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

Recent Submissions

  • Religiosity and COVID-19: Impact on Use of Remote Worship and Changes in Self-Reported Social Support

    Mosavel, Maghboeba; Hoadley, Ariel; Akinkugbe, Aderonke A.; Garcia, Dina T.; Bauerle Bass, Sarah; Hoadley|0000-0003-1360-0358 (2022-08-11)
    This study examines associations between changes in the use of remote worship services and changes in the types of social support among religious adults during the COVID-19 pandemic. Materials and Methods: Cross-sectional, web survey data (n = 461; 15 May to 6 July 2020) were collected during the COVID-19 pandemic. Multinomial logistic regression models calculated unadjusted odds of increases and decreases of three types of perceived social support from before to during COVID-19 based on remote worship use. Results: Adults who initiated use of remote worship had lower odds of gaining social support for personal problems (OR: 0.38; 95% CI: 0.19, 0.79) and greater odds of reporting less ease of getting practical help from neighbors (OR: 1.77; 95% CI: 1.04, 3.02) compared to adults who never used or stopped using remote worship. Adults who continued using remote worship services were more likely to report less ease of getting practical help from their neighbors (OR: 2.23; 95% CI: 1.17, 4.25) and decreased interest and concern felt from other people (OR: 2.62; 95% CI: 1.24, 5.51) than adults who never used or stopped using remote worship. Conclusions: Adults who initiated and continued using remote worship during the COVID-19 pandemic had poorer perceived social support outcomes relative to adults who never used or stopped using remote services. Despite continued engagement with their religious communities, adults participating in worship remotely may have had residual personal, emotional, and instrumental social support needs that remote worship did not mitigate.
  • The post-scarcity world and the post-pandemic office

    Mehra, Salil K. (2022-08-16)
    We are not yet in the post-scarcity world that John Maynard Keynes famously envisioned, and vaccines have only recently allowed us to hope that a post-COVID-19 future may arrive soon. However, it is not too early to consider the impact of both on the traditional office, and on attempts to bring it back for reasons that may be socially harmful. One lesson of the pandemic is that many workers can be as—or even more—productive working from home, thanks chiefly to software such as Zoom, Microsoft Teams, and Slack, among others, which enable better collaboration across distances than was previously possible. At the turn of the century, we moved toward an economy in which important products were increasingly characterized by low marginal costs of production, such as pharmaceuticals and software. Over the past decade, we have seen fixed costs reduced in some situations—consider how Uber greatly eliminates the need for a central taxi dispatcher, and makes use of idle capital invested in personal vehicles. The traditional office represents a massive fixed cost for many industries; tech-driven work-from-home greatly reduces the need for this fixed cost. While software, Internet connectivity and the cloud are not free, preliminary estimates suggest that replacing traditional offices with work-from-home greatly lowers costs, creates economic efficiencies and, relatedly, reduces environmental harm. That said, the story of work-from-home is not one of unbridled optimism. Real estate firms and local governments are already trying to use law as a tool to return workers to the pre-pandemic traditional office. Various levels of government seek to return workers to physical offices, often motivated by declines in tax receipts. Attempts to bolster a return to the traditional office may raise fixed costs for firms and generate substantial avoidable environmental damage. This Chapter recommends competition advocacy to counterbalance state and local attempts to prevent the efficient disruption of the traditional office's fixed costs. Work-from-home represents an important step toward the post-scarcity world; but without a focus on what amounts to state-and-local protectionism in this sphere, we could wind up taking another step backwards.
  • Characteristics and Outcomes of People With Gout Hospitalized Due to COVID-19: Data From the COVID-19 Global Rheumatology Alliance Physician-Reported Registry

