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ObjectiveThe second round of the serial cross-sectional sentinel-based population survey to assess active infection, seroprevalence, and their evolution in the general population across Karnataka was conducted. Additionally, a longitudinal study among participants identified as COVID-19 positive in the first survey round was conducted to assess the clinical sensitivity of the testing kit used. MethodsThe cross-sectional study of 41,228 participants across 290 healthcare facilities in all 30 districts of Karnataka was done among three groups of participants (low, moderate, and high-risk). Consenting participants were subjected to real-time reverse transcription-polymerase chain reaction (RT-PCR) testing, and antibody (IgG) testing. ResultsOverall weighted adjusted seroprevalence of IgG was 15.6% (95% CI: 14.9-16.3), crude IgG prevalence was 15.0% and crude active prevalence was 0.5%. Statewide infection fatality rate (IFR) was estimated as 0.11%, and COVID-19 burden estimated between 26.1 to 37.7% (at 90% confidence). Clinical sensitivity of the IgG ELISA test kit was estimated as [≥]38.9%. ConclusionThe sentinel-based population survey helped identify districts that needed better testing, reporting, and clinical management. The state was far from attaining natural immunity during the survey and hence must step up vaccination coverage and enforce public health measures to prevent the spread of COVD-19.
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As the pandemic of COVID-19 caused by the coronavirus SARS-CoV-2 continues, the selection of genomic variants which can influence how the pandemic progresses is of growing concern. Of particular concern, are those variants that carry mutations/amino acid changes conferring higher transmission, more severe disease, re-infection, and immune escape. These can broadly be classified as Variants of Concern (VOCs). VOCs have been reported from several parts of the world- UK (lineage B.1.1.7), South Africa (lineage B.1.351) and, Brazil (lineage P.1/B.1.1.28). The conditions that contribute to the emergence of VOCs are not well understood. International travel remains an important means of spread. To track importation, spread, and the emergence of variants locally; we sequenced whole genomes of SARS-CoV-2 from international travellers (n=75) entering Karnataka, a state in South India, between Dec 22, 2020- Jan 31, 2021, and from positive cases in the city of Bengaluru (n=108), between Nov 22, 2020- Jan 22, 2021. The resulting 176 SARS-CoV-2 genomes could be classified into 34 lineages, that were either imported (73/176) or circulating (103/176) in this time period. The lineage B.1.1.7 (a.k.a the UK variant) was the major lineage imported into the state (24/73, 32.9%), followed by B.1.36 (20/73, 27.4%) and B.1 (14/73, 19.2%). We identified B.1.36 (45/103; 43.7%), B.1 (26/103; 25.2%), B.1.1.74 (5/103; 4.9%) and B.1.468 (4/103; 3.9%) as the major variants circulating in Bengaluru city. A distinct clade within the B.1.36 lineage was associated with a local outbreak. Analysis of the complete genomes predicted multiple amino acid replacements in the Spike protein. In total, we identified nine amino acid changes (singly or in pairs) in the Receptor Binding Domain of the Spike protein. Of these, the amino acid replacement N440K was found in 37/65 (56.92%) sequences in the B.1.36 lineage. The E484K amino acid change which is present in both VOCs, B.1.351 and P.1/B.1.1.28, was found in a single circulating virus in the B.1.36 lineage. This study highlights the introduction of VOCs by travel and the local circulation of viruses with amino acid replacements in the Spike protein. These were spread across lineages, suggesting that multiple paths can lead to the emergence of VOCs, this, in turn, highlights the need to sequence and limit outbreaks of SARS-CoV-2 locally. Our data support the use of concentrated and continued genomic surveillance of SARS-CoV-2 to direct public health measures, suggest revisions to vaccines, and serve as an early warning system to prepare for a surge in COVID-19 cases.
