Publications by authors named "Alberto Paniz-Mondolfi"

126 Publications

Evaluation of the diagnostic performance of nine commercial RT-PCR kits for the detection of SARS-CoV-2 in Colombia.

J Med Virol 2021 Apr 29. Epub 2021 Apr 29.

Centro de Investigaciones en Microbiología y Biotecnología-UR (CIMBIUR), Facultad de Ciencias Naturales, Universidad del Rosario, Bogotá, Colombia.

The ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has led to the design and development of multiple reverse-transcription polymerase chain reaction kits aimed to facilitate the rapid scale-up of molecular testing for massive screening. We evaluated the diagnostic performance of nine commercial kits, which showed optimal performance and high discriminatory power. However, we observed differences in terms of sensitivity, specificity, and E gene Ct Values and discuss these results in light of the influence of SARS-CoV-2 genetic variability and its potential impact in current molecular diagnostic assays.
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http://dx.doi.org/10.1002/jmv.27051DOI Listing
April 2021

Malaria in Venezuela: Gabaldón's legacy scattered to the winds.

Lancet Glob Health 2021 May;9(5):e584-e585

Área de Enfermedades Infecciosas, Clínica Universidad de Navarra, Pamplona 31008, Spain; ISGlobal, Hospital Clínic - Universitat de Barcelona, Barcelona, Spain; Ifakara Health Institute, Ifakara, Tanzania.

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http://dx.doi.org/10.1016/S2214-109X(21)00007-3DOI Listing
May 2021

Deciphering the introduction and transmission of SARS-CoV-2 in the Colombian Amazon Basin.

PLoS Negl Trop Dis 2021 04 15;15(4):e0009327. Epub 2021 Apr 15.

Centro de Investigaciones en Microbiología y Biotecnología-UR (CIMBIUR), Facultad de Ciencias Naturales, Universidad del Rosario, Bogotá, Colombia.

Background: The SARS-CoV-2 pandemic has forced health authorities across the world to take important decisions to curtail its spread. Genomic epidemiology has emerged as a valuable tool to understand introductions and spread of the virus in a specific geographic location.

Methodology/principal Findings: Here, we report the sequences of 59 SARS-CoV-2 samples from inhabitants of the Colombian Amazonas department. The viral genomes were distributed in two robust clusters within the distinct GISAID clades GH and G. Spatial-temporal analyses revealed two independent introductions of SARS-CoV-2 in the region, one around April 1, 2020 associated with a local transmission, and one around April 2, 2020 associated with other South American genomes (Uruguay and Brazil). We also identified ten lineages circulating in the Amazonas department including the P.1 variant of concern (VOC).

Conclusions/significance: This study represents the first genomic epidemiology investigation of SARS-CoV-2 in one of the territories with the highest report of indigenous communities of the country. Such findings are essential to decipher viral transmission, inform on global spread and to direct implementation of infection prevention and control measures for these vulnerable populations, especially, due to the recent circulation of one of the variants of concern (P.1) associated with major transmissibility and possible reinfections.
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http://dx.doi.org/10.1371/journal.pntd.0009327DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8078805PMC
April 2021

Broad SARS-CoV-2 cell tropism and immunopathology in lung tissues from fatal COVID-19.

J Infect Dis 2021 Apr 10. Epub 2021 Apr 10.

Cancer Virology Program, UPMC Hillman Cancer Center and Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.

Background: COVID-19 patients manifest with pulmonary symptoms reflected by diffuse alveolar damage (DAD), excessive inflammation, and thromboembolism. The mechanisms mediating these processes remain unclear.

Methods: We performed multicolor staining for SARS-CoV-2 proteins and lineage markers to define viral tropism and lung pathobiology in 5 autopsy cases.

Results: Lung parenchyma showed severe DAD with thromboemboli. Viral infection was found in an extensive range of cells including pneumocyte type II, ciliated, goblet, club-like and endothelial cells. Over 90% infiltrating immune cells were positive for viral proteins including macrophages, monocytes, neutrophils, and natural killer (NK), B and T cells. Most but not all infected cells were ACE2-positive. The numbers of infected and ACE2-positive cells are associated with extensive tissue damage. Infected tissues exhibited high inflammatory cells including macrophages, monocytes, neutrophils and NK cells, and low B- but abundant T-cells consisting of mainly T helper cells, few cytotoxic T cells, and no T regulatory cell. Robust interleukin-6 expression was present in most cells, with or without infection.

