bluuebunny/crossref_metadata_2025 huggingface dataset:
COVID-19 causing HELLP-like syndrome in pregnancy and role of angiogenic factors for differential diagnosis
Authors: Figueras Francesc , LLurba Elisa , Martinez-Portilla Raigam , Mora Josefina , Crispi Fatima , Gratacos Eduard
Published: July 2020

Importance: The clinical presentation of hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome is one of the more severe forms of preeclampsia. COVID-19 infection exhibits signs that are shared with preeclampsia and HELLP syndrome, which may lead to needless interventions and iatrogenic preterm delivery.
Objective: We evaluated the prevalence of HELLP-like signs in pregnant women admitted for COVID-19 and the value of angiogenic factors to rule out preeclampsia.
Methods: a consecutive series of 27 pregnant women beyond 20 weeks of gestation, with symptomatic COVID-19. Clinical and analytical features were recorded and those cases with signs of HELLP syndrome were tested for sFlt-1/PlGF ratio.
Results: Seven patients (25.9%) presented at least one sign of suspected HELLP syndrome, of which 2 (7.4%) were diagnosed clinically with PE because of hypertension and high transaminases and 5 (18.5%) had only elevated transaminases. sFlt-1/PlGF ratio was normal in 6 of 7.
Conclusion: Symptomatic COVID-19 may simulate severe preeclampsia in pregnancy. Angiogenic factors may be essential to avoid false diagnosis and needless interventions.

These data were presented in a Virtual Symposium on Covid-19 and Pregnancy on 17 April: 2020:(http://medicinafetalbarcelona.org/simposiocovid19/ [Spanish] and https://medicinafetalbarcelona.org/symposiumcovid19/ [English]
Associations of Loneliness and Social Isolation with Healthspan and Lifespan in the US Health and Retirement Study
Authors: Crowe CL , Domingue BW , Hu G , Keyes KM , Kwon Dy , Belsky DW
Published: July 2020

Background

Loneliness and social isolation are emerging public health challenges for aging populations.

Methods

We followed N=11,302 US Health and Retirement Study (HRS) participants aged 50-95 from 2006-2014 to measure persistence of experiences of loneliness and exposure to social isolation. We tested associations of longitudinal loneliness and social isolation phenotypes with disability, morbidity, mortality, and biological aging through 2018.

Results

During follow-up, 18% of older adults met criteria for loneliness, with 6% meeting criteria at two or more follow-up assessments. For social isolation, these fractions were 21% and 8%. HRS participants who experienced loneliness and were exposed to social isolation were at increased risk for disease, disability, and mortality. Those experiencing persistent loneliness were at a 57% increased hazard of mortality compared to those who never experienced loneliness. For social isolation, the increase was 28%. Effect-sizes were somewhat larger for counts of prevalent activity limitations and somewhat smaller for counts of prevalent chronic diseases. Covariate adjustment for socioeconomic and psychological risks attenuated but did not fully explain associations. Older adults who experienced loneliness and were exposed to social isolation also exhibited physiological indications of advanced biological aging (Cohen’s-d for persistent loneliness and social isolation=0.26 and 0.21, respectively). For loneliness, but not social isolation, persistence was associated with increased risk.

Conclusion

Deficits in social connectedness prevalent in a national sample of US older adults were associated with morbidity, disability, and mortality and with more advanced biological aging. Bolstering social connectedness to interrupt experiences of loneliness may promote healthy aging.
COVID-19 severity is predicted by earlier evidence of accelerated aging
Authors: Kuo Chia-Ling , Pilling Luke C. , Atkins Janice L , Masoli Jane AH , Delgado João , Tignanelli Christopher , Kuchel George A , Melzer David , Beckman Kenneth B , Levine Morgan E.
Published: July 2020

With no known treatments or vaccine, COVID-19 presents a major threat, particularly to older adults, who account for the majority of severe illness and deaths. The age-related susceptibility is partly explained by increased comorbidities including dementia and type II diabetes [1]. While it is unclear why these diseases predispose risk, we hypothesize that increased biological age, rather than chronological age, may be driving disease-related trends in COVID-19 severity with age. To test this hypothesis, we applied our previously validated biological age measure (PhenoAge) [2] composed of chronological age and nine clinical chemistry biomarkers to data of 347,751 participants from a large community cohort in the United Kingdom (UK Biobank), recruited between 2006 and 2010. Other data included disease diagnoses (to 2017), mortality data (to 2020), and the UK national COVID-19 test results (to May 31, 2020) [3]. Accelerated aging 10-14 years prior to the start of the COVID-19 pandemic was associated with test positivity (OR=1.15 per 5-year acceleration, 95% CI: 1.08 to 1.21, p=3.2×10−6) and all-cause mortality with test-confirmed COVID-19 (OR=1.25, per 5-year acceleration, 95% CI: 1.09 to 1.44, p=0.002) after adjustment for demographics including current chronological age and pre-existing diseases or conditions. The corresponding areas under the curves were 0.669 and 0.803, respectively. Biological aging, as captured by PhenoAge, is a better predictor of COVID-19 severity than chronological age, and may inform risk stratification initiatives, while also elucidating possible underlying mechanisms, particularly those related to inflammaging.
The emergence of COVID-19 in Indonesia: analysis of predictors of infection and mortality using independent and clustered data approaches
Authors: Burhan Erlina , Syam Ari Fahrial , Rahyussalim Ahmad Jabir , Prasenohadi  , Wulung Navy G Lolong , Susanto Agus Dwi , Ketut Sajinadiyasa I Gede , Puspitorini Dewi , Lestari Dewi , Widyahening Indah Suci , Setiawaty Vivi , Ocviyanti Dwiana , Putri Kartika Qonita , Guntara Aswin , Rianda Davrina , Shankar Anuraj H , Agustina Rina
Published: July 2020

