https://www.nature.com/articles/s41392-022-00941-z.pdf

SARS-CoV-2 spike L452R mutation increases Omicron variant fusogenicity and infectivity as well as host glycolysis

Rouleaux (stacked clumps) of red blood cells (RBCs) observed in the blood of COVID-19 patients in three studies call attention to the properties of several enveloped virus strains dating back to seminal findings of the 1940s. For COVID-19, key such properties are: (1) SARS-CoV-2 binds to RBCs in vitro and also in the blood of COVID-19 patients; (2) although ACE2 is its target for viral fusion and replication, SARS-CoV-2 initially attaches to sialic acid (SA) terminal moieties on host cell membranes via glycans on its spike protein; (3) certain enveloped viruses express hemagglutinin esterase (HE), an enzyme that releases these glycan-mediated bindings to host cells, which is expressed among betacoronaviruses in the common cold strains but not the virulent strains, SARS-CoV, SARS-CoV-2 and MERS. The arrangement and chemical composition of the glycans at the 22 N-glycosylation sites of SARS-CoV-2 spike protein and those at the sialoglycoprotein coating of RBCs allow exploration of specifics as to how virally induced RBC clumping may form. The in vitro and clinical testing of these possibilities can be sharpened by the incorporation of an existing anti-COVID-19 therapeutic that has been found in silico to competitively bind to multiple glycans on SARS-CoV-2 spike protein.

/pdf/a-deadly-embrace-hemagglutination-mediated-by-sars-cov-2-3d94f0g8.pdf

A Deadly Embrace: Hemagglutination Mediated by SARS-CoV-2 Spike Protein at Its 22 N-Glycosylation Sites, Red Blood Cell Surface Sialoglycoproteins, and Antibody

Significance Bronchial epithelia are the primary target for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Here, we reconstituted bronchial epithelia from adult and child donors and show that SARS-CoV-2 infections spread fast, resulting in the formation and synchronized release of large clusters of infected cells and syncytia into the apical lumen, contributing to virus dissemination. Some epithelia, for the most part from children, revealed an intrinsic resistance to infection and virus spread. This infection control correlates with faster type III interferon secretion and can be transferred to permissive epithelia through exogenous interferon application. Child epithelia also showed a muted inflammatory response compared with adult, suggesting a specific and age-adapted epithelial response to SARS-CoV-2 infection that may explain why children are less susceptible to severe COVID-19.

Bronchial epithelia from adults and children: SARS-CoV-2 spread via syncytia formation and type III interferon infectivity restriction

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9425700

Genomic and epidemiologic surveillance of SARS-CoV-2 in Southern Brazil and identification of a new Omicron-L452R sublineage

There are limited data comparing the transmission rates and kinetics of viable virus shedding of the Omicron variant to those of the Delta variant. We compared these rates in hospitalized patients infected with Delta and Omicron variants. We prospectively enrolled adult patients with COVID‐19 admitted to a tertiary care hospital in South Korea between September 2021 and May 2022. Secondary attack rates were calculated by epidemiologic investigation, and daily saliva samples were collected to evaluate viral shedding kinetics. Genomic and subgenomic SARS‐CoV‐2 RNA was measured by PCR, and virus culture was performed from daily saliva samples. A total of 88 patients with COVID‐19 who agreed to daily sampling and were interviewed, were included. Of the 88 patients, 48 (59%) were infected with Delta, and 34 (41%) with Omicron; a further 5 patients gave undetectable or inconclusive RNA PCR results and 1 was suspected of being coinfected with both variants. Omicron group had a higher secondary attack rate (31% [38/124] vs. 7% [34/456], p < 0.001). Survival analysis revealed that shorter viable virus shedding period was observed in Omicron variant compared with Delta variant (median 4, IQR [1−7], vs. 8.5 days, IQR [5–12 days], p < 0.001). Multivariable analysis revealed that moderate‐to‐critical disease severity (HR: 1.96), and immunocompromised status (HR: 2.17) were independent predictors of prolonged viral shedding, whereas completion of initial vaccine series or first booster‐vaccinated status (HR: 0.49), and Omicron infection (HR: 0.44) were independently associated with shorter viable virus shedding. Patients with Omicron infections had higher transmission rates but shorter periods of transmissible virus shedding than those with Delta infections.

Annie Bernier

Papers

The Mechanism and Consequences of SARS-CoV-2 Spike-Mediated Fusion and Syncytia Formation.