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

Recent Submissions

  • Distinctive Role of the Systemic Inflammatory Profile in Non-Small-Cell Lung Cancer Younger and Elderly Patients Treated with a PD-1 Immune Checkpoint Blockade: A Real-World Retrospective Multi-Institutional Analysis

    Center for Biotechnology, Sbarro Institute for Cancer Research and Molecular Medicine (Temple University) (2021-11-15)
    An immune checkpoint blockade with mAbs to PD-1 and PD-L1 is an expanding therapeutic option for mNSCLC patients. This treatment strategy is based on the use of mAbs able to restore the anti-tumor activity of intratumoral T cells inhibited by PD-1 binding to PD-L1/2 on tumor and inflammatory cells. It has been speculated that a chronic status of systemic inflammation as well as the immunosenescence physiologically occurring in elderly patients may affect the efficacy of the treatment and the occurrence of irAEs. We performed a multi-institutional retrospective study aimed at evaluating the effects of these mAbs (nivolumab or atezolizumab) in 117 mNSCLC patients younger (90 cases) and older (27 cases) than 75 years in correlation with multiple inflammatory parameters (NLR, CRP, ESR, LDH and PCT). No differences were observed when the cohorts were compared in terms of the frequency of PFS, OS, inflammatory markers and immune-related adverse events (irAEs). Similarly, the occurrence of irAEs was strictly correlated with a prolonged OS survival in both groups. On the contrary, a negative correlation between the high baseline levels of inflammatory markers and OS could be demonstrated in the younger cohort only. Overall, PD-1/PD-L1-blocking mAbs were equally effective in young and elderly mNSCLC patients; however, the detrimental influence of a systemic inflammation at the baseline was only observed in young patients, suggesting different aging-related inflammation immunoregulative effects.
  • Novel Knowledge-Based Transcriptomic Profiling of Lipid Lysophosphatidylinositol-Induced Endothelial Cell Activation

    Center for Cardiovascular Research (Temple University); Center for Microbiology and Immunology (Temple University); Alzheimer's Center (Temple University); Center for Inflammation and Lung Research (Temple University) (2021-11-29)
    To determine whether pro-inflammatory lipid lysophosphatidylinositols (LPIs) upregulate the expressions of membrane proteins for adhesion/signaling and secretory proteins in human aortic endothelial cell (HAEC) activation, we developed an EC biology knowledge-based transcriptomic formula to profile RNA-Seq data panoramically. We made the following primary findings: first, G protein-coupled receptor 55 (GPR55), the LPI receptor, is expressed in the endothelium of both human and mouse aortas, and is significantly upregulated in hyperlipidemia; second, LPIs upregulate 43 clusters of differentiation (CD) in HAECs, promoting EC activation, innate immune trans-differentiation, and immune/inflammatory responses; 72.1% of LPI-upregulated CDs are not induced in influenza virus-, MERS-CoV virus- and herpes virus-infected human endothelial cells, which hinted the specificity of LPIs in HAEC activation; third, LPIs upregulate six types of 640 secretomic genes (SGs), namely, 216 canonical SGs, 60 caspase-1-gasdermin D (GSDMD) SGs, 117 caspase-4/11-GSDMD SGs, 40 exosome SGs, 179 Human Protein Atlas (HPA)-cytokines, and 28 HPA-chemokines, which make HAECs a large secretory organ for inflammation/immune responses and other functions; fourth, LPIs activate transcriptomic remodeling by upregulating 172 transcription factors (TFs), namely, pro-inflammatory factors NR4A3, FOS, KLF3, and HIF1A; fifth, LPIs upregulate 152 nuclear DNA-encoded mitochondrial (mitoCarta) genes, which alter mitochondrial mechanisms and functions, such as mitochondrial organization, respiration, translation, and transport; sixth, LPIs activate reactive oxygen species (ROS) mechanism by upregulating 18 ROS regulators; finally, utilizing the Cytoscape software, we found that three mechanisms, namely, LPI-upregulated TFs, mitoCarta genes, and ROS regulators, are integrated to promote HAEC activation. Our results provide novel insights into aortic EC activation, formulate an EC biology knowledge-based transcriptomic profile strategy, and identify new targets for the development of therapeutics for cardiovascular diseases, inflammatory conditions, immune diseases, organ transplantation, aging, and cancers.
  • Hyperlipidemia May Synergize with Hypomethylation in Establishing Trained Immunity and Promoting Inflammation in NASH and NAFLD