Background

Analyses of correlates of SARS-CoV-2 infection or mortality have usually assessed individual predictors. This study aimed to determine if patterns of combined predictors may better identify risk of infection and mortality

Methods

For the period of March 2ndto 10th2020, the first 9 days of the COVID-19 pandemic in Indonesia, we selected all 18 confirmed cases, of which 6 died, and all 60 suspected cases, of which 1 died; and 28 putatively negative patients with pneumonia and no travel history. We recorded data for travel, contact history, symptoms, haematology, comorbidities, and chest x-ray. Hierarchical cluster analyses (HCA) and principal component analyses (PCA) identified cluster and covariance patterns for symptoms or haematology which were analysed with other predictors of infection or mortality using logistic regression.

Results

For univariate analyses, no significant association with infection was seen for fever, cough, dyspnoea, headache, runny nose, sore throat, gastrointestinal complaints (GIC), or haematology. A PCA symptom component for fever, cough, and GIC tended to increase risk of infection (OR 3.41; 95% CI 1.06-14; p=0.06), and a haematology component with elevated monocytes decreased risk (OR 0.26; 0.07-0.79; 0.027). Multivariate analysis revealed that an HCA cluster of 3-5 symptoms, typically fever, cough, headache, runny nose, sore throat but little dyspnoea and no GIC tended to reduce risk (aOR 0.048; <0.001–0.52; 0.056). In univariate analyses for death, an HCA cluster of cough, fever and dyspnoea had increased risk (OR 5.75; 1.06 − 31.3, 0.043), but no other individual predictor, cluster or component was associated. Other significant predictors of infection were age ≥ 45, international travel, contact with COVID-19 patient, and pneumonia. Diabetes and history of contact were associated with higher mortality.

Conclusions

Cluster groups and co-variance patterns may be stronger correlates of SARS-CoV-2 infection than individual predictors. Comorbidities may warrant careful attention as would COVID-19 exposure levels.
Inhibitory KIR-Ligand Interactions and Relapse Protection Following HLA Matched Allogeneic HCT for AML
Authors: Krieger Elizabeth , Qayyum Rehan , Toor Amir
Published: July 2020

Killer immunoglobulin-like receptor (KIR) and KIR-ligand (KIRL) interactions play an important role in natural killer cell mediated graft versus leukemia effect (GVL) after hematopoietic stem cell transplant (HCT) for AML. Mathematically accounting for KIR-KIRL interactions may identify donors with optimal NK cell mediated alloreactivity and GVL. In this retrospective study of 2359 donor recipient pairs (DRP) who underwent unrelated donor (URD) HCT for AML, KIR-KIRL interaction scores were determined. Relapse risk was significantly reduced in donor-recipient pairs (DRP) with higher inhibitory KIR-KIRL interaction and missing KIRL (mKIR) scores, with HR=0.86 (P=0.01) & HR=0.84 (P=0.02) respectively. This effect was not observed with activating KIR-KIRL interactions. The inhibitory KIR-KIRL (iKIR) interaction score components were summed to give an inhibitory-missing ligand (IM-KIR) score, which if it was 5 as opposed to <5, was also associated with a lower relapse risk, SHR 0.8 (P=0.004). Acute and chronic graft vs. host disease (GVHD), survival, GRFS and relapse free survival were not significantly different. However, TRM was increased among those with IM-KIR=5, HR, 1.32 (P=0.01). Among those with HLA matched DRP, anti-thymocyte globulin recipients with IM-KIR=5, had a lower relapse rate HR, 0.61 (p=0.001), however TRM was increased in these patients with a HR, 1.49 (p=0.034). This study demonstrates that unrelated DRPs with high inhibitory KIR content scores confer relapse protection, albeit with increased TRM. Clinical trials utilizing donors with a higher iKIR content in conjunction with novel strategies to reduce TRM should be considered for URD HCT recipients with AML to optimize clinical outcomes.

Highlights

Inhibitory and missing KIR-KIRL interactions, both individually and collectively are predictive of relapse following URD HCT for AML.

Amongst 8/8 HLA matched donor recipient pair relapse reduction was observed in those undergoing in vivo T cell depletion with ATG.

TRM is increased in patients with greater magnitude of inhibitory and missing KIR-KIRL interactions.
Clinical importance of reporting SARS-CoV-2 viral loads across the different stages of the COVID-19 pandemic
Authors: Moraz M. , Jacot D. , Papadimitriou-Olivgeris M. , Senn L. , Greub G. , Jaton K. , Opota O.
Published: July 2020

On April 25th, corresponding to the first deconfinement phase after the end of the lockdown in Switzerland, a universal admission screening strategy for COVID-19 was introduced in our hospital. All patients, including asymptomatic patients were tested for SARS-CoV-2 by quantitative reverse transcription polymerase chain reaction (RT-PCR). In addition to a qualitative answer, providing viral load values to the RT-PCR results not only helped the clinician to evaluate the stage of the infection but addressed patient contagiousness and guided infection control decisions. Here, we discuss the importance of reporting viral load values when a shift from a symptomatic to a universal screening strategy was performed.
Carer reported experiences: supporting someone with a rare disease
Authors: McMullan Julie , Crowe Ashleen L. , Downes Kirsten , McAneney Helen , McKnight Amy Jayne
Published: July 2020

Background

The uniqueness and complexity of rare diseases, together with a perceived lack of understanding from health professionals, can make caring for someone with a rare disease extremely challenging. Carers are often forced to become ‘expert’ patients alongside people they care for. Due to the demands placed upon carers it is essential that appropriate support is available for them to ensure they can continue to carry out this vital role. This exploratory study researched challenges carers face when looking after someone with a rare disease and identify how they could be better supported in this role.