Conclusions: In fatal COVID-19 lungs, there are broad SARS-CoV-2 cell tropisms, extensive infiltrated innate immune cells, and activation and depletion of adaptive immune cells, contributing to severe tissue damage, thromboemboli, excess inflammation and compromised immune responses.
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http://dx.doi.org/10.1093/infdis/jiab195DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8083355PMC
April 2021

Concerns about influenza H5N8 outbreaks in humans and birds: Facing the next airborne pandemic?

Travel Med Infect Dis 2021 Apr 3;41:102054. Epub 2021 Apr 3.

Department of Pathology, Molecular and Cell-Based Medicine, Laboratory of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Instituto de Investigaciones Biomédicas IDB/Incubadora Venezolana de la Ciencia, Barquisimeto, Venezuela.

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http://dx.doi.org/10.1016/j.tmaid.2021.102054DOI Listing
April 2021

Perception of COVID-19 Vaccination Amongst Physicians in Colombia.

Vaccines (Basel) 2021 Mar 19;9(3). Epub 2021 Mar 19.

Latin American Network of Coronavirus Disease 2019 Research (LANCOVID), Pereira, Risaralda 660003, Colombia.

: The SARS-CoV-2/COVID-19 pandemic has triggered the need to develop rapidly effective and safe vaccines to prevent infection, particularly in those at-risk populations such as medical personnel. This study's objective was to assess the perception of COVID-19 vaccination amongst Colombian physicians featuring two different scenarios of COVID-19 vaccination. : A cross-sectional analytical study was carried out through an online survey directed at medical staff in several cities in Colombia. The percentage of physicians who have a positive perception to be vaccinated and the associated factors that determine that decision were determined. A binomial regression analysis adjusted for age and sex was carried out, taking as a dependent variable the acceptance of free vaccination with an effectiveness of 60 and 80%. The most significant factors were determined in the non-acceptance of vaccination. : Between 77.0% and 90.7% of physicians in Colombia accept COVID-19 vaccination, according to the scenario evaluated where the vaccine's effectiveness was 60 or 80%, respectively. Medical specialty, having never paid for a vaccine, recommending the administration of the vaccine to their parents or people over 70 years, and dispensing the vaccine to their children, were the factors to consider to be vaccinated for free with an effectiveness of 60% and 80%. : There is a high perception of the intention to vaccinate physicians in Colombia against COVID-19, and this is very similar to that of the general population.
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http://dx.doi.org/10.3390/vaccines9030287DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8003713PMC
March 2021

Phylogenomic Evidence of Reinfection and Persistence of SARS-CoV-2: First Report from Colombia.

Vaccines (Basel) 2021 Mar 19;9(3). Epub 2021 Mar 19.

Icahn School of Medicine at Mount Sinai, New York, NY 10001, USA.

The continuing evolution of SARS-CoV-2 and the emergence of novel variants have raised concerns about possible reinfection events and potential changes in the coronavirus disease 2019 (COVID-19) transmission dynamics. Utilizing Oxford Nanopore technologies, we sequenced paired samples of three patients with positive RT-PCR results in a 1-2-month window period, and subsequent phylogenetics and genetic polymorphism analysis of these genomes was performed. Herein, we report, for the first time, genomic evidence of one case of reinfection in Colombia, exhibiting different SARS-CoV-2 lineage classifications between samples (B.1 and B.1.1.269). Furthermore, we report two cases of possible viral persistence, highlighting the importance of deepening our understanding on the evolutionary intra-host traits of this virus throughout different timeframes of disease progression. These results emphasize the relevance of genomic surveillance as a tool for understanding SARS-CoV-2 infection dynamics, and how this may translate effectively to future control and mitigations efforts, such as the national vaccination program.
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http://dx.doi.org/10.3390/vaccines9030282DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8003345PMC
March 2021

Pathophysiology of SARS-CoV-2: the Mount Sinai COVID-19 autopsy experience.

Mod Pathol 2021 Apr 1. Epub 2021 Apr 1.

Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its associated clinical syndrome COVID-19 are causing overwhelming morbidity and mortality around the globe and disproportionately affected New York City between March and May 2020. Here, we report on the first 100 COVID-19-positive autopsies performed at the Mount Sinai Hospital in New York City. Autopsies revealed large pulmonary emboli in six cases. Diffuse alveolar damage was present in over 90% of cases. We also report microthrombi in multiple organ systems including the brain, as well as hemophagocytosis. We additionally provide electron microscopic evidence of the presence of the virus in our samples. Laboratory results of our COVID-19 cohort disclose elevated inflammatory markers, abnormal coagulation values, and elevated cytokines IL-6, IL-8, and TNFα. Our autopsy series of COVID-19-positive patients reveals that this disease, often conceptualized as a primarily respiratory viral illness, has widespread effects in the body including hypercoagulability, a hyperinflammatory state, and endothelial dysfunction. Targeting of these multisystemic pathways could lead to new treatment avenues as well as combination therapies against SARS-CoV-2 infection.
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http://dx.doi.org/10.1038/s41379-021-00793-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8015313PMC
April 2021

Florid Infection of the Placenta Associated With Intrauterine Fetal Demise.

