title: Attitudes Towards Digital Health Technology: Introducing the Digital Health Scale

abstract:
ObjectiveThe study sought to investigate the relationship between attitude towards digital health technology and age, gender and frequency of use of digital health technology and to consider whether age, gender and frequency of use present potential barriers to accessing future healthcare in the UK. Differences in technological affinity are likely to lead to differences in the adoption of digital health technology and subsequent inequalities in healthcare between older and younger people and between men and women.

DesignThe study represents an example of a technology adoption study employing a survey-based cross sectional correlational design. Attitude towards digital health technology was measured using the 20 item Digital Health Scale. Age, gender, frequency of use of health technology and employment status data were gathered using a demographics questionnaire. The opportunity sample (N = 247) included volunteer participants aged 16-84 years (M = 31.7, SD = 19.35, 156 females and 91 males).

ResultsResults indicated a significant negative correlation between age and positive attitude towards digital health technology (r = -0.24, p < .01). Gender differences in attitudes towards digital health technology were non-significant (p > .05). Significant differences in frequency of use were also found, where occasional and frequent use resulted in more positive attitudes than never having used digital health technology (p < 0.05) and participants reporting frequent use were significantly older than those reporting never or occasional use (p < .05)

ConclusionFindings identified age, but not gender, as a significant factor in attitude towards digital health technology, suggesting that continued and increased reliance on digital technology in healthcare may lead to age, but not gender, related inequalities in access to healthcare in the UK. That frequent users of digital health technology were also older, highlights the greater demand for healthcare services by older individuals and is further evidence for the potential of digital healthcare to lead to age related inequalities in access to and provision of healthcare. Recommendations for successful application of digital healthcare technology are considered in the light of these findings.


title: Association between City-wide Lockdown and COVID-19 Hospitalization Rates in Multigenerational Households in New York City

abstract:
BackgroundCity-wide lockdowns and school closures have demonstrably impacted COVID-19 transmission. However, simulation studies have suggested an increased risk of COVID-19 related morbidity for older individuals inoculated by house-bound children. This study examines whether the March 2020 lockdown in New York City (NYC) was associated with higher COVID-19 hospitalization rates in neighborhoods with larger proportions of multigenerational households.

MethodsWe obtained daily age-segmented COVID-19 hospitalization counts in each of 166 ZIP code tabulation areas (ZCTAs) in NYC. Using Bayesian Poisson regression models that account for spatiotemporal dependencies between ZCTAs, as well as socioeconomic risk factors, we conducted a difference-in-differences study amongst ZCTA-level hospitalization rates from February 23 to May 2, 2020. We compared ZCTAs in the lowest quartile of multigenerational housing to other quartiles before and after the lockdown.

FindingsAmong individuals over 55 years, the lockdown was associated with higher COVID-19 hospitalization rates in ZCTAs with more multigenerational households. The greatest difference occurred three weeks after lockdown: Q2 vs. Q1: 54% increase (95% Bayesian credible intervals: 22 - 96%); Q3 vs. Q1: 48%, (17 - 89%); Q4 vs. Q1: 66%, (30 - 211%). After accounting for pandemic-related population shifts, a significant difference was observed only in Q4 ZCTAs: 37% (7 -76%).

InterpretationBy increasing house-bound mixing across older and younger age groups, city-wide lockdown mandates imposed during the growth of COVID-19 cases may have inadvertently, but transiently, contributed to increased transmission in multigenerational households.

FundingNational Center for Advancing Translational Sciences; Clinical and Translational Science Center at Weill Cornell Medical College.

category: health policy


title: Local SARS-CoV-2 peptide-specific Immune Responses in Convalescent and Uninfected Human Lung Tissue Models

abstract: Multi-specific and long-lasting T cell immunity have been recognized as indicators for long term protection against pathogens including the novel coronavirus SARS-CoV-2, the causative agent of the COVID-19 pandemic. Functional significance of peripheral memory T cells in individuals recovering from COVID-19 (COVID-19+) are beginning to be appreciated; but little is known about lung resident memory T cells (lung TRM) in SARS-CoV-2 infection. Here, we utilize a perfused three dimensional (3D) human lung tissue model and identify pre-existing local T cell immunity against SARS-CoV-2 proteins in lung tissues. We report ex vivo maintenance of functional multi-specific IFN-{gamma} secreting lung TRM in COVID-19+ and their induction in lung tissues of vaccinated COVID-19+. Importantly, we identify SARS-CoV-2 peptide-responding B cells and IgA+ plasma cells in lung tissues of COVID-19+ in ex vivo 3D-tissue models. Our study highlights the importance of balanced and local anti-viral immune response in the lung with persistent induction of TRM and IgA+ plasma cells for future protection against SARS-CoV-2 infection. Further, our data suggest that inclusion of multiple viral antigens in vaccine approaches may broaden the functional profile of memory T cells to combat the severity of coronavirus infection.

category: infectious diseases


title: Local SARS-CoV-2 peptide-specific Immune Responses in Lungs of Convalescent and Uninfected Human Subjects


title: The missing microbes: Bifidobacterium and Faecalibacterium depletion and loss of microbiome diversity as potential susceptibility markers for SARS-CoV-2 infection and severity

abstract:
ObjectiveThe study objective was to compare gut microbiome diversity and composition in SARS-CoV-2 polymerase chain reaction (PCR)-positive patients whose symptoms ranged from asymptomatic to severe, versus PCR-negative exposed controls.

DesignUsing a cross-sectional design, we performed shotgun next-generation sequencing (NGS) on stool samples to evaluate gut microbiome composition and diversity in both patients with SARS-CoV-2 PCR- confirmed infections, that had presented to Ventura Clinical Trials for care from March 2020 through October 2021, and SARS-CoV-2 PCR-negative exposed controls. Patients were classified as being asymptomatic or having mild, moderate, or severe symptoms based on NIH criteria. Exposed controls were individuals with prolonged or repeated close contact with patients with SARS-CoV-2 infection or their samples, e.g. household members of patients or frontline healthcare workers. Microbiome diversity and composition were compared between patients and exposed controls at all taxonomic levels.

ResultsCompared with controls (n=20), severely symptomatic SARS-CoV-2 infected patients (n=28) had significantly less bacterial diversity (Shannon Index, P=0.0499; Simpson Index, P=0.0581), and positive patients overall had lower relative abundances of Bifidobacterium (P<0.0001), Faecalibacterium (P=0.0077), and Roseburium (P=0.0327), while having increased Bacteroides (P=0.0075). Interestingly, there was an inverse association between disease severity and abundance of the same bacteria.

ConclusionWe hypothesize that low bacterial diversity and depletion of Bifidobacterium genera either before or after infection led to reduced pro-immune function, thereby allowing SARS-CoV-2 infection to become symptomatic. This particular dysbiosis pattern may be a susceptibility marker for symptomatic severity from SARS-CoV-2 infection and may be amenable to pre-, intra-, or post infection intervention.Keywords: SARS-CoV-2, COVID, Microbiome, Bifidobacterium, Faecalibacterium, Bacteriodes, Shannon Index, Simpson Index, Severity, Microbiota

Registrationclinicaltrials.gov NCT04031469 (PCR -) and 04359836 (PCR+)

O_TBL View this table:
org.highwire.dtl.DTLVardef@173dbe8org.highwire.dtl.DTLVardef@16a75b5org.highwire.dtl.DTLVardef@55d55eorg.highwire.dtl.DTLVardef@12b2302org.highwire.dtl.DTLVardef@107663d_HPS_FORMAT_FIGEXP  M_TBL C_TBL


title: The lost microbes of COVID-19: Bifidobacteria depletion and decreased microbiome diversity are a predictability marker of severe COVID 19, a cross sectional study


title: The lost microbes of COVID-19: Bifidobacterium, Faecalibacterium depletion and decreased microbiome diversity associated with SARS-CoV-2 infection severity


title: A randomized controlled trial of antibody response to 2019-20 cell-based inactivated and egg-based live attenuated influenza vaccines in children and young adults

abstract:
BackgroundHemagglutination inhibition (HAI) titers to the live-attenuated influenza vaccine (LAIV4) are typically lower than its counterpart egg-based inactivated influenza vaccines (IIV). Similar comparisons have not been made between LAIV4 and the 4-strain, cell-culture inactivated influenza vaccine (ccIIV4). We compared healthy children and young adult HAI titers against the 2019-2020 LAIV4 and ccIIV4.

MethodsParticipants aged 4-21 years were randomized 1:1 to receive ccIIV4 (n =100) or LAIV4 (n=98). Blood was drawn prevaccination and on day 28 (21-35) post vaccination. HAI assays against egg-grown A/H1N1, A/H3N2, both vaccine B strains and cell-grown A/H3N2 antigens were conducted. Outcomes were geometric mean titers (GMT) and geometric mean fold rise (GMFR) in titers.

