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The Omicron variant of SARS-CoV-2 is capable of infecting unvaccinated, vaccinated and previously-infected individuals due to its ability to evade neutralization by antibodies. With multiple sub-lineages of Omicron emerging in the last 12 months, there is inadequate information on the quantitative antibody response generated upon natural infection with Omicron variant and whether these antibodies offer cross-protection against other sub-lineages of Omicron variant. In this study, we characterized the growth kinetics of Kappa, Delta and Omicron variants of SARS-CoV-2 in Calu-3 cells. Relatively higher amounts infectious virus titers, cytopathic effect and disruption of epithelial barrier functions was observed with Delta variant whereas infection with Omicron sub-lineages led to a more robust induction of interferon pathway, lower level of virus replication and mild effect on epithelial barrier. The replication kinetics of BA.1, BA.2 and BA.2.75 sub-lineages of the Omicron variant were comparable in cell culture and natural infection in a subset of individuals led to a significant increase in binding and neutralizing antibodies to the Delta variant and all the three sub-lineages of Omicron but the level of neutralizing antibodies were lowest against the BA.2.75 variant. Finally, we show that Cu 2+ , Zn 2+ and Fe 2+ salts inhibited in vitro RdRp activity but only Cu 2+ and Fe 2+ inhibited both the Delta and Omicron variants in cell culture. Thus, our results suggest that high levels of interferons induced upon infection with Omicron variant may counter virus replication and spread. Waning neutralizing antibody titers rendered subjects susceptible to infection by Omicron variants and natural Omicron infection elicits neutralizing antibodies that can cross-react with other sub-lineages of Omicron and other variants of concern.

Many adults in India have received at least one dose of COVID-19 vaccine with or without a prior history SARS-CoV-2 infection. However, there is limited information on the effect of prior immunity on antibody response upon vaccination in India. As immunization of individuals continues, we aimed to assess whether pre-existing antibodies are 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. Here we show 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 against the Omicron variant. Boosting of antibodies showed negative correlation with baseline neutralizing antibody titers. Serosurveillance studies show a heterogenous mix of the Indian population with immunity to COVID-19 due to vaccination or natural infection. Here, the authors enrol subjects representative of the general population, to assess whether pre-existing antibodies are further boosted by a single dose of an inactivated SARS-CoV-2 vaccines, BBV152.

Background: With the rapid increase in COVID-19 cases and the discovery of new viral variants within India over multiple waves, the expensive reagents and time-consuming sample pretreatment required for qPCR analysis have led to slower detection of the disease. The vast Indian population demands an inexpensive and competent sample preparation strategy for rapid detection of the disease facilitating early and efficient containment of the disease.Methods: In this study, we have surveyed the spread of COVID-19 infection over Faridabad, Haryana, India for 6 months. We also devised a simple single-step method for total RNA extraction using a single tube and compared its efficacy with the commercially available RNA isolation kits.Findings: Our findings suggest that determining Ct values for samples subjected to the One Pot RNA extraction method was as efficient as the commercially available kits but delivers a subtle advantage in a way, by minimizing the cost, labor and sample preparation time.Conclusion: This novel crude RNA extraction method is stable and capable of operating in developing countries like India for low resource settings, without the use of expensive reagents and instruments. Additionally, this method can be further adapted to pooling samples strategies owing to its high sensitivity.

Background SARS-CoV-2 infections caused mild-to-moderate illness. However, a sizable portion of infected people experience a rapid progression of hyper-inflammatory and hypoxic respiratory illness that necessitates an effective and safer remedy to combat COVID-19. Methods A total of 150 COVID-19-positive patients with no to mild symptoms, between the age groups 19–65 years were enrolled in this randomized, open-labeled three-armed clinical trial. Among them, 136 patients completed the study with RT-PCR negative reports. The patients received herbal drugs orally (Group A ( Adhatoda vasica ; AV; 500 mg; n  = 50); Group B ( Tinospora cordifolia ; TC; 500 mg; n  = 43), and Group C (AV + TC; 250 mg each; n  = 43)) for 14 days. Clinical symptoms, vital parameters, and viral clearance were taken as primary outcomes, and biochemical, hematological parameters, cytokines, and biomarkers were evaluated at three time points as secondary outcomes. Results We found that the mean viral clearance time was 13.92 days (95% confidence interval [CI] 12.85–14.99) in Group A, 13.44 days (95% confidence interval [CI] 12.14–14.74) in Group B, and 11.86 days (95% confidence interval [CI] 10.62–13.11) days in Group C. Over a period of 14 days, the mean temperature in Groups A, and B significantly decreased linearly. In Group A, during the trial period, eosinophils, and PT/INR increased significantly, while monocytes, SGOT, globulin, serum ferritin, and HIF-1α, a marker of hypoxia reduced significantly. On the other hand, in Group B hsCRP decreased at mid-treatment. Eosinophil levels increased in Group C during the treatment, while MCP-3 levels were significantly reduced. Conclusions All the patients of the three-armed interventions recovered from COVID-19 and none of them reported any adverse effects from the drugs. Group C patients (AV + TC) resulted in a quicker viral clearance as compared to the other two groups. We provide the first clinical report of AV herbal extract acting as a modifier of HIF-1α in COVID-19 patients along with a reduction in levels of ferritin, VEGF, and PT/INR as the markers of hypoxia, inflammation, and thrombosis highlighting the potential use in progression stages, whereas the TC group showed immunomodulatory effects. Trial registration Clinical Trials Database -India (ICMR-NIMS), CTRI/2020/09/028043. Registered 24th September 2020, https://www.ctri.nic.in/Clinicaltrials/pdf_generate.php?trialid=47443&EncHid=&modid=&compid=%27,%2747443det%27 Graphical Abstract

