Rice Coronavirus Research

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Works related to coronaviruses that are authored by members of the Rice community.

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A predictive model of the temperature-dependent inactivation of coronaviruses
(AIP, 2020) Yap, Te Faye; Liu, Zhen; Shveda, Rachel A.; Preston, Daniel J.
The COVID-19 pandemic has stressed healthcare systems and supply lines, forcing medical doctors to risk infection by decontaminating and reusing single-use personal protective equipment. The uncertain future of the pandemic is compounded by limited data on the ability of the responsible virus, SARS-CoV-2, to survive across various climates, preventing epidemiologists from accurately modeling its spread. However, a detailed thermodynamic analysis of experimental data on the inactivation of SARS-CoV-2 and related coronaviruses can enable a fundamental understanding of their thermal degradation that will help model the COVID-19 pandemic and mitigate future outbreaks. This work introduces a thermodynamic model that synthesizes existing data into an analytical framework built on first principles, including the rate law for a first-order reaction and the Arrhenius equation, to accurately predict the temperature-dependent inactivation of coronaviruses. The model provides much-needed thermal decontamination guidelines for personal protective equipment, including masks. For example, at 70 °C, a 3-log (99.9%) reduction in virus concentration can be achieved, on average, in 3 min (under the same conditions, a more conservative decontamination time of 39 min represents the upper limit of a 95% interval) and can be performed in most home ovens without reducing the efficacy of typical N95 masks as shown in recent experimental reports. This model will also allow for epidemiologists to incorporate the lifetime of SARS-CoV-2 as a continuous function of environmental temperature into models forecasting the spread of the pandemic across different climates and seasons.
A rapid, low-cost, and highly sensitive SARS-CoV-2 diagnostic based on whole-genome sequencing
(Public Library of Science, 2023) Adastra, Per A.; Durand, Neva C.; Mitra, Namita; Pulido, Saul Godinez; Mahajan, Ragini; Blackburn, Alyssa; Colaric, Zane L.; Theisen, Joshua W. M.; Weisz, David; Dudchenko, Olga; Gnirke, Andreas; Rao, Suhas S. P.; Kaur, Parwinder; Aiden, Erez Lieberman; Aiden, Aviva Presser; Center for Theoretical Biological Physics
Early detection of SARS-CoV-2 infection is key to managing the current global pandemic, as evidence shows the virus is most contagious on or before symptom onset. Here, we introduce a low-cost, high-throughput method for diagnosing and studying SARS-CoV-2 infection. Dubbed Pathogen-Oriented Low-Cost Assembly & Re-Sequencing (POLAR), this method amplifies the entirety of the SARS-CoV-2 genome. This contrasts with typical RT-PCR-based diagnostic tests, which amplify only a few loci. To achieve this goal, we combine a SARS-CoV-2 enrichment method developed by the ARTIC Network (https://artic.network/) with short-read DNA sequencing and de novo genome assembly. Using this method, we can reliably (>95% accuracy) detect SARS-CoV-2 at a concentration of 84 genome equivalents per milliliter (GE/mL). The vast majority of diagnostic methods meeting our analytical criteria that are currently authorized for use by the United States Food and Drug Administration with the Coronavirus Disease 2019 (COVID-19) Emergency Use Authorization require higher concentrations of the virus to achieve this degree of sensitivity and specificity. In addition, we can reliably assemble the SARS-CoV-2 genome in the sample, often with no gaps and perfect accuracy given sufficient viral load. The genotypic data in these genome assemblies enable the more effective analysis of disease spread than is possible with an ordinary binary diagnostic. These data can also help identify vaccine and drug targets. Finally, we show that the diagnoses obtained using POLAR of positive and negative clinical nasal mid-turbinate swab samples 100% match those obtained in a clinical diagnostic lab using the Center for Disease Control’s 2019-Novel Coronavirus test. Using POLAR, a single person can manually process 192 samples over an 8-hour experiment at the cost of ~$36 per patient (as of December 7th, 2022), enabling a 24-hour turnaround with sequencing and data analysis time. We anticipate that further testing and refinement will allow greater sensitivity using this approach.