    Center for Cardiovascular Research and Inflammation (Temple University); Center for Translational and Clinical Lung Research (Temple University) (2021-11-23)
    We performed a panoramic analysis on both human nonalcoholic steatohepatitis (NASH) microarray data and microarray/RNA-seq data from various mouse models of nonalcoholic fatty liver disease NASH/NAFLD with total 4249 genes examined and made the following findings: (i) human NASH and NAFLD mouse models upregulate both cytokines and chemokines; (ii) pathway analysis indicated that human NASH can be classified into metabolic and immune NASH; methionine- and choline-deficient (MCD)+high-fat diet (HFD), glycine N-methyltransferase deficient (GNMT-KO), methionine adenosyltransferase 1A deficient (MAT1A-KO), and HFCD (high-fat-cholesterol diet) can be classified into inflammatory, SAM accumulation, cholesterol/mevalonate, and LXR/RXR-fatty acid β-oxidation NAFLD, respectively; (iii) canonical and noncanonical inflammasomes play differential roles in the pathogenesis of NASH/NAFLD; (iv) trained immunity (TI) enzymes are significantly upregulated in NASH/NAFLD; HFCD upregulates TI enzymes more than cytokines, chemokines, and inflammasome regulators; (v) the MCD+HFD is a model with the upregulation of proinflammatory cytokines and canonical and noncanonical inflammasomes; however, the HFCD is a model with upregulation of TI enzymes and lipid peroxidation enzymes; and (vi) caspase-11 and caspase-1 act as upstream master regulators, which partially upregulate the expressions of cytokines, chemokines, canonical and noncanonical inflammasome pathway regulators, TI enzymes, and lipid peroxidation enzymes. Our findings provide novel insights on the synergies between hyperlipidemia and hypomethylation in establishing TI and promoting inflammation in NASH and NAFLD progression and novel targets for future therapeutic interventions for NASH and NAFLD, metabolic diseases, transplantation, and cancers.
  • Protection of Hamsters Challenged with SARS-CoV-2 Variants of Concern by Two Doses of MVC-COV1901 Vaccine Followed by a Single Dose of Beta Variant Version of MVC-COV1901

    Kuo, Tsun-Yung; Lien, Chia-En; Lin, Yi-Jiun; Lin, Meei-Yun; Wu, Chung-Chin; Tang, Wei-Hsuan; Campbell, John D.; Traquina, Paula; Chuang, Ya-Shan; Liu, Luke Tzu-Chi; Cheng, Jinyi; Chen, Charles (2022-01-06)
    The current fight against COVID-19 is compounded by the Variants of Concern (VoCs), which can diminish the effectiveness of vaccines and potentially increase viral transmission and severity of disease. MVC-COV1901 is a protein subunit vaccine based on the prefusion SARS-CoV-2 spike protein (S-2P) and is adjuvanted with CpG 1018 and aluminum hydroxide. In this study, we used the Delta variant to challenge hamsters inoculated with S-2P from the Wuhan wildtype and the Beta variant in two-dose or three-dose regimens. Two doses of wildtype S-2P followed by the third dose of Beta variant was shown to induce the highest neutralizing antibody titer against live SARS-CoV-2 of the wildtype and all current VoCs, as well as improved neutralization against Omicron variant pseudovirus compared to three doses of wildtype S-P. All regimens of vaccination were able to protect hamsters from SARS-CoV-2 Delta variant challenge and resulted in reduced lung live virus titer and pathology. Three doses of vaccination also significantly reduced lung viral RNA titer, regardless of whether the wildtype or Beta variant S-2P was used as the third dose. Based on the immunogenicity and viral challenge data, two doses of wildtype S-2P followed by the third dose of Beta variant S-2P induced potent antibody immune responses against the VoCs.
  • Obesity and Metabolic Dysregulation in Children Provide Protective Influenza Vaccine Responses