ResultsGMTs to A/H1N1, A/H3N2 and B/Victoria increased following both ccIIV and LAIV and to B/Yamagata following ccIIV (p<0.05). The GMFR range was 2.4-3.0 times higher for ccIIV4 than for LAIV4 (p<0.001). Within vaccine types, egg-grown A/H3N2 GMTs were higher (p<0.05) than cell-grown GMTs [ccIIV4 day 28: egg=205 (95% CI: 178-237); cell=136 (95% CI:113-165); LAIV4 day 28: egg=96 (95% CI: 83-112); cell=63 (95% CI: 58-74)]. The GMFR to A/H3N2 cell-grown and egg-grown antigens were similar. Pre-vaccination titers inversely predicted GMFR.

ConclusionThe HAI response to ccIIV4 was greater than LAIV4 in this study of mostly older children, and day 0 HAI titers inversely predicted GMFR for both vaccines. For both vaccines, the A/H3N2 cell-grown antigen levels were lower than egg-grown, but the GMFR for cell-grown and egg-grown did not differ significantly within vaccine type.

Clinical Trials NoNCT03982069


title: UTTARAKHAND COVID-19 CASES AND DEATHS: COMPARING THE DEMOGRAPHICS AND SUGGESTIVE STRATEGY TO PREVENT SIMILAR PANDEMICS IN FUTURE

abstract: Coronavirus disease 19 (Covid-19) is causing a dramatic impact on human life worldwide. As of June 11 2021, later one has attributed more than 174 million confirmed cases and over 3.5 million deaths globally. Nonetheless, a World Bank Group flagship report features Covid-19 induced global crisis as the strongest post-recession since World WarII. Currently, all approved therapeutics or vaccines are strictly allowed for emergency use. Hence, in the absence of pharmaceutical interventions, it is vital to analyze data set covering the growth rates of positive human cases, number of recoveries, other factors, and future strategies to manage the growth of fatal Covid-19 effectively. The Uttarakhand state of India is snuggled in the lap of the Himalayas and occupies more people than Israel, Switzerland, Hong Kong, etc. This study analyzed state Covid-19 data, fetched from an authenticated government repository using Python 3.9 from April 1, 2020, to February 28, 2021. In the first wave, plain areas of Uttarakhand covering the districts Dehradun, Haridwar, Nainital, and U. S. Nagar were severely affected and reported peak positive cases during the 21st - 26th week. Other hands, the hilly terrains of Uttarakhand districts, including Chamoli, Pauri Garhwal, and Rudraprayag, reported a high number of positive cases between the 30th and 31st week, and other hilly districts reported an increase in Covid-19 cases during the 34th to 38th week. The highest recovery rate was attributed to the hilly district Rudraprayag. The analysis also revealed that a very high doubling rate was seen during the last week of May to the first week of Jun 2020. At last, based on this blueprint, we have suggested 6-points solutions for preventing the next pandemic.


title: A semi-parametric, state-space compartmental model with time-dependent parameters for forecasting COVID-19 cases, hospitalizations, and deaths

abstract: Short-term forecasts of the dynamics of COVID-19 in the period up to its decline following mass vaccination was a task that received much attention but proved difficult to do with high accuracy. However, the availability of standardized forecasts and versioned data sets from this period allows for continued work in this area. Here we introduce the Gaussian Infection State Space with Time-dependence (GISST) forecasting model. We evaluate its performance in 1-4 week ahead forecasts of COVID-19 cases, hospital admissions, and deaths in the state of California made with official reports of COVID-19, Googles mobility reports, and vaccination data available each week. Evaluation of these forecasts with a weighted interval score shows them to consistently outperform a naive baseline forecast and often score closer to or better than a high-performing ensemble forecaster. The GISST model also provides parameter estimates for a compartmental model of COVID-19 dynamics, includes a regression submodel for the transmission rate, and allows for parameters to vary over time according to a random walk. GISST provides a novel, balanced combination of computational efficiency, model interpretability, and applicability to large multivariate data sets that may prove useful in improving the accuracy of infectious disease forecasts.

category: epidemiology


title: Heterologous prime-boost immunization with CoronaVac and Convidecia

abstract:
BackgroundThe safety and immunogenicity of heterologous prime-boost COVID-19 vaccine regimens with one shot of a recombinant adenovirus type-5-vectored COVID-19 vaccine Convidecia has not been reported.

MethodsWe conducted a randomized, controlled, observer-blinded trial of heterologous prime-boost immunization with CoronaVac and Convidecia in healthy adults 18-59 years of age. Eligible participants who were primed with one or two doses of CoronaVac were randomly assigned at a 1:1 ratio to receive a booster dose of Convidecia or CoronaVac. Participants were masked to the vaccine received but not to the three-dose or two-dose regimen. The occurrences of adverse reactions within 28 days after the vaccination were documented. The geometric mean titers of neutralizing antibodies against live SARS-CoV-2 virus were measured at 14 and 28 days after the booster vaccination.

ResultsBetween May 25 and 26, 2021, a total of 300 participants were enrolled. Participants who received a booster shot with a heterologous dose of Convidecia reported increased frequencies of solicited injection-site reactions than did those received a homogeneous dose of CoronaVac, but frequencies of systemic reactions. The adverse reactions were generally mild to moderate. The heterologous immunization with Convidecia induced higher live viral neutralizing antibodies than did the homogeneous immunization with CoronaVac (197.4[167.7, 232.4] vs. 33.6[28.3, 39.8] and 54.4[37. 9, 78.0] vs. 12.8[9.3, 17.5]) at day 14 in the three- and two-dose regimen cohort, respectively.

ConclusionsThe heterologous prime-boost regimen with Convidecia after the priming with CoronaVac was safe and significantly immunogenic than a homogeneous boost with CoronaVac (ClinicalTrials.gov, number NCT04892459).


title: Suicide and self-harm in low- and middle- income countries during the COVID-19 pandemic: A systematic review

abstract:
There is widespread concern over the potential impact of the COVID-19 pandemic on suicide and self-harm globally, particularly in low- and middle-income countries (LMIC) where the burden of these behaviours is greatest. We synthesised the evidence from the published literature on the impact of the pandemic on suicide and self-harm in LMIC.

This review is nested within a living systematic review that continuously identifies published evidence (all languages) through a comprehensive automated search of multiple databases (PubMed; Scopus; medRxiv, PsyArXiv; SocArXiv; bioRxiv; the WHO COVID-19 database; and the COVID-19 Open Research Dataset by Semantic Scholar (up to 11/2020), including data from Microsoft Academic, Elsevier, arXiv and PubMed Central.) All articles identified by the 4th August 2021 were screened. Papers reporting on data from a LMIC and presenting evidence on the impact of the pandemic on suicide or self-harm were included.

A total of 22 studies from LMIC were identified representing data from 12 countries. There was an absence of data from Africa. The reviewed studies mostly report on the early months of COVID-19 and were generally methodologically poor. Few studies directly assessed the impact of the pandemic. The most robust evidence, from time-series studies, indicate either a reduction or no change in suicide and self-harm behaviour.

As LMIC continue to experience repeated waves of the virus and increased associated mortality, against a backdrop of vaccine inaccessibility and limited welfare support, continued efforts are needed to track the indirect impact of the pandemic on suicide and self-harm in these countries.

category: public and global health


title: Unraveling the COVID-19 hospitalization dynamics in Spain using publicly available data

abstract:
BackgroundOne of the main challenges of the ongoing COVID-19 pandemic is to be able to make sense of available, but often heterogeneous and noisy data, to characterize the evolution of the SARS-CoV-2 infection dynamics, with the additional goal of having better preparedness and planning of healthcare services. This contribution presents a data-driven methodology that allows exploring the hospitalization dynamics of COVID-19, exemplified with a study of 17 autonomous regions in Spain.

MethodsWe use data on new daily cases and hospitalizations reported by the Ministry of Health of Spain to implement a Bayesian inference method that allows making short and mid-term predictions of bed occupancy of COVID-19 patients in each of the autonomous regions of the country.

FindingsWe show how to use given and generated temporal series for the number of daily admissions and discharges from hospital to reproduce the hospitalization dynamics of COVID-19 patients. For the case-study of the region of Aragon, we estimate that the probability of being admitted to hospital care upon infection is 0{middle dot}090 [0{middle dot}086-0{middle dot}094], (95% C.I.), with the distribution governing hospital admission yielding a median interval of 3{middle dot}5 days and an IQR of 7 days. Likewise, the distribution on the length of stay produces estimates of 12 days for the median and 10 days for the IQR. A comparison between model parameters for the regions analyzed allows to detect differences and changes in policies of the health authorities.

