Publications by authors named "Marcela Mercado-Reyes"

19 Publications

  • Page 1 of 1

Reduced levels of convalescent neutralizing antibodies against SARS-CoV-2 B.1+L249S+E484K lineage.

Virus Res 2021 Nov 12;308:198629. Epub 2021 Nov 12.

Fundación Banco Nacional de Sangre Hemolife, Bogotá, Colombia; Faculty of Science, Universidad Antonio Nariño, Calle 23 #116-31, Bodega 26, Bogotá, Colombia. Electronic address:

The E484K mutation at the SARS-CoV-2 Spike protein emerged independently in different variants around the world and has been widely associated with immune escape from neutralizing antibodies generated during previous infection or vaccination. In this work, the B.1 + L249S+E484K lineage was isolated along with A.1, B.1.420, and B.1.111 SARS-CoV-2 lineages without the E484K mutation and the neutralizing titer of convalescent sera was compared using microneutralization assays. While no significant differences in the neutralizing antibody titers were found between A.1 and B.lineages without the E484K mutation, the neutralizing titers against B.1 + L249S+E484K were 1.5, 1.9, 2.1, and 1.3-fold lower than against A.1, B.1.420, B.1.111-I, and B.1.111-II, respectively. However, molecular epidemiological data indicate that there is no increase in the transmissibility rate associated with this new lineage. This study supports the capability of new variants with the E484K mutation to be resistant to neutralization by humoral immunity, and therefore the need to intensify surveillance programs to determine if these lineages represent a risk for public health.
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http://dx.doi.org/10.1016/j.virusres.2021.198629DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8585963PMC
November 2021

Seroprevalence of the SARS-CoV-2 antibody in healthcare workers: a multicentre cross-sectional study in 10 Colombian cities.

Occup Environ Med 2021 Nov 5. Epub 2021 Nov 5.

Grupo de investigación en Salud Ambiental y Laboral, Instituto Nacional de Salud, Bogotá, Colombia.

Background: Healthcare workers are at increased risk of infection due to occupational exposure to SARS-CoV-2-infected patients. The objective of this study was to determine the seroprevalence of SARS-CoV-2 in healthcare workers in Colombia.

Methods: This study is a cross-sectional study focused on estimating the seroprevalence of SARS-CoV-2 antibodies in healthcare workers from 65 hospitals in 10 cities in Colombia during the second semester of 2020. The seroprevalence was determined using an automated immunoassay (Abbott SARS-CoV-2 CLIA IgG). The study included a survey to establish the sociodemographic variables and the risk of infection. A multivariate model was used to evaluate the association between the results of seroprevalence and risk factors.

Results: The global seroprevalence of antibodies against SARS-CoV-2 was 35% (95% Bayesian CI 33% to 37%). All the personnel reported the use of protective equipment. General services personnel and nurses presented the highest ratios of seroprevalence among the healthcare workers. Low socioeconomic strata have shown a strong association with seropositivity.

Conclusion: This study estimates the prevalence of SARS-CoV-2 infection among healthcare workers. Even though all the personnel reported the use of protective equipment, the seroprevalence in the general services personnel and nurses was high. Also, a significant difference by cities was observed.
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http://dx.doi.org/10.1136/oemed-2021-107487DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8577941PMC
November 2021

Pregnancy, Birth, Infant, and Early Childhood Neurodevelopmental Outcomes among a Cohort of Women with Symptoms of Zika Virus Disease during Pregnancy in Three Surveillance Sites, Project (VEZ), Colombia, 2016-2018.

Trop Med Infect Dis 2021 Oct 12;6(4). Epub 2021 Oct 12.

National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, GA 30329, USA.

