Life Sciences Commons^™

Igg Antibodies To Sars-Cov-2 In Asymptomatic Blood Donors At Two Time Points In Karachi, Muhammad Hasan, Bushra Moiz, Shama Qaiser, Kiran I. Masood, Zara Ghous, Areeba Hussain, Natasha Bahadur Ali, Syed Hani Abidi, Kulsoom Ghias, Erum Khan, Zahra Hasan

Department of Pathology and Laboratory Medicine

Introduction: An estimated 1.5 million cases were reported in Pakistan until 23 March, 2022. However, SARS-CoV-2 PCR testing capacity has been limited and the incidence of COVID-19 infections is unknown. Volunteer healthy blood donors can be a control population for assessment of SARS-CoV-2 exposure in the population. We determined COVID-19 seroprevalence during the second pandemic wave in Karachi in donors without known infections or symptoms in 4 weeks prior to enrollment.
Materials and methods: We enrolled 558 healthy blood donors at the Aga Khan University Hospital between December 2020 and February 2021. ABO blood groups were determined. Serum IgG reactivity …

Experimental Infection Of Brazilian Free-Tailed Bats (Tadarida Brasiliensis) With Two Strains Of Sars-Cov-2, Angela M. Bosco-Lauth, Stephanie M. Porter, Karen A. Fox, Mary E. Wood, Daniel Neubaum, Marissa Quilici

USDA Wildlife Services: Staff Publications

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is presumed to have originated from wildlife and shares homology with other bat coronaviruses. Determining the susceptibility of North American bat species to SARS-CoV-2 is of utmost importance for making decisions regarding wildlife management, public health, and conservation. In this study, Brazilian free-tailed bats (Tadarida brasiliensis) were experimentally infected with two strains of SARS-CoV-2 (parental WA01 and Delta variant), evaluated for clinical disease, sampled for viral shedding and antibody production, and analyzed for pathology. None of the bats (n = 18) developed clinical disease associated with infection, shed infectious virus, or …

Antibody Responses To Sars-Cov-2 After Infection Or Vaccination In Children And Young Adults With Inflammatory Bowel Disease., Joelynn Dailey, Lina Kozhaya, Mikail Dogan, Dena Hopkins, Blaine Lapin, Katherine Herbst, Michael Brimacombe, Kristen Grandonico, Fatih Karabacak, John Schreiber, Bruce Tsan-Liang Liang, Juan C Salazar, Derya Unutmaz, Jeffrey S Hyams

Faculty Research 2022

BACKGROUND: Characterization of neutralization antibodies to SARS-CoV-2 infection or vaccination in children and young adults with inflammatory bowel disease (IBD) receiving biologic therapies is crucial.

METHODS: We performed a prospective longitudinal cohort study evaluating SARS-CoV-2 spike protein receptor binding domain (S-RBD) IgG positivity along with consistent clinical symptoms in patients with IBD receiving infliximab or vedolizumab. Serum was also obtained following immunization with approved vaccines. The IgG antibody to the spike protein binding domain of SARS-CoV-2 was assayed with a fluorescent bead-based immunoassay that takes advantage of the high dynamic range of fluorescent molecules using flow cytometry. A sensitive and …

Combining Genomic And Epidemiological Data To Compare The Transmissibility Of Sars-Cov-2 Variants Alpha And Iota., Mary E Petrone, Jessica E Rothman, Mallery I Breban, Isabel M Ott, Alexis Russell, Erica Lasek-Nesselquist, Hamada Badr, Kevin Kelly, Gregory Omerza, Nicholas Renzette, Anne E Watkins, Chaney C Kalinich, Tara Alpert, Anderson F Brito, Rebecca Earnest, Irina R Tikhonova, Christopher Castaldi, John P Kelly, Matthew Shudt, Jonathan Plitnick, Erasmus Schneider, Steven Murphy, Caleb Neal, Eva Laszlo, Ahmad Altajar, Claire Pearson, Anthony Muyombwe, Randy Downing, Jafar Razeq, Linda Niccolai, Madeline S Wilson, Margaret L Anderson, Jianhui Wang, Chen Liu, Pei Hui, Shrikant Mane, Bradford P Taylor, William P Hanage, Marie L Landry, David R Peaper, Kaya Bilguvar, Joseph R Fauver, Chantal B F Vogels, Lauren M Gardner, Virginia E Pitzer, Kirsten St George, Mark D Adams, Nathan D Grubaugh

