Assessing the Burden of COVID-19 among Children Aged 6-14 Years in Karnataka, India: A Cross-sectional Survey.

Background: India experienced three coronavirus disease (COVID-19) waves, with the third attributed to the highly contagious Omicron variant. Before the national vaccination rollout for children above 6, understanding severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobulin G (IgG) positivity in the pediatric population was essential. This study aims to assess the burden of Covid-19 infection and to estimate the seroprevalence in children aged 6 to 14 years in the state of Karnataka. Material and Methods: We surveyed 5,358 children aged 6-14 across Karnataka using 232 health facilities, from June 6 to 14, 2022. We determined the sample size using the PPS (Population Proportional to Size) technique and employed cluster sampling. We tested all participants for SARS-CoV-2 IgG with an enzyme-linked immunosorbent assay (ELISA) kit and SARS-CoV-2 RNA with reverse transcription-polymerase chain reaction (RT-PCR). We sequenced samples with a cycle threshold (CT) value below 25 using whole genomic sequencing (WGS). Result: We found an adjusted seroprevalence of IgG at 75.38% statewide, and we found 0.04% of children RT-PCR positive for COVID-19. We determined a case-to-infection ratio of 1:37 and identified the SARS-CoV-2 strains as Omicron, BA.5, and BA.2.10. Conclusion: The study showed a high seroprevalence of IgG among children with low active infection. Omicron, BA. 5, and BA. 2.10 variants were detected through WGS.

Corrigendum to "Second round statewide sentinel-based population survey for estimation of the burden of active infection and anti-SARS-CoV-2 IgG antibodies in the general population of Karnataka, India, during January-February 2021" [IJID Regions Vol 1(2021) pages 107-116].

[This corrects the article DOI: 10.1016/j.ijregi.2021.10.008.].

The burden of active infection and anti-SARS-CoV-2 IgG antibodies in the general population: Results from a statewide sentinel-based population survey in Karnataka, India.

OBJECTIVE: To estimate the burden of active infection and anti-SARS-CoV-2 IgG antibodies in Karnataka, India, and to assess variation across geographical regions and risk groups. METHODS: A cross-sectional survey of 16,416 people covering three risk groups was conducted between 3-16 September 2020 using the state of Karnataka's infrastructure of 290 healthcare facilities across all 30 districts. Participants were further classified into risk subgroups and sampled using stratified sampling. 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 (either IgG or active or both), while multinomial regression identified predictors. RESULTS: The overall adjusted total prevalence of COVID-19 in Karnataka was 27.7% (95% CI 26.1-29.3), IgG 16.8% (15.5-18.1) and active infection fraction 12.6% (11.5-13.8). The case-to-infection ratio was 1:40 and the infection fatality rate was 0.05%. Influenza-like symptoms or contact with a COVID-19-positive patient were good predictors of active infection. RAT kits had higher sensitivity (68%) in symptomatic people compared with 47% in asymptomatic people. CONCLUSION: This sentinel-based population survey was the first comprehensive survey in India to provide accurate estimates of the COVID-19 burden. The findings provide a reasonable approximation of the population immunity threshold levels. Using existing surveillance platforms coupled with a syndromic approach and sampling framework enabled this model to be replicable.

Descriptive epidemiology of SARS-CoV-2 infection in Karnataka state, South India: Transmission dynamics of symptomatic vs. asymptomatic infections.