InterpretationThe amount of data that is currently available is limited, and sometimes unreliable, hindering our understanding of many aspects of this pandemic. We have observed important regional differences, signaling that to properly compare very different populations, it is paramount to acknowledge all the diversity in terms of culture, socio-economic status and resource availability. To better understand the impact of this pandemic, much more data, disaggregated and properly annotated, should be made available.


title: Greater Covid-19 Severity and Mortality in Hospitalized Patients in Second (Delta Variant) Wave Compared to the First: Single Centre Prospective Study in India

abstract:
Background & ObjectiveCovid-19 pandemic has led to multiple waves secondary to mutations in SARS-CoV-2 and emergence of variants of concern (VOC). Clinical characteristics of delta (B.1.617.2) VOC are not well reported. To compare demographic, clinical and laboratory features and outcomes in the second Covid-19 wave in India (delta VOC) with the previous wave we performed a registry-based study.

MethodsSuccessive SARS-CoV-2 reverse transcriptase-polymerase chain reaction (RT-PCR) confirmed Covid-19 patients presenting to our Advanced Covid Care hospital were prospectively recruited. In the first phase (wave) from March-December 2020, 1395 of 7476 (18.7%) suspected patients tested positive and 863 (61.89%) hospitalized, while in second wave from January-July 2021 out of 1641 confirmed cases out of 8680 (19.4%) suspected 388 (23.6%) were hospitalized. Details of clinical and laboratory features at admission to hospital, management and outcomes in the two waves have been compared.

ResultsIn both cohorts, majority were men and 20% less than 40 years. Prevalence of hypertension, diabetes and cardiovascular diseases was more than 20%. Second wave patients had similar pre-hospitalization symptom duration but had significantly greater cough, fever and shortness of breath and lower SpO2 at presentation with greater lymphopenia, C-reactive proteins, interleukin-6, ferritin, lactic dehydrogenase and transaminases. In the second vs first wave patients, requirement of supplementary oxygen (47.9% vs 34.3%), prone positioning (89.2 vs 38.6%), high flow nasal oxygen(15.7 vs 9.1%), non-invasive ventilation (14.4 vs 9.5%), invasive ventilation (16.2 vs 9.5%), steroids (94.1 vs 85.9%), remdesivir (91.2 vs 76.0%) and anticoagulants (94.3 vs 76.0%) was greater (p<0.001). Median (IQR) length of stay [8 (6-10) vs 7 (5-10) days] as well as ICU stay [9 (5-13) vs 6 (2-10) days] was more in second wave (p<0.001). In-hospital deaths occurred in 173 patients (13.9%) and were significantly more in the second wave, 75 (19.3%), compared to the first, 98 (11.5%); unadjusted odds ratio (95% CI) 1.84 (1.32-2.55) which did not change significantly with adjustment for age and sex (2.03, 1.44-2.86), and age, sex and comorbidities (2.09, 1.47-2.95). Greater disease severity at presentation was associated with mortality in both the waves.

ConclusionsCovid-19 patients hospitalized during the second wave of the epidemic (delta variant) had more severe disease with greater dyspnea, hypoxia, hematological and biochemical abnormalities compared to first wave patients. They had greater length of stay in intensive care unit, oxygen requirement, non-invasive and invasive ventilatory support. The in-hospital mortality in the second wave was double of the first.


title: Development and validation of an enzyme immunoassay for detection and quantification of SARS-CoV-2 salivary IgA and IgG

abstract: Oral fluids offer a non-invasive sampling method for the detection of antibodies. Quantification of IgA and IgG antibodies in saliva allows studies of the mucosal and systemic immune response after natural infection or vaccination. We developed and validated an enzyme immunoassay (EIA) to detect and quantify salivary IgA and IgG antibodies against the prefusion-stabilized form of the SARS-CoV-2 spike protein. Normalization against total antibody isotype was performed to account for specimen differences, such as collection time and sample volume. Saliva samples collected from 187 SARS-CoV-2 confirmed cases enrolled in 2 cohorts and 373 pre-pandemic saliva samples were tested. The sensitivity of both EIAs was high (IgA: 95.5%; IgG: 89.7%) without compromising specificity (IgA: 99%; IgG: 97%). No cross reactivity with seasonal coronaviruses was observed. The limit of detection for SARS-CoV-2 salivary IgA and IgG assays were 1.98 ng/mL and 0.30 ng/mL, respectively. Salivary IgA and IgG antibodies were detected earlier in patients with mild COVID-19 symptoms than in severe cases. However, severe cases showed higher salivary antibody titers than those with a mild infection. Salivary IgA titers quickly decreased after 6 weeks in mild cases but remained detectable until at least week 10 in severe cases. Salivary IgG titers remained high for all patients, regardless of disease severity. In conclusion, EIAs for both IgA and IgG had high specificity and sensitivity for the confirmation of current or recent SARS-CoV-2 infections and evaluation of the IgA and IgG immune response.


title: Is life-course neighbourhood deprivation associated with frailty and frailty progression from age 70 to 82 in the Lothian Birth Cohort 1936?

abstract:
BackgroundNeighbourhood features have been postulated as key predictors of frailty. However, evidence is mainly limited to cross-sectional studies without indication of long-term impact and developmental timing of the exposures. This study explored how neighbourhood social deprivation (NSD) across the life course is associated with frailty and frailty progression among older Scottish adults.

MethodsParticipants (n=323) were from the Lothian Birth Cohort 1936 with historical measures of NSD in childhood (1936-1955), early adulthood (1956-1975) and mid-to-late adulthood (1976-2014). Frailty was measured five times between the ages of 70 and 82 years using the Frailty Index. Confounder-adjusted life-course models were assessed using a structured modelling approach with least angle regression; associations were estimated for frailty at baseline using linear regression, and for frailty progression using linear mixed-effects models.

ResultsAccumulation was the most appropriate life-course model for males; greater accumulated NSD was associated with higher frailty at age 70 (b=0.017; 95%CI: 0.005, 0.029; P=0.007) with dominant exposure times in childhood and mid-to-late adulthood. Among females, mid-to-late adulthood sensitive period was the best-fit life-course model and higher NSD in this period was associated with widening frailty trajectories between age 70 and 82 (b=0.005; 95%CI: 0.0004, 0.009, P=0.033).

ConclusionsThis is the first investigation of the life-course impact of neighbourhood deprivation on frailty in a cohort of older adults with residential information across their lives. Future research should explore neighbourhood mechanisms linking deprivation to frailty. Policies designed to address neighbourhood deprivation and inequalities across the full life course may support healthy ageing.

Key messagesO_LINeighbourhood context might be associated with old-age frailty, but existing investigations are mainly based on cross-sectional data with limited understanding of the relative importance of exposure timing during the life course.
C_LIO_LIUsing a structured approach, we investigated how neighbourhood social deprivation across the life course is associated with frailty, and frailty progression, in a sample of older Scottish adults.
C_LIO_LIAmong males, accumulated neighbourhood social deprivation was moderately associated with frailty at age 70 but not with subsequent frailty trajectories; widening frailty trajectories between age 70 and 82 conditional on deprivation during mid-to-late adulthood were identified among females.
C_LIO_LIGendered experiences of living in deprived areas from childhood onwards may contribute to frailty which should be considered in policies supporting healthy ageing.
C_LI


title: SARS-CoV-2 circulation in the school setting: A systematic review and meta-analysis

abstract:
BackgroundThe contribution of children to viral spread in schools is still under debate.

We conducted a systematic review and meta-analysis of studies to investigate SARS-CoV-2 transmission in the school setting.

MethodsLiterature searches from April, 2021 and repeated on May, 15th 2021 yielded a total of 1088 publications: screening, contact tracing and seroprevalence studies.

MOOSE guidelines were followed and data analyzed using random-effects models.

ResultsFrom screening studies involving more than 120,000 subjects, we estimated 0.31% (95% Confidence Interval [CI] 0.05-0.81%) SARS-CoV-2 point prevalence in schools. Contact tracing studies, involving a total of 112,622 contacts of children and adults, showed that onward viral transmission was limited (2.54%; 95%CI 0.76-5.31). Young index cases were found to be 74% significantly less likely than adults to favor viral spread (Odds Ratio [OR]=0.26; 95%CI 0.11-0.63) and were less susceptible to infection (OR=0.60; 95% CI 0.25-1.47). Finally, from seroprevalence studies, with a total of 17,879 subjects involved, we estimated that children are 43% significantly less likely than adults to test positive for antibodies (OR=0.57; 95%CI: 0.49-0.68).

In conclusion, testing all subjects in schools, independently of symptoms, students less likely than adults favor viral spread and SARS-CoV-2 circulation in schools was found to be limited.

KEY POINTSO_ST_ABSQuestionC_ST_ABSWhat is the infectivity and susceptibility of students and staff exposed to SARS-CoV-2 in the school setting?

FindingsThis systematic review and meta-analysis of all available data shows that SARS-CoV-2 viral spread is limited and child-to-adult transmission in the school setting scarce.

Summary estimates indicate that young index cases were 74% significantly less likely than adults to favor viral spread and children are 43% less susceptible than adults.