Pediatr Dev Pathol 2021 Mar 17:1093526621999026. Epub 2021 Mar 17.

Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, New York.

is a gram-positive, rod-shaped bacterium that is commonly implicated in foodborne illness but has also become increasingly recognized as a source of serious non-gastrointestinal infections, including sepsis, meningitis, and pneumonia. Non-gastrointestinal infections have been identified in children, especially in neonates; however, there are no previously described cases of fetal demise associated with placental infection. We present a case of acute chorioamnionitis-related intrauterine fetal demise of twin A at 17 weeks gestation, noted two days after selective termination of twin B. Histological examination revealed numerous gram-positive bacilli in placental tissue, as well as fetal vasculature, in the setting of severe acute necrotizing chorioamnionitis and subchorionitis, intervillous abscesses, acute villitis, and peripheral acute funisitis. Cultures of maternal blood and placental tissue both yielded growth of . This case underscores the importance of as a human pathogen, and specifically demonstrates its potential as an agent of severe intraamniotic and placental infection with poor outcomes for the fetus.
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http://dx.doi.org/10.1177/1093526621999026DOI Listing
March 2021

Characterizing SARS-CoV-2 genome diversity circulating in South American countries: Signatures of potentially emergent lineages?

Int J Infect Dis 2021 Apr 20;105:329-332. Epub 2021 Feb 20.

Centro de Investigaciones en Microbiología y Biotecnología-UR (CIMBIUR), Facultad de Ciencias Naturales, Universidad del Rosario, Bogotá, Colombia. Electronic address:

Objectives: To evaluate the genomic diversity and geographic distribution of SARS-CoV-2 lineages in South America.

Methods: SARS-CoV-2 lineages from a public dataset of 5583 South American genome assemblies were analyzed. Polymorphisms in the main open reading frames were identified and compared to those in the main lineages of epidemiological concern: B.1.1.7 (UK) and B.1.351 (South Africa).

Results: Across 16 South American countries, 169 lineages were identified; major lineage B had the greatest diversity and broadest geographic distribution. Seventeen predominant lineages were analyzed revealing 2 dominant lineages of concern: P.1 (Brazilian variant) and B.1.1.7 with 94 and 28 genomes, respectively, both with 33 polymorphisms (other lineages displayed ≤24 polymorphisms). A high number of polymorphisms were detected with a limited number of common variable positions, in common with the profile of the main lineages of epidemiological concern.

Conclusions: The ever-increasing genetic diversity of SARS-CoV-2 continues to lead to novel lineage emergence. Various variants and lineages are now present across South America, dominated by major lineage B. The circulation of P.1 and B.1.1.7 and the high number of polymorphisms highlight the importance of genomic surveillance to determine introduction events, identify transmission chains, trace emergence, and implement prevention, vaccination and control strategies.
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http://dx.doi.org/10.1016/j.ijid.2021.02.073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7895695PMC
April 2021

Will the emergent SARS-CoV2 B.1.1.7 lineage affect molecular diagnosis of COVID-19?

J Med Virol 2021 May 9;93(5):2566-2568. Epub 2021 Feb 9.

Department of Pathology, Molecular and Cell-Based Medicine, Laboratory of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

As the coronavirus disease 2019 pandemic keep tackling global public health systems worldwide. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) genome keeps mutating. In that regard, the recent emergence of the B.1.1.7 lineage in the UK has called the attention of global authorities. One point of concern is that if this lineage can be detected by traditional molecular schemes for SARS-CoV-2 detection. Herein, we showed that this lineage does not affect the Berlin-Charité protocol but can challenge the available commercial kits directed to the Spike (S) gene. All efforts should be made to continue to monitor SARS-CoV-2 genomes for potential variants that can impair diagnostic testing and lead to false negative results.
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http://dx.doi.org/10.1002/jmv.26823DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8013853PMC
May 2021

Risk factors for antimony treatment failure in American Cutaneous Leishmaniasis in Northwestern-Argentina.