A Recombinant Protein XBB.1.5 RBD/Alum/CpG Vaccine Elicits High Neutralizing Antibody Titers against Omicron Subvariants of SARS-CoV-2
(2023) Thimmiraju, Syamala Rani; Adhikari, Rakesh; Villar, Maria Jose; Lee, Jungsoon; Liu, Zhuyun; Kundu, Rakhi; Chen, Yi-Lin; Sharma, Suman; Ghei, Karm; Keegan, Brian; Versteeg, Leroy; Gillespie, Portia M.; Ciciriello, Allan; Islam, Nelufa Y.; Poveda, Cristina; Uzcategui, Nestor; Chen, Wen-Hsiang; Kimata, Jason T.; Zhan, Bin; Strych, Ulrich; Bottazzi, Maria Elena; Hotez, Peter J.; Pollet, Jeroen
(1) Background: We previously reported the development of a recombinant protein SARS-CoV-2 vaccine, consisting of the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein, adjuvanted with aluminum hydroxide (alum) and CpG oligonucleotides. In mice and non-human primates, our wild-type (WT) RBD vaccine induced high neutralizing antibody titers against the WT isolate of the virus, and, with partners in India and Indonesia, it was later developed into two closely resembling human vaccines, Corbevax and Indovac. Here, we describe the development and characterization of a next-generation vaccine adapted to the recently emerging XBB variants of SARS-CoV-2. (2) Methods: We conducted preclinical studies in mice using a novel yeast-produced SARS-CoV-2 XBB.1.5 RBD subunit vaccine candidate formulated with alum and CpG. We examined the neutralization profile of sera obtained from mice vaccinated twice intramuscularly at a 21-day interval with the XBB.1.5-based RBD vaccine, against WT, Beta, Delta, BA.4, BQ.1.1, BA.2.75.2, XBB.1.16, XBB.1.5, and EG.5.1 SARS-CoV-2 pseudoviruses. (3) Results: The XBB.1.5 RBD/CpG/alum vaccine elicited a robust antibody response in mice. Furthermore, the serum from vaccinated mice demonstrated potent neutralization against the XBB.1.5 pseudovirus as well as several other Omicron pseudoviruses. However, regardless of the high antibody cross-reactivity with ELISA, the anti-XBB.1.5 RBD antigen serum showed low neutralizing titers against the WT and Delta virus variants. (4) Conclusions: Whereas we observed modest cross-neutralization against Omicron subvariants with the sera from mice vaccinated with the WT RBD/CpG/Alum vaccine or with the BA.4/5-based vaccine, the sera raised against the XBB.1.5 RBD showed robust cross-neutralization. These findings underscore the imminent opportunity for an updated vaccine formulation utilizing the XBB.1.5 RBD antigen.
A trivalent protein-based pan-Betacoronavirus vaccine elicits cross-neutralizing antibodies against a panel of coronavirus pseudoviruses
(Springer Nature, 2024) Thimmiraju, Syamala Rani; Adhikari, Rakesh; Redd, JeAnna R.; Villar, Maria Jose; Lee, Jungsoon; Liu, Zhuyun; Chen, Yi-Lin; Sharma, Suman; Kaur, Amandeep; Uzcategui, Nestor L.; Ronca, Shannon E.; Chen, Wen-Hsiang; Kimata, Jason T.; Zhan, Bin; Strych, Ulrich; Bottazzi, Maria Elena; Hotez, Peter J.; Pollet, Jeroen
The development of broad-spectrum coronavirus vaccines is essential to prepare for future respiratory virus pandemics. We demonstrated broad neutralization by a trivalent subunit vaccine, formulating the receptor-binding domains of SARS-CoV, MERS-CoV, and SARS-CoV-2 XBB.1.5 with Alum and CpG55.2. Vaccinated mice produced cross-neutralizing antibodies against all three human Betacoronaviruses and others currently exclusive to bats, indicating the epitope preservation of the individual antigens during co-formulation and the potential for epitope broadening.
Advancing methods for wastewater disease surveillance of antibiotic resistance and SARS-CoV-2
(2022-09-19) Lou, Esther; Stadler, Lauren B.
