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Since May 2022, Monkeypox, a zoonotic Orthopox DNA virus was reported in more than 102 countries indicating expansion of its geographic range. We analyzed the complete genomes sequences of Monkeypox cases from Kerala (n=5 travelled from UAE) and Delhi (n=5 no travel history), India confirmed during July to August 2022. All the retrieved MPXV sequences from India covering 90 to 99% genome belong to A.2 lineage of clade IIb. The A.2 MPXV lineage divided in three sub clusters; first cluster Kerala n=5, Delhi n=2 aligned with the USA-2022 ON674051.1; while second of Delhi n=3 aligned with USA-2022 ON675438.1 and third consists of the UK, USA and Thailand. Recent update in MPXV lineage designated all the five sequences from Kerala as A.2.1. In addition to known 16 single nucleotide polymorphisms (SNPs) along with 13 APOBEC3 cytosine deaminase activity determined specific lineage defining mutations in A.2 lineage, 25 additional APOBEC3 mutations were found in 10 reported sequences. The study emphasizes need of enhancing genomic surveillance to understand the mutation and its linkage.
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We have investigated six COVID recovered cases with two doses of Covishield vaccination followed by reinfection. The primary SARS-CoV-2 infection found to occur with B.1 and reinfection with Omicron BA.1 and BA.2 variants. The genomic characterization and duration between two infections confirms these cases as SARS-CoV-2 reinfection. The mutation analysis of the reinfection cases correlated with immune evasion potential of BA.1 and BA.2 sub lineages. The immune response determined at different time intervals demonstrated boost post two dose vaccination, decline in pre-reinfection sera post 7 months and rise post reinfection. Apparently, these cases suffered from SARS-CoV-2 reinfection with the declined hybrid immunity acquired from primary infection and two dose covishield vaccination. This suggests the need for booster dose of vaccination. Besides this, multiple non-pharmaceutical interventions should be used to cope up with SARS-CoV-2 infection.
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The recent emergence of highly mutated SARS-CoV-2 Omicron variant has debilitating effect on public health system of the affected countries worldwide. Currently India is facing third wave of COVID-19 pandemic and going through a severe crisis. Within short span of time, the variant has shown high transmissibility and capability of evading the immune response generated against natural infection and vaccination. The immune escape potential of Omicron is a serious concern and further needs to be explored. In the present study, we have assessed the IgG and neutralizing antibody (NAb) response in breakthrough individuals vaccinated with two doses ChAdOx1 nCoV-19 vaccine (n=25), breakthrough individuals vaccinated with two doses of BNT162b2 mRNA vaccine (n=8) and unvaccinated individuals (n=6). All these individuals were infected with Omicron variant. The IgG antibody activity in the sera of the ChAdOx1 nCoV-19 and BNT162b2 mRNA breakthrough individuals was comparable with S1-RBD, while it was lesser in BNT162b2 mRNA breakthrough individuals with N protein and inactivated whole antigen IgG ELISA. BNT162b2 mRNA breakthrough individuals showed moderate reduction in NAb GMTs compared to ChAdOx1 nCoV-19 against Alpha, Beta and Delta. However, 3-fold higher reduction was observed with omicron variant in BNT162b2 mRNA than ChAdOx1 nCoV-19. Apparently, Alpha variant was modestly resistant to the sera of unvaccinated individuals than Beta, Delta and Omicron. Our study demonstrated substantial immune response in the individuals infected with Omicron. The neutralizing antibodies could effectively neutralize the Omicron and other VOCs including the most prevalent Delta variant.
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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.
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Due to failure of virus isolation of Omicron variant in Vero CCL-81 from the clinical specimens of COVID-19 cases, we infected Syrian hamsters and then passage into Vero CCL-81 cells. The Omicron sequences were studied to assess if hamster could incorporate any mutation to changes its susceptibility. L212C mutation, Tyrosine 69 deletion, and C25000T nucleotide change in spike gene and absence of V17I mutation in E gene was observed in sequences of hamster passage unlike human clinical specimen and Vero CCL-81 passages. No change was observed in the furin cleavage site in any of the specimen sequence which suggests usefulness of these isolates in future studies.
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BackgroundWe 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. MethodsQuantitative 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 epicenter 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. ResultsNipah 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. ConclusionsStringent 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.
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The emergence of SARS-CoV-2 Delta variant and its derivatives has created grave public health problem worldwide. The high transmissibility associated with this variant has led to daily increase in the number of SARS-CoV-2 infections. Delta variant has slowly dominated the other variants of concern. Subsequently, Delta has further mutated to Delta AY.1 to Delta AY.126. Of these, Delta AY.1 has been reported from several countries including India and considered to be highly infectious and probable escape mutant. Considering the possible immune escape, we had already evaluated the efficacy of the BBV152 against Delta and Delta AY.1 variants. Here, we have evaluated the neutralizing potential of sera of COVID-19 naive vaccinees (CNV) immunized with two doses of vaccine, COVID-19 recovered cases immunized with two doses of vaccine (CRV) and breakthrough infections (BTI) post immunization with two doses of vaccine against Delta, Delta AY.1 and B.1.617.3 using 50% plaque reduction neutralization test (PRNT50). Our study observed low NAb titer in CNV group against all the variants compared to CRV and BTI groups. Delta variant has shown highest reduction of 27.3-fold in NAb titer among CNV group compared to other groups and variants. Anti-S1-RBD IgG immune response among all the groups was also substantiated with NAb response. Compromised neutralization was observed against Delta and Delta AY.1 compared B.1 in all three groups. However, it provided protection against severity of the disease and fatality.