PLoS Negl Trop Dis 2021 01 26;15(1):e0009003. Epub 2021 Jan 26.

Facultad de Ciencias de la Salud, Universidad Nacional de Salta, Salta, Argentina.

Background: To date, there is no specific literature available on the determinants for therapeutic failure (TF) with meglumine antimoniate (MA) in Northwestern-Argentina. This study aimed to identify epidemiological, clinical, and treatment-related factors that could be involved in TF.

Methodology/principal Findings: We performed a case-control study. Cases were represented by patients who showed TF after administration of the first course of MA treatment, whereas, controls were determined as patients who evolved towards healing after the first MA cycle received. Crude Odds Ratios and their corresponding 90% confidence intervals (CI) were calculated, and risk factors were then tested by multivariate analysis using logistic binary regression. Three hundred and eighty-four patients with a presumptive diagnosis of ACL were recruited, and 153 with a positive diagnosis were selected. We included in the study 71 patients, who underwent specific treatment with MA, presented complete data on response to treatment, and had a minimum post-treatment follow-up of 6 months in cutaneous leishmaniasis, and 12 months in mucosal leishmaniasis. Of these, 34 (47.9%) presented TF. In the initial analysis, TF was significantly associated with the geographical area of disease acquisition (p = 0.036), the presence of mucosal lesions (p = 0.042), the presence of concomitant skin and mucosal lesions (p = 0.002), and lesion age ≥ 6 months (p = 0.018). Risk factors influencing TF in the final multivariate model included the geographical area where the disease was acquired (adjusted Odd Ratio 8.062; 95% CI 1.914-33.959; p = 0.004), and lesion age ≥ 6 months (adjusted Odd Ratio 10.037; 95% CI 1.383-72.843; p = 0.023).

Conclusions/significance: The results of the present study suggest the existence of some risk factors linked to TF in Northwestern-Argentina, which deserve further investigation. Herein we recorded a high percentage of TF and we described clinical and epidemiological characteristics associated with TF that could be taken into account improving the clinical management of patients.
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http://dx.doi.org/10.1371/journal.pntd.0009003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7864468PMC
January 2021

Malaria in Southern Venezuela: The hottest hotspot in Latin America.

PLoS Negl Trop Dis 2021 01 25;15(1):e0008211. Epub 2021 Jan 25.

Griffin Laboratory, Wadsworth Center, New York State Department of Health. Albany, New York, United States of America.

Malaria elimination in Latin America is becoming an elusive goal. Malaria cases reached a historical ~1 million in 2017 and 2018, with Venezuela contributing 53% and 51% of those cases, respectively. Historically, malaria incidence in southern Venezuela has accounted for most of the country's total number of cases. The efficient deployment of disease prevention measures and prediction of disease spread to new regions requires an in-depth understanding of spatial heterogeneity on malaria transmission dynamics. Herein, we characterized the spatial epidemiology of malaria in southern Venezuela from 2007 through 2017 and described the extent to which malaria distribution has changed country-wide over the recent years. We found that disease transmission was focal and more prevalent in the southeast region of southern Venezuela where two persistent hotspots of Plasmodium vivax (76%) and P. falciparum (18%) accounted for ~60% of the total number of cases. Such hotspots are linked to deforestation as a consequence of illegal gold mining activities. Incidence has increased nearly tenfold over the last decade, showing an explosive epidemic growth due to a significant lack of disease control programs. Our findings highlight the importance of spatially oriented interventions to contain the ongoing malaria epidemic in Venezuela. This work also provides baseline epidemiological data to assess cross-border malaria dynamics and advocates for innovative control efforts in the Latin American region.
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http://dx.doi.org/10.1371/journal.pntd.0008211DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7861532PMC
January 2021

Postmortem Findings Associated With SARS-CoV-2: Systematic Review and Meta-analysis.

Am J Surg Pathol 2021 05;45(5):587-603

Department of Pathology, University of Michigan, Ann Arbor, MI.

