A collection of articles related to coronaviruses that have been authored by researchers at Temple University.

Recent Submissions

  • Recent Zoonotic Spillover and Tropism Shift of a Canine Coronavirus Is Associated with Relaxed Selection and Putative Loss of Function in NTD Subdomain of Spike Protein

    Institute for Genomics and Evolutionary Medicine (Temple University) (2022-04-21)
    A canine coronavirus (CCoV) has now been reported from two independent human samples from Malaysia (respiratory, collected in 2017–2018; CCoV-HuPn-2018) and Haiti (urine, collected in 2017); these two viruses were nearly genetically identical. In an effort to identify any novel adaptations associated with this apparent shift in tropism we carried out detailed evolutionary analyses of the spike gene of this virus in the context of related Alphacoronavirus 1 species. The spike 0-domain retains homology to CCoV2b (enteric infections) and Transmissible Gastroenteritis Virus (TGEV; enteric and respiratory). This domain is subject to relaxed selection pressure and an increased rate of molecular evolution. It contains unique amino acid substitutions, including within a region important for sialic acid binding and pathogenesis in TGEV. Overall, the spike gene is extensively recombinant, with a feline coronavirus type II strain serving a prominent role in the recombinant history of the virus. Molecular divergence time for a segment of the gene where temporal signal could be determined, was estimated at around 60 years ago. We hypothesize that the virus had an enteric origin, but that it may be losing that particular tropism, possibly because of mutations in the sialic acid binding region of the spike 0-domain.
  • Staying active after rehab: Physical activity perspectives with a spinal cord injury beyond functional gains

    Baehr, Laura A.; Kaimal, Girija; Hiremath, Shivayogi; Trost, Zina; Finley, Margaret; Hiremath|0000-0002-9708-1411 (2022-03-23)
    Lifestyle physical activity following spinal cord injury (SCI) is critical for functional independence, mental wellness, and social participation, yet nearly 50% of individuals with SCI report no regular exercise. The objective of this study was to better understand factors leading to this participation gap by capturing the physical activity perspectives of individuals living with SCI. We completed small group interviews with nine individuals living with SCI across the United States. Iterative thematic analysis systematically revealed meaningful core concepts related to physical activity engagement with SCI. Emergent themes revealed challenges to lifestyle physical activity behavior including gaps in physical activity education, isolation during psychological adjustment, and knowledge limitations in community exercise settings. A secondary theme related to the COVID-19 pandemic emerged, highlighting additional environmental constraints affecting participation. Our findings suggest that most physical activity education is delivered during inpatient rehabilitation and is related to physical function. Lifetime physical activity strategies are achieved through self-education and peer networking. Personal motivators for physical activity include secondary condition prevention, while social and emotional barriers prevent regular adherence. These findings can inform the development and delivery of physical activity programs to maximize physical activity engagement in individuals living with chronic SCI.
  • SCENTinel 1.1 rapidly screens for COVID-19 related olfactory disorders

    Monell Chemical Senses Center (2022-03-23)
    The COVID-19 pandemic has increased the prevalence of people suffering from olfactory disorders. In the absence of quick, population-wide olfactory tests, we developed SCENTinel, a rapid, inexpensive smell test to assess odor detection, intensity, and identification ability, which can discriminate anosmia (e.g., total smell loss) from normosmia (e.g., normal sense of smell) using a single odor. A new version, SCENTinel 1.1, extends the original test with one of four possible odors and a hedonic subtest (“how pleasant is the odor”). The purpose of this study was to determine if SCENTinel 1.1 can discriminate other types of olfactory disorders common to COVID-19, such as hyposmia (e.g., reduced sense of smell), parosmia (e.g., distorted odor perception), and phantosmia (e.g., odor sensation without an odor source). Participants (N=381) were divided into three groups based on their self-reported olfactory function: quantitative smell disorder (anosmia or hyposmia, N=135), qualitative smell disorder (parosmia and/or phantosmia; n=86), and normosmia (N=66). SCENTinel 1.1 classifies anosmia and normosmia groups with high sensitivity (AUC=0.94), similar to SCENTinel 1.0 (AUC=0.95). SCENTinel 1.1 also accurately discriminates quantitative from qualitative (AUC=0.76), and normosmia (AUC=0.84), and normosmia from qualitative (AUC=0.73) groups. We also considered a subset of participants who only reported one type of olfactory disorder. SCENTinel 1.1 discriminates hyposmia from parosmia (AUC=0.89), and anosmia (AUC=0.78); as well as parosmia from anosmia (AUC=0.82). Participants with parosmia had a significantly lower hedonic score than those without parosmia, indicating odor distortions are unpleasant. SCENTinel 1.1 is a rapid smell test that can discriminate quantitative (anosmia, hyposmia) and qualitative (parosmia, phantosmia) olfactory disorders, and it is among the only direct tests to rapidly screen for parosmia.
  • Intranasal Nanoemulsion Adjuvanted S-2P Vaccine Demonstrates Protection in Hamsters and Induces Systemic, Cell-Mediated and Mucosal Immunity in Mice

