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Serial Population Based Serosurvey of Antibodies to SARS-Cov-2 in a Low and High Transmission Area of Karachi, Pakistan

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Serial Population Based Serosurvey of Antibodies to SARS-Cov-2 in a Low and High Transmission Area of Karachi, Pakistan medRxiv preprint doi: https://doi.org/10.1101/2020.07.28.20163451; this version posted July 29, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . Serial population based serosurvey of antibodies to SARS-CoV-2 in a low and high transmission area of Karachi, Pakistan Imran Nisar MSc1, Nadia Ansari MSc1, Mashal Amin MSc1, Farah Khalid MSc1, Aneeta Hotwani1, Najeeb Rehman1, Arjumand Rizvi MPhil1, Arslan Memon MPH2, Zahoor Ahmed2, Ashfaque Ahmed2, Junaid Iqbal PhD1, Ali Faisal Saleem MSc1, Uzma Bashir PhD3, Daniel B Larremore PhD4, Bailey Fosdick PhD5, Fyezah Jehan MSc1 1 Department of Paediatrics and Child Health, The Aga Khan University, Stadium Road, Karachi, Pakistan. 2 Health Department, Government of Sindh, Pakistan 3World Health Organisation Country Office, Pakistan 4University of Colorado Boulder, Colorado, USA 5Colorado State University, Colorado, USA ABSTRACT Background Pakistan is among the first low- and middle-income countries affected by COVID-19 pandemic. Monitoring progress through serial sero-surveys, particularly at household level, in densely populated urban communities can provide insights in areas where testing is non-uniform. Methods Two serial cross-sectional household surveys were performed in April (phase 1) and June (phase 2) 2020 each in a low- (District Malir) and high-transmission (District East) area of Karachi, Pakistan. Household were selected using simple random sampling (Malir) and systematic random sampling (East). Individual participation rate from consented households was 82.3% (1000/1215 eligible) in phase 1 and 76.5% (1004/1312 eligible) in phase 2. All household members or their legal guardians answered questions related to symptoms of Covid-19 and provided blood for testing with commercial Elecsys® Anti-SARS-CoV-2 immunoassay targeting combined IgG and 1 NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice. medRxiv preprint doi: https://doi.org/10.1101/2020.07.28.20163451; this version posted July 29, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . IgM. Seroprevalence estimates were computed for each area and time point independently. Given correlation among household seropositivity values, a Bayesian regression model accounting for household membership, age and gender was used to estimate seroprevalence. These estimates by age and gender were then post-stratified to adjust for the demographic makeup of the respective district. The household conditional risk of infection was estimated for each district and its confidence interval were obtained using a non-parametric bootstrap of households. Findings Post-stratified seroprevalence was estimated to be 0.2% (95% CI 0-0.7) in low-and 0.4% (95% CI 0 - 1.3) in high-transmission areas in phase 1 and 8.7% (95% CI 5.1-13.1) in low- and 15.1% (95% CI 9.4 -21.7) in high-transmission areas in phase 2, with no consistent patterns between prevalence rates for males and females. Conditional risk of infection estimates (possible only for phase 2) were 0.31 (95% CI 0.16-0.47) in low- and 0.41(95% CI 0.28-0.52) in high-transmission areas. Of the 166 participants who tested positive, only 9(5.4%) gave a history of any symptoms. Interpretation A large increase in seroprevalence to SARS-CoV-2 infection is seen, even in areas where transmission is reported to be low. Mostly the population is still seronegative. A large majority of seropositives do not report any symptoms. The probability that an individual in a household is infected, given that another household member is infected is high in both the areas. These results emphasise the need to enhance surveillance activities of COVID-19 especially in low-transmission sites and provide insights to risks of household transmission in tightly knit neighbourhoods in urban LMIC settings. 