Coronavirus Disease 2019 (COVID-19), caused by the novel Severe Acute Respiratory Syndrome-associated Coronavirus 2 (SARS-CoV-2), has become a global threat to public health. COVID-19 is more pathogenic and infectious than the prior 2002 pandemic caused by SARS-CoV-1. The pathogenesis of certain disease manifestations in COVID-19 such as diffuse alveolar damage (DAD) are thought to be similar to SARS-CoV-1. However, the exact pathogenesis of COVID-19 related deaths remains poorly understood. The aim of this article was to systematically summarize the rapidly emerging literature regarding COVID-19 autopsies. A meta-analysis was also conducted based on data accrued from preprint and published articles on COVID-19 (n=241 patients) and the results compared with postmortem findings associated with SARS-CoV-1 deaths (n=91 patients). Both autopsy groups included mostly adults of median age 70 years with COVID-19 and 50 years with SARS-CoV-1. Overall, prevalence of DAD was more common in SARS-CoV-1 (100.0%) than COVID-19 (80.9%) autopsies (P=0.001). Extrapulmonary findings among both groups were not statistically significant except for hepatic necrosis (P <0.001), splenic necrosis (P<0.006) and white pulp depletion (P <0.001) that were more common with SARS-CoV-1. Remarkable postmortem findings in association with COVID-19 apart from DAD include pulmonary hemorrhage, viral cytopathic effect within pneumocytes, thromboembolism, brain infarction, endotheliitis, acute renal tubular damage, white pulp depletion of the spleen, cardiac myocyte necrosis, megakaryocyte recruitment, and hemophagocytosis.
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http://dx.doi.org/10.1097/PAS.0000000000001650DOI Listing
May 2021

Epidemiological characterisation of asymptomatic carriers of COVID-19 in Colombia: a cross-sectional study.

BMJ Open 2020 12 7;10(12):e042122. Epub 2020 Dec 7.

Grupo de Investigaciones Microbiológicas-UR (GIMUR), Departamento de Biología, Facultad de Ciencias Naturales, Universidad del Rosario, Bogotá, Colombia

Introduction: Asymptomatic carriers (AC) of the new SARS-CoV-2 represent an important source of spread for COVID-19. Early diagnosis of these cases is a powerful tool to control the pandemic. Our objective was to characterise patients with AC status and identify associated sociodemographic factors.

Methods: Using a cross-sectional design and the national database of daily occurrence of COVID-19, we characterised 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).

Results: 76.162 ACs (12.1%; 95% CI 12.0% to 12.2%) were identified, mainly before epidemiological week 35. Age≤26 years (1.18; 1.09 to 1.28), male sex (1.51; 1.40 to 1.62), cases imported from Venezuela, Argentina, Brazil, Germany, Puerto Rico, Spain, USA or Mexico (12.6; 3.03 to 52.5) and autochthonous cases (22.6; 5.62 to 91.4) increased the risk of identifying ACs. We also identified groups of departments with moderate (1.23; 1.13 to 1.34) and strong (19.8; 18.6 to 21.0) association with ACs.

Conclusion: Sociodemographic characteristics strongly associated with AC were identified, which may explain its epidemiological relevance and usefulness to optimise mass screening strategies and prevent person-to-person transmission.
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http://dx.doi.org/10.1136/bmjopen-2020-042122DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7722836PMC
December 2020

After SARS-CoV-2, will H5N6 and other influenza viruses follow the pandemic path?

Infez Med 2020 Dec;28(4):475-485

Laboratory of Medical Microbiology, Department of Pathology, Molecular and Cell-based Medicine, The Mount Sinai Hospital-Icahn School of Medicine at Mount Sinai, New York, USA; Laboratorio de Señalización Celular y Bioquímica de Parásitos, Instituto de Estudios Avanzados (IDEA), Caracas, Venezuela; Academia Nacional de Medicina, Caracas, Venezuela.

While the world is focused on attending, controlling, and mitigating the current pandemic of COVID-19, caused by the SARS-CoV-2, other viral threats are possibly emerging and reemerging especially in Asia, posing a risk for the spread in that region and beyond. A predictable threat is the avian influenza virus, especially H5N6, which has recently led to significant outbreaks in China and the Philippines, deserving more attention and control. In the current review, we assess the history of this highly pathogenic reemerging virus, as well as the contemporary implications of poultry outbreaks occurring in some Asian countries. We also look at outbreaks due to other strains not only in Asia but also across Europe and Africa, according to recent reports from the World Organization of Animal Health (OIE).
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December 2020

SARS-CoV-2 spread across the Colombian-Venezuelan border.

Infect Genet Evol 2020 12 4;86:104616. Epub 2020 Nov 4.

Grupo de Investigaciones Microbiológicas-UR (GIMUR), Departamento de Biología, Facultad de Ciencias Naturales, Universidad del Rosario, Bogotá, Colombia.

Introduction: Venezuela and Colombia both adopted measures of containment early in response to the COVID-19 pandemic. However, Venezuela's 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.

Methods: We 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.