    Ganesan, Shyamala; Acosta, Hugo; Brigolin, Chris; Orange, Kallista; Trabbic, Kevin; Chen, Charles; Lien, Chia-En; Lin, Yi-Jiun; Lin, Meei-Yun; Chuang, Ya-Shan; Fattom, Ali; Bitko, Vira (2022-03-23)
    With the rapid progress made in the development of vaccines to fight the SARS-CoV-2 pandemic, almost >90% of vaccine candidates under development and a 100% of the licensed vaccines are delivered intramuscularly (IM). While these vaccines are highly efficacious against COVID-19 disease, their efficacy against SARS-CoV-2 infection of upper respiratory tract and transmission is at best temporary. Development of safe and efficacious vaccines that are able to induce robust mucosal and systemic immune responses are needed to control new variants. In this study, we have used our nanoemulsion adjuvant (NE01) to intranasally (IN) deliver stabilized spike protein (S-2P) to induce immunogenicity in mouse and hamster models. Data presented demonstrate the induction of robust immunity in mice resulting in 100% seroconversion and protection against SARS-CoV-2 in a hamster challenge model. There was a significant induction of mucosal immune responses as demonstrated by IgA- and IgG-producing memory B cells in the lungs of animals that received intranasal immunizations compared to an alum adjuvanted intramuscular vaccine. The efficacy of the S-2P/NE01 vaccine was also demonstrated in an intranasal hamster challenge model with SARS-CoV-2 and conferred significant protection against weight loss, lung pathology, and viral clearance from both upper and lower respiratory tract. Our findings demonstrate that intranasal NE01-adjuvanted vaccine promotes protective immunity against SARS-CoV-2 infection and disease through activation of three arms of immune system: humoral, cellular, and mucosal, suggesting that an intranasal SARS-CoV-2 vaccine may play a role in addressing a unique public health problem and unmet medical need.
  • Visits to the Pediatric Emergency Department for Eye Conditions Before and During the COVID-19 Pandemic

    Jin, Jing; Bules, Lauren; Doctor, Kaynan; Hendricks, Dorothy; Callaghan, Katherine; Reid, Julia E.; Salvin, Jonathan; Lehman, Sharon; Fasiuddin, Airaj; Piatt, Joseph (2022-03-24)
    Introduction: The use of the emergency department (ED) has been increasing, and many visits occur for non-urgent conditions. A similar trend was found among adult visits to the ED for ocular conditions. In this study we analyzed the impact of sociodemographic factors, presentation timing, and the COVID-19 pandemic on pediatric ED (PED) encounters for ophthalmologic conditions. It is important to identify the multifold factors associated with overutilization of the ED for non-urgent conditions. Caring for these patients in an outpatient clinical setting is safe and effective and could decrease ED crowding; it would also prevent delays in the care of other patients with more urgent medical problems and lower healthcare costs. Methods: We retrospectively reviewed electronic health records of PED ocular-related encounters at two children’s hospitals before (January 2014-May 2018) and during the COVID-19 pandemic (March 2020-February 2021). Encounters were categorized based on the International Classification of Diseases codes into “emergent,” “urgent,” and non-urgent” groups. We analyzed associations between sociodemographic factors and degrees of visit urgency. We also compared visit frequencies, degrees of urgency, and diagnoses between pre-pandemic and pandemic data. Results: Pre-pandemic ocular-related PED encounters averaged 1,738 per year. There were highly significant sociodemographic associations with degrees of urgency in PED utilization. During the 12-month pandemic timeframe, encounter frequency contracted to 183. Emergent visits decreased from 21% to 11%, while the proportions of urgent and non-urgent encounters were mostly unchanged. The most common pre-pandemic urgent diagnosis was corneal abrasion (50%), while visual disturbance was most common during the pandemic (92%). During both time periods, eye trauma was the most frequent emergent encounter and conjunctivitis was the most common non-urgent encounter. Conclusion: Sociodemographic factors may be associated with different types of PED utilization for ocular conditions. Unnecessary visits constitute major inefficiency from a healthcare-systems standpoint. The marked decrease in PED utilization and differing proportions of ocular conditions encountered during the pandemic may reflect a decrease in incidence of many of those conditions by social distancing; these changes may also reflect altered parental decisions about seeking care.
  • Selection Analysis Identifies Clusters of Unusual Mutational Changes in Omicron Lineage BA.1 That Likely Impact Spike Function