Methods

To be eligible to participate, respondents had to be adults caring for someone with a rare disease. Mixed methods were used including an online survey (n=57 respondents) where carers highlighted a need for better support specific to their mental health needs, liaising with health and social care professionals, financial, communication, training and respite options. During a facilitated workshop (n=32 attendees) discussions focused on challenges carers face as well as priorities to better support carer needs in the future.

Results

While carers reported several positive aspects of their caring role, the majority of comments highlighted challenges such as sub-optimal interactions with healthcare professionals, insufficient (or absent) emotional, psychological and social support, lack of financial support, and lack of awareness of existing support services.

Conclusion

It is important that strategies are put in place to ensure that carers take the time they need to care for themselves and raise awareness of available support options for carers of people with a rare disease(s) from health and social care providers, charities, or support groups.

Strengths and limitations of this study

This study provides insight into current challenges, and some requested solutions, based on reported experiences from carers of people with a rare disease in the UK and Ireland.

The use of an online survey promoted flexibility and accessibility for person’s unable to attend the in-person workshop

The facilitated workshop enabled carers to network, discussing challenges and potential solutions with their peers.

Responses in this exploratory study are based upon people who were self-motivated to participate.
Diaper need is associated with risk for food insecurity in a statewide sample of WIC participants
Authors: Belarmino Emily H. , Malinowski Amy , Flynn Karen
Published: July 2020

Diaper need is a form of material hardship that acutely affects families with young children, is not currently addressed by US antipoverty programs, and has received little public or scientific attention. This study examined the association between diaper need and risk for food insecurity in a statewide sample of participants in the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC). Families enrolled in Vermont WIC in August 2019 were invited to an online survey. Generalized linear models were used to estimate the relationship between risk for food insecurity measured by the Hunger Vital Sign tool and diaper need, with and without adjustment for household factors. Follow-up questions asked those with diaper need what they do when they run out of diapers and those without diaper need how they access enough diapers. Complete data were available for 501 households. Over half (52.3%) were at risk for food insecurity and nearly one-third (32.5%) reported diaper need. The odds of experiencing risk for food insecurity were 3.852 (95% CI=2.557, 5.803) times greater for families with diaper need than for families that had enough diapers. The association persisted with adjustment for location, age of respondent, number of children in diapers, and length of time participating in WIC (adjusted OR=4.036, 95% CI=2.645, 6.160). Strategies to avoid running out of diapers included borrowing, stretching supplies, switching to cloth or underwear, and buying on credit. It is possible that public health interventions that address diaper need may reduce food insecurity in households with children.
Diagnostic value of skin manifestation of SARS-CoV-2 infection
Authors: Bataille V. , Visconti A. , Rossi N. , Murray B. , Bournot A. , Wolf J. , Ourselin S. , Steves C. , Spector T.D. , Falchi M.
Published: July 2020

SARS-CoV-2 causes multiple immune-related reactions at various stages of the disease. The wide variety of skin presentations has delayed linking these to the virus. Previous studies had attempted to look at the prevalence and timing of SARS-COV-2 rashes but were based on mostly hospitalized severe cases and had little follow up. Using data collected on a subset of 336,847 eligible UK users of the COVID Symptom Study app, we observed that 8.8% of the swab positive cases (total: 2,021 subjects) reported either a body rash or an acral rash, compared to 5.4% of those with a negative swab test (total: 25,136). Together, these two skin presentations showed an odds ratio (OR) of 1.67 (95% confidence interval [CI]: 1.41-1.96) for being swab positive. Skin rashes were also predictive in the larger untested group of symptomatic app users (N=54,652), as 8.2% of those who had reported at least one classical COVID-19 symptom, i.e., fever, persistent cough, and/or anosmia, also reported a rash. Data from an independent online survey of 11,546 respondents with a rash showed that in 17% of swab positive cases, the rash was the initial presentation. Furthermore, in 21%, the rash was the only clinical sign. Skin rashes cluster with other COVID-19 symptoms, are predictive of a positive swab test and occur in a significant number of cases, either alone or before other classical symptoms. Recognising rashes is important in identifying new and earlier COVID-19 cases.
Addition of Tocilizumab to the standard of care reduces mortality in severe COVID-19: A systematic review and meta-analysis
Authors: Boregowda Umesha , Perisetti Abhilash , Nanjappa Arpitha , Gajendran Mahesh , Goyal Hemant
Published: July 2020

Introduction

Tocilizumab is an anti-interleukin-6 antibody that has been used for the treatment of severe coronavirus disease 2019 (COVID-19). However, the concrete evidence of its benefit in reducing the mortality in severe COVID-19 is lacking. Therefore, we performed a systematic review and meta-analysis of relevant studies that compared the efficacy of Tocilizumab in severe COVID-19 vs. standard of care alone.

Methods

Literature search for studies that compared ‘Tocilizumab’ and ‘Standard of care’ in the treatment of COVID-19 was done using major online databases from December 2019 to June 14th, 2020. Search words ‘ Tocilizumab,’ ‘anti-interleukin-6 antibody,’ and ‘COVID-19’ or ‘coronavirus 2019’ in various combinations were used. Articles in the form of abstracts, letters without original data, case reports, and reviews were excluded. Data was gathered on an excel sheet, and statistical analysis was performed using Review Manager 5.3.

