Publications by authors named "Emilia Mia Sordillo"

32 Publications

Editorial: Advances in the Molecular Biology of Trypanosomatid Pathogens: New Strategies Against Ancient Enemies.

Front Cell Infect Microbiol 2021 6;11:777008. Epub 2021 Oct 6.

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

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http://dx.doi.org/10.3389/fcimb.2021.777008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8526921PMC
October 2021

Evidence for retained spike-binding and neutralizing activity against emerging SARS-CoV-2 variants in serum of COVID-19 mRNA vaccine recipients.

EBioMedicine 2021 Nov 20;73:103626. Epub 2021 Oct 20.

Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Pathology, Molecular and Cell Based Medicine Icahn School of Medicine at Mount Sinai, New York, NY, USA; Division of Infectious Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA; The Global Health and Emerging Pathogen Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Electronic address:

Background: Highly efficacious vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed. However, the emergence of viral variants that are more infectious than the earlier SARS-CoV-2 strains is concerning. Several of these viral variants have the potential to partially escape neutralizing antibody responses, warranting continued immune-monitoring.

Methods: We used a panel of 30 post-mRNA vaccination sera to determine neutralization and RBD and spike binding activity against a number of emerging viral variants. The virus neutralization was determined using authentic SARS-CoV-2 clinical isolates in an assay format that mimics physiological conditions.

Findings: We tested seven currently circulating viral variants of concern/interest, including the three Iota sublineages, Alpha (E484K), Beta, Delta and Lambda in neutralization assays. We found only small decreases in neutralization against Iota and Delta. The reduction was stronger against a sub-variant of Lambda, followed by Beta and Alpha (E484K). Lambda is currently circulating in parts of Latin America and was detected in Germany, the US and Israel. Of note, reduction in a receptor binding domain and spike binding assay that also included Gamma, Kappa and A.23.1 was negligible.

Interpretation: Taken together, these findings suggest that mRNA SARS-CoV-2 vaccines may remain effective against these viral variants of concern/interest and that spike binding antibody tests likely retain specificity in the face of evolving SARS-CoV-2 diversity.

Funding: This work is part of the PARIS/SPARTA studies funded by the NIAID Collaborative Influenza Vaccine Innovation Centers (CIVIC) contract 75N93019C00051. In addition, this work was also partially funded by the Centers of Excellence for Influenza Research and Surveillance (CEIRS, contract # HHSN272201400008C), the JPB Foundation, the Open Philanthropy Project (research grant 2020-215611 (5384), by anonymous donors and by the Serological Sciences Network (SeroNet) in part with Federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. 75N91019D00024, Task Order No. 75N91020F00003.
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http://dx.doi.org/10.1016/j.ebiom.2021.103626DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8527879PMC
November 2021

Human anti-neuraminidase antibodies reduce airborne transmission of clinical influenza virus isolates in the guinea pig model.

J Virol 2021 Oct 20:JVI0142121. Epub 2021 Oct 20.