Faculty Research 2022

SARS-CoV-2 variants shaped the second year of the COVID-19 pandemic and the discourse around effective control measures. Evaluating the threat posed by a new variant is essential for adapting response efforts when community transmission is detected. In this study, we compare the dynamics of two variants, Alpha and Iota, by integrating genomic surveillance data to estimate the effective reproduction number (R_t) of the variants. We use Connecticut, United States, in which Alpha and Iota co-circulated in 2021. We find that the R_t of these variants were up to 50% larger than that of other variants. We then …

Comparative Transmissibility Of Sars-Cov-2 Variants Delta And Alpha In New England, Usa., Rebecca Earnest, Rockib Uddin, Nicholas Matluk, Nicholas Renzette, Sarah E Turbett, Katherine J Siddle, Christine Loreth, Gordon Adams, Christopher H Tomkins-Tinch, Mary E Petrone, Jessica E Rothman, Mallery I Breban, Robert Tobias Koch, Kendall Billig, Joseph R Fauver, Chantal B F Vogels, Kaya Bilguvar, Bony De Kumar, Marie L Landry, David R Peaper, Kevin Kelly, Greg Omerza, Heather Grieser, Sim Meak, John Martha, Hannah B Dewey, Susan Kales, Daniel Berenzy, Kristin Carpenter-Azevedo, Ewa King, Richard C Huard, Vlad Novitsky, Mark Howison, Josephine Darpolor, Akarsh Manne, Rami Kantor, Sandra C Smole, Catherine M Brown, Timelia Fink, Andrew S Lang, Glen R Gallagher, Virginia E Pitzer, Pardis C Sabeti, Stacey Gabriel, Bronwyn L Macinnis, New England Variant Investigation Team, Ryan Tewhey, Mark D Adams, Daniel J Park, Jacob E Lemieux, Nathan D Grubaugh

Faculty Research 2022

The SARS-CoV-2 Delta variant rose to dominance in mid-2021, likely propelled by an estimated 40%-80% increased transmissibility over Alpha. To investigate if this ostensible difference in transmissibility is uniform across populations, we partner with public health programs from all six states in New England in the United States. We compare logistic growth rates during each variant's respective emergence period, finding that Delta emerged 1.37-2.63 times faster than Alpha (range across states). We compute variant-specific effective reproductive numbers, estimating that Delta is 63%-167% more transmissible than Alpha (range across states). Finally, we estimate that Delta infections generate on average 6.2 (95% …

Efficient Targeted Transgenesis Of Large Donor Dna Into Multiple Mouse Genetic Backgrounds Using Bacteriophage Bxb1 Integrase., Benjamin E. Low, Vishnu Hosur, Simon Lesbirel, Michael V. Wiles

Faculty Research 2022

The development of mouse models of human disease and synthetic biology research by targeted transgenesis of large DNA constructs represent a significant genetic engineering hurdle. We developed an efficient, precise, single-copy integration of large transgenes directly into zygotes using multiple mouse genetic backgrounds. We used in vivo Bxb1 mediated recombinase-mediated cassette exchange (RMCE) with a transgene "landing pad" composed of dual heterologous Bxb1 attachment (att) sites in cis, within the Gt(ROSA)26Sor safe harbor locus. RMCE of donor was achieved by microinjection of vector DNA carrying cognate attachment sites flanking the donor transgene with Bxb1-integrase mRNA. This approach achieves perfect vector-free …

Stepping-Stones And Mediators Of Pandemic Expansion: A Context For Humans As Ecological Super-Spreaders, Eric P. Hoberg, Walter A. Boeger, Daniel R. Brooks, Valeria Trivellone, Salvatore J. Agosta

MANTER: Journal of Parasite Biodiversity

Humans represent ecological super-spreaders in the dissemination and introduction of pathogens. These processes, consistent with the dynamics of the Stockholm paradigm, are exemplified in the origin and globalized distributions of SARS-CoV-2 since initial recognition in central Asia during 2019 and 2020. SARS-like viruses are not widespread in mammals but appear widespread in chiropterans. Bats are isolated ecologically from most other assemblages of mammals in terrestrial systems. Humans may be the stepping-stone hosts for broad global dissemination and wider infection (given the opportunity) among diverse assemblages of mammals in which host and viral capacity are compatible. Human globalization mediated insertion in …

