title: "We felt like part of a production system": a qualitative study on women's experience of mistreatment during childbirth in Switzerland

abstract:
IntroductionMistreatment during childbirth is an issue of global magnitude that not only violates fundamental human rights but also seriously impacts womens well-being. The purpose of this study was to gain a better understanding of the phenomenon by exploring the individual experiences of women who reported mistreatment during childbirth in Switzerland.

Materials and MethodsThis project used a mixed methods approach to investigate womens experiences of mistreatment during childbirth in general and informal coercion specifically: the present qualitative study expands on the findings from a nationwide online survey on childbirth experience. It combines inductive with theory-guided thematic analysis to study the 7753 comments women wrote in the survey and the subsequent interviews with 11 women who reported being mistreated during childbirth.

ResultsThe women described a wide range of experiences of mistreatment during childbirth in both the survey comments and the interviews. Out of all survey participants who wrote at least one comment (n = 3547), 28% described one or more experiences of mistreatment. Six of the seven types of mistreatment listed in Bohren and colleagues typology of mistreatment during childbirth were found, the most frequent of which were ineffective communication and lack of informed consent. Five further themes were identified in the interviews: informal coercion, risk factors for mistreatment, consequences of mistreatment, examples of good care, and whats needed to improve maternity care.

ConclusionThe findings from this study show that experiences of mistreatment are a reality in Swiss maternity care and give insight into womens individual experiences as well as how these affect them during and after childbirth. This study emphasises the need to respect womens autonomy in order to prevent mistreatment and empower women to actively participate in decisions. Both individual and systemic efforts are required to prevent mistreatment and guarantee respectful, dignified, and high-quality maternity care for all.

category: obstetrics and gynecology


title: Systematic review of Economic studies of Partner Notification and management interventions for sexually transmitted infections including HIV in men who have sex with men

abstract:
ObjectivesMen who have sex with men (MSM) are disproportionately affected by sexually transmitted infections (STIs). Partner notification (PN) to identify, test and treat sex partners of MSM with bacterial STIs is challenging because MSM often report larger numbers of sex partners and a higher proportion of one-off partners who may be difficult to engage. However, one-off partners contribute disproportionately to onward transmission. Economic research on PN has typically focused on heterosexual people and evidence of effectiveness of PN in MSM is scant. We conducted a systematic review of economic studies of PN interventions in MSM to inform the development of a novel PN intervention for MSM with one-off partners.

MethodSix electronic databases were searched up to June 2020. Cost studies and full economic evaluations, which focused on PN and/or testing and treatment (in the context of PN) of sex partners of MSM with STIs, and/or HIV, were included. A two-stage categorisation process was used for study selection and a narrative synthesis was reported.

ResultsTwenty-six studies of a possible 1909 met the selection criteria. Sixteen focused on MSM but only three of these were on PN. Few studies reported on patients characteristics and settings. Most studies were cost-utility analyses with outcomes reported as quality-adjusted life years (QALYs) which were derived from studies on heterosexual people.

ConclusionsNone of the identified studies specifically addressed cost-effectiveness of PN in MSM. The few studies identified as potentially relevant relied on costs and QALYs data from studies in heterosexual people, which may be inappropriate given the different patterns of sexual partnerships reported by these two groups. The lack of evidence on efficient PN approaches for MSM, a group with a high burden of infection, supports the need for new interventions tailored to the needs and preferences of MSM with parallel economic evaluation.

category: health economics


title: Health-related quality of life of female sex workers living with HIV in South Africa

abstract:
IntroductionHealth-related quality of life (HRQoL) is an important HIV outcome beyond viral suppression. However, there are limited data characterizing HRQoL of key populations including female sex workers (FSW) living with HIV.

MethodsWe used baseline data (June 22, 2018-March 23, 2020) of FSW who were diagnosed with HIV and enrolled into a randomized trial in Durban, South Africa. HRQoL information was collected by a generic preference-accompanied tool with five domains (EQ-5D), and summarized into a single score (range 0-1) which represents health utility. We employed multivariable beta regression models to identify determinants of HRQoL and to estimate subgroup-specific HRQoL score. Using external estimates of life expectancy and population size, we estimated the number of quality adjusted life years reduced among FSW living with HIV in South Africa associated with violence and drug use.

ResultsOf 1363 individuals (mean age: 32.4 years; mean HRQoL score: 0.857) in our analysis, 62.6% used drugs, 61.3% experienced physical or sexual violence, and 64.6% self-reported taking antiretroviral treatment (ART). The following were associated with a reduction in the average marginal HRQoL score: older age (per decade: 0.018 [95% confidence interval (CI): 0.008, 0.027]), drug use (0.022 [0.007, 0.036]), experience of violence (0.024 [0.010, 0.038]), and moderate (vs. no) level of internalized stigma (0.023 [0.004, 0.041]). Current ART use was associated with a 0.015-point (-0.001, 0.031) increase in the HRQoL score. The estimated mean (95%CI) HRQoL scores ranged from 0.838 (0.816, 0.860) for FSW who used drugs, experienced violence, and were not on ART; to 0.899 (0.883, 0.916) for FSW who did not use drugs nor experience violence and were on ART. Our results can be translated into a reduction in 37,184 and 39,722 quality adjusted life years related to drug use and experience of violence, respectively in South Africa.

ConclusionsThese results demonstrate the association of ART with higher HRQoL among FSW and the need to further address structural risks including drug use, violence, and stigma. Population-specific estimates of HRQoL score can be further used to calculate quality-adjusted life years in economic evaluations of individual and structural interventions addressing the needs of FSW living with HIV.

Clinical Trial RegistrationNCT03500172 (April 17, 2018)

category: hiv aids


title: Health-related quality of life of female sex workers living with HIV in South Africa: a cross-sectional study


title: Antibody longevity and cross-neutralizing activity following SARS-CoV-2 wave 1 and B.1.1.7 infections

abstract: As SARS-CoV-2 variants continue to emerge globally, a major challenge for COVID-19 vaccination is the generation of a durable antibody response with cross-neutralizing activity against both current and newly emerging viral variants. Cross-neutralizing activity against major variants of concern (B.1.1.7, P.1 and B.1.351) has been observed following vaccination, albeit at a reduced potency, but whether vaccines based on the Spike glycoprotein of these viral variants will produce a superior cross-neutralizing antibody response has not been fully investigated. Here, we used sera from individuals infected in wave 1 in the UK to study the long-term cross-neutralization up to 10 months post onset of symptoms (POS), as well as sera from individuals infected with the B.1.1.7 variant to compare cross-neutralizing activity profiles. We show that neutralizing antibodies with cross-neutralizing activity can be detected from wave 1 up to 10 months POS. Although neutralization of B.1.1.7 and B.1.351 is lower, the difference in neutralization potency decreases at later timepoints suggesting continued antibody maturation and improved tolerance to Spike mutations. Interestingly, we found that B.1.1.7 infection also generates a cross-neutralizing antibody response, which, although still less potent against B.1.351, can neutralize parental wave 1 virus to a similar degree as B.1.1.7. These findings have implications for the optimization of vaccines that protect against newly emerging viral variants.

category: infectious diseases


title: Altered neutrophil phenotype and function in non-ICU COVID-19 patients correlated with disease severity

abstract:
RationalInfection with the SARS-CoV2 virus is associated with elevated neutrophil counts. Evidence of neutrophil dysfunction in COVID-19 is based predominantly on transcriptomics or single functional assays. Cell functions are interwoven pathways, and so understanding the effect of COVID-19 across the spectrum of neutrophil function may identify tractable therapeutic targets.

ObjectivesExamine neutrophil phenotype and functional capacity in COVID-19 patients versus age-matched controls (AMC)

MethodsIsolated neutrophils from 41 hospitalised, non-ICU COVID-19 patients and 23 AMC underwent ex vivo analyses for migration, bacterial phagocytosis, ROS generation, NET formation (NETosis) and cell surface receptor expression. DNAse 1 activity was measured, alongside circulating levels of cfDNA, MPO, VEGF, IL-6 and sTNFRI. All measurements were correlated to clinical outcome. Serial sampling on day 3-5 post hospitalisation were also measured.

ResultsCompared to AMC, COVID-19 neutrophils demonstrated elevated transmigration (p=0.0397) and NETosis (p=0.0366), but impaired phagocytosis (p=0.0236) associated with impaired ROS generation (p<0.0001). Surface expression of CD54 (p<0.0001) and CD11c (p=0.0008) was significantly increased and CD11b significantly decreased (p=0.0229) on COVID-19 patient neutrophils. COVID-19 patients showed increased systemic markers of NETosis including increased cfDNA (p=0.0153) and impaired DNAse activity (p<0.0.001). MPO (p<0.0001), VEGF (p<0.0001), TNFRI (p<0.0001) and IL-6 (p=0.009) were elevated in COVID-19, which positively correlated with disease severity by 4C score.

ConclusionCOVID-19 is associated with neutrophil dysfunction across all main effector functions, with altered phenotype, elevated migration, impaired antimicrobial responses and elevated NETosis. These changes represent a clear mechanism for tissue damage and highlight that targeting neutrophil function may help modulate COVID-19 severity.

category: intensive care and critical care medicine


title: Recognition and inhibition of SARS-CoV-2 by humoral innate immunity pattern recognition molecules

abstract: The humoral arm of innate immunity includes diverse molecules with antibody-like functions, some of which serve as disease severity biomarkers in COVID-19. The present study was designed to conduct a systematic investigation of the interaction of humoral fluid phase pattern recognition molecules (PRM) with SARS-CoV-2. Out of 10 PRM tested, the long pentraxin PTX3 and Mannose Binding Lectin (MBL) bound the viral Nucleoprotein and Spike, respectively. MBL bound trimeric Spike, including that of variants of concern, in a glycan- dependent way and inhibited SARS-CoV-2 in three in vitro models. Moreover, upon binding to Spike, MBL activated the lectin pathway of complement activation. Genetic polymorphisms at the MBL locus were associated with disease severity. These results suggest that selected humoral fluid phase PRM can play an important role in resistance to, and pathogenesis of, COVID-19, a finding with translational implications.

category: allergy and immunology


title: A Cross-sectional Study of Clinical COVID-19 Myocarditis

abstract:
BackgroundCOVID-19 myocarditis is becoming increasingly appreciated as a complication of COVID-19. There are significant hurdles to formal diagnosis with endomyocardial biopsy or cardiac MRI whether by resource limitations, patient instability, or isolation precautions. Therefore, further exploratory analysis is needed to clinically define the characteristics and spectrum of severity of COVID-19 myocarditis.

