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2.
Journal of Communication in Healthcare ; 15(1):44-53, 2022.
Article in English | GIM | ID: covidwho-1890698

ABSTRACT

Background: Health advice in the wake of the COVID-19 pandemic has called upon the public to re-evaluate risk associated with recently routine behavior. However, differences in demographics, situational circumstances, and psychological dispositions create inequities in how people are able to respond to risks presented by the virus. Method: Within a sample of 482 Americans, we examined the frequency of behavior reconceptualized as 'risky' by CDC public health guidelines released on 30 March 2020. We applied a cluster analysis using a data-driven persona framework from the field of user-design research, using only situational and dispositional (i.e. psychological) variables to identify profiles of individuals.

3.
PubMed; 2021.
Preprint in English | PubMed | ID: ppcovidwho-333686

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) has now caused over 2 million deaths worldwide and continues to expand. Currently, much is unknown about functionally neutralizing human antibody responses and durability to SARS-CoV-2. Using convalescent sera collected from 101 COVID-19 recovered individuals 21-212 days after symptom onset with forty-eight additional longitudinal samples, we measured functionality and durability of serum antibodies. We also evaluated associations between individual demographic and clinical parameters with functional neutralizing antibody responses to COVID-19. We found robust antibody durability out to six months, as well as significant positive associations with the magnitude of the neutralizing antibody response and male sex. We also show that SARS-CoV-2 convalescent neutralizing antibodies are higher in individuals with cardio-metabolic comorbidities. SIGNIFICANCE: In this study we found that neutralizing antibody responses in COVID-19 convalescent individuals vary in magnitude but are durable and correlate well with RBD Ig binding antibody levels compared to other SARS-CoV-2 antigen responses. In our cohort, higher neutralizing antibody titers are independently and significantly associated with male sex compared to female sex. We also show for the first time, that higher convalescent antibody titers in male donors are associated with increased age and symptom grade. Furthermore, cardio-metabolic co-morbidities are associated with higher antibody titers independently of sex. Here, we present an in-depth evaluation of serologic, demographic, and clinical correlates of functional antibody responses and durability to SARS-CoV-2.

