ABSTRACT
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.
ABSTRACT
El tratamiento de pacientes inmunosuprimidos con agentes anti-factor de necrosis tumoral alfa (TNF-alfa), representa un desafío en tanto se trata de fármacos con un efecto inmonomodulador que presuponen un aumento en el riesgo de infecciones oportunistas. Presentamos un paciente de 42 años, coinfectado con el virus de inmunodeficiencia humana (HIV) y hepatitis C (HCV), con eritrodermia y artritis psoriática severa en respuesta al tratamiento con metotrexato, tratado con etanercept. Durante el primer año de tratamiento no se reportaron efectos adversos ni infecciones oportunistas. Si bien ha habido reportes de eritrodermia y de artritis psoriásica tratados con etanercept, asociados o no a infección por HIV y/o HCV, en nuestro conocimiento, este es el primer caso reportado con una presentación concomitante de eritrodermia psoriásica y artritis psoriásica en un paciente coinfectado con HIV y HCV tratado existosamente con un agente anti-TNF-alfa.
The use of anti tumor necrosis factor alfa (TNF-alfa) agents in immunosuppressed patients, represents a challenge in as much as this drugs with an immune modulator effect, pose a raise in the risk for opportunistic infections. We present a 42 year old patient, co-infected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV), with erythroderma and severe psoriatic arthritis, without response to methotrexate, treated with etanercept. No adverse effects, or opportunistic infections were reported during the first year of treatment. This it is the first report of a successful treatment with an anti-TNF alfa agent in a patient with a concomitant presentation of psoriatic erythroderma, severe psoriatic arthritis, co-infected with HIV and HCV.