Passive Immunity Trial for Our Nation (PassITON): study protocol for a randomized placebo-control clinical trial evaluating COVID-19 convalescent plasma in hospitalized adults (preprint)

Background: Convalescent plasma is being used widely as a treatment for coronavirus disease 2019 (COVID-19). However, the clinical efficacy of COVID-19 convalescent plasma is unclear. Methods: : The Pass ive I mmunity T rial for O ur N ation (PassITON), is a multicenter, placebo-controlled, blinded, randomized clinical trial being conducted in the United States to provide high-quality evidence on the efficacy of COVID-19 convalescent plasma as a treatment for adults hospitalized with symptomatic disease. Adults hospitalized with COVID-19 with respiratory symptoms for less than 14 days are eligible. Enrolled patients are randomized in a 1:1 ratio to 1 unit (200-399 mL) of COVID-19 convalescent plasma that has demonstrated neutralizing function using a SARS-CoV-2 chimeric virus neutralization assay. Study treatments are administered in a blinded fashion and patients are followed for 28 days. The primary outcome is clinical status 14 days after study treatment as measured on a 7-category ordinal scale assessing mortality, respiratory support, and return to normal activities of daily living. Key secondary outcomes include mortality and oxygen-free days. The trial is projected to enroll 1000 patients and is designed to detect an odds ratio ≤ 0.73 for the primary outcome. Discussion: This trial will provide the most robust data available to date on the efficacy of COVID-19 convalescent plasma for the treatment of adults hospitalized with acute moderate to severe COVID-19. These data will be useful to guide the treatment of COVID-19 patients in the current pandemic and for informing decisions about whether developing a standardized infrastructure for collecting and disseminating convalescent plasma to prepare for future viral pandemics is indicated. Trial Registration: ClinicalTrials.gov: NCT04362176. Date of trial registration: April 24, 2020, https://clinicaltrials.gov/ct2/show/NCT04362176

Use of a Novel Liquid Bead-Array Assay to Determine Correlation between SARS-CoV-2 Binding Antibody Level and COVID-19 Disease Severity (preprint)

A detailed understanding of the adaptive host response to SARS-CoV-2 infection in humans is urgently needed, as questions abound regarding serologic responses and the development of antibody-mediated immunity against COVID-19. We developed a highly sensitive, high-throughput, and efficient assay using liquid bead array technology. We observed advantages over traditional indirect ELISA for the detection and quantification of binding IgG against the receptor binding domain (RBD) of SARS-CoV-2. Using this sensitive and highly reproducible assay, we sought to determine whether the severity of COVID-19 symptoms is correlated with SARS-CoV-2 binding IgG level. We measured SARS-CoV-2 RBD IgG levels from 67 subjects who had recovered from PCR-confirmed, symptomatic COVID-19. Samples were obtained approximately 6 weeks post-symptom onset. We found that COVID-19 symptom severity, assessed on an 8-point severity scale, strongly correlated with RBD IgG level (p<0.001), with and without adjustment for covariates of age, sex, and time from symptom onset. These findings have substantial implications for public policy surrounding assessments of antibody responses and possible immunity, as not all cases of COVID-19 can be assumed to generate a protective antibody response, and mild disease in particular is capable of generating very low-level anti-RBD IgG levels. These findings also have important implications for the selection of donors for convalescent plasma to be used as a therapeutic, and other scenarios where antibody level, rather than mere presence or absence, is relevant.