Scroll through the 7 publications from CERID labs, PIs, and lab technicians publications that have hit the PubMed stands since the end of September! Read on for highlights from the abstract and the diseases studied in this month’s publication roundup by following the links! Publications are listed by the date published. All descriptions of the work have been paraphrased from the publications' respective abstracts and are cited as such.
Adjuvant molecules, particularly toll like receptor (TLR) agonists have been in development for decades, though until now only a natural TLR 4 ligand (mono-phosphoryl lipid A, MPL) has been incorporated into licensed vaccine products, in formulations than enhance and complement the MPL activity. The inclusion of MPL-based formulations into vaccines has been based on enhancing antibody responses to subunit antigens, and has provided important proof-of-concept for enhancing desired immune responses to defined molecular targets. Challenges remain in adjuvant development, particularly for those that stimulated effective T cell responses for both preventative and therapeutic vaccines. The discovery of molecules, many based on RNA, that stimulate innate and adaptive immune responses and have the ability to stimulate potent CD8 T cell responses, has opened the door for development of a new generation of vaccines. Read the full article here!
Influenza epidemics and pandemics cause significant morbidity and mortality. An effective response to a potential pandemic requires the infrastructure to rapidly detect, characterise, and potentially contain new and emerging influenza strains at both an individual and population level. The objective of this study is to use data gathered simultaneously from community and hospital sites to develop a model of how influenza enters and spreads in a population. Starting in the 2018-2019 season, we have been enrolling individuals with acute respiratory illness from community sites throughout the Seattle metropolitan area, including clinics, childcare facilities, Seattle-Tacoma International Airport, workplaces, college campuses and homeless shelters. At these sites, we collect clinical data and mid-nasal swabs from individuals with at least two acute respiratory symptoms. Additionally, we collect residual nasal swabs and data from individuals who seek care for respiratory symptoms at four regional hospitals. Samples are tested using a multiplex molecular assay, and influenza whole genome sequencing is performed for samples with influenza detected. Geospatial mapping and computational modelling platforms are in development to characterise the regional spread of influenza and other respiratory pathogens. The study was approved by the University of Washington's Institutional Review Board (STUDY00006181). Results will be disseminated through talks at conferences, peer-reviewed publications and on the study website (www.seattleflu.org). Read the full article here!
SARS-CoV-2-specific antibodies may protect from reinfection and disease, providing the rationale for administration of plasma containing SARS-CoV-2 neutralizing antibodies (nAb) as a treatment for COVID-19. The clinical factors and laboratory assays to streamline plasma donor selection, and the durability of nAb responses, are incompletely understood. Adults with virologically-documented SARS-CoV-2 infection in a convalescent plasma donor screening program were tested for serum IgG to SARS-CoV-2 spike protein S1 domain, nucleoprotein (NP), and for nAb. Amongst 250 consecutive persons studied a median of 67 days since symptom onset, 243/250 (97%) were seropositive on one or more assays. Sixty percent of donors had nAb titers ≥1:80. Correlates of higher nAb titer included older age (adjusted OR [AOR] 1.03/year of age, 95% CI 1.00-1.06), male sex (AOR 2.08, 95% CI 1.13-3.82), fever during acute illness (AOR 2.73, 95% CI 1.25-5.97), and disease severity represented by hospitalization (AOR 6.59, 95% CI 1.32-32.96). Receiver operating characteristic (ROC) analyses of anti-S1 and anti-NP antibody results yielded cutoffs that corresponded well with nAb titers, with the anti-S1 assay being slightly more predictive. NAb titers declined in 37 of 41 paired specimens collected a median of 98 days (range, 77-120) apart (P<0.001). Seven individuals (2.8%) were persistently seronegative and lacked T cell responses. Nab titers correlated with COVID-19 severity, age, and sex. Standard commercially available SARS-CoV-2 IgG results can serve as useful surrogates for nAb testing. Functional nAb levels were found to decline and a small proportion of COVID-19 survivors lack adaptive immune responses. Read the full article here!
Identifying risk factors for SARS-CoV-2 infection could help health systems improve testing and screening strategies. Identify demographic factors, comorbid conditions, and symptoms independently associated with testing positive for SARS-CoV-2. Observational cross-sectional study. Veterans Health Administration. Persons tested for SARS-CoV-2 nucleic acid by polymerase chain reaction (PCR) between March 1 and May 14, 2020. Associations between demographic characteristics, diagnosed comorbid conditions, and documented symptoms with testing positive for SARS-CoV-2. Of 88,747 persons tested, 10,131 (11.4%) were SARS-CoV-2 PCR positive. Positivity was associated with older age (≥80 vs. <50 years: aOR 2.16, 95% CI 1.97-2.37), male sex (aOR 1.45, 95% CI 1.34-1.57), regional SARS-CoV-2 burden (≥2,000 vs. <400 cases/million: aOR 5.43, 95% CI 4.97-5.93), urban residence (aOR 1.78, 95% CI 1.70-1.87), Black (aOR 2.15, 95% CI 2.05-2.26) or American Indian/Alaska Native/Pacific Islander (aOR 1.26, 95% CI 1.05-1.52) vs. White race, and Hispanic ethnicity (aOR 1.52, 95% CI 1.40-1.65). Obesity and diabetes were the only two medical conditions associated with testing positive. Documented fevers, chills, cough, and diarrhea were also associated with testing positive. The population attributable fraction of positive tests was highest for regional SARS-CoV-2 burden (35.3%), followed by demographic variables (27.2%), symptoms (12.0%), obesity (10.5%), and diabetes (0.4%). Lack of information on SARS-CoV-2 exposures or the indications for testing which may affect the likelihood of testing positive. The majority of positive SARS-CoV-2 tests were attributed to regional SARS-CoV-2 burden, demographic characteristics and obesity with a minor contribution of chronic comorbid conditions. Read the full article here!