SARS-CoV-2 antibody magnitude and detectability are driven by disease severity, timing, and assay (preprint)

Serosurveillance studies are critical for estimating SARS-CoV-2 transmission and immunity, but interpretation of results is currently limited by poorly defined variability in the performance of antibody assays to detect seroreactivity over time in individuals with different clinical presentations. We measured longitudinal antibody responses to SARS-CoV-2 in plasma samples from a diverse cohort of 128 individuals over 160 days using 14 binding and neutralization assays. For all assays, we found a consistent and strong effect of disease severity on antibody magnitude, with fever, cough, hospitalization, and oxygen requirement explaining much of this variation. We found that binding assays measuring responses to spike protein had consistently higher correlation with neutralization than those measuring responses to nucleocapsid, regardless of assay format and sample timing. However, assays varied substantially with respect to sensitivity during early convalescence and in time to seroreversion. Variations in sensitivity and durability were particularly dramatic for individuals with mild infection, who had consistently lower antibody titers and represent the majority of the infected population, with sensitivities often differing substantially from reported test characteristics (e.g., amongst commercial assays, sensitivity at 6 months ranged from 33% for ARCHITECT IgG to 98% for VITROS Total Ig). Thus, the ability to detect previous infection by SARS-CoV-2 is highly dependent on the severity of the initial infection, timing relative to infection, and the assay used. These findings have important implications for the design and interpretation of SARS-CoV-2 serosurveillance studies.

SARS-CoV-2 Community Transmission During Shelter-in-Place in San Francisco (preprint)

ABSTRACT Background: We characterized SARS-CoV-2 infections in a densely-populated, majority Latinx San Francisco community six-weeks into the city's shelter-in-place order. Methods: We offered SARS-CoV-2 reverse transcription-PCR and antibody (Abbott ARCHITECT IgG) testing, regardless of symptoms, to all residents (>=4 years) and workers in a San Francisco census tract (population: 5,174) at outdoor, community-mobilized events over four days. We estimated SARS-CoV-2 point prevalence (PCR-positive) and cumulative incidence (antibody or PCR-positive) in the census tract and evaluated risk factors for recent (PCR-positive/antibody-negative) versus prior infection (antibody-positive/PCR-negative). SARS-CoV-2 genome recovery and phylogenetics were used to measure viral strain diversity, establish viral lineages present, and estimate number of introductions. Results: We tested 3,953 persons: 40% Latinx; 41% White; 9% Asian/Pacific Islander; and 2% Black. Overall, 2.1% (83/3,871) tested PCR-positive: 95% were Latinx and 52% asymptomatic when tested. 1.7% of residents and 6.0% of workers (non-census tract residents) were PCR-positive. Among 2,598 census tract residents, estimated point prevalence of PCR-positives was 2.3% (95%CI: 1.2-3.8%): 3.9% (95%CI: 2.0-6.4%) among Latinx vs. 0.2% (95%CI: 0.0-0.4%) among non-Latinx persons. Estimated cumulative incidence among residents was 6.1% (95%CI: 4.0-8.6%). Prior infections were 67% Latinx, 16% White, and 17% other ethnicities. Among recent infections, 96% were Latinx. Risk factors for recent infection were Latinx ethnicity, inability to shelter-in-place and maintain income, frontline service work, unemployment, and household income

SARS-CoV-2 seroprevalence and neutralizing activity in donor and patient blood from the San Francisco Bay Area (preprint)

We report very low SARS-CoV-2 seroprevalence in two San Francisco Bay Area populations. Seropositivity was 0.26% in 387 hospitalized patients admitted for non-respiratory indications and 0.1% in 1,000 blood donors. We additionally describe the longitudinal dynamics of immunoglobulin-G, immunoglobulin-M, and in vitro neutralizing antibody titers in COVID-19 patients. Neutralizing antibodies rise in tandem with immunoglobulin levels following symptom onset, exhibiting median time to seroconversion within one day of each other, and there is >93% positive percent agreement between detection of immunoglobulin-G and neutralizing titers.