    Kainth, Mundeep K.; Fishbein, Joanna S.; Aydillo, Teresa; Escalera, Alba; Odusanya, Rachael; Grammatikopoulos, Kalliopi; Scotto, Tiffany; Sethna, Christine B.; Garcia-Sastre, Adolfo; Deutschman, Clifford S. (2022-01-11)
    The most effective intervention for influenza prevention is vaccination. However, there are conflicting data on influenza vaccine antibody responses in obese children. Cardio-metabolic parameters such as waist circumference, cholesterol, insulin sensitivity, and blood pressure are used to subdivide individuals with overweight or obese BMI into ‘healthy’ (MHOO) or ‘unhealthy’ (MUOO) metabolic phenotypes. The ever-evolving metabolic phenotypes in children may be elucidated by using vaccine stimulation to characterize cytokine responses. We conducted a prospective cohort study evaluating influenza vaccine responses in children. Participants were identified as either normal-weight children (NWC) or overweight/obese using BMI. Children with obesity were then characterized using metabolic health metrics. These metrics consisted of changes in serum cytokine and chemokine concentrations measured via multiplex assay at baseline and repeated at one month following vaccination. Changes in NWC, MHOO and MUOO were compared using Chi-square/Fisher’s exact test for antibody responses and Kruskal–Wallis test for cytokines. Differences in influenza antibody responses in normal, MHOO and MUOO children were statistically indistinguishable. IL-13 was decreased in MUOO children compared to NWC and MHOO children (p = 0.04). IL-10 approached a statistically significant decrease in MUOO compared to MHOO and NWC (p = 0.07). Influenza vaccination does not provoke different responses in NCW, MHOO, or MUOO children, suggesting that obesity, whether metabolically healthy or unhealthy, does not alter the efficacy of vaccination. IL-13 levels in MUO children were significantly different from levels in normal and MHOO children, indicating that the metabolically unhealthy phenotypes may be associated with an altered inflammatory response. A larger sample size with greater numbers of metabolically unhealthy children may lend more insight into the relationship of chronic inflammation secondary to obesity with vaccine immunity.
  • Providing Quality of Care in Fragile and Vulnerable Settings: Lessons from South Sudan

    Gianaris, Kevin; Atem, Jacob; Chen, Allison P.; Chang, Alexander; Russell, Anna; Hsu, Edbert B.; Chang|0000-0002-5104-2468 (2021-12-22)
    Background: In 2020, the World Health Organization (WHO) released a report concerning planning and actions to provide quality of care in fragile, conflict-affected, and vulnerable areas. South Sudan, the world’s newest country, has encountered both natural and man-made disasters in recent years that have posed marked challenges to delivery of care. The Southern Sudan Healthcare Organization (SSHCO) operates as a non-governmental organization (NGO) in this setting, delivering and improving healthcare through war, flooding, and infectious outbreaks. Objective: The goal of this paper is to highlight the challenges faced in providing care in South Sudan from an NGO perspective and apply the recent WHO guidelines on quality of care to optimize practical implementation. Method: Each of the WHO’s eight elements for quality of care in South Sudan were examined in relation to the experience of SSHCO from 2013–2021. Analysis included: 1. summary of the WHO element; 2. examples of successful implementation; 3. barriers to implementation; and 4. recommendations to improve implementation. Findings: The team found that communication and coordination were the most important aspects of improving quality of care in South Sudan. These should be prioritized and include intergovernmental partners, the local and national Ministry of Health (MOH), NGOs, and community stakeholders. Communication and coordination should foster community engagement, improved data collecting and reporting, and sharing of publicly accessible information. Better clinical staff training and governance are also required to ensure the most effective use of limited resources. Conclusion: South Sudan faces many barriers to quality of care with communication and coordination identified among the foremost issues. Practical application of the WHO elements of quality of care can assist NGOs in effectively identifying areas for improvement to deliver better quality essential health services.
  • Editorial: Molecular Mechanisms and Signaling in Endothelial Cell Biology and Vascular Heterogeneity

    Center for Cardiovascular Research (Temple University); Center for Metabolic Disease Research (Temple University) (2021-12-17)
  • Association of abnormal pulmonary vasculature on CT scan for COVID-19 infection with decreased diffusion capacity in follow up: A retrospective cohort study

    COVID-19 Research Group (Temple University) (2021-10-15)
    Background: Coronavirus Disease 2019 (COVID-19) is a respiratory viral illness causing pneumonia and systemic disease. Abnormalities in pulmonary function tests (PFT) after COVID-19 infection have been described. The determinants of these abnormalities are unclear. We hypothesized that inflammatory biomarkers and CT scan parameters at the time of infection would be associated with abnormal gas transfer at short term follow-up. Methods: We retrospectively studied subjects who were hospitalized for COVID-19 pneumonia and discharged. Serum inflammatory biomarkers, CT scan and clinical characteristics were assessed. CT images were evaluated by Functional Respiratory Imaging with automated tissue segmentation algorithms of the lungs and pulmonary vasculature. Volumes of the pulmonary vessels that were ≤5mm (BV5), 5-10mm (BV5_10), and ≥10mm (BV10) in cross sectional area were analyzed. Also the amount of opacification on CT (ground glass opacities). PFT were performed 2–3 months after discharge. The diffusion capacity of carbon monoxide (DLCO) was obtained. We divided subjects into those with a DLCO <80% predicted (Low DLCO) and those with a DLCO ≥80% predicted (Normal DLCO). Results: 38 subjects were included in our cohort. 31 out of 38 (81.6%) subjects had a DLCO<80% predicted. The groups were similar in terms of demographics, body mass index, comorbidities, and smoking status. Hemoglobin, inflammatory biomarkers, spirometry and lung volumes were similar between groups. CT opacification and BV5 were not different between groups, but both Low and Normal DLCO groups had lower BV5 measures compared to healthy controls. BV5_10 and BV10 measures were higher in the Low DLCO group compared to the normal DLCO group. Both BV5_10 and BV10 in the Low DLCO group were greater compared to healthy controls. BV5_10 was independently associated with DLCO<80% in multivariable logistic regression (OR 1.29, 95% CI 1.01, 1.64). BV10 negatively correlated with DLCO% predicted (r = -0.343, p = 0.035). Conclusions: Abnormalities in pulmonary vascular volumes at the time of hospitalization are independently associated with a low DLCO at follow-up. There was no relationship between inflammatory biomarkers during hospitalization and DLCO. Pulmonary vascular abnormalities during hospitalization for COVID-19 may serve as a biomarker for abnormal gas transfer after COVID-19 pneumonia.
  • The durability of immunity against reinfection by SARS-CoV-2: a comparative evolutionary study