    Institute for Genomics and Evolutionary Medicine (Temple University) (2022-03-24)
    Among the 30 nonsynonymous nucleotide substitutions in the Omicron S-gene are 13 that have only rarely been seen in other SARS-CoV-2 sequences. These mutations cluster within three functionally important regions of the S-gene at sites that will likely impact (1) interactions between subunits of the Spike trimer and the predisposition of subunits to shift from down to up configurations, (2) interactions of Spike with ACE2 receptors, and (3) the priming of Spike for membrane fusion. We show here that, based on both the rarity of these 13 mutations in intrapatient sequencing reads and patterns of selection at the codon sites where the mutations occur in SARS-CoV-2 and related sarbecoviruses, prior to the emergence of Omicron the mutations would have been predicted to decrease the fitness of any virus within which they occurred. We further propose that the mutations in each of the three clusters therefore cooperatively interact to both mitigate their individual fitness costs, and, in combination with other mutations, adaptively alter the function of Spike. Given the evident epidemic growth advantages of Omicron overall previously known SARS-CoV-2 lineages, it is crucial to determine both how such complex and highly adaptive mutation constellations were assembled within the Omicron S-gene, and why, despite unprecedented global genomic surveillance efforts, the early stages of this assembly process went completely undetected.
  • The COVID-19 Outbreak in South Korea: Lessons to Be Learned

    Joon Lee, Hark; Kang, Richard; Kim, Michelle; Kong, Justin; Shim, Woo Jun; Kim, Kunmin; Chung, Paul S. (2022-06-20)
    The Coronavirus 2019 (COVID-19) is a novel type of coronavirus-related disease that has over 4 million confirmed cases worldwide as of May 13th, 2020. With over 200 countries impacted by the pandemic, many countries have taken drastic measures such as temporary closure of international borders. The purpose of this thesis is to examine the South Korean response to COVID-19 and the keys to successful containment of the disease. Real time analysis was performed on data provided by the Centers for Disease Control (CDC). Comparisons of disease containment among countries with the highest confirmed cases were normalized for population size differences by taking the proportion of confirmed cases to population size. We further compared the disease outbreak in Seoul, a very urban environment, to the whole country of South Korea, to compare public health in urban and rural environments. We found that the efficient partnership between the private sector and the state led to rapid development in testing kits, which was integral to the South Korean response to COVID-19. In addition, the South Koreans’ community spirit, approval of government-led interventions, and societal norm of wearing masks were also efficient social responses to the spreading disease. In this paper, we navigate the impacts of a universal healthcare system and its ability to battle infectious diseases and the efficacy of various governmental actions in response to a public health crisis.
  • SARS-CoV-2 Causes Lung Inflammation through Metabolic Reprogramming and RAGE

