ABSTRACT
The immunity acquired after natural infection or vaccinations against SARS-CoV-2 tend to wane with time. Vaccine effectiveness also varies with the variant of infection. Here, we compared the protective efficacy of COVAXIN following 2 and 3 dose immunizations against the Delta variant and also studied the efficacy of COVAXIN against Omicron variants in a Syrian hamster model. The antibody response, clinical observations, viral load reduction and lung disease severity after virus challenge were studied. Protective response in terms of the reduction in lung viral load and lung lesions were observed in both the 2 dose as well as 3 doses COVAXIN immunized group when compared to placebo group following the Delta variant challenge. In spite of the comparable neutralizing antibody response against the homologous vaccine strain in both the 2 dose and 3 dose immunized groups, considerable reduction in the lung disease severity was observed in the 3 dose immunized group post Delta variant challenge indicating the involvement of cell mediated immune response also in protection. In the vaccine efficacy study against the Omicron variants i.e., BA.1 and BA.2, lesser virus shedding, lung viral load and lung disease severity were observed in the immunized groups in comparison to the placebo groups. The present study shows that administration of COVAXIN booster dose will enhance the vaccine effectiveness against the Delta variant infection and give protection against the Omicron variants BA.1.1 and BA.2.
Subject(s)
Lung DiseasesABSTRACT
SARS-CoV-2 Omicron variant is rampantly spreading across the globe. Animal models are useful in understanding the disease characteristics as well as properties of emerging SARS-CoV-2 variants. We assessed the pathogenicity and immune response generated by BA.1 sub-lineage of SARS-CoV-2 Omicron variant with R346K mutation in 5 to 6-week old Syrian hamsters. Virus shedding, organ viral load, lung disease and immune response generated were sequentially assessed. The disease characteristics of Omicron were found to be similar to that of other SARS-CoV-2 variants of concerns in hamsters like high viral replication in the respiratory tract and interstitial pneumonia. The infected hamsters demonstrated lesser body weight gain in comparison to the uninfected control hamsters. Viral RNA could be detected in nasal washes and respiratory organs (nasal turbinate, trachea, bronchi and lungs) till 10 and 14 days respectively. The clearance of the virus was observed from nasal washes and lungs by day 7. Neutralizing antibody response against Omicron variant was detected from day 5 with rising antibody titers till 14 days. However, the cross-neutralization titre of the sera against other variants showed severe reduction ie., 7 fold reduction against Alpha and no titers against B.1, Beta and Delta. This preliminary data shows that Omicron variant infection can produce moderate to severe lung disease and the neutralizing antibodies produced in response to Omicron variant infection shows poor neutralizing ability against other co-circulating SARS-CoV-2 variants like Delta which necessitates caution as it may lead to increased cases of reinfection.
Subject(s)
Weight Gain , Lung Diseases , Lung Diseases, InterstitialABSTRACT
Background: We report here a Nipah virus (NiV) outbreak in Kozhikode district of Kerala state, India which had caused fatal encephalitis in an adolescent male and the outbreak response which led to the successful containment of the disease and the related investigations. Methods: Quantitative real-time RT-PCR, ELISA based antibody detection and whole genome sequencing were performed to confirm the Nipah virus infection. Contacts of the index case were traced and isolated based on risk categorization. Bats from the areas near the epicentre of the outbreak were sampled for throat swabs, rectal swabs and blood samples for Nipah virus screening by real time RT-PCR and anti-Nipah virus bat IgG ELISA. Plaque reduction neutralization test was performed for the detection of neutralizing antibodies. Results: Nipah viral RNA and anti-NiV IgG antibodies were detected in the serum of the index case. Rapid establishment of an onsite NiV diagnostic facility and contact tracing helped in quick containment of the outbreak. NiV sequences retrieved from the clinical specimen of the index case formed a sub-cluster with the earlier reported Nipah I genotype sequences from India with more than 95% similarity. Anti-NiV IgG positivity could be detected in 21% of Pteropus medius and 37.73% of Rousettus leschenaultia. Neutralizing antibodies against NiV could be detected in P.medius. Conclusions: Stringent surveillance and awareness campaigns needs to be implemented in the area to reduce human-bat interactions and minimize spill over events which can lead to sporadic outbreaks of NiV.
