The emergence of highly transmissible SARS-CoV-2 variants has led to surges in cases and the need for global genomic surveillance. While some variants rapidly spread worldwide, other variants only persist nationally. There is a need for more fine-scale analysis to understand transmission dynamics at a country scale. For instance, the Mu variant of interest, also known as lineage B.1.621, was first detected in Colombia and was responsible for a large local wave but only a few sporadic cases elsewhere. To provide a better understanding of the epidemiology of SARS-Cov-2 variants in Colombia, we used 14,049 complete SARS-CoV-2 genomes from the 32 states of Colombia, and performed Bayesian phylodynamic analyses to estimate the time of variants introduction, their respective effective reproductive number, and effective population size, and the impact of disease control measures. We detected a total of 188 SARS-CoV-2 Pango lineages circulating in Colombia since the start of the pandemic. We showed that the effective reproduction number oscillated drastically throughout the first two years of the pandemic, with Mu showing the highest transmissibility (Re and growth rate estimation). Our results reinforce that genomic surveillance programs are essential for countries to make evidence-driven interventions towards the emergence and circulation of novel SARS-CoV-2 variants.
AO_SCPLOWBSTRACTC_SCPLOWPersistent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections have been reported in immune-compromised individuals and people undergoing immune-modulatory treatments. Although intrahost evolution has been documented, to our knowledge, no direct evidence of subsequent transmission and stepwise adaptation is available. Here we describe sequential persistent SARS-CoV-2 infections in three individuals that led to the emergence, forward transmission, and continued evolution of a new Omicron sublineage, BA.1.23, over an eight-month period. The initially transmitted BA.1.23 variant encoded seven additional amino acid substitutions within the spike protein (E96D, R346T, L455W, K458M, A484V, H681R, A688V), and displayed substantial resistance to neutralization by sera from boosted and/or Omicron BA.1-infected study participants. Subsequent continued BA.1.23 replication resulted in additional substitutions in the spike protein (S254F, N448S, F456L, M458K, F981L, S982L) as well as in five other virus proteins. Our findings demonstrate that the Omicron BA.1 lineage can diverge further from its already exceptionally mutated genome during persistent infection in more than one host, and also document ongoing transmission of these novel variants. There is an urgent need to implement strategies to prevent prolonged SARS-CoV-2 replication and to limit the spread of newly emerging, neutralization-resistant variants in vulnerable patients.
IntroductionVenezuela and Colombia both adopted measures of containment early in response to the COVID-19 pandemic. However, Venezuelas ongoing humanitarian crisis has decimated its health care system, and forced millions of Venezuelans to flee through its porous border with Colombia. The extensive shared border, and illegal cross-border transit through improvised trails between the two countries are major challenges for public health authorities. We report the first SARS-CoV-2 genomes from Venezuela, and present a snapshot of the SARS-CoV-2 epidemiologic landscape in the Colombian-Venezuelan border region. MethodsWe sequenced and assembled viral genomes from total RNA extracted from nasopharyngeal (NP) clinical specimens using a custom reference-based analysis pipeline. Three assemblies obtained were subjected to typing using the Phylogenetic Assignment of Named Global Outbreak LINeages Pangolin tool. A total of 376 publicly available SARS-CoV-2 genomes from South America were obtained from the GISAID database to perform comparative genomic analyses. Additionally, the Wuhan-1 strain was used as reference. ResultsWe found that two of the SARS-CoV-2 genomes from Venezuela belonged to the B1 lineage, and the third to the B.1.13 lineage. We observed a point mutation in the Spike protein gene (D614G substitution), previously reported to be associated with increased infectivity, in all three Venezuelan genomes. An additional three mutations (R203K/G204R substitution) were present in the nucleocapsid (N) gene of one Venezuelan genome. ConclusionsGenomic sequencing demonstrates similarity between SARS-CoV-2 lineages from Venezuela and viruses collected from patients in bordering areas in Colombia and from Brazil, consistent with cross-border transit despite administrative measures including lockdowns. The presence of mutations associated with increased infectivity in the 3 Venezuelan genomes we report and Colombian SARS-CoV-2 genomes from neighboring borders areas may pose additional challenges for control of SARS-CoV-2 spread in the complex epidemiological landscape in Latin American countries. Public health authorities should carefully follow the progress of the pandemic and its impact on displaced populations within the region.
