Natural evolution of SARS-CoV-2 variants in K18-ACE2 mice gives rise to more virulent virus and variant alleles associated with treatment resistance. (preprint)

Background: The continuing COVID-19 pandemic is partially due to viral evolution decreasing vaccine and treatment efficacies. Predicting viral evolution is difficult. Others have found that serial infections of the original SARS-CoV-2 isolate in non transgenic mice is accompanied with selection of alleles (such as Spike 417N, 493H and 501Y) conferring adaptation and greater binding affinity for the murine ACE2 receptor, enhanced infectivity, and lethal phenotype in mice. We designed a study to investigate long-term viral evolution's impact in K18-ACE2 mice with virus closer related to the Omicron sub-lineage. Methods: We serially infected SARS-CoV-2-naive mice with either the B.1.351 (Beta) or the B.1.617.2 (Delta) variant across twenty passages without selective pressures. We sequenced virus across passages, annotating variant alleles changing in frequency using published tools, tracking alleles suspected of decreasing vaccine/treatment efficacy. We evaluated virulence in animals infected with virus isolated at study completion and determined antibody neutralization sensitivity using sera from vaccinated individuals. Results and Conclusions: We observed variant alleles with documented roles in vaccine-elicited immunity evasion. This included the Omicron-associated mutation spike S371F that arose de-novo during our study. Passage 20 (P20) viruses were more virulent that their P0 counterpart with P20 Delta lineage being significantly more resistant to antibody neutralization. These developments occurred within two months of the study starting, suggesting that our model can rapidly emulate pandemic progression in mammals. While our model lacked selective pressures, such as pre-existing SARS-CoV-2 immunity, these conditions could readily be adapted. Such modeling could enable development of more evolution-resistant treatments.

Evaluation of real-life use of Point-Of-Care Rapid Antigen TEsting for SARS-CoV-2 in schools for outbreak control (EPOCRATES) (preprint)

AbstractO_ST_ABSBackgroundC_ST_ABSWe evaluated the use of rapid antigen detection tests (RADT) for the diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in school settings to determine RADTs performance compared to PCR. MethodsIn this real-world, prospective observational cohort study, high-school students and staff were recruited from two high-schools in Montreal (Canada) and followed from January 25th to June 10th, 2021. Twenty-five percent of asymptomatic participants were tested weekly by RADT (nasal) and PCR (gargle). Class contacts of cases were tested. Symptomatic participants were tested by RADT (nasal) and PCR (nasal and gargle). The number of cases and outbreaks were compared to other high schools in the same area. ResultsOverall, 2,099 students and 286 school staff members consented to participate. The overall RADTs specificity varied from 99.8 to 100%, with a lower sensitivity, varying from 28.6% in asymptomatic to 83.3% in symptomatic participants. Secondary cases were identified in 10 of 35 classes. Returning students to school after a 7-day quarantine, with a negative PCR on D6-7 after exposure, did not lead to subsequent outbreaks. Of cases for whom the source was known, 37 of 57 (72.5%) were secondary to household transmission, 13 (25%) to intra-school transmission and one to community contacts between students in the same school. ConclusionRADT did not perform well as a screening tool in asymptomatic individuals. Reinforcing policies for symptom screening when entering schools and testing symptomatic individuals with RADT on the spot may avoid subsequent significant exposures in class. Table of Contents SummaryRapid antigen tests were compared to standard PCR to diagnose SARS-CoV-2 infections in high-school students. They performed better in symptomatic individuals. Whats Known on This SubjectRapid antigen detection tests (RADT) are often used to diagnose respiratory pathogens at the point-of-care. Their performance characteristics vary, but they usually have high specificity and moderate sensitivity compared with PCR. What This Study AddsRADT sensitivity ranged from 28.6% in asymptomatic individuals to 83.3% in symptomatic individuals. Return to school after 7 days of quarantine was safe in exposed students. Secondary cases were identified in 28% of classes with an index case.