    Molecular Studies of Neurodegenerative Diseases Lab; FELS Cancer Institute for Personalized Medicine (2022-05-06)
    Clinical studies indicate that patients infected with SARS-CoV-2 develop hyperinflammation, which correlates with increased mortality. The SARS-CoV-2/COVID-19-dependent inflammation is thought to occur via increased cytokine production and hyperactivity of RAGE in several cell types, a phenomenon observed for other disorders and diseases. Metabolic reprogramming has been shown to contribute to inflammation and is considered a hallmark of cancer, neurodegenerative diseases, and viral infections. Malfunctioning glycolysis, which normally aims to convert glucose into pyruvate, leads to the accumulation of advanced glycation end products (AGEs). Being aberrantly generated, AGEs then bind to their receptor, RAGE, and activate several pro-inflammatory genes, such as IL-1b and IL-6, thus, increasing hypoxia and inducing senescence. Using the lung epithelial cell (BEAS-2B) line, we demonstrated that SARS-CoV-2 proteins reprogram the cellular metabolism and increase pyruvate kinase muscle isoform 2 (PKM2). This deregulation promotes the accumulation of AGEs and senescence induction. We showed the ability of the PKM2 stabilizer, Tepp-46, to reverse the observed glycolysis changes/alterations and restore this essential metabolic process.
  • Emergency Medical Services Prehospital Response to the COVID-19 Pandemic in the US: A Brief Literature Review

    Ventura, Christian Angelo I.; Denton, Edward E.; David, Jessia Anastacia; Schoenfelder, Brianna; Mela, Lillian; Lumia, Rebecca P.; Rudi, Rachel B.; Haldar, Barnita; Schoenfelder|0000-0003-2258-074X (2022-05-30)
    This study aimed to analyze prehospital Emergency Medical Services (EMS) response to the COVID-19 pandemic in the US through a brief systematic review of available literature in context with international prehospital counterparts. An exploration of the NCBI repository was performed using a search string of relevant keywords which returned n=5128 results; articles that met the inclusion criteria (n=77) were reviewed and analyzed in accordance with PRISMA and PROSPERO recommendations. Methodical quality was assessed using critical appraisal tools, and the Egger’s test was used for risk of bias reduction upon linear regression analysis of a funnel plot. Sources of heterogeneity as defined by P < 0.10 or I^2 > 50% were interrogated. Findings were considered within ten domains: structural/systemic; clinical outcomes; clinical assessment; treatment; special populations; dispatch/activation; education; mental health; perspectives/experiences; and transport. Findings suggest, EMS clinicians have likely made significant and unmeasured contributions to care during the pandemic via nontraditional roles, ie, COVID-19 testing and vaccine deployment. EMS plays a critical role in counteracting the COVID-19 pandemic in addition to the worsening opioid epidemic, both of which disproportionately impact patients of color. As such, being uniquely influential on clinical outcomes, these providers may benefit from standardized education on care and access disparities such as racial identity. Access to distance learning continuing education opportunities may increase rates of provider recertification. Additionally, there is a high prevalence of vaccine hesitancy among surveyed nationally registered EMS providers. Continued rigorous investigation on the impact of COVID-19 on EMS systems and personnel is warranted to ensure informed preparation for future pandemic and infectious disease responses.
  • The COVID-19 Impact and Culture Nexus in Japan: Insights for the Global Community

    Pratt, Cornelius; Carr, Ronald Lee; Pratt|0000-0002-8033-9818 (2022-05-09)
    This opinion column identifies and reflects on the defining moments in Japan's sprint toward acquiring herd immunity by the end of 2021. As of this writing, COVID-19 conversations across the globe are becoming less and less concerning, as wealthy nations ramp up testing and triple-vaccinate their citizens, as COVID-19-related infection and hospitalization rates fall significantly, or, as is the case of the less developed countries of the Global South, concerted efforts are being made to have a sizable number of residents tested for COVID-19 and inoculated with their first shot. In developed economies, the pendulum of healthcare uneasiness is pivoting toward a simple issue—endemicity—as governments ease or phase out COVID-19 restrictions, as the disease is increasingly being viewed through the lens of, say, the seasonal flu, and as agitation against COVID-19 mandates leads to protests in countries such as the Netherlands, France and Canada. The world will get by, the argument goes, by coexisting with COVID-19 as it does with a host of other diseases, including the seasonal influenza, dengue, and malaria. But applying such a view now to the pandemic may be inadvisable, as Tedros Adhanom Ghebreyesus, director general of the World Health Organization, asserts: “We're concerned that a narrative has taken hold in some countries that because of vaccines, and because of Omicron's high transmissibility and lower severity, preventing transmission is no longer possible and no longer necessary. Nothing could be further from the truth. More transmission means more disease.” But the world need not have been so ravaged by the pandemic only if it had looked around to remind itself about commonsensical steps that could have been considered in response.
  • Experience with telemedicine among rheumatology clinicians during the COVID-19 pandemic: an international survey