MeaningOverall, SARS-CoV-2 circulation in schools was limited and could be reasonably controlled with appropriate mitigation measures.


title: Vulnerability and informal caregiver: a scoping review.

abstract:
ObjectiveThis review paper examines the concept of vulnerability in the overall literature and its relation to informal caregivers.

Vulnerability is frequently associated with the sense of being at risk of harm instead of being acknowledged as a human trait to embrace.

Taking a cue from two well-known videos of Brene Brown on how to enact "vulnerability," we aimed to see if emotional vulnerability - posed/explored as strength or weakness - exists in the informal care context, potentially acting as a powerful resource that teaches individuals to look inward and inspires them to work on themselves.

DesignScoping review

Data sourcesFollowing PRISMA-ScR checklist for scoping review, the literature was searched in various databases, including PubMed, Scopus and ScienceDirect.

Study selection and data extractionWe systematically searched for: 1) observational studies, experimental studies, and systematic reviews 2) that examined the topic of emotional vulnerability in a caregiving context 3) that were relevant to informal caregivers of older adults 4) that were published from 1976 to 2021 5) in English 6) that included populations [≥]18 years old 7) and excluded conceptualization of vulnerability outside of the emotional perspective (i.e., environmental, financial, social, biological, genetic, medical). Two reviewers independently reviewed titles and abstracts, reviewed the full text of relevant articles, and extracted the data

ResultsFrom 2502 articles, 21 were determined as eligible.

ConclusionThe reviewed articles showed the complexity of the vulnerability construct and several different approaches taken to explore this topic. This research concludes the value of vulnerability for human beings. The paucity of literature on the concept of vulnerability for informal caregivers offers a promising avenue for future research in this field.

Article summary: Strengths and limitations of this studyO_LIThis study reviews the conceptualization of vulnerability across literature from 1976 to date, which was never done before
C_LIO_LIThis study draws a unique parallel between vulnerability in formal care settings and informal care
C_LIO_LIThis study re-defines the concept of emotional vulnerability in informal care
C_LIO_LIThe study lacks more concrete first-person perspectives on vulnerability shared by informal caregivers, hence more concrete involvement of informal caregivers would be desirable for representative understanding of the concept of emotional vulnerability in informal care.
C_LI

category: psychiatry and clinical psychology


title: Detection of SARS CoV-2 contamination in the Operating Room and Birthing Room Setting: Risks to attending health care workers

abstract:
BackgroundThe exposure risks to front-line health care workers who are in close proximity for prolonged periods of time, caring for COVID-19 patients undergoing surgery or obstetrical delivery is unclear. Understanding of sample types that may harbour virus is important for evaluating risk.

ObjectivesTo determine if SARS-CoV-2 viral RNA from patients with COVID-19 undergoing surgery or obstetrical care is present in: 1) the peritoneal cavity of males and females 2) the female reproductive tract, 3) the environment of the surgery or delivery suite (surgical instruments, equipment used, air or floors) and 4) inside the masks of the attending health care workers.

MethodsThe presence of SARS-CoV-2 viral RNA in patient, environmental and air samples was identified by real time reverse transcriptase polymerase chain reaction (RT-PCR). Air samples were collected using both active and passive sampling techniques.

ResultsIn this multi-centre observational case series, 32 patients with COVID-19 underwent urgent surgery or obstetrical delivery and 332 patient and environmental samples were collected and analyzed to determine if SARS-CoV-2 RNA was present. SARS-CoV-2 RNA was detected in: 4/24(16.7%) patient samples, 5/60(8.3%) floor, 1/54(1.9%) air, 10/23(43.5%) surgical instruments/equipment, 0/24 cautery filters and 0/143 inner surface of mask samples.

ConclusionsWhile there is evidence of SARS-CoV-2 RNA in the surgical and obstetrical operative environment (6% of samples taken), the finding of no detectable virus inside the masks worn by the medical teams would suggest a low risk of infection for our health care workers using appropriate personal protective equipment (PPE).

category: occupational and environmental health


title: Impact and Equality of Expanding Pre-Exposure Prophylaxis (PrEP) for Men who have Sex with Men in Los Angeles County

abstract:
BackgroundRacial and ethnic minority men who have sex with men (MSM) are disproportionately affected by HIV/AIDS in Los Angeles County (LAC), an important epicenter in the battle to end HIV.

ObjectiveTo examine tradeoffs between effectiveness and equality of PrEP allocation strategies among different racial and ethnic groups of MSM in LAC.

Design, Setting, and PopulationWe developed a microsimulation model of HIV among MSM in LAC using county epidemic surveillance and survey data to capture demographic trends and subgroup-specific partnership patterns, disease progression, patterns of PrEP use, and patterns for viral suppression.

InterventionWe simulated interventions where an additional 3000, 6000, or 9000 PrEP prescriptions are provided annually in addition to current levels, following different allocation scenarios to each racial/ethnic group (Black, Hispanic, or White).

MeasurementsWe estimated cumulative infections averted and measures of equality, after 15 years (2021-2035), relative to base case (no intervention).

ResultsOf the policies evaluated, targeting PrEP preferentially to Black individuals would result in the largest reductions in incidence and disparities. This outcome was robust to different partnership preference assumptions, though the magnitude of impact differs.

LimitationsWe limit analysis to MSM, who bear the majority of HIV/AIDS burden in LAC. We do not consider transmission via injection drug use or mother-to-child transmission, nor do we capture individual network transmission effects. We assume no improvements in the prevention-diagnosis-treatment cascade besides increased PrEP use.

ConclusionsWe find there is little trade-off between effectiveness and equality of outcome when choosing groups to target for PrEP in LAC - by focusing on MSM with the highest HIV incidence (Black), we can reduce both overall infections and racial/ethnic disparities.

category: hiv aids


title: The international and intercontinental spread and expansion of antimicrobial-resistant Salmonella Typhi

abstract: The emergence of increasingly antimicrobial-resistant (AMR) Salmonella enterica serovar Typhi (S. Typhi) threatens to undermine effective treatment and control. Here, aiming to investigate the temporal and geographic patterns of emergence and spread of AMR S. Typhi, we sequenced 3,489 S. Typhi isolated from prospective surveillance in South Asia and combined these with a global collection of 4,169 S. Typhi genomes. Our analysis revealed that independent acquisition of plasmids and homoplastic mutations conferring AMR have occurred repeatedly in multiple lineages of S. Typhi, predominantly arising in South Asia. We found evidence of frequent international and intercontinental transfers of AMR S. Typhi, followed by rapid expansion and replacement of antimicrobial-susceptible clades.


title: Severe COVID-19 is associated with sustained biochemical disturbances and prolonged symptomatology; A retrospective single-centre cohort study

abstract:
IntroductionCoronavirus disease 2019 (COVID-19) is associated with significant acute clinical manifestations, and reports indicate that some patients experience prolonged symptomatology and morbidity. These late clinical manifestations have been termed Post-Acute Sequelae of COVID-19 (PASC) and hypothesised to be associated with clinical severity in the acute infection phase and biochemical abnormalities.

AimEvaluate the incidence of PASC in previously hospitalised COVID-19 patients and compare the admission and follow-up levels of biochemical parameters stratified according to baseline clinical severity.

MethodsN = 168 COVID-19 patients previously hospitalised at the Zan Mitrev Clinic in Skopje, North Macedonia, with matched laboratory data at baseline and follow-up clinical visit > 30 days post-discharge, were stratified according to National Institute of Health clinical severity guidelines as mild, moderate, severe or critical according to admission clinical presentation. We assessed the incidence of PASC and compared the biochemical profile.

ResultsThe median hospitalisation and clinical follow-up period were 11 (9-20) and 53 (30-105) days. The overall incidence of PASC was 56.5% (95/168); most PASC cases were confined to the severe sub-group (61/101, 61.4%). Contrary to mild and moderate cases and a healthy "non-COVID-19" control cohort, we observed that severe COVID-19 cases experienced sustained biochemical disturbances, most notably elevated D-dimers and Ferritin of 600 ng/ml (283-1168) and 432 ng/ml (170-916), respectively.

ConclusionsPreviously hospitalised severe COVID-19 patients are more likely to experience Post-Acute Sequelae of COVID-19 and prolonged biochemical disturbances, evident by abnormal values of D-dimers and Ferritin.


title: The early impact of vaccination against SARS-CoV-2 in Region Stockholm, Sweden

abstract:
Vaccination against SARS-CoV-2 started in Region Stockholm, Sweden in December 2020 with those in long-term care facilities or receiving home care vaccinated first followed by those aged over 80 years. In this population-based, retrospective cohort study, we performed a Poisson regression to model the expected incidence of infections and deaths which we compared to the observed incidence and compared this to an unvaccinated control group of those aged 18-79 years. The aim of this study was to measure the early impact of the vaccination programme in Region Stockholm.