4.
American Journal of Kidney Diseases ; 79(4):S99-S100, 2022.
Article in English | Web of Science | ID: covidwho-1776999
5.
Biophysical Journal ; 121(3):359A-360A, 2022.
Article in English | Web of Science | ID: covidwho-1755600
6.
Achdout, H.; Aimon, A.; Bar-David, E.; Barr, H.; Ben-Shmuel, A.; Bennett, J.; Bilenko, V. A.; Bilenko, V. A.; Boby, M. L.; Borden, B.; Bowman, G. R.; Brun, J.; Bvnbs, S.; Calmiano, M.; Carbery, A.; Carney, D.; Cattermole, E.; Chang, E.; Chernyshenko, E.; Chodera, J. D.; Clyde, A.; Coffland, J. E.; Cohen, G.; Cole, J.; Contini, A.; Cox, L.; Cvitkovic, M.; Dias, A.; Donckers, K.; Dotson, D. L.; Douangamath, A.; Duberstein, S.; Dudgeon, T.; Dunnett, L.; Eastman, P. K.; Erez, N.; Eyermann, C. J.; Fairhead, M.; Fate, G.; Fearon, D.; Fedorov, O.; Ferla, M.; Fernandes, R. S.; Ferrins, L.; Foster, R.; Foster, H.; Gabizon, R.; Garcia-Sastre, A.; Gawriljuk, V. O.; Gehrtz, P.; Gileadi, C.; Giroud, C.; Glass, W. G.; Glen, R.; Glinert, I.; Godoy, A. S.; Gorichko, M.; Gorrie-Stone, T.; Griffen, E. J.; Hart, S. H.; Heer, J.; Henry, M.; Hill, M.; Horrell, S.; Huliak, V. D.; Hurley, M. F. D.; Israely, T.; Jajack, A.; Jansen, J.; Jnoff, E.; Jochmans, D.; John, T.; De Jonghe, S.; Kantsadi, A. L.; Kenny, P. W.; Kiappes, J. L.; Kinakh, S. O.; Koekemoer, L.; Kovar, B.; Krojer, T.; Lee, A.; Lefker, B. A.; Levy, H.; Logvinenko, I. G.; London, N.; Lukacik, P.; Macdonald, H. B.; MacLean, B.; Malla, T. R.; Matviiuk, T.; McCorkindale, W.; McGovern, B. L.; Melamed, S.; Melnykov, K. P.; Michurin, O.; Mikolajek, H.; Milne, B. F.; Morris, A.; Morris, G. M.; Morwitzer, M. J.; Moustakas, D.; Nakamura, A. M.; Neto, J. B.; Neyts, J.; Nguyen, L.; Noske, G. D.; Oleinikovas, V.; Oliva, G.; Overheul, G. J.; Owen, D.; Pai, R.; Pan, J.; Paran, N.; Perry, B.; Pingle, M.; Pinjari, J.; Politi, B.; Powell, A.; Psenak, V.; Puni, R.; Rangel, V. L.; Reddi, R. N.; Reid, S. P.; Resnick, E.; Ripka, E. G.; Robinson, M. C.; Robinson, R. P.; Rodriguez-Guerra, J.; Rosales, R.; Rufa, D.; Saar, K.; Saikatendu, K. S.; Schofield, C.; Shafeev, M.; Shaikh, A.; Shi, J.; Shurrush, K.; Singh, S.; Sittner, A.; Skyner, R.; Smalley, A.; Smeets, B.; Smilova, M. D.; Solmesky, L. J.; Spencer, J.; Strain-Damerell, C.; Swamy, V.; Tamir, H.; Tennant, R.; Thompson, W.; Thompson, A.; Tomasio, S.; Tsurupa, I. S.; Tumber, A.; Vakonakis, I.; Van Rij, R. P.; Vangeel, L.; Varghese, F. S.; Vaschetto, M.; Vitner, E. B.; Voelz, V.; Volkamer, A.; Von Delft, F. f, Von Delft, A.; Walsh, M.; Ward, W.; Weatherall, C.; Weiss, S.; White, K. M.; Wild, C. F.; Wittmann, M.; Wright, N.; Yahalom-Ronen, Y.; Zaidmann, D.; Zidane, H.; Zitzmann, N..
Embase; 2020.
Preprint in English | EMBASE | ID: ppcovidwho-330569

ABSTRACT

The COVID-19 pandemic is a stark reminder that a barren global antiviral pipeline has grave humanitarian consequences. Future pandemics could be prevented by accessible, easily deployable broad-spectrum oral antivirals and open knowledge bases that derisk and accelerate novel antiviral discovery and development. Here, we report the results of the COVID Moonshot, a fully open-science structure-enabled drug discovery campaign targeting the SARS-CoV-2 main protease. We discovered a novel chemical scaffold that is differentiated to current clinical candidates in terms of toxicity and pharmacokinetics liabilities, and developed it into orally-bioavailable inhibitors with clinical potential. Our approach leverages crowdsourcing, high throughput structural biology, machine learning, and exascale molecular simulations. In the process, we generated a detailed map of the structural plasticity of the main protease, extensive structure-activity relationships for multiple chemotypes, and a wealth of biochemical activity data. In a first for a structure-based drug discovery campaign, all compound designs (>18,000 designs), crystallographic data (>500 ligand-bound X-ray structures), assay data (>10,000 measurements), and synthesized molecules (>2,400 compounds) for this campaign were shared rapidly and openly, creating a rich open and IP-free knowledgebase for future anti-coronavirus drug discovery.