Epidemiology, Clinical Ramifications, And Cellular Pathogenesis Of Covid-19 Mrna-Vaccination-Induced Adverse Cardiovascular Outcomes: A State-Of-The-Heart Review, Talal Almas, Sarah Rehman, Eyad Mansour, Tarek Khedro, Ali Alansari, Jahanzeb Malik, Norah Alshareef, Vikneswaran Raj Nagarajan, Abdulla Hussain Al-Awaid, Reema Alsufyani

Medical College Documents

The coronavirus disease 2019 (COVID-19) has overwhelming healthcare systems globally. To date, a myriad of therapeutic regimens has been employed in an attempt to curb the ramifications of a severe COVID-19 infection. Amidst the ongoing pandemic, the advent and efficacious uptake of COVID-19 vaccination has significantly reduced disease-related hospitalizations and mortality. Nevertheless, many side-effects are being reported after COVID-19 vaccinations and myocarditis is the most commonly reported sequelae post vaccination. Majority of these diseases are associated with COVID-19 mRNA vaccines. Various studies have established a temporal relationship between these complications, yet the causality and the underlying pathogenesis remain hypothetical. In …

Hsp90 Inhibitors Modulate Sars-Cov-2 Spike Protein Subunit 1-Induced Human Pulmonary Microvascular Endothelial Activation And Barrier Dysfunction, Ruben Manuel Luciano Colunga Biancatelli, Pavel Solopov, Betsy W. Gregory, Yara Khodour, John D. Catravas

Bioelectrics Publications

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused more than 5 million deaths worldwide. Multiple reports indicate that the endothelium is involved during SARS-Cov-2-related disease (COVID-19). Indeed, COVID-19 patients display increased thrombophilia with arterial and venous embolism and lung microcapillary thrombotic disease as major determinants of deaths. The pathophysiology of endothelial dysfunction in COVID-19 is not completely understood. We have investigated the role of subunit 1 of the SARS-CoV-2 spike protein (S1SP) in eliciting endothelial barrier dysfunction, characterized dose and time relationships, and tested the hypothesis that heat shock protein 90 (HSP90) inhibitors would prevent and repair such injury. S1SP …

A Review Of Coronaviruses Associated With Kawasaki Disease: Possible Implications For Pathogenesis Of The Multisystem Inflammatory Syndrome Associated With Covid-19, Fatima Farrukh Shahbaz, Russell Seth Martins, Abdullah Umair, Ronika Devi Ukrani, Kauser Jabeen, M Rizwan Sohail, Erum Khan

Medical College Documents

Multisystem Inflammatory Syndrome in Children (MIS-C), representing a new entity in the spectrum of manifestations of COVID-19, bears symptomatic resemblance with Kawasaki Disease (KD). This review explores the possible associations between KD and the human coronaviruses and discusses the pathophysiological similarities between KD and MIS-C and proposes implications for the pathogenesis of MIS-C in COVID-19. Since 2005, when a case-control study demonstrated the association of a strain of human coronavirus with KD, several studies have provided evidence regarding the association of different strains of the human coronaviruses with KD. Thus, the emergence of the KD-like disease MIS-C in COVID-19 may …

The Low Abundance Of Cpg In The Sars-Cov-2 Genome Is Not An Evolutionarily Signature Of Zap, Ali Afrasiabi, Hamid Alinejad-Rokny, Azad Khosh, Mostafa Rahnama, Nigel Lovell, Zhenming Xu, Diako Ebrahimi

Plant Pathology Faculty Publications

The zinc finger antiviral protein (ZAP) is known to restrict viral replication by binding to the CpG rich regions of viral RNA, and subsequently inducing viral RNA degradation. This enzyme has recently been shown to be capable of restricting SARS-CoV-2. These data have led to the hypothesis that the low abundance of CpG in the SARS-CoV-2 genome is due to an evolutionary pressure exerted by the host ZAP. To investigate this hypothesis, we performed a detailed analysis of many coronavirus sequences and ZAP RNA binding preference data. Our analyses showed neither evidence for an evolutionary pressure acting specifically on CpG …