Wastewater-based epidemiology (WBE), which involves using biological indicators in sewage to provide information on the overall health of a community, is a powerful tool to monitor public health. WBE offers several advantages that make it complementary to conventional clinical surveillance: it is rapid and resource-efficient, enables broad monitoring of large populations, is able to detect symptomatic and asymptomatic infections, and is not biased by health seeking behavior or access to healthcare resources. Recent studies have shown that WBE is a powerful tool for estimating community-level prevalence of COVID-19 by measuring levels of SARS-CoV-2 RNA in wastewater, and for predicting the prevalence of clinical antibiotic resistance by screening wastewater for antibiotic resistance genes. Furthermore, WBE has enabled global collaboration through national (e.g., National Wastewater Surveillance System (NWSS) on COVID-19) and international (e.g., the Enhanced Gonococcal Antimicrobial Surveillance Program) programs to advance the integration of WBE into public health response. Despite the surge of interest in applying WBE, there are currently no standardized methods for wastewater disease monitoring, including how and when to collect samples, what methods to use for analysis, and how to interpret the data to inform action. Without a more complete understanding of the methodological challenges involved in characterizing target indicators in wastewater samples, our ability to leverage WBE for routine monitoring and international collaboration is limited. This dissertation aims to evaluate the strengths and weaknesses of several current methods used for wastewater monitoring of antimicrobial resistance (AMR) and SARS-CoV-2 and discuss implications of method selection for future WBE work. The research focuses on four objectives, corresponding to the four chapters presented in this dissertation: (1) characterize the impact of wastewater sampling designs (i.e., grab and composite sampling) on the ARG removal rates achieved by a wastewater treatment plant (WWTP), (2) elucidate the fate of different forms of cell-associated and cell-free ARGs in an emerging wastewater treatment process, (3) compare two targeted methods (i.e., RT-ddPCR and targeted amplicon sequencing) for monitoring SARS-CoV-2 mutations in wastewater, and (4) evaluate short- and long-read metagenomics and a targeted method (epicPCR) for tracking ARG host range across a WWTP. Sampling design is critical to the collection of representative samples for WBE and for estimating removal rates of genes across wastewater treatment processes. We compared grab and composite sampling in terms of their effects on removal rates for a suite of genes, including several clinically-relevant ARGs (blaNDM-1, blaOXA-1, MCR-1, MCR-5, MCR-10, and qnrA). We find that the diurnal variation of ARG loading in the WWTP influent and effluent created significantly different instantaneous ARG removal rates among all grab samples collected throughout a day, indicating grab sampling can introduce bias to ARG removal calculations. Overall, using composite samples are more representative for WBE and for assessing removal of ARGs across wastewater treatment processes as compared to grab sampling which may overestimate ARG removal rates. The form of the ARG, specifically whether it is cell-free or cell-associated, is critical to understanding ARG removal across wastewater treatment processes. We found that the fraction of cell-associated ARGs decreased whereas the fraction of cell-free ARGs increased in the treated effluent as the influent organic loading rate was gradually increased. The results indicate that the ARGs in treated effluent can transit between cell-associated and cell-free DNA in response to changing operational conditions, which should be considered to better evaluate the total ARGs in the wastewater treatment system. WBE has been widely applied to track SARS-CoV-2 infections in communities and in some cases to identify circulating variants of concern. There are several different methods that have been applied to screen for variants of concern in wastewater. We compared targeted methods for screening for SARS-CoV-2 variants of concern in wastewater samples. The results demonstrated that RT-ddPCR is more sensitive and should be applied for mutation quantification or variant confirmation in wastewater, whereas detection via targeted amplicon sequencing was influenced by the depth of sequencing, viral load, and mutation concentration. These findings caution the use of quantitative measurements of SARS-CoV-2 variants in wastewater samples determined solely based on targeted amplicon sequencing. We compared targeted and untargeted methods for ARG detection in wastewater. The results demonstrate that despite its significantly lower sequencing depth, long-read sequencing outperforms short-read sequencing with higher sensitivity for detecting ARGs, especially for ARGs associated with mobile genetic elements (MGEs). In addition, long-read sequencing consistently revealed a wider range of ARG hosts compared to short-read sequencing. Nonetheless, the host range detected by long-read sequencing represented only a subset of the host range detected by a targeted method, epicPCR (Emulsion, Paired Isolation, and Concatenation PCR). Taken together, the results have implications for future WBE, particularly in terms of method selection: 1) collect composite samples rather than grab samples to acquire a representative view of the monitoring targets in a population; 2) include different forms of DNA (cell-associated and cell-free) to analyze ARGs because effluent ARGs are present in both forms and can transition between these forms in response to environmental conditions; 3) apply RT-ddPCR for quantitative analysis and early variant detection if targets are known; and 4) use long-read sequencing for routine wastewater AMR surveillance and use epicPCR to obtain a high-resolution host range of clinically relevant ARGs. The findings provided by this research contribute to establishing a scientific consensus on method selection for WBE, thus advancing it as a routine tool for public health surveillance.