ObjectivesThe aim of this study was to describe the clinical course, echocardiographic, and laboratory testing across suspected fulminant and non-fulminant clinically defined COVID-19 myocarditis.

MethodsIn a cross-sectional observational study of 19 patients with clinically defined COVID-19 myocarditis, we report presenting symptoms, clinical course, laboratory findings, and echocardiographic results stratified by non-fulminant and fulminant myocarditis. Student t-test and univariate logistic regression are used to compare laboratory findings across fulminant and non-fulminant cases.

FindingsAmong 19 patients, there was no prior history of coronary artery disease, atrial fibrillation, or heart failure; 21.1% of patients died; and 78.9% of cases required supplemental oxygen. A significantly higher geometric mean D-dimer and ferritin were observed in patients with fulminant compared to non-fulminant suspected myocarditis. 26.3% of cases had pericardial effusions. 10 out of the 16 with available echocardiographic data had normal left ventricular systolic function.

ConclusionsIn this cross-sectional analysis, we provide a practical clinical depiction of patients with clinical COVID-19 myocarditis across fulminant and non-fulminant cases. Statistically significant elevations in inflammatory markers in fulminant versus non-fulminant cases generate hypothesis regarding the role of systemic inflammation in driving severity of COVID-19 myocarditis.

category: cardiovascular medicine


title: Seroprevalence of SARS-CoV-2 Antibodies Among Rural Healthcare Workers

abstract: The objective of this longitudinal cohort study was to determine the seroprevalence of antibodies to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in healthcare workers employed at healthcare clinics in three rural counties in eastern South Dakota and western Minnesota from May 13, 2020 through December 22, 2020. Three blood draws were performed at five clinical sites and tested for the presence of antibodies against the SARS-CoV-2 virus. Serum samples were tested for the presence of antibodies using a fluorescent microsphere immunoassay (FMIA), neutralization of SARS-CoV-2 Spike-pseudotyped particles (SARS-CoV-2pp) assay, and serum virus neutralization (SVN) assay. The seroprevalence was determined to be 1/336 (0.29%) for samples collected from 5/13/20-7/13/20, 5/260 (1.92%) for samples collected from 8/13/20-9/25/20, and 35/235 (14.89%) for samples collected from 10/16/20-12/22/20. Eight of the 35 (22.8%) seropositive individuals identified in the final draw did not report a previous diagnosis with COVID-19. There was a high correlation (>90%) among the FMIA and virus neutralization assays. Each clinical sites seroprevalence was higher than the cumulative incidence for the general public in each respective county as reported by state public health agencies. As of December 2020, there was a high percentage (85%) of seronegative individuals in the study population.

category: epidemiology


title: Establishing the causal role of intimate partner violence and abuse on depressive symptoms in young adults: a population-based cohort study

abstract:
BackgroundPrevious studies have shown an association between experience of intimate partner violence and abuse (IPVA) and depression. Whether this is a causal relationship or explained by prior vulnerability that influences the risk of both depression and IPVA is not known.

Methods and FindingsWe analysed data from the Avon Longitudinal Study of Parents and Children prospective cohort (N=1,764 women, 1,028 men). To assess the causal association between IPVA at 18-21 years old and logged depressive symptom scores at age 23, we used: i) multivariable linear regression, ii) inverse probability of treatment weighting (IPTW), and iii) difference-in-difference (DID) analysis, which compared the mean change in logged depressive symptom scores between ages 16 and 23 between those who experienced IPVA and those who did not.

Women who experienced IPVA had on average 26% higher depressive symptom score after adjustment for measured confounders (ratio of geometric means 1.26, 95% CI 1.13 to 1.40). In men, the difference was 5% (ratio of geometric means 1.05, 95% CI 0.92 to 1.21). Results from IPTW analysis were similar. In the DID analysis, there was no evidence that being exposed to IPVA affected the change in depressive symptom scores over time compared to being in the non-exposed group for either women (difference-in-differences: 1%, -12% to 16%) or men (-1%, -19% to 20%).

ConclusionsMultivariable linear regression and IPTW suggested an association between IPVA and higher depressive symptom score in women but not men, but DID analysis indicated a null effect in both women and men. This suggests the causal origins of higher depressive symptoms in this young adult population are likely to reflect prior vulnerability that leads to both higher depressive symptoms and increased risk of IPVA exposure.

Key messagesO_LIWomen and, to a lesser degree, men who experience IPVA between the ages of 18-21 years old tend to have higher levels of depressive symptoms at age 23 years than people who do not.
C_LIO_LIIn women, the association between IPVA and higher depressive symptoms remained after adjustment for measured confounders or use of inverse probability of treatment weighting, whereas in men, the association attenuated to the null after adjustment for measured confounders or use of inverse probability of treatment weighting.
C_LIO_LIHowever, the change in depressive symptoms between ages 16 and 23 years was the same in people who experience IPVA and people who did not, for both women and men. This suggests that the higher levels of depressive symptoms in people who experience IPVA is likely to be driven by prior vulnerability that affects the risk of both IPVA exposure and depressive symptoms, highlighting that IPVA is one of a series of challenges being navigated by psychologically vulnerable young adults.
C_LI


title: The UK Coronavirus Job Retention Scheme and changes in diet, physical activity and sleep during the COVID-19 pandemic: Evidence from eight longitudinal studies

abstract:
BackgroundIn March 2020 the UK implemented the Coronavirus Job Retention Scheme (furlough) to minimize job losses. Our aim was to investigate associations between furlough and diet, physical activity, and sleep during the early stages of the COVID-19 pandemic.

MethodsWe analysed data from 25,092 participants aged 16 to 66 years from eight UK longitudinal studies. Changes in employment (including being furloughed) were defined by comparing employment status pre- and during the first lockdown. Health behaviours included fruit and vegetable consumption, physical activity, and sleeping patterns. Study-specific estimates obtained using modified Poisson regression, adjusting for socio-demographic characteristics and pre-pandemic health and health behaviours, were statistically pooled using random effects meta-analysis. Associations were also stratified by sex, age, and education.

ResultsAcross studies, between 8 and 25% of participants were furloughed. Compared to those who remained working, furloughed workers were slightly less likely to be physically inactive (RR:0.85, [0.75-0.97], I2=59%) and did not differ in diet and sleep behaviours, although findings for sleep were heterogenous (I2=85%). In stratified analyses, furlough was associated with low fruit and vegetable consumption among males (RR=1.11; 95%CI: 1.01-1.22; I2: 0%) but not females (RR=0.84; 95%CI: 0.68-1.04; I2: 65%). Considering change in these health behaviours, furloughed workers were more likely than those who remained working to report increased fruit and vegetable consumption, exercise, and hours of sleep.

ConclusionsThose furloughed exhibited broadly similar levels of health behaviours to those who remained in employment during the initial stages of the pandemic. There was little evidence to suggest that such social protection policies if used in the post-pandemic recovery period and during future economic crises would have adverse impacts on population health behaviours.


title: Raman spectroscopy on blood serum probes of patients with end-stage liver disease

abstract: Raman spectroscopy has shown to be a promising method for the examination of biomedical samples. However, until now, its efficacy has not been established in clinical diagnostics. In this study, Raman spectroscopys potential application in medical laboratories is evaluated for a large variety (38) of biomarkers. Given 234 serum samples from a cohort of patients with different stages of liver disease, we performed Raman spectroscopy at 780nm excitation wavelength. The Raman spectra were analyzed in combination with the results of routine diagnostics using specifically developed complex mathematical algorithms, including fluorescence filtering, frequency subset selection and several overfitting circumventing strategies, such as independent validation. With the results of this cohort, which were validated in 328 independent samples, a significant proof-of-concept study was completed. This study highlights the need to prevent overfitting and to use independent data for validation. The results reveal that Raman spectroscopy has high potential for use in medical laboratory diagnostics to simultaneously quantify multiple biomarkers.

category: gastroenterology


title: Modern contraceptive use among adolescent girls and young women in Benin: a mixed-methods study

abstract:
ObjectivesThe study aimed to assess the determinants of modern contraceptive method use among young women in Benin.

DesignA mixed-methods design.

Setting and participantsWe used the Benin 2017-18 Demographic and Health Survey datasets for quantitative analysis. Data collection was conducted using multiple-cluster sampling method and through household survey. Qualitative part was conducted in the city of Allada, one of the Fon cultural capitals. The participants were purposively selected.

OutcomesContraceptive prevalence rate, unmet need for modern method, and percentage of demand satisfied by a modern method for currently married and sexually active unmarried women were measured in the quantitative part. Access barriers and utilization of modern methods were assessed in the qualitative part.

ResultsOverall, 8.5% (95%CI: 7.7-9.5%) among young women ages 15 to 24 were using modern contraceptives and 13% (95%CI: 12.1-14.0%) among women ages 25 or more. Women 15-24 had a higher unmet need, and a lower demand satisfied by modern contraceptive methods compared to women aged 25 or more. 60.8% (56.9-64.7%) of all unmarried young women had unmet need for modern contraceptives. Young women were more likely to use male condoms which they obtain mainly from for-profit outlets, pharmacies, and relatives. The factors associated with demand satisfied by a modern method were literacy, being unmarried, knowing a greater number of modern contraceptive methods, and experiencing barriers in access to health services. On the other hand, the qualitative study found that barriers to using modern methods include community norms about pre-marital sexual intercourse, perceptions about young womens fertility, spousal consent, and the use of non-modern contraceptives.

ConclusionContraceptive use is low among young women in Benin. The use of modern contraceptives is influenced by socio-demographic factors and social norms. Appropriate interventions might promote comprehensive sexuality education, increase community engagement, provide youth-friendly services, and address gender inequalities.