Infections and deaths reduced substantially amongst the first two groups targeted for SARS-CoV-2 vaccination with an estimated total 3112 infections prevented, and 854 deaths prevented in these two groups from 4 weeks after the introduction of vaccination through to 2nd May 2021.


title: Association Between SARS-CoV-2 RNAemia and Post-Acute Sequelae of COVID-19.

abstract: Determinants of Post-Acute Sequelae of COVID-19 are not known. Here we show that 75% of patients with viral RNA in blood (RNAemia) at presentation were symptomatic in the post-acute phase. RNAemia at presentation successfully predicted PASC, independent of patient demographics, initial disease severity, and length of symptoms.


title: SUDMEX CONN: The Mexican MRI dataset of patients with cocaine use disorder

abstract: Cocaine use disorder (CUD) is a substance use disorder (SUD) characterized by compulsion to seek, use and abuse of cocaine, with severe health and economic consequences for the patients, their families and society. Due to the lack of successful treatments and high relapse rate, more research is needed to understand this and other SUD. Here, we present the SUDMEX CONN dataset, a Mexican open dataset of CUD patients and matched healthy controls that includes demographic, cognitive, clinical, and magnetic resonance imaging (MRI) data. MRI data includes: 1) structural (T1-weighted), 2) multishell high-angular resolution diffusion-weighted (DWI-HARDI) and 3) functional (resting state fMRI) sequences. The repository contains unprocessed MRI data available in brain imaging data structure (BIDS) format with corresponding metadata available at the OpenNeuro data sharing platform. Researchers can pursue brain variability between these groups or use a single group for a larger population sample.

category: addiction medicine


title: Pericapsular nerve group block for hip fracture is safe and effective in the emergency department: a prospective observational study comparing pericapsular nerve group block to fascia iliaca compartment block and femoral nerve block.

abstract:
BackgroundThe pericapsular nerve group (PENG) block was first described for the treatment of hip fracture, including neck of femur, in 2018. We hypothesise that the PENG block is safe and effective for patients with hip fracture when provided by emergency physicians and trainees in the emergency department (ED), for which it may be superior to fascia iliaca compartment block (FICB) and femoral nerve block (FNB).

MethodsFrom October 2019 to July 2020, consecutive patients receiving regional anaesthesia for hip fracture in the ED of a single large regional hospital were prospectively enrolled. Pain scores were assessed prior to regional anaesthesia then at 15, 30 and 60 minutes after regional anaesthesia. Maximal reduction in pain scores within 60 minutes were assessed using the Visual Analogue Scale (at rest and on movement) or the Pain Assessment IN Advanced Dementia tool (at rest). Patients were followed for opioid use for 12 hours after regional anaesthesia and adverse events over the duration of their admission.

ResultsThere were 67 eligible patients during the enrolment period, with 52 (78%) prospectively enrolled. Thirty-three received femoral blocks (19 FICB, 14 FNB) and 19 received a PENG block. There was no difference in maximum pain score reduction between the groups whether measured at rest or on movement. Clinicians providing the PENG block were less experienced in the technique than those providing FICB or FNB. There was no difference in adverse effects between groups. Although opioid use was similar between the groups, more patients were opioid free after a PENG block.

ConclusionsAlthough there was no difference in maximal pain score reduction, this study demonstrated that the PENG block was feasible and could be provided safely and effectively to patients with hip fracture in the ED. On this basis, a larger randomised controlled study should now be designed.

Key MessagesWhat is already known on this subject

{square}There is a solid neuroanatomical rationale to suggest the PENG block may provide superior anaesthesia of hip fractures than FNB or FICB.
{square}The technique utilises bony sonographic and tactile landmarks which make it an ideal block for emergency physicians to safely and effectively perform.
{square}What this study adds
{square}This is the first comparative study of the PENG block to FNB or FICB in patients with hip fracture in ED, which will provide a scaffold for future research.
{square}This pragmatic observation of evolving practice showed that emergency physicians and trainees inexperienced in the technique could provide it safely and effectively in the ED

category: emergency medicine


title: An observational study of clinical and health system factors associated with catheter ablation and early ablation treatment for atrial fibrillation in Australia

abstract:
ObjectiveTo investigate clinical and health system factors associated with receiving catheter ablation (CA) for non-valvular atrial fibrillation (AF).

Study Design and SettingWe used hospital administrative data linked with death registrations in New South Wales, Australia for patients with a primary diagnosis of AF between 2009 and 2017. We investigated factors associated with receiving CA (using Cox regression) and early ablation (using logistic regression).

ResultsCardioversion during index admission (hazard ratio [HR] 1.96; 95% CI 1.75 - 2.19), year of index admission (HR 1.07; 1.07; 95% CI 1.05 - 1.10), private patient status (HR 2.65; 95% CI 2.35 - 2.97), and living in more advantaged areas (HR 1.18; 95% CI 1.13 - 1.22) were associated with a higher likelihood of receiving CA. Private patient status (odds ratio [OR] 2.04; 95% CI 1.59 - 2.61) and a history of cardioversion (OR 1.25; 95% CI 1.0 - 1.57) and diabetes (OR 1.6; 95% CI 1.06 - 2.41) were associated with receiving early ablation.

ConclusionBeyond clinical factors, private patients are more likely to receive CA and earlier ablation than their public counterparts. Whether the earlier access to ablation procedures in private patients is leading to differences in outcomes among patients with atrial fibrillation remains to be explored.

O_TEXTBOXWhat is new?O_LIKey findings
O_LIPrivate patient status had the strongest effect on the likelihood and odds of receiving catheter ablation and early ablation compared to other clinical and health system factors
C_LIO_LICardioversion during index admission, year of index admission, and living in more advantaged areas were associated with a higher likelihood of receiving catheter ablation, while older age and a history of congestive heart failure, hypertension, diabetes, and myocardial infarction were associated with a lower likelihood of receiving catheter ablation.
C_LIO_LICardioversion during index admission and a history of diabetes were also associated with higher odds of receiving early ablation.
C_LI
C_LIO_LIWhat it adds
O_LIGiven the growing evidence of the effectiveness of catheter ablation for treating atrial fibrillation, this study demonstrates the associations between clinical and health system factors and receiving catheter ablation and early ablation.
C_LI
C_LIO_LIImplications
O_LIClinicians and policymakers should review existing policies to ensure effective procedures for atrial fibrillation are available to the whole population, rather than those who are more advantaged.
C_LI
C_LI

C_TEXTBOX


title: Two new compartmental epidemiological models and their equilibria

abstract:
AO_SCPLOWBSTRACTC_SCPLOWCompartmental models have long served as important tools in mathematical epidemiology, with their usefulness highlighted by the recent COVID-19 pandemic. However, most of the classical models fail to account for certain features of this disease and others like it, such as the ability of exposed individuals to recover without becoming infectious, or the possibility that asymptomatic individuals can indeed transmit the disease but at a lesser rate than the symptomatic. Furthermore, the rise of new disease variants and the imperfection of vaccines suggest that concept of endemic equilibrium is perhaps more pertinent than that of herd immunity.

Here we propose a new compartmental epidemiological model and study its equilibria, characterizing the stability of both the endemic and disease-free equilibria in terms of the basic reproductive number. Moreover, we introduce a second compartmental model, generalizing our first, which accounts for vaccinated individuals, and begin an analysis of its equilibria.


title: The prevalence of adaptive immunity to COVID-19 and reinfection after recovery, a comprehensive systematic review and meta-analysis of 12 011 447 individuals

abstract:
ObjectivesThis study aims to estimate the prevalence and longevity of detectable SARS-CoV-2 antibodies as well as memory cells T and B after recovery. In addition, the prevalence of COVID-19 reinfection, and the preventive efficacy of previous infection with SARS-CoV-2 were investigated.

Methods and analysesA synthesis of existing research was conducted. The Cochrane Library for COVID-19 resources, the China Academic Journals Full Text Database, PubMed, and Scopus as well as preprint servers were searched for studies conducted between 1 January 2020 to 1 April 2021. We included studies with the relevant outcomes of interest. All included studies were assessed for methodological quality and pooled estimates of relevant outcomes were obtained in a meta-analysis using a bias adjusted synthesis method. Proportions were synthesized with the Freeman-Tukey double arcsine transformation and binary outcomes using the odds ratio (OR). Heterogeneity between included studies was assessed using the I2 and Cochrans Q statistics and publication bias was assessed using Doi plots.

ResultsFifty-four studies, from 18 countries, with around 12 000 000 individuals, followed up to 8 months after recovery were included. At 6-8 months after recovery, the prevalence of SARS-CoV-2 specific immunological memory remained high; IgG - 90.4% (95%CI 72.2-99.9, I2=89.0%, 5 studies), CD4+ - 91.7% (95%CI 78.2 - 97.1, one study), and memory B cells 80.6% (95%CI 65.0-90.2, one study) and the pooled prevalence of reinfection was 0.2% (95%CI 0.0 - 0.7, I2 = 98.8, 9 studies). Individuals previously infected with SARS-CoV-2 had an 81% reduction in odds of a reinfection (OR 0.19, 95% CI 0.1 - 0.3, I2 = 90.5%, 5 studies).