Results

Sixteen studies were eligible from 693 initial studies, including 3,641 patients (64% males). There were thirteen retrospective studies and three prospective studies. There were 2,488 patients in the standard of care group (61.7%) and 1,153 patients (68.7%) in the Tocilizumab group. The death rate in the tocilizumab group, 22.4% (258/1153), was lower than the standard of care group, 26.21% (652/2,488) (Pooled odds ratio 0.57 [95% CI 0.36-0.92] p=0.02). There was a significant heterogeneity (Inconsistency index= 80%) among the included studies.

Conclusion

The addition of Tocilizumab to the standard of care might reduce the mortality in severe COVID-19. Larger randomized clinical trials are needed to validate these findings.
In-house modification and improvement of the CDC real-time PCR diagnostic assay for SARS-CoV-2 detection
Authors: Das Srirupa , Dowell-Martino Candice , Arrigo Lisa , Fiedler Paul N. , Lobo Sandra
Published: July 2020

The world is currently facing an unprecedented pandemic caused by the novel coronavirus SARS-CoV-2 (COVID-19) which was first reported in late 2019 by China to the World Health Organization (WHO). The containment strategy for COVID-19, which has non-specific flu-like symptoms and where upwards of 80% of the affected has either mild or no symptoms, is critically centered upon diagnostic testing, tracking and isolation. Thus, the development of specific and sensitive diagnostic tests for COVID-19 is key towards the first successful step of disease management. Public health organizations like the WHO and the US-based Centers for Disease Control and Prevention (CDC) have developed real-time PCR (RT-PCR) based diagnostic tests to aid in the detection of acute infection. In this study we sought to modify the CDC RT-PCR diagnostic assay protocol to increase its sensitivity and to make the assay directly portable to health care providers in a community-based hospital setting. A number of modifications to the original protocol were tested. Increasing the RT-PCR annealing temperature by 7°C to 62°C was associated with the most significant improvement in sensitivity, wherein the cycle-threshold (Ct) value for the N2 assay was reduced by ∼3 units, in effect both reducing the overall number of inconclusive results and yielding N1/N2 assays to have similar Ct values. The limit of detection of the modified assay was also improved (0.86 RNA copies/µl for both nCoV 2019_N1/N2 assays) compared to the CDC RT-PCR diagnostic assay (1 and 3.16 RNA copies/µl for nCoV 2019_N1 and N2 assay, respectively). Using this modification, there was no significant effect on SARS-CoV-2 detection rate when viral RNA extraction was performed either manually or through an automated extraction method. We believe this modified protocol allows for more sensitive detection of the virus which in turn will be useful for pandemic management.
Genetic associations for two biological age measures point to distinct aging phenotypes
Authors: Kuo Chia-Ling , Pilling Luke C. , Liu Zuyun , Atkins Janice L. , Levine Morgan E.
Published: July 2020

Biological age measures outperform chronological age in predicting various aging outcomes, yet little is known regarding genetic predisposition. We performed genome-wide association scans of two age-adjusted biological age measures (PhenoAgeAcceleration and BioAgeAcceleration), estimated from clinical biochemistry markers1,2 in European-descent participants from UK Biobank. The strongest signals were found in the APOE gene, tagged by the two major protein-coding SNPs, PhenoAgeAccel—rs429358 (APOE e4 determinant) (p=1.50×10−72); BioAgeAccel—rs7412 (APOE e2 determinant) (p=3.16×10−60). Interestingly, we observed inverse APOE e2 and e4 associations and unique pathway enrichments when comparing the two biological age measures. Genes associated with BioAgeAccel were enriched in lipid related pathways, while genes associated with PhenoAgeAccel showed enrichment for immune system, cell function, and carbohydrate homeostasis pathways, suggesting the two measures capture different aging domains. Our study reaffirms that aging patterns are heterogenous across individuals, and the manner in which a person ages may be partly attributed to genetic predisposition.
Commercial Serology Assays Predict Neutralization Activity Against SARS-CoV-2
Authors: Suhandynata Raymond T. , Hoffman Melissa A. , Huang Deli , Tran Jenny T. , Kelner Michael J. , Reed Sharon L. , McLawhon Ronald W. , Voss James E. , Nemazee David , Fitzgerald Robert L.
Published: July 2020

Background

Currently it is unknown whether a positive serology results correlates with protective immunity against SARS-CoV-2. There are also concerns regarding the low positive predictive value of SARS-CoV-2 serology tests, especially when testing populations with low disease prevalence.

Methods

A neutralization assay was validated in a set of PCR confirmed positive specimens and in a negative cohort. 9,530 specimens were screened using the Diazyme SARS-CoV-2 IgG serology assay and all positive results (N=164) were reanalyzed using the neutralization assay, the Roche total immunoglobin assay, and the Abbott IgG assay. The relationship between the magnitude of a positive SARS-CoV-2 serology result and the levels of neutralizing antibodies detected was correlated. Neutralizing antibody titers (ID50) were also longitudinally monitored in SARS-CoV-2 PCR confirmed patients.

Results

The SARS-CoV-2 neutralization assay had a PPA of 96.6% with a SARS-CoV-2 PCR test and a NPA of 98.0% across 100 negative controls. ID50 neutralization titers positively correlated with all three clinical serology platforms. Longitudinal monitoring of hospitalized PCR confirmed COVID-19 patients demonstrates they made high neutralization titers against SARS-CoV-2. PPA between the Diazyme IgG assay alone and the neutralization assay was 50.6%, while combining the Diazyme IgG assay with either the Roche or Abbott platforms increased the PPA to 79.2% and 78.4%, respectively.