Aging and Burnout for Nurses in an Acute Care Setting: The First Wave of COVID-19
(MDPI, 2023) Beier, Margaret E.; Cockerham, Mona; Branson, Sandy; Boss, Lisa
We examined the relationship between age, coping, and burnout during the peak of the COVID-19 pandemic with nurses in Texas (N = 376). Nurses were recruited through a professional association and snowball sampling methodology for the cross-sectional survey study. Framed in lifespan development theories, we expected that nurse age and experience would be positively correlated with positive coping strategies (e.g., getting emotional support from others) and negatively correlated with negative coping strategies (e.g., drinking and drug use). We also expected age to be negatively related to the emotional exhaustion and depersonalization facets of burnout and positively related to the personal accomplishment facet of burnout. Findings were largely supported in that age was positively associated with positive coping and personal accomplishment and age and experience were negatively correlated with negative coping and depersonalization. Age was not, however, associated with emotional exhaustion. Mediation models further suggest that coping explains some of the effect of age on burnout. A theoretical extension of lifespan development models into an extreme environment and practical implications for coping in these environments are discussed.
Alpha 1 Antitrypsin is an Inhibitor of the SARS-CoV-2–Priming Protease TMPRSS2
(Case Western Reserve University, 2021) Azouz, Nurit P.; Klingler, Andrea M.; Callahan, Victoria; Akhrymuk, Ivan V.; Elez, Katarina; Raich, Lluís; Henry, Brandon M.; Benoit, Justin L.; Benoit, Stefanie W.; Noé, Frank; Kehn-Hall, Kylene; Rothenberg, Marc E.
Background: Host proteases have been suggested to be crucial for dissemination of MERS, SARS-CoV, and SARS-CoV-2 coronaviruses, but the relative contribution of membrane versus intracellular proteases remains controversial. Transmembrane serine protease 2 (TMPRSS2) is regarded as one of the main proteases implicated in the coronavirus S protein priming, an important step for binding of the S protein to the angiotensin-converting enzyme 2 (ACE2) receptor before cell entry. Methods: We developed a cell-based assay to identify TMPRSS2 inhibitors. Inhibitory activity was established in SARS-CoV-2 viral load systems. Results: We identified the human extracellular serine protease inhibitor (serpin) alpha 1 anti-trypsin (A1AT) as a novel TMPRSS2 inhibitor. Structural modeling revealed that A1AT docked to an extracellular domain of TMPRSS2 in a conformation that is suitable for catalysis, resembling similar serine protease inhibitor complexes. Inhibitory activity of A1AT was established in a SARS-CoV-2 viral load system. Notably, plasma A1AT levels were associated with COVID-19 disease severity. Conclusions: Our data support the key role of extracellular serine proteases in SARS CoV-2 infections and indicate that treatment with serpins, particularly the FDA-approved drug A1AT, may be effective in limiting SARS-CoV-2 dissemination by affecting the surface of the host cells.
Already vulnerable neighborhoods are hardest hit by COVID-19 job losses
(Kinder Institute for Urban Research, 2020)
An interactive dashboard created by the Kinder Institute’s Houston Community Data Connections shows job-loss estimates in each Harris County community. The numbers can be further broken down by industry and neighborhood. Many of the areas impacted most by the economic downturn are home to low-income renters, the working poor and single-parent households.
Analysis of bronchoalveolar lavage fluid metatranscriptomes among patients with COVID-19 disease
(Springer Nature, 2022) Jochum, Michael; Lee, Michael D.; Curry, Kristen; Zaksas, Victoria; Vitalis, Elizabeth; Treangen, Todd; Aagaard, Kjersti; Ternus, Krista L.
To better understand the potential relationship between COVID-19 disease and hologenome microbial community dynamics and functional profiles, we conducted a multivariate taxonomic and functional microbiome comparison of publicly available human bronchoalveolar lavage fluid (BALF) metatranscriptome samples amongst COVID-19 (n = 32), community acquired pneumonia (CAP) (n = 25), and uninfected samples (n = 29). We then performed a stratified analysis based on mortality amongst the COVID-19 cohort with known outcomes of deceased (n = 10) versus survived (n = 15). Our overarching hypothesis was that there are detectable and functionally significant relationships between BALF microbial metatranscriptomes and the severity of COVID-19 disease onset and progression. We observed 34 functionally discriminant gene ontology (GO) terms in COVID-19 disease compared to the CAP and uninfected cohorts, and 21 GO terms functionally discriminant to COVID-19 mortality (q < 0.05). GO terms enriched in the COVID-19 disease cohort included hydrolase activity, and significant GO terms under the parental terms of biological regulation, viral process, and interspecies interaction between organisms. Notable GO terms associated with COVID-19 mortality included nucleobase-containing compound biosynthetic process, organonitrogen compound catabolic process, pyrimidine-containing compound biosynthetic process, and DNA recombination, RNA binding, magnesium and zinc ion binding, oxidoreductase activity, and endopeptidase activity. A Dirichlet multinomial mixtures clustering analysis resulted in a best model fit using three distinct clusters that were significantly associated with COVID-19 disease and mortality. We additionally observed discriminant taxonomic differences associated with COVID-19 disease and mortality in the genus Sphingomonas, belonging to the Sphingomonadacae family, Variovorax, belonging to the Comamonadaceae family, and in the class Bacteroidia, belonging to the order Bacteroidales. To our knowledge, this is the first study to evaluate significant differences in taxonomic and functional signatures between BALF metatranscriptomes from COVID-19, CAP, and uninfected cohorts, as well as associating these taxa and microbial gene functions with COVID-19 mortality. Collectively, while this data does not speak to causality nor directionality of the association, it does demonstrate a significant relationship between the human microbiome and COVID-19. The results from this study have rendered testable hypotheses that warrant further investigation to better understand the causality and directionality of host–microbiome–pathogen interactions.