    Jatuworapruk, Kanon; Montgomery, Anna; Gianfrancesco, Milena; Conway, Richard; Durcan, Laura; Graef, Elizabeth R.; Jayatilleke, Arundathi; Keen, Helen; Kilian, Adam; Young, Kristen; Carmona, Loreto; Cogo, Adriana Karina; Duarte-Garcia, Ali; Gossec, Laure; Hasseli, Rebecca; Hyrich, Kimme L.; Langlois, Vincent; Sigurdardottir, Valgerdur; Sparks, Jeffrey A.; Strangfeld, Anja; Xavier, Ricardo M.; Bhana, Suleman; Gore-Massy, Monique; Hausmann, Jonathan S.; Liew, Jean W.; Sirotich, Emily; Sufka, Paul; Wallace, Zach; Machado, Pedro M.; Yazdany, Jinoos; Grainger, Rebecca; Robinson, Philip C.; Jayatilleke|0000-0003-0875-4280 (2022-08-24)
    Objective: To describe people with gout who were diagnosed with coronavirus disease 2019 (COVID-19) and hospitalized and to characterize their outcomes. Methods: Data on patients with gout hospitalized for COVID-19 between March 12, 2020, and October 25, 2021, were extracted from the COVID-19 Global Rheumatology Alliance registry. Descriptive statistics were used to describe the demographics, comorbidities, medication exposures, and COVID-19 outcomes including oxygenation or ventilation support and death. Results: One hundred sixty-three patients with gout who developed COVID-19 and were hospitalized were included. The mean age was 63 years, and 85% were male. The majority of the group lived in the Western Pacific Region (35%) and North America (18%). Nearly half (46%) had two or more comorbidities, with hypertension (56%), cardiovascular disease (28%), diabetes mellitus (26%), chronic kidney disease (25%), and obesity (23%) being the most common. Glucocorticoids and colchicine were used pre-COVID-19 in 11% and 12% of the cohort, respectively. Over two thirds (68%) of the cohort required supplemental oxygen or ventilatory support during hospitalization. COVID-19-related death was reported in 16% of the overall cohort, with 73% of deaths documented in people with two or more comorbidities. Conclusion: This cohort of people with gout and COVID-19 who were hospitalized had high frequencies of ventilatory support and death. This suggests that patients with gout who were hospitalized for COVID-19 may be at risk of poor outcomes, perhaps related to known risk factors for poor outcomes, such as age and presence of comorbidity.
  • Regulatory reliance pathways during health emergencies: enabling timely authorizations for COVID-19 vaccines in Latin America

    can der Zee, Ivar T.; Vreman, Rick A.; Liberti, Lawrence; Alanis Garza, Mario; Liberti|0000-0003-3815-1165 (2022-08-18)
    Objectives. To map the timing and nature of regulatory reliance pathways used to authorize COVID-19 vaccines in Latin America. Methods. An observational study was conducted assessing the characteristics of all COVID-19 vaccine authorizations in Latin America. For every authorization it was determined whether reliance was used in the authorization process. Subgroups of reference national regulatory authorities (NRAs) and non-reference NRAs were compared. Results. 56 authorizations of 10 different COVID-19 vaccines were identified in 18 countries, of which 25 (44.6%) used reliance and 12 (21.4%) did not. For the remaining 19 (33.0%) it was not possible to determine whether reliance was used. Reference agencies used reliance less often (40% of authorizations with a known pathway) compared to non-reference agencies (100%). The median review time was just 15 days and does not meaningfully differ between reliance and non-reliance authorizations. Conclusions. This study demonstrated that for these vaccines, despite reliance pathways being associated with numerous rapid authorizations, independent authorization review times were not considerably longer than reliance reviews; reliance pathways were not a prerequisite for rapid authorization. Nevertheless, reliance pathways provided rapid authorizations in response to the COVID-19 emergency.
  • A Phase I, Prospective, Randomized, Open-labeled Study to Evaluate the Safety, Tolerability, and Immunogenicity of Booster Dose with MVC-COV1901 or MVC-COV1901(Beta) SARS-CoV-2 Vaccine in Adults