Conclusions

For the first time, we demonstrate that three widely available clinical serology assays positively correlate with SARS-CoV-2 neutralization activity observed in COVID-19 patients. When a two-platform screen and confirm approach was used for SARS-CoV-2 serology, nearly 80% of two-platform positive specimens had neutralization titers (ID50 >50).

Clinical performance of a SARS-CoV-2 neutralization assay was evaluated using SARS-CoV-2 PCR confirmed patients and SARS-CoV-2 negative individuals. The neutralization assay was compared with results from SARS-CoV-2 positive serology specimens. We demonstrate that positive SARS-CoV-2 serology results correlate with the presence of neutralization activity against SARS-CoV-2. We show a high false positive rate when using a single SARS-CoV-2 serology platform to screen populations with low disease prevalence; and confirm that using a two-platform approach for COVID-19 seropositives greatly improves positive predictive value for neutralization.
Association of Cancer with Risk and Mortality of COVID-19: Results from the UK Biobank
Authors: Shi Zhuqing , Resurreccion W. Kyle , Wang Chi-Hsiung , Wei Jun , Na Rong , Zheng S. Lilly , Billings Liana K. , Helfand Brian T. , Khandekar Janardan , Xu Jianfeng
Published: July 2020

Although cancer has been associated with COVID-19 risk and mortality in hospital-based studies, few population-based studies have been reported. Utilizing data from the UK Biobank (UKB), a population-based prospective cohort, we formally tested the association of over 44 different types of cancer with COVID-19 infection and mortality among 7,661 subjects who were tested by June 17, 2020. Compared to non-cancer subjects, cancer subjects (N=1,521) had significantly lower overall risk for COVID-19 infection [odds ratio (OR) and 95% confidence interval (CI): 0.79 (0.68-0.92), P=2.60E-03]. However, a trend of higher risk for COVID-19 mortality was found among 256 COVID-19 positive cancer patients, especially for hematologic cancers such as non-Hodgkin lymphoma [3.82 (1.17-12.01), P=0.02]. In cancer patients, while few demographic, lifestyle, genetic and comorbidity factors predicted risk for COVID-19 infection, older age, male sex, heart disease and hypertension significantly predicted COVID-19 mortality. The lower risk for COVID-19 infection is likely due to extra caution in COVID-19 prevention and more testing among cancer patients, an encouraging finding that demonstrates the feasibility of intervention. These results, if confirmed in future releases of UKB data and other independent populations, may provide guidance for COVID-19 prevention and treatment among cancer patients.
Perceived preparedness to respond to the COVID-19 pandemic: A study with healthcare workers in Ghana
Authors: Afulani Patience A. , Gyamerah Akua O. , Aborigo Raymond , Nutor Jerry John , Malechi Hawa , Laar Amos , Sterling Mona , Awoonor-Williams John Koku
Published: July 2020

Introduction

Healthcare workers’ (HCWs) preparedness to respond to pandemics is critical to containing disease spread. Low-resource countries, however, experience barriers to preparedness due to limited resources. In Ghana, a country with a constrained healthcare system and high COVID-19 cases, we examined HCWs’ perceived preparedness to respond to COVID-19 and associated factors.

Methods

472 HCWs completed questions in a cross-sectional self-administered online survey. Perceived preparedness was assessed using a 15-question scale (Cronbach alpha=0.91) and summative scores were created (range=0-45). Higher scores meant greater perceived preparedness. We used linear regression with robust standard errors to examine associations between perceived preparedness and potential predictors.

Results

The average preparedness score was 24 (SD=8.9); 27.8% of HCWs felt prepared. In multivariate analysis, factors associated with higher perceived preparedness were: training (β=3.35, 95%CI: to 4.69); having adequate PPE (β=2.27, 95%CI: 0.26 to 4.29), an isolation ward (β=2.74, 95%CI: 1.15 to 4.33), and protocols for screening (β=2.76, 95%CI: 0.95 to 4.58); and good perceived communication from management (β=5.37, 95%CI: 4.03 to 7.90). When added to the model, perceived knowledge decreased the effect of training by 28.0%, although training remained significant, suggesting a partial mediating role. Perceived knowledge was associated with a 6-point increase in perceived preparedness score (β=6.04, 95%CI: 4.19 to 7.90).

Conclusion

HCWs reported low perceived preparedness to respond to COVID-19. Training, clear protocols, PPE availability, isolation wards, and communication play an important role in increasing preparedness. Government stakeholders must institute necessary interventions to increase HCWs’ preparedness to respond to the ongoing pandemic and prepare for future pandemics.

Strengths and limitations of this study

This is one of the few studies globally to empirically examine Healthcare workers’ (HCWs) perceived preparedness to respond to COVID-19, and the first study to do so among HCWs in Ghana and in Africa.

We developed a perceived preparedness for COVID-19 scale and conducted psychometric analysis to confirm its validity and reliability; this scale can facilitate similar research in other settings.

We show that providers have low perceived preparedness to respond to the COVID-19 pandemic, and that this is associated with a lack of training on COVID-19, PPE, clear protocols, and isolation wards, as well as poor communication from management.

The use of an online survey with recruitment via social media may have accounted for a relatively young sample.

