March 2020 and February 2021 in 43 institutions from 18 countries, enrolling 2184 pregnant women aged ≥18 years; a total of 2071 women were included in the analyses. For each woman diagnosed with COVID-19, 2 nondiagnosed women delivering or initiating antenatal care at the same institution were also enrolled. The main exposures were preexisting diabetes mellitus, high body mass index (overweight or obesity was defined as a body mass index ≥25 kg/m2), and gestational diabetes mellitus in pregnancy. The main outcome was a confirmed diagnosis of COVID-19 based on a real-time polymerase chain reaction test, antigen test, antibody test, radiological pulmonary findings, or ≥2 predefined COVID-19 symptoms at any time during pregnancy or delivery. Relationships of exposures and COVID-19 diagnosis were assessed using generalized linear models with a Poisson distribution and log link function, with robust standard errors to account for model misspecification. Furthermore, we conducted sensitivity analyses: (1) restricted to those with a real-time polymerase chain reaction test or an antigen test in the last week of pregnancy, (2) restricted to those with a real-time polymerase chain reaction test or an antigen test during the entire pregnancy, (3) generating values for missing data using multiple imputation, and (4) analyses controlling for month of enrollment. In addition, among women who were diagnosed with COVID-19, we examined whether having gestational diabetes mellitus, diabetes mellitus, or high body mass index increased the risk of having symptomatic vs asymptomatic COVID-19. RESULTS: COVID-19 was associated with preexisting diabetes mellitus (risk ratio, 1.94; 95% confidence interval, 1.55-2.42), overweight or obesity (risk ratio, 1.20; 95% confidence interval, 1.06-1.37), and gestational diabetes mellitus (risk ratio, 1.21; 95% confidence interval, 0.99-1.46). The gestational diabetes mellitus association was specifically among women requiring insulin, whether they were of normal weight (risk ratio, 1.79; 95% confidence interval, 1.06-3.01) or overweight or obese (risk ratio, 1.77; 95% confidence interval, 1.28-2.45). A somewhat stronger association with COVID-19 diagnosis was observed among women with preexisting diabetes mellitus, whether they were of normal weight (risk ratio, 1.93; 95% confidence interval, 1.18-3.17) or overweight or obese (risk ratio, 2.32; 95% confidence interval, 1.82-2.97). When the sample was restricted to those with a real-time polymerase chain reaction test or an antigen test in the week before delivery or during the entire pregnancy, including missing variables using imputation or controlling for month of enrollment, the observed associations were comparable. CONCLUSION: Diabetes mellitus and overweight or obesity were risk factors for COVID-19 diagnosis in pregnancy, and insulin-dependent gestational diabetes mellitus was associated with the disease. Therefore, it is essential that women with these comorbidities are vaccinated.

10.
Acta Medica International ; 8(2):94-99, 2021.
Article in English | ProQuest Central | ID: covidwho-1605163

ABSTRACT

Introduction: The surveillance case definitions for coronavirus disease 2019 (COVID-19) in children adapted from adult guidelines emphasized the presence of fever and/or respiratory symptoms as the criteria for suspicion and testing. The clinical course of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in Indian children is still not well described. Materials and Methods: This observational study was done at a dedicated COVID-19 tertiary care hospital of Haryana, India, between April 1, 2020 and December 31, 2020, with due approval of Institutional Ethics Committee. A total of 86 SARS-CoV-2 positive inpatient children in the age group of 1 month − 12 years were enrolled to outline the clinical course and outcome of acute illness longitudinally over initial 2 weeks of infection. Clinical management and hospital discharge policy was guided by public health authorities and prevailing scientific evidence which were updated and notified time to time as the pandemic evolved. Descriptive statistics were applied to analyze the study variables. Results: Majority children (48/86;56%) remained asymptomatic throughout 2-week surveillance period, 35 (41%) suffered mild, 2 (2%) moderate, and 1 (1%) severe disease. All children had intact survival. Comorbid condition(s) were present in five (6%) children. Among infants and the subset of children with premorbid condition(s), the proportion of children suffering symptomatic illness (88% and 80%, respectively) and moderate-severe illness (25% and 40%, respectively) was quite high. Respiratory symptoms (68%) and fever (50%) were the most common symptoms. Gastrointestinal symptoms were present in 26% symptomatic children. Fever was the only symptom in 11% children;and 16% children had only gastrointestinal symptoms without any fever or respiratory symptom(s). Conclusion: Acute SARS-CoV-2 infection in children is commonly asymptomatic, or a mild illness with not only respiratory but also non-respiratory manifestations. Thus, a high index of suspicion for SARS-CoV-2 infection is required by the treating physicians in this subgroup of population as they might play an important role in virus transmission and amplification. In case the testing is deferred among asymptomatic contacts or children with mild symptoms, they may be presumed SARS-CoV-2 infected, isolated, and managed accordingly.