Strengths and limitations of this studyO_LIThis study used a nationally representative survey data which allows generalizability at the national level.
C_LIO_LIWe used a mixed methods design which enables us to compare and discuss the large-scale quantitative data with qualitative information from the ground.
C_LIO_LIThe quantitative information could have been affected by recall errors and biases.
C_LI

category: public and global health


title: The mental health impact of COVID-19 racial and ethnic discrimination against Asian American and Pacific Islanders

abstract: Hate crimes against Asian American/ Pacific Islanders (AAPIs) have surged in the United States during the COVID-19 pandemic to alarming new levels. We analyzed data from the Healthy Minds Study, and found that COVID-19 related racial/ethnic discrimination was associated with greater odds of having depression, anxiety, non-suicidal self-injury, binge drinking, and suicidal ideation among AAPI university students (N=1697). Findings suggest that the COVID-19 pandemic precipitated discrimination, which has been linked to mental health problems, calling for more preventive interventions to address the AAPI population, especially given their low rates of formal treatment utilization.

category: psychiatry and clinical psychology


title: Robustness and bias of European excess death estimates in 2020 under varying model specifications

abstract: Various procedures are in use to calculate excess deaths during the ongoing COVID-19 pandemic. Using weekly death counts from 20 European countries, we evaluate the robustness of excess death estimates to the choice of model for expected deaths and perform a cross-validation analysis to assess the error and bias in each models predicted death counts. We find that the different models produce very similar patterns of weekly excess deaths but disagree substantially on the level of excess. While the exact country ranking along percent excess death in 2020 is sensitive to the choice of model the top and bottom ranks are robustly identified. On the country level, the 5-year average death rate model tends to produce the lowest excess death estimates, whereas high excess deaths are produced by the popular 5-year average death count and Euromomo-style Serfling models. Cross-validation revealed these estimates to be biased under a causal interpretation of "expected deaths had COVID-19 not happened."


title: Brain atrophy progression in Parkinson's disease is shaped by connectivity and local vulnerability

abstract:
Atrophy in multiple brain regions has been reported in the early stages of Parkinsons Disease, but there have been few longitudinal studies. How intrinsic properties of the brain, such as anatomical connectivity, local cell type distribution and gene expression combine to determine the pattern of disease progression remains unknown. One hypothesis proposes that the disease stems from prion-like propagation of misfolded alpha-synuclein via the connectome that might cause varying degrees of tissue damage based on local properties.

Here we used MRI data from the Parkinson Progression Markers Initiative to test this model by mapping the progression of brain atrophy over one, two and four years and relating it to brain structural and functional connectivity, cell type expression and gene ontology enrichment analyses. In this longitudinal study, we derived atrophy progression maps for the three time points using deformation-based morphometry applied to T1-weighted MRI from 74 de novo Parkinsons Disease patients (50 Men: 24 Women) and 157 healthy control participants (115 Men: 42 Women). After regressing out the expected age and sex effects associated with normal aging, we found that atrophy significantly progressed over two and four years in the caudate, nucleus accumbens, hippocampus, and the temporal, parietal, occipital and posterior cingulate cortex. This progression was shaped by both structural and functional brain connectivity. Also, the progression of atrophy was more pronounced in regions with a higher expression of genes related to synapses and was related to the prevalence of oligodendrocytes and endothelial cells.

In sum, we demonstrate that the progression of atrophy in Parkinsons Disease is in line with the prion-like propagation hypothesis of alpha-synuclein and provide evidence that synapses may be especially vulnerable to synucleinopathy. In addition to identifying vulnerable brain regions, this study reveals different factors that may be implicated in the neurotoxic mechanisms leading to progression in Parkinsons Disease.

category: pathology


title: A multi-component, community-based strategy to facilitate COVID-19 vaccine uptake among Latinx populations: from theory to practice

abstract:
BackgroundCOVID-19 vaccine coverage in the Latinx community depends on delivery systems that overcome barriers such as institutional distrust, misinformation, and access to care. We hypothesized that a community-centered vaccination strategy that included mobilization, vaccination, and "activation" components could successfully reach an underserved Latinx population, utilizing its social networks to boost vaccination coverage.

Methods and FindingsOur community-academic-public health partnership, "Unidos en Salud," utilized a theory-informed approach to design our "Motivate, Vaccinate, and Activate" COVID-19 vaccination strategy. Our strategys design was guided by the PRECEDE Model and sought to address and overcome predisposing, enabling, and reinforcing barriers to COVID-19 vaccination faced by Latinx individuals in San Francisco. We evaluated our prototype outdoor, "neighborhood" vaccination program located in a central commercial and transport hub in the Mission District in San Francisco, using the Reach, Effectiveness, Adoption, Implementation and Maintenance (RE-AIM) framework during a 16-week period from February 1, 2021 to May 19, 2021. Programmatic data, city-wide COVID-19 surveillance data, and a survey conducted between May 2, 2021 and May 19, 2021 among 997 vaccinated clients [≥]16 years old were used in the evaluation.

There were 20,792 COVID-19 vaccinations administered at the neighborhood site during the 16-week evaluation period. Vaccine recipients had a median age of 43 (IQR 32-56) years, 53.9% were male and 70.5% were Latinx, 14.1% white, 7.7% Asian, 2.4% Black, and 5.3% other. Latinx vaccinated clients were substantially more likely than non-Latinx clients to have an annual household income of less than $50,000 a year (76.1% vs. 33.5%), be a first-generation immigrant (60.2% vs. 30.1%), not have health insurance (47.3% vs. 16.0%), and not have access to primary care provider (62.4% vs. 36.2%). The most frequently reported reasons for choosing vaccination at the site were its neighborhood location (28.6%), easy and convenient scheduling (26.9%) and recommendation by someone they trusted (18.1%); approximately 99% reported having an overall positive experience, regardless of ethnicity. Notably, 58.3% of clients reported that they were able to get vaccinated earlier because of the neighborhood vaccination site, 98.4% of clients completed both vaccine doses, and 90.7% said that they were more likely to recommend COVID-19 vaccination to family and friends after their experience; these findings did not substantially differ according to ethnicity. There were 40.3% of vaccinated clients who said they still knew at least one unvaccinated person (64.6% knew [≥]3). Among clients who received both vaccine doses (n=729), 91.0% said that after their vaccination experience, they had personally reached out to at least one unvaccinated person they knew (61.6% reached out to [≥]3) to recommend getting vaccinated; 83.0% of clients reported that one or more friends, and/or family members got vaccinated as a result of their outreach, including 18.9% who reported 6 or more persons got vaccinated as a result of their influence.

ConclusionsA multi-component, "Motivate, Vaccinate, and Activate" community-based strategy addressing barriers to COVID-19 vaccination for the Latinx population reached the intended population, and vaccinated individuals served as ambassadors to recruit other friends and family members to get vaccinated.


title: Neutralizing anti-DNase1L3 antibodies derive from autoreactive VH4-34+ B cells and associate with the interferon signature in SLE

abstract: DNase1L3 deficiency is an inborn error of immunity that causes monogenic systemic lupus erythematosus (SLE) in humans. Here, we identified that one third of patients with sporadic SLE have antibodies to DNase1L3. Like DNase1L3 deficiency, we found that patients with anti-DNase1L3 antibodies have features associated with immune pathways activated by immunogenic self-DNA, including elevated antibodies to dsDNA and prominent expression of the interferon and myeloid/neutrophil signatures. Interestingly, 40-80% of anti-DNase1L3 antibodies in SLE serum contain the 9G4 idiotype, which is encoded by the autoreactive heavy-chain gene segment VH4-34. Sequence and functional analysis of four anti-DNase1L3 monoclonal antibodies generated from SLE patients experiencing disease-associated flares showed that these antibodies were derived from self-reactive 9G4+ switched memory B cells. These antibodies are highly enriched in somatic hypermutations, indicating that they originated from antigen-experienced cells, and have neutralizing activity against DNase1L3. Together, the data demonstrate that autoantibodies to DNase1L3 phenocopy pathogenic mechanisms associated with DNase1L3 deficiency. Moreover, the finding that autoreactive B cells bearing the 9G4 idiotype produce dominant serum autoantibodies, including antibodies to DNase1L3, underscores VH4-34+ B cells as sensible therapeutic targets for specific depletion of pathogenic B cells in SLE.

category: rheumatology


title: Extended Invariant Information Clustering is Effective for Leave-One- Site-Out Cross-Validation in Resting State Functional Connectivity Modelling

abstract: Herein, we propose a new deep neural network model based on invariant information clustering (IIC), proposed by Ji et al., to improve the modeling performance of the leave-one-site-out cross-validation (LOSO-CV) for a multi-source dataset. Our Extended IIC (EIIC) is a type of contrastive learning; however, unlike the original IIC, it is characterized by transfer learning with labeled data pairs, but without the need for a data augmentation technique. Each site in LOSO-CV is left out in turn from the remaining sites used for training and receives a value for modeling evaluation. We applied the EIIC to the resting state functional connectivity magnetic resonance imaging dataset of the Autism Brain Imaging Data Exchange. The challenging nature of brain analysis for autism spectrum disorder (ASD) can be attributed to the variability of subjects, particularly the rapid change in the neural system of children as the target ASD age group. However, EIIC demonstrated higher LOSO-CV classification accuracy for the majority of scanning locations than previously used methods. Particularly, with the adjustment of a mini-batch size, EIIC outperformed other classifiers with an accuracy >0.8 for the sites with highest mean age of the subjects. Considering its effectiveness, our proposed method might be promising for harmonization in other domains, owing to its simplicity and intrinsic flexibility. We are currently submitting this manuscript to Frontiers in Neuroinformatics.

category: neurology


title: Assessing the role of polygenic background on the penetrance of monogenic forms in Parkinson's disease.

abstract:
BackgroundSeveral rare and common variants are associated with Parkinsons disease. However, there is still an incomplete penetrance in the carriers of rare variants associated with Parkinsons disease. To address this issue, we investigated whether a PRS calculated from significant GWAS SNPs affects the penetrance of Parkinsons disease among carriers of rare monogenic variants in known Parkinsons disease genes and those with a family history.

MethodsWe calculated the PRS based on common variants and selected the carriers of rare monogenic variants by using the exome data from UK Biobank. Individuals were divided into three risk categories based on PRS: low (<10%), intermediate (10%-90%), and high (>90%) risk groups. We then compared how PRS affects Parkinsons disease risk among carriers of rare monogenic variants and those with family-history.

ResultsWe observed a two-fold higher odds ratio for a carrier of a monogenic variant that had a high PRS (OR 4.07,95% CI, 1.72-8.08) compared to carriers with a low PRS (OR 1.91, 95% CI, 0.31-6.05). In the same line, carriers with a first-degree family history and with >90% PRS have even a higher risk of developing PD (OR 23.53, 95%CI 5.39-71.54) compared to those with <90% PRS (OR 9.54, 95% CI 3.32-21.65).

ConclusionsOur results show that PRS, carrier status, and family history contribute independently and additively to the Parkinsons disease risk.

category: genetic and genomic medicine


title: Breast and prostate cancer risk: the interplay of polygenic risk, high-impact monogenic variants, and family history

abstract:
PurposeInvestigate to which extent polygenic risk scores (PRS), high-impact monogenic variants, and family history affect breast and prostate cancer risk by assessing cancer prevalence and cancer cumulative lifetime incidence.

