Affinity of Anti-Spike Antibodies in SARS-CoV-2 Patient Plasma and Its Effect on COVID-19 Antibody Assays (preprint)

Background: Measuring anti-spike protein antibodies in human plasma or serum is commonly used to determine prior exposure to SARS-CoV-2 infection and to assess the anti-viral protection capacity. According to the mass-action law, a lesser concentration of tightly binding antibody can produce the same quantity of antibody-antigen complexes as higher concentrations of lower affinity antibody. Thus, measurements of antibody levels reflect both affinity and concentration. These two fundamental parameters cannot be disentangled in clinical immunoassays, and so produce a bias which depends on the assay format. Methods: To determine the apparent affinity of anti-spike protein antibodies, a small number of antigen-coated magnetic microparticles were imaged by fluorescence microscopy after probing antigen-antibody equilibria directly in patient plasma. Direct and indirect anti-SARS-CoV-2 immunoassays were used to measure antibody levels in the blood of infected and immunized individuals. Findings: We observed affinity maturation of antibodies in convalescent and vaccinated individuals, showing that higher affinities are achieved much faster by vaccination. We demonstrate that direct and indirect immunoassays for measuring anti-spike protein antibodies depend differently on antibody affinity which, in turn, affects accurate interpretation of the results. Interpretation: Direct immunoassays show substantial antibody affinity dependence. This makes them useful for identifying past SARS-CoV-2 exposure. Indirect immunoassays provide more accurate quantifications of anti-viral antibody levels. Funding: No external funding sources were used in this study.Declaration of Interest: All authors are employed by Abbott LabsEthical Approval: Patient plasma/serum samples used for this study were purchased from New York Biologics (Southampton, NY), Access Biologicals, LLC (Vista, CA) and New York Blood Center (New York, NY). The samples purchased from Access Biologicals LLC were collected under an IRB protocol approved by Ballad Health System IRB. The samples purchased from New York Biologics were collected under an IRB approved by Ethical and Independent Review Services (E&I). The patient plasma samples purchased from New York Blood Center (New York, NY), were collected from volunteer blood donors who consented to the use of their samples for research purposes at the time of collection.

Family Physicians' Perception of the New mRNA COVID-19 Vaccines.

INTRODUCTION: This study was conducted to assess family physicians' perception of the US Food and Drug Administration-approved mRNA Coronavirus disease 2019 (COVID-19) vaccines, their plans to be vaccinated with an approved mRNA COVID-19 vaccine, and their support for vaccination of patients and family members. METHODS: The authors conducted a cross-sectional survey of 307 practicing family physicians, full-time faculty physicians, and resident physicians in Kansas from December 14, 2020, to December 31, 2020. The study participants completed an anonymous, 20-item survey assessing family physicians' concerns about exposure to COVID-19 and their perceptions of the mRNA COVID-19 vaccines to control SARS-CoV-2. A mixed-method approach was used to collect, analyze, and interpret the data. RESULTS: There was a 51.1% response rate. The proportion of family physicians who reported their intentions to be vaccinated for COVID-19 was significantly higher than those who were hesitant to receive the mRNA vaccines (90.6% vs 9.4%; χ2 [1, n = 307] = 201.9.1; P < .0001). Among those who were willing to be vaccinated with an approved mRNA COVID-19 vaccine, the main reasons were to prevent COVID-19 infection; protect self, family, and community; contribute to herd immunity; inspire confidence that the vaccines are safe and end the pandemic and bring life back to normal. CONCLUSION: Our findings suggest a significantly positive association between a physician's concerns and their willingness to be vaccinated with an approved mRNA COVID-19 vaccine. With the authorization of 2 new mRNA COVID-19 vaccines, future studies should investigate the number of physicians in our study who received the vaccine.

Expanding access to SARS-CoV-2 IgG and IgM serologic testing using fingerstick whole blood, plasma, and rapid lateral flow assays (preprint)

Serologic testing for SARS-CoV-2 antibodies can be used to confirm diagnosis, estimate seroprevalence, screen convalescent plasma donors, and assess vaccine efficacy. Several logistical and infrastructure challenges limit access to SARS-CoV-2 serologic testing. Dried blood spot (DBS) samples have been used for serology testing of various diseases in resource-limited settings. We examined the use of DBS samples and capillary blood (fingerstick) plasma collected in Microtainer tubes for SARS-CoV-2 testing with the automated Abbott ARCHITECT SARS-CoV-2 IgG (List 6R86) and IgM assays and use of venous whole blood with a prototype PANBIO rapid point-of-care lateral flow SARS-CoV-2 IgG assay. The ARCHITECT SARS-CoV-2 IgG assay was initially optimized for use with DBS, venous and capillary plasma, and venous whole blood collected from patients with symptoms and PCR-confirmed COVID-19 and negative asymptomatic controls. Assay linearity and reproducibility was confirmed with 3 contrived DBS samples, with sample stability and signal recovery after 14 days at room temperature. ARCHITECT SARS-CoV-2 IgG and IgM assay results showed high concordance between fingerstick DBS and venous DBS samples, and between fingerstick DBS and venous whole blood samples (n=61). Discordant results were seen in 3 participants (2 IgG, 1 IgM) who were in the process of seroreversion at the time of sample collection and had results near the assay cutoff. Use of fingerstick plasma collected in Microtainer tubes (n=109) showed 100% concordant results (R2=0.997) with matched patient venous plasma on the ARCHITECT SARS-CoV-2 IgG assay. High concordance of assay results (92.9% positive, 100% negative) was also observed for the PANBIO SARS-CoV-2 IgG assay compared to the ARCHITECT SARS-CoV-2 IgG assay run with matched venous plasma (n=61). Fingerstick DBS and plasma samples are easy and inexpensive to collect and, along with the use of rapid point-of-care testing platforms, will expand access to SARS-CoV-2 serology testing, particularly in resource-limited areas.

The Role of Robotics in Infectious Disease Crises (preprint)

The recent coronavirus pandemic has highlighted the many challenges faced by the healthcare, public safety, and economic systems when confronted with a surge in patients that require intensive treatment and a population that must be quarantined or shelter in place. The most obvious and pressing challenge is taking care of acutely ill patients while managing spread of infection within the care facility, but this is just the tip of the iceberg if we consider what could be done to prepare in advance for future pandemics. Beyond the obvious need for strengthening medical knowledge and preparedness, there is a complementary need to anticipate and address the engineering challenges associated with infectious disease emergencies. Robotic technologies are inherently programmable, and robotic systems have been adapted and deployed, to some extent, in the current crisis for such purposes as transport, logistics, and disinfection. As technical capabilities advance and as the installed base of robotic systems increases in the future, they could play a much more significant role in future crises. This report is the outcome of a virtual workshop co-hosted by the National Academy of Engineering (NAE) and the Computing Community Consortium (CCC) held on July 9-10, 2020. The workshop consisted of over forty participants including representatives from the engineering/robotics community, clinicians, critical care workers, public health and safety experts, and emergency responders. It identifies key challenges faced by healthcare responders and the general population and then identifies robotic/technological responses to these challenges. Then it identifies the key research/knowledge barriers that need to be addressed in developing effective, scalable solutions. Finally, the report ends with the following recommendations on how to implement this strategy.