RESUMEN
We identified 11 conserved stretches in over 6.3 million SARS-CoV-2 genomes including all the major variants of concerns. Each conserved stretch is ≥100 nucleotides in length with ≥99.9% conservation at each nucleotide position. Interestingly, six of the eight conserved stretches in ORF1ab overlapped significantly with well-folded experimentally verified RNA secondary structures. Furthermore, two of the conserved stretches were mapped to regions within the S2-subunit that undergo dynamic structural rearrangements during viral fusion. In addition, the conserved stretches were significantly depleted for zinc-finger antiviral protein (ZAP) binding sites, which facilitated the recognition and degradation of viral RNA. These highly conserved stretches in the SARS-CoV-2 genome were poorly conserved at the nucleotide level among closely related ß-coronaviruses, thus representing ideal targets for highly specific and discriminatory diagnostic assays. Our findings highlight the role of structural constraints at both RNA and protein levels that contribute to the sequence conservation of specific genomic regions in SARS-CoV-2.
RESUMEN
BACKGROUND: Epidemiological studies focused on primary healthcare needs of persons experiencing homelessness (PEH) are often based on data from specialist homeless healthcare services. AIM: To explore the presentation of PEH, coding of homelessness, and associated health conditions in mainstream primary care general practices in England. DESIGN & SETTING: EMIS electronic database search of medical records was conducted across 48 general practices in a clinical commissioning group (CCG), representing one of the most socioeconomically deprived regions in England, which also lacks a specialist primary healthcare service for PEH. METHOD: Key terms and codes were used to identify PEH, their respective diagnoses across 22 health conditions, and prescribed medications over the past 4 years. RESULTS: From a population of approximately 321 000, 43 (0.013%) people were coded as PEH, compared with a homelessness prevalence of 0.5% in the English general population. Mental health conditions were the most prevalent diagnoses among the PEH registrants (56.6%); the recorded prevalence of other common long-term conditions in PEH was lower than the levels observed in PEH registered with specialist homelessness health services. CONCLUSION: In a population with approximately four times higher rate of statutory homelessness, PEH representation in mainstream general practices was under-represented by several folds. As homelessness overlaps with mental health, substance misuse, and long-term health conditions, consistent coding of homelessness in medical records is imperative in order to offer tailored support and prevention actions when patients present for services.