Project (VEZ), an intensified surveillance of pregnant women with symptoms of the Zika virus disease (ZVD) in Colombia, aimed to evaluate the relationship between symptoms of ZVD during pregnancy and adverse pregnancy, birth, and infant outcomes and early childhood neurodevelopmental outcomes. During May-November 2016, pregnant women in three Colombian cities who were reported with symptoms of ZVD to the national surveillance system, or with symptoms of ZVD visiting participating clinics, were enrolled in Project VEZ. Data from maternal and pediatric (up to two years of age) medical records were abstracted. Available maternal specimens were tested for the presence of the Zika virus ribonucleic acid and/or anti-Zika virus immunoglobulin antibodies. Of 1213 enrolled pregnant women with symptoms of ZVD, 1180 had a known pregnancy outcome. Results of the Zika virus laboratory testing were available for 569 (48.2%) pregnancies with a known pregnancy outcome though testing timing varied and was often distal to the timing of symptoms; 254 (21.5% of the whole cohort; 44.6% of those with testing results) were confirmed or presumptive positive for the Zika virus infection. Of pregnancies with a known outcome, 50 (4.2%) fetuses/infants had Zika-associated brain or eye defects, which included microcephaly at birth. Early childhood adverse neurodevelopmental outcomes were more common among those with Zika-associated birth defects than among those without and more common among those with laboratory evidence of a Zika virus infection compared with the full cohort. The proportion of fetuses/infants with any Zika-associated brain or eye defect was consistent with the proportion seen in other studies. Enhancements to Colombia's existing national surveillance enabled the assessment of adverse outcomes associated with ZVD in pregnancy.
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http://dx.doi.org/10.3390/tropicalmed6040183DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8544689PMC
October 2021

Characterization of the emerging B.1.621 variant of interest of SARS-CoV-2.

Infect Genet Evol 2021 11 14;95:105038. Epub 2021 Aug 14.

Group Genomics of Emerging Microorganisms. Dirección de Investigación en Salud Pública, Instituto Nacional de Salud, Bogotá, Colombia; Dirección de Investigación en Salud Pública, Instituto Nacional de Salud, Bogotá, Colombia.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genetic diversity has the potential to impact the virus transmissibility and the escape from natural infection- or vaccine-elicited neutralizing antibodies. Here, representative samples from circulating SARS-CoV-2 in Colombia between January and April 2021, were processed for genome sequencing and lineage determination following the nanopore amplicon ARTIC network protocol and PANGOLIN pipeline. This strategy allowed us to identify the emergence of the B.1.621 lineage, considered a variant of interest (VOI) with the accumulation of several substitutions affecting the Spike protein, including the amino acid changes I95I, Y144T, Y145S and the insertion 146 N in the N-terminal domain, R346K, E484K and N501Y in the Receptor binding Domain (RBD) and P681H in the S1/S2 cleavage site of the Spike protein. The rapid increase in frequency and fixation in a relatively short time in Magdalena, Atlantico, Bolivar, Bogotá D.C, and Santander that were near the theoretical herd immunity suggests an epidemiologic impact. Further studies will be required to assess the biological and epidemiologic roles of the substitution pattern found in the B.1.621 lineage.
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http://dx.doi.org/10.1016/j.meegid.2021.105038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8364171PMC
November 2021

Novel Highly Divergent SARS-CoV-2 Lineage With the Spike Substitutions L249S and E484K.

Front Med (Lausanne) 2021 28;8:697605. Epub 2021 Jun 28.

Dirección de Investigación en Salud Pública, Instituto Nacional de Salud, Bogotá, Colombia.

COVID-19 pandemics has led to genetic diversification of SARS-CoV-2 and the appearance of variants with potential impact in transmissibility and viral escape from acquired immunity. We report a new and highly divergent lineage containing 21 distinctive mutations (10 non-synonymous, eight synonymous, and three substitutions in non-coding regions). The amino acid changes L249S and E484K located at the CTD and RBD of the Spike protein could be of special interest due to their potential biological role in the virus-host relationship. Further studies are required for monitoring the epidemiologic impact of this new lineage.
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http://dx.doi.org/10.3389/fmed.2021.697605DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8273171PMC
June 2021

Epidemiological and viral features of a cohort of SARS-CoV-2 symptomatic and asymptomatic individuals in an area of the Colombian Caribbean.

Ann Clin Microbiol Antimicrob 2020 Dec 7;19(1):58. Epub 2020 Dec 7.

Instituto de Investigaciones Biológicas del Trópico, Facultad de Medicina Veterinaria y Zootecnia, Universidad de Córdoba, Montería, Colombia.

Background: Severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) is an emerging viral pandemic disease. In the last 6 months, SARS-CoV-2 has caused millions of reported cases and hundreds of thousands of deaths. As other world regions, South America has not contained the pandemic's advance since it lacks the hospital and economic capacities. Public health implications of transmission, while the asymptomatic/presymptomatic infection is a critical concern at the current pandemic.