Subject(s)
COVID-19 , Tumor Virus Infections , EncephalitisABSTRACT
Background: The recent emergence of new SARS-CoV-2 lineage B.1.617 in India has been associated with a surge in the number of daily infections. This variant has combination of specific mutations L452R, E484Q and P681R reported to possibly enhance the transmissibility with likelihood of escaping the immunity. We investigated the viral load and pathogenic potential of B.1.617.1 in Syrian golden hamsters. Methods: Two groups of Syrian golden hamsters (9 each) were inoculated intranasally with SARS CoV-2 isolates, B.1 (D614G) and B.1.617.1 respectively. The animals were monitored daily for the clinical signs and body weight. The necropsy of three hamsters each was performed on 3, 5- and 7-days post-infection (DPI). Throat swab (TS), nasal wash (NW) and organ samples (lungs, nasal turbinate, trachea) were collected and screened using SARS-CoV-2 specific Real-time RT-PCR. Results: The hamsters infected with B.1.617.1 demonstrated increased body weight loss compared to B.1 variant. The highest viral load was observed in nasal turbinate and lung specimens of animals infected with B.1.167.1 on 3 DPI. Neutralizing antibody (NAb) and IgG response in hamsters of both the groups were observed from 5 and 7 DPI respectively. However, higher neutralizing antibody titers were observed against B.1.167.1. Gross pathology showed pronounced lung lesions and hemorrhage with B.1.671 compared to B.1. Conclusions: B.1617.1 and B.1 variant varied greatly in their infectiousness, pathogenesis in hamster model. This study demonstrates higher pathogenicity in hamsters evident with reduced body weight, higher viral load in lungs and pronounced lung lesions as compared to B.1 variant.
Subject(s)
Hemorrhage , Lung Diseases , Tracheomalacia , Weight LossABSTRACT
The emergence of SARS-CoV-2 variants has posed a serious challenge to public health system and vaccination programs across the globe. We have studied the pathogenicity and virus shedding pattern of the SARS-CoV-2 VOC 202012/01 and compared with D614G variant in Syrian hamsters. VOC 202012/01 could produce disease in hamsters characterized by body weight loss and respiratory tract tropism but mild lung pathology. Further, we also documented that neutralizing antibodies developed against VOC 202012/01 could equally neutralize D614G variant. Higher load of VOC 202012/01 in the nasal wash specimens was observed during the first week of infection outcompeting the D614G variant. The findings suggest increased fitness of VOC 202012/01 to the upper respiratory tract which could lead to higher transmission. Further investigations are needed to understand the transmissibility of new variants.
Subject(s)
Weight Loss , Respiratory Tract DiseasesABSTRACT
Vaccines remain the key protective measure to achieve herd immunity to control the disease burden and stop COVID-19 pandemic. We have developed and assessed the immunogenicity and protective efficacy of two formulations (1mg and 2mg) of ZyCoV-D (a plasmid DNA based vaccine candidates) administered through Needle Free Injection System (NFIS) and syringe-needle (intradermal) in rhesus macaques with three dose vaccine regimens. The vaccine candidate 2mg dose administered using Needle Free Injection System (NFIS) elicited a significant immune response with development of SARS-CoV-2 S1 spike region specific IgG and neutralizing antibody (NAb) titers during the immunization phase and significant enhancement in the levels after the virus challenge. In 2 mg NFIS group the IgG and NAb titers were maintained and showed gradual rise during the immunization period (15 weeks) and till 2 weeks after the virus challenge. It also conferred better protection to macaques evident by the viral clearance from nasal swab, throat swab and bronchoalveolar lavage fluid specimens in comparison with macaques from other immunized groups. In contrast, the animals from placebo group developed high levels of viremia and lung disease following the virus challenge. Besides this, the vaccine candidate also induced increase lymphocyte proliferation and cytokines response (IL-6, IL-5).The administration of the vaccine candidate with NFIS generated a better immunogenicity response in comparison to syringe-needle (intradermal route). The study demonstrated immunogenicity and protective efficacy of the vaccine candidate, ZyCoV-D in rhesus macaques.
