Through real-world surveillance of viral isolates from COVID-19 patients, researchers are able to anticipate the emergence of SARS-COV-2.
By gathering SARS-COV-2 specimens from successive COVID-19 patients, junior associate professor Kazuo Takayama (Cell Growth and Disruption Department) and a cooperative team of researchers in Japan have recently uncovered critical components involved for producing novel variations. The specificity of SARS-COV-2 OMICRON VARIANT BF.5, which infected patients over a period of months, was clarified by the study. The group emphasized how this respiratory infection has wide-ranging effects.
Only modest amounts of antibodies against SARS-COV-2 were found in the samples by researchers because of the patients’ prolonged immunosuppression due to eosinophilic fasciitis. Nevertheless, they found cytolytic granules in the patients’ serum, indicating that CD8+ T cells and NK (natural killer) cells were active.
Next-generation sequencing methods were used by researchers to examine the viral genomic sequences from swab samples. Viral genomes notably mutated at 10 sites between the first and second sample time points (day 0 and day 17); however, during subsequent sample collection intervals (days 18-56 and days 57-119), this changed to 27 and 37 sites, suggesting that the virus could rapidly accumulate mutations if left unchecked for longer than two months. By infecting human IPSC-derived lung organoids with each viral isolate, researchers evaluated the virus’s resistance potential and its impact on host cells by applying their experience with organoid technology. They found that the levels of viral generation and gene expression were constant throughout the isolates, suggesting that the infection of SARS-COV-2 remains infectious for the duration of the usual infection.
Researchers also looked into the sensitivity to antiviral medications and antibody therapy, including sotrovimab for anti-spike protein antibody therapy and remdesivir. Since all of the viral isolates had spike protein mutations (G339D or R346T), which made them resistant to sotrovimab, they all showed strong resistance to antibody therapy despite their great sensitivity to remdesivir treatment. These results imply that, in spite of the numerous mutations acquired during persistent infection, susceptibility and sensitivity to antiviral therapies stayed mostly unaltered.
The S protein amino acid sequence was the focus of a comparative phylogenetic analysis with new SARS-COV-2 variants to see if analyzing viral divergence in patients with chronic SARS-COV-2 infections could help forecast viral evolution. Significantly, a number of mutations (D574N, S975N, S1003I, and A1174V) that were uncommon prior to the existence of BF.5 were found at rates higher than 1% in progeny of ancestral variations, indicating a greater chance of emergence under strain pressure from BF.5. In order to verify this theory, the research team looked at the prevalence of these mutations in variations that emerged after the BF.5 strain.
Specifically, mutations D574N and S1003I were detected in more than 1% of offspring of lineage-derived variations (Ba.5.24, Ba.5.2.36, CG.1, BF.7.26, and BQ.1.1.21), indicating possible consequences for viral evolution in patients who are constantly infected as well as practical ramifications.
To sum up, the research indicates that it is possible to approximate the rate of viral evolution in patients who are continually infected, in tandem with the possibility of real-world viral development. To assess the generalizability of these results, it is imperative to include more individuals who are infected on a continual basis, as individual differences may distort the course of viral evolution.
