RESUMO
The emergence of the new Brazilian variant of concern, P.1 lineage (Gamma), raised concern about its impact on the epidemiological profile of COVID-19 cases due to its higher transmissibility rate and immune evasion ability. Using 272 whole-genome sequences combined with epidemiological data, we showed that P.1 introduction in Sao Jose do Rio Preto, Sao Paulo, Brazil, was followed by the displacement of eight circulating SARS-CoV-2 variants and a rapid increase in prevalence two months after its first detection. Our findings support that the P.1 variant is associated with an increase in mortality risk and severity of COVID-19 cases in younger aged groups, which corresponds to the unvaccinated population at the time. Moreover, our data highlight the beneficial effects of vaccination indicated by a pronounced reduction of severe cases and deaths in immunized individuals, reinforcing the need for rapid and massive vaccination.
RESUMO
COVID-19 is prevalent in the elderly. Old individuals are more likely to develop pneumonia and respiratory failure due to alveolar damage, suggesting that lung senescence may increase the susceptibility to SARS-CoV-2 infection and replication. Considering that human coronavirus (HCoVs; SARS-CoV-2 and SARS-CoV) require host cellular factors for infection and replication, we analyzed Genotype-Tissue Expression (GTEx) data to test whether lung aging is associated with transcriptional changes in human protein-coding genes that potentially interact with these viruses. We found decreased expression of the gene tribbles homolog 3 (TRIB3) during aging in male individuals, and its protein was predicted to interact with HCoVs nucleocapsid protein and RNA-dependent RNA polymerase. Using publicly available lung single-cell data, we found TRIB3 expressed mainly in alveolar epithelial cells that express SARS-CoV-2 receptor ACE2. Functional enrichment analysis of age-related genes, in common with SARS-CoV-induced perturbations, revealed genes associated with the mitotic cell cycle and surfactant metabolism. Given that TRIB3 was previously reported to decrease virus infection and replication, the decreased expression of TRIB3 in aged lungs may help explain why older male patients are related to more severe cases of the COVID-19. Thus, drugs that stimulate TRIB3 expression should be evaluated as a potential therapy for the disease.