    Lien, Chia-En; Liu, Ming-Che; Wang, Ning-Chi; Liu, Luke Tzu-Chi; Wu, Chung-Chin; Tang, Wei-Hsuan; Lian, Wei-Cheng; Huang, Kuan-Ying A.; Chen, Charles; Chen|0000-0001-6888-009X (2022-08-31)
    Background: The use of variant-based severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine as a booster is being evaluated to overcome reduced neutralisation of variants induced by the original SARS-CoV-2 vaccine and waning protection over time. Methods: This is a phase one, prospective, randomized, and open-labeled trial to study the safety and immunogenicity of a booster dose consisting of a subunit vaccine based on the stabilized prefusion SARS-CoV-2 spike protein, MVC-COV1901 or its Beta version, MVC-COV1901-Beta. One-hundred and seven participants aged ≥18 and <55 years, who received two or three prior doses of MVC-COV1901 vaccines, were enrolled and were to receive a booster dose of either 15 mcg of MVC-COV1901, 15 mcg or 25 mcg of MVC-COV1901-Beta in 1:1:1 ratio. The primary endpoints were the incidences of adverse events and immunogenicity of the booster dose from Visit 2 (the day of the booster) to Visit 5 (four weeks after the booster). Cellular immunity was also investigated with memory B cell (MBC) and T cell assays. Findings: Adverse reactions after either MVC-COV1901 or MVC-COV1901-Beta booster doses after two or three doses of MVC-COV1901 were comparable and mostly mild and transient. At four weeks after the booster dose, participants with two prior doses of MVC-COV1901 exhibited numerically higher levels of neutralising antibodies against SARS-CoV-2 or Beta variant than participants with three prior doses of MVC-COV1901 regardless of the type of booster used. However, compared to 15 mcg of MVC-COV1901, 25 mcg of MVC-COV1901-Beta significantly improved neutralising antibody titre against Beta variant and BA.4/BA.5 Omicron variant pseudoviruses. The booster dose also significantly increased the proportion of spike-specific MBCs, including those of Beta and Omicron variants. Interpretation: MVC-COV1901-Beta can be effectively used as a booster dose against SARS-CoV-2, including the circulating BA.4/BA.5 Omicron variant.
  • Factors associated with severe COVID-19 in people with idiopathic inflammatory myopathy: results from the COVID-19 Global Rheumatology Alliance physician-reported registry

    Yeoh, Su-Ann; Gianfrancesco, Milena; Lawson-Tovey, Saskia; Hyrich, Kimme L.; Strangfeld, Anja; Gossec, Laure; Carmona, Loreto; Mateus, Elsa F.; Schafer, Martin; Richez, Christophe; Hachulla, Eric; Holmqvist, Marie; Scire, Carlo Alberto; Lorenz, Hanns-Martin; Voll, Reinhard E.; Hasseli, Rebecca; Jayatilleke, Arundathi; Hsu, Tiffany Y-T.; D'Silva, Kristin M.; Pimentel-Quiroz, Victor R.; Vasquez del Mercado, Monica; Katsuyuki Shinjo, Samuel; Torres dos Reis Neto, Edgard; Ferreira da Rocha Junior, Laurindo; de Oliveira e Silva Montana, Ana Carolina; Pons-Estel, Guillermo J.; Ornella, Sofia; D'Angelo Exeni, Maria Eugenia; Velozo, Edson; Jordan, Paula; Sirotich, Emily; Hausmann, Jonathan S.; Liew, Jean W.; Jacobsohn, Lindsay; Gore-Massy, Monique; Sufka, Paul; Grainger, Rebecca; Bhana, Suleman; Wallace, Zachary; Robinson, Philip C.; Yazdany, Jinoos; Machado, Pedro M.; Jayatilleke|0000-0003-0875-4280 (2022-09-13)
    Objectives: To investigate factors associated with severe COVID-19 in people with idiopathic inflammatory myopathy (IIM). Methods: Demographic data, clinical characteristics and COVID-19 outcome severity of adults with IIM were obtained from the COVID-19 Global Rheumatology Alliance physician-reported registry. A 3-point ordinal COVID-19 severity scale was defined: (1) no hospitalisation, (2) hospitalisation (and no death) and (3) death. ORs were estimated using multivariable ordinal logistic regression. Sensitivity analyses were performed using a 4-point ordinal scale: (1) no hospitalisation, (2) hospitalisation with no oxygen (and no death), (3) hospitalisation with oxygen/ventilation (and no death) and 4) death. Results: Of 348 patients, 48% were not hospitalised, 39% were hospitalised (and did not die) and 13% died. Older age (OR=1.59/decade, 95% CI 1.31 to 1.91), high disease activity (OR=3.50, 95% CI 1.25 to 9.83; vs remission), ≥2 comorbidities (OR=2.63, 95% CI 1.39 to 4.98; vs none), prednisolone-equivalent dose >7.5 mg/day (OR=2.40, 95% CI 1.09 to 5.28; vs no intake) and exposure to rituximab (OR=2.71, 95% CI 1.28 to 5.72; vs conventional synthetic disease-modifying antirheumatic drugs only) were independently associated with severe COVID-19. In addition to these variables, in the sensitivity analyses, male sex (OR range: 1.65–1.83; vs female) was also significantly associated with severe outcomes, while COVID-19 diagnosis after 1 October 2020 (OR range: 0.51–0.59; vs on/before 15 June 2020) was significantly associated with less severe outcomes, but these associations were not significant in the main model (OR=1.57, 95% CI 0.95 to 2.59; and OR=0.61, 95% CI 0.37 to 1.00; respectively). Conclusions: This is the first large registry data on outcomes of COVID-19 in people with IIM. Older age, male sex, higher comorbidity burden, high disease activity, prednisolone-equivalent dose >7.5 mg/day and rituximab exposure were associated with severe COVID-19. These findings will enable risk stratification and inform management decisions for patients with IIM.
  • Structurally Modified Bioactive Peptide Inhibits SARS-CoV-2 Lentiviral Particles Expression