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

The public health burden caused by influenza virus infections is not adequately addressed with existing vaccines and antivirals. Identifying approaches that interfere with human-to-human transmission of influenza viruses remains a pressing need. The importance of neuraminidase (NA) activity for the replication and spread of influenza viruses led us to investigate whether broadly reactive human anti-NA monoclonal antibodies (mAbs) could affect airborne transmission of the virus using the guinea pig model. In that model, infection with recent influenza virus clinical isolates resulted in 100% transmission from inoculated donors to recipients in an airborne transmission setting. Anti-NA mAbs were administered either to the inoculated animals on days 1, 2, and 4 after infection or to the naïve contacts on days 2 and 4 after donor infection. Administration of NA-1G01, a broadly cross-reactive anti-NA mAb, to either the donor or recipient reduced transmission of the A/New York City/PV02669/2019 (H1N1) and A/New York City/PV01148/2018 (H3N2) viruses. Administration of 1000-3C05, an anti-N1 mAb, to either the donor or recipient reduced transmission of A/New York City/PV02669/2019 (H1N1) virus but did not reduce transmission of A/New York City/PV01148 (H3N2) virus. Conversely, 229-2C06, an anti-N2 mAb, reduced transmission of A/New York City/PV01148 (H3N2) but did not impact transmission of A/New York City/PV02669/2019 (H1N1) virus. Our work demonstrates that anti-NA mAbs could be further developed into prophylactic or therapeutic agents to prevent influenza virus transmission and thus control viral spread. The burden of influenza remains substantial despite unremitting efforts to reduce the magnitude of seasonal influenza epidemics and prepare for pandemics. While vaccination remains the mainstay of these efforts, current vaccines are designed to stimulate an immune response against the viral hemagglutinin. Interest in the role immunity against neuraminidase plays in influenza virus infection and transmission has recently surged. Human antibodies that bind broadly to neuraminidases of diverse influenza viruses and protect mice against lethal viral challenge have previously been characterized. Here, we show that three such antibodies inhibit the neuraminidase activity of recent isolates and reduce their airborne transmission in a guinea pig model. In addition to contributing to the accumulating support for incorporating neuraminidase as a vaccine antigen, these findings also demonstrate the potential of direct administration of anti-neuraminidase antibodies to individuals infected with influenza virus and to individuals for post-exposure prophylaxis to prevent the spread of influenza.
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http://dx.doi.org/10.1128/JVI.01421-21DOI Listing
October 2021

Modified methicillin-resistant Staphylococcus aureus detected in neonatal intensive care patients.

J Antimicrob Chemother 2021 10;76(11):2774-2777

Department of Genetics and Genomics Sciences, Icahn School of Medicine at Mount Sinai, New York City, NY, USA.

Objectives: As part of an active MRSA surveillance programme in our neonatal ICU, we identified nares surveillance cultures from two infants that displayed heterogeneity in methicillin resistance between isolated subclones that lacked mecA and mecC.

Methods: The underlying mechanism for the modified Staphylococcus aureus (MODSA) methicillin-resistance phenotype was investigated by WGS.

Results: Comparison of finished-quality genomes of four MODSA and four MSSA subclones demonstrated that the resistance changes were associated with unique truncating mutations in the gene encoding the cyclic diadenosine monophosphate phosphodiesterase enzyme GdpP or a non-synonymous substitution in the gene encoding PBP2.

Conclusions: These two cases highlight the difficulty in identifying non-mecA, non-mecC-mediated MRSA isolates in the clinical microbiology laboratory, which leads to difficulties in implementing appropriate therapy and infection control measures.
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http://dx.doi.org/10.1093/jac/dkab266DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8521402PMC
October 2021

SARS-CoV-2 in Transit: Characterization of SARS-CoV-2 Genomes From Venezuelan Migrants in Colombia.

Int J Infect Dis 2021 Sep 29;110:410-416. Epub 2021 Jul 29.

Instituto de Investigaciones Biomédicas IDB/Emerging Pathogens Network-Incubadora Venezolana de la Ciencia, Cabudare, Venezuela; Department of Pathology, Molecular, and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Electronic address:

Objectives: To evaluate the genomic epidemiology of SARS-CoV-2 from Venezuelan migrants living in Colombia.

Methods: This study sequenced SARS-CoV-2 from 30 clinical specimens collected from Venezuelan migrants. Genomes were compared with the Wuhan reference genome to identify polymorphisms, reconstruct phylogenetic relationships and perform comparative genomic analyses. Geographic, sociodemographic and clinical data were also studied across genotypes.

Results: This study demonstrated the presence of six distinct SARS-CoV-2 lineages circulating among Venezuelan migrants, as well as a close relationship between SARS-CoV-2 genomic sequences obtained from individuals living in the Venezuelan-Colombian border regions of La Guajira (Colombia) and Zulia (Venezuela). Three clusters (C-1, C-2 and C-3) were well supported by phylogenomic inference, supporting the hypothesis of three potential transmission routes across the Colombian-Venezuelan border. These genomes included point mutations previously associated with increased infectivity. A mutation (L18F) in the N-terminal domain of the spike protein that has been associated with compromised binding of neutralizing antibodies was found in 2 of 30 (6.6%) genomes. A statistically significant association was identified with symptomatology for cluster C2.