    Institute for Genomics and Evolutionary Medicine (Temple University) (2021-10-01)
    Background: Among the most consequential unknowns of the devastating COVID-19 pandemic are the durability of immunity and time to likely reinfection. There are limited direct data on SARS-CoV-2 long-term immune responses and reinfection. The aim of this study is to use data on the durability of immunity among volutionarily close coronavirus relatives of SARS-CoV-2 to estimate times to reinfection by a comparative evolutionary analysis of related viruses SARS-CoV, MERS-CoV, human coronavirus (HCoV)-229E, HCoV-OC43, and HCoV-NL63. Methods: We conducted phylogenetic analyses of the S, M, and ORF1b genes to reconstruct a maximum-likelihood molecular phylogeny of human-infecting coronaviruses. This phylogeny enabled comparative analyses of peak-normalised nucleocapsid protein, spike protein, and whole-virus lysate IgG antibody optical density levels, in conjunction with reinfection data on endemic human-infecting coronaviruses. We performed ancestral and descendent states analyses to estimate the expected declines in antibody levels over time, the probabilities of reinfection based on antibody level, and the anticipated times to reinfection after recovery under conditions of endemic transmission for SARS-CoV-2, as well as the other human-infecting coronaviruses. Findings: We obtained antibody optical density data for six human-infecting coronaviruses, extending from 128 days to 28 years after infection between 1984 and 2020. These data provided a means to estimate profiles of the typical antibody decline and probabilities of reinfection over time under endemic conditions. Reinfection by SARS-CoV-2 under endemic conditions would likely occur between 3 months and 5·1 years after peak antibody response, with a median of 16 months. This protection is less than half the duration revealed for the endemic coronaviruses circulating among humans (5–95% quantiles 15 months to 10 years for HCoV-OC43, 31 months to 12 years for HCoV-NL63, and 16 months to 12 years for HCoV-229E). For SARS-CoV, the 5–95% quantiles were 4 months to 6 years, whereas the 95% quantiles for MERS-CoV were inconsistent by dataset. Interpretation: The timeframe for reinfection is fundamental to numerous aspects of public health decision making. As the COVID-19 pandemic continues, reinfection is likely to become increasingly common. Maintaining public health measures that curb transmission—including among individuals who were previously infected with SARS-CoV-2—coupled with persistent efforts to accelerate vaccination worldwide is critical to the prevention of COVID-19 morbidity and mortality.
  • Perspectives on Humanizing and Liberatory Qualitative Research with Racially/Ethnically Minoritized Youth

    Savage, Shawn S.; Johnson, Royel M.; Kenney, Alex J.; Haynes, DaVonti' D. (2021-10-01)
    The visible impacts of COVID-19 and racial injustice have resulted in renewed funding commitments and research within minoritized communities. However, this work is too often anchored in deficit and damage-centered research approaches and practices. In this brief, we call on the qualitative research community to reframe their perspectives and terminate harmful, pain-driven research. We underscore the importance of humanizing and liberatory approaches to research with youth who are racially/ethnically minoritized. Specifically, we contend that the emotional health and overall well-being of youth are impacted by the approaches employed by researchers and the experiences racially/ethnically minoritized youth have with research. Thus, we offer specific anti-oppressive strategies and recommendations for qualitative researchers to consider in their work with racial/ethnically minoritized youth and communities.
  • The impact of COVID-19 on people ageing with an intellectual disability in Ireland: Protocol for a follow-up survey