Single-Cell Multi-Omics Reveals Dyssynchrony Of The Innate And Adaptive Immune System In Progressive Covid-19., Avraham Unterman, Tomokazu S Sumida, Nima Nouri, Xiting Yan, Amy Y Zhao, Victor Gasque, Jonas C Schupp, Hiromitsu Asashima, Yunqing Liu, Carlos Cosme, Wenxuan Deng, Ming Chen, Micha Sam Brickman Raredon, Kenneth B Hoehn, Guilin Wang, Zuoheng Wang, Giuseppe Deiuliis, Neal G Ravindra, Ningshan Li, Christopher Castaldi, Patrick Wong, John Fournier, Santos Bermejo, Lokesh Sharma, Arnau Casanovas-Massana, Chantal B F Vogels, Anne L Wyllie, Nathan D Grubaugh, Anthony Melillo, Hailong Meng, Yan Stein, Maksym Minasyan, Subhasis Mohanty, William E Ruff, Inessa Cohen, Khadir Raddassi, Laura E Niklason, Albert I Ko, Ruth R Montgomery, Shelli F Farhadian, Akiko Iwasaki, Albert C Shaw, David Van Dijk, Hongyu Zhao, Steven H Kleinstein, David A Hafler, Naftali Kaminski, Charles S Dela Cruz

Faculty Research 2022

Dysregulated immune responses against the SARS-CoV-2 virus are instrumental in severe COVID-19. However, the immune signatures associated with immunopathology are poorly understood. Here we use multi-omics single-cell analysis to probe the dynamic immune responses in hospitalized patients with stable or progressive course of COVID-19, explore V(D)J repertoires, and assess the cellular effects of tocilizumab. Coordinated profiling of gene expression and cell lineage protein markers shows that S100A

Tracking Cryptic Sars-Cov-2 Lineages Detected In Nyc Wastewater, Davida S. Smyth, Monica Trujillo, Devon A. Gregory, Kristen Cheung, Anna Gao, Maddie Graham, Yue Guan, Caitlyn Guldenpfennig, Irene Hoxie, Sherin Kannoly, Nanami Kubota, Terri D. Lyddon, Michelle Markman, Clayton Rushford, Kaung Myat San, Geena Sompanya, Fabrizio Spagnolo, Reinier Suarez, Emma Teixeiro, Mark Daniels, Marc C. Johnson, John J. Dennehy

Publications and Research

Tracking SARS-CoV-2 genetic diversity is strongly indicated because diversifying selection may lead to the emergence of novel variants resistant to naturally acquired or vaccine-induced immunity. To monitor New York City (NYC) for the presence of novel variants, we deep sequence most of the receptor binding domain coding sequence of the S protein of SARS-CoV-2 isolated from the New York City wastewater. Here we report detecting increasing frequencies of novel cryptic SARS-CoV-2 lineages not recognized in GISAID’s EpiCoV database. These lineages contain mutations that had been rarely observed in clinical samples, including Q493K, Q498Y, E484A, and T572N and share many mutations …

Methodology To Estimate Natural- And Vaccine-Induced Antibodies To Sars-Cov-2 In A Large Geographic Region, Stacia M Desantis, Luis G León-Novelo, Michael D Swartz, Ashraf S Yaseen, Melissa A Valerio-Shewmaker, Yashar Talebi, Frances A Brito, Jessica A Ross, Harold W Kohl, Sarah E Messiah, Steve H Kelder, Leqing Wu, Shiming Zhang, Kimberly A Aguillard, Michael O Gonzalez, Onyinye S Omega-Njemnob, David Lakey, Jennifer A Shuford, Stephen Pont, Eric Boerwinkle

Journal Articles

Accurate estimates of natural and/or vaccine-induced antibodies to SARS-CoV-2 are difficult to obtain. Although model-based estimates of seroprevalence have been proposed, they require inputting unknown parameters including viral reproduction number, longevity of immune response, and other dynamic factors. In contrast to a model-based approach, the current study presents a data-driven detailed statistical procedure for estimating total seroprevalence (defined as antibodies from natural infection or from full vaccination) in a region using prospectively collected serological data and state-level vaccination data. Specifically, we conducted a longitudinal statewide serological survey with 88,605 participants 5 years or older with 3 prospective blood draws beginning …