    Chock, Eugenia Yupei; Putman, Michael; Conway, Richard; Danila, Maria I.; Hoyer, Bimba; Hsieh, Evelyn; Jayatilleke, Arundathi; Kilian, Adam; Leipe, Jan; Liew, Jean W.; Machado, Pedro M.; Robinson, Philip C.; Singh, Namrata; Ung, Natasha; Yeoh, Su-Ann; Wallace, Zachary S.; Grainger, Rebecca; Cappelli, Laura C.; Jayatilleke|0000-0003-0875-4280 (2022-05-12)
    Objective: The aim was to assess rheumatology clinicians’ perceptions of telemedicine and their experiences before and during the coronavirus disease 2019 (COVID-19) pandemic. Methods: We conducted a cross-sectional online survey and collected responses from rheumatology clinicians worldwide, between November 2020 and February 2021, regarding use and perceptions of telemedicine in rheumatology. We summarized data with descriptive statistics and qualitative analysis for free-text responses. Results: The survey was completed by 349 rheumatology clinicians from 49 countries; 59% were female and about two-thirds were in the 30–50 years age group. Academic affiliations were held by 55% of participants, and 44% were from North America. Before the pandemic, 24% of participants had experience with telemedicine, whereas about three-quarters used telemedicine for the first time during the pandemic. Overall, 56% thought they provided less adequate care with telemedicine. More than half of clinicians felt that telemedicine was adequate for evaluating crystalline arthritis, inflammatory arthritis and lupus flares. Telemedicine was felt to be inadequate for flares of myositis, vasculitis and scleroderma. Technical problems were reported in 29% of telemedicine encounters and were most commonly related to patient-encountered difficulties. Conclusion: Most rheumatology clinicians used telemedicine for the first time during the pandemic. The quality of care provided was thought to be inferior to that provided in person for specific clinical situations. Additional efforts are needed to address barriers to effective telemedicine, such as patient-related technology issues, challenges with building rapport and performing a physical examination, and to define the appropriate scope of clinical scenarios conducive to telemedicine.
  • Proton pump inhibitor therapy usage and associated hospitalization rates and critical care outcomes of COVID-19 patients

    Shupp, Brittney; Mehta, Sagar V.; Chirayath, Subin; Patel, Nishit; Aiad, Mina; Sapin, Jared; Stoltzfus, Jill; Schneider, Yecheskel (2022-05-09)
    Proton Pump Inhibitors (PPI) are one of the most prescribed medications in the United States. However, PPIs have been shown to increase the risk of enteric infections. Our study aims to evaluate the correlation between PPI and COVID-19 severity. We performed a retrospective cohort study on patients who tested positive for SARS-CoV-2 from March to August 2020. Patients were categorized based on PPI user status. Primary outcomes included need for hospital or ICU admission and 30-day mortality. Secondary outcomes looked to determine the severity of COVID-19 infection and effect of comorbid conditions. 2,594 patients were reviewed. The primary outcomes of our study found that neither active nor past PPI use was associated with increased hospital admission or 30-day mortality following completion of multivariate analysis. Additionally, there was no association between COVID-19 infection and the strength of PPI dosing (low, standard, high). However, the following covariates were independently and significantly associated with increased admission: age, male gender, diabetes, COPD, composite cardiovascular disease, kidney disease, and obesity. The following covariates were associated with increased mortality: age, male gender, COPD, and kidney disease. In conclusion, the high risk features and comorbidities of PPI users were found to have a stronger correlation to severe COVID-19 infection and poor outcomes as opposed to the use of PPI therapy.
  • The Use of Photovoice Methodology to Assess Health Needs and Identify Opportunities Among Migrant Transgender Women in the U.S.-Mexico Border