    McCarron, Mary; Allen, Andrew; McCausland, Darren; Haigh, Margaret; Luus, Retha; Rosmin Bavussantakath, Fathima; Sheerin, Fintan; Mulryan, Niamh; Burke, Eilish; McGlinchey, Eimear; Flannery, Fidelma; McCallion, Philip; McCallion|0000-0001-5129-6399 (2021-10-15)
    Background: The COVID-19 pandemic and associated lockdowns have had a dramatic impact on many people, but individuals with an intellectual disability, given the prevalence of congregate living and high levels of co-morbid conditions, may be particularly vulnerable at this time. A prior initial survey of participants of the Intellectual Disability Supplement to the Irish Longitudinal Study on Ageing (IDS-TILDA) found that, despite a majority of participants being tested, only a small proportion had tested positive for COVID-19. Furthermore, despite some reporting positive aspects to the lockdown, a similar proportion were experiencing stress or anxiety during the pandemic.The pandemic and lockdowns have continued, and it is possible that experiences and consequences have changed over time. Aim: To explore over time and in greater depth the impact of COVID-19 and associated lockdowns and to further establish rates of infection, rates of vaccination and participants’ experiences. Methods: A structured questionnaire for people with intellectual disability participating in the IDS-TILDA longitudinal study, to be administered by telephone/video in summer 2021. Where participants are unable to respond independently, a proxy respondent will be invited to either assist the participant or answer questions on their behalf. This questionnaire will include questions from the first COVID-19 questionnaire, with extra questions assessing “long COVID” (i.e. COVID-19 lasting for 12 weeks or longer), infection control behaviours, changes in mental health, social contacts and loneliness, frailty, healthcare, and incidence of vaccination. Impact: The results of this survey will be used to inform healthcare provision for people with intellectual disability during the latter stages of the lockdown and into the future.
  • Mechanism of a COVID-19 nanoparticle vaccine candidate that elicits a broadly neutralizing antibody response to SARS-CoV-2 variants

    Fels Institute for Cancer Research and Molecular Biology (Temple University) (2021-10-20)
    Vaccines that induce potent neutralizing antibody (NAb) responses against emerging variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are essential for combating the coronavirus disease 2019 (COVID-19) pandemic. We demonstrated that mouse plasma induced by self-assembling protein nanoparticles (SApNPs) that present 20 rationally designed S2GΔHR2 spikes of the ancestral Wuhan-Hu-1 strain can neutralize the B.1.1.7, B.1.351, P.1, and B.1.617 variants with comparable potency. The adjuvant effect on vaccine-induced immunity was investigated by testing 16 formulations for the multilayered I3-01v9 SApNP. Using single-cell sorting, monoclonal antibodies (mAbs) with diverse neutralization breadth and potency were isolated from mice immunized with the receptor binding domain (RBD), S2GΔHR2 spike, and SApNP vaccines. The mechanism of vaccine-induced immunity was examined in the mouse model. Compared with the soluble spike, the I3-01v9 SApNP showed sixfold longer retention, fourfold greater presentation on follicular dendritic cell dendrites, and fivefold stronger germinal center reactions in lymph node follicles.
  • Investigating the Relationships Between Public Health Literacy and Public Trust in Physicians in China's Control of COVID-19: A Cross-Sectional Study

    Chen, Dongjin; Zhou, Qian; Pratt, Cornelius B.; Su, Zhenhua; Gu, Zheng (2021-10-28)
    Objective: Public trust in physicians and public health literacy (HL) are important factors that ensure the effectiveness of health-care delivery, particularly that provided during the SARS-CoV-2 pandemic. This study investigates HL as a predictor of public trust in physicians in China's ongoing efforts to control COVID-19. Methods: Data were gathered in February 2020 during the peak of the disease in China. Based on Nutbeam's conceptualization of HL, we measure HL vis-à-vis COVID-19 by using a six-item scale that includes two items each for functional, interactive, and critical HL. Trust in physicians was measured by assessing physicians' capability to diagnose COVID-19. A rank-sum test and ordinal logit regression modeling were used to analyze the data. Results: Two key findings: (a) trust in physician handling of treatment for COVID-19 is reported by about 74% of respondents; and (b) five of the six HL measures are positive predictors of public trust in physician treatment of the disease, with functional HL1 having the highest level of such association (coefficient 0.285, odds ratio 1.33%, p < 0.01). Conclusions: Improving public HL is important for better public-physician relationships, as well as for nations' efforts to contain the pandemic, serving as a possible behavioral, non-clinical antidote to COVID-19. Being confronted with the unprecedented virus, humans need trust. Health education and risk communication can improve public compliance with physicians' requirements and build a solid foundation for collective responses.
  • Characterization of raloxifene as potential pharmacological agent against SARS-CoV-2 and its variants