BACKGROUND: The huge surge in COVID-19 cases in Karnataka state, India, during early phase of the pandemic especially following return of residents from other states and countries required investigation with respect to transmission dynamics, clinical status, demographics, comorbidities and mortality. Knowledge on the role of symptomatic and asymptomatic cases in transmission of SARS-CoV-2 was not available. METHODS: The study included all the cases reported from March 8 - May 31, 2020. Individuals with a history of international or domestic travel from high burden states, Influenza-like Illness or Severe Acute Respiratory Illness and high-risk contacts of COVID-19 cases were included. Detailed analysis based on contact tracing data available from the line-list of state surveillance unit was performed using cluster network analysis software. FINDINGS: Amongst the 3404 COVID-19 positive cases, 3096 (91%) were asymptomatic while 308 (9%) were symptomatic. Majority of asymptomatic cases were in the age range of 16 and 45 years while symptomatic cases were between 31 and 65 years. Mortality rate was especially higher among middle-aged and elderly cases with co-morbidities, 34/38 (89·4%). Cluster network analysis of 822 cases indicated that the secondary attack rate, size of the cluster and superspreading events were higher when the source case was symptomatic as compared to an asymptomatic. INTERPRETATION: Our findings indicate that both asymptomatic and symptomatic SARS-CoV-2 cases transmit the infection, although symptomatic cases were the main driving force within the state during the beginning of the pandemic. Considering the large proportion of asymptomatic cases, their ability to spread infection cannot be overlooked. Notwithstanding the limitations and bias in identifying asymptomatic cases, the findings have major implications for testing policies. Active search, early testing and treatment of symptomatic elderly patients with comorbidities should be prioritized for containing the spread of COVID-19 and reducing mortality. FUNDING: Intermediate Fellowship, Wellcome Trust-DBT India Alliance to Giridhara R Babu, Grant number: IA/CPHI/14/1/501499.

Second round statewide sentinel-based population survey for estimation of the burden of active infection and anti-SARS-CoV-2 IgG antibodies in the general population of Karnataka, India, during January-February 2021.

Objective: Demonstrate the feasibility of using the existing sentinel surveillance infrastructure to conduct the second round of the serial cross-sectional sentinel-based population survey. Assess active infection, seroprevalence, and their evolution in the general population across Karnataka. Identify local variations for locally appropriate actions. Additionally, assess the clinical sensitivity of the testing kit used on account of variability of antibody levels in the population. Methods: The 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). The geographical spread was sufficient to capture local variations. Consenting participants were subjected to real-time reverse transcription-polymerase chain reaction (RT-PCR) testing, and antibody (IgG) testing. Clinical sensitivity was assessed by conducting a longitudinal study among participants identified as COVID-19 positive in the first survey round. Results: Overall weighted adjusted seroprevalence of IgG was 15.6% (95% CI: 14.9-16.3), crude IgG prevalence was 15.0% and crude active infection 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). Further, Cases-to-infections ratio (CIR) varied 3-35 across units and IFR varied 0.04-0.50% across units. Clinical sensitivity of the IgG ELISA test kit was estimated as ≥38.9%. Conclusion: We demonstrated the feasibility and simplicity of sentinel-based population survey in measuring variations in subnational and local data, useful for locally appropriate actions in different locations. The sentinel-based population survey thus 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.

Genomic epidemiology reveals multiple introductions and spread of SARS-CoV-2 in the Indian state of Karnataka.

Karnataka, a state in south India, reported its first case of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection on March 8, 2020, more than a month after the first case was reported in India. We used a combination of contact tracing and genomic epidemiology to trace the spread of SARS-CoV-2 in the state up until May 21, 2020 (1578 cases). We obtained 91 genomes of SARS-CoV-2 which clustered into seven lineages (Pangolin lineages-A, B, B.1, B.1.80, B.1.1, B.4, and B.6). The lineages in Karnataka were known to be circulating in China, Southeast Asia, Iran, Europe and other parts of India and are likely to have been imported into the state both by international and domestic travel. Our sequences grouped into 17 contact clusters and 24 cases with no known contacts. We found 14 of the 17 contact clusters had a single lineage of the virus, consistent with multiple introductions and most (12/17) were contained within a single district, reflecting local spread. In most of the 17 clusters, the index case (12/17) and spreaders (11/17) were symptomatic. Of the 91 sequences, 47 belonged to the B.6 lineage, including eleven of 24 cases with no known contact, indicating ongoing transmission of this lineage in the state. Genomic epidemiology of SARS-CoV-2 in Karnataka suggests multiple introductions of the virus followed by local transmission in parallel with ongoing viral evolution. This is the first study from India combining genomic data with epidemiological information emphasizing the need for an integrated approach to outbreak response.