Association of anticoagulation dose and survival in hospitalized COVID‐19 patients: A retrospective propensity score‐weighted analysis
(Wiley, 2020) Ionescu, Filip; Jaiyesimi, Ishmael; Petrescu, Ioana; Lawler, Patrick R.; Castillo, Edward; Munoz‐Maldonado, Yolanda; Imam, Zaid; Narasimhan, Mangala; Abbas, Amr E.; Konde, Anish; Nair, Girish B.
Background: Hypercoagulability may contribute to COVID‐19 pathogenicity. The role of anticoagulation (AC) at therapeutic (tAC) or prophylactic doses (pAC) is unclear. Objectives: We evaluated the impact on survival of different AC doses in COVID‐19 patients. Methods: Retrospective, multi‐center cohort study of consecutive COVID‐19 patients hospitalized between March 13 and May 5, 2020. Results: A total of 3480 patients were included (mean age, 64.5 years [17.0]; 51.5% female; 52.1% black and 40.6% white). 18.5% (n = 642) required intensive care unit (ICU) stay. 60.9% received pAC (n = 2121), 28.7% received ≥3 days of tAC (n = 998), and 10.4% (n = 361) received no AC. Propensity score (PS) weighted Kaplan‐Meier plot demonstrated different 25‐day survival probability in the tAC and pAC groups (57.5% vs 50.7%). In a PS–weighted multivariate proportional hazards model, AC was associated with reduced risk of death at prophylactic (hazard ratio [HR] 0.35 [95% confidence interval {CI} 0.22‐0.54]) and therapeutic doses (HR 0.14 [95% CI 0.05‐0.23]) compared to no AC. Major bleeding occurred more frequently in tAC patients (81 [8.1%]) compared to no AC (20 [5.5%]) or pAC (46 [2.2%]) subjects. Conclusions: Higher doses of AC were associated with lower mortality in hospitalized COVID‐19 patients. Prospective evaluation of efficacy and risk of AC in COVID‐19 is warranted.
Balancing economic and epidemiological interventions in the early stages of pathogen emergence
(AAAS, 2023) Dobson, Andy; Ricci, Cristiano; Boucekkine, Raouf; Gozzi, Fausto; Fabbri, Giorgio; Loch-Temzelides, Ted; Pascual, Mercedes; Baker Institute for Public Policy
The global pandemic of COVID-19 has underlined the need for more coordinated responses to emergent pathogens. These responses need to balance epidemic control in ways that concomitantly minimize hospitalizations and economic damages. We develop a hybrid economic-epidemiological modeling framework that allows us to examine the interaction between economic and health impacts over the first period of pathogen emergence when lockdown, testing, and isolation are the only means of containing the epidemic. This operational mathematical setting allows us to determine the optimal policy interventions under a variety of scenarios that might prevail in the first period of a large-scale epidemic outbreak. Combining testing with isolation emerges as a more effective policy than lockdowns, substantially reducing deaths and the number of infected hosts, at lower economic cost. If a lockdown is put in place early in the course of the epidemic, it always dominates the “laissez-faire” policy of doing nothing.