Objective: Describe the socio-demographic, clinical, and viral features of a cohort of SARS-CoV-2 infected individuals from the Colombian Caribbean.

Methods: Six hundred eighty-six clinical samples of suspected SARS-CoV-2 infection cases and contacts individuals from several hospital centers in the department of Córdoba, Colombia, were received at our laboratory between April 9th and May 16th, 2020. RNA was extracted using lysis buffers and spin columns. The samples were tested for SARS-CoV-2 by reverse transcription real-time polymerase chain reaction (RT-qPCR) using commercially available multiplex real-time PCR assay for simultaneous detection of 3 target genes of SARS-CoV-2 (Allplex™, 2019-nCoV assay, Korea). Viral copies quantification was done using a standard curve constructed from seriated dilutions of a SARS-CoV-2 positive control. Statics descriptive methods were used.

Results: Thirty-five nasopharyngeal samples were positive for SARS-CoV-2 infection; the average age was 43 (range, 1-95 years). Seventeen of 35 (49%) of the patients showed symptoms. Most of them had a cough, fever, and odynophagia; three of the patients reported having arthralgia. Only two patients required hospitalization. None of the patients had known co-morbidities. RT-qPCR results show that two of the symptomatic patients had significantly higher RNA copies than the rest. Eighteen of 35 (51%) individuals were asymptomatic, and the average age was 30 (range, 6-61 years). Four asymptomatic individuals showed a higher copy than some symptomatic patients; nonetheless, the average of RNA copies 8.26 × 10 was lower than the symptomatic.

Conclusions: This study shows that asymptomatic patients may develop infections with a high number of RNA copies. Since a considerable percentage of infections may be asymptomatic/presymptomatic, enhanced testing approaches may be needed to detect these persons. Due the occurrence of a large proportion of infections being a result from transmission originated in asymptomatic/presymptomatic individuals, public health interventions in Colombia should be based on two steps: a massive molecular screening, and viral load quantification. Finally, a remarkable issue in our study is the average age of symptomatic and asymptomatic groups (43 and 30 respectively) which may be important because of the economic impact that has been caused by the coronavirus pandemic and may be probably the cause of the reduced lethality observed in the country and the department at the time of this study.
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http://dx.doi.org/10.1186/s12941-020-00397-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7720255PMC
December 2020

Genomic Epidemiology of Severe Acute Respiratory Syndrome Coronavirus 2, Colombia.

Emerg Infect Dis 2020 12;26(12):2854-2862

Coronavirus disease (COVID-19) in Colombia was first diagnosed in a traveler arriving from Italy on February 26, 2020. However, limited data are available on the origins and number of introductions of COVID-19 into the country. We sequenced the causative agent of COVID-19, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), from 43 clinical samples we collected, along with another 79 genome sequences available from Colombia. We investigated the emergence and importation routes for SARS-CoV-2 into Colombia by using epidemiologic, historical air travel, and phylogenetic observations. Our study provides evidence of multiple introductions, mostly from Europe, and documents >12 lineages. Phylogenetic findings validate the lineage diversity, support multiple importation events, and demonstrate the evolutionary relationship of epidemiologically linked transmission chains. Our results reconstruct the early evolutionary history of SARS-CoV-2 in Colombia and highlight the advantages of genome sequencing to complement COVID-19 outbreak investigations.
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http://dx.doi.org/10.3201/eid2612.202969DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7706936PMC
December 2020

COVID-19 Infection Detection and Prevention by SARS-CoV-2 Active Antigens: A Synthetic Vaccine Approach.

Vaccines (Basel) 2020 Nov 18;8(4). Epub 2020 Nov 18.

Departamento de Farmacia, Universidad Nacional de Colombia- Sede Bogotá, Carrera 30#45-03, Bogotá DC 111321, Colombia.