Findings are based on self-reported data from a cross-sectional survey, thus, there may be social desirability bias and associations described are not causal.
Epidemiological characteristics of COVID-19 patients in Samarinda, East Kalimantan, Indonesia
Authors: Paramita Swandari , Isnuwardana Ronny , Rahmadi Anton , Rafshodia Osa , Kusasih Ismid
Published: July 2020

Introduction

Coronavirus Disease (COVID-19) is caused by SARS-CoV-2 infection. Indonesia announced the first COVID-19 case on 2 March 2020. East Kalimantan has been determined as the new capital of Indonesia since 2019. This makes Samarinda as the capital of East Kalimantan has been focused for its capability of handling COVID-19 patients. We report the epidemiological characteristics and immunofluorescence assay results of these patients.

Methods

All patients with positive confirmed COVID-19 by RT-PCR were admitted to hospitals and quarantine center in Samarinda. We retrospectively analyzed data from the daily report of the Samarinda City and East Kalimantan Health Office information system.

Results

By June 25, 2020, 64 patients had been identified as having positive confirmed COVID-19. The mean age of the patients was 37.3 ± 13.8 years. Most of the patients were men (57 [90.6%] patients). Thirty-nine COVID-19 patients were imported cases with a history of traveling from South Sulawesi. Most of the patients were admitted to the Quarantine Center of Samarinda City. The mean duration from the first hospital admission for isolation to discharge was 25.6 ± 13.1 days. There was only one death case of COVID-19 patients in Samarinda. There were the highest confirmed cases of COVID-19 in Samarinda in early June 2020. There was a declining trend in the age of COVID-19 patients and the duration of isolation time in the hospital.

Discussion

Imported cases still contributed to the increase of COVID-19 cases in Samarinda. Younger age of COVID-19 patients was more involved in frequent mobility which makes them cause the spread of the disease. Activation of the national reference laboratory for the COVID-19 examination in Samarinda has reduced the length of time patients treated in hospitals.

Conclusion

The epidemiological characteristics of COVID-19 patients show the ability of local governments to deal with this pandemic. This can be seen from the low case fatality rate in Samarinda.
Surface area-to-volume ratio, not cellular rigidity, determines red blood cell traversal through small capillaries
Authors: Namvar Arman , Blanch Adam J. , Dixon Matthew W. , Carmo Olivia M. S. , Liu Boyin , Tiash Snigdha , Looker Oliver , Andrew Dean , Chan Li-Jin , Tham Wai-Hong , Lee Peter V. S. , Rajagopal Vijay , Tilley Leann
Published: July 2020

The remarkable deformability of red blood cells (RBCs) depends on the viscoelasticity of the plasma membrane and cell contents and the surface area to volume (SA:V) ratio; however, it remains unclear which of these factors is the key determinant for passage through small capillaries. We used a microfluidic device to examine the traversal of normal, stiffened, swollen, parasitised and immature RBCs. We show that dramatic stiffening of RBCs had no measurable effect on their ability to traverse small channels. By contrast, a moderate decrease in the SA:V ratio had a marked effect on the equivalent cylinder diameter that is traversable by RBCs of similar stiffness. We developed a finite element model that provides a coherent rationale for the experimental observations, based on the nonlinear mechanical behaviour of the RBC membrane skeleton. We conclude that the SA:V ratio should be given more prominence in studies of RBC pathologies.
Single-cell analysis of mosquito hemocytes identifies signatures of immune cell subtypes and cell differentiation
Authors: Kwon Hyeogsun , Mohammed Mubasher , Franzén Oscar , Ankarklev Johan , Smith Ryan C.
Published: July 2020

Mosquito immune cells, known as hemocytes, are integral to cellular and humoral responses that limit pathogen survival and mediate immune priming. However, without reliable cell markers and genetic tools, studies of mosquito immune cells have been limited to morphological observations, leaving several aspects of their biology uncharacterized. Here, we use single-cell RNA sequencing (scRNA-seq) to characterize mosquito immune cells, demonstrating an increased complexity to previously defined prohemocyte, oenocytoid, and granulocyte subtypes. Through functional assays relying on phagocytosis, phagocyte depletion, and RNA-FISH experiments, we define markers to accurately distinguish immune cell subtypes and provide evidence for immune cell maturation and differentiation. In addition, gene-silencing experiments demonstrate the importance of lozenge in defining the mosquito oenocytoid cell fate. Together, our scRNA-seq analysis provides an important foundation for studies of mosquito immune cell biology and a valuable resource for comparative invertebrate immunology.
Lymphatic type-1 interferon responses are critical for control of systemic reovirus dissemination
Authors: Phillips Matthew B. , Zita Marcelle Dina , Howells Morgan A. , Weinkopff Tiffany , Boehme Karl W.
Published: July 2020

Mammalian orthoreovirus (reovirus) spreads from the site of infection to every organ system in the body via the blood. However, mechanisms that underlie reovirus hematogenous spread remain undefined. Non-structural protein σ1s is a critical determinant of reovirus bloodstream dissemination that is required for efficient viral replication in many types of cultured cells. Here, we used the specificity of the σ1s protein for promoting hematogenous spread as a platform to uncover a role for lymphatic type-1 interferon (IFN-1) responses in limiting reovirus systemic dissemination. We found that replication of a σ1s-deficient reovirus was restored to wild-type levels in cells with defective type-1 interferon a-receptor (IFNAR1) signaling.In vivo, reovirus spreads systemically following oral inoculation of neonatal mice, whereas the σ1s-null virus remains localized to the intestine. We found that σ1s enables reovirus spread in the presence of a functional IFN-1 response, as the σ1s-deficient reovirus disseminated comparably to wild-type virus in IFNAR1-/-mice. Lymphatics are hypothesized to mediate reovirus spread from the intestine to the bloodstream. IFNAR1 deletion from cells expressing lymphatic vessel endothelium receptor-1 (LYVE-1), a marker for lymphatic endothelial cells, enabled the σ1s-deficient reovirus to disseminate systemically. Together, our findings indicate that IFN-1 responses in lymphatics limit reovirus dissemination. Our data further suggest that the lymphatics are an important conduit for reovirus hematogenous spread.