    Institute for Computational Molecular Science (Temple University) (2022-09-26)
    Coronavirus disease 2019 (COVID-19), the current global pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Various pharmaceuticals are being developed to counter the spread of the virus. The strategy of repurposing known drugs and bioactive molecules is a rational approach. A previously described molecule, Ile-Arg-Trp (IRW), is a bioactive tripeptide that exhibits an ability to boost angiotensin converting enzyme-2 (ACE2) expression in animals and cells. Given the importance of SARS-CoV-2 S receptor binding domain (RBD)-ACE2 interaction in SARS-CoV-2 pathophysiology, we synthesized various IRW analogs intending to mitigate the RBD-ACE-2 interaction. Herein, we describe two analogs of IRW, A9 (Acetyl-Ile-Arg-Trp-Amide) and A14 (Formyl-Ile-Arg-Trp-Amide) which lowered the SARS-CoV-2 S RBD-ACE2 (at 50 µM) in vitro. The free energy of binding suggested that A9 and A14 interacted with the SARS-CoV-2 S RBD more favorably than ACE2. The calculated MMGBSA ΔG of spike binding for A9 was −57.22 kcal/mol, while that of A14 was −52.44 kcal/mol. A14 also inhibited furin enzymatic activity at various tested concentrations (25, 50, and 100 µM). We confirmed the effect of the two potent analogs using SARS-CoV-2 spike protein overexpressing cells. Both peptides lowered the protein expression of SARS-CoV-2 spike protein at the tested concentration (50 µM). Similarly, both peptides, A9 and A14 (50 µM), also inhibited pseudotyped lentiviral particles with SARS-CoV-2 Spike in ACE2 overexpressing cells. Further, the molecular dynamics (MD) calculations showed the interaction of A9 and A14 with multiple residues in spike S1 RBD. In conclusion, novel peptide analogs of ACE2 boosting IRW were prepared and confirmed through in vitro, cellular, and computational evaluations to be potential seed candidates for SARS-CoV-2 host cell binding inhibition.
  • Cardiac implantable device interrogation in left ventricular systolic dysfunction reveals physiologic abnormalities prior to symptom onset in COVID-19: a case series

    Delfiner, Matthew; Bocchese, Matthew; Dalsania, Raj; Alhassani, Zaineb; Keihl, Joshua; Vaidya, Anjali; Brisco-Bacik, Meredith A.; Whitman, Isaac; Delfiner|0000-0002-0967-1017; Whitman|0000-0002-2329-7690 (2022-10-03)
    Background: COVID-19 has affected individuals across the globe, and those with cardiac implantable electronic devices (CIEDs) likely represent a high-risk group. These devices can be interrogated to reveal information about the patient activity, heart rate parameters, and respiratory rate. Case summary: Four patients with CIEDs and left ventricular dysfunction were admitted to a single institution for COVID-19 infection. Each patient survived hospitalization, and none required intensive care. Retrospectively, CIED interrogation revealed each patient had decreased activity level prior to their reporting COVID-19 symptoms. Similarly, respiratory rate increased before symptom onset for three of the patients, while one did not have these data available. Of the three patients with heart rate variability (HRV) available, two had decreased HRV before they developed symptoms. After hospital discharge, these parameters returned to their baseline. Discussion: This case series suggests physiologic changes identifiable through interrogation of CIEDs may occur prior to the reported onset of COVID-19 symptoms. These data may provide objective evidence on which to base more sensitive assessments of infectious risk when performing contact tracing in communities.
  • Nephrology Trainee Education Needs Assessment: Five Years and a Pandemic Later

