Serial SARS-CoV-2 Seropravelence Studies in Delhi July-August 2020: Indications of Pre-existing Cross-reactive Antibodies and Implications for Disease Progression
Two seropravelence studies were undertaken in Delhi, the city-state capital of India, in July-August 2020, exactly one month apart, to test for SARS-CoV-2 antibodies. Virus-tested (mostly RT-PCR) caseloads corresponding to these surveys, as of 13 days earlier to ensure antibody generation, were compared. The survey conducted June 26-July 10 (sample size 21387) showed 23.48% seropravelence, (extrapolated to 4.48 mn of Delhi population of 19.1 mn), which was 79-times higher than corresponding virus-tested positives totaling 56746. Survey conducted August 1-7 (15311 samples) showed 29.1% antibody-positive (5.56 mn population), and was 44x of virus-tested positive total of 125096. Pointing out that all serological surveys world-over have shown antibody-positives to be higher than virus-test positives by multiples 7x to 80x, this study seeks to examine why the multiple should decline so drastically in one month, from 79x to 44x.
Statistical adjustments were performed for Sampling Error and Sensitivity/Specificity of the diagnostic kits. Indigenously developed COVID KAVACH ELISA tests for IgG antibodies to the SARS-CoV-2 virus were used for the surveys. Significantly, statistical adjustments were also done to account for the Testing Volumes and (Spot) Positivity rates at the two different times. [Spot Positivity is defined in the study and is the closest estimate of current or fresh positivity.] After all statistical revisions, the antibody-positive to virus-test positive multiples stood at 53x and 37x for the two surveys. Calculating across the two sets of data, and other sensitivity analysis, the study indicates that there is a significant proportion of pre-existing cross-reactive antibodies (possibly to the HCoV viruses), that are seropositive in SARS-CoV-2 antibody tests, to the extent of 16%-19% of the population. The study also infers that there is an Amplification Factor of 15 in the Delhi serostudies: ie, each virus-test positive represents 14 more who are possibly asymptomatic and untested.
The study forecasts a seropravelence 31%-34% for the 3rd serial serosurvey scheduled in September, whose results expected 22nd September. Limitations of the study are discussed, notably the absence of any research paper on the survey techniques, antibody testing controversies, and the statistical adjustment for Testing Volumes. The study discusses how Chain-of-Transmission protocols and Decreasing Susceptible Population work in unison to slow down a pandemic, and analyses the disease progression graph of Delhi in that context. The implications of 16%-19% pre-existing antibodies on disease progression in Delhi are discussed.
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Posted 21 Sep, 2020
Serial SARS-CoV-2 Seropravelence Studies in Delhi July-August 2020: Indications of Pre-existing Cross-reactive Antibodies and Implications for Disease Progression
Posted 21 Sep, 2020
Two seropravelence studies were undertaken in Delhi, the city-state capital of India, in July-August 2020, exactly one month apart, to test for SARS-CoV-2 antibodies. Virus-tested (mostly RT-PCR) caseloads corresponding to these surveys, as of 13 days earlier to ensure antibody generation, were compared. The survey conducted June 26-July 10 (sample size 21387) showed 23.48% seropravelence, (extrapolated to 4.48 mn of Delhi population of 19.1 mn), which was 79-times higher than corresponding virus-tested positives totaling 56746. Survey conducted August 1-7 (15311 samples) showed 29.1% antibody-positive (5.56 mn population), and was 44x of virus-tested positive total of 125096. Pointing out that all serological surveys world-over have shown antibody-positives to be higher than virus-test positives by multiples 7x to 80x, this study seeks to examine why the multiple should decline so drastically in one month, from 79x to 44x.
Statistical adjustments were performed for Sampling Error and Sensitivity/Specificity of the diagnostic kits. Indigenously developed COVID KAVACH ELISA tests for IgG antibodies to the SARS-CoV-2 virus were used for the surveys. Significantly, statistical adjustments were also done to account for the Testing Volumes and (Spot) Positivity rates at the two different times. [Spot Positivity is defined in the study and is the closest estimate of current or fresh positivity.] After all statistical revisions, the antibody-positive to virus-test positive multiples stood at 53x and 37x for the two surveys. Calculating across the two sets of data, and other sensitivity analysis, the study indicates that there is a significant proportion of pre-existing cross-reactive antibodies (possibly to the HCoV viruses), that are seropositive in SARS-CoV-2 antibody tests, to the extent of 16%-19% of the population. The study also infers that there is an Amplification Factor of 15 in the Delhi serostudies: ie, each virus-test positive represents 14 more who are possibly asymptomatic and untested.
The study forecasts a seropravelence 31%-34% for the 3rd serial serosurvey scheduled in September, whose results expected 22nd September. Limitations of the study are discussed, notably the absence of any research paper on the survey techniques, antibody testing controversies, and the statistical adjustment for Testing Volumes. The study discusses how Chain-of-Transmission protocols and Decreasing Susceptible Population work in unison to slow down a pandemic, and analyses the disease progression graph of Delhi in that context. The implications of 16%-19% pre-existing antibodies on disease progression in Delhi are discussed.
Figure 1
Figure 2