Transmission cluster of COVID-19 cases from Uruguay: emergence and spreading of a novel SARS-CoV-2 ORF6 deletion

BACKGROUND Evolutionary changes in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) include indels in non-structural, structural, and accessory open reading frames (ORFs) or genes. OBJECTIVES We track indels in accessory ORFs to infer evolutionary gene patterns and epidemiological links between outbreaks. METHODS Genomes from Coronavirus disease 2019 (COVID-19) case-patients were Illumina sequenced using ARTIC_V3. The assembled genomes were analysed to detect substitutions and indels. FINDINGS We reported the emergence and spread of a unique 4-nucleotide deletion in the accessory ORF6, an interesting gene with immune modulation activity. The deletion in ORF6 removes one repeat unit of a two 4-nucleotide repeat, which shows that directly repeated sequences in the SARS-CoV-2 genome are associated with indels, even outside the context of extended repeat regions. The 4-nucleotide deletion produces a frameshifting change that results in a protein with two inserted amino acids, increasing the coding information of this accessory ORF. Epidemiological and genomic data indicate that the deletion variant has a single common ancestor and was initially detected in a health care outbreak and later in other COVID-19 cases, establishing a transmission cluster in the Uruguayan population. MAIN CONCLUSIONS Our findings provide evidence for the origin and spread of deletion variants and emphasise indels' importance in epidemiological studies, including differentiating consecutive outbreaks occurring in the same health facility.

Megacities, migration and an evolutionary approach to bipolar disorder: a study of Sardinian immigrants in Latin America

Objective: To determine whether people with a Sardinian genetic background who live in the megacities of South America have a higher frequency of hypomania than residents of Sardinia. Methods: A community survey of Sardinian immigrants was carried out in four Brazilian metropoles (n=218) and Buenos Aires (n=306). The results were compared with those of a study involving a similar methodology (Mood Disorder Questionnaire [MDQ] as a screening tool) conducted in seven Italian regions, including a sub-sample from Sardinia. Results: There was a higher prevalence of lifetime hypomania among Sardinians living in the Brazilian metropoles than among those living in Sardinia. This result was also consistent with Sardinian immigrants in Buenos Aires. After stratification by sex and age, the lifetime prevalence of MDQ scores ≥ 8 among Sardinians in South-American megacities and Sardinia was 8.6% vs. 2.9%, respectively (p < 0.0001). Conclusions: The higher frequency of hypomania in migrant populations appears to favor an evolutionary view in which mood disorders may be a maladaptive aspect of a genetic background with adaptive characteristics.

An evolutionary approach to mania studying Sardinian immigrants to Argentina

Objective: To ascertain lifetime prevalence of positivity to a screening questionnaire for bipolar disorders (BD) in Sardinian immigrants to Argentina and residents of Sardinia and assess whether such positivity affects quality of life (QoL) in either group. Our hypothesis is that screen positivity for BD may be more frequent in immigrants. Methods: Observational study. Subjects were randomly selected from the membership lists of associations of Sardinian immigrants in Argentina. A study carried out in Sardinia using the same methodology was used for comparison. The Mood Disorder Questionnaire was used to screen for mania/hypomania and the Short-Form Health Survey-12 to measure QoL. Results: A higher prevalence of manic/hypomanic episodes was found in Sardinian immigrants to Argentina (p < 0.0001; odds ratio = 3.0, 95% confidence interval 1.87-4.77). Positivity at screening was associated with a lower QoL both in Sardinian immigrants to Argentina and in residents of Sardinia. Conclusions: To the best of our knowledge, this is the first study to show a higher lifetime prevalence of manic/hypomanic episodes in a general-population sample of individuals who migrated to a foreign country. Our results are in agreement with the hypothesis that hyperactive/novelty-seeking features may represent an adaptive substrate in certain conditions of social change.