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The recent emergence of B.1.617 lineage has created grave public health problem in India. The lineage further mutated to generate sub-lineages B.1.617.1 (Kappa), B.1.617.2 (Delta), B.1.617.3. Apparently, the Delta variant has slowly dominated the other variants including B.1.617.1 (Kappa), B.1.617.2 (Delta), B.1.617.3. With this, World Health Organization has described this sub-lineage as variant of concern. The high transmissibility associated with Delta variant has led to second wave of pandemic in India which affected millions of people. Besides this, variant of concerns has been reported to show lower neutralization to several approved vaccines. This has led to breakthrough infections after completion of vaccination regimen. There is limited information available on the duration of protective immune response post-infection, vaccination or breakthrough infection with SARS-CoV-2. In this study, we have evaluated immune response in sera of the Covishield vaccinated individuals belonging to category: I. one dose vaccinated, II. two doses vaccinated, III. COVID-19 recovered plus one dose vaccinated, IV. COVID-19 recovered plus two doses vaccinated and V. breakthrough COVID-19 cases. The findings of the study demonstrated that the breakthrough cases and the COVID-19 recovered individuals with one or two dose of vaccine had relatively higher protection against Delta variant in comparison to the participants who were administered either one or two doses of Covishield. Prior vaccination results in less severe disease against subsequent infection provide evidence that both humoral and cellular immune response play an important role in protection.
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Recently, multiple SARS-CoV-2 variants have been detected across the globe. The recent emergence of B.1.617 lineage has created serious public health problem in India. The high transmissibility was observed with this lineage which has led to daily increase in the number of SARS-CoV-2 infections. Apparently, the sub-lineage B.1.617.2 has slowly dominated the other variants including B1617.1, B.617.3 and B.1.1.7. With this, World Health Organization has described B.1.617.2 as variant of concern. Besides this, variant of concern B.1.351 has been also reported from India, known to showreducedefficacyfor many approved vaccines. With the increasing threat of the SARS-CoV-2 variants, it is imperative to assess the efficacy of the currently available vaccines against these variants. Here, we have evaluated the neutralization potential of sera collected from COVID-19 recovered cases (n=20) and vaccinees with two doses of BBV152 (n=17) against B.1.351 and B.1.617.2 compared to the prototype B.1 (D614G) variant.The finding of the study demonstrated a reduction in neutralization titers with sera of COVID-19 recovered cases(3.3-fold and 4.6-fold) and BBV152 vaccinees (3. 0 and 2.7 fold) against B.1.351 and B.1.617.2 respectively.Although, there is reduction in neutralization titer, the whole-virion inactivated SARS-CoV-2 vaccine (BBV152) demonstrates protective response against VOC B.1351 and B.1.617.2.
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Covishield comprises the larger proportion in the vaccination program in India. Hence, it is of utmost importance to understand neutralizing capability of vaccine against the B.1.617.1 variant which is considered to responsible for surge of the cases in India. The neutralizing-antibody (NAb) titer against B.1.167.1 and prototype B.1 variant (D614G) was determined of the vaccine sera (4 weeks after second dose) of COVID-19 naive subjects (n=43) and COVID-19 recovered subjects (n=18). The results demonstrated that sera of COVID-19 recovered subjects (n=18) who received two doses of Covishield have higher NAb response compared to the COVID-19 naive with a significant difference (p<0.0001) in NAb titer against B.1 and B.1.617.1 In-spite of reduction in the neutralizing titer against B.1.617.1 variant; Covishield vaccine-induced antibodies are likely to be protective to limit the severity and mortality of the disease in the vaccinated individuals.
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BackgroundThe 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. MethodsTwo 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. ResultsThe 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. ConclusionsB.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. SummaryB.1.617.1 is the new SARS-CoV-2 lineage that emerged in India. Maximal body weight loss and higher viral load in hamsters infected with B.1.617.1. It caused pronounced lung lesions in hamsters compared to B.1 variant which demonstrates the pathogenic potential of B.1.617.1.
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The drastic rise in the number of cases in Maharashtra, India has created a matter of concern for public health experts. Twelve isolates of VUI lineage B.1.617 were propagated in VeroCCL81 cells and characterized. Convalescent sera of the COVID-19 cases and recipients of BBV152 (Covaxin) were able to neutralize VUI B.1.617.
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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. One-Sentence SummarySARS-CoV-2 VOC 202012/01 infected hamsters demonstrated high viral RNA shedding through the nasal secretions and significant body weight loss with mild lung pathology compared to the D614G variant.
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Ticks are distributed worldwide and can harbour and transmit a range of pathogenicmicroorganisms that affect livestock and humans. Most tick-borne diseases arecaused by tick-borne viruses. Two major tick-borne virus zoonotic diseases,Kyasanur forest disease (KFD) and Crimean–Congo haemorrhagic fever (CCHF),are notifiable in India and are associated with high mortality rates. KFD virus wasfirst identified in 1957 in Karnataka state; the tick Haemaphysalis spinigera is themain vector. During 2012–2013, cases were reported from previously unaffectedareas in Karnataka, and newer areas of Kerala and Tamil Nadu states. Thesereports may be the result of improved active surveillance or may reflect alteredvirus transmission because of environmental change. CCHF is distributed in Asia,Africa and some part of Europe; Hyalomma spp. ticks are the main vectors. Theexistence of CCHF in India was first confirmed in 2011 in Gujarat state. In 2013, anon-nosocomial CCHF outbreak in Amreli district, as well as positive tick, animaland human samples in various areas of Gujarat state, suggested that the virus iswidespread in Gujarat state, India. The emergence of KFD and CCHF in variousIndian states emphasizes the need for nationwide surveillance among animalsand humans. There is a need for improved diagnostic facilities, more containmentlaboratories, better public awareness, and implementation of thorough tick controlin affected areas during epidemics.