11.
J Clin Virol ; 146: 105060, 2022 01.
Article in English | MEDLINE | ID: covidwho-1587311

ABSTRACT

Over 90% of the COVID-19 patients manifest mild/moderate symptoms or are asymptomatic. Although comorbidities and dysregulation of immune response have been implicated in severe COVID-19, the host factors that associate with asymptomatic or mild infections have not been characterized. We have collected serial samples from 23 hospitalized COVID-19 patients with mild symptoms and measured the kinetics of SARS-CoV-2 viral load in respiratory samples and markers of inflammation in serum samples. We monitored seroconversion during the acute phase of illness and quantitated the amount of total IgG against the receptor-binding domain of SARS-CoV-2 and estimated the virus neutralization potential of these antibodies. Viral load decreased by day 8 in all the patients but the detection of viral RNA in saliva samples did not correlate well with viral RNA detection in nasopharyngeal/oropharyngeal swab samples. 25% of the virus-positive patients had no detectable neutralizing antibodies in the serum and in other cases, the efficiency of antibodies to neutralize SARS-CoV-2 B1.1.7 strain was lower as compared to the circulating virus isolate. Decrease in viral load coincided with increase in neutralizing antibodies and interferon levels in serum. Most patients showed no increase in inflammatory cytokines such as IL-1ß or IL-6, however, elevated levels of IL-7 and other inflammatory mediators such as TNF-α and IL-8 was observed. These data suggest that most mild infections are associated with absence of inflammation coupled with an active innate immune response, T-cell activation and neutralizing antibodies.


Subject(s)
COVID-19 , Antibodies, Viral , Humans , Immunity , SARS-CoV-2 , Viral Load
12.
Lancet ; 398(10317): 2173-2184, 2021 12 11.
Article in English | MEDLINE | ID: covidwho-1586227

ABSTRACT

BACKGROUND: We report the clinical efficacy against COVID-19 infection of BBV152, a whole virion inactivated SARS-CoV-2 vaccine formulated with a toll-like receptor 7/8 agonist molecule adsorbed to alum (Algel-IMDG) in Indian adults. METHODS: We did a randomised, double-blind, placebo-controlled, multicentre, phase 3 clinical trial in 25 Indian hospitals or medical clinics to evaluate the efficacy, safety, and immunological lot consistency of BBV152. Adults (age ≥18 years) who were healthy or had stable chronic medical conditions (not an immunocompromising condition or requiring treatment with immunosuppressive therapy) were randomised 1:1 with a computer-generated randomisation scheme (stratified for the presence or absence of chronic conditions) to receive two intramuscular doses of vaccine or placebo administered 4 weeks apart. Participants, investigators, study coordinators, study-related personnel, the sponsor, and nurses who administered the vaccines were masked to treatment group allocation; an unmasked contract research organisation and a masked expert adjudication panel assessed outcomes. The primary outcome was the efficacy of the BBV152 vaccine in preventing a first occurrence of laboratory-confirmed (RT-PCR-positive) symptomatic COVID-19 (any severity), occurring at least 14 days after the second dose in the per-protocol population. We also assessed safety and reactogenicity throughout the duration of the study in all participants who had received at least one dose of vaccine or placebo. This report contains interim results (data cutoff May 17, 2021) regarding immunogenicity and safety outcomes (captured on days 0 to 56) and efficacy results with a median of 99 days for the study population. The trial was registered on the Indian Clinical Trials Registry India, CTRI/2020/11/028976, and ClinicalTrials.gov, NCT04641481 (active, not recruiting). FINDINGS: Between Nov 16, 2020, and Jan 7, 2021, we recruited 25 798 participants who were randomly assigned to receive BBV152 or placebo; 24 419 received two doses of BBV152 (n=12 221) or placebo (n=12 198). Efficacy analysis was dependent on having 130 cases of symptomatic COVID-19, which occurred when 16 973 initially seronegative participants had at least 14 days follow-up after the second dose. 24 (0·3%) cases occurred among 8471 vaccine recipients and 106 (1·2%) among 8502 placebo recipients, giving an overall estimated vaccine efficacy of 77·8% (95% CI 65·2-86·4). In the safety population (n=25 753), 5959 adverse events occurred in 3194 participants. BBV152 was well tolerated; the same proportion of participants reported adverse events in the vaccine group (1597 [12·4%] of 12 879) and placebo group (1597 [12·4%] of 12 874), with no clinically significant differences in the distributions of solicited, unsolicited, or serious adverse events between the groups, and no cases of anaphylaxis or vaccine-related deaths. INTERPRETATION: BBV152 was highly efficacious against laboratory-confirmed symptomatic COVID-19 disease in adults. Vaccination was well tolerated with no safety concerns raised in this interim analysis. FUNDING: Bharat Biotech International and Indian Council of Medical Research.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/prevention & control , Immunogenicity, Vaccine , Vaccines, Inactivated/immunology , Adjuvants, Immunologic , Adult , COVID-19 Nucleic Acid Testing , Double-Blind Method , Female , Humans , India , Male
13.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-293156

ABSTRACT

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.