Methods200,643 individuals from the UK Biobank were stratified as follows: 1. carriers or non-carriers of high impact constitutive, monogenic variants in cancer susceptibility genes, 2. high or non-high PRS (90th percentile threshold), 3. with or without a family history of cancer.

Multivariable logistic regression was used to compare the odds ratio (OR) across the different groups while Cox proportional hazards models were used to compute the cumulative incidence through life.

ResultsBreast and prostate cancer cumulative incidence by age 70 is 7% and 5% for non-carriers with non-high PRS and reaches 37% and 32% among carriers of high-impact variants in cancer susceptibility genes with high PRS.

The additional presence of family history is associated with a further increase of the risk of developing cancer reaching an OR of 14 and 21 for breast and prostate cancer, respectively.

ConclusionHigh PRS confers a cancer risk comparable to high-impact monogenic variants. Family history, monogenic variants, and PRS contribute additively to breast and prostate cancer risk.


title: Whole-exome sequencing of the mummified remains of Cangrande della Scala (1291-1329 CE) indicates the first known case of late-onset Pompe disease

abstract: Mummified remains of relevant historical figures are nowadays an important source of information to retrace data concerning their private life and health, especially when historical archives are not available. Next-generation-sequencing was proved to be a valuable tool to unravel the characteristics of these individuals through their genetic heritage. Using the strictest criteria currently available for the validation of ancient DNA sequences, whole-genome and whole-exome sequencing were generated from the mummy remains of an Italian nobleman died almost 700 years ago, Cangrande della Scala. While its genome sequencing could not yield sufficient coverage for in depth investigation, exome sequencing could overcome the limitations of this approach to achieve significantly high coverage on coding regions, thus allowing to perform the first extensive exome analysis of a mummy genome. Similar to a standard "clinical exome analysis" conducted on modern DNA, an in-depth variant annotation, high-quality filtering and interpretation was performed, leading to the identification of a genotype associated with late-onset Pompe disease (glycogen storage disease type II). This genetic diagnosis was concordant with the limited clinical history available for Cangrande della Scala, who likely represents the earliest known case of this autosomal recessive metabolic disorder.


title: Relevance of prediction scores derived from the SARS-CoV-2 first wave, in the UK COVID-19 second wave, for early discharge, severity and mortality: a PREDICT COVID UK prospective observational cohort study

abstract:
ObjectiveProspectively validate two prognostic scores, pre-hospitalisation (SOARS) and hospitalised mortality prediction (4C Mortality Score), derived from the coronavirus disease 2019 (COVID-19) first wave, in the evolving second wave with prevalent B.1.1.7 and parent D614 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, in two large United Kingdom (UK) cohorts.

DesignProspective observational cohort study of SOARS and 4C Mortality Score in PREDICT (single site) and multi-site ISARIC (International Severe Acute Respiratory and Emerging Infections Consortium) cohorts.

SettingProtocol-based data collection in UK COVID-19 second wave, between October 2020 and January 2021, from PREDICT and ISARIC cohorts.

Participants1383 from single site PREDICT cohort and 20,595 from multi-site ISARIC cohort.

Main outcome measuresRelevance of SOARS and 4C Mortality Score derived from the COVID-19 first wave, determining in-hospital mortality and safe discharge in the UK COVID-19 second wave.

ResultsData from 1383 patients (median age 67y, IQR 52-82; mortality 24.7%) in the PREDICT and 20,595 patients from the ISARIC (mortality 19.4%) cohorts showed both SOARS and 4C Mortality Score remained relevant despite the B.1.1.7 variant and treatment advances. SOARS had AUC of 0.8 and 0.74, while 4C Mortality Score had an AUC of 0.83 and 0.91 for hospital mortality, in the PREDICT and ISARIC cohorts respectively, therefore effective in evaluating both safe discharge and in-hospital mortality. 19.3% (231/1195, PREDICT cohort) and 16.7% (2550/14992, ISARIC cohort) with a SOARS of 0-1 were potential candidates for home discharge to a virtual hospital (VH) model. SOARS score implementation resulted in low re-admission rates, 11.8% (27/229), and low mortality, 0.9% (2/229), in the VH pathway. Use is still suboptimal to prevent admission, as 8.1% in the PREDICT cohort and 9.5% in the ISARIC cohort were admitted despite SOARS score of 0-1.

ConclusionSOARS and 4C Mortality Score remains valid, providing accurate prognostication despite evolving viral subtype and treatment advances, which have altered mortality. Both scores are easily implemented within urgent care pathways with a scope for admission avoidance. They remain safe and relevant to their purpose, transforming complex clinical presentations into tangible numbers, aiding objective decision making.

Trial registrationNHS HRA registration and REC approval (20/HRA/2344, IRAS ID 283888).


title: Bovine Colostrum Derived Antibodies Against SARS-CoV-2 Show Great Potential to Serve as a Prophylactic Agent

abstract:
Severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) until now imposes a serious burden to health systems globally. Despite worldwide vaccination, social distancing and wearing masks, the spread of the virus is still ongoing. One of the mechanisms how neutralizing antibodies (NAbs) block virus entry into cells encompasses interaction inhibition between the cell surface receptor angiotensin-converting enzyme 2 (ACE2) and the spike (S) protein of SARS-CoV-2. SARS-CoV-2 specific NAb development can be induced in the blood of cattle. Pregnant cows produce NAbs upon immunization, and antibodies move into the colostrum just before calving. Here we immunized cows with SARS-CoV-2 S1 receptor binding domain (RBD) protein in proper adjuvant solutions, followed by one boost with SARS-CoV-2 trimeric S protein, and purified immunoglobulins from colostrum. We demonstrate that this preparation indeed blocks interaction between the trimeric S protein and ACE2 in different in vitro assays. Moreover, we describe the formulation of purified immunoglobulin preparation into a nasal spray. When administered to human subjects, the formulation persists on the nasal mucosa for at least 4 hours as determined by a clinical study. Therefore, we are presenting a solution that shows great potential to serve as a prophylactic agent against SARS-CoV-2 infection as an additional measure to vaccination and wearing masks. Moreover, our technology allows for a rapid and versatile adaption for preparing prophylactic treatments against other diseases by using the defined characteristics of antibody movement into the colostrum.

SignificanceSARS-CoV-2 infections continue to be a high-risk factor for mankind. Antibodies with the potential to neutralize the virus and thus its entry into the host cell have been shown to impose a potent measure against the infection. Human derived neutralizing antibodies are therapeutics and thus fall under the legislation of drugs. However, an alternative could be the purification of efficient neutralizing antibodies from other species. Here, we present immunization of pregnant cows with spike protein of SARS-CoV-2 which results in high quantities of colostrum immunoglobulins that can be easily harvested and safely purified within a remarkably short time. The colostrum immunoglobulin preparation has a great potential to serve in formulations that can be used as prophylactic agent against SARS-CoV-2 infection.


title: Single-dose mRNA vaccine effectiveness against SARS-CoV-2, including P.1 and B.1.1.7 variants: a test-negative design in adults 70 years and older in British Columbia, Canada

abstract:
IntroductionRandomized-controlled trials of mRNA vaccine protection against SARS-CoV-2 included relatively few elderly participants. We assess singe-dose mRNA vaccine effectiveness (VE) in adults [≥]70-years-old in British Columbia (BC), Canada where the second dose was deferred by up to 16 weeks and where a spring 2021 wave uniquely included co-dominant circulation of B.1.1.7 and P.1 variants of concern (VOC).

MethodsAnalyses included community-dwelling adults [≥]70-years-old with specimen collection between April 4 (epidemiological week 14) and May 1 (week 17). Adjusted VE was estimated by test-negative design through provincial laboratory and immunization data linkage. Cases were RT-PCR test-positive for SARS-CoV-2 and controls were test-negative. Vaccine status was defined by receipt of a single-dose [≥]21 days before specimen collection, but a range of intervals was assessed. In variant-specific analyses, test-positive cases were restricted to those genetically-characterized as B.1.1.7, P.1 or non-VOC.

ResultsVE analyses included 16,993 specimens: 1,226 (7.2%) test-positive cases and 15,767 test-negative controls. Of 1,131 (92%) viruses genetically categorized, 509 (45%), 314 (28%) and 276 (24%) were B.1.1.7, P.1 and non-VOC lineages, respectively. VE was negligible at 14% (95% CI 0-26) during the period 0-13 days post-vaccination but increased from 43% (95% CI 30-53) at 14-20 days to 75% (95% CI 63-83) at 35-41 days post-vaccination. VE at [≥]21 days was 65% (95% CI 58-71) overall: 72% (95% CI 58-81), 67% (95% CI 57-75) and 61% (95% CI 45-72) for non-VOC, B.1.1.7 and P.1, respectively.

ConclusionsA single dose of mRNA vaccine reduced the risk of SARS-CoV-2 in adults [≥]70-years-old by about two-thirds, with protection only minimally reduced against B.1.1.7 and P.1 variants. Substantial single-dose protection in older adults reinforces the option to defer the second dose when vaccine supply is scarce and broader first-dose coverage is needed.


title: A novel RT-LAMP workflow for rapid salivary diagnostics of COVID-19 and effects of age, gender and time from symptom onset

abstract:
ObjectivesRapid diagnostics is pivotal to curb SARS-CoV-2 transmission, and saliva has emerged as a practical alternative to naso/oropharyngeal (NOP) specimens. We aimed to develop a direct RT-LAMP workflow for viral detection in saliva, and to provide more information regarding its potential in COVID-19 diagnostics.

MethodsClinical and contrived specimens were used to screen/optimize formulations and sample processing protocols. Salivary viral load was determined in symptomatic patients to evaluate clinical performance (n = 90) and to characterize saliva based on age, gender and time from onset of symptoms (n = 49).

ResultsThe devised workflow achieved 93.2% sensitivity, 97% specificity, and 0.895 Kappa for salivas containing >102 copies/L. Further analyses in saliva showed peak viral load in the first days of symptoms and lower viral loads in females, particularly among young individuals (<38 years). NOP RT-PCR data did not yield relevant associations.

ConclusionsThis novel saliva RT-LAMP workflow can be applied to point-of-care testing. This work reinforces that saliva better correlates with transmission dynamics than NOP specimens, and reveals gender differences that may reflect higher transmission by males. To maximize detection, testing should be done immediately after symptom onset, especially in females.

