SARS-CoV-2 genomic characterization and clinical manifestation of the COVID-19 outbreak in Uruguay

Abstract

COVID-19 is a respiratory illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and declared by the World Health Organization a global public health emergency. Among the severe outbreaks across South America, Uruguay has become known for curtailing SARS-CoV-2 exceptionally well. To understand the SARS-CoV-2 introductions, local transmissions, and associations with genomic and clinical parameters in Uruguay, we sequenced the viral genomes of 44 outpatients and inpatients in a private healthcare system in its capital, Montevideo, from March to May 2020. We performed a phylogeographic analysis using sequences from our cohort and other studies that indicate a minimum of 23 independent introductions into Uruguay, resulting in five major transmission clusters. Our data suggest that most introductions resulting in chains of transmission originate from other South American countries, with the earliest seeding of the virus in late February 2020, weeks before the borders were closed to all non-citizens and a partial lockdown implemented. Genetic analyses suggest a dominance of S and G clades (G, GH, GR) that make up >90% of the viral strains in our study. In our cohort, lethal outcome of SARS-CoV-2 infection significantly correlated with arterial hypertension, kidney failure, and ICU admission (FDR < 0.01), but not with any mutation in a structural or non-structural protein, such as the spike D614G mutation. Our study contributes genetic, phylodynamic, and clinical correlation data about the exceptionally well-curbed SARS-CoV-2 outbreak in Uruguay, which furthers the understanding of disease patterns and regional aspects of the pandemic in Latin America.

SARS-CoV-2 Infectivity and Severity of COVID-19 According to SARS-CoV-2 Variants: Current Evidence

“…The frequency of S protein 614G was significantly associated with high fatality rates in several countries, as reported in studies which analyzed SARS-CoV-2 sequences from GISAID database [8,10,11]. However, clinical studies showed that this mutation did not correlate with severity of COVID-19, including mortality, transfer to ICU, mechanic ventilation, or length of stay at hospital [30,37,41,42,44,45].…”

“…A clinical study by Long et al showed that infection with SARS-CoV-2 variants harboring the D614G substitution was not associated with disease severity, overall mortality, transfer to ICU, mechanical ventilation and length of stay at hospital [41]. This result was supported by other research [33,45]. In a study conducted among 44 Vietnamese patients, 85 mutations covering 67 variant types were reported, of which P323L and D614G variants were the most frequent (present in 40/44 patients), followed by C241U (39/44) and GGG to AAC at 28881-3 variants (33/44).…”

“…Of the 63 publications included, five were non-peer reviewed preprints [16,17,52,54,66]. Eleven articles reported in vitro, in silico or animal model studies [15,18,19,[22][23][24][25][26][27][28][29]; nineteen articles reported clinical studies [16,[37][38][39][41][42][43][44][45][46][47][48][49]51,[70][71][72][73]. The remaining 33 articles analyzed SARS-CoV-2 genomes downloaded from the GISAID or other available databases with patient status [8][9][10][11]20,21,[30][31][32][33][34][35][36]40,50,…”

“…A total of 45 articles addressed the effect of viral mutations on severity of COVID-19 in patients, of which fifteen studies (five bigdata analyses [21,30,33,34,40] and ten clinical studies [39,[41][42][43][44][45][46][47][48][49]) showed no association between SARS-CoV-2 variants and severity of disease. Three studies (one bigdata analysis [50] and two clinical studies [17,51]) reported that the SARS-CoV-2 variants were significantly associated with decrease in severity of disease.…”

Analysis Of SARS-CoV-2 Genomes Of Samples From Peru

“…En Uruguay, el análisis genético muestra que los clados S y G (G, GH, GR) dominan, representando más del 90% de las cepas del virus en nuestro estudio; el resultado fatal de la infección por SARS-CoV-2 está significativamente relacionado con la hipertensión, Insuficiencia renal e ingreso en UCI (FDR <0,01), pero no hay mutaciones en proteínas estructurales o no estructurales como la proteína pico D614G (12) . Al igual que en Perú, países de Norteamérica como Canadá ha rastreado al clado GR con mayor frecuencia, seguidos de los clados G y GH, y en menor frecuencia los clados S y L, estos últimos fueron identificados en la misma frecuencia en Estados Unidos, no obstante, en este país se ha identificado con más frecuencia al clado GH seguidos de los clados GR y G; en México, no ocurre lo mismo, ya que los clados más frecuentes son GR y G seguido del GH, siendo igual en el caso de los clados S y L siendo muy menores, además de que en esta parte del continente americano se encontraron los clados O y V (11) .…”