A recently emerged sub-lineage of Omicron, BA.5, together with BA.4, caused a fifth wave of coronavirus disease (COVID-19) in South Africa and subsequently emerged as a predominant strain globally due to its high transmissibility. The lethality of BA.5 infection has not been studied in an acute hACE2 transgenic (hACE2.Tg) mouse model. Here, we investigated tissue-tropism and immuno-pathology induced by BA.5 infection in hACE2.Tg mice. Our data show that intranasal infection of BA.5 in hACE2.Tg mice resulted in attenuated pulmonary infection and pathology with diminished COVID-19-induced clinical and pathological manifestations. BA.5, similar to Omicron (B.1.1.529), infection led to attenuated production of inflammatory cytokines, anti-viral response and effector T cell response as compared to the ancestral strain of SARS-CoV-2, Wuhan-Hu-1. We show that mice recovered from B.1.1.529 infection showed robust protection against BA.5 infection associated with reduced lung viral load and pathology. Together, our data provide insights as to why BA.5 infection escapes previous SARS-CoV-2 exposure induced-T cell immunity but may result in milder immuno-pathology and alleviated chances of re-infectivity in Omicron-recovered individuals. Intranasal infection of SARS-CoV-2 BA.5 in an acute hACE2 transgenic (hACE2.Tg) mouse model provides insights into BA.5 infection pathology.

Measuring SARS-CoV-2-specific T cell responses is crucial to understanding an individual’s immunity to COVID-19. However, high inter- and intra-assay variability make it difficult to define T cells as a correlate of protection against COVID-19. To address this, we performed systematic review and meta-analysis of 495 datasets from 94 original articles evaluating SARS-CoV-2-specific T cell responses using three assays – Activation Induced Marker (AIM), Intracellular Cytokine Staining (ICS), and Enzyme-Linked Immunospot (ELISPOT), and defined each assay’s quantitative range. We validated these ranges using samples from 193 SARS-CoV-2-exposed individuals. Although IFNγ ELISPOT was the preferred assay, our experimental validation suggested that it under-represented the SARS-CoV-2-specific T cell repertoire. Our data indicate that a combination of AIM and ICS or FluoroSpot assay would better represent the frequency, polyfunctionality, and compartmentalization of the antigen-specific T cell responses. Taken together, our results contribute to defining the ranges of antigen-specific T cell assays and propose a choice of assay that can be employed to better understand the cellular immune response against viral diseases.

The underlying factors contributing to the evolution of SARS-CoV-2-specific T cell responses 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 (0–3, 7–9, and 14–16 days post-COVID-19 positivity) from young, mildly symptomatic, active COVID-19 patients infected during the first wave in mid-2020. We observed that anti-RBD IgG and viral neutralization are significantly reduced against the delta variant, compared to the ancestral strain. In contrast, compared to the ancestral strain, T cell responses remain preserved against the delta and omicron variants. We determined innate immune responses during the early stage of active infection, in response to TLR 3/7/8-mediated activation in PBMCs and serum metabolomic profiling. Correlation analysis indicated PBMCs-derived proinflammatory cytokines, IL-18, IL-1β, and IL-23, and the abundance of plasma metabolites involved in arginine biosynthesis were predictive of a robust SARS-CoV-2-specific Th1 response at a later stage (two weeks after PCR positivity). These observations may contribute to designing effective vaccines and adjuvants that promote innate immune responses and metabolites to induce a long-lasting anti-SARS-CoV-2-specific T cell response.