HIGHLIGHTS- Development of DGS, a dithiothreitol/guanidine-based solution for stabilization of the viral genome that increases sensitivity for SARS-CoV-2 detection in saliva;
- Rapid, cost-effective RT-LAMP assay workflow for viral detection in saliva without need of RNA extraction;
- Insights into the differences in viral load between saliva and naso-oropharyngeal specimens, and correlation with age, gender and time from symptom onset;


title: Development of low-cost serological immunoassay to detect antiviral antibodies to Sars-Cov-2 Spike protein

abstract: Seroconversion to SARS-CoV-2 has been widely studied to evaluate infection spreading for epidemiological purpose, or even in studies of protective immunity in convalescent or vaccinated individuals. The viral particle has an envelope harboring the spike glycoprotein, which can be used as an antigen for assay development, to detect antiviral antibodies to SARS-CoV-2. Since several vaccines encode a spike subunit, the full length spike-based immunoassay should be a universal tool to evaluate seroconversion. In this manuscript, we propose a low-cost ELISA that can be used to detect antiviral IgG to SARS-CoV-2 in human serum.


title: CHA2DS2-VASc score on admission to predict mortality in COVID-19 patients: A meta-analysis

abstract:
BackgroundCHA2DS2-VASc score is used in non-valvular AF patients to predict thromboembolic risk. Recent studies have tried to evaluate CHA2DS2-VASc score on admission in COVID-19 patients to predict mortality.

MethodsWe conducted a literature search on 14 April 2021 to retrieve all published studies, pre-prints and grey literature related to the predictive power of CHA2DS2-VASc score in COVID-19 patients of admission and mortality. Screening of studies and data extraction was done by two authors independently. We used the Quality in Prognosis Studies (QUIPS) tool for the methodological quality assessment of the included studies.

ResultsFive studies involving 5,941 patients reported the predictive value of CHA2DS2-VASc score for mortality in COVID-19 patients. The pooled sensitivity (SEN), specificity (SPE) and area under curve were 0.72 (95% CI 0.63-0.79), 0.74 (95% CI 0.67-0.81) and 0.80 (95% CI 0.76-0.83).

ConclusionsCHA2DS2-VASc score at admission has good predictive value for mortality in patients with COVID-19 infection and can help clinicians identify potentially severe cases early. Early initiation of effective management in these cases may help in reducing overall mortality due to COVID-19.

Trial registryWe prospectively registered this meta-analysis on PROSPERO database (Reg number: CRD42021248398).


title: Namilumab or infliximab compared to standard of care in hospitalised patients with COVID-19 (CATALYST): a phase 2 randomised adaptive trial

abstract:
BackgroundDysregulated inflammation is associated with poor outcomes in Coronavirus disease 2019 (COVID-19). We assessed the efficacy of namilumab, a granulocyte-macrophage colony-stimulating factor inhibitor and infliximab, a tumour necrosis factor inhibitor in hospitalised patients with COVID-19 in order to prioritise agents for phase 3 trials.

MethodsIn this randomised, multi-arm, parallel group, open label, adaptive phase 2 proof-of-concept trial (CATALYST) we recruited hospitalised patients [≥] 16 years with COVID-19 pneumonia and C-reactive protein (CRP) [≥] 40mg/L in nine UK hospitals. Participants were randomly allocated with equal probability to usual care, or usual care plus a single 150mg intravenous dose of namilumab (150mg) or infliximab (5mg/kg). Randomisation was stratified for ward versus ICU. The primary endpoint was improvement in inflammation in intervention arms compared to control as measured by CRP over time, analysed using Bayesian multi-level models. ISRCTN registry number 40580903.

FindingsBetween 15th June 2020 and 18th February 2021 we randomised 146 participants: 54 to usual care, 57 to namilumab and 35 to infliximab. The probabilities that namilumab and infliximab were superior to usual care in reducing CRP over time were 97% and 15% respectively. Consistent effects were seen in ward and ICU patients and aligned with clinical outcomes, such that the probability of discharge (WHO levels 1-3) at day 28 was 47% and 64% for ICU and ward patients on usual care, versus 66% and 77% for patients treated with namilumab. 134 adverse events occurred in 30/55 (54.5%) namilumab patients compared to 145 in 29/54 (53.7%) usual care patients. 102 events occurred in 20/29 (69.0%) infliximab patients versus 112 events in 17/34 (50.0%) usual care patients.

InterpretationNamilumab, but not infliximab, demonstrated proof-of-concept evidence for reduction in inflammation in hospitalised patients with COVID-19 pneumonia which was consistent with secondary clinical outcomes. Namilumab should be prioritised for further investigation in COVID-19.

FundingMedical Research Council.


title: High throughput sequencing based detection of SARS-CoV-2 prevailing in wastewater of Pune, West India

abstract: Given a large number of SARS-CoV-2 infected individuals, clinical detection has proved challenging. The wastewater-based epidemiological paradigm would cover the clinically escaped asymptomatic individuals owing to the faecal shedding of the virus. We hypothesised using wastewater as a valuable resource for analysing SARS-CoV-2 mutations circulating in the wastewater of Pune region (Maharashtra; India), one of the most affected during the covid-19 pandemic. We conducted a case study in open wastewater drains from December 2020-March 2021 to assess the presence of SARS-CoV-2 nucleic acid and further detect mutations using ARTIC protocol of MinION sequencing. The analysis revealed 108 mutations across six samples categorised into 40 types of mutations. We report the occurrence of mutations associated with B.1.617 lineage in March-2021 samples, simultaneously also reported as a Variant of Concern (VoC) responsible for the rapid increase in infections. The study also revealed four mutations; S:N801, S:C480R, NSP14:C279F and NSP3:L550del not currently reported from wastewater or clinical data in India but reported in the world. Further, a novel mutation NSP13:G206F mapping to NSP13 region was observed from wastewater. Notably, S:P1140del mutation was observed in December 2020 samples while it was reported in February 2021 from clinical data, indicating the instrumentality of wastewater data in early detection. This is the first study in India to conclude that wastewater-based epidemiology to identify mutations associated with SARS-CoV-2 virus from wastewater as an early warning indicator system.


title: COVID-19 infections in day care centres in Germany: Social and organizational determinants of infections in children and staff in the second and third wave of the pandemic

abstract:
BackgroundDuring the SARS-CoV-2 pandemic, German early childhood education and care (ECEC) centres organised childrens attendance variably (i.e., reduced opening hours, emergency support for few children only or full close-down). Further, protection and hygiene measures like fixed children/staff groups, ventilation and surface disinfection were introduced among ECEC centres. To inform or modify public health measures in ECEC, we investigate the occurrence of SARS-CoV-2 infections among children and staff of ECEC centres in light of social determinants (socioeconomic status of the children) and recommended structural and hygiene measures. We focus on the question if the relevant factors differ between the 2nd (when no variant of concern (VOC) circulated) and the 3rd wave (when VOC B.1.1.7 (Alpha) predominated).

MethodsBased on panel data from a weekly online survey of ECEC centre managers (calendar week 36/2020 to 22/2021, ongoing) including approx. 8500 centres, we estimate the number of SARS-CoV-2 infections in children and staff using random-effect-within-between (REWB) panel models for count data in the 2nd and 3rd wave.

ResultsCentres with a high proportion of children with low socioeconomic status (SES) have a higher risk of infections in staff and children. Strict contact restrictions between groups like fixed group assignments among children and fixed staff assignments to groups prevent infections. Both effects tend to be stronger in the 3rd wave.

ContributionECEC centres with a large proportion of children from a low SES background and lack of using fixed child/staff cohorts experience higher COVID-19 rates. Centres should be supported in maintaining recommended measures over the long run. Preventive measures such as vaccination of staff should be prioritised in centres with large proportions of low SES children.


title: COVID-19 infections in day care centres in Germany: Social and organisational determinants of infections in children and staff in the second and third wave of the pandemic


title: Functional dependence of COVID-19 growth rate on lockdown conditions and rate of vaccination.

abstract:
It is shown that derived from the solution of differential equations analytical model adequately describes development epidemics with changes in both lockdown conditions and the effective rate of mass vaccination of the population. As in previous studies, the control calculations are in good agreement with observations at all stages of epidemic growth. One of the two model coefficients is uniquely related to the lockdown efficiency parameter. We obtained an approximate correlation between this parameter and the main conditions of lockdown, in particular, physical distancing, reduction in social contacts and strictness of the mask regime.

The calculation of the incident over a seven-day period using the proposed model is in good agreement with the observational data. Analysis of both curves shows that a better agreement can be obtained by taking into account the lag time of the epidemic response of about 10 days.

From the reverse calculation a time-varying curve of the infection rate associated with the "new" virus strain under mutation conditions is obtained, which is qualitatively confirmed by the sequencing data.

Based on these studies, it is possible to conclude that the ASILV analytical model developed here can be used to reliably and promptly predict epidemic development under conditions of lockdown and mass vaccination without the use of numerical methods.

The functional relationships identified allow us to conduct a rapid analysis of the impact of each of the model parameters on the overall process of the epidemic.

In contrast to previous studies, the calculations of the proposed model were performed using EXCEL, rather than a standard calculator. This is due to the need to account for multiple changes in lockdown conditions and vaccination rates.


title: Antipsychotics, Prolactin and Breast Cancer

abstract:
ObjectiveAntipsychotic drugs are well established to alter circulating prolactin levels by blocking dopamine D-2 receptors in the pituitary. Prolactin activates many genes important in the development of breast cancer. The aim of this study was to evaluate the risk of breast cancer in women exposed to antipsychotic drugs, stratified by prolactin elevating potential (high, mid, and low), compared to women taking anticonvulsants and/or lithium.

MethodsThe IBM MarketScan Commercial and Medicaid Databases were used to establish a large, observational cohort of women taking antipsychotics drugs compared to control drugs. Invasive breast cancer was identified using diagnostic codes. Bivariable and multivariable Cox proportional hazards models were used to evaluate the risk of breast cancer by antipsychotic drug exposure, both as pooled antipsychotics and by prolactin specific categories.

ResultsA total of 2,708 (0.2%) cases of invasive breast cancer were identified among 1,562,839 women. Exposure to antipsychotics with high prolactin elevating potential was associated with a 23% increased risk of breast cancer (aHR 1.23; 95% CI, 1.11-1.35), whereas mid and low prolactin categories of antipsychotics were not significant.