    Sbarro Health Research Organization (Temple University) (2021-10-24)
    The new coronavirus that emerged, called SARS-CoV-2, is the causative agent of the COVID-19 pandemic. The identification of potential drug candidates that can rapidly enter clinical trials for the prevention and treatment of COVID-19 is an urgent need, despite the recent introduction of several new vaccines for the prevention and protection of this infectious disease, which in many cases becomes severe. Drug repurposing (DR), a process for studying existing pharmaceutical products for new therapeutic indications, represents one of the most effective potential strategies employed to increase the success rate in the development of new drug therapies. We identified raloxifene, a known Selective Estrogen Receptor Modulator (SERM), as a potential pharmacological agent for the treatment of COVID-19 patients. Following a virtual screening campaign on the most relevant viral protein targets, in this work we report the results of the first pharmacological characterization of raloxifene in relevant cellular models of COVID-19 infection. The results obtained on all the most common viral variants originating in Europe, United Kingdom, Brazil, South Africa and India, currently in circulation, are also reported, confirming the efficacy of raloxifene and, consequently, the relevance of the proposed approach. Taken together, all the information gathered supports the clinical development of raloxifene and confirms that the drug can be proposed as a viable new option to fight the pandemic in at least some patient populations. The results obtained so far have paved the way for a first clinical study to test the safety and efficacy of raloxifene, just concluded in patients with mild to moderate COVID-19.
  • Strategies to evaluate outcomes in long-COVID-19 and post-COVID survivors

    Center for Biotechnology, Sbarro Institute for Cancer Research and Molecular Medicine (Temple University) (2021-10-30)
    SARS-CoV-2 infection can impact the physical, cognitive, mental health of patients, especially in those recovered in intensive care units. Moreover, it was proved that the effects of the virus may persist for weeks or months. The term long-COVID or post-COVID syndrome is commonly used for indicating a variety of physical and psychological symptoms that continue after the resolution of the acute phase. This narrative review is aimed at providing an updated overview of the impact of physical, cognitive, and psychological health disorders in COVID-19 survivors, by summarizing the data already published in literature in the last year. Studies cited were found through PubMed searches. We also presented an overview of the post-COVID-19 health consequences on three important aspects: nutritional status, neurological disorders, and physical health. Moreover, to activate a correct health planning policy, a multidisciplinary approach for addressing the post- COVID-19 issue, has been proposed. Finally, the involvement of health professionals is necessary even after the pandemic, to reduce expected post-pandemic psychosocial responses and mental health disorders.
  • Characteristics and growth of the genetic HIV transmission network of Mexico City during 2020

    Institute for Genomics and Evolutionary Medicine (Temple University) (2021-11-11)
    Introduction: Molecular surveillance systems could provide public health benefits to focus strategies to improve the HIV care continuum. Here, we infer the HIV genetic network of Mexico City in 2020, and identify actively growing clusters that could represent relevant targets for intervention. Methods: All new diagnoses, referrals from other institutions, as well as persons returning to care, enrolling at the largest HIV clinic in Mexico City were invited to participate in the study. The network was inferred from HIV pol sequences, using pairwise genetic distance methods, with a locally hosted, secure version of the HIV-TRACE tool: Seguro HIV-TRACE. Socio-demographic, clinical and behavioural metadata were overlaid across the network to design focused prevention interventions. Results: A total of 3168 HIV sequences from unique individuals were included. One thousand and one-hundred and fifty (36%) sequences formed 1361 links within 386 transmission clusters in the network. Cluster size varied from 2 to 14 (63% were dyads). After adjustment for covariates, lower age (adjusted odds ratio [aOR]: 0.37, p<0.001; >34 vs. <24 years), being a man who has sex with men (MSM) (aOR: 2.47, p = 0.004; MSM vs. cisgender women), having higher viral load (aOR: 1.28, p<0.001) and higher CD4+ T cell count (aOR: 1.80, p<0.001; ≥500 vs. <200 cells/mm3) remained associated with higher odds of clustering. Compared to MSM, cisgender women and heterosexual men had significantly lower education (none or any elementary: 59.1% and 54.2% vs. 16.6%, p<0.001) and socio-economic status (low income: 36.4% and 29.0% vs. 18.6%, p = 0.03) than MSM. We identified 10 (2.6%) clusters with constant growth, for prioritized intervention, that included intersecting sexual risk groups, highly connected nodes and bridge nodes between possible sub-clusters with high growth potential. Conclusions: HIV transmission in Mexico City is strongly driven by young MSM with higher education level and recent infection. Nevertheless, leveraging network inference, we identified actively growing clusters that could be prioritized for focused intervention with demographic and risk characteristics that do not necessarily reflect the ones observed in the overall clustering population. Further studies evaluating different models to predict growing clusters are warranted. Focused interventions will have to consider structural and risk disparities between the MSM and the heterosexual populations.
  • Exploring factors associated with pregnant women’s experiences of material hardship during COVID-19: a cross-sectional Qualtrics survey in the United States

