RESUMEN
OBJECTIVES: This study aimed to explore associations between the molecular characterization of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and disease severity in ambulatory and hospitalized patients in two main Colombian epicentres during the first year of the coronavirus disease 2019 pandemic. METHODS: In total, 1000 patients with SARS-CoV-2 infection were included in this study. Clinical data were collected from 997 patients, and 678 whole-genome sequences were obtained by massively parallel sequencing. Bivariate, multi-variate, and classification and regression tree analyses were run between clinical and genomic variables. RESULTS: Age >88 years, and infection with lineages B.1.1, B.1.1.388, B.1.523 or B.1.621 for patients aged 71-88 years were associated with death [odds ratio (OR) 6.048036, 95% confidence interval (CI) 1.346567-32.92521; P=0.01718674]. The need for hospitalization was associated with higher age and comorbidities. The hospitalization rate increased significantly for patients aged 38-51 years infected with lineages A, B, B.1.1.388, B.1.1.434, B.1.153, B.1.36.10, B.1.411, B.1.471, B.1.558 or B.1.621 (OR 8.368427, 95% CI 2.573145-39.10672, P=0.00012). Associations between clades and clinical outcomes diverged from previously reported data. CONCLUSIONS: Infection with lineage B.1.621 increased the hospitalization and mortality rates. These findings, plus the rapidly increasing prevalence in Colombia and other countries, suggest that lineage B.1.621 should be considered as a 'variant of interest'. If associated disease severity is confirmed, possible designation as a 'variant of concern' should be considered.
Asunto(s)
COVID-19 , SARS-CoV-2 , Adulto , Anciano , Anciano de 80 o más Años , COVID-19/epidemiología , Colombia/epidemiología , Genómica , Humanos , Estudios Longitudinales , Persona de Mediana Edad , Pandemias , SARS-CoV-2/genéticaRESUMEN
The severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is the etiopathogenic agent of COVID-19, a condition that has led to a formally recognized pandemic by March 2020 (World Health Organization -WHO). The SARS-CoV-2 genome is constituted of 29,903 base pairs, that code for four structural proteins (N, M, S, and E) and more than 20 non-structural proteins. Mutations in any of these regions, especially in those that encode for the structural proteins, have allowed the identification of diverse lineages around the world, some of them named as Variants of Concern (VOC) and Variants of Interest (VOI), according to the WHO and CDC. In this study, by using Next Generation Sequencing (NGS) technology, we sequenced the SARS-CoV-2 genome of 422 samples from Colombian residents, all of them collected between April 2020 and January 2021. We obtained genetic information from 386 samples, leading us to the identification of 14 new lineages circulating in Colombia, 13 of which were identified for the first time in South America. GH was the predominant GISAID clade in our sample. Most mutations were either missense (53.6%) or synonymous mutations (37.4%), and most genetic changes were located in the ORF1ab gene (63.9%), followed by the S gene (12.9%). In the latter, we identified mutations E484K, L18F, and D614G. Recent evidence suggests that these mutations concede important particularities to the virus, compromising host immunity, the diagnostic test performance, and the effectiveness of some vaccines. Some important lineages containing these mutations are the Alpha, Beta, and Gamma (WHO Label). Further genomic surveillance is important for the understanding of emerging genomic variants and their correlation with disease severity.