Since its emergence in Wuhan (China) on December 2019 the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has rapidly spread worldwide. After its arrival in South America in February 2020 the virus has expanded throughout the region infecting over 900,000 individuals with approximately 41,000 reported deaths to date. In response to the rapidly growing number of cases, a number of different primer-probe sets have been developed. However, despite being highly specific most of these primer-probe sets are known to exhibit variable sensitivity. Currently, there are more than 700 SARS-CoV2 whole genome sequences deposited in databases from Brazil, Chile, Ecuador, Colombia, Uruguay, Peru and Argentina. To test how regional viral diversity may impact oligo binding sites and affect test performance, we reviewed all available primer-probe sets targeting the E, N and RdRp genes against available South American SARS-CoV-2 genomes checking for nucleotide variations in annealing sites. Results from this in silico analysis showed no nucleotide variations on the E-gene target region, in contrast to the N and RdRp genes which showed massive nucleotide variations within oligo binding sites. In lines with previous data, our results suggest that E-gene stands as the most conserved and reliable target when considering single-gene target testing for molecular diagnosis of SARS-CoV-2 in South America.
ObjectiveAsymptomatic carriers (AC) of the new Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) represent an important source of spread for Coronavirus Disease 2019 (COVID-19). Early diagnosis of these cases is a powerful tool to control the pandemic. Our objective was to characterize patients with AC status and identify associated sociodemographic factors. MethodsUsing a cross-sectional design and the national database of daily occurrence of COVID-19, we characterized both socially and demographically all ACs. Additional Correspondence Analysis and Logistic Regression Model were performed to identify characteristics associated with AC state (OR, 95% CI). Results2338 ACs (11.8%; 95% CI, 11.3-12.2%) were identified, mainly in epidemiological week 18 [EW] (3.98; 3.24-4.90). Age [≤] 39 years (1.56; 1.42-1.72). Male sex (1.39; 1.26-1.53), cases imported from Argentina, Spain, Peru, Brazil, Costa Rica or Mexico (3.37; 1.47-7.71) and autochthonous cases (4.35; 2.12-8.93) increased the risk of identifying AC. We also identified groups of departments with moderate (3.68; 3.13-4.33) and strong (8.31; 6.10-7.46) association with AC. DiscussionSociodemographic characteristics strongly associated with AC were identified, which may explain its epidemiological relevance and usefulness to optimize mass screening strategies and prevent person-to-person transmission.
We performed phylogenomic analysis of severe acute respiratory syndrome coronavirus-2 (SARS-CoV2) from 88 infected individuals across different regions of Colombia. Eleven different lineages were detected, suggesting multiple introduction events. Pangolin lineages B.1 and B.1.5 were the most frequent, with B.1 being associated with prior travel to high-risk areas. Article Summary LineWe sequenced 88 genomes of SARS-CoV2 from Colombia finding 11 lineages and eight different introduction events
BACKGROUNDSevere Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) and its associated clinical syndrome COVID-19 are causing overwhelming morbidity and mortality around the globe, disproportionately affecting New York City. A comprehensive, integrative autopsy series that advances the mechanistic discussion surrounding this disease process is still lacking. METHODSAutopsies were performed at the Mount Sinai Hospital on 67 COVID-19 positive patients and data from the clinical records were obtained from the Mount Sinai Data Warehouse. The experimental design included a comprehensive microscopic examination carried out by a team of expert pathologists, along with transmission electron microscopy, immunohistochemistry, RNA in situ hybridization, as well as immunology and serology assays. RESULTSLaboratory results of our COVID-19 cohort show elevated inflammatory markers, abnormal coagulation values, and elevated cytokines IL-6, IL-8 and TNF. Autopsies revealed large pulmonary emboli in four cases. We report microthrombi in multiple organ systems including the brain, as well as conspicuous hemophagocytosis and a secondary hemophagocytic lymphohistiocytosis-like syndrome in many of our patients. We provide electron microscopic, immunofluorescent and immunohistochemical evidence of the presence of the virus and the ACE2 receptor in our samples. CONCLUSIONSWe report a comprehensive autopsy series of 67 COVID-19 positive patients revealing that this disease, so far conceptualized as a primarily respiratory viral illness, also causes endothelial dysfunction, a hypercoagulable state, and an imbalance of both the innate and adaptive immune responses. Novel findings reported here include an endothelial phenotype of ACE2 in selected organs, which correlates with clotting abnormalities and thrombotic microangiopathy, addressing the prominent coagulopathy and neuropsychiatric symptoms. Another original observation is that of macrophage activation syndrome, with hemophagocytosis and a hemophagocytic lymphohistiocytosis-like disorder, underlying the microangiopathy and excessive cytokine release. We discuss the involvement of critical regulatory pathways.
New York City (NYC) has emerged as one of the epicenters of the current SARS-CoV2 pandemic. To identify the early events underlying the rapid spread of the virus in the NYC metropolitan area, we sequenced the virus causing COVID19 in patients seeking care at the Mount Sinai Health System. Phylogenetic analysis of 84 distinct SARS-CoV2 genomes indicates multiple, independent but isolated introductions mainly from Europe and other parts of the United States. Moreover, we find evidence for community transmission of SARS-CoV2 as suggested by clusters of related viruses found in patients living in different neighborhoods of the city.