7.
Embase;
Preprint in English | EMBASE | ID: ppcovidwho-327049

ABSTRACT

Despite the efficacy of vaccines, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has killed over 5 million individuals worldwide and continues to spread in countries where the vaccines are not yet widely available or its citizens are hesitant to become vaccinated. Therefore, it is critical to unravel the molecular mechanisms that allow SARS-CoV-2 and other coronaviruses to infect and overtake the host machinery of human cells. Coronavirus replication triggers endoplasmic reticulum (ER) stress and activation of the unfolded protein response (UPR), a key host cell pathway widely believed essential for viral replication. We examined the activation status and requirement of the master UPR sensor IRE1a kinase/RNase and its downstream transcription factor effector XBP1s, which is processed through an IRE1a-mediated mRNA splicing event, in human lung-derived cells infected with betacoronaviruses. We found human respiratory coronavirus OC43 (HCoV-OC43), Middle East respiratory syndrome coronavirus (MERS-CoV), and the murine coronavirus (MHV) all induce ER stress and strongly trigger the kinase and RNase activities of IRE1a as well as XBP1 splicing. In contrast, SARS-CoV-2 only partially activates IRE1a whereby it autophosphorylates, but its RNase fails to splice XBP1. Moreover, IRE1a was dispensable for optimal replication in human cells for all coronaviruses tested. Our findings demonstrate that IRE1a activation status differs upon infection with distinct betacoronaviruses and is not essential for efficient replication of any of them. Our data suggest that SARS-CoV-2 actively inhibits the RNase of autophosphorylated IRE1a through an unknown mechanism, perhaps as a strategy to eliminate detection by the host immune system.

8.
Embase;
Preprint in English | EMBASE | ID: ppcovidwho-327045

ABSTRACT

The GISAID database contains more than 100,000 SARS-CoV-2 genomes, including sequences of the recently discovered SARS-CoV-2 omicron variant and of prior SARS-CoV-2 strains that have been collected from patients around the world since the beginning of the pandemic. We applied unsupervised cluster analysis to the SARS-CoV-2 genomes, assessing their similarity at a genome-wide level based on the Jaccard index and principal component analysis. Our analysis results show that the omicron variant sequences are most similar to sequences that have been submitted early in the pandemic around January 2020. Furthermore, the omicron variants in GISAID are spread across the entire range of the first principal component, suggesting that the strain has been in circulation for some time. This observation supports a long-term infection hypothesis as the omicron strain origin.

9.
Embase;
Preprint in English | EMBASE | ID: ppcovidwho-326915

ABSTRACT

Middle East respiratory syndrome coronavirus (MERS-CoV) emerged into humans in 2012, causing highly lethal respiratory disease. The severity of disease may be in part because MERS-CoV is adept at antagonizing early innate immune pathways - interferon (IFN) production and signaling, protein kinase R (PKR), and oligoadenylate synthetase ribonuclease L (OAS/RNase L) - generated in response to viral double-stranded (ds)RNA generated during genome replication. This is in contrast to SARS-CoV-2, which we recently reported activates PKR and RNase L and to some extent, IFN signaling. We previously found that MERS-CoV accessory proteins NS4a (dsRNA binding protein) and NS4b (phosphodiesterase) could weakly suppress these pathways, but ablation of each had minimal effect on virus replication. Here we investigated the antagonist effects of the conserved coronavirus endoribonuclease (EndoU), in combination with NS4a or NS4b. Inactivation of EndoU catalytic activity alone in a recombinant MERS-CoV caused little if any effect on activation of the innate immune pathways during infection. However, infection with recombinant viruses containing combined mutations with inactivation of EndoU and deletion of NS4a or inactivation of the NS4b phosphodiesterase promoted robust activation of the dsRNA-induced innate immune pathways. This resulted in ten-fold attenuation of replication in human lung derived A549 and primary nasal cells. Furthermore, replication of these recombinant viruses could be rescued to the level of WT MERS-CoV by knockout of host immune mediators MAVS, PKR, or RNase L. Thus, EndoU and accessory proteins NS4a and NS4b together suppress dsRNA-induced innate immunity during MERS-CoV infection in order to optimize viral replication.