Background: The COVID-19 pandemic prompted unprecedented vaccine development efforts against SARS-CoV-2. India, which was one of the countries most impacted by COVID-19, developed its indigenous vaccine in addition to utilizing the ones developed by other countries. While antibody levels and neutralizing antibody titres are considered initial correlates of immune protection, long-term protection from the pathogen relies on memory B and T cells and their recall responses. In this regard, global research has primarily focused on mRNA-based vaccines. The studies on immune memory response, particularly B cell memory response induced by the vaccines given to Indians, remain relatively obscure. Methods: We assessed Receptor Binding Domain-specific memory B cells in the peripheral circulation and their ability to secrete antigen-specific antibodies among Indians vaccinated with Covaxin (BBV152), Covishield (AZD1222), Corbevax (BECOV2D), and Sputnik Light, as well as unvaccinated individuals. Results: Corbevax and Sputnik Light conferred better antibody-secreting cell (ASC) responses over time compared to other groups. Conclusions: These findings contribute to our understanding of vaccine-induced immune memory in the Indian population; providing insights that could inform future vaccine strategies.

Background Due to waning immunity and emerging variants, protection following primary intramuscular Covid-19 vaccinations is decreasing, so health agencies have been proposing heterologous booster vaccinations. Here, we report immunogenicity and safety evaluation of heterologous booster vaccination with an intranasal, adenovirus vectored SARS-CoV-2 vaccine (BBV154) in healthy adults, who were previously primed with two doses of either Covaxin® or Covishield™. We compare results with use of a homologous booster vaccination combination. Methods This was a randomized, open-label phase 3 trial conducted to evaluate immunogenicity and safety of a booster dose of intranasal BBV154 vaccine or intramuscular EUA approved Covid-19 vacines in India. Healthy participants of ≥18 years age with no history of SARS-CoV-2 infection, who received two doses of Covaxin ® or Covishield™ at least 6 ± 1 months earlier were enrolled. The primary outcome was the neutralising antibody titers against wild-type virus using a plaque-reduction neutralization test (PRNT 50 ). Other outcomes measured were humoral (IgG), mucosal (IgA) and cell mediated responses. The protocol was registered #NCT05567471 and approved by National Regulatory Authority (India) #CTRI/2022/02/039992. Results In this phase 3 trial, a total of 875 participants were randomized into 5 Groups in a ratio of 2:1:2:1:1 to receive either booster dose of BBV154 or Covaxin or Covishield. Based on per-protocol population, at Day 56, neutralization antibody titres were 564.1 (479·1, 664·1), 578.1 (436·9, 764·9), 655.5 (533·3, 805·8), 625.4 (474·7, 824·0), 650.1 (519·7, 813·1) for Group 1 to 5 respectively. This study was conducted, whilst the Omicron variant was prevalent. There were varying levels of severity of infection across different study sites with varied baseline antibody titers. Consequently, the average neutralization (PRNT 50 ) antibody titers are similar across all Groups on day 56 and exhibited large differences within the Group, depending on the study site. All booster vaccinations are well tolerated and reported no serious adverse events; in particular, study participants boosted with BBV154 had significantly fewer solicited local adverse events than those primed and boosted with Covishield. Conclusions These findings demonstrate that impact of booster across different cohorts is governed by infection status of the individual and geographical diversity, thus necessitating large cohorts, well distributed studies before Covid-19 booster effects are interpreted. Plain language summary We undertook a clinical trial to compare the booster dose effect of two currently used COVID vaccines (Covaxin® or Covishield™), with a newly developed intranasal COVID vaccine. The booster dose was given 6 months after two initial doses of COVID vaccines. We measured levels of antibodies, which are proteins that help the body to identify and destroy the SARS-CoV-2 virus following vaccination. The effect on antibodies was similar for all vaccination groups, whilst with the new vaccine there were fewer adverse events. This data, combined with the ease of administration, confirms that our new intranasal vaccine is safe and effective and can therefore be included in vaccination programs for COVID-19. Venkateshwar et al., explored the effect of Heterologous intranasal iNCOVACC® vaccination as a booster to two-dose intramuscular Covid-19 vaccinations (either by Covishield or Covaxin) in a controlled, randomised, open-label phase 3 clinical trial. This study also aimed to compare these results with homologous booster vaccinations by Covishield or Covaxin.

Micro minerals have a great impact on animal's reproductive physiology and its imbalance causes various problems leading to lowered reproductive efficiency and resultant monetary loss to the dairy industry. Adequate micro minerals supplementation is required as most of the roughages, greens, concentrates and even most of commercial feeds available to Indian market are deficient in trace mineral elements. Often correcting an imbalance in mineral levels can sole a nagging problem by improving reproductive performance and health with little additional cost. As terrain and agro climatic area of India is quite diverse, so one therapeutic treatment may not be suitable for other regions. Hence there is a need to map of the various nutrient status in soil, fodder and animal, so that accordingly an area specific mineral may me supplemented.