ConclusionIn the largest study of antipsychotics taken by women, a modest risk between antipsychotic drug use and the risk for breast cancer was observed, with a differential higher association with high prolactin elevating drugs. Residual confounding factors included incomplete information on parity, race and socioeconomic status, and differential outpatient visits. Clinicians should consider monitoring serum prolactin levels and adopting vigilant mammography screening practices, especially in older women taking category one antipsychotics.


title: Depressive and anxiety symptoms and COVID-19-related factors among men and women in Nigeria

abstract: Despite the greater adverse economic impacts in low and middle-income (LAMI) compared to high-income countries, fewer studies have investigated the associations between COVID-19-related stressor and mental health in LAMI countries. The objectives of this study were to determine the associations between COVID-19-related stressors and anxiety and depressive symptoms while controlling for known risk and protective factors and to investigate any sex differences. An online survey was carried out to assess sociodemographic, psychosocial (previous mental health conditions, sexual orientation, intimate partner violence and perceived social support) and COVID-19-related variables. Hierarchical linear regression was carried out with anxiety and depressive symptoms as separate outcomes. Of the COVID-19-related factors, testing positive for COVID-19 infection, having COVID-19 symptoms, having other medical conditions, self-isolating due to COVID-19 symptoms, worry about infection, perception of the pandemic as a threat to income and isolation during the lockdown were significantly associated with higher anxiety and depressive symptoms. Of these, worry about infection, isolation during lockdown and disruption due to the pandemic retained independent associations with both outcomes. The variance in anxiety and depressive symptoms explained by COVID-19-related factors was larger in women (6.1% and respectively) compared to men (6.1% and respectively). COVID-19-related stressors are associated with higher anxiety and depressive symptoms, with these effects being larger in men compared to women. Enhancing social support can be an affordable strategy to mitigate this risk but this needs to be investigated using appropriate designs.


title: Assessing the Impact of Mask Usage on COVID-19 Transmission Using a Computer Simulation

abstract:
BackgroundCOVID-19, caused by SARS-CoV-2, is highly contagious and causes substantial morbidity and mortality. Mask usage has been advocated by health professionals to minimize its spread. Thus, it is important to develop a simulation that models SARS-CoV-2 spread in indoor environments to evaluate mask usage effectiveness.

MethodsA visual computer simulation was developed with Pygame in Python 3. A virtual indoor supermarket is simulated by a given flow of customers with an initial infection percentage and mask usage percentage who enter, move around, and exit a supermarket with shelves, tables and cashiers to demonstrate a systems dynamic complexity, i.e. nonlinear interactions of system elements over time. A supermarket was simulated with initial infection rates of 5%, 10%, and 20% and mask use percentages of 0%, 25%, 50% 75%, and 100%. The environmental settings (e.g. shelf number and location) and total customers (N=200) were kept constant.

ResultsThe number of infected customers increased as the percentage of mask usage decreased (p < 0.01). At 5% initial infection, almost no infections were observed at 50% mask usage, with a logarithmic best-fit model (R2 = 0.947). At 10% initial infection, the association between mask usage and decrease in number of infections was best fit with a linear model (R2 = 0.924). For 20% initial infection, a quadratic model was the best fit (R2 = 0.934). While a linear model suggests proportional decreases in infection, the quadratic model suggests more significant reductions in infections at higher rates of mask use (i.e. increasing mask usage from 5% to 10% is less impactful than from 65% to 70%).

ConclusionThe results suggest that mask usage has a significant impact on decreasing COVID-19 transmission. Ideally, mask usage should be as high as possible to achieve more significant reductions in COVID-19 infections. Various parameters can be adjusted during simulation as we learn more about SARS-CoV-2 to guide policies for minimizing COVID-19 transmission.


title: The influence of sex, gender, age, and ethnicity on psychosocial factors and substance use throughout phases of the COVID-19 pandemic

abstract:
The SARS-CoV-2 (COVID-19) pandemic has had profound physical and mental health effects on populations around the world. Limited empirical research has used a gender-based lens to evaluate the mental health impacts of the pandemic, overlooking the impact of public health measures on marginalized groups, such as women, and the gender diverse community. This study used a gender-based analysis to determine the prevalence of psychosocial symptoms and substance use by age, ethnicity, income, rurality, education level, Indigenous status, and sexual orientation.

Participants in the study were recruited from previously established cohorts as a part of the COVID-19 Rapid Evidence Study of a Provincial Population-Based Cohort for Gender and Sex (RESPPONSE) study. Those who agreed to participate were asked to self-report symptoms of depression, anxiety, pandemic stress, loneliness, alcohol use, and cannabis use across five phases of the pandemic as well as retrospectively before the pandemic.

For all psychosocial outcomes, there was a significant effect of time with all five phases of the pandemic being associated with more psychosocial symptoms relative to pre-COVID levels (p < .0001). Gender was significantly associated with all outcomes (p < .0001) with men exhibiting lower scores (i.e., less symptoms) than women and gender diverse participants, and women exhibiting lower scores than the gender diverse group. Other significant predictors were age (younger populations experiencing more symptoms, p < .0001), ethnicity (Chinese/Taiwanese individuals experiencing less symptoms, p = .005), and Indigenous status (Indigenous individuals experiencing more symptoms, p < .0001). Alcohol use and cannabis use increased relative to pre-pandemic levels, and women reported a greater increase in cannabis use than men (p < .0001). Our findings highlight the need for policy makers and leaders to proactively consider gender when tailoring public health measures for future pandemics.


title: Breakthrough infection with SARS-CoV-2 and its predictors among healthcare workers in a medical college and hospital complex in Delhi, India

abstract:
IntroductionThe study objective was to determine the breakthrough infection rate of Covid-19 (SARS-CoV-2) infection in those vaccinated with either BBV152 or AZD1222 (ChAdOx1-S) vaccine among healthcare workers (HCWs).

MethodsA cross-sectional analysis was conducted a medical college and hospital complex in Delhi, India through telephonic interviews among HCWs who had received at-least one dose of a Covid-19 vaccine during January to March 2021. Breakthrough infections were operationally defined as occurrence of Covid-19 infection [≥]14 days after administration of two doses of either Covid-19 vaccine.

ResultsWe enrolled 325 HCWs with mean (SD) age of 29.1 (9.9) years including 211 (64.9%) males. Two seventy nine (85.8%) HCWs were fully vaccinated while 46 (14.2%) were partially vaccinated. There were 168 (51.7%) BBV152 and 157 (48.3%) AZD1222 (ChAdOx1-S) recipients.

A total of 37 (11.3%, 95% C.I. 8.3, 15.3) breakthrough infections were observed in the HCWs. The median (IQR) time until incidence of Covid-19 breakthrough infection since receiving second dose of either Covid-19 vaccine was 47 (28.5, 55) days. Additionally, 20 (6.1%) non-breakthrough Covid-19 infections were recorded in the HCWs post vaccination with either a single dose of a Covid-19 vaccine or both doses but prior to a period of 14 days since administration of the second dose.

Most breakthrough infection cases (94.4%) were mild and did not require supplemental oxygen therapy. HCWs without a history of natural Covid-19 infection and recovery prior to vaccination were 3.8 times more at risk to contract a Covid-19 infection or reinfection in spite of vaccination with at-least one dose of either Covid-19 vaccine.

ConclusionNearly one in nine HCWs experienced a Covid-19 breakthrough infection in the present study.


title: Testing for SARS-CoV-2 among cruise ship travelers repatriated to the United States, February to March 2020

abstract:
BackgroundIn early 2020, an outbreak of coronavirus disease 2019 occurred among passengers and crew of the Diamond Princess cruise ship. During February 16-17, some US citizens, residents, and their partners voluntarily repatriated to the US from Japan.

MethodsWe conducted a retrospective, longitudinal evaluation of repatriated travelers where the outcome of interest was a positive test for SARS-CoV-2. Travelers who tested positive for SARS-CoV-2 were isolated in hospitals or at home under county isolation orders and underwent serial testing by real-time reverse transcription polymerase chain reaction (RT-PCR) approximately every other day, as contemporaneous US guidance required two consecutive negative tests collected [≥]24 hours apart and symptom improvement before release from isolation.

ResultsAmong quarantined repatriated travelers, 14% tested positive for SARS-CoV-2. One-fifth of infected travelers initially tested negative but were identified on subsequent testing. All infected travelers remained asymptomatic or developed mild symptoms during isolation. Many travelers remained in prolonged isolation because of persistent viral detection based on contemporaneous policies.

ConclusionOur findings support testing within 3-5 days after possible SARS-CoV-2 exposure to comprehensively identify infections and mitigate transmission and lend support to symptom- and time-based isolation recommendations, rather than test-based criteria.


title: Inverse planning for radiofrequency ablation in cancer therapy using multiple damage models

abstract: Radiofrequency ablation (RFA) offers localized and minimally invasive treatment of small-to-medium sized inoperable tumors. In RFA, tissue is ablated with high temperatures obtained from electrodes (needles) inserted percutaneously or via an open surgery into the target. RFA treatments are generally not planned in a systematic way, and do not account for nearby organs-at-risk (OARs), potentially leading to sub-optimal treatments and inconsistent treatment quality. We therefore develop a mathematical framework to design RFA treatment plans that provide complete ablation while minimizing healthy tissue damage. Borrowing techniques from radiosurgery inverse planning, we design a two-stage approach where we first identify needle positions and orientations, called needle orientation optimization, and then compute the treatment time for optimal thermal dose delivery, called thermal dose optimization. Several different damage models are used to determine both target and OAR damage. We present numerical results on three clinical case studies. Our findings indicate a need for high source voltage for short tip length (conducting portion of the needle) or fewer needles, and low source voltage for long tip length or more needles to achieve full coverage. Further, more needles yields a larger ablation volume and consequently more OAR damage. Finally, the choice of damage model impacts the source voltage, tip length, and needle quantity.

category: radiology and imaging


title: Emergence of Severe Metastatic Hypervirulent Klebsiella pneumoniae infections in Texas

abstract:
BackgroundHypervirulent Klebsiella pneumoniae (hvKp) infections have mainly been described in Asia. Two patients in the age group of 30 to 50 years presented within a two month period to a tertiary referral hospital in Texas with septic shock, hepatic abscess and septic thrombophlebitis. Blood cultures were positive for Klebsiella pneumoniae (isolates 2020CK-00441 and 2021CK-00720 respectively).

MethodsWhole genome sequencing was performed using paired-end Illumina MiSeq reads for both isolates. Nanopore sequencing to obtain a closed genome was performed for 2020CK-00441.

Results2020CK-00441 belonged to ST23 type while 2021CK-00720 was a ST65 type isolate. Kleborate analyses predicted with high confidence that both the isolates were hvKp. Phylogenetic analyses showed that the two strains are not closely related to each other or to any other known hvKp isolates. Both the isolates had yersiniabactin, colibactin, aerobactin and salmochelin producing loci which likely confer these isolates hvKp phenotype. 2020CK-00441 had a unique pK2044 like plasmid.