ConclusionAround 90% of people previously infected with SARS-CoV-2 had evidence of immunological memory to SARS-CoV-2, which was sustained for at least 6-8 months after recovery, and had a low risk of reinfection.

RegistrationPROSPERO: CRD42020201234

What is already known on this topicIndividuals who recover from COVID-19 may have immunity against future infection but the proportion who develop immunity is uncertain. Further, there is uncertainty about the proportion of individuals who get reinfected with COVID-19.

What this study addsUsing data from 54 studies with follow up time up to 8 months after recovery, during the period February 2020-February 2021, we found that, post-COVID-19, up to 90% of individuals had antibodies and memory T and B cells against SARS-CoV-2. We also found a pooled prevalence of reinfection of 0.2%, and that infection conferred an 81% decrease in odds of reinfection with SARS-CoV-2, compared to unimmunized individuals without previous COVID-19.

This review of 12 million individuals presents evidence that most individuals who recover from COVID-19 develop immunological memory to SARS-CoV-2, which was still detectable for up to 8 months. Further, reinfection after recovery from COVID-19 was rare during the first 8 months after recovery, with a prevalence below 1%, while prior infection confers protection with an odds ratio of 0.19 and a preventive efficacy of 80% at a baseline prevalence of 5% for COVID-19 in a community.

Implications of all the available evidenceIndividuals with a history of COVID-19 infection have immunity against the disease for up to 8 months, although this period could be longer. These individuals could be prioritized last for COVID-19 vaccinations or considered for single dose vaccinations.

StrengthsThis comprehensive review addresses key questions on prevalent immunological memory and risk of reinfection in individuals with prior confirmed COVID-19 using robust systematic review methods.

LimitationsSome of the included studies which examined prevalent immunological memory were small studies which were affected by loss to follow up. The review did not examine evidence for immunity against the new divergent variants, which may be more likely to have immune evasion behaviour and may present a higher risk of reinfection. Lastly, the review did not examine the effect of the severity of COVID-19 on both immunological memory and the risk of reinfection.


title: The prevalence of adaptive immunity to COVID-19 and reinfection after recovery, a comprehensive systematic review and meta-analysis


title: Prenatal Selective Serotonin Reuptake Inhibitor Exposure, Depression and Brain Morphology in Middle Childhood: Results from the ABCD Study

abstract:
ObjectivePrenatal selective serotonin reuptake inhibitor (SSRI) exposure has been inconsistently linked to depression. Potential neural intermediaries remain understudied. We examined whether prenatal SSRI exposure is associated with depressive symptoms and brain structure during middle childhood.

MethodsPrenatal SSRI exposure (retrospective caregiver-report), depressive symptoms (caregiver-reported Child Behavior Checklist) and brain structure (MRI-derived subcortical volume; cortical thickness and surface area) were assessed in children (analytic ns=5,420-7,528; 235 with prenatal SSRI exposure; 9-10 years old) who completed the baseline session of the Adolescent Brain and Cognitive DevelopmentSM Study. Covariates included familial (e.g., 1st degree relative depression density), pregnancy (e.g., planned pregnancy), and child (e.g., birthweight) variables. Matrix spectral decomposition was used to address multiple testing.

ResultsThere was no evidence that prenatal SSRI exposure was associated with child depression after accounting for recent maternal depressive symptoms. Prenatal SSRI exposure was associated with greater left superior parietal surface area (b=145.3 mm2, p=0.00038) and lateral occipital cortical thickness (b=0.0272 mm, p=0.0000079), neither of which was associated with depressive symptoms.

ConclusionsOur findings, combined with adverse associations of prenatal exposure to maternal depression and the utility of SSRIs for treating depression, suggest that risk for child depression during middle childhood should not discourage SSRI use during pregnancy. It will be important for future work to examine associations between prenatal SSRI exposure and depression through young adulthood, when risk for depression increases.


title: Infectiousness of places: The impact of human settlement and activity space in the transmission of COVID-19

abstract:
Places are fundamental factors in the spread of epidemics, as they are where people agglomerate and interact. This paper explores how different types of places--activity spaces at micro-level and human settlements at macro-level--impact the transmission of infections using evidences from COVID-19. We examine eleven types of activity spaces and find heterogeneous impacts across countries, yet we also find that non-essential activity spaces tend to have larger impacts than essential ones. Contrary to common beliefs, settlement size and density are not positively associated with reproduction numbers. Further, the impacts of closing activity spaces vary with settlement types and are consistently lower in larger settlements in all sample countries, suggesting more complex pattern of virus transmission in large settlements. This work takes first steps in systematically evaluating the epistemological risks of places at multiple scales, which contributes to knowledge in urban resilience, health and livability.

TeaserActivity spaces and human settlement characteristics impact the spread of epidemics in multiple ways and should be considered in policy making.


title: Aversive memory formation in humans is determined by an amygdala-hippocampus phase code

abstract: Memory for aversive events is central to survival, but can also become maladaptive in psychiatric disorders. Emotional memory relies on the amygdala and hippocampus, but the neural dynamics of their communication during emotional memory encoding remain unknown. Using simultaneous intracranial recordings from both structures in human patients, we show that in response to emotionally aversive, but not neutral, visual stimuli, the amygdala transmits unidirectional influence on the hippocampus through theta oscillations. Critically, successful emotional memory encoding depends on the precise amygdala theta phase to which hippocampal gamma activity and neuronal firing couple. The phase difference between subsequently remembered vs. not-remembered emotional stimuli translates to [~]25-45 milliseconds, a time period that enables lagged coherence between amygdala and downstream hippocampal gamma activity. These results reveal a mechanism whereby amygdala theta phase coordinates transient coherence between amygdala and hippocampal gamma activity to facilitate the encoding of aversive memories in humans.

category: neurology


title: Brain age as a surrogate marker for information processing speed in multiple sclerosis

abstract:
BackgroundData from neuro-imaging techniques allow us to estimate a brains age. Brain age is easily interpretable as "how old the brain looks", and could therefore be an attractive communication tool for brain health in clinical practice. This study aimed to investigate its clinical utility.

ObjectivesTo investigate the relationship between brain age and information processing speed in MS.

MethodsA ridge-regression model was trained to predict age from brain MRI volumetric features and sex in a healthy control dataset (HC_train, n=1690). This model was used to predict brain age in two test sets: HC_test (n=50) and MS_test (n=201). Brain-Predicted Age Difference (BPAD) was calculated as BPAD=brain age minus chronological age. Information processing speed was assessed with the Symbol Digit Modalities Test (SDMT).

ResultsBrain age was significantly related to SDMT scores in the MS_test dataset (r=-0.44, p<.001), and contributed uniquely to variance in SDMT beyond chronological age, reflected by a significant correlation between BPAD and SDMT (r=-0.21, p=0.003) and a significant weight (-0.21, p=0.011) in a multivariate regression equation with age.

ConclusionsBrain age is a candidate biomarker for information processing speed in MS and an easy to grasp metric for brain health.


title: Immunogenicity of Pfizer mRNA COVID-19 vaccination followed by J&J adenovirus COVID-19 vaccination in two CLL patients

abstract:
ImportanceIndividuals with Chronic Lymphocytic Leukemia have significant immune disfunction, often further disrupted by treatment. While currently available COVID-19 vaccinations are highly effective in immunocompetent individuals, they are often poorly immunogenic in CLL patients. It is important to understand the role heterologous boost would have in patients who did not respond to the recommended two-dose mRNA vaccine series with a SARS-CoV-2 specific immune response

ObjectiveTo characterize the immune response of two CLL patients who failed to seroconvert after initial mRNA vaccine series following a third, heterologous, COVID-19 vaccination with Ad26.COV2.S.

DesignTwo subjects with CLL were enrolled in an IRB-approved observational longitudinal cohort study of the immune response to COVID-19 vaccination. After enrollment, they received a third vaccination with Ad26.COV2.S. Blood was drawn prior to original vaccination series, four weeks after mRNA vaccination, and again four weeks after third vaccination.

SettingEligible subjects were approached by oncologist overseeing CLL treatment and informed about study, at time of enrollment subjects consented to join the cohort study.

ParticipantsSixteen subjects enrolled in the larger CLL cohort study, of whom two subjects received a third COVID-19 vaccination and were included in this analysis. Subject 1 is CLL treatment naive, while Subject 2 is currently on active treatment.

Main Outcome(s) and Measure(s)SARS-CoV-2 specific immune response, including plasma antibodies, memory B-cells, CD4 and CD8 T-cells were assessed prior to vaccination (baseline) as well as post vaccination series and post third dose.