IMPORTANCE

Type-1 interferon (IFN-1) responses are a critical component of the host response to viral infections. However, the contribution of specific cell and tissue types to control of viral infections is not known. Here, we found that reoviruses lacking nonstructural protein were more sensitive to IFN-1 responses than wild-type reovirus, indicating that σ1s is important for reovirus resistance to IFN-1 responses. The σ1s protein also is a key determinant of reovirus systemic spread. We used tissue-specific IFNAR1 deletion in combination with the IFN-1-sensitive σ1s-null reovirus as a tool to identify a role for lymphatics in reovirus dissemination. We used Cre-lox technology to delete type-1 interferon a-receptor (IFNAR1) in lymphatic cells and found that the IFN-1-sensitive σ1s-deficient reovirus disseminated in mice with lymphatic endothelial cells-specific deletion of IFNAR1. Together, our results indicate that IFN-1 responses in lymphatics are critical for controlling reovirus systemic spread.
Deterministic and stochastic rules of branching govern dendritic morphogenesis of sensory neurons
Authors: Palavalli Amrutha , Tizón-Escamilla Nicolás , Rupprecht Jean-François , Lecuit Thomas
Published: July 2020

Dendrite morphology is necessary for the correct integration of inputs that neurons receive. The branching mechanisms allowing neurons to acquire their type-specific morphology remain unclear. Classically, axon and dendrite patterns were shown to be guided by molecules providing deterministic cues. However, the extent to which deterministic and stochastic mechanisms, based upon purely statistical bias, contribute to the emergence of dendrite shape is largely unknown. We address this issue using theDrosophilaclass I vpda multi-dendritic neurons. Detailed quantitative analysis of vpda dendrite morphogenesis indicates that the primary branch grows very robustly in a fixed direction while secondary branch numbers and lengths showed fluctuations characteristic of stochastic systems. Live tracking dendrites and computational modeling revealed how neuron shape emerges from few local statistical parameters of branch dynamics. We report key opposing aspects of how tree architecture feedbacks on the local probability of branch shrinkage. Child branches promote stabilization of parent branches while self-repulsion promotes shrinkage. Finally, we show that self-repulsion, mediated by the adhesion molecule Dscam1, indirectly patterns the growth of secondary branches by spatially restricting their direction of stable growth perpendicular to the primary branch. Thus, the stochastic nature of secondary branch dynamics and the existence of geometric feedback emphasizes the importance of self-organization in neuronal dendrite morphogenesis.
Ferroptosis response segregates small cell lung cancer (SCLC) neuroendocrine subtypes
Authors: Bebber Christina M. , Thomas Emily S. , Chen Zhiyi , Stroh Jenny , Androulidaki Ariadne , Schmitt Anna , Höhne Michaela N. , Stüker Lukas , de Pádua Alves Cleidson , Khonsari Armin , Dammert Marcel A. , Parmaksiz Fatma , Beleggia Filippo , Sos Martin L. , Riemer Jan , George Julie , Brodesser Susanne , Thomas Roman K. , Reinhardt H. Christian , von Karstedt Silvia
Published: July 2020

Bi-allelic loss ofTP53andRB1in treatment-naïve small cell lung cancer (SCLC) suggests strong selective pressure to inactivate regulated cell death pathways prior to therapy. Yet, which regulated cell death pathways remain available in treatment-naïve SCLC is unknown. Here, through systemic analysis of cell death pathway availability, we identify non-neuroendocrine (NE) and NE SCLC subtypes to segregate by their response to ferroptosis, a recently described iron-dependent type of regulated necrosis. While we identify that in treatment-naïve SCLC extrinsic apoptosis and necroptosis are incapacitated, we find non-NE SCLC to be exquisitely sensitive to ferroptosis induced through pharmacological and genetic means. Mechanistically, non-NE SCLC as opposed to NE SCLC presents with an oxygenated lipidome priming non-NE SCLC for ferroptosis. ASCL1+ NE SCLC, in turn, is resistant to ferroptosis but acquires selective addiction to the thioredoxin (TRX) anti-oxidant pathway. Importantly, co-cultures mimicking non-NE/NE intratumoral heterogeneity selectively deplete non-NE populations upon induction of ferroptosis while eliminating NE cell populations only upon TRX pathway. As a consequence, combined induction of ferroptosis and inhibition of the TRX pathway broadly kills established non-NE and NE tumors in xenografts and genetically engineered mouse models of SCLC. Moreover, patient-derived treatment-naïve and refractory NE SCLC models are selectively killed via this regime. In SCLC, combined low expression of GPX4 and TRX reductase 1 (TXNRD1) identifies a patient subset with drastically improved overall survival. These data identify ferroptosis as an SCLC subtype-specific vulnerability and suggest repurposing ferroptosis induction with TRX pathway inhibition to specifically address intratumoral NE/non-NE heterogeneity in SCLC.

