SARS-CoV-2 Omicron Variant Infection of Individuals with High Titer Neutralizing Antibodies Post-3rd mRNA Vaccine Dose (preprint)

BackgroundVaccination with COVID-19 mRNA vaccines prevent hospitalization and severe disease caused by wildtype SARS-CoV-2 and several variants, and likely prevented infection when serum neutralizing antibody (NAb) titers were >1:160. Preventing infection limits viral replication resulting in mutation, which can lead to the emergence of additional variants. MethodsDuring a longitudinal study to evaluate durability of a three-dose mRNA vaccine regimen (2 primary doses and a booster) using a rapid test that semi-quantitatively measures NAbs, the Omicron variant emerged and quickly spread globally. We evaluated NAb levels measured prior to symptomatic breakthrough infection, in groups infected prior to and after the emergence of Omicron. ResultsDuring the SARS-CoV-2 Delta variant wave, 93% of breakthrough infections in our study occurred when serum NAb titers were <1:80. In contrast, after the emergence of Omicron, study participants with high NAb titers that had received booster vaccine doses became symptomatically infected. NAb titers prior to infection were [≥]1:640 in 64% of the Omicron-infected population, [≥]1:320 (14%), and [≥]1:160 (21%). DiscussionThese results indicate that high titers of NAbs elicited by currently available mRNA vaccines do not protect against infection with the Omicron variant, and that mild to moderate symptomatic infections did occur in a vaccinated and boosted population, although did not require hospitalization.

Development of a Rapid Point-Of-Care Test that Measures Neutralizing Antibodies to SARS-CoV-2 (preprint)

As increasing numbers of people recover from and are vaccinated against COVID-19, tests are needed to measure levels of protective, neutralizing antibodies longitudinally to help determine duration of immunity. We developed a lateral flow assay (LFA) that measures levels of neutralizing antibodies in plasma, serum or whole blood. The LFA is based on the principle that neutralizing antibodies inhibit binding of the spike protein receptor-binding domain (RBD) to angiotensin-converting enzyme 2 (ACE2). The test classifies high levels of neutralizing antibodies in sera that were titered using authentic SARS-CoV-2 and pseudotype neutralization assays with an accuracy of 98%. Sera obtained from patients with seasonal coronavirus did not prevent RBD from binding to ACE2. As a demonstration for convalescent plasma therapy, we measured conversion of non-immune plasma into strongly neutralizing plasma. This is the first report of a neutralizing antibody test that is rapid, highly portable and relatively inexpensive that might be useful in assessing COVID-19 vaccine immunity.

Retrospective Clinical Evaluation of Four Lateral Flow Assays for the Detection of SARS-CoV-2 Antibodies (preprint)

Coronavirus disease 2019 (COVID-19) is a potentially life-threatening respiratory infection caused by severe acute respiratory coronavirus 2 (SARS-CoV-2), for which numerous serologic assays are available. In a CLIA laboratory setting, we used a retrospective sample set (n = 457) to evaluate two lateral flow immunoassays (LFIAs; two iterations of Rapid Response COVID-19 Test Cassette, BTNX Inc.) and a subset of to evaluate SARS-COV-2 IgG/IgM Rapid Test, ACON Laboratories (n = 200); and Standard Q COVID-19 IgM/IgG Duo, SD BIOSENSOR (n = 155) for their capacity to detect of SARS-CoV-2 IgG. In a cohort of primarily hospitalized patients with RT-PCR confirmed COVID-19, the BTNX assays demonstrated 95% and 92% agreement with the Abbott SARS-CoV-2 IgG assay and sensitivity was highest at [≥] 14 days from symptom onset [BTNX kit 1, 95%; BTNX kit 2, 91%]. ACON and SD assays demonstrated 99% and 100% agreement with the Abbott assay at [≥] 14 days from symptom onset. Specificity was measured using 74 specimens collected prior to SARS-CoV-2 circulation in the United States and 31 "cross-reactivity challenge" specimens, including those from patients with a history of seasonal coronavirus infection and was 98% for BTNX kit 1 and ACON and 100% for BTNX kit 2 and SD. Taken with data from EUA assays, these results suggest that LFIAs may provide adequate results for rapid detection of SARS-CoV-2. Replicating these results in fingerstick blood in outpatient populations, would further support the possibility that LFIAs may be useful to increase access to serologic testing