Birthing Between the “Traditional” and the “Modern”: DāĪ Practices and Childbearing Women’s Choices During COVID-19 in Pakistan
(Frontiers Media S.A., 2021) Ali, Inayat; Sadique, Salma; Ali, Shahbaz; Davis-Floyd, Robbie
Pregnancy and birth are biological phenomena that carry heavy cultural overlays, and pregnant and birthing women need care and attention during both ordinary and extraordinary times. Most Pakistani pregnant women now go to doctors and hospitals for their perinatal care. Yet traditional community midwives, called DāĪ in the singular and Dāyūn in the plural, still attend 24% of all Pakistani births, primarily in rural areas. In this article, via data collected from 16 interviews—5 with Dāyūn and 11 with mothers, we explore a maternity care system in tension between the past and the present, the DāĪ and the doctor. We ask, what does the maternity care provided by the Dāyūn look like during times of normalcy, and how does it differ during COVID-19? We look at the roles the DāĪ has traditionally performed and how these roles have been changing, both in ordinary and in Covidian circumstances. Presenting the words of the Dāyūn we interviewed, all from Pakistan’s Sindh Province, we demonstrate their practices and show that these have not changed during this present pandemic, as these Dāyūn, like many others in Sindh Province, do not believe that COVID-19 is real—or are at least suspect that it is not. To contextualize the Dāyūn, we also briefly present local mother’s perceptions of the Dāyūn in their regions, which vary between extremely positive and extremely negative. Employing the theoretical frameworks of “authoritative knowledge” and of critical medical anthropology, we highlight the dominance of “modern” biomedicine over “traditional” healthcare systems and its effects on the Dāyūn and their roles within their communities. Positioning this article within Pakistan’s national profile, we propose formally training and institutionalizing the Dāyūn in order to alleviate the overwhelming burdens that pandemics—present and future—place on this country’s fragile maternity care system, to give mothers more—and more viable—options at all times, and to counterbalance the rising tide of biomedical hegemony over pregnancy and birth.
Blocked by Gender: Disparities in COVID19 infection detection in Tamil Nadu, India
(Frontiers Media S.A., 2022) Samanta, Tannistha; Gopalan, Kaushik; Devi, Tanmay
Globally, a gender gap in COVID-19 has been noted with men reporting higher share of both morbidity and deaths compared to women. While the gender gap in fatalities has been similar across the globe, there have been interesting disparities in the detection of COVID-19 cases in men and women. While wealthier, more developed nations have generally seen similar case detection in men and women, LMICs especially in Asia have seen far greater proportion of COVID-19 cases among men than women. We utilize age and sex-disaggregated data from the southern Indian state of Tamil Nadu across two waves of the pandemic (May 2020 – Nov 2020, and March 2021, to June 2021) and find that there were only ~70% as many detected COVID-19 cases among women as there were among men. Our initial reading suggested that this might be a protective effect of lower labor force participation rates among women across much of South Asia. However, subsequent sero-prevalence results from Tamil Nadu conducted on October-November 2020, and June-July, 2021 suggest that infection incidence has been similar among men and women; as is the case in countries with better health infrastructure. This empirical puzzle suggests that reduced case detection among women cannot be immediately associated with limited public exposure, but rather evidence of a chronic neglect of women in healthcare access. Overall, we contend that an attention to the gender context holds promise to effective interventions in detection and prevention that goes beyond the traditional epidemiological logic of diseases.
Building local capacity for cervical cancer prevention in low resource settings: Changing strategy during the COVID-19 pandemic
(ISGH, 2021) Salcedo, Mila P.; Varon, Melissa L.; Phoolcharoen, Natacha; Osman, Nafissa; David, Ernestina; Rangeiro, Ricardina; Changule, Dercia; Andrade, Viviane; Neves, Andrea; Doughtie, Kathleen M.; Carns, Jennifer; Lorenzoni, Cesaltina; Baker, Ellen; Schmeler, Kathleen M.
In low- and middle-income countries (LMIC), where the great majority of cervical cancer cases occur, there is a shortage of health care providers trained to diagnose and treat pre-invasive cervical disease. The cervical cancer regional incidence and mortality rates are highest in sub-Saharan Africa and South-Eastern Asia [1]. In many resource-constrained regions, the shortage of trained providers limits the scale-up of quality cervical cancer screening, diagnosis and treatment services. In Mozambique, cervical cancer is the primary cause of cancer and cancer-related deaths among women [2,3]. Since 2016 we have provided in-person support and training to gynecologists and nurses in Mozambique. Cervical cancer prevention training, included teaching skills of colposcopy, cervical biopsy and loop electrosurgical excision procedure (LEEP) [4] Completion of hands-on training was followed by patient care with the trainers in local clinics. Participation in monthly Project ECHO (Extension of Community Healthcare Outcomes) telementoring sessions was encouraged to reinforce and amplify knowledge and skills. Since March 2020 travel has been restricted due to coronavirus disease (COVID-19). We have therefore adapted the way we deliver this training and provide support to colleagues in Mozambique so that capacity building efforts continue.