    Johnson, Laura; Johnson|0000-0002-1882-8186 (2021-11-08)
    Background: The COVID-19 pandemic has exacerbated the financial insecurity of women and their families globally. Some studies have explored the impact of financial strain among pregnant women, in particular, during the pandemic. However, less is known about the factors associated with pregnant women’s experiences of material hardship. Methods: This cross-sectional study used a non-probability sample to examine the factors associated with pregnant women’s experiences of material hardship during the COVID-19 pandemic. In January 2021, 183 pregnant women living in the United States participated in an online Qualtrics panel survey. In addition to socio-demographic characteristics, individuals were asked about their finances and predictors of financial well-being, mental health symptoms, and intimate partner violence (IPV) experiences. Chi-square analysis and one-way ANOVA were used to examine whether women’s experiences with material hardship and associated factors differed by income level (i.e., less than $20,000; $20,000 to $60,000; more than $60,000). Ordinary least squares regression was used to calculate unadjusted and adjusted estimates. Results: Study findings showed that the majority of women in the sample experienced at least one form of material hardship in the past year. Individuals with an annual household income less than $20,000 reported the highest average number of material hardships experienced (M = 3.7, SD = 2.8). Compared to women with household incomes less than $20,000, women with incomes of more than $60,000 reported significantly fewer material hardships, less financial strain, and higher levels of financial support, economic self-efficacy, and economic-self-sufficiency. Women with incomes of $60,000 or more also reported significantly lower levels of psychological abuse, and a smaller percentage met the cut-off for anxiety. Economic self-sufficiency, financial strain, posttraumatic stress disorder, and economic abuse were all significantly associated with material hardship. Conclusions: A contribution of this study is that it highlights the significant, positive association between economic abuse, a unique form of IPV, and material hardship among pregnant women during the pandemic. These findings suggest the need for policy and practice interventions that help to ameliorate the financial insecurity experienced by some pregnant women, as well as respond to associated bidirectional vulnerabilities (e.g., mental health symptoms, experiences of IPV).
  • 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) (2021-11-17)
    A recent study reported the occurrence of Canine Coronavirus (CCoV) in nasopharyngeal swabs from a small number of patients hospitalized with pneumonia during a 2017-18 period in Sarawak, Malaysia. Because the genome sequence for one of these isolates is available, we conducted comparative evolutionary analyses of the spike gene of this strain (CCoV-HuPn-2018), with other available Alphacoronavirus 1 spike sequences. The most N-terminus subdomain (0-domain) of the CCoV-HuPn-2018 spike protein has sequence similarity to Transmissible Gastroenteritis Virus (TGEV) and CCoV2b strains, but not to other members of the type II Alphacoronaviruses (i.e., CCoV2a and Feline CoV2-FCoV2). This 0-domain in CCoV-HuPn-2018 has evidence for relaxed selection pressure, an increased rate of molecular evolution, and a number of unique amino acid substitutions relative to CCoV2b and TGEV sequences. A region of the 0-domain determined to be key to sialic acid binding and pathogenesis in TGEV had clear differences in amino acid sequences in CCoV-HuPn-2018 relative to both CCoV2b (enteric) and TGEV (enteric and respiratory). The 0-domain of CCoV-HuPn-2018 also had several sites inferred to be under positive diversifying selection, including sites within the signal peptide. Downstream of the 0-domain, FCoV2 shared sequence similarity to the CCoV2b and TGEV sequences, with analyses of this larger alignment identifying positively selected sites in the putative Receptor Binding Domain (RBD) and Connector Domain (CD). Recombination analyses strongly implicated a particular FCoV2 strain in the recombinant history of CCoV-HuPn-2018 with molecular divergence times estimated at around 60 years ago. We hypothesize that CCoV-HuPn-2018 had an enteric origin, but that it has lost that particular tropism, because of mutations in the sialic acid binding region of the spike 0-domain. As selection pressure on this region was reduced, the virus evolved a respiratory tropism, analogous to other Alphacoronavirus 1, such as Porcine Respiratory Coronavirus (PRCV), that have lost this region entirely. We also suggest that signals of positive selection in the signal peptide as well as other changes in the 0-domain of CCoV-HuPn-2018 could represent an adaptive role in this new host and that this could be in part due to the different spatial distribution of the N-linked glycan repertoire for this strain.
  • Sextus chest radiograph severity score correlates to clinical outcomes in patients with COVID-19: A cross-sectional study