ResultsOf the two subjects who received Ad26.COV2.S doses, Subject 1 seroconverted, had RBD-specific memory B-cells as well as spike-specific CD4 T-cells while Subject 2 did not. Both subjects had a spike-specific CD8 T-cell response after original mRNA vaccination series that was further boosted after third dose (Subject 1), or remained stable (Subject 2).

Conclusions and RelevanceThe results of this study, however small, is especially promising to CLL individuals who did not seroconvert following initial mRNA vaccination series. Especially those that are treatment naive, not currently in active treatment, or who may consider vaccination before beginning active treatment.

category: allergy and immunology


title: Long-term corticosteroid therapy for patients with severe coronavirus disease 2019 (COVID-19)

abstract:
earlier and longer corticosteroid therapy with methylprednisolone could reduce the mortality and/or rate of ICU admission by 26% in patients with severe COVID-19, hospitalized in conventional medical ward.

BackgroundLow dose of dexamethasone reduced mortality in hospitalized COVID-19 patients who required respiratory support. Less is known about the efficacy of other corticosteroids in severe COVID-19 patients. This study was designed to determine if longer and earlier corticoid therapy in severe COVID-19 patients is associated with reduced mortality and/or reduced rate of ICU admission for worsening of respiratory state.

MethodsWe performed a retrospective study with patients aged [≥] 18 years, with epidemiological and/or radiological suspected COVID-19, hospitalized in a regional hospital GHRMSA Mulhouse, France. Twenty-three patients received methylprednisolone (MP) as compassionate use, 1 mg/kg/day for seven days followed by prednisolone at a gradually reduced dosage, for 4 to 6 weeks. MP was started one week after COVID-19 symptoms first appeared. The primary composite outcome was mortality and/or ICU admission during hospitalisation.

ResultsBetween March 14th to June 5th 2020, 255 patients were screened, 181 were included, and 92 were analysed, 23 patients treated with MP and 69 received standard care. SARS-CoV2 infection was confirmed by reverse transcriptase polymerase chain reaction (RT-PCR) in 82.3%. The overall composite outcome was higher in the control group: 42/69 patients (60.9%) versus 8/23 (34.8%) in the interventional group (p= 0.018). The correction of lymphopenia between days 1 to 7 was associated with better outcome (p=0.006).

ConclusionThese results suggest that earlier and longer corticosteroid therapy with methylprednisolone could reduce the mortality and/or rate of ICU admission in patients with severe COVID-19, hospitalized in conventional medical ward.

category: respiratory medicine


title: Immune responses in COVID-19 respiratory tract and blood reveal mechanisms of disease severity

abstract: Although the respiratory tract is the primary site of SARS-CoV-2 infection and the ensuing immunopathology, respiratory immune responses are understudied and urgently needed to understand mechanisms underlying COVID-19 disease pathogenesis. We collected paired longitudinal blood and respiratory tract samples (endotracheal aspirate, sputum or pleural fluid) from hospitalized COVID-19 patients and non-COVID-19 controls. Cellular, humoral and cytokine responses were analysed and correlated with clinical data. SARS-CoV-2-specific IgM, IgG and IgA antibodies were detected using ELISA and multiplex assay in both the respiratory tract and blood of COVID-19 patients, although a higher receptor binding domain (RBD)-specific IgM and IgG seroconversion level was found in respiratory specimens. SARS-CoV-2 neutralization activity in respiratory samples was detected only when high levels of RBD-specific antibodies were present. Strikingly, cytokine/chemokine levels and profiles greatly differed between respiratory samples and plasma, indicating that inflammation needs to be assessed in respiratory specimens for the accurate assessment of SARS-CoV-2 immunopathology. Diverse immune cell subsets were detected in respiratory samples, albeit dominated by neutrophils. Importantly, we also showed that dexamethasone and/or remdesivir treatment did not affect humoral responses in blood of COVID-19 patients. Overall, our study unveils stark differences in innate and adaptive immune responses between respiratory samples and blood and provides important insights into effect of drug therapy on immune responses in COVID-19 patients.


title: Effectiveness of the mRNA BNT162b2 vaccine six months after vaccination: findings from a large Israeli HMO

abstract:
Israel is currently experiencing a new wave of CoVid-19 infection, six months after implementing a national vaccination campaign. We carried out three discrete analyses using data from a large Israeli HMO to determine whether IgG levels of those fully vaccinated drop over time, the relationship between IgG titer and subsequent PCR-confirmed infection, and compare PCR-confirmed infection rates by period of vaccination. We found that mean IgG antibody levels steadily decreased over the six-month period in the total tested population, and in all age groups. An inverse relationship was found between IgG titer and subsequent CoVid-19 infection (PCR-positive). Those participants vaccinated in the first two months of the campaign were more likely to become infected than those subsequently vaccinated. The 60+ vaccinated had lower initial IgG levels, and were at greater risk of infection. The findings support the decision to add a booster vaccine for those aged 60 and over.

Article Summary LineThe BNT162b2 vaccine was found to be less effective in protecting against Covid-19 infection after six months, and vaccination with a third dose is indicated.


title: Durability analysis of the highly effective BNT162b2 vaccine against COVID-19

abstract: SARS-CoV-2 breakthrough infections have been increasingly reported in fully vaccinated individuals. We conducted a test-negative case-control study to assess the durability of protection after full vaccination with BNT162b2, defined as 14 days after the second dose, against polymerase chain reaction (PCR)-confirmed symptomatic SARS-CoV-2 infection, in a national medical practice between February 1, 2021 and August 22, 2021. We fit conditional logistic regression (CLR) models stratified on residential county and calendar time of testing to assess the association between time elapsed since vaccination and the odds of symptomatic infection or non-COVID-19 hospitalization (negative control), adjusted for several covariates. The primary population included 652 individuals who had a positive symptomatic test after full vaccination with BNT162b2 (cases) and 5,946 individuals with at least one negative symptomatic test after full vaccination (controls). The adjusted odds of symptomatic infection were higher 120 days after full vaccination versus at the date of full vaccination (Odds Ratio [OR]: 3.21, 95% confidence interval [CI]: 1.33-7.74). Importantly, the odds of infection were still lower 150 days after the first BNT162b2 dose as compared to 4 days after the first dose (OR: 0.3, 95% CI: 0.19-0.45), when immune protection approximates the unvaccinated status. Low rates of COVID-19 associated hospitalization or death in this cohort precluded analyses of these severe outcomes. The odds of experiencing a non-COVID-19 hospitalization decreased with time since vaccination, suggesting a possible underestimation of waning protection by this approach due to confounding factors. Taken together, these data constitute an early signal for waning protection against symptomatic illness while also providing reassurance that BNT162b2 continues to protect against symptomatic SARS-CoV-2 infection several months after full vaccination. Continued surveillance of COVID-19 vaccine durability, particularly against severe disease, is critical to guide effective and equitable strategies to respond to the pandemic, including distribution of booster doses, development of new vaccines, and implementation of both pharmaceutical and nonpharmaceutical interventions.


title: Susceptibility to postmortem (co)-pathologies in antemortem atrophy-based subtypes of Alzheimer's disease

abstract:
ObjectivesTo investigate whether antemortem atrophy-based subtypes of Alzheimers disease (AD) may be differentially susceptible to individual or concomitance of AD and non-AD (co)-pathologies, assessed neuropathologically at postmortem.

MethodsWe selected 31 individuals from the AD neuroimaging initiative with: an antemortem magnetic resonance imaging scan evaluating brain atrophy available within two years before death; an antemortem diagnosis of AD dementia or prodromal AD; and postmortem neuropathological confirmation of AD. Antemortem atrophy-based subtypes was modeled as a continuous phenomenon in terms of two recently proposed dimensions: typicality (ranging from limbic-predominant AD to hippocampal-sparing AD subtypes) and severity (ranging from typical AD to minimal atrophy AD subtypes). Postmortem neuropathological evaluation included global and regional outcomes: AD hallmark pathologies of amyloid-beta and tau; non-AD co-pathologies of alpha-synuclein Lewy body and TDP-43; and the overall concomitance across these four (co)-pathologies. Partial correlation and linear regression models were used to assess the association between antemortem atrophy-based subtypes and postmortem neuropathological outcomes.

ResultsWe observed significant global and regional associations between antemortem typicality and postmortem (co)-pathologies including tau, alpha-synuclein Lewy bodies and TDP-43. Antemortem typicality demonstrated stronger regional associations with concomitance of multiple postmortem (co)-pathologies in comparison to antemortem severity. Our findings suggest the following susceptibilities of atrophy-based subtypes: limbic-predominant AD towards higher burden of tau and TDP-43 pathologies while hippocampal-sparing AD towards lower burdens; limbic-predominant AD and typical AD towards higher burden of alpha-synuclein Lewy body pathology while hippocampal-sparing AD and minimal-atrophy AD towards lower burdens.