10.
Blood ; 138:2982, 2021.
Article in English | EMBASE | ID: covidwho-1582330

ABSTRACT

Introduction: The COVID-19 pandemic presented exceptional challenges to caring for adults with sickle cell disease (SCD) and necessitated a rapid transition to telemedicine, disrupting established care systems within a population that already faces unique and challenging medical needs. Although implementation of telemedicine care assumed reliable patient access to the requisite technology, as well as adequate spaces in which to complete visits, pre-pandemic barriers to in-person visits were also considerable, and many patients lacked access to reliable transportation and childcare or could not afford to miss work to attend clinic. Given the scarcity of research on the acceptability of telemedicine care for SCD patients, the pandemic has provided a critical and necessary opportunity to study patient satisfaction when using telemedicine modalities for regular SCD care. The objective of this study was to identify which patient groups rate telemedicine high in satisfaction and usability. Methods: We surveyed 99 patients of the Sickle Cell Clinic for adults at Johns Hopkins who had any form of SCD, were age 18 or above, and participated in at least one video visit between March-July 2020. Telemedicine satisfaction was assessed by the Telemedicine Satisfaction Questionnaire (TSQ), and usability was assessed by the System Usability Scale (SUS). Patients' engagement in their healthcare was assessed by the Patient Activation Measure (PAM13). We conducted linear regression with TSQ and SUS as outcomes and participant characteristics as predictors. Results: Participant characteristics (briefly, mean age 39, 95% African American, 72% female, and 81% with education level above high school) and their association with TSQ and SUS are shown in Table 1. Mean SUS was 72/100 (SD 15), slightly above the defined average usability of 68;mean TSQ was 4.1 (SD 0.5) on a 5-point Likert scale. Participants tended to prefer video visits for their regular care (mean rating of 6.6/10, SD 2.9) but not for management of acute pain (mean rating of 4.9/10, SD 3.2). Participants who preferred video visits for regular SCD care reported higher SUS (p<0.01) and TSQ (p<0.001). We examined the effects of age, sex, income, and education level on TSQ and SUS;higher SUS was associated with an education level above high school (p<0.05), but no other associations were consistently significant. Higher SUS was also associated with having private insurance compared to public insurance (p<0.01) and being employed full-time compared to being unemployed (p<0.05). Disability status was negatively associated with SUS (p<0.05) but not TSQ. PAM13 was associated with higher telemedicine approval as measured by both TSQ and SUS (p<0.01). Conclusions: Our findings suggest that telemedicine has above-average usability and high satisfaction for SCD patients, regardless of age, sex, and income. Patients who were more engaged with their healthcare were more likely to rate telemedicine satisfaction and usability high. Because SUS was negatively associated with disability, lower education level, public insurance, and unemployment, patients within these groups may need more assistance with telemedicine. To improve usability, clinics may consider incorporating support services for patients who have difficulty using telemedicine platforms. Altogether, telemedicine demonstrates promising acceptability to SCD patients across multiple demographic groups and may serve as another method in the toolkit for increasing accessibility to high quality care for these patients. [Formula presented] Disclosures: Lanzkron: Pfizer: Current holder of individual stocks in a privately-held company;Bluebird Bio: Consultancy;Novo Nordisk: Consultancy;GBT: Research Funding;Teva: Current holder of individual stocks in a privately-held company;Shire: Research Funding;CSL Behring: Research Funding;Novartis: Research Funding;Imara: Research Funding.

