Analysis of serological surveys of antibodies to SARS-CoV-2 in the United States to estimate parameters needed for transmission modeling and to evaluate and improve the accuracy of predictions.

Seroprevalence studies can estimate proportions of the population that have been infected or vaccinated, including infections that were not reported because of the lack of symptoms or testing. Based on information from studies in the United States from mid-summer 2020 through the end of 2021, we describe proportions of the population with antibodies to SARS-CoV-2 as functions of age and time. Slices through these surfaces at arbitrary times provide initial and target conditions for simulation modeling. They also provide the information needed to calculate age-specific forces of infection, attack rates, and - together with contact rates - age-specific probabilities of infection on contact between susceptible and infectious people. We modified the familiar Susceptible-Exposed-Infectious-Removed (SEIR) model to include features of the biology of COVID-19 that might affect transmission of SARS-CoV-2 and stratified by age and location. We consulted the primary literature or subject matter experts for contact rates and other parameter values. Using time-varying Oxford COVID-19 Government Response Tracker assessments of US state and DC efforts to mitigate the pandemic and compliance with non-pharmaceutical interventions (NPIs) from a YouGov survey fielded in the US during 2020, we estimate that the efficacy of social-distancing when possible and mask-wearing otherwise at reducing susceptibility or infectiousness was 31% during the fall of 2020. Initialized from seroprevalence among people having commercial laboratory tests for purposes other than SARS-CoV-2 infection assessments on 7 September 2020, our age- and location-stratified SEIR population model reproduces seroprevalence among members of the same population on 25 December 2020 quite well. Introducing vaccination mid-December 2020, first of healthcare and other essential workers, followed by older adults, people who were otherwise immunocompromised, and then progressively younger people, our metapopulation model reproduces seroprevalence among blood donors on 4 April 2021 less well, but we believe that the discrepancy is due to vaccinations being under-reported or blood donors being disproportionately vaccinated, if not both. As experimenting with reliable transmission models is the best way to assess the indirect effects of mitigation measures, we determined the impact of vaccination, conditional on NPIs. Results indicate that, during this period, vaccination substantially reduced infections, hospitalizations and deaths. This manuscript was submitted as part of a theme issue on "Modelling COVID-19 and Preparedness for Future Pandemics."

Limitations introduced by a low participation rate of SARS-CoV-2 seroprevalence data.

BACKGROUND: There has been a large influx of COVID-19 seroprevalence studies, but comparability between the seroprevalence estimates has been an issue because of heterogeneities in testing platforms and study methodology. One potential source of heterogeneity is the response or participation rate. METHODS: We conducted a review of participation rates (PR) in SARS-CoV-2 seroprevalence studies collected by SeroTracker and examined their effect on the validity of study conclusions. PR was calculated as the count of participants for whom the investigators had collected a valid sample, divided by the number of people invited to participate in the study. A multivariable beta generalized linear model with logit link was fitted to determine if the PR of international household and community-based seroprevalence studies was associated with the factors of interest, from 1 December 2019 to 10 March 2021. RESULTS: We identified 90 papers based on screening and were able to calculate the PR for 35 out of 90 papers (39%), with a median PR of 70% and an interquartile range of 40.92; 61% of the studies did not report PR. CONCLUSIONS: Many SARS-CoV-2 seroprevalence studies do not report PR. It is unclear what the median PR rate would be had a larger portion not had limitations in reporting. Low participation rates indicate limited representativeness of results. Non-probabilistic sampling frames were associated with higher participation rates but may be less representative. Standardized definitions of participation rate and data reporting necessary for the PR calculations are essential for understanding the representativeness of seroprevalence estimates in the population of interest.

Use of Self-Collected Dried Blood Spots and a Multiplex Microsphere Immunoassay to Measure IgG Antibody Response to COVID-19 Vaccines.