ConclusionsHvKp strains capable of causing devastating metastatic septic infections have emerged in Texas. These isolates are unique when compared to other hvKp strains of the world. Country wide surveillance and whole genome sequencing of these strains is essential to prevent a major public health emergency in USA.

category: respiratory medicine


title: Association between Preventive Measures against Workplace Infection and Preventive Behavior against Personal Infection

abstract:
ObjectivesTo prevent the spread of coronavirus disease 2019 (COVID-19) infection, it is necessary for each individual to adopt infection prevention behavior. We investigated the effect of infection control measures implemented in the workplace on personal infection prevention behavior.

MethodsWe conducted a self-administered questionnaire survey through the Internet from December 22 to 25, 2020, during which period COVID-19 was spreading. Among respondents aged 20 to 65 years (n=27,036), a total of 21,915 workers were included in the analysis after excluding self-employed workers (n=2,202), workers in small/home offices (n=377), and agriculture, forestry, and fisheries workers (n=212), etc., whose personal infection prevention behavior was almost the same as infection control measures taken in the workplace.

ResultsThe results showed that as the number of infection control measures in the workplace increased, implementation of infection prevention behavior by individuals also significantly increased. However, the relationship differed depending on the type of personal infection prevention behavior. Specifically, infection control measures against COVID-19 in the workplace may affect personal infection prevention behavior.

ConclusionImplementation of infection control measures in the workplace appears to deepen personal understanding of infection prevention behaviors, and increases awareness of the importance of individual infection prevention behavior and its implementation by all individuals. These findings may be applicable not only to COVID-19 measures but also to responses to other emerging infections and seasonal influenza.

category: occupational and environmental health


title: Incidence and outcome of cancer in 16- to 17-year-old adolescents in a tertiary referral hospital

abstract:
BACKGROUNDAdolescents have a unique cancer profile that includes typical childhood cancers such as acute lymphoblastic leukemia (ALL) and adult-type cancers like melanoma and thyroid cancer. In Finland, adolescents above 16 years have been largely treated in adult oncology centers in contrast to many Western countries in which the minimum admittance age is 18 years. The aim of this study was to investigate characteristics, therapy and outcome of cancer in adolescents aged 16 to 17 years.

MATERIALS AND METHODSThis retrospective cohort study included adolescents aged 16 to under 18 years at the time of cancer diagnosis between 2000 and 2019 in Tampere University Hospital, a regional tertiary referral center. Clinical data were retrieved from hospital medical records and included diagnosis, clinical and laboratory parameters, therapy and outcome. In addition to standard descriptive statistical analyses, the Kaplan-Meier method and Cox regression modelling were applied to study the outcome and associated factors.

RESULTSA total of 93 patients were diagnosed with a malignant tumor at the age of 16 or 17 years. Males were more often diagnosed with a cancer (62%), while non-CNS (non-central nervous system) solid cancers were the most common entities (76%) and Hodgkin lymphoma was the most common cancer diagnosis (31%). Seventy patients completed their therapy in the referral center and were followed up for a median of 5.4 years. The majority of patients were treated in the adult department (69%). Complete remission was achieved for 89% of patients, while 21% experienced tumor recurrence. The 5-year event-free survival was 65% (95% CI, 54% to 79%) and overall survival 82% (95% CI, 73% to 93%).

CONCLUSIONSThe majority of cancers in adolescents of 16 to 17 years of age are solid cancers. Patient outcome in our cohort was favorable and is in line with previously published data.

category: oncology


title: A Chinese host genetic study discovered type I interferons and causality of cholesterol levels and WBC counts on COVID-19 severity

abstract: As of early May 2021, the ongoing pandemic COVID-19 has caused over 160 million of infections and over 3 million deaths worldwide. Many risk factors, such as age, gender, and comorbidities, have been studied to explain the variable symptoms of infected patients. However, these effects may not fully account for the diversity in disease severity. Here, we present a comprehensive analysis of a broad range of patients laboratory and clinical assessments to investigate the genetic contributions to COVID-19 severity. By performing GWAS analysis, we discovered several concrete associations for laboratory features. Based on these findings, we performed Mendelian randomization (MR) analysis to investigate the causality of laboratory traits on disease severity. From the MR study, we identified two causal traits, cholesterol levels and WBC counts. The functional gene related to cholesterol levels is ApoE and people with particular ApoE genotype are more likely to have higher cholesterol levels, facilitating the process that SARS-CoV-2 binds on its receptor ACE2 and aggravating COVID-19 disease. The functional gene related to WBC counts is MHC system that plays a central role in the immune system. The host immune response to the SARS-CoV-2 infection greatly affects the patients severity status and clinical outcome. Additionally, our gene-based and GSEA analysis revealed interferon pathways, including type I interferon receptor binding, regulation of IFNA signaling, and SARS coronavirus and innate immunity. We hope that our work will make a contribution in studying the genetic mechanisms of disease illness and serve as useful reference for the clinical diagnosis and treatment of COVID-19.


title: Poor antibody response to BioNTech/Pfizer COVID-19 vaccination in SARS-CoV-2 naïve residents of nursing homes

abstract:
BackgroundResidents of nursing homes (NH) are at high risk of COVID-19 related morbidity and death and may respond poorly to vaccination because of old age and frequent comorbidities.

MethodsForty residents and forty staff members either naive or previously infected with SARS-CoV-2 were recruited in two NH in Belgium before immunization with two doses of 30{micro}g BNT162b2 mRNA vaccine at day 0 and day 21. Binding antibodies (Ab) to SARS-CoV-2 receptor binding domain (RBD), spike domains S1 and S2, RBD Ab avidity, and neutralizing Ab against SARS-CoV-2 wild type and B.1.351 variant were assessed at days 0, 21, 28, and 49.

ResultsSARS-CoV-2 naive residents had lower Ab responses to BNT162b2 mRNA vaccination than naive staff. These poor responses involved lower levels of IgG to all domains of the vaccine antigen, lower avidity of RBD IgG, and lower levels of Ab neutralizing the vaccine strain. No naive resident had detectable neutralizing Ab to the B.1.351 variant. High and comparable Ab responses were observed in residents and staff previously infected with SARS-CoV-2. Clustering analysis revealed that poor vaccine responders not only included naive residents but also naive staff, emphasizing the heterogeneity of responses to mRNA vaccination in the general population.

ConclusionsThe poor Ab responses to mRNA vaccination observed in infection naive residents and in some naive staff members of NH suggest suboptimal protection against breakthrough infection, especially with variants of concern. Adapted vaccination regimens may be needed to provide optimal protection against COVID-19 to vulnerable populations.

SummaryPoor antibody responses to COVID-19 mRNA vaccination were observed in SARS-CoV-2 infection naive residents and some naive staff members of nursing homes. This suggests suboptimal protection against breakthrough infection, especially with variants of concern, and the need for adapted vaccination regimens.


title: Post-Acute COVID Syndrome, the Aftermath of Mild to Severe COVID-19 in Brazilian Patients

abstract:
ObjectiveTo describe persistent symptoms after acute COVID-19 in different spectrum of disease severity in a population from an upper/middle income country, and identify the main clinical features impacting the quality of life.

DesignCross-sectional study.

SettingOutpatient clinic from a public post-COVID-19 health center (CPC) at Bahia-Brazil, a state where 80% are black or mixed race.

ParticipantsPatients admitted between August 2020 and February 2021 with symptoms at least one month after the onset of COVID-19.

Main outcome measuresPACS and related disorders such as hospitalization one month or later after disease onset, biochemical dysregulation and reduced quality of life (EQ-5D-5L questionnaire).

ResultsAmong 683 individuals assisted at CPC in this period, 602 were recruited. Patients had average of 52 ({+/-}14.6) years, 355 (59%) were female, 528 (88%) black/brown. Individuals were classified as mild (39.9%), moderate (27.9%) or severe (32.2%) during acute illness if outpatient, hospitalized non-UCI or UCI, respectively. Most patients reported a polysymptomatic profile, in median eight (IQR=6-9) acute symptoms. The most frequent residual symptoms were dyspnea (66%), fatigue (62%) and chest pain (43%). Women were more affected regardless disease severity at acute stage: presented more residual symptoms [4 (2-6) vs 3 (2-4)] and a higher impact in quality of life. Altered HbA1c [(184/275 (66.9%)], high CRP levels [195/484 (40.3%)] and anemia [143/545 (26.2%)] were the most common abnormalities in laboratory exams. 76 patients presented HbA1c above 6.4% although only 42 referred previous diagnosis of diabetes mellitus. After one month of disease onset, 30 patients required hospitalization, including seven cases with mild acute illness. Hospital admission after acute disease was required on 30 patients, seven (23%) were mild. Quality of life had been affected for 357/404 (88.4%) patients according to EuroQoL (EQ-5D-5L), mainly the domains of anxiety/depression [severe or extreme anxiety for 79/401 (19.7%)] and pain/discomfort [severe or extreme pain for 71/403 (17.6%)]. The median EuroQoL Global Score was 70 [IQR 50-80]. PACS symptoms such as dyspnea, chest pain, and fatigue, was associated with decreased quality of life.

ConclusionsPACS, such as dyspnea, chest pain and fatigue, occurred after variable degree of disease severity. Among this majority black/mixed-race patients, woman seemed to be more affected. Other consequences included post-acute hospitalization, and abnormal glucose metabolism and reduced quality of life.

Summary BoxSection 1: What is already known on this topic:

{checkmark}Post-Acute COVID Syndrome (PACS) comprises a set of persistent or new-onset symptoms after illness onset.
{checkmark}As far as we know, there are no studies describing PACS in a population principally black and mixed-race. Additionally, few studies have addressed PACS among outpatients.

Section 2: What this study adds:

{checkmark}Similar PACS were reported after mild, moderate and severe illness. Dyspnea, fatigue and chest pain were the most prevalent symptoms in this population presenting majority of black/mixed-race patients.
{checkmark}Women presented more residual symptoms, a higher frequency of myalgia and worse score for mobility, usual activities, anxiety/depression, and pain.
{checkmark}Hospitalization may occur one month or later after mild or moderate/severe acute infection due to respiratory and vascular disorders. Abnormal glucose metabolism was detected in the absence of previous diagnosis of diabetes mellitus.


title: Highly-specific memory B cells generation after the 2nd dose of BNT162b2 vaccine compensate for the decline of serum antibodies and absence of mucosal IgA

abstract:
Specific memory B cells and antibodies are reliable read-out of vaccine efficacy. We analyzed these biomarkers after one and two doses of BNT162b2 vaccine. The second dose significantly increases the level of highly-specific memory B cells and antibodies. Two months after the second dose, specific antibody levels decline, but highly specific memory B cells continue to increase thus predicting a sustained protection from COVID-19.