One Sentence Summary

The SCLC non-neuroendocrine subtype is sensitive to ferroptosis
Evolutionary responses to codon usage of horizontally transferred genes inPseudomonas aeruginosa
Authors: Callens Martijn , Scornavacca Celine , Bedhomme Stéphanie
Published: July 2020

Prokaryote genome evolution is characterized by the frequent gain of genes through horizontal gene transfer (HGT). For a gene, being horizontally transferred can represent a strong change in its genomic and physiological context. If the codon usage of a transferred gene deviates from that of the receiving organism, the fitness benefits it provides can be reduced due to a mismatch with the expression machinery. Consequently, transferred genes with a deviating codon usage can be selected against or elicit evolutionary responses that enhance their integration. In this study, a comparative genomics approach was used to investigate evolutionary responses after the horizontal transfer of genes with diverse degrees of codon usage mismatch inPseudomonas aeruginosa. Selection on codon usage of genes acquired through HGT was observed, with the overall codon usage converging towards that of the core genome over evolutionary time. This pattern seemed to be mainly driven by selective retention of transferred genes with an initial codon usage similar to that of the core genes. Gene amelioration, through the accumulation of synonymous mutations after HGT, did not seem to systematically affect transferred genes. Additionally, variation in the copy number of tRNA genes was often associated with the acquisition of genes for which the observed variation could enhance their expression. This provides evidence that compensatory evolution might be an important mechanism for the integration of horizontally transferred genes.
Disruption of a Hedgehog-Foxf1-Rspo2 Signaling Axis Leads to Tracheomalacia and a Loss of Sox9+ Tracheal Chondrocytes
Authors: Nasr Talia , Chaturvedi Praneet , Agarwal Kunal , Kinney Jessica L. , Daniels Keziah , Trisno Stephen L. , Ustiyan Vladimir , Shannon John M. , Wells James M. , Sinner Debora , Kalinichenko Vladimir V. , Zorn Aaron M.
Published: July 2020

Congenital tracheomalacia, resulting from incomplete tracheal cartilage development, is a relatively common birth defect that severely impairs breathing in neonates. Mutations in the Hedgehog (HH) pathway and downstream Gli transcription factors are associated with tracheomalacia in patients and mouse models; however, the underlying molecular mechanisms are unclear. Using multipleHH/Glimouse mutants including one that mimics Pallister-Hall Syndrome, we show that excessive Gli repressor activity prevents specification of tracheal chondrocytes. Lineage tracing experiments show that Sox9+ chondrocytes arise from HH-responsive splanchnic mesoderm in the fetal foregut that expresses the transcription factor Foxf1. Disrupted HH/Gli signaling results in 1) loss of Foxf1 which in turn is required to support Sox9+ chondrocyte progenitors and 2) a dramatic reduction inRspo2, a secreted ligand that potentiates Wnt signaling known to be required for chondrogenesis. These results reveal a HH-Foxf1-Rspo2 signaling axis that governs tracheal cartilage development and informs the etiology of tracheomalacia.

SUMMARY STATEMENT

This work provides a mechanistic basis for tracheomalacia in patients with Hedgehog pathway mutations.
EGF signaling in bowel carcinoma cells utilizes higher order architectures of EGFR and HER2
Authors: Wollman Adam J. M. , Fournier Charlotte , Llorente-Garcia Isabel , Harriman Oliver , Hargreaves Alex L. , Shashkova Sviatlana , Zhou Peng , Liu Ta-Chun , Ouaret Djamila , Wilding Jenny , Kusumi Akihiro , Bodmer Walter , Leake Mark C.
Published: July 2020

Epidermal growth factor (EGF) signaling regulates normal cell development, however EGF receptor (EGFR) overexpression is reported in several carcinomas. Despite structural and biochemical evidence that EGF-EGFR ligation activates signaling through monomer-dimer transitions, live cell mechanistic details remain contentious. We report single-molecule multispectral TIRF of human epithelial carcinoma cells transfected with fluorescent EGFR, and of CHO-K1 cells containing fluorescent EGFR and HER2, enabling super-resolved localization to quantify receptor architectures and spatiotemporal dynamics upon EGF ligation. Using inhibitors that block binding to EGFR, and time-dependent kinetics modelling, we find that pre-activated EGFR consist predominantly of preformed clusters that contain a mixture of EGFR and HER2, whose stoichiometry increases following EGF activation. Although complicated by EGFR internalization and recycling, our observation of an EGFR:EGF stoichiometry >1 for plasma membrane colocalized EGFR/EGF foci soon after activation may indicate preferential binding of EGF ligand to EGFR monomers, negative cooperativity and preferential ligated-unligated dimerization of monomers.
Viscoelastic relaxation of collagen networks provides a self-generated directional cue during collective migration
Authors: Clark Andrew G. , Maitra Ananyo , Jacques Cécile , Simon Anthony , Pérez-González Carlos , Trepat Xavier , Voituriez Raphaël , Vignjevic Danijela Matic
Published: July 2020

There is growing evidence that the physical properties of the cellular environment can impact cell migration. However, it is not currently understood how active physical remodeling of the network by cells affects their migration dynamics. Here, we study collective migration of small clusters of cells on deformable collagen-1 networks. Combining theory and experiments, we find that cell clusters, despite displaying no apparent internal polarity, migrate persistently and generate asymmetric collagen gradients during migration. We find that persistent migration can arise from viscoelastic relaxation of collagen networks, and reducing the viscoelastic relaxation time by chemical crosslinking leads to a reduction in migration persistence. Single cells produce only short range network deformations that relax on shorter timescales, which leads to lower migration persistence. This physical model provides a mechanism for self-generated directional migration on viscoelastic substrates in the absence of internal biochemical cues.