    Chavez-Baray, Silvia M.; Martinez, Omar; Chaparro, Perla; Moya, Eva M. (2022-05-19)
    Psychosocial, social and structural conditions have rarely been studied among transgender women in the U.S.-Mexico Border. This study used Photovoice methodology to empower migrant transgender women of color (TWC) to reflect on realities from their own perspectives and experiences and promote critical dialogue, knowledge, and community action. Sixteen participants documented their daily experiences through photography, engaged in photo-discussions to assess needs and identify opportunities, and developed a community-informed Call to Action. Four major themes emerged from the participants' photographs, discussions, and engagement: (1) mental health, (2) migration experiences and challenges, (3) stigma, discrimination, and resiliency, and (4) impact of the COVID-19 pandemic. Through active community engagement, a Call to Action was developed. A binational advisory committee of decision makers and scholars reviewed a set of recommendations to better respond to the needs of TWC in the U.S.-Mexico Border. Photovoice served as an empowerment tool for TWC to assess the myriad of syndemic conditions, including mental health, stigma, discrimination and COVID-19, affecting them daily and identify initiatives for change.
  • The SARS-CoV-2 spike protein binds and modulates estrogen receptors

    Solis, Oscar; Beccari, Andrea R.; Iaconis, Daniela; Talarico, Carmine; Ruiz-Bedoya, Camilo A.; Nwachukwu, Jerome C.; Cimini, Annamaria; Castelli, Vanessa; Bertini, Riccardo; Montopoli, Monica; Cocetta, Veronica; Borocci, Stefano; Prandi, Ingrid G.; Flavahan, Kelly; Bahr, Melissa; Napiorkowski, Anna; Chillemi, Giovanni; Ooka, Masato; Yang, Xiaoping; Zhang, Shiliang; Xia, Menghang; Zheng, Wei; Bonaventura, Jordi; Pomper, Jody E.; Morales, Marisela; Rosenberg, Avi Z.; Nettles, Kendall W.; Jain, Sanjay K.; Allegretti, Marcello; Michaelides, Michael; Cimini|0000-0002-2737-7970 (2022-05-23)
    The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein binds angiotensin-converting enzyme 2 (ACE2) at the cell surface, which constitutes the primary mechanism driving SARS-CoV-2 infection. Molecular interactions between the transduced S and endogenous proteins likely occur post-infection, but such interactions are not well understood. We used an unbiased primary screen to profile the binding of full-length S against >9,000 human proteins and found significant S-host protein interactions, including one between S and human estrogen receptor alpha (ERα). After confirming this interaction in a secondary assay, we used bioinformatics, supercomputing, and experimental assays to identify a highly conserved and functional nuclear receptor coregulator (NRC) LXD-like motif on the S2 subunit and an S-ERα binding mode. In cultured cells, S DNA transfection increased ERα cytoplasmic accumulation, and S treatment induced ER-dependent biological effects and ACE2 expression. Noninvasive multimodal PET/CT imaging in SARS-CoV-2-infected hamsters using [18F]fluoroestradiol (FES) localized lung pathology with increased ERα lung levels. Postmortem experiments in lung tissues from SARS-CoV-2-infected hamsters and humans confirmed an increase in cytoplasmic ERα expression and its colocalization with S protein in alveolar macrophages. These findings describe the discovery and characterization of a novel S-ERα interaction, imply a role for S as an NRC, and are poised to advance knowledge of SARS-CoV-2 biology, COVID-19 pathology, and mechanisms of sex differences in the pathology of infectious disease.
  • Characterization of raloxifene as a potential pharmacological agent against SARS-CoV-2 and its variants

