CalScope: Monitoring SARS-CoV-2 Seroprevalence from Vaccination and Prior Infection in Adults and Children in California May 2021– July 2021 (preprint)

ABSTRACT Importance Understanding how SARS-CoV-2 seroprevalence varies regionally across California is critical to the public health response to the pandemic. Objective To estimate how many Californians have antibodies against SARS-CoV-2 from prior infection or vaccination. Design Wave 1 of CalScope: a repeated cross-sectional serosurvey of adults and children enrolled between April 20, 2021 and June 16, 2021. Setting A population-based random sample of households in seven counties in California (Alameda, El Dorado, Kern, Los Angeles, Monterey, San Diego, and Shasta) were invited to complete an at-home SARS-CoV-2 antibody test and survey instrument. Participants Invitations were sent to 200,000 randomly selected households in the seven counties. From each household, 1 adult (18 years and older) and 1 child (aged 6 months to 17 years) could enroll in the study. There were no exclusion criteria. Main Outcome(s) and Measures All specimens were tested for antibodies against the nucleocapsid and spike proteins of SARS-CoV-2. The primary outcome was serostatus category, which was determined based on antibody test results and self-reported vaccination status: seronegative, antibodies from infection only, antibodies from infection and vaccination, and antibodies from vaccination alone. We used inverse probability of selection weights and iterative proportional fitting to account for non-response. Results 11,161 households enrolled in wave 1 of CalScope, with 7,483 adults and 1,375 children completing antibody testing. As of June 2021, 27% (95%CI [23%, 31%]) of adults and 30% (95%CI [24%, 36%]) of children had evidence of prior SARS-CoV-2 infection; 33% (95%CI [28%, 37%]) of adults and 57% (95%CI [48%, 66%]) of children were seronegative. Serostatus varied regionally. Californians 65 years or older were most likely to have antibodies from vaccine alone (59%; 95%CI [48%, 69%]) and children between 5-11 years old were most likely to have antibodies from prior infection alone (36%; 95%CI [21%, 52%]). Conclusions and Relevance As of June 2021, a third of adults in California and most children under 18 remained seronegative. Seroprevalence varied regionally and by demographic group, suggesting that some regions or populations might remain more vulnerable to subsequent surges than others. Key Points Question What is the prevalence of vaccine and infection derived antibodies against SARS-CoV-2 in adults and children in California? Findings In this population-based serosurvey that included 11,161 households, as of June 2021, 33% of adults and 57% of children were seronegative; 18% of adults and 26% of children had antibodies from infection alone; 9% of adults and 5% of children had antibodies from both infection and vaccination; and 41% of adults and 13% of children had antibodies from vaccination alone. Meaning Serostatus varied considerably across geographic regions, suggesting that certain areas might be at increased risk for future COVID-19 surges.

Detection of SARS-CoV-2 neutralizing antibodies with a cell-free PCR assay (preprint)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to more than 4 million confirmed infections worldwide and over 300,000 deaths. While Remdesivir has recently received FDA emergency use authorization for treatment of SARS-CoV-2 infection, convalescent plasma (CP) with high titers of SARS-CoV-2 neutralizing antibodies (NAbs) from recovered donors remains a promising and widely accessible method to mitigate severe disease symptoms. Here, we describe the development and validation of a cell-free neutralization PCR assay using SARS-CoV-2 spike protein S1 and human ACE2 receptor-DNA conjugates. By comparing with samples collected prior to the outbreak, we confirmed that NAbs were specifically detected in COVID-19 cases. Using our unique assay, the NAb signals are detectable as early as 10 days after onset of symptoms and continue to rise, plateauing after 18 days. Notably, we showed that the use of licensed pathogen reduction technology to inactivate potentially contaminating infectious pathogens in CP did not alter NAb signals, paving a path to safely administer effective CP therapies. The described neutralization PCR assay can serve as a qualification tool to easily identify suitable CP donors of a potentially lifesaving therapy. In addition, this assay tool is readily deployable in standard laboratories with biosafety level 2 capability, and can yield results within 2-3 hr. This advancement can facilitate research on factors driving diverse COVID-19 disease manifestations, and to evaluate the impact of various CP processing protocols on CP therapeutic efficacy.

A serological assay to detect SARS-CoV-2 antibodies in at-home collected finger-prick dried blood spots (preprint)

Accurate surveillance of coronavirus disease 2019 (COVID-19) incidence requires large-scale testing of the population. Current testing methods require in-person collection of biospecimens by a healthcare worker, limiting access of individuals who do not have access to testing facilities while placing both the patient and healthcare worker at risk of exposure to infection. We report the development and validation of a at-home finger-prick dried blood spot collection kit and an analysis method. We demonstrated 100% sensitivity and specificity using at-home collected specimens across the US. Such methods may facilitate the conduct of unbiased serosurveys within hard to reach populations and help reduce the sample collection burden of serological testing on both health care systems and individuals alike.