RESUMO
COVID-19, caused by the SARS-COV-2 virus, induces numerous immunological reactions linked to the severity of the clinical condition of those infected. The surface Spike protein (S protein) present in Sars-CoV-2 is responsible for the infection of host cells. This protein presents a high rate of mutations, which can increase virus transmissibility, infectivity, and immune evasion. Therefore, we propose to evaluate, using immunoinformatic techniques, the predicted epitopes for the S protein of seven variants of Sars-CoV-2. MHC class I and II epitopes were predicted and further assessed for their immunogenicity, interferon-gamma (IFN-γ) inducing capacity, and antigenicity. For B cells, linear and structural epitopes were predicted. For class I MHC epitopes, 40 epitopes were found for the clades of Wuhan, Clade 2, Clade 3, and 20AEU.1, Gamma, and Delta, in addition to 38 epitopes for Alpha and 44 for Omicron. For MHC II, there were differentially predicted epitopes for all variants and eight equally predicted epitopes. These were evaluated for differences in the MHC II alleles to which they would bind. Regarding B cell epitopes, 16 were found in the Wuhan variant, 14 in 22AEU.1 and in Clade 3, 15 in Clade 2, 11 in Alpha and Delta, 13 in Gamma, and 9 in Omicron. When compared, there was a reduction in the number of predicted epitopes concerning the Spike protein, mainly in the Delta and Omicron variants. These findings corroborate the need for updates seen today in bivalent mRNA vaccines against COVID-19 to promote a targeted immune response to the main circulating variant, Omicron, leading to more robust protection against this virus and avoiding cases of reinfection. When analyzing the specific epitopes for the RBD region of the spike protein, the Omicron variant did not present a B lymphocyte epitope from position 390, whereas the epitope at position 493 for MHC was predicted only for the Alpha, Gamma, and Omicron variants.
RESUMO
Globally, lung cancer is the leading cause of cancer death. Previous trials demonstrated that low-dose computed tomography lung cancer screening of high-risk individuals can reduce lung cancer mortality by 20% or more. Lung cancer screening has been approved by major guidelines in the United States, and over 4,000 sites offer screening. Adoption of lung screening outside the United States has, until recently, been slow. Between June 2017 and May 2019, the Ontario Lung Cancer Screening Pilot successfully recruited 7,768 individuals at high risk identified by using the PLCOm2012noRace lung cancer risk prediction model. In total, 4,451 participants were successfully screened, retained and provided with high-quality follow-up, including appropriate treatment. In the Ontario Lung Cancer Screening Pilot, the lung cancer detection rate and the proportion of early-stage cancers were 2.4% and 79.2%, respectively; serious harms were infrequent; and sensitivity to detect lung cancers was 95.3% or more. With abnormal scans defined as ones leading to diagnostic investigation, specificity was 95.5% (positive predictive value, 35.1%), and adherence to annual recall and early surveillance scans and clinical investigations were high (>85%). The Ontario Lung Cancer Screening Pilot provides insights into how a risk-based organized lung screening program can be implemented in a large, diverse, populous geographic area within a universal healthcare system.