Results: We 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. Additionally, three mutations (R203K/G204R substitution) were present in the nucleocapsid (N) gene of one Venezuelan genome.

Conclusions: Genomic 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.
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http://dx.doi.org/10.1016/j.meegid.2020.104616DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7609240PMC
December 2020

SARS-CoV-2 in the Amazon region: A harbinger of doom for Amerindians.

PLoS Negl Trop Dis 2020 10 29;14(10):e0008686. Epub 2020 Oct 29.

Icahn School of Medicine at Mount Sinai, New York, United States.

As the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic continues to expand, healthcare resources globally have been spread thin. Now, the disease is rapidly spreading across South America, with deadly consequences in areas with already weakened public health systems. The Amazon region is particularly susceptible to the widespread devastation from Coronavirus disease 2019 (COVID-19) because of its immunologically fragile native Amerindian inhabitants and epidemiologic vulnerabilities. Herein, we discuss the current situation and potential impact of COVID-19 in the Amazon region and how further spread of the epidemic wave could prove devastating for many Amerindian people living in the Amazon rainforest.
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http://dx.doi.org/10.1371/journal.pntd.0008686DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7595282PMC
October 2020

COVID-19: Staging of a New Disease.

Cancer Cell 2020 11 10;38(5):594-597. Epub 2020 Oct 10.

Department of Anesthesiology, Perioperative and Pain Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Coronavirus disease 2019 (COVID-19), like cancer, is a complex disease with clinical phases of progression. Initially conceptualized as a respiratory disease, COVID-19 is increasingly recognized as a multi-organ and heterogeneous illness. Disease staging is a method for measuring the progression and severity of an illness using objective clinical and molecular criteria. Integral to cancer staging is "metastasis," defined as the spread of a disease-producing agent, including neoplastic cells and pathogens such as certain viruses, from the primary site to distinct anatomic locations. Staging provides valuable frameworks and benchmarks for clinical decision-making in patient management, improved prognostication, and evidence-based treatment selection.
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http://dx.doi.org/10.1016/j.ccell.2020.10.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7547574PMC
November 2020

Humoral response and PCR positivity in patients with COVID-19 in the New York City region, USA: an observational study.

Lancet Microbe 2020 Nov 25;1(7):e283-e289. Epub 2020 Sep 25.

Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic. The proportion of infected individuals who seroconvert is still an open question. In addition, it has been shown in some individuals that viral genome can be detected up to 3 months after symptom resolution. We investigated both seroconversion and PCR positivity in a large cohort of convalescent serum donors in the New York City (NY, USA) region.

Methods: In this observational study, we ran an outreach programme in the New York City area. We recruited participants via the REDCap (Vanderbilt University, Nashville, TN, USA) online survey response. Individuals with confirmed or suspected SARS-CoV-2 infection were screened via PCR for presence of viral genome and via ELISA for presence of anti-SARS-CoV-2 spike antibodies. One-way ANOVA and Fisher's exact test were used to measure the association of age, gender, symptom duration, and days from symptom onset and resolution with positive antibody results.

Findings: Between March 26 and April 10, 2020, we measured SARS-CoV-2 antibody titres in 1343 people. Of the 624 participants with confirmed SARS-CoV-2 infection who had serologies done after 4 weeks, all but three seroconverted to the SARS-CoV-2 spike protein, whereas 269 (37%) of 719 participants with suspected SARS-CoV-2 infection seroconverted. PCR positivity was detected up to 28 days from symptom resolution.

Interpretation: Most patients with confirmed COVID-19 seroconvert, potentially providing immunity to reinfection. We also report that in a large proportion of individuals, viral genome can be detected via PCR in the upper respiratory tract for weeks after symptom resolution, but it is unclear whether this signal represents infectious virus. Analysis of our large cohort suggests that most patients with mild COVID-19 seroconvert 4 weeks after illness, and raises questions about the use of PCR to clear positive individuals.

Funding: None.
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http://dx.doi.org/10.1016/S2666-5247(20)30120-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7518831PMC
November 2020

Findings of Hepatic Severe Acute Respiratory Syndrome Coronavirus-2 Infection.

Cell Mol Gastroenterol Hepatol 2021 28;11(3):763-770. Epub 2020 Sep 28.

Division of Liver Diseases and Recanati-Miller Transplant Institute, Icahn School of Medicine at Mount Sinai, New York, New York.

Background & Aims: Liver injury due to coronavirus disease 2019 (COVID-19) is being increasingly recognized. Abnormal liver chemistry tests of varying severities occur in a majority of patients. However, there is a dearth of accompanying liver histologic studies in these patients.