COVID-19, a global pandemic causing to date more than 50 million cases and more than a million deaths, has to be controlled. SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) was identified as the causative agent. Controversy about this virus origin and infectious mechanism for adapting to humans remains a matter for discussion. Among all strategies for obtaining safe and potent vaccines, approaches based on attenuated-killed virus and non-replicating RNA viral vectors are demonstrating promising results. However, specificity of viral components targeted by human antibodies so far has not been demonstrated. A consistent strategy for obtaining functional-active antigens from SARS-CoV-2 specific ligands lead us to propose and test a number of synthetic components. From hundreds of starting sequences only fifteen fulfilled the design requirements and were produced as monomer and polymer forms and immuno-chemically tested. The design was based on worldwide representative reported virus genomes. A bioinformatics scheme by conventional methods and knowledge on MHC-I and II antigen processing mechanisms and HLA haplotype-restriction was performed including sensitive and resistant human populations to virus infection. Covid-19 patients' sera reactivity for synthetic SARS-CoV-2-designed components have proven a high recognition of specific molecules, as well as some evidence for a long-lasting humoral immune response.
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http://dx.doi.org/10.3390/vaccines8040692DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7712209PMC
November 2020

SARS-CoV-2 sequencing: The technological initiative to strengthen early warning systems for public health emergencies in Latin America and the Caribbean

Biomedica 2020 10 30;40(Supl. 2):188-197. Epub 2020 Oct 30.

Grupo de Salud Materna y Perinatal, Dirección de Investigación en Salud Pública, Instituto Nacional de Salud, Bogotá, Colombia; Dirección de Investigación en Salud Pública, Instituto Nacional de Salud, Bogotá, D.C., Colombia.

The COVID-19 pandemic caused by SARS-CoV-2 is a public health problem on a scale unprecedented in the last 100 years, as has been the response focused on the rapid genomic characterization of SARS-CoV-2 in virtually all regions of the planet. This pandemic emerged during the era of genomic epidemiology, a science fueled by continued advances in next-generation sequencing. Since its recent appearance, genomic epidemiology included the precise identification of new lineages or species of pathogens and the reconstruction of their genetic variability in real time, evidenced in past outbreaks of influenza H1N1, MERS, and SARS. However, the global and uncontrolled scale of this pandemic created a scenario where genomic epidemiology was put into practice en masse, from the rapid identification of SARS-CoV-2 to the registration of new lineages and their active surveillance throughout the world. Prior to the COVID-19 pandemic, the availability of genomic data on circulating pathogens in several Latin America and the Caribbean countries was scarce or nil. With the arrival of SARS-CoV-2, this scenario changed significantly, although the amount of available information remains scarce and, in countries such as Colombia, Brazil, Argentina, and Chile, the genomic information of SARS-CoV-2 was obtained mainly by research groups in genomic epidemiology rather than the product of a public health surveillance policy or program. This indicates the need to establish public health policies aimed at implementing genomic epidemiology as a tool to strengthen surveillance and early warning systems against threats to public health in the region.
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http://dx.doi.org/10.7705/biomedica.5841DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7676827PMC
October 2020

SARS-CoV-2 and RT-PCR in asymptomatic patients: Results of a cohort of workers at El Dorado International Airport in Bogotá, 2020

Biomedica 2020 10 30;40(Supl. 2):166-172. Epub 2020 Oct 30.

Dirección de Investigación en Salud Pública, Instituto Nacional de Salud, Bogotá, D.C., Colombia.

Introduction: The 2019 coronavirus pandemic (COVID-19) has caused around 25 million cases worldwide. Asymptomatic patients have been described as potential sources of transmission. However, there are difficulties to detect them and to establish their role in the dynamics of virus transmission, which hinders the implementation of prevention strategies. Objective: To describe the behavior of asymptomatic SARS-CoV-2 virus infection in a cohort of workers at the El Dorado “Luis Carlos Galán Sarmiento” International Airport in Bogotá, Colombia. Materials and methods: A prospective cohort of 212 workers from the El Dorado airport was designed. The follow-up began in June, 2020. A survey was used to characterize health and work conditions. Every 21 day, a nasopharyngeal swab was taken to identify the presence of SARS-CoV-2 using RT-PCR. We analyzed the behavior of the cycle threshold (ORF1ab and N genes) according to the day of follow-up. Results: In the first three follow-ups of the cohort, we found an incidence of SARS-CoV-2 infection of 16.51%. The proportion of positive contacts was 14.08%. The median threshold for cycle threshold was 33.53. Conclusion: We characterized the asymptomatic SARS-CoV-2 infection in a cohort of workers. The identification of asymptomatic infected persons continues to be a challenge for epidemiological surveillance systems.
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http://dx.doi.org/10.7705/biomedica.5802DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7676845PMC
October 2020

Isolation and characterization of an early SARS-CoV-2 isolate from the 2020 epidemic in Medellín, Colombia

Biomedica 2020 10 30;40(Supl. 2):148-158. Epub 2020 Oct 30.