    Sbarro Health Research Organization (Temple University) (2022-05-25)
    The new coronavirus SARS-CoV-2 is the causative agent of the COVID-19 pandemic, which so far has caused over 6 million deaths in 2 years, despite new vaccines and antiviral medications. Drug repurposing, an approach for the potential application of existing pharmaceutical products to new therapeutic indications, could be an effective strategy to obtain quick answers to medical emergencies. Following a virtual screening campaign on the most relevant viral proteins, we identified the drug raloxifene, a known Selective Estrogen Receptor Modulator (SERM), as a new potential agent to treat mild-to-moderate COVID-19 patients. In this paper we report a comprehensive pharmacological characterization of raloxifene in relevant in vitro models of COVID-19, specifically in Vero E6 and Calu-3 cell lines infected with SARS-CoV-2. A large panel of the most common SARS-CoV-2 variants isolated in Europe, United Kingdom, Brazil, South Africa and India was tested to demonstrate the drug’s ability in contrasting the viral cytopathic effect (CPE). Literature data support a beneficial effect by raloxifene against the viral infection due to its ability to interact with viral proteins and activate protective estrogen receptor-mediated mechanisms in the host cells. Mechanistic studies here reported confirm the significant affinity of raloxifene for the Spike protein, as predicted by in silico studies, and show that the drug treatment does not directly affect Spike/ACE2 interaction or viral internalization in infected cell lines. Interestingly, raloxifene can counteract Spike-mediated ADAM17 activation in human pulmonary cells, thus providing new insights on its mechanism of action. A clinical study in mild to moderate COVID-19 patients (NCT05172050) has been recently completed. Our contribution to evaluate raloxifene results on SARS-CoV-2 variants, and the interpretation of the mechanisms of action will be key elements to better understand the trial results, and to design new clinical studies aiming to evaluate the potential development of raloxifene in this indication.
  • A Multicenter Phase 2 Randomized Controlled Study on the Efficacy and Safety of Reparixin in the Treatment of Hospitalized Patients with COVID-19 Pneumonia

    Sbarro Health Research Organization (Temple University) (2022-05-26)
    Acute lung injury and acute respiratory distress syndrome are common complications in patients with coronavirus disease 2019 (COVID-19). Poor outcomes in patients with COVID-19 are associated with cytokine release syndrome. Binding of interleukin-8 (CXCL8/IL-8) to its chemokine receptors, CXCR1/2, may mediate this inflammatory process. The aim of this clinical trial was to determine if CXCR1/2 blockade with reparixin can improve clinical outcomes in hospitalized patients with severe COVID-19 pneumonia. The dose and safety of reparixin have been investigated in clinical trials of patients with metastatic breast cancer.
  • Modeling for the Stringency of Lock-Down Policies: Effects of Macroeconomic and Healthcare Variables in Response to the COVID-19 Pandemic

    Santini, Giunio; Fordellone, Mario; Boffo, Silvia; Signoriello, Simona; de Vito, Danila; Chiodini, Paolo; Boffo|0000-0002-6352-160X (2022-05-25)
    Background: The spread of COVID-19 has been characterized by unprecedented global lock-downs. Although, the extent of containment policies cannot be explained only through epidemic data. Previous studies already focused on the relationship between the economy and healthcare, focusing on the impact of diseases in countries with a precarious economic situation. However, the pandemic caused by SARS-CoV-2 drew most countries of the world into a precarious economic situation mostly caused by the global and local lock-downs policies. Methods: A discriminant analysis performed via partial least squares procedure was applied to evaluate the impact of economic and healthcare variables on the containment measures adopted by 39 countries. To collect the input variables (macroeconomic, healthcare, and medical services), we relied on official databases of international organizations, such as The World Bank and WHO. Results: The stringency lock-down policies could not only be influenced by the epidemical data, but also by previous features of the selected countries, such as economic and healthcare conditions. Conclusions: Indeed, economic and healthcare variables also contributed to shaping the implemented lock-down policies.
  • Comparison of BNT162b2-, mRNA-1273- and Ad26.COV2.S-Elicited IgG and Neutralizing Titers against SARS-CoV-2 and Its Variants