Methods: The current report details the clinical courses of 2 patients having severe COVID-19 hepatitis. Liver biopsies were analyzed under light microscopy, portions of liver tissue were hybridized with a target probe to the severe acute respiratory syndrome coronavirus-2 S gene, and small sections from formalin-fixed paraffin-embedded liver tissue were processed for electron microscopy.

Results: The liver histology of both cases showed a mixed inflammatory infiltrate with prominent bile duct damage, endotheliitis, and many apoptotic bodies. In situ hybridization and electron microscopy suggest the intrahepatic presence of severe acute respiratory syndrome coronavirus-2, the findings of which may indicate the possibility of direct cell injury.

Conclusions: On the basis of the abundant apoptosis and severe cholangiocyte injury, these histopathologic changes suggest a direct cytopathic injury. Furthermore, some of the histopathologic changes may resemble acute cellular rejection occurring after liver transplantation. These 2 cases demonstrate that severe COVID-19 hepatitis can occur even in the absence of significant involvement of other organs.
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http://dx.doi.org/10.1016/j.jcmgh.2020.09.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7521427PMC
March 2021

Rationale for Use of Amiodarone and Its Derivatives for Treatment of Chagas' Disease and Leishmaniasis.

Curr Pharm Des 2020 Sep 28. Epub 2020 Sep 28.

Institute for Health Sciences, Mount Sinai St Luke's & Mount Sinai West, New York. United States.

The repurposing or repositioning of previously-approved drugs has become an accepted strategy for expansion of the pharmacopeia for neglected diseases. Accordingly, amiodarone, an inexpensive and extensively-used class III antiarrhythmic has been proposed as a treatment for Chagas' disease and leishmaniasis. Amiodarone has a potent trypanocidal and leishmanicidal action, mainly acting through the disruption of parasite intracellular Ca2+ homeostasis, which is a recognized target of different drugs that have activity against trypanosomatids. Amiodarone collapses the mitochondrial electrochemical potential (Δφm) and induces the rapid alkalinization of parasite acidocalcisomes, driving a large increase in the intracellular Ca2+ concentration. Amiodarone also inhibits oxidosqualene cyclase activity, a key enzyme in the ergosterol synthesis pathway that is essential for trypanosomatid survival. In combination, these three effects lead to parasite death. Dronedarone, a drug synthesized with the objective of minimizing some of the adverse effects of amiodarone, displays trypanocidal and leishmanicidal activity through the same mechanisms, but curiously, being more potent on Leishmaniasis than its predecessor. In vitro studies suggest that other recently-synthesized benzofuran derivatives can act through the same mechanisms, and produce similar effects on different trypanosomatid species. Recently, the combination of amiodarone plus itraconazole, has been used successfully to treat 121 dogs naturally-infected by T. cruzi, strongly supporting the potential therapeutic use of this combination against human trypanosomatid infections.
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http://dx.doi.org/10.2174/1381612826666200928161403DOI Listing
September 2020

Bats in ecosystems and their Wide spectrum of viral infectious potential threats: SARS-CoV-2 and other emerging viruses.

Int J Infect Dis 2021 Jan 20;102:87-96. Epub 2020 Aug 20.

Public Health and Infection Research Group and Incubator, Faculty of Health Sciences, Universidad Tecnológica de Pereira, Pereira, Risaralda, Colombia; Master in Clinical Epidemiology and Biostatistics, Universidad Cientifica del Sur, Lima, Peru; Grupo de Investigación Biomedicina, Faculty of Medicine, Fundación Universitaria Autónoma de las Américas, Pereira, Risaralda, Colombia. Electronic address:

Bats have populated earth for approximately 52 million years, serving as natural reservoirs for a variety of viruses through the course of evolution. Transmission of highly pathogenic viruses from bats has been suspected or linked to a spectrum of potential emerging infectious diseases in humans and animals worldwide. Examples of such viruses include Marburg, Ebolavirus, Nipah, Hendra, Influenza A, Dengue, Equine Encephalitis viruses, Lyssaviruses, Madariaga and Coronaviruses, involving the now pandemic Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Herein, we provide a narrative review focused in selected emerging viral infectious diseases that have been reported from bats.
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http://dx.doi.org/10.1016/j.ijid.2020.08.050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7440229PMC
January 2021

The arrival and spread of SARS-CoV-2 in Colombia.

J Med Virol 2021 02 13;93(2):1158-1163. Epub 2020 Aug 13.