Grupo de Inmunovirología, Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia.

Introduction: SARS-CoV-2 has been identified as the new coronavirus causing an outbreak of acute respiratory disease in China in December, 2019. This disease, currently named COVID-19, has been declared as a pandemic by the World Health Organization (WHO). The first case of COVID-19 in Colombia was reported on March 6, 2020. Here we characterize an early SARS-CoV-2 isolate from the pandemic recovered in April, 2020. Objective: To describe the isolation and characterization of an early SARS-CoV-2 isolate from the epidemic in Colombia. Materials and methods: A nasopharyngeal specimen from a COVID-19 positive patient was inoculated on different cell lines. To confirm the presence of SARS-CoV-2 on cultures we used qRT-PCR, indirect immunofluorescence assay, transmission and scanning electron microscopy, and next-generation sequencing. Results: We determined the isolation of SARS-CoV-2 in Vero-E6 cells by the appearance of the cytopathic effect three days post-infection and confirmed it by the positive results in the qRT-PCR and the immunofluorescence with convalescent serum. Transmission and scanning electron microscopy images obtained from infected cells showed the presence of structures compatible with SARS-CoV-2. Finally, a complete genome sequence obtained by next-generation sequencing allowed classifying the isolate as B.1.5 lineage. Conclusion: The evidence presented in this article confirms the first isolation of SARSCoV-2 in Colombia. In addition, it shows that this strain behaves in cell culture in a similar way to that reported in the literature for other isolates and that its genetic composition is consistent with the predominant variant in the world. Finally, points out the importance of viral isolation for the detection of neutralizing antibodies, for the genotypic and phenotypic characterization of the strain and for testing compounds with antiviral potential.
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http://dx.doi.org/10.7705/biomedica.5834DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7676823PMC
October 2020

Substitutions in Spike and Nucleocapsid proteins of SARS-CoV-2 circulating in South America.

Infect Genet Evol 2020 11 17;85:104557. Epub 2020 Sep 17.

Unidad de Secuenciación y Genómica, Grupo de Investigación Básica y Aplicada en Enfermedades Emergentes, Dirección de Investigación en Salud Pública, Instituto Nacional de Salud, Bogotá 111321, Colombia; Dirección de Investigación en Salud Pública, Instituto Nacional de Salud, Bogotá 111321, Colombia.

SARS-CoV-2 is a new member of the genus Betacoronavirus, responsible for the COVID-19 pandemic. The virus crossed the species barrier and established in the human population taking advantage of the spike protein high affinity for the ACE receptor to infect the lower respiratory tract. The Nucleocapsid (N) and Spike (S) are highly immunogenic structural proteins and most commercial COVID-19 diagnostic assays target these proteins. In an unpredictable epidemic, it is essential to know about their genetic variability. The objective of this study was to describe the substitution frequency of the S and N proteins of SARS-CoV-2 in South America. A total of 504 amino acid and nucleotide sequences of the S and N proteins of SARS-CoV-2 from seven South American countries (Argentina, Brazil, Chile, Ecuador, Peru, Uruguay, and Colombia), reported as of June 3, and corresponding to samples collected between March and April 2020, were compared through substitution matrices using the Muscle algorithm. Forty-three sequences from 13 Colombian departments were obtained in this study using the Oxford Nanopore and Illumina MiSeq technologies, following the amplicon-based ARTIC network protocol. The substitutions D614G in S and R203K/G204R in N were the most frequent in South America, observed in 83% and 34% of the sequences respectively. Strikingly, genomes with the conserved position D614 were almost completely replaced by genomes with the G614 substitution between March to April 2020. A similar replacement pattern was observed with R203K/G204R although more marked in Chile, Argentina and Brazil, suggesting similar introduction history and/or control strategies of SARS-CoV-2 in these countries. It is necessary to continue with the genomic surveillance of S and N proteins during the SARS-CoV-2 pandemic as this information can be useful for developing vaccines, therapeutics and diagnostic tests.
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http://dx.doi.org/10.1016/j.meegid.2020.104557DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7497549PMC
November 2020

Molecular analysis of several in-house rRT-PCR protocols for SARS-CoV-2 detection in the context of genetic variability of the virus in Colombia.