Serosurveys can determine the extent and spread of a pathogen in populations. However, collection of venous blood requires trained medical staff. Dried blood spots (DBS) are a suitable alternative because they can be self-collected and stored/shipped at room temperature. As COVID-19 vaccine deployment began in early 2021, we rapidly enrolled laboratory employees in a study to evaluate IgG antibody levels following vaccination. Participants received a DBS collection kit, self-collection instructions, and a brief questionnaire. Three DBS were collected by each of 168 participants pre- and/or postvaccination and tested with a multiplex microsphere immunoassay (MIA) that separately measures IgG antibodies to SARS-CoV-2 spike-S1 and nucleocapsid antigens. Most DBS (99.6%, 507/509) were suitable for testing. Participants with prior SARS-CoV-2 infection (n = 7) generated high S antibody levels after the first vaccine dose. Naïve individuals (n = 161) attained high S antibody levels after the second dose. Similar antibody levels were seen among those vaccinated with Moderna (n = 29) and Pfizer-BioNTech (n = 137). For those receiving either mRNA vaccine, local side effects were more common after the first vaccine dose, whereas systemic side effects were more common after the second dose. Individuals with the highest antibody levels in the week prior to the second vaccine dose experienced more side effects from the second dose. Our study demonstrated that combining self-collected DBS and a multiplex MIA is a convenient and effective way to assess antibody levels to vaccination and could easily be used for population serosurveys of SARS-CoV-2 or other emerging pathogens. IMPORTANCE Serosurveys are an essential tool for assessing immunity in a population (1, 2). However, common barriers to effective serosurveys, particularly during a pandemic, include high-costs, resources required to collect venous blood samples, lack of trained laboratory technicians, and time required to perform the assay. By utilizing self-collected dried blood spots (DBS) and our previously developed high-throughput microsphere immunoassay, we were able to significantly reduce many of these common challenges. Participants were asked to self-collect three DBS before and/or after they received their COVID-19 vaccines to measure antibody levels following vaccination. Participants successfully collected 507 DBS that were tested for IgG antibodies to the spike and nucleocapsid proteins of SARS-CoV-2. When used with self-collected DBS, our relatively low-cost assay significantly reduced common barriers to collecting serological data from a population and was able to effectively assess antibody response to vaccination.

Adapting Lot Quality Assurance Sampling to accommodate imperfect diagnostic tests: application to COVID-19 serosurveillance in Haiti.

BACKGROUND: Lot Quality Assurance Sampling (LQAS), a tool used for monitoring health indicators in low resource settings resulting in "high" or "low" classifications, assumes that determination of the trait of interest is perfect. This is often not true for diagnostic tests, with imperfect sensitivity and specificity. Here, we develop Lot Quality Assurance Sampling for Imperfect Tests (LQAS-IMP) to address this issue and apply it to a COVID-19 serosurveillance study design in Haiti. METHODS: We first derive a modified procedure, LQAS-IMP, that accounts for the sensitivity and specificity of a diagnostic test to yield correct classification errors. We then apply the novel LQAS-IMP to design an LQAS system to classify prevalence of SARS-CoV-2 antibodies among healthcare workers at eleven Zanmia Lasante health facilities in Haiti. Finally, we show the performance of the LQAS-IMP procedure in a simulation study. RESULTS: We found that when an imperfect diagnostic test is used, the classification errors in the standard LQAS procedure are larger than specified. In the modified LQAS-IMP procedure, classification errors are consistent with the specified maximum classification error. We then utilized the LQAS-IMP procedure to define valid systems for sampling at eleven hospitals in Haiti. CONCLUSION: The LQAS-IMP procedure accounts for imperfect sensitivity and specificity in system design; if the accuracy of a test is known, the use of LQAS-IMP extends LQAS to applications for indicators that are based on laboratory tests, such as SARS-CoV-2 antibodies.

High prevalence of SARS-CoV-2 antibodies in pregnant women after the second wave of infections in the inner-city of Johannesburg, Gauteng Province, South Africa.

OBJECTIVES: After South Africa's second wave of COVID-19, this study estimated the SARS-CoV-2 seroprevalence among pregnant women in inner-city Johannesburg, South Africa. METHODS: In this cross-sectional survey, 500 pregnant women who were non-COVID-19-vaccinated (aged ≥12 years) were enrolled, and demographic and clinical data were collected. Serum samples were tested using the Wantai SARS-CoV-2 spike antibody enzyme-linked immunosorbent assay and Roche Elecsys® anti-SARS-CoV-2 nucleocapsid antibody assays. Seropositivity was defined as SARS-CoV-2 antibodies on either (primary) or both (secondary) assays. Univariate Poisson regression assessed risk factors associated with seropositivity. RESULTS: The median age was 27.4 years, and HIV prevalence was 26.7%. SARS-CoV-2 seroprevalence was 64.0% (95% confidence interval [CI]: 59.6-68.2%) on the primary and 54% (95% CI: 49.5-58.4%) on the secondary measure. Most (96.6%) women who were SARS-CoV-2-seropositive reported no symptoms. On the Roche assay, we detected lower seroprevalence among women living with HIV than women without HIV (48.9% vs 61.7%, P-value = 0.018), and especially low levels among women living with HIV with a clusters of differentiation 4 <350 cells/ml compared with women without immune suppression (22.2% vs 56.4%, prevalence rate ratio = 0.4; 95% CI: 0.2-0.9; P-value = 0.046). CONCLUSION: Pregnant women attending routine antenatal care had a high SARS-CoV-2 seroprevalence after the second wave in South Africa, and most had asymptomatic infections. Seroprevalence surveys in pregnant women present a feasible method of monitoring the course of the pandemic over time.

Optimizing the implementation of a participant-collected, mail-based SARS-CoV-2 serological survey in university-affiliated populations: lessons learned and practical guidance.