Subject(s)
COVID-19ABSTRACT
Innovative strategies are required to manage COVID-19 in the communities. Back to Roots was a collaborative, community-based pilot intervention project in the British Asian community. To assess the efficacy and safety of Ayurveda intervention in relieving symptoms of mild-to-moderate COVID-19, a community based participatory research framework was used. Prospectively 28 patients were enrolled with confirmed COVID-19 clinical stages of mild-to-moderate COVID-19, symptomatic, and between 20 to 70{square}years of age. Routine management was followed by all patients managing at home, additionally patents taking Ayurveda intervention for 14 consecutive days. The efficacy and safety of Ayurveda intervention were evaluated. There were suggestions of Ayurvedas advantage in improved symptoms relief, clinical recovery in 7 days. However, a control group was not included but data triangulations from separate usual care found the difference statistically significant. Ayurveda intervention may potentially have a beneficial effect on patients with COVID{square}19, especially for those with mild to moderate symptoms. A further definitive large{square}scale clinical trial is necessary.
Subject(s)
COVID-19ABSTRACT
Background: Guduchi Ghan Vati (aqueous extract of Tinospora cordifolia) is an essential herbal plant in Indian traditional medicine (Ayurveda) that is well documented as an immunomodulator and antimicrobial agent. A recent in silico study found the therapeutic efficacy of Guduchi against SARS-CoV-2. Based on available evidence, we conducted a feasibility study of the safety and efficacy of Guduchi Ghan Vati in asymptomatic patients with covid-19. Patients and methods: An open label, feasibility trial was conducted on 46 patients in the hospital setting. A single-arm study with no control group and blinding was executed in Jodhpur, Rajasthan, India. All patients orally received 2 tablets (1000 mg) twice daily for 2 weeks. Clinical parameters were collected at baseline, day 3, day 7 and day 14. Patients were continuously monitored for side effects and adverse reactions during the study period. . Results: Out of 46 asymptomatic patients included in the study, 40 completed the 14-day follow-up period. None developed any Covid-19 symptoms after admission to the hospital. On day 3 post-treatment, viral clearance was reported in 16 (32.5%) patients. By the end of D-7, 38 (95%) patients had viral load disappearance. Follow-up at D-14 showed that all participants tested negative. Conclusion: In adult patients with asymptomatic Covid-19, Gudhuchi Ghan Vati could be effective. Randomized controlled trials with larger sample sizes in patients with Covid-19 are urgently needed to confirm the definite benefit with Ayurveda.
Subject(s)
COVID-19ABSTRACT
The availability of a safe and effective vaccine would be the eventual measure to deal with SARS-CoV-2 threat. Here, we have developed and assessed the immunogenicity and protective efficacy of an inactivated SARS-CoV-2 vaccine (BBV152) in hamsters. Three dose vaccination regime with three formulations of BBV152 induced significant titres of SARS-CoV-2 specific IgG and neutralizing antibodies. The formulation with imidazoquinoline adsorbed on alum adjuvant remarkably generated a quick and robust immune response. Th1 biased immune response was demonstrated by the detection of IgG2 antibodies. Post-SARS-CoV-2 infection, vaccinated hamsters did not show any histopathological changes in the lungs. The protection of the hamsters was evident by the rapid clearance of the virus from lower respiratory tract, reduced virus load in upper respiratory tract, absence of lung pathology and robust humoral immune response. These findings confirm the immunogenic potential of BBV152 and further protection of hamsters challenged with SARS-CoV-2.