Infect Genet Evol 2020 10 4;84:104390. Epub 2020 Jun 4.

Unidad de Secuenciación y Genómica, Dirección de Investigación en Salud Pública, Instituto Nacional de Salud, Bogotá 111321, Colombia; Grupo de Salud Materna y Perinatal, Dirección de Investigación en Salud Pública, Instituto Nacional de Salud, Bogotá 111321, Colombia; Dirección de Investigación en Salud Pública, Instituto Nacional de Salud, Bogotá 111321, Colombia. Electronic address:

The COVID-19 pandemic caused by SARS-CoV-2 is a public health problem unprecedented in the recent history of humanity. Different in-house real-time RT-PCR (rRT-PCR) methods for SARS-CoV-2 diagnosis and the appearance of genomes with mutations in primer regions have been reported. Hence, whole-genome data from locally-circulating SARS-CoV-2 strains contribute to the knowledge of its global variability and the development and fine tuning of diagnostic protocols. To describe the genetic variability of Colombian SARS-CoV-2 genomes in hybridization regions of oligonucleotides of the main in-house methods for SARS-CoV-2 detection, RNA samples with confirmed SARS-CoV-2 molecular diagnosis were processed through next-generation sequencing. Primers/probes sequences from 13 target regions for SARS-CoV-2 detection suggested by 7 institutions and consolidated by WHO during the early stage of the pandemic were aligned with Muscle tool to assess the genetic variability potentially affecting their performance. Finally, the corresponding codon positions at the 3' end of each primer, the open reading frame inspection was identified for each gene/protein product. Complete SARS-CoV-2 genomes were obtained from 30 COVID-19 cases, representative of the current epidemiology in the country. Mismatches between at least one Colombian sequence and five oligonucleotides targeting the RdRP and N genes were observed. The 3' end of 4 primers aligned to the third codon position, showed high risk of nucleotide substitution and potential mismatches at this critical position. Genetic variability was detected in Colombian SARS-CoV-2 sequences in some of the primer/probe regions for in-house rRT-PCR diagnostic tests available at WHO COVID-19 technical guidelines; its impact on the performance and rates of false-negative results should be experimentally evaluated. The genomic surveillance of SARS-CoV-2 is highly recommended for the early identification of mutations in critical regions and to issue recommendations on specific diagnostic tests to ensure the coverage of locally-circulating genetic variants.
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http://dx.doi.org/10.1016/j.meegid.2020.104390DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7272177PMC
October 2020

Spatial distribution of the relative risk of Zika virus disease in Colombia during the 2015-2016 epidemic from a Bayesian approach.

Int J Gynaecol Obstet 2020 Jan;148 Suppl 2:55-60

Department of Public Health, Universidad del Norte, Barranquilla, Colombia.

Objective: To determine the spatial distribution of the risk of Zika virus disease in each region of Colombia during the 2015-2016 epidemic.

Methods: An ecological study was designed to estimate the risks for each Colombian region using first-order neighbors, covariate effects, and three adjacent periods of time (beginning, development, and end of the epidemic) to analyze the spatial distribution of the disease based on a Bayesian hierarchical model.

Results: Spatial distribution of the estimated risks of Zika virus disease showed that it increased in a strip that crosses the central area of the country from west to east. Analysis of the three time periods showed greater risk of the disease in the central and southern zones-Arauca and Santander-where the increase in risk was four times higher during the peak phase compared with the initial phase of the outbreak.

Conclusion: In the identified high-risk areas, integrated surveillance systems for Zika virus disease and its complications must be strengthened to provide up-to-date and accurate epidemiological information. This information would allow those involved in policy and decision making to identify new outbreaks and risk clusters, enabling more focused and accurate measures to target at-risk populations.
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http://dx.doi.org/10.1002/ijgo.13048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7065154PMC
January 2020

Genomic epidemiology supports multiple introductions and cryptic transmission of Zika virus in Colombia.