390 words 2 medRxiv preprint doi: https://doi.org/10.1101/2020.07.28.20163451; this version posted July 29, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . RESEARCH IN CONTEXT Evidence before this study Pakistan is the fifth most populous country in the world. The pandemic reached here in late February 2020 and so far more than 269000 confirmed cases have been registered with over 5500 deaths. Karachi, the largest city in Pakistan has also seen most number of cases and deaths However, true extent of transmission in the community is not known as testing rates have been low resulting in under reporting of cases and omission of mildly symptomatic and asymptomatic cases Population based serosurveys can help understand true magnitude of the spread and its variation with sociodemographic and other factors We searched PubMed and its specific hub LitCovid, medRxiv and bioRxiv preprint servers up to July 25, 2020, for epidemiological studies using the terms “seroprevalence” or “seroepidemiology” and “SARS-CoV-2” for articles in English language. Although there has been a recent surge in the number of serosurveys that have been done globally, many of them fail to meet the appropriate epidemiological and laboratory requirements of internal and external validity. No survey from Pakistan was identified. Added value of this study This is the first population-based seroprevalence study on estimates of antibodies against SARS- CoV-2 from Pakistan. We recruited more than 2000 participants across all age groups from one low transmission and one high transmission area in Karachi in two phases. Our findings show a huge jump in seroprevalence in both low and high transmission areas. Our findings suggest that in our population around 95% of individuals who have developed antibodies against SARS-CoV- 2 were asymptomatic. Additionally, our results indicate that children and adolescents have similar seroprevalence as adults and seroprevalence does not vary by sex. We used a FDA approved lab assay for measuring antibodies. Implications of all the available evidence There was a huge increase seen in seroprevalence observed in both low and high transmission areas over a short period of time. Our results suggest that almost 95% of people with SARS- CoV-2 infection remained asymptomatic in our population, which has important public health implications. 3 medRxiv preprint doi: https://doi.org/10.1101/2020.07.28.20163451; this version posted July 29, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . INTRODUCTION The global COVID19 pandemic has resulted in more than 15.5 million confirmed cases (until July 24) and more than 633000 deaths, with an estimated case fatality rate (CFR) of 4.1 %.(1) Pakistan was among the first of low- and middle income countries to be affected, and since then, there have been 269000 cases with 5709 deaths (CFR 2.1 %).(2) The epidemic started in Sindh province with the first case identified in Karachi on 26th Feb 2020 in a traveller returning from a religious congregation in Iran. The first few cases were limited to this cohort however, by mid-March, cases without a history of travel appeared indicating local transmission. Since then Karachi has seen the largest number of cases (~83000 or 31% of all cases) in Pakistan. An ideal surveillance strategy would provide nationally representative data by correctly and actively identifying incident cases through widespread nasopharyngeal (NP) swabbing and reverse transcription polymerase chain reaction (RT-PCR). However, this ideal testing strategy is limited on both supply and demand sides. On the supply side, equipment, reagents, and NP-swabs are limited in Pakistan (as elsewhere). On the demand side, the stigma of forced isolation and fear of lockdown decrease interest in testing and limit case reporting. These issues are further exacerbated by imperfect test sensitivity and high levels of pre-symptomatic and asymptomatic transmission which undermine symptom-based surveillance strategies.(3) Population-based sero surveys can be ideal to follow the epidemic,(4) and support decision making for introduction of a vaccine and strategize target populations.(5) However, high quality reliable population based surveys can also be expensive and challenging to conduct, especially in the face of an ongoing pandemic. They mandate proper training and personal protective equipment for the data collectors and allaying fear and anxiety in potential participants to avoid non-response bias. One approach that mitigates these potential issues is a household-based approach to serosurveys. Sampling the entire household can ease procedures of data collection and blood sampling, and operational feasibility can be increased by covering a smaller geographical area and comparing a high incidence and a low incidence area as per disease and case notification data. The World Health Organization (WHO) Unity Studies provide early investigation protocols for performing household level serosurveys for Covid-19 in the population.(6) 4 medRxiv preprint doi: https://doi.org/10.1101/2020.07.28.20163451; this version posted July 29, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license .
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