Conclusion: The close phylogenetic relationships between SARS-CoV-2 genomes from Venezuelan migrants and from people living at the Venezuela-Colombian border support the importance of human movements for the spread of COVID-19 and for emerging virus variants.
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http://dx.doi.org/10.1016/j.ijid.2021.07.069DOI Listing
September 2021

SARS-CoV-2 mRNA vaccination induces functionally diverse antibodies to NTD, RBD, and S2.

Cell 2021 07 8;184(15):3936-3948.e10. Epub 2021 Jun 8.

Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. Electronic address:

In this study we profiled vaccine-induced polyclonal antibodies as well as plasmablast-derived mAbs from individuals who received SARS-CoV-2 spike mRNA vaccine. Polyclonal antibody responses in vaccinees were robust and comparable to or exceeded those seen after natural infection. However, the ratio of binding to neutralizing antibodies after vaccination was greater than that after natural infection and, at the monoclonal level, we found that the majority of vaccine-induced antibodies did not have neutralizing activity. We also found a co-dominance of mAbs targeting the NTD and RBD of SARS-CoV-2 spike and an original antigenic-sin like backboost to spikes of seasonal human coronaviruses OC43 and HKU1. Neutralizing activity of NTD mAbs but not RBD mAbs against a clinical viral isolate carrying E484K as well as extensive changes in the NTD was abolished, suggesting that a proportion of vaccine-induced RBD binding antibodies may provide substantial protection against viral variants carrying single E484K RBD mutations.
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http://dx.doi.org/10.1016/j.cell.2021.06.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8185186PMC
July 2021

Molecular evidence of SARS-CoV-2 in New York before the first pandemic wave.

Nat Commun 2021 06 8;12(1):3463. Epub 2021 Jun 8.

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

Numerous reports document the spread of SARS-CoV-2, but there is limited information on its introduction before the identification of a local case. This may lead to incorrect assumptions when modeling viral origins and transmission. Here, we utilize a sample pooling strategy to screen for previously undetected SARS-CoV-2 in de-identified, respiratory pathogen-negative nasopharyngeal specimens from 3,040 patients across the Mount Sinai Health System in New York. The patients had been previously evaluated for respiratory symptoms or influenza-like illness during the first 10 weeks of 2020. We identify SARS-CoV-2 RNA from specimens collected as early as 25 January 2020, and complete SARS-CoV-2 genome sequences from multiple pools of samples collected between late February and early March, documenting an increase prior to the later surge. Our results provide evidence of sporadic SARS-CoV-2 infections a full month before both the first officially documented case and emergence of New York as a COVID-19 epicenter in March 2020.
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http://dx.doi.org/10.1038/s41467-021-23688-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187428PMC
June 2021

RT-PCR/MALDI-TOF mass spectrometry-based detection of SARS-CoV-2 in saliva specimens.

J Med Virol 2021 Sep 19;93(9):5481-5486. Epub 2021 May 19.

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

As severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infections continue, there is a substantial need for cost-effective and large-scale testing that utilizes specimens that can be readily collected from both symptomatic and asymptomatic individuals in various community settings. Although multiple diagnostic methods utilize nasopharyngeal specimens, saliva specimens represent an attractive alternative as they can rapidly and safely be collected from different populations. While saliva has been described as an acceptable clinical matrix for the detection of SARS-CoV-2, evaluations of analytic performance across platforms for this specimen type are limited. Here, we used a novel sensitive RT-PCR/MALDI-TOF mass spectrometry-based assay (Agena MassARRAY®) to detect SARS-CoV-2 in saliva specimens. The platform demonstrated high diagnostic sensitivity and specificity when compared to matched patient upper respiratory specimens. We also evaluated the analytical sensitivity of the platform and determined the limit of detection of the assay to be 1562.5 copies/ml. Furthermore, across the five individual target components of this assay, there was a range in analytic sensitivities for each target with the N2 target being the most sensitive. Overall, this system also demonstrated comparable performance when compared to the detection of SARS-CoV-2 RNA in saliva by the cobas® 6800/8800 SARS-CoV-2 real-time RT-PCR Test (Roche). Together, we demonstrate that saliva represents an appropriate matrix for SARS-CoV-2 detection on the novel Agena system as well as on a conventional real-time RT-PCR assay. We conclude that the MassARRAY® system is a sensitive and reliable platform for SARS-CoV-2 detection in saliva, offering scalable throughput in a large variety of clinical laboratory settings.
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http://dx.doi.org/10.1002/jmv.27069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8242556PMC
September 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