BMC Infect Dis 2019 Nov 12;19(1):963. Epub 2019 Nov 12.

Department of Epidemiology, University of Washington, Seattle, Washington, United States.

Background: Colombia was the second most affected country during the American Zika virus (ZIKV) epidemic, with over 109,000 reported cases. Despite the scale of the outbreak, limited genomic sequence data were available from Colombia. We sought to sequence additional samples and use genomic epidemiology to describe ZIKV dynamics in Colombia.

Methods: We sequenced ZIKV genomes directly from clinical diagnostic specimens and infected Aedes aegypti samples selected to cover the temporal and geographic breadth of the Colombian outbreak. We performed phylogeographic analysis of these genomes, along with other publicly-available ZIKV genomes from the Americas, to estimate the frequency and timing of ZIKV introductions to Colombia.

Results: We attempted PCR amplification on 184 samples; 19 samples amplified sufficiently to perform sequencing. Of these, 8 samples yielded sequences with at least 50% coverage. Our phylogeographic reconstruction indicates two separate introductions of ZIKV to Colombia, one of which was previously unrecognized. We find that ZIKV was first introduced to Colombia in February 2015 (95%CI: Jan 2015 - Apr 2015), corresponding to 5 to 8 months of cryptic ZIKV transmission prior to confirmation in September 2015. Despite the presence of multiple introductions, we find that the majority of Colombian ZIKV diversity descends from a single introduction. We find evidence for movement of ZIKV from Colombia into bordering countries, including Peru, Ecuador, Panama, and Venezuela.

Conclusions: Similarly to genomic epidemiological studies of ZIKV dynamics in other countries, we find that ZIKV circulated cryptically in Colombia. More accurately dating when ZIKV was circulating refines our definition of the population at risk. Additionally, our finding that the majority of ZIKV transmission within Colombia was attributable to transmission between individuals, rather than repeated travel-related importations, indicates that improved detection and control might have succeeded in limiting the scale of the outbreak within Colombia.
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http://dx.doi.org/10.1186/s12879-019-4566-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6852897PMC
November 2019

Dengue, chikungunya and zika virus coinfection: results of the national surveillance during the zika epidemic in Colombia.

Epidemiol Infect 2019 01;147:e77

Department of Medicine, Health Sciences Division,Universidad del Norte and Hospital Universidad del Norte,Barranquilla,Colombia.

Our objective was to determine the frequency of zika (ZIKV), chikungunya (CHIKV) and dengue (DENV) virus coinfection and describe the mortality cases that occurred during the epidemiologic surveillance of the ZIKV epidemic in Colombia. We analysed all cases of suspected ZIKV infection that were reported to the National Institute of Health (October 2015-December 2016). DENV, CHIKV and ZIKV RNA were detected in serum or tissue samples using polymerase chain reaction assay. Medical records of the fatal cases were reviewed. We identified that 23 871 samples were processed. The frequency of viral agents was 439 (1.84%) for DENV, 257 (1.07%) for CHIKV and 10118 (42.38%) for ZIKV. Thirty-four (0.14%) cases of coinfection were identified. The CHIKV-ZIKV coinfection was present in 28 cases (82.3%), DENV-CHIKV in three (8.8%) and DENV-ZIKV in three (8.8%). Seven (20.6%) coinfection cases were fatal (two DENV-CHIKV cases and five CHIKV-ZIKV cases). Two cases were foetal deaths and the others were related to neurological syndrome and sepsis. In conclusion, the frequency of arbovirus coinfection during epidemic of ZIKV was low, and CHIKV-ZIKV coinfection was the most common. Mortality was high among coinfection patients. The role of each virus in the mortality cases of coinfection warrants further studies.
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http://dx.doi.org/10.1017/S095026881800359XDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518562PMC
January 2019

Ocular Histopathologic Features of Congenital Zika Syndrome.

JAMA Ophthalmol 2017 11;135(11):1163-1169

Florida Lions Ocular Pathology Laboratory, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami.

Importance: Congenital Zika syndrome (CZS) is known to be associated with severe malformations in newborns. Although microcephaly is the hallmark of this disease, the ocular findings are important given the severe visual impairment that has been observed in these patients. Regardless of the increased number of CZS cases reported, to date, no studies have described the ocular histopathologic findings of this entity.