    Ko, Benjamin S.; Pivert, Kurtis A.; Rope, Rob; Burgner, Anna M.; Waitzman, Joshua S.; Halbach, Susan M.; Boyle, Suzanne; Chan, Lili; Sozio, Stephen M.; Boyle|0000-0003-4722-6149 (2022-10-28)
  • Fluvoxamine for Outpatient Treatment of COVID-19: A Decentralized, Placebo-controlled, Randomized, Platform Clinical Trial

    Accelerating COVID-19 Therapeutic Interventions and Vaccines - 6 Study Group (2022-11-01)
    Background: The effectiveness of fluvoxamine to shorten symptom duration or prevent hospitalization among outpatients in the US with mild to moderate symptomatic coronavirus disease 2019 (COVID-19) is unclear. Design: ACTIV-6 is an ongoing, decentralized, double-blind, randomized, placebo-controlled platform trial testing repurposed medications in outpatients with mild to moderate COVID-19. A total of 1288 non-hospitalized adults aged ≥30 years with confirmed COVID-19 experiencing ≥2 symptoms of acute infection for ≤7 days prior to randomization were randomized to receive fluvoxamine 50 mg or placebo twice daily for 10 days. The primary outcome was time to sustained recovery, defined as the third of 3 consecutive days without symptoms. Secondary outcomes included composites of hospitalization or death with or without urgent or emergency care visit by day 28. Results: Of 1331 participants randomized (mean [SD] age, 48.5 [12.8] years; 57% women; 67% reported receiving at least 2 doses of a SARS-CoV-2 vaccine), 1288 completed the trial (n=614 placebo, n=674 fluvoxamine). Median time to recovery was 13 days (IQR 12–13) in the placebo group and 12 days (IQR 11–14) in the fluvoxamine group (hazard ratio [HR] 0.96, 95% credible interval [CrI] 0.86–1.07; posterior probability for benefit [HR>1]=0.22). Twenty-six participants (3.9%) in the fluvoxamine group were hospitalized or had urgent or emergency care visits compared with 23 (3.8%) in the placebo group (HR 1.1, 95% CrI 0.6–1.8; posterior probability for benefit [HR<1]=0.340). One participant in the fluvoxamine group and 2 in the placebo group were hospitalized; no deaths occurred. Adverse events were uncommon in both groups. Conclusions: Treatment with fluvoxamine 50 mg twice daily for 10 days did not improve time to recovery, compared with placebo, among outpatients with mild to moderate COVID-19. These findings do not support the use of fluvoxamine at this dose and duration in patients with mild to moderate COVID-19.
  • Racial and Ethnic Disparities in Outpatient Treatment of COVID-19 ― United States, January–July 2022

    Boehmer, Tegan K.; Koumans, Emily H.; Skillen, Elizabeth L.; Kappelman, Michael D.; Carton, Thomas W.; Patel, Aditiben; August, Euna M.; Bernstein, Ryan; Denson, Joshua L.; Draper, Christine; Gundlapalli, Adi V.; Paranjape, Anuradha; Puro, Jon; Rao, Preetika; Siegel, David A.; Trick, William E.; Walker, Chastity L.; Block, Jason P.; Paranjape|0000-0003-3151-9932 (2022-10-28)
  • Neuro–Immune Interactions in Severe COVID-19 Infection

    Sbarro Institute for Cancer Research and Molecular Medicine (Temple University); Center for Biotechnology (Temple University) (2022-11-29)
    SARS-CoV-2 is a new coronavirus that has affected the world since 2019. Interstitial pneumonia is the most common clinical presentation, but additional symptoms have been reported, including neurological manifestations. Severe forms of infection, especially in elderly patients, present as an excessive inflammatory response called “cytokine storm”, which can lead to acute respiratory distress syndrome (ARDS), multiorgan failure and death. Little is known about the relationship between symptoms and clinical outcomes or the characteristics of virus–host interactions. The aim of this narrative review is to highlight possible links between neurological involvement and respiratory damage mediated by pathological inflammatory pathways in SARS-CoV-2 infection. We will focus on neuro–immune interactions and age-related immunity decline and discuss some pathological mechanisms that contribute to negative outcomes in COVID-19 patients. Furthermore, we will describe available therapeutic strategies and their effects on COVID-19 neurological symptoms.
  • RASCL: Rapid Assessment of Selection in CLades through molecular sequence analysis