Asunto(s)
COVID-19/epidemiología , Genoma Viral , Mutación , SARS-CoV-2/genética , Glicoproteína de la Espiga del Coronavirus/genética , Proteínas Virales/genética , COVID-19/transmisión , COVID-19/virología , Colombia/epidemiología , Monitoreo Epidemiológico , Evolución Molecular , Expresión Génica , Humanos , Filogenia , Poliproteínas/genética , Poliproteínas/metabolismo , SARS-CoV-2/clasificación , SARS-CoV-2/patogenicidad , Glicoproteína de la Espiga del Coronavirus/metabolismo , Factores de Tiempo , Proteínas Virales/metabolismo , Secuenciación Completa del GenomaRESUMEN
IMPORTANCE: The effect of high-flow oxygen therapy vs conventional oxygen therapy has not been established in the setting of severe COVID-19. OBJECTIVE: To determine the effect of high-flow oxygen therapy through a nasal cannula compared with conventional oxygen therapy on need for endotracheal intubation and clinical recovery in severe COVID-19. DESIGN, SETTING, AND PARTICIPANTS: Randomized, open-label clinical trial conducted in emergency and intensive care units in 3 hospitals in Colombia. A total of 220 adults with respiratory distress and a ratio of partial pressure of arterial oxygen to fraction of inspired oxygen of less than 200 due to COVID-19 were randomized from August 2020 to January 2021, with last follow-up on February 10, 2021. INTERVENTIONS: Patients were randomly assigned to receive high-flow oxygen through a nasal cannula (n = 109) or conventional oxygen therapy (n = 111). MAIN OUTCOMES AND MEASURES: The co-primary outcomes were need for intubation and time to clinical recovery until day 28 as assessed by a 7-category ordinal scale (range, 1-7, with higher scores indicating a worse condition). Effects of treatments were calculated with a Cox proportional hazards model adjusted for hypoxemia severity, age, and comorbidities. RESULTS: Among 220 randomized patients, 199 were included in the analysis (median age, 60 years; n = 65 women [32.7%]). Intubation occurred in 34 (34.3%) randomized to high-flow oxygen therapy and in 51 (51.0%) randomized to conventional oxygen therapy (hazard ratio, 0.62; 95% CI, 0.39-0.96; P = .03). The median time to clinical recovery within 28 days was 11 (IQR, 9-14) days in patients randomized to high-flow oxygen therapy vs 14 (IQR, 11-19) days in those randomized to conventional oxygen therapy (hazard ratio, 1.39; 95% CI, 1.00-1.92; P = .047). Suspected bacterial pneumonia occurred in 13 patients (13.1%) randomized to high-flow oxygen and in 17 (17.0%) of those randomized to conventional oxygen therapy, while bacteremia was detected in 7 (7.1%) vs 11 (11.0%), respectively. CONCLUSIONS AND RELEVANCE: Among patients with severe COVID-19, use of high-flow oxygen through a nasal cannula significantly decreased need for mechanical ventilation support and time to clinical recovery compared with conventional low-flow oxygen therapy. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04609462.
Asunto(s)
COVID-19/complicaciones , Intubación Intratraqueal/estadística & datos numéricos , Terapia por Inhalación de Oxígeno/métodos , Oxígeno/uso terapéutico , Insuficiencia Respiratoria/terapia , Anciano , Anciano de 80 o más Años , COVID-19/terapia , Enfermedad Crítica/mortalidad , Enfermedad Crítica/terapia , Femenino , Humanos , Unidades de Cuidados Intensivos , Intubación Intratraqueal/efectos adversos , Masculino , Persona de Mediana Edad , Terapia por Inhalación de Oxígeno/instrumentación , Respiración Artificial , Insuficiencia Respiratoria/etiología , Insuficiencia Respiratoria/mortalidad , SARS-CoV-2 , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: Adequate testing is critically important for control of the SARS-CoV-2 pandemic. Antibody testing is an option for case management and epidemiologic studies, with high specificity and variable sensitivity. However, characteristics of local populations may affect performance of these tests. For this reason, the National Institute of Health (INS) and regulatory agencies in Colombia require verification of diagnostic accuracy of tests introduced to the Colombian market. METHODS: We conducted a validation study of the Abbott SARS-CoV-2 test for qualitative detection of IgG using the Abbott Architect i2000SR. Participants and retrospective samples were included from patients with suspected SARS-CoV-2 infection, age ≥18 years, and ≥8 days elapsed since initiation of symptoms. Pre-pandemic plasma samples (taken before October 2019) were used as controls. We estimated the sensitivity, specificity and agreement (kappa) of the Abbott IgG test compared to the gold standard (RT-PCR). RESULTS: The overall sensitivity was 83.1% (95% CI: 75.4-100). Sensitivity among patients with ≥14 days since the start of symptoms was 85.7%, reaching 88% in samples collected from patients with COVID-19 symptoms onset >60 days. Specificity was 100% and the kappa index of agreement was 0.804 (95% CI: 0.642-0.965). CONCLUSIONS: Our findings show high sensitivity and specificity of the Abbott IgG test in a Colombian population, which meet the criteria set by the Colombian INS to aid in the diagnosis of COVID-19. Data from our patient groups also suggest that IgG response is detectable in a high proportion of individuals (88.1%) during the first two months following onset of symptoms.