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BackgroundGlobally, the routinely used case-based reporting and IgG serosurveys underestimate the actual prevalence of COVID-19. Simultaneous estimation of IgG antibodies and active SARS-CoV-2 markers can provide a more accurate estimation. MethodsA cross-sectional survey of 16416 people covering all risk groups was done between 3-16 September 2020 using the state of Karnatakas infrastructure of 290 hospitals across all 30 districts. All participants were subjected to simultaneous detection of SARS-CoV-2 IgG using a commercial ELISA kit, SARS-CoV-2 antigen using a rapid antigen detection test (RAT), and reverse transcription-polymerase chain reaction (RT-PCR) for RNA detection. Maximum-likelihood estimation was used for joint estimation of the adjusted IgG, active, and total prevalence, while multinomial regression identified predictors. FindingsThe overall adjusted prevalence of COVID-19 in Karnataka was 27 {middle dot}3% (95% CI: 25 {middle dot}7-28 {middle dot}9), including IgG 16 {middle dot}4% (95% CI: 15 {middle dot}1 - 17 {middle dot}7) and active infection 12 {middle dot}7% (95% CI: 11 {middle dot}5-13 {middle dot}9). The case-to-infection ratio was 1:40, and the infection fatality rate was 0 {middle dot}05%. Influenza-like symptoms or contact with a COVID-19 positive patient are good predictors of active infection. The RAT kits had higher sensitivity (68%) in symptomatic participants compared to 47% in asymptomatic. InterpretationThis is the first comprehensive survey providing accurate estimates of the COVID-19 burden anywhere in the world. Further, our findings provide a reasonable approximation of population immunity threshold levels. Using the RAT kits and following the syndromic approach can be useful in screening and monitoring COVID-19. Leveraging existing surveillance platforms, coupled with appropriate methods and sampling framework, renders our model replicable in other settings.
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Background: In this report, we describe the epidemiology of SARS-CoV-2 infection, specifically examining how the symptomatic persons drove the transmission in the state of Karnataka, India, during the lockdown phase. Methods: The study included all the cases reported from March 8 to May 31, 2020 in the state. Any person with history of international or domestic travel from high burden states, those presenting with Influenza-like or Severe Acute Respiratory Illness and high-risk contacts of COVID19 cases, who were SARS-CoV-2 RT-PCR positive were included. Detailed analysis based on contact tracing data available from line-list of the state surveillance unit was performed using cluster analysis software package. Findings: Amongst the 3404 COVID-19 positive cases, 3096 (91%) were asymptomatic while 308 (9%) were symptomatic. Majority of the asymptomatic cases were in the age range of 16-50 years while symptomatic cases were between 31-65 years. Most of those affected were males. Cluster analysis of 822 cases indicated that the secondary attack rate, size of the cluster (dispersion) and occurrence of overt clinical illness is significantly higher when the index case in a cluster was symptomatic compared to an asymptomatic. Interpretation: Our findings indicate that both asymptomatic and symptomatic SARS-CoV-2 cases transmit the infection; however, the main driving force behind the spread of infection within the state was significantly higher from symptomatic cases. This has major implications for policies related to testing. Active search for symptomatic cases, subjecting them to testing and treatment should be prioritized for containing the spread of COVID-19.
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An earlier version of this manuscript was removed owing to inclusion of confidential information relating to an individual
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PURPOSE: Myeloid differentiation factor 88 (Myd88), a ubiquitous Toll-like receptor adaptor molecule, has been reported to play important roles in B cell responses to infections and vaccination. The present study evaluated the effects of genetic adjuvanting with Myd88 on the immune responses to a plasmid DNA rabies vaccine. MATERIALS AND METHODS: Plasmids encoding rabies glycoprotein alone (pIRES-Rgp) or a fragment of Myd88 gene in addition (pIRES-Rgp-Myd) were constructed and administered intramuscularly or intrademally in Swiss albino mice (on days 0, 7, and 21). Rabies virus neutralizing antibody (RVNA) titres were estimated in the mice sera on days 14 and 28 by rapid fluorescent focus inhibition test. The protective efficacy of the constructs was evaluated by an intracerebral challenge with challenge virus standard virus on day 35. RESULTS: Co-expression of Myd88 increased RVNA responses to pIRES-Rgp by 3- and 2-folds, following intramuscular and intradermal immunization, respectively. pIRES-Rgp protected 80% of the mice following intramuscular and intradermal immunizations, while pIRES-Rgp-Myd afforded 100% protection following similar administrations. CONCLUSION: Genetic adjuvanting with Myd88 enhanced the RVNA responses and protective efficacy of a plasmid DNA rabies vaccine. This strategy might be useful for rabies vaccination of canines in the field, and needs further evaluation.