    Sun, Justin; Yu, Daohai; Yoo, Kevin; Choi, Robert; Lu, Xiaoning; Standiford, Taylor; Cohen, Gary; Marchetti, Nathaniel; Agosto, Omar; Kumaran, Maruti; Maresky, Hillel; Sun|0000-0002-1879-1598 (2021-11-12)
    The value of chest radiography (CXR) in detection and as an outcome predictor in the management of patients with coronavirus disease-2019 (COVID-19) has not yet been fully understood. To validate a standardized CXR scoring system and assess its prognostic value in hospitalized patients found to have COVID-19 by imaging criteria and to compare it to computed tomography (CT). In this cross-sectional chart review study, patients aged 18-years or older who underwent chest CT at a single institution with an imaging-based diagnosis of COVID-19 between March 15, 2020 to April 15, 2020 were included. Each patient's CXR and coronal CT were analyzed for opacities in a 6-zonal assessment method and aggregated into a “Sextus score.” Inter-reader variability and correlation between CXR and coronal CT images were investigated to validate this scoring system. Univariable and multiple logistic regression techniques were used to investigate relationships between CXR scores and clinical parameters in relation to patient outcomes. One hundred twenty-four patients (median [interquartile range] age 58.5 [47.5–69.0] years, 72 [58%] men, 58 [47%] Blacks, and 35 [28%] Hispanics) were included. The CXR Sextus score (range: 0–6) was reliable (inter-rater kappa = 0.76; 95% confidence interval [CI]: 0.69–0.83) and correlated strongly with the CT Sextus score (Spearman correlation coefficient = 0.75, P < .0001). Incremental increases of CXR Sextus scores of 2 points were found to be an independent predictor of intubation (adjusted odds ratio [95% CI]: 4.49 [1.98, 10.20], P = .0003) and prolonged hospitalization (≥10 days) (adjusted odds ratio [95% CI]: 4.06 [1.98, 8.32], P = .0001). The CXR Sextus score was found to be reproducible and CXR-CT severity scores were closely correlated. Increasing Sextus scores were associated with increased risks for intubation and prolonged hospitalization for patients with COVID-19 in a predominantly Black population. The CXR Sextus score may provide insight into identifying and monitoring high-risk patients with COVID-19.
  • SARS-CoV-2 antibody prevalence in Sierra Leone, March 2021: a cross-sectional, nationally representative, age-stratified serosurvey

    Barrie, Mohamed Bailor; Lakoh, Sulaiman; Kelly, J. Daniel; Sam Kanu, Joseph; Squire, James Sylvester; Koroma, Zikan; Bah, Silleh; Sankoh, Osman; Brima, Abdulai; Ansumana, Rashid; Goldberg, Sarah A.; Chitre, Smit; Osuagwu, Chidinma; Frankfurter, Raphael; Maeda, Justin; Barekye, Bernard; Numbere, Tamuno-Wari; Abdulaziz, Mohammed; Mounts, Anthony; Blanton, Curtis; Singh, Tushar; Samai, Mohamed; Vandi, Mohamed; Richardson, Eugene T. (2021-11-11)
    Introduction: As of 26 March 2021, the Africa Centres for Disease Control and Prevention had reported 4 159 055 cases of COVID-19 and 111 357 deaths among the 55 African Union member states; however, no country has published a nationally representative serosurvey as of October 2021. Such data are vital for understanding the pandemic’s progression on the continent, evaluating containment measures, and policy planning. Methods: We conducted a cross-sectional, nationally representative, age-stratified serosurvey in Sierra Leone in March 2021 by randomly selecting 120 Enumeration Areas throughout the country and 10 randomly selected households in each of these. One to two persons per selected household were interviewed to collect information on sociodemographics, symptoms suggestive of COVID-19, exposure history to laboratory-confirmed COVID-19 cases, and history of COVID-19 illness. Capillary blood was collected by fingerstick, and blood samples were tested using the Hangzhou Biotest Biotech RightSign COVID-19 IgG/IgM Rapid Test Cassette. Total seroprevalence was estimated after applying sampling weights. Results: The overall weighted seroprevalence was 2.6% (95% CI 1.9% to 3.4%). This was 43 times higher than the reported number of cases. Rural seropositivity was 1.8% (95% CI 1.0% to 2.5%), and urban seropositivity was 4.2% (95% CI 2.6% to 5.7%). Discussion: Overall seroprevalence was low compared with countries in Europe and the Americas (suggesting relatively successful containment in Sierra Leone). This has ramifications for the country’s third wave (which started in June 2021), during which the average number of daily reported cases was 87 by the end of the month:this could potentially be on the order of 3700 actual infections per day, calling for stronger containment measures in a country with only 0.2% of people fully vaccinated. It may also reflect significant under-reporting of incidence and mortality across the continent.

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