The rapid spread of SARS-CoV-2 is largely driven by pre-symptomatic or mildly symptomatic individuals transmitting the virus. Serological tests to identify antibodies against SARS-CoV-2 are important tools to characterize subclinical infection exposure.During the summer of 2020, a mail-based serological survey with self-collected dried blood spot (DBS) samples was implemented among university affiliates and their household members in Massachusetts, USA. Described are challenges faced and novel procedures used during the implementation of this study to assess the prevalence of SARS-CoV-2 antibodies amid the pandemic.Important challenges included user-friendly remote and contact-minimized participant recruitment, limited availability of some commodities and laboratory capacity, a potentially biased sample population, and policy changes impacting the distribution of clinical results to study participants. Methods and lessons learned to surmount these challenges are presented to inform design and implementation of similar sero-studies.This study design highlights the feasibility and acceptability of self-collected bio-samples and has broad applicability for other serological surveys for a range of pathogens. Key lessons relate to DBS sampling, supply requirements, the logistics of packing and shipping packages, data linkages to enrolled household members, and the utility of having an on-call nurse available for participant concerns during sample collection. Future research might consider additional recruitment techniques such as conducting studies during academic semesters when recruiting in a university setting, partnerships with supply and shipping specialists, and using a stratified sampling approach to minimize potential biases in recruitment.

Comparative performance data for multiplex SARS-CoV-2 serological assays from a large panel of dried blood spot specimens.

The extent of the COVID-19 pandemic will be better understood through serosurveys and SARS-CoV-2 antibody testing. Dried blood spot (DBS) samples will play a central role in large scale serosurveillance by simplifying biological specimen collection and transportation, especially in Canada. Direct comparative performance data on multiplex SARS-CoV-2 assays resulting from identical DBS samples are currently lacking. In our study, we aimed to provide performance data for the BioPlex 2200 SARS-CoV-2 IgG (Bio-Rad), V-PLEX SARS-CoV-2 Panel 2 IgG (MSD), and Elecsys Anti-SARS-CoV-2 (Roche) commercial assays, as well as for two highly scalable in-house assays (University of Ottawa and Mount Sinai Hospital protocols) to assess their suitability for DBS-based SARS-CoV-2 DBS serosurveillance. These assays were evaluated against identical panels of DBS samples collected from convalescent COVID-19 patients (n = 97) and individuals undergoing routine sexually transmitted and bloodborne infection (STBBI) testing prior to the COVID-19 pandemic (n = 90). Our findings suggest that several assays are suitable for serosurveillance (sensitivity >97% and specificity >98%). In contrast to other reports, we did not observe an improvement in performance using multiple antigen consensus-based rules to establish overall seropositivity. This may be due to our DBS panel which consisted of samples collected from convalescent COVID-19 patients with significant anti-spike, -receptor binding domain (RBD), and -nucleocapsid antibody titers. This study demonstrates that biological specimens collected as DBS coupled with one of several readily available assays are useful for large-scale COVID-19 serosurveillance.

Prevalence and predictors of anti-SARS-CoV-2 serology in a highly vulnerable population of Rio de Janeiro: A population-based serosurvey.

Background: COVID-19 serosurveys allow for the monitoring of the level of SARS-CoV-2 transmission and support data-driven decisions. We estimated the seroprevalence of anti-SARS-CoV-2 antibodies in a large favela complex in Rio de Janeiro, Brazil. Methods: A population-based panel study was conducted in Complexo de Manguinhos (16 favelas) with a probabilistic sampling of participants aged ≥1 year who were randomly selected from a census of individuals registered in primary health care clinics that serve the area. Participants answered a structured interview and provided blood samples for serology. Multilevel regression models (with random intercepts to account for participants' favela of residence) were used to assess factors associated with having anti-S IgG antibodies. Secondary analyses estimated seroprevalence using an additional anti-N IgG assay. Findings: 4,033 participants were included (from Sep/2020 to Feb/2021, 22 epidemic weeks), the median age was 39·8 years (IQR:21·8-57·7), 61% were female, 41% were mixed-race (Pardo) and 23% Black. Overall prevalence was 49·0% (95%CI:46·8%-51·2%) which varied across favelas (from 68·3% to 31·4%). Lower prevalence estimates were found when using the anti-N IgG assay. Odds of having anti-S IgG antibodies were highest for young adults, and those reporting larger household size, poor adherence to social distancing and use of public transportation. Interpretation: We found a significantly higher prevalence of anti-S IgG antibodies than initially anticipated. Disparities in estimates obtained using different serological assays highlight the need for cautious interpretation of serosurveys estimates given the heterogeneity of exposure in communities, loss of immunological biomarkers, serological antigen target, and variant-specific test affinity. Funding: Fundação Oswaldo Cruz, Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação de Amparo a Pesquisa do Estado do Rio de Janeiro (FAPERJ), the European Union's Horizon 2020 research and innovation programme, Royal Society, Serrapilheira Institute, and FAPESP.