The plasmablast response to SARS-CoV-2 mRNA vaccination is dominated by non-neutralizing antibodies and targets both the NTD and the RBD.

medRxiv 2021 May 1. Epub 2021 May 1.

Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

In this study we profiled vaccine-induced polyclonal antibodies as well as plasmablast derived mAbs from individuals who received SARS-CoV-2 spike mRNA vaccine. Polyclonal antibody responses in vaccinees were robust and comparable to or exceeded those seen after natural infection. However, the ratio of binding to neutralizing antibodies after vaccination was greater than that after natural infection and, at the monoclonal level, we found that the majority of vaccine-induced antibodies did not have neutralizing activity. We also found a co-dominance of mAbs targeting the NTD and RBD of SARS-CoV-2 spike and an original antigenic-sin like backboost to seasonal human coronaviruses OC43 and HKU1. Neutralizing activity of NTD mAbs but not RBD mAbs against a clinical viral isolate carrying E484K as well as extensive changes in the NTD was abolished, suggesting that a proportion of vaccine induced RBD binding antibodies may provide substantial protection against viral variants carrying single E484K RBD mutations.
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http://dx.doi.org/10.1101/2021.03.07.21253098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7987037PMC
May 2021

Real-Time Investigation of a Large Nosocomial Influenza A Outbreak Informed by Genomic Epidemiology.

Clin Infect Dis 2020 Nov 30. Epub 2020 Nov 30.

Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY.

Background: Nosocomial respiratory virus outbreaks represent serious public health challenges. Rapid and precise identification of cases and tracing of transmission chains is critical to end outbreaks and to inform prevention measures.

Methods: We combined conventional surveillance with influenza A virus (IAV) genome sequencing to identify and contain a large IAV outbreak in a metropolitan healthcare system. A total of 381 individuals, including 91 inpatients and 290 health care workers (HCWs), were included in the investigation.

Results: During a 12-day period in early 2019, infection preventionists identified 89 HCWs and 18 inpatients as cases of influenza-like illness (ILI), using an amended definition without the requirement for fever. Sequencing of IAV genomes from available nasopharyngeal (NP) specimens identified 66 individuals infected with a nearly identical strain of influenza A H1N1pdm09 (43 HCWs, 17 inpatients, and 6 with unspecified affiliation). All HCWs infected with the outbreak strain had received the seasonal influenza virus vaccination. Characterization of five representative outbreak viral isolates did not show antigenic drift. In conjunction with IAV genome sequencing, mining of electronic records pinpointed the origin of the outbreak as a single patient and a few interactions in the emergency department that occurred one day prior to the index ILI cluster.

Conclusions: We used precision surveillance to delineate a large nosocomial IAV outbreak, mapping the source of the outbreak to a single patient rather than HCWs as initially assumed based on conventional epidemiology. These findings have important ramifications for more effective prevention strategies to curb nosocomial respiratory virus outbreaks.
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http://dx.doi.org/10.1093/cid/ciaa1781DOI Listing
November 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

Repeated cross-sectional sero-monitoring of SARS-CoV-2 in New York City.

Nature 2021 02 3;590(7844):146-150. Epub 2020 Nov 3.

