Limited Cross-Variant Immunity after Infection with the SARS-CoV-2 Omicron Variant Without Vaccination (preprint)

SARS-CoV-2 Delta and Omicron strains are the most globally relevant variants of concern (VOCs). While individuals infected with Delta are at risk to develop severe lung disease 1 , Omicron infection causes less severe disease, mostly upper respiratory symptoms 2,3 . The question arises whether rampant spread of Omicron could lead to mass immunization, accelerating the end of the pandemic. Here we show that infection with Delta, but not Omicron, induces broad immunity in mice. While sera from Omicron-infected mice only neutralize Omicron, sera from Delta-infected mice are broadly effective against Delta and other VOCs, including Omicron. This is not observed with the WA1 ancestral strain, although both WA1 and Delta elicited a highly pro-inflammatory cytokine response and replicated to similar titers in the respiratory tracts and lungs of infected mice as well as in human airway organoids. Pulmonary viral replication, pro-inflammatory cytokine expression, and overall disease progression are markedly reduced with Omicron infection. Analysis of human sera from Omicron and Delta breakthrough cases reveals effective cross-variant neutralization induced by both viruses in vaccinated individuals. Together, our results indicate that Omicron infection enhances preexisting immunity elicited by vaccines, but on its own may not induce broad, cross-neutralizing humoral immunity in unvaccinated individuals.

Omicron mutations enhance infectivity and reduce antibody neutralization of SARS-CoV-2 virus-like particles (preprint)

The Omicron SARS-CoV-2 virus contains extensive sequence changes relative to the earlier arising B.1, B.1.1 and Delta SARS-CoV-2 variants that have unknown effects on viral infectivity and response to existing vaccines. Using SARS-CoV-2 virus-like particles (SC2-VLPs), we examined mutations in all four structural proteins and found that Omicron showed increased infectivity relative to B.1, B.1.1 and similar to Delta, a property conferred by S and N protein mutations. Thirty-eight antisera samples from individuals vaccinated with tozinameran (Pfizer/BioNTech), elasomeran (Moderna), Johnson & Johnson vaccines and convalescent sera from unvaccinated COVID-19 survivors had moderately to dramatically reduced efficacy to prevent cell transduction by VLPs containing the Omicron mutations. The Pfizer/BioNTech and Moderna vaccine antisera showed strong neutralizing activity against VLPs possessing the ancestral spike protein (B.1, B.1.1), with 3-fold reduced efficacy against Delta and 15-fold lower neutralization against Omicron VLPs. Johnson & Johnson antisera showed minimal neutralization of any of the VLPs tested. Furthermore, the monoclonal antibody therapeutics Casirivimab and Imdevimab had robust neutralization activity against B.1, B.1.1 or Delta VLPs but no detectable neutralization of Omicron VLPs. Our results suggest that Omicron is at least as efficient at assembly and cell entry as Delta, and the antibody response triggered by existing vaccines or previous infection, at least prior to boost, will have limited ability to neutralize Omicron. In addition, some currently available monoclonal antibodies will not be useful in treating Omicron-infected patients.

Local monitoring of SARS-CoV-2 Variants in Two Large California Counties in 2021 (preprint)

Introduction: Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continues to persist due to mutations resulting in newer, more infectious variants of concern. The initial government response to COVID-19 failed to engage the private sector. Engaging the private sector could have bolstered the national capacity to process diagnostic tests and track variants of concern for disease for public health surveillance. We aimed to leverage an ongoing private SARS-CoV-2 testing laboratory’s infrastructure to monitor SARS-CoV-2 variants in two large California counties.Methods: Study enrollment was offered to adults aged 18 years or older in Los Angeles County and Riverside County in California who recently tested positive for SARS-CoV-2 by polymerase chain reaction (PCR) with a cycle threshold value less than or equal to 30 cycles. Trained healthcare workers directly observed self-collection of oral fluid or anterior nares specimens within 5 days of study enrollment. Specimens were transported and stored at 8°C or cooler. RNA was extracted from samples. Samples underwent library preparation and were sequenced. Sequencing data were filtered by quality criteria. High-quality genomic data were analyzed to identify SARS-CoV-2 lineages. Participant and genomic data were analyzed using statistical tools and visualized with toolkits. The study was approved by Advarra Institutional Review Board (Pro00053729).Results: From May 27, 2021 to September 9, 2021, 503 participants were enrolled and underwent specimen collection. Of those enrolled, there were 238 (47.3%) females, 329 (63.6%) vaccinated, and 221 (43.9%) of Hispanic or Spanish origin. Of the cohort, 496 (98.6%) had symptoms at the time of collection. Among the 503 participants, 443 (88.1%) nasal specimens and 353 (70.2%) oral specimens yielded sequencing results. Over our study period, the prevalence of the Alpha variant of SARS-CoV-2 decreased (initially 23.1% [95% confidence interval (95% CI): 0% to 0.49%] to 0% [95% CI: 0.0% to 0.0%]) as the prevalence of the Delta variant of SARS-CoV-2 increased (initially 33.3% [95% CI: 0.0% to 100.0%] to 100.0% [95% CI: 100.0% to 100.0%]). A strain that carried mutations of both Delta and Mu was identified.Conclusion: We found that outpatient SARS-CoV-2 variant surveillance could be conducted in private laboratory in a timely and accurate manner. The prevalence of different variants changed over time. A higher proportion of nasal specimens yielded results when compared to oral specimens. Timely outpatient SARS-CoV-2 variant surveillance could be used for public health efforts to identify changes in SARS-CoV-2 strain epidemiology in local areas. Government agencies should engage private laboratories in the surveillance of diseases that threaten the public’s health to supplement national disease reporting networks.