Objectives: To evaluate the presence of Zika virus (ZIKV) antigens and describe the associated ocular histopathologic features of 4 cases of CZS.

Design, Setting, And Participants: In this observational case series performed from June 19, 2015, through April 30, 2017, ocular tissue samples from 4 deceased fetuses with a diagnosis of CZS from the National Institute of Health in Colombia were sent to the Florida Lions Ocular Pathology Laboratory for evaluation.

Main Outcomes And Measures: The microscopic features of each specimen were described, and immunostaining was performed using a ZIKV NS2B protein antibody.

Results: Ocular tissue samples from the 4 deceased fetuses (2 female, 2 male) ranging from 21.5 to 29 weeks' gestation with a diagnosis of CZS were studied. The 4 eyes manifested with pupillary membranes, immature anterior chamber angles, loss of pigment and thinning of the retinal pigment epithelium, choroidal thinning, undifferentiated nuclear layers of the retina, and a perivascular inflammatory infiltrate within the choroid. The optic nerve, present in 2 of the eyes, demonstrated atrophy. Expression of ZIKV antigen was present in the iris in cases 1, 3, and 4; the neural retina and choroid in case 1; and in the optic nerve in case 4.

Conclusions And Relevance: Loss of retinal pigment epithelium, the presence of a thin choroid, a perivascular choroidal inflammatory infiltrate, and atrophic changes within the optic nerve were consistently present. These findings may be attributed to ZIKV infection and warrant further study.
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http://dx.doi.org/10.1001/jamaophthalmol.2017.3595DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5710450PMC
November 2017

Chikungunya Pathogenesis: From the Clinics to the Bench.

J Infect Dis 2016 Dec;214(suppl 5):S446-S448

Division of Health Sciences, Faculty of Medicine, Universidad del Norte and Hospital Universidad del Norte, Barranquilla, Colombia.

Chikungunya alphavirus has caused large epidemics worldwide and leads to acute incapacitating polyarthralgia. The inflammatory reaction over several days will drive robust innate and humoral responses essential to control the infection. Critically, fatal cases and mother-to-child transmission have also been described. Chikungunya can give rise to chronic musculoskeletal diseases, which can last for months to years, particularly in elderly individuals, and occasionally leads to seronegative rheumatoid arthritis-like pathologies. Histopathological studies of patient biopsy specimens and animal models have revealed that chikungunya virus can hide in tissue sanctuaries, and ongoing research should help to decipher the inflammatory mechanisms of tissue injuries.
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http://dx.doi.org/10.1093/infdis/jiw362DOI Listing
December 2016

Prevalence of cagA, vacA, babA2 and iceA genes in H. pylori strains isolated from Colombian patients with functional dyspepsia.

Pol J Microbiol 2012 ;61(1):33-40

Laboratorio de Microbiología Especial, Grupo de Enfermedades Infecciosas, Departamento de Microbiología Facultad de Ciencias, Pontificia Universidad Javeriana, Bogotá, D.C. Colombia.

The clinical outcome of Helicobacter pylori infection has been particularly associated with virulence genotypes. These genotypes are useful as molecular markers in the identification of patients that are infected and at high risk for developing more severe gastric pathologies. Our main objective was to determine the prevalence of virulence genotypes cagA, vacA, iceA and babA2 of H. pylori, in patients with functional dyspepsia who are infected with the bacteria. H. pylori genotypes babA2 and cagA as well as vacA and iceA allelic variants were identified by PCR in 122 isolates resulting from 79 patients with functional dyspepsia. A high prevalence of genes cagA+ (71%), vacAs1am1 (34%), babA2 (57%) and iceA1 (87%) was found. The most frequent combined genotype found were cagA+/vacAs1am1/babA2+/iceA1 and cagA-/vacAs1am1/babA2+/iceA1, regardless of any family history of gastric cancer or MALT lymphoma. The very virulent genotype cagA+/vacAs1am1/babA2+/iceA1 prevailed in the studied patients with functional dyspepsia. Our results provide information about the prevalence of four of the more important virulent factors and constitute new evidence on the prevalence of the most virulent H. pylori genotype in patients with functional dyspepsia.
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July 2012
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