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

In late 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first detected in China and has since caused a pandemic of coronavirus disease 2019 (COVID-19). The first case of COVID-19 in New York City was officially confirmed on 1 March 2020 followed by a severe local epidemic. Here, to understand seroprevalence dynamics, we conduct a retrospective, repeated cross-sectional analysis of anti-SARS-CoV-2 spike antibodies in weekly intervals from the beginning of February to July 2020 using more than 10,000 plasma samples from patients at Mount Sinai Hospital in New York City. We describe the dynamics of seroprevalence in an 'urgent care' group, which is enriched in cases of COVID-19 during the epidemic, and a 'routine care' group, which more closely represents the general population. Seroprevalence increased at different rates in both groups; seropositive samples were found as early as mid-February, and levelled out at slightly above 20% in both groups after the epidemic wave subsided by the end of May. From May to July, seroprevalence remained stable, suggesting lasting antibody levels in the population. Our data suggest that SARS-CoV-2 was introduced in New York City earlier than previously documented and describe the dynamics of seroconversion over the full course of the first wave of the pandemic in a major metropolitan area.
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http://dx.doi.org/10.1038/s41586-020-2912-6DOI Listing
February 2021

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

The Rationale for Use of Amiodarone and its Derivatives for the Treatment of Chagas' Disease and Leishmaniasis.

Curr Pharm Des 2021 ;27(15):1825-1833

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

The repurposing or repositioning of previously-approved drugs has become an accepted strategy for the 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 Ca 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 Ca 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 to minimize 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 and 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
June 2021

Positive, again! What to make of "re-positive" SARS-CoV-2 molecular test results.

EBioMedicine 2020 Oct 22;60:103011. Epub 2020 Sep 22.

Department of Pathology, Molecular and Cell Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States.

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http://dx.doi.org/10.1016/j.ebiom.2020.103011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7506438PMC
October 2020

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

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

Multisystem inflammatory syndrome in children related to COVID-19: A New York City experience.

J Med Virol 2021 01 5;93(1):424-433. Epub 2020 Oct 5.

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

In December 2019, the 2019, a novel coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) first emerged in Wuhan, China. This has now spread worldwide and was declared a pandemic by March 2020. Initially, the pediatric population was described as a low risk for severe COVID-19. However, reports have emerged recently of cases of COVID-19 in children with a systemic inflammatory disease, with features that overlap with Kawasaki disease (KD). We describe the first 15 cases with the multi-systeminflammatory syndrome in children (MIS-C), temporally related to COVID-19, who presented for care to a tertiary pediatric referral center in New York City. We discuss the disproportionate burden of disease among Hispanic/Latino and Black/African American ancestry, the distinct cytokine signature across the disease spectrum (IL-1/IL-6), and the potential role and pathogenesis of SARS-CoV-2 in this new clinical entity.
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http://dx.doi.org/10.1002/jmv.26224DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7361761PMC
January 2021

Introductions and early spread of SARS-CoV-2 in the New York City area.

Science 2020 07 29;369(6501):297-301. Epub 2020 May 29.

Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

New York City (NYC) has emerged as one of the epicenters of the current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. To identify the early transmission events underlying the rapid spread of the virus in the NYC metropolitan area, we sequenced the virus that causes coronavirus disease 2019 (COVID-19) in patients seeking care at the Mount Sinai Health System. Phylogenetic analysis of 84 distinct SARS-CoV-2 genomes indicates multiple, independent, but isolated introductions mainly from Europe and other parts of the United States. Moreover, we found evidence for community transmission of SARS-CoV-2 as suggested by clusters of related viruses found in patients living in different neighborhoods of the city.
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http://dx.doi.org/10.1126/science.abc1917DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7259823PMC
July 2020

Central nervous system involvement by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2).

J Med Virol 2020 Jul;92(7):699-702

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

Neurologic sequelae can be devastating complications of respiratory viral infections. We report the presence of virus in neural and capillary endothelial cells in frontal lobe tissue obtained at postmortem examination from a patient infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Our observations of virus in neural tissue, in conjunction with clinical correlates of worsening neurologic symptoms, pave the way to a closer understanding of the pathogenic mechanisms underlying central nervous system involvement by SARS-CoV-2.
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http://dx.doi.org/10.1002/jmv.25915DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7264598PMC
July 2020

Human Papillomavirus (HPV69/HPV73) Coinfection associated with Simultaneous Squamous Cell Carcinoma of the Anus and Presumed Lung Metastasis.