Icahn School of Medicine at Mount Sinai, New York, New York.

We performed phylogenomic analysis of severe acute respiratory syndrome coronavirus-2 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.
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http://dx.doi.org/10.1002/jmv.26393DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7436700PMC
February 2021

A review of the main histopathological findings in coronavirus disease 2019.

Hum Pathol 2020 11 2;105:74-83. Epub 2020 Aug 2.

Latin American Network of Coronavirus Disease 2019-COVID-19 Research (LANCOVID-19), Pereira, Risaralda, 660003, Colombia; Master of Clinical Epidemiology and Biostatistics, Universidad Científica del Sur, Lima, 15046, Peru; Public Health and Infection Research Group, Faculty of Health Sciences, Universidad Tecnologica de Pereira, Pereira, Risaralda, 660001, Colombia; Grupo de Investigación Biomedicina, Faculty of Medicine, Fundación Universitaria Autónoma de Las Americas, Pereira, Risaralda, 660003, Colombia. Electronic address:

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, has been declared by the World Health Organization as an emerging public health problem of global importance and classified as a pandemic. SARS-CoV-2 infection can result in diverse, multiorgan pathology, the most significant being in the lungs (diffuse alveolar damage in its different phases, microthrombi, bronchopneumonia, necrotizing bronchiolitis, viral pneumonia), heart (lymphocytic myocarditis), kidney (acute tubular injury), central nervous system (microthrombi, ischemic necrosis, acute hemorrhagic infarction, congestion, and vascular edema), lymph nodes (hemophagocytosis and histiocytosis), bone marrow (hemophagocytosis), and vasculature (deep vein thrombosis). An understanding of the spectrum and frequency of histologic findings in COVID-19 is essential for gaining a better understanding of disease pathophysiology and its ongoing impact on public health. To this end, we conducted a systematic meta-analysis of histopathologic observations to date and review the reported findings.
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http://dx.doi.org/10.1016/j.humpath.2020.07.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7395947PMC
November 2020

Kawasaki disease seasonality in Venezuela supports an arbovirus infection trigger.

J Med Virol 2020 Aug 2. Epub 2020 Aug 2.

Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, New York.

Kawasaki disease (KD) is an inflammatory disease primarily affecting infants and young children, whose etiology remains uncertain. Observational studies of the overlap between KD outbreaks and seasonal peaks of arboviral infections, suggest the possible role of these pathogens as triggers of KD. In Venezuela, regions with the highest reported arboviral infections simultaneously have the highest incidence of KD. One proposed explanation for this association involves the role of proinflammatory mediators, interleukin-1 (IL-1), IL-6, tumor necrosis factor, and vascular endothelial growth factor as mediators of coronary endothelial damage. The promotion of inflammation and tissue destruction by these cytokines is thought to contribute to the coronary endothelial damage experienced in KD. The utilization of overlapping KD and arboviral infection trends contribute to the comprehension of KD etiology, with improvements in diagnosis, prognosis and treatment.
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http://dx.doi.org/10.1002/jmv.26381DOI Listing
August 2020

Severe rapidly progressive Guillain-Barré syndrome in the setting of acute COVID-19 disease.

J Neurovirol 2020 10 27;26(5):797-799. Epub 2020 Jul 27.

Division of Neuromuscular Diseases and Clinical Neurophysiology Laboratories, Department of Neurology, Icahn School of Medicine, Mount Sinai Hospital, 1468 Madison Avenue, New York, NY, 10029, USA.

There is concern that the global burden of coronavirus disease of 2019 (COVID-19) due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection might yield an increased occurrence of Guillain-Barré syndrome (GBS). It is currently unknown whether concomitant SARS-CoV-2 infection and GBS are pathophysiologically related, what biomarkers are useful for diagnosis, and what is the optimal treatment given the medical comorbidities, complications, and simultaneous infection. We report a patient who developed severe GBS following SARS-CoV-2 infection at the peak of the initial COVID-19 surge (April 2020) in New York City and discuss diagnostic and management issues and complications that may warrant special consideration in similar patients.
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http://dx.doi.org/10.1007/s13365-020-00884-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7384559PMC
October 2020

Fatal Pulmonary Thromboembolism in SARS-CoV-2-Infection.

Cardiovasc Pathol 2020 Sep - Oct;48:107227. Epub 2020 May 12.

Icahn School of Medicine at Mount Sinai, New York, New York, USA.

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http://dx.doi.org/10.1016/j.carpath.2020.107227DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7214296PMC
August 2020