14.
J Gen Virol ; 102(4)2021 04.
Article in English | MEDLINE | ID: covidwho-1393559

ABSTRACT

Reactive oxygen species (ROS) are chemically active species which are involved in maintaining cellular and signalling processes at physiological concentrations. Therefore, cellular components that regulate redox balance are likely to play a crucial role in viral life-cycle either as promoters of viral replication or with antiviral functions. Zinc is an essential micronutrient associated with anti-oxidative systems and helps in maintaining a balanced cellular redox state. Here, we show that zinc chelation leads to induction of reactive oxygen species (ROS) in epithelial cells and addition of zinc restores ROS levels to basal state. Addition of ROS (H2O2) inhibited dengue virus (DENV) infection in a dose-dependent manner indicating that oxidative stress has adverse effects on DENV infection. ROS affects early stages of DENV replication as observed by quantitation of positive and negative strand viral RNA. We observed that addition of ROS specifically affected viral titres of positive strand RNA viruses. We further demonstrate that ROS specifically altered SEC31A expression at the ER suggesting a role for SEC31A-mediated pathways in the life-cycle of positive strand RNA viruses and provides an opportunity to identify drug targets regulating oxidative stress responses for antiviral development.


Subject(s)
Dengue Virus/drug effects , Hydrogen Peroxide/pharmacology , Reactive Oxygen Species/pharmacology , Virus Replication , Zinc/pharmacology , Adolescent , Aedes , Animals , Caco-2 Cells , Child , Child, Preschool , Chlorocebus aethiops , Cricetinae , Dengue/virology , Dengue Virus/physiology , Humans , Oxidative Stress , RNA, Viral
15.
Eur J Pediatr ; 181(2): 513-527, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1351298

ABSTRACT

This observational study done during April-December 2020 at a tertiary-care hospital in Haryana (India) enrolled 152 SARS-CoV-2-exposed neonates. Among them, 150 neonates had perinatal SARS-CoV-2 exposure and 2 neonates had late postnatal exposure. Stable infant-mother dyads were roomed-in with precautions to support breastfeeding. Nasopharyngeal swabs collected from neonates were tested for SARS-CoV-2 by reverse transcriptase-polymerase chain reaction (RT-PCR) test. There was a high incidence of prematurity (23%), low birth weight (31%), intrauterine fetal distress (16%), perinatal asphyxia (6%), admission to neonatal intensive care unit (24%), and mortality (1.3%) among neonates with perinatal SARS-CoV-2 exposure. In this sub-group, 20 neonates tested positive for SARS-CoV-2 in nasopharyngeal swab sample(s). A recent official publication by the World Health Organization emphasizes that the perinatal SARS-CoV-2-exposed neonates found RT-PCR positive once in upper respiratory (non-sterile) sample must document viral persistence in another non-sterile sample for confirmation of mother-to-child virus transmission. With this approach, only one neonate was confirmed intrapartum transmission. A telephonic follow-up in discharged neonates at 1 month of age or 1 month postexposure recorded them all to be asymptomatic and doing well.Conclusion: Neonates with perinatal SARS-CoV-2 exposure constitute a high-risk group and it is not uncommon to get a positive RT-PCR report in upper respiratory sample(s) from these babies. Majority of them do not demonstrate viral persistence. Clinical outcomes are favorable in breastfed infants roomed-in with their asymptomatic-mild symptomatic SARS-CoV-2-infected mothers following appropriate safety protocols. What is Known: •Neonates with perinatal exposure suffer a high burden of morbidities and mortality. •Still, an uncertainty exists about rooming-in and breastfeeding among neonates born to SARS-CoV-2 positive mothers. What is New: •With the policy of mother-infant rooming-in and supporting breastfeeding, none of the neonate suffered clinical illness compatible with postnatal SARS-CoV-2 transmission and infection. •Around 13% perinatal exposed neonates demonstrated SARS-CoV-2 RNA in nasopharyngeal swab samples but the majority of them did not demonstrate viral persistence.


Subject(s)
COVID-19 , Infectious Disease Transmission, Vertical , Milk, Human , Animals , Female , Humans , Infant, Newborn , Infectious Disease Transmission, Vertical/prevention & control , Milk, Human/immunology , Mothers , Pregnancy , Pregnancy Complications, Infectious/diagnosis , RNA, Viral , SARS-CoV-2
17.
Am J Trop Med Hyg ; 105(1): 66-72, 2021 05 18.
Article in English | MEDLINE | ID: covidwho-1232647

ABSTRACT

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.


Subject(s)
COVID-19/blood , COVID-19/virology , SARS-CoV-2 , Adolescent , Adult , Antibodies, Viral/blood , COVID-19/epidemiology , Child , Child, Preschool , Cohort Studies , Female , Humans , Immunoglobulin G/blood , India/epidemiology , Infant , Male , Middle Aged , Prospective Studies , Risk Factors , SARS-CoV-2/immunology , Seroconversion , Young Adult
18.
Front Microbiol ; 11: 618097, 2020.
Article in English | MEDLINE | ID: covidwho-1069731

ABSTRACT

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.

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