O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=112 SRC="FIGDIR/small/21258284v1_ufig1.gif" ALT="Figure 1">
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org.highwire.dtl.DTLVardef@1700325org.highwire.dtl.DTLVardef@deb172org.highwire.dtl.DTLVardef@53f056org.highwire.dtl.DTLVardef@c7a98d_HPS_FORMAT_FIGEXP  M_FIG Graphical Abstract

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title: Analysis of cell-mediated immunity in people with long Covid.

abstract:
IntroductionThe objective of this study is to analyse the specific immune response against SARS-CoV-2 in those affected by Long Covid (LC), attributable to T cells (cell-mediated immunity) and to carry out a parallel analysis of the humoral response and lymphocyte typing.

MethodologyDescriptive cross-sectional study of 74 patients with LC for at least 4 months since diagnosis. The collected data were: information on the COVID-19 episode and the persistent symptoms, medical history and a specific cell-mediated immunity to SARS-CoV-2 through flow cytometry, assessing the release of interferon-gamma (IFN-{gamma}) by T4 lymphocytes, T8 lymphocytes and NK cells. Descriptive and comparative analyses were carried out.

ResultsPatients with LC had negative serology for Covid-19 in 89% of cases but 96% showed specific cellular immunity to SARS-CoV-2 an average of 9.5 months after infection: 89% of this response corresponded to T8 lymphocytes, 58% to NK cells, and 51% to T4 lymphocyte (20% negligibly positive). Most of them had altered immune cell typing and we found that T4 lymphocyte counts were low in 34% of cases and NK cell high in 64%. Macrophage populations were detected in the peripheral blood of 7% of them. Patients displayed a higher percentage of illnesses related to &[Prime]abnormal&[Prime] immune responses, either preceding SARS-CoV-2 infection (43%) or following it in 23% of cases.

ConclusionThe immune system appears to have an important involvement in the development of LC and viral persistence could be the cause or consequence of it. Further analysis with a control group should be performed.


title: Response of Unvaccinated US Adults to Official Information About the Pause in Use of the Johnson & Johnson-Janssen COVID-19 Vaccine

abstract: On April 13, 2021 the Centers for Disease Control and Prevention (CDC) and Food and Drug Administration (FDA) recommended in a pause in use of the Johnson & Johnson (J&J)-Janssen COVID-19 vaccine due to reports of cerebral venous sinus thrombosis (CVST) in recently vaccinated individuals. The announcement of the pause required development of a coordinated communication strategy under extreme time pressure and careful messaging by stakeholders to mitigate reduced public confidence in COVID-19 vaccines, as was observed following the temporary suspension of the Oxford-AstraZeneca vaccine in many countries. In this survey study, we evaluated understanding and impressions of the CDCs public online information about the J&J-Janssen pause among unvaccinated US adults.


title: Post-COVID-19 Perceived Stigma-Discrimination Scale: Psychometric Development and Evaluation

abstract: The COVID-19 survivors face social stigmatization, even with negative tests. Valid and reliable instruments are required to quantify the stigma-discrimination complex associated with COVID-19 (COVID-19-CED). The study aimed to adapt and evaluate a scale to measure COVID-19-CED in COVID-19 survivors. A validation study was done with 330 COVID-19 survivors between 18 and 89 years. The COVID-19 Perceived Discrimination Scale (C-19-PDS) was used, which was adapted from the Tuberculosis Perceived Discrimination Scale. An exploratory factor analysis (EFA), confirmatory factor analysis (CFA), internal consistency, and differential item functioning (DIF) were performed using the classical theory of tests. EFA showed a one-dimensional solution for the items of C-19-PDS; however, CFA showed poor goodness-of-fit indicators. The 5-item version of the C-19-PDS showed better goodness-of-fit indicators, high internal consistency, and non-gender DIF. In conclusion, the 5-item version of the C-19-PDS is one-dimensional, with high internal consistency, and without gender DIF. This instrument is recommended to evaluate COVID-19-CED in the Colombian population.


title: Priorities for Future Research about Screen Use and Adolescent Mental Health: A Participatory Prioritization Study

abstract:
This study aimed to identify research priorities for future research on screen use and adolescent mental health, from the perspectives of young people, parents/carers, and teachers.

MethodsThe study design was informed by the James Lind Alliance Priority Setting Partnership approach. A three-stage consensus-based process of consultation to identify research priorities using qualitative and quantitative methods. Research was guided by a steering group comprising researchers, third sector partners, clinicians, parents/carers and young people. A Young Peoples Advisory Group contributed at each stage.

ResultsInitial steps generated 26 research questions of importance to children and young people; these were ranked by 357 participants (229 children and young people and 128 adults). Consensus was reached for the prioritization of four topics for future research: (i) the impact of exposure to adult content on young peoples mental health and relationships; (ii) the relationship between screen use and the wellbeing of young people from vulnerable groups; (iii) the impact of screen use on brain development; and (iv) the relationship between screen use and sleep.

Additionally, young participants prioritized questions about online bullying, advertisements targeting young people, and the relationship between social media and specific mental health conditions. Research topics of interest arising specifically during the pandemic included the effects on adolescent mental health of exposure to constant news updates and online racial bias, and how young people take part in activism online

ConclusionThese findings will enable researchers and funders to conduct research that is needs-oriented and relevant to the target audience.

O_TEXTBOXKey points and relevance of the study{blacksquare} Evidence about the effects of screen use on adolescent mental health is weak and has been driven by researchers and technology developers.
{blacksquare}Young people, parents and teachers prioritized research questions about exposure to adult content online; wellbeing of vulnerable populations; impact of screen use on development; and relation of screen use with sleep.
{blacksquare}Young people additionally prioritized research questions related to social media and developing specific mental disorders, online bullying, and companies exploiting adolescents vulnerabilities (for example through targeted publicity).
{blacksquare}Findings should inform calls for research and funding allocation in order to develop evidence-based policy and guidelines about screen use.

C_TEXTBOX


title: g-CXR-Net: A Graphic Application for the Rapid Recognition of SARS-CoV-2 from Chest X-Rays

abstract: g-CXR-Net is a graphic application for the rapid recognition of SARS-CoV-2 from Antero/Posterior chest X-rays. It employs the Artificial Intelligence engine of CXR-Net (arXiv:2103.00087) to generate masks of the lungs overlapping the heart and large vasa, probabilities for Covid vs. non-Covid assignment, and high resolution heat maps that identify the SARS associated lung regions.


title: Dementia is strongly associated with medial temporal atrophy even after accounting for neuropathologies

abstract:
ObjectiveBrain atrophy is associated with degenerative neuropathologies as well as clinical status of dementia. Whether dementia influences atrophy independent of neuropathologies is not known. In this study, we examined the pattern of atrophy associated with dementia while accounting for the most common dementia-related neuropathologies.

MethodsWe used data from National Alzheimers Coordinating Center (NACC, N=129) and Alzheimers Disease Neuroimaging Initiative (ADNI, N=47) participants with suitable in-vivo 3D-T1w MRI and autopsy data. We determined dementia status at visit closest to MRI. We examined the following dichotomized neuropathological variables: Alzheimers disease neuropathology, hippocampal sclerosis, Lewy Bodies, cerebral amyloid angiopathy, atherosclerosis. Voxel-based morphometry (VBM) identified areas associated with dementia after accounting for neuropathologies. Identified regions of interest were further analyzed. We used multiple linear regression models adjusted for neuropathologies and demographic variables.

ResultsWe found strong associations for dementia with volumes of the hippocampus, amygdala, and parahippocampus (semi-partial correlations[≥]0.28, P<0.0001 for all regions in NACC; semi-partial correlations[≥]0.35, P[≤]0.01 for hippocampus and parahippocampus in ADNI). Dementia status accounted for more unique variance in atrophy in these structures ([~]8%) compared with neuropathological variables; the only exception was hippocampal sclerosis which accounted for more variance in hippocampal atrophy (10%).

ConclusionEven after accounting for the most common neuropathologies, dementia still had among the strongest correlations with atrophy of medial temporal lobe structures. This suggests that atrophy of the medial temporal lobe is most related to clinical status of dementia as opposed to Alzheimers or other neuropathologies.


title: WHAT ABOUT USING SNIFFIN STICKS 12 SCREENING TEST TO IDENTIFY POST-COVID-19 OLFACTORY DISORDERS?

abstract:
BackgroundOlfactory impairment is a major sequela of SARS-CoV-2 infection and has a negative impact on daily life quality. Olfactory loss can be assessed in many ways but seems to be little realized in a daily clinical practice. The sniffin Sticks test - 12 items (SST-12) can be used in quick olfactory disorders screening. Its use in a post-covid19 situation was the main objective of this work.

MethodologyConsecutive patients consulting to the ENT department with post-Covid-19 olfactory loss were included. The clinical examination included an analog scale for the self-assessment of olfactory recovery (VAS), self-reported salt and sugar intake, a nasofibroscopy, the complete Sniffin Stick Test (SST) and the SST-12.

ResultsAmong the 54 patients included, based on the SST-12, 14,8% (n=8) of the patients could be classified as normosmic (SST-12[≥]11), 48,1% (n=26) as hyposmic (6< SST-12<10) and 37% (n=20) as functional anosmic (SST-12[≤]6). We report excellent and significant correlations between SST-12 and SST or VAS assessments. Salt and Sugar increased intake seems significantly related to SST-12 results.

ConclusionsSST-12 is a reliable way to screen post-COVID-19 olfactory disorders could be used in a daily clinical practice and might be used to prevent bad diet habits and so cardiovascular risk.

category: otolaryngology


title: Financial Meltdown in Swing Hospitals during the COVID-19 Outbreak

abstract: Hospitals in Japan have complete autonomy in deciding whether to admit COVID-19 patients, similar to that of the US. Taking this into account, we estimated the effect of admitting COVID-19 patients on hospital profits, using instrumental variable (IV) regression. Using IVs related to government intervention enabled us to not only estimate the effect of admitting COVID-19 patients among "swing hospitals," where both options (to admit or to not admit COVID-19 patients) could potentially be realized but to also evaluate the effect of government intervention on such hospitals. Our empirical results revealed that monthly profits per bed decreased by approximately JPY 600,000 ({approx} USD 6,000) among swing hospitals, which is 15 times the average monthly profits in 2019. This overwhelming financial damage indicates that it would be costly for swing hospitals to treat COVID-19 patients because of their low suitability for admitting such patients. Given the implications of our main results, we propose an alternative strategy to handling surges in patients with new infectious diseases.

category: health economics