11.
Blood ; 138:1893, 2021.
Article in English | EMBASE | ID: covidwho-1582208

ABSTRACT

Introduction Individuals with Sickle Cell Disease (SCD) require regular, and specialized treatment to manage their health. The COVID-19 pandemic disrupted in person medical visits for all individuals, with a rapid transition to telemedicine to provide medical care. Emerging data shows that the use of telemedicine may provide easier access to care and remove barriers to clinic attendance and improve access to appropriate medical care. Objective The purpose of this study was to use qualitative methods to understand the patients' experiences with telemedicine, identify patient preferences for type of appointment, and possible suggestions to improve telemedicine care. Methods Patients from the Johns Hopkins Sickle Cell Center for Adults who had at least one telemedicine visit were invited to participate in a semi structured interview via zoom meeting or telephone. The interview asked participants about their satisfaction with telemedicine care, barriers to telemedicine, benefits and risks of telemedicine and possible telemedicine improvements. Interviews were recorded, transcribed and coded by two independent raters using thematic analyses to understand the experiences of telemedicine during the COVID-19 pandemic. Results Overall, 30 adults with SCD who had at least one telemedicine visit were invited to participate and completed their interview (mean age 41 years ± xx, 67% female, 93% Black/African American, 3% Multi-Race, 3% Other). “…I can't ignore the convenience of not having to worry about transportation. that there's nothing to stop me from getting there.” During a SCD pain crisis it can it challenging to move and receive treatment as one participant reported “Maybe sometimes I might have pain…then moving around makes it difficult. So, getting in the car and finding somebody to drive you to a hospital or to whatever clinic would be difficult”. Being able to access specialized SCD care even while in pain is important. Having the option of either having telemedicine or in person visits was important to SCD patients “I could treat my crisis here at home. I don't have to go to the emergency room for it. So, if I can see my doctor in the tele-visit appointment and it's going to be constantly every day. And when it's getting worse, then I could go to the emergency room more if needed. If it's not needed, I don't even need to go”. Another emerging theme amongst participants was despite the benefits from telemedicine, they also wanted to continue having in-person visits when they needed. SCD participants felt due to their SCD they still needed to see their doctor in person but it did not have to be for every visit “Well, I think telemedicine, for me, can be used in a setting where there's no such an emergency. Like if I'm having a routine exam, I don't mind having the telemedicine. But if. I'm not feeling well. I don't want to be having a telemedicine”. SCD participants felt they needed a physical exam periodically. “The only thing I didn't like about it was if I'm having some discomfort or some pain. there was no way for the physician to physically examine me”. Along with the lack of physical exam, there were concerns about the lack of vital signs “. the drawbacks would be the lack of the vitals being taken or there's not the personal touch and stuff”. Conclusion The COVID-19 pandemic has presented many obstacles for patients to receive care. People living with SCD found telemedicine to be a positive tool to receive treatment. Patients reported the desire to continue with telemedicine even after the COVID -19 pandemic. Telemedicine allows for more accessibility for a group of individuals who already have numerous barriers to treatment. Future research can seek to identify the impact that telemedicine has on no-show rates, health care utilization, and the impact telemedicine has on patient reported quality of life. Disclosures: Lanzkron: Teva: Current holder of individual stocks in a privately-held company;Shire: Research Funding;GBT: Research Funding;CSL Behring: Research Funding;Novo N rdisk: Consultancy;Bluebird Bio: Consultancy;Pfizer: Current holder of individual stocks in a privately-held company;Imara: Research Funding;Novartis: Research Funding.

12.
Genetic Epidemiology ; 45(7):807-807, 2021.
Article in English | Web of Science | ID: covidwho-1436769
13.
Investigative Ophthalmology and Visual Science ; 62(8), 2021.
Article in English | EMBASE | ID: covidwho-1378589

ABSTRACT

Purpose : COVID-19 and associated mitigation measures have caused unprecedented global disruption. It is not known whether there are disproportionate challenges for persons with a sensory disability. Our cross-sectional study assesses this impact of the pandemic on persons with and without visual or hearing loss. Methods : Experts from diverse disciplines developed a 34-item survey instrument, the Coronavirus Disability Survey, which includes items on general and psychological health, instrumental activities of daily living, isolation, financial and transportation challenges, and information access. The study population included 112 adults with moderate or worse visual impairment (<20/60 in better-seeing eye), 108 with hearing loss (defined using ICD10 codes), and 155 age/sex-matched controls recruited from the University of Michigan (UM) Health System. Survey administration was via email or telephone. The UM IRB approved this study and all participants provided informed consent. Results : Participants reported similarly high levels of disruption of their daily lives with 80% reporting a fair amount or a lot of disruption. Groups reported similar levels of COVID exposure (21%) and infection (45% of exposed). In the visual loss (VL) group, 18% reported a lot of difficulty or being unable to access routine medical care compared with 12% of hearing loss (HL) and 10% of control (C) groups (p=.02). The reasons for increased difficulty with instrumental activities of daily living varied: among those with VL 62% had difficulty due to fear of exposure (54% HI, 45% C);38% said the person assisting them was worried about exposure (6% HI, 7% C);and 12% cited decreased availability of public transportation (2% HI, 3% C). A greater proportion with VL began relying more on family for assistance (31% VI, 7% HI, 13% C) (p<.001 for all comparisons). Among all participants, 30% reported difficulty accessing trusted information about the pandemic;11% of those with VL found the information difficult to see or hear (1% HL, 2% C;p<.001). Conclusions : Individuals with VL may face increased disruption of their daily activities stemming from the pandemic and related mitigation measures, including in accessing healthcare, transportation, and information. Data-driven public health and policy decisions may benefit from a deeper understanding of the differential impact of the pandemic on these vulnerable groups.