Subject(s)
COVID-19ABSTRACT
The COVID-19 pandemic is a global health crisis that has severely affected mankind and posed a great challenge to the public health system of affected countries. The availability of a safe and effective vaccine is the need of the hour to overcome this crisis. Here, we have developed and assessed the protective efficacy and immunogenicity of an inactivated SARS-CoV-2 vaccine (BBV152) in rhesus macaques (Macaca mulata). Twenty macaques were divided into four groups of five animals each. One group was administered a placebo while three groups were immunized with three different vaccine candidates at 0 and 14 days. All the macaques were challenged with SARS-CoV-2 fourteen days after the second dose. The protective response was observed with increasing SARS-CoV-2 specific IgG and neutralizing antibody titers from 3rd-week post-immunization. Viral clearance was observed from bronchoalveolar lavage fluid, nasal swab, throat swab, and lung tissues at 7 days post-infection in the vaccinated groups. No evidence of pneumonia was observed by histopathological examination in vaccinated groups, unlike the placebo group which showed features of interstitial pneumonia and localization of viral antigen in the alveolar epithelium and macrophages by immunohistochemistry. Data from this study substantiate the immunogenicity of the vaccine candidates and BBV152 is being evaluated in Phase I clinical trials in India (NCT04471519).
Subject(s)
COVID-19ABSTRACT
Globally the devastating consequence of COVID-19 or Severe Acute Respiratory Syndrome-Coronavirus (SARS-CoV-2) has posed danger on the life of living beings. Doctors and scientists throughout the world are working day and night to combat the proliferation or transmission of this deadly disease in terms of technology, finances, data repositories, protective equipment, and many other services. Rapid and efficient detection of COVID-19 reduces the rate of spreading this deadly disease and early treatment improve the recovery rate. In this paper, we proposed a new framework to exploit powerful features extracted from the autoencoder and Gray Level Co-occurence Matrix (GLCM), combined with random forest algorithm for the efficient and fast detection of COVID-19 using computed tomographic images. The model's performance is evident from its 97.78% accuracy, 96.78% recall, and 98.77% specificity.
Subject(s)
COVID-19 , Severe Acute Respiratory SyndromeABSTRACT
Background Coronavirus disease 2019 (Covid-19) has been declared global emergency with immediate safety, preventative and curative measures to control the spread of virus. Confirmed cases are treated with clinical management as they are diagnosed but so far, there is no effective treatment or vaccine yet for Covid-19. Ayurveda has been recommended by preventative and clinical management guidelines in India and several clinical trials are ongoing. But there is no study to assess impact of Ayurveda on Covid-19. Methods Objective of present study was to evaluate the clinical outcome in Covid-19 confirmed asymptomatic to mild symptomatic patients who had received Ayurveda and compare with control (who has not received Ayurveda or any support therapy). Patients having Ayurveda intervention (Guduchi Ghan Vati-extract of Tinospora cordifolia) were included from Jodhpur Covid Care Centre and non-recipients were taken from Jaipur Covid Care Centre between May 15 to June 15, 2020. Total 91 patients, who were asymptomatic at the time of hospital admission and between 18 -75 years of age, were included in the study to analyse retrospectively. Results In control group, 11.7% developed mild symptoms after average 1.8 days and none in Ayurveda group reported any symptoms. Significant difference was reported between the group of patients taking Guduchi Ghan Vati (n=40) and patients in standard care (n=51) in terms of virologic clearance at day-7 (97.5% vs 15.6% respectively; p=0.000), at day 14 (100% vs 82.3%) days to stay in hospital ( 6.4 vs 12.8 respectively; p< 0.0001) . Conclusion Results of the study suggest that Guduchi Ghan Vati, a common and widely used Ayurveda preparation, could benefit treating asymptomatic Covid-19 patients. Larger, randomised controlled Trials are required to confirm the findings. Keywords: Ayurveda, Guduchi Ghan