Viruses 2020 03 22;12(3). Epub 2020 Mar 22.

Department of Pathology, Molecular, and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

Background: Human papillomaviruses (HPVs) have been linked to a variety of human cancers. As the landscape of HPV-related neoplasia continues to expand, uncommon and rare HPV genotypes have also started to emerge. Host-virus interplay is recognized as a key driver in HPV carcinogenesis, with host immune status, virus genetic variants and coinfection highly influencing the dynamics of malignant transformation. Immunosuppression and tissue tropism are also known to influence HPV pathogenesis.

Methods: Herein, we present a case of a patient who, in the setting of HIV positivity, developed anal squamous cell carcinoma associated with HPV69 and later developed squamous cell carcinoma in the lungs, clinically presumed to be metastatic disease, associated with HPV73. Consensus PCR screening for HPV was performed by real-time PCR amplification of the L1 gene region, amplification of the E6 regions with High-Resolution Melting Curve Analysis followed by Sanger sequencing confirmation and phylogenetic analysis.

Results: Sanger sequencing of the consensus PCR amplification product determined that the anal tissue sample was positive for HPV 69, and the lung tissue sample was positive for HPV 73.

Conclusions: This case underscores the importance of recognizing the emerging role of these rare "possibly carcinogenic" HPV types in human carcinogenesis.
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http://dx.doi.org/10.3390/v12030349DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7150817PMC
March 2020

Disruption of Intracellular Calcium Homeostasis as a Therapeutic Target Against .

Front Cell Infect Microbiol 2020 14;10:46. Epub 2020 Feb 14.

Instituto de Estudios Avanzados, Caracas, Venezuela.

There is no effective cure for Chagas disease, which is caused by infection with the arthropod-borne parasite, . In the search for new drugs to treat Chagas disease, potential therapeutic targets have been identified by exploiting the differences between the mechanisms involved in intracellular Ca homeostasis, both in humans and in trypanosomatids. In the trypanosomatid, intracellular Ca regulation requires the concerted action of three intracellular organelles, the endoplasmic reticulum, the single unique mitochondrion, and the acidocalcisomes. The single unique mitochondrion and the acidocalcisomes also play central roles in parasite bioenergetics. At the parasite plasma membrane, a Ca-ATPase (PMCA) with significant differences from its human counterpart is responsible for Ca extrusion; a distinctive sphingosine-activated Ca channel controls Ca entrance to the parasite interior. Several potential anti-trypansosomatid drugs have been demonstrated to modulate one or more of these mechanisms for Ca regulation. The antiarrhythmic agent amiodarone and its derivatives have been shown to exert trypanocidal effects through the disruption of parasite Ca homeostasis. Similarly, the amiodarone-derivative dronedarone disrupts Ca homeostasis in epimastigotes, collapsing the mitochondrial membrane potential (ΔΨ), and inducing a large increase in the intracellular Ca concentration ([Ca]) from this organelle and from the acidocalcisomes in the parasite cytoplasm. The same general mechanism has been demonstrated for SQ109, a new anti-tuberculosis drug with potent trypanocidal effect. Miltefosine similarly induces a large increase in the [Ca] acting on the sphingosine-activated Ca channel, the mitochondrion and acidocalcisomes. These examples, in conjunction with other evidence we review herein, strongly support targeting Ca homeostasis as a strategy against Chagas disease.
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http://dx.doi.org/10.3389/fcimb.2020.00046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7040492PMC
June 2021

Exposure Risk Events in 10 Clinical Laboratories, New York City, USA, 2015 to 2017.

J Clin Microbiol 2020 01 28;58(2). Epub 2020 Jan 28.

Occupational Health Services, Montefiore Medical Center, Bronx, New York, USA.