14.
Critical Care Medicine ; 49(1):150-150, 2021.
Article in English | Web of Science | ID: covidwho-1326646
15.
Critical Care Medicine ; 49(1 SUPPL 1):150, 2021.
Article in English | EMBASE | ID: covidwho-1194011

ABSTRACT

INTRODUCTION: Caring for critically ill children with known or suspected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections requires significant changes to usual pediatric intensive care unit operations related to infection control policies and frequent evolution of clinical care practice. We hypothesized that patients with known or suspected SARS-CoV-2 would more often experience delays in timely antibiotic administration. METHODS: We performed a retrospective cohort study including all children with suspected sepsis admitted to our tertiary PICU from March 16 through June 18, 2020. Suspected sepsis was defined by an order for a broadspectrum antibiotic and blood culture. Children with known or suspected SARS-CoV-2 were defined by admission to the Pediatric Special Treatment Unit (PSTU), an isolation unit within the PICU dedicated to care of SARS-CoV-2 patients. The primary outcome of median time to antibiotic administration was compared using the Mann-Whitney-U test. Secondary outcomes included the proportion of antibiotics administered within 1 hour of the order and sepsis pathway utilization. Fisher's exact test was used for comparison of secondary outcomes. RESULTS: A total of 155 sepsis episodes were evaluated, including 14 with known/suspected SARS-CoV-2 and 141 with non-SARS-CoV-2 sepsis. Median time to antibiotic administration was 70.5 minutes in known/suspected SARSCoV- 2 versus 103 minutes in non-SARS-CoV-2 sepsis (NS). Secondary outcomes were also not different between groups. Known/suspected SARS-CoV-2 patients received 36% of new antibiotics within 60 minutes as compared to 46% of non-SARS-CoV-2 patients. Pathway utilization was 29% in known/suspected SARS-CoV-2 and 23% in non-SARSCoV- 2 patients. CONCLUSIONS: Despite significant operational changes enacted to care for SARS-CoV-2 patients, time to antibiotic administration and utilization of the sepsis pathway were no different than in non-SARS-CoV-2 patients with suspected sepsis. Operational challenges may have been overcome by a staffing model that emphasized attending physicians as well as a higher nurse to patient ratio for this population.

16.
Neuropsychopharmacology ; 45(SUPPL 1):61-61, 2020.
Article in English | Web of Science | ID: covidwho-1001415
17.
PubMed; 2020.
Preprint in English | PubMed | ID: ppcovidwho-2681

ABSTRACT

Age is the dominant risk factor for infectious diseases, but the mechanisms linking the two are incompletely understood1,2. Age-related mosaic chromosomal alterations (mCAs) detected from blood-derived DNA genotyping, are structural somatic variants associated with aberrant leukocyte cell counts, hematological malignancy, and mortality3-11. Whether mCAs represent independent risk factors for infection is unknown. Here we use genome-wide genotyping of blood DNA to show that mCAs predispose to diverse infectious diseases. We analyzed mCAs from 767,891 individuals without hematological cancer at DNA acquisition across four countries. Expanded mCA (cell fraction >10%) prevalence approached 4% by 60 years of age and was associated with diverse incident infections, including sepsis, pneumonia, and coronavirus disease 2019 (COVID-19) hospitalization. A genome-wide association study of expanded mCAs identified 63 significant loci. Germline genetic alleles associated with expanded mCAs were enriched at transcriptional regulatory sites for immune cells. Our results link mCAs with impaired immunity and predisposition to infections. Furthermore, these findings may also have important implications for the ongoing COVID-19 pandemic, particularly in prioritizing individual preventive strategies and evaluating immunization responses.

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