    Center for Substance Abuse Research (Temple University); Center for Metabolic Disease Research (Temple University) (2022-05-27)
    Because the vaccine-elicited antibody and neutralizing activity against spike protein of SARS-CoV-2 are associated with protection from COVID-19, it is important to determine the levels of specific IgG and neutralization titers against SARS-CoV-2 elicited by the vaccines. While three widely used vaccine brands (Pfizer-BNT162b2, Moderna-mRNA-1273 and Johnson-Ad26.COV2.S) are effective in preventing SARS-CoV-2 infection and alleviating COVID-19 illness, they have different efficacy against COVID-19. It is unclear whether the differences are due to varying ability of the vaccines to elicit a specific IgG antibody response and neutralization activity against spike protein of the virus. In this study, we compared the plasma IgG and neutralization titers against spike proteins of wild-type SARS-CoV-2 and eight variants in healthy subjects who received the mRNA-1273, BNT162b2 or Ad26.COV2.S vaccine. We demonstrated that subjects vaccinated with Ad26.COV2.S vaccine had significantly lower levels of IgG and neutralizing titers as compared to those who received the mRNA vaccines. While the linear regression analysis showed a positive correlation between IgG levels and neutralizing activities against SARS-CoV-2 WT and the variants, there was an overall reduction in neutralizing titers against the variants in subjects across the three groups. These findings suggest that people who received one dose of Ad26.COV2.S vaccine have a more limited IgG response and lower neutralization activity against SARS-CoV-2 WT and its variants than recipients of the mRNA vaccines. Thus, monitoring the plasma or serum levels of anti-SARS-CoV-2 spike IgG titer and neutralization activity is necessary for the selection of suitable vaccines, vaccine dosage and regimens.
  • Conserved recombination patterns across coronavirus subgenera

    Institute for Genomics and Evolutionary Medicine (Temple University) (2022-06-14)
    Recombination contributes to the genetic diversity found in coronaviruses and is known to be a prominent mechanism whereby they evolve. It is apparent, both from controlled experiments and in genome sequences sampled from nature, that patterns of recombination in coronaviruses are non-random and that this is likely attributable to a combination of sequence features that favour the occurrence of recombination break points at specific genomic sites, and selection disfavouring the survival of recombinants within which favourable intra-genome interactions have been disrupted. Here we leverage available whole-genome sequence data for six coronavirus subgenera to identify specific patterns of recombination that are conserved between multiple subgenera and then identify the likely factors that underlie these conserved patterns. Specifically, we confirm the non-randomness of recombination break points across all six tested coronavirus subgenera, locate conserved recombination hot- and cold-spots, and determine that the locations of transcriptional regulatory sequences are likely major determinants of conserved recombination break-point hotspot locations. We find that while the locations of recombination break points are not uniformly associated with degrees of nucleotide sequence conservation, they display significant tendencies in multiple coronavirus subgenera to occur in low guanine-cytosine content genome regions, in non-coding regions, at the edges of genes, and at sites within the Spike gene that are predicted to be minimally disruptive of Spike protein folding. While it is apparent that sequence features such as transcriptional regulatory sequences are likely major determinants of where the template-switching events that yield recombination break points most commonly occur, it is evident that selection against misfolded recombinant proteins also strongly impacts observable recombination break-point distributions in coronavirus genomes sampled from nature.
  • Virtual Community Engagement Studio (V-CES): Engaging Mothers With Mental Health and Substance Use Conditions in Research

    Zisman-Ilani, Yaara; Buell, Jennifer; Mazel, Shayna; Henning, Shannon; Nicholson, Joanne; Zisman-Ilani|0000-0001-6852-2583 (2022-06-15)
    Active engagement of community stakeholders is increasingly encouraged in behavioral health research, often described as a co-production approach. Community stakeholders (e.g., patients, providers, policy makers, advocates) play a leading role together with research investigators in conducting the various phases of research, including conceptualization, design, implementation, and the interpretation and dissemination of findings. The concept of co-production has promising benefits for both the target population and the research outcomes, such as producing person-centered interventions with greater acceptability and usability potential. However, it is often the case that neither researchers nor community members are trained or skilled in co-production methods. The field of behavioral health research lacks tools and methods to guide and promote the engagement of diverse stakeholders in the research process. The purpose of this methods paper is to describe the Virtual Community Engagement Studio (V-CES) as a new method for engaging vulnerable populations like mothers with mental health and substance use conditions in research. We piloted the method in collaboration with the Maternal Mental Health Research Collaborative (MMHRC), focusing on one of the most vulnerable, under-researched populations, mothers coping with mental health and/or substance abuse disorders. Our pilot included mothers and providers who work with them as Community Experts to inform all phases of research design and implementation, and the interpretation and application of findings. The aim of this article is to describe the V-CES as a powerful tool that supports the engagement of mothers with mental health and/or substance use disorders and other community stakeholders in research, to provide examples of its use, and to make recommendations for future use, based on lessons learned. The V-CES toolkit is available for use with this target population as well as others.

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