Camostat mesylate inhibits SARS-CoV-2 activation by TMPRSS2-related proteases and its metabolite GBPA exerts antiviral activity
(Elsevier, 2021) Hoffmann, Markus; Hofmann-Winkler, Heike; Smith, Joan C.; Krüger, Nadine; Arora, Prerna; Sørensen, Lambert K.; Søgaard, Ole S.; Hasselstrøm, Jørgen Bo; Winkler, Michael; Hempel, Tim; Raich, Lluís; Olsson, Simon; Danov, Olga; Jonigk, Danny; Yamazoe, Takashi; Yamatsuta, Katsura; Mizuno, Hirotaka; Ludwig, Stephan; Noé, Frank; Kjolby, Mads; Braun, Armin; Sheltzer, Jason M.; Pöhlmann, Stefan
Background: Antivirals are needed to combat the COVID-19 pandemic, which is caused by SARS-CoV-2. The clinically-proven protease inhibitor Camostat mesylate inhibits SARS-CoV-2 infection by blocking the virus-activating host cell protease TMPRSS2. However, antiviral activity of Camostat mesylate metabolites and potential viral resistance have not been analyzed. Moreover, antiviral activity of Camostat mesylate in human lung tissue remains to be demonstrated. Methods: We used recombinant TMPRSS2, reporter particles bearing the spike protein of SARS-CoV-2 or authentic SARS-CoV-2 to assess inhibition of TMPRSS2 and viral entry, respectively, by Camostat mesylate and its metabolite GBPA. Findings: We show that several TMPRSS2-related proteases activate SARS-CoV-2 and that two, TMPRSS11D and TMPRSS13, are robustly expressed in the upper respiratory tract. However, entry mediated by these proteases was blocked by Camostat mesylate. The Camostat metabolite GBPA inhibited recombinant TMPRSS2 with reduced efficiency as compared to Camostat mesylate. In contrast, both inhibitors exhibited similar antiviral activity and this correlated with the rapid conversion of Camostat mesylate into GBPA in the presence of serum. Finally, Camostat mesylate and GBPA blocked SARS-CoV-2 spread in human lung tissue ex vivo and the related protease inhibitor Nafamostat mesylate exerted augmented antiviral activity. Interpretation: Our results suggest that SARS-CoV-2 can use TMPRSS2 and closely related proteases for spread in the upper respiratory tract and that spread in the human lung can be blocked by Camostat mesylate and its metabolite GBPA. Funding: NIH, Damon Runyon Foundation, ACS, NYCT, DFG, EU, Berlin Mathematics center MATH+, BMBF, Lower Saxony, Lundbeck Foundation, Novo Nordisk Foundation.
Circulating ACE2-expressing extracellular vesicles block broad strains of SARS-CoV-2
(Springer Nature, 2022) El-Shennawy, Lamiaa; Hoffmann, Andrew D.; Dashzeveg, Nurmaa Khund; McAndrews, Kathleen M.; Mehl, Paul J.; Cornish, Daphne; Yu, Zihao; Tokars, Valerie L.; Nicolaescu, Vlad; Tomatsidou, Anastasia; Mao, Chengsheng; Felicelli, Christopher J.; Tsai, Chia-Feng; Ostiguin, Carolina; Jia, Yuzhi; Li, Lin; Furlong, Kevin; Wysocki, Jan; Luo, Xin; Ruivo, Carolina F.; Batlle, Daniel; Hope, Thomas J.; Shen, Yang; Chae, Young Kwang; Zhang, Hui; LeBleu, Valerie S.; Shi, Tujin; Swaminathan, Suchitra; Luo, Yuan; Missiakas, Dominique; Randall, Glenn C.; Demonbreun, Alexis R.; Ison, Michael G.; Kalluri, Raghu; Fang, Deyu; Liu, Huiping
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the pandemic of the coronavirus induced disease 2019 (COVID-19) with evolving variants of concern. It remains urgent to identify novel approaches against broad strains of SARS-CoV-2, which infect host cells via the entry receptor angiotensin-converting enzyme 2 (ACE2). Herein, we report an increase in circulating extracellular vesicles (EVs) that express ACE2 (evACE2) in plasma of COVID-19 patients, which levels are associated with severe pathogenesis. Importantly, evACE2 isolated from human plasma or cells neutralizes SARS-CoV-2 infection by competing with cellular ACE2. Compared to vesicle-free recombinant human ACE2 (rhACE2), evACE2 shows a 135-fold higher potency in blocking the binding of the viral spike protein RBD, and a 60- to 80-fold higher efficacy in preventing infections by both pseudotyped and authentic SARS-CoV-2. Consistently, evACE2 protects the hACE2 transgenic mice from SARS-CoV-2-induced lung injury and mortality. Furthermore, evACE2 inhibits the infection of SARS-CoV-2 variants (α, β, and δ) with equal or higher potency than for the wildtype strain, supporting a broad-spectrum antiviral mechanism of evACE2 for therapeutic development to block the infection of existing and future coronaviruses that use the ACE2 receptor.