    Institute for Genomics and Evolutionary Medicine (Temple University) (2022-11-02)
    An important unmet need revealed by the COVID-19 pandemic is the near-real-time identification of potentially fitness-altering mutations within rapidly growing SARS-CoV-2 lineages. Although powerful molecular sequence analysis methods are available to detect and characterize patterns of natural selection within modestly sized gene-sequence datasets, the computational complexity of these methods and their sensitivity to sequencing errors render them effectively inapplicable in large-scale genomic surveillance contexts. Motivated by the need to analyze new lineage evolution in near-real time using large numbers of genomes, we developed the Rapid Assessment of Selection within CLades (RASCL) pipeline. RASCL applies state of the art phylogenetic comparative methods to evaluate selective processes acting at individual codon sites and across whole genes. RASCL is scalable and produces automatically updated regular lineage-specific selection analysis reports: even for lineages that include tens or hundreds of thousands of sampled genome sequences. Key to this performance is (i) generation of automatically subsampled high quality datasets of gene/ORF sequences drawn from a selected “query” viral lineage; (ii) contextualization of these query sequences in codon alignments that include high-quality “background” sequences representative of global SARS-CoV-2 diversity; and (iii) the extensive parallelization of a suite of computationally intensive selection analysis tests. Within hours of being deployed to analyze a novel rapidly growing lineage of interest, RASCL will begin yielding JavaScript Object Notation (JSON)-formatted reports that can be either imported into third-party analysis software or explored in standard web-browsers using the premade RASCL interactive data visualization dashboard. By enabling the rapid detection of genome sites evolving under different selective regimes, RASCL is well-suited for near-real-time monitoring of the population-level selective processes that will likely underlie the emergence of future variants of concern in measurably evolving pathogens with extensive genomic surveillance.
  • Prolonged mask wearing does not alter the oral microbiome, salivary flow rate or gingival health status – A pilot study

    Oral Microbiome Research Laboratory (Temple University) (2022-11-10)
    The COVID-19 pandemic has resulted in the widespread use of N95 respirators and surgical masks, with anecdotal reports among healthcare providers and the public of xerostomia, halitosis, and gingivitis, a consortium of symptoms colloquially termed “mask mouth”. However, this has not been scientifically verified. The aim of this study was to assess changes in salivary flow rate, gingival health status and oral microbiome associated with prolonged mask use. A total of 25 dental students (mean age = 26.36 ± 1.58) were included in the study and evaluated at three time points: T1, at the end of at least 2 months of full-day mask wear (7.26 ± 1.56 hours/day); T2, at the end of a period of minimal mask use (1.13 ± 1.13 hours/day); and T3, at the end of 2-3 weeks of resuming full-day mask wear (6.93 ± 1.80 hours/day). Unstimulated whole saliva (UWS) flow rate, xerostomia (on a quantitative scale of 10), gingival index (GI) and plaque index (PI) were assessed at each time point. The salivary microbiome was characterized using 16S rRNA gene sequencing. Overall, UWS flow rates were normal (mean of 0.679 ml/min) and xerostomia, PI and GI scores were low (Mean of 3.11, 0.33 and 0.69, respectively) with no significant differences as a result of prolonged mask wearing. Similarly, there were no significant microbial changes at a false discovery rate (FDR) ≤ 0.05. However, some trends were identified using a nominal p-value cut-off of ≤ 0.01, namely Gemella sanguinis, Streptococcus sp. Oral taxon 066 and Oral taxon 058 were associated with prolonged mask wear. Trends were also seen by gender, race and age, for example an increase in P. gingivalis and P. intermedia with age. In conclusion, we found no evidence that prolonged mask wear adversely affects oral health. The findings support that the oral microbiome of healthy individuals is resilient.
  • 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.
  • 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; Chen|0000-0001-6888-009X (2022-11-02)
    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.
  • 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.

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