From 2015 to 2017, 11 confirmed brucellosis cases were reported in New York City, leading to 10 exposure risk events ( events) in 7 clinical laboratories (CLs). Most patients had traveled to countries where brucellosis is endemic and presented with histories and findings consistent with brucellosis. CLs were not notified that specimens might yield a hazardous organism, as the clinicians did not consider brucellosis until they were notified that bacteremia with was suspected. In 3 events, the CLs did not suspect that slow-growing, small Gram-negative bacteria might be harmful. Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), which has a limited capacity to identify biological threat agents (BTAs), was used during 4 events, which accounted for 84% of exposures. In 3 of these incidents, initial staining of liquid media showed Gram-positive rods or cocci, including some cocci in chains, suggesting streptococci. Over 200 occupational exposures occurred when the unknown isolates were manipulated and/or tested on open benches, including by procedures that could generate infectious aerosols. During 3 events, the CLs examined and/or manipulated isolates in a biological safety cabinet (BSC); in each CL, the CL had previously isolated Centers for Disease Control and Prevention recommendations to prevent laboratory-acquired brucellosis (LAB) were followed; no seroconversions or LAB cases occurred. Laboratory assessments were conducted after the events to identify facility-specific risks and mitigations. With increasing MALDI-TOF MS use, CLs are well-advised to adhere strictly to safe work practices, such as handling and manipulating all slow-growing organisms in BSCs and not using MALDI-TOF MS for identification until BTAs have been ruled out.
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http://dx.doi.org/10.1128/JCM.01096-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6989065PMC
January 2020

Hemorrhagic bullous lesions due to Bacillus cereus in a cirrhotic patient.

Cutis 2014 Dec;94(6):E15-7

Department of Pathology and Laboratory Medicine, St. Luke's-Roosevelt Hospital Center, 1111 Amsterdam Ave, New York, NY 10025, USA.

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December 2014

Staphylococcal enterocolitis: forgotten but not gone?

Dig Dis Sci 2010 May 16;55(5):1200-7. Epub 2009 Jul 16.

Division of Gastroenterology, Department of Medicine, St. Luke's-Roosevelt Hospital Center, New York, NY 10025, USA.

Purpose: Staphylococcus aureus may cause antibiotic-associated diarrhea and enterocolitis, with or without preceding antibiotic use, in immunocompromised adults or infants, or individuals with predisposing conditions, but there is little appreciation of this condition clinically. CLINICAL DISEASE: The main clinical feature that helps to differentiate staphylococcal enterocolitis (SEC) from Clostridium difficile-associated diarrhea is large-volume, cholera-like diarrhea in the former case. A predominance of gram-positive cocci in clusters on gram stain of stool or biopsy specimens and the isolation of S. aureus as the dominant or sole flora support the diagnosis.

Pathogenesis: The pathogenesis of SEC requires the interaction of staphylococcal enterotoxins, which function as superantigens, with interstitial epithelial lymphocytes and intestinal epithelial cells (IECs).

Management: Most SEC represents recent S. aureus acquisition, so that improved infection prevention practices can reduce disease recurrence. Management should include aggressive fluid management and repletion and oral vancomycin.
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http://dx.doi.org/10.1007/s10620-009-0886-1DOI Listing
May 2010

Toxic shock-like syndrome associated with staphylococcal enterocolitis in an HIV-infected man.

Clin Infect Dis 2007 Jun 9;44(12):e121-3. Epub 2007 May 9.

Division of Gastroenterology, Department of Medicine and Pathology, St. Luke's-Roosevelt Hospital Center, New York, NY 10025, USA.

A human immunodeficiency virus-infected individual developed severe secretory diarrhea due to infection with Staphylococcus aureus. When octreotide therapy was initiated, a toxic shock-like syndrome developed that was associated with fever, multisystem organ damage, and ultimately, desquamation of the palms and soles. The isolate was methicillin susceptible and produced enterotoxins B and C. This is, to our knowledge, the first reported case of toxic shock syndrome to develop secondary to staphylococcal enterocolitis in an adult.
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http://dx.doi.org/10.1086/518286DOI Listing
June 2007
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