Confident futures: Community-based organizations as first responders and agents of change in the face of the Covid-19 pandemic
(Elsevier, 2022) Roels, Nastasja Ilonka; Estrella, Amarilys; Maldonado-Salcedo, Melissa; Rapp, Rayna; Hansen, Helena; Hardon, Anita
This comparative study of community organizations serving marginalized youth in New York City and Amsterdam utilized a novel ethnographic approach called reverse engineering to identify techniques for social change that are active in each organization, adaptable and translatable to other contexts. It found that youth-serving organizations led flexible responses to the crisis of COVID-19 as it affected those marginalized by race, immigrant status, housing instability, religion and gender. The organizations employed techniques that they had previously developed to cultivate youth well-being – among them connectivity, safe space, and creativity – to mount tailored responses to COVID-19 related crises. In New York City, these groups addressed crises of material survival resources (personal protective equipment, food, housing) whereas in Amsterdam, youth-serving organizations focused on social connections and emotional well-being as the government met more of participants’ material needs.
Contact Tracing Apps: Lessons Learned on Privacy, Autonomy, and the Need for Detailed and Thoughtful Implementation
(JMIR, 2021) Hogan, Katie; Macedo, Briana; Macha, Venkata; Barman, Arko; Jiang, Xiaoqian; Data to Knowledge Lab
The global and national response to the COVID-19 pandemic has been inadequate due to a collective lack of preparation and a shortage of available tools for responding to a large-scale pandemic. By applying lessons learned to create better preventative methods and speedier interventions, the harm of a future pandemic may be dramatically reduced. One potential measure is the widespread use of contact tracing apps. While such apps were designed to combat the COVID-19 pandemic, the time scale in which these apps were deployed proved a significant barrier to efficacy. Many companies and governments sprinted to deploy contact tracing apps that were not properly vetted for performance, privacy, or security issues. The hasty development of incomplete contact tracing apps undermined public trust and negatively influenced perceptions of app efficacy. As a result, many of these apps had poor voluntary public uptake, which greatly decreased the apps’ efficacy. Now, with lessons learned from this pandemic, groups can better design and test apps in preparation for the future. In this viewpoint, we outline common strategies employed for contact tracing apps, detail the successes and shortcomings of several prominent apps, and describe lessons learned that may be used to shape effective contact tracing apps for the present and future. Future app designers can keep these lessons in mind to create a version that is suitable for their local culture, especially with regard to local attitudes toward privacy-utility tradeoffs during public health crises.
COVID-19 and the value of safe transport in the United States
(Springer Nature, 2021) Medlock, Kenneth B.; Temzelides, Ted; Hung, Shih Yu (Elsie); Center for Energy Studies, James A. Baker III Institute for Public Policy
We investigate the connection between the choice of transportation mode used by commuters and the probability of COVID-19 transmission. This interplay might influence the choice of transportation means for years to come. We present data on commuting, socioeconomic factors, and COVID-19 disease incidence for several US metropolitan areas. The data highlights important connections between population density and mobility, public transportation use, race, and increased likelihood of transmission. We use a transportation model to highlight the effect of uncertainty about transmission on the commuters’ choice of transportation means. Using multiple estimation techniques, we found strong evidence that public transit ridership in several US metro areas has been considerably impacted by COVID-19 and by the policy responses to the pandemic. Concerns about disease transmission had a negative effect on ridership, which is over and above the adverse effect from the observed reduction in employment. The COVID-19 effect is likely to reduce the demand for public transport in favor of lower density alternatives. This change relative to the status quo will have implications for fuel use, congestion, accident frequency, and air quality. More vulnerable communities might be disproportionally affected as a result. We point to the need for additional studies to further quantify these effects and to assist policy in planning for the post-COVID-19 transportation future.
COVID-19 in the Americas and the erosion of human rights for the poor
(Public Library of Science, 2020) Hotez, Peter J.; Huete-Perez, Jorge A.; Bottazzi, Maria Elena; James A Baker III Institute for Public Policy

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