DiscussionThrough a direct antemortem-to-postmortem validation, our study highlights the importance of understanding heterogeneity in AD in relation to concomitance of AD and non-AD pathologies. Our findings provide a deeper understanding of both global and regional vulnerabilities of the biological subtypes of AD brain towards (co)-pathologies. Relative involvement of both AD hallmark and non-AD (co)-pathologies will enhance prevailing knowledge of biological heterogeneity in AD and could thus, contribute towards tracking disease progression and designing clinical trials in the future.


title: Analytic approaches to clinical validation of results from preclinical models of glioblastoma: a systematic review

abstract:
IntroductionAnalytic approaches to clinical validation of results from preclinical models are important in assessment of their relevance to human disease. This systematic review examined consistency in reporting of glioblastoma cohorts from The Cancer Genome Atlas (TCGA) or Chinese Glioma Genome Atlas (CGGA) and assessed whether studies included patient characteristics in their survival analyses.

MethodsWe searched Embase and Medline on 02Feb21 for studies using preclinical models of glioblastoma published after Jan2008 that used data from TCGA or CGGA to validate the association between at least one molecular marker and overall survival in adult patients with glioblastoma. Main data items included cohort characteristics, statistical significance of the survival analysis, and model covariates.

ResultsThere were 58 eligible studies from 1,751 non-duplicate records investigating 126 individual molecular markers. In 14 studies published between 2017 and 2020 using TCGA RNA microarray data that should have the same cohort, the median number of patients was 464.5 (interquartile range 220.5-525). Of the 15 molecular markers that underwent more than one univariable or multivariable survival analyses, five had discrepancies between studies. Covariates used in the 17 studies that used multivariable survival analyses were age (76.5%), pre-operative functional status (35.3%), sex (29.4%) MGMT promoter methylation (29.4%), radiotherapy (23.5%), chemotherapy (17.6%), IDH mutation (17.6%) and extent of resection (5.9%).

ConclusionPreclinical glioblastoma studies that used TCGA for validation did not provide sufficient information about their cohort selection and there were inconsistent results. Transparency in reporting and the use of analytic approaches that adjust for clinical variables can improve the reproducibility between studies.

category: oncology


title: Additional heterologous versus homologous booster vaccination in immunosuppressed patients without SARS-CoV-2 antibody seroconversion after primary mRNA vaccination: a randomized controlled trial

abstract:
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-induced coronavirus disease 2019 (COVID-19) has led to exponentially rising mortality, particularly in immunosuppressed patients, who inadequately respond to conventional COVID-19 vaccination. In this blinded randomized clinical trial (EudraCT 2021-002348-57) we compare the efficacy and safety of an additional booster vaccination with a vector versus mRNA vaccine in non-seroconverted patients. We assigned 60 patients under rituximab treatment, who did not seroconvert after their primary mRNA vaccination with either BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna), to receive a third dose, either using the same mRNA or the vector vaccine ChAdOx1 nCoV-19 (Oxford-AstraZeneca). Patients were stratified according to the presence of peripheral B-cells. The primary efficacy endpoint was the difference in the SARS-CoV-2 antibody seroconversion rate between vector (heterologous) and mRNA (homologous) vaccinated patients by week four. Key secondary endpoints included the overall seroconversion and cellular immune response; safety was assessed at weeks one and four.

Seroconversion rates at week four were comparable between vector (6/27 patients, 22%) and mRNA (9/28, 32%) vaccine (p=0.6). Overall, 27% of patients seroconverted; specific T-cell responses were observed in 20/20 (100%) vector versus 13/16 (81%) mRNA vaccinated patients. Newly induced humoral and/or cellular responses occurred in 9/11 (82%) patients. No serious adverse events, related to immunization, were observed. This enhanced humoral and/or cellular immune response supports an additional booster vaccination in non-seroconverted patients irrespective of a heterologous or homologous vaccination regimen.


title: Previous COVID-19 infection and antibody levels after vaccination

abstract:
BackgroundThe emergence of new COVID-19 variants of concern coupled with a global inequity in vaccine access and distribution, prompted many public health authorities to circumvent the vaccine shortages by altering vaccination protocols and prioritizing high-risk individuals. Those with previous COVID-19 infection may have not been prioritized due to existing humoral immunity.

ObjectiveWe aim to study the association between previous COVID-19 infection and antibody levels after COVID-19 vaccination.

MethodsA serological analysis to measure SARS-CoV-2 IgG, IgA and neutralizing antibodies was performed on individuals who received one or two doses of either BNT162b2 or ChAdOx1 vaccines in Kuwait. Generalized linear regression models adjusted for individual characteristics and comorbidities were fitted to study the average levels of IgG and neutralizing antibodies in vaccinated individuals based who had previous COVID-19 infection compared to those who had not.

ResultsA total of 1025 individuals were recruited. The mean levels of IgG, IgA and neutralizing antibodies were higher in vaccinated subjects with previous COVID-19 infection when compared with those vaccinated without previous COVID-19 infection. Regression analysis showed a steeper slope of decline for IgG in vaccinated individuals without previous COVID-19 infection in comparison with vaccinated individuals with previous COVID-19 infection.

ConclusionPrevious COVID-19 infection appears to elicit robust and sustained levels of SARS-CoV-2 antibodies in vaccinated individuals. Given the inconsistent supply of COVID-19 vaccines in many countries due to the global inequity, our results point towards wider vaccination plans to especially cover individuals without previous COVID-19 infection.


title: Landscape of SARS-CoV-2 genomic surveillance, public availability extent of genomic data, and epidemic shaped by variants: a global descriptive study

abstract:
BackgroundGenomic surveillance has shaped our understanding of SARS-CoV-2 variants, which have proliferated globally in 2021. Characterizing global genomic surveillance, sequencing coverage, the extent of publicly available genomic data coupled with traditional epidemiologic data can provide evidence to inform SARS-CoV-2 surveillance and control strategies.

MethodsWe collected country-specific data on SARS-CoV-2 genomic surveillance, sequencing capabilities, public genomic data, and aggregated publicly available variant data. We divided countries into three levels of genomic surveillance and sequencing availability based on predefined criteria. We downloaded the merged and deduplicated SARS-CoV-2 sequences from multiple public repositories, and used different proxies to estimate the sequencing coverage and public availability extent of genomic data, in addition to describing the global dissemination of variants.

FindingsSince the start of 2021, the COVID-19 global epidemic clearly featured increasing circulation of Alpha, which was rapidly replaced by the Delta variant starting around May 2021 and reaching a global prevalence of 96.6% at the end of July 2021. SARS-CoV-2 genomic surveillance and sequencing availability varied markedly across countries, with 63 countries performing routine genomic surveillance and 79 countries with high availability of SARS-CoV-2 sequencing. Less than 3.5% of confirmed SARS-CoV-2 infections were sequenced globally since September 2020, with the lowest sequencing coverage in the WHO regions of Eastern Mediterranean, South East Asia, and Africa. Across different variants, 28-52% of countries with explicit reporting on variants shared less than half of their variant sequences in public repositories. More than 60% of demographic and 95% of clinical data were absent in GISAID metadata accompanying sequences.

InterpretationOur findings indicated an urgent need to expand sequencing capacity of virus isolates, enhance the sharing of sequences, the standardization of metadata files, and supportive networks for countries with no sequencing capability.

Research in context

Evidence before this studyOn September 3, 2021, we searched PubMed for articles in any language published after January 1, 2020, using the following search terms: ("COVID-19" OR "SARS-CoV-2") AND ("Global" OR "Region") AND ("genomic surveillance" OR "sequencing" OR "spread"). Among 43 papers identified, few papers discussed the global diversity in genomic surveillance, sequencing, public availability of genomic data, as well as the global spread of SARS-CoV-2 variants. A paper from Furuse employed the publicly GISAID data to evaluate the SARS-CoV-2 sequencing effort by country from the perspectives of "fraction", "timeliness", and "openness". Another viewpoint paper by Case Western Reserve Universitys team discussed the impediments of genomic surveillance in several countries during the COVID-19 pandemic. The paper as reported by Campbell and colleagues used the GISAID data to present the global spread and estimated transmissibility of recently emerged SARS-CoV-2 variants. We also found several studies that reported the country-level genomic surveillance and spread of variants. To our knowledge, no research has quantitatively depicted the global SARS-CoV-2 genomic surveillance, sequencing ability, and public availability extent of genomic data.

Added value of this studyThis study collected country-specific data on SARS-CoV-2 genomic surveillance, sequencing capabilities, public genomic data, and aggregated publicly available variant data as of 20 August 2021. We found that genomic surveillance strategies and sequencing availability is globally diverse. Less than 3.5% of confirmed SARS-CoV-2 infections were sequenced globally since September 2020. Our analysis of publicly deposited SARS-CoV-2 sequences and officially reported number of variants implied that the public availability extent of genomic data is low in some countries, and more than 60% of demographic and 95% of clinical data were absent in GISAID metadata accompanying sequences. We also described the pandemic dynamics shaped by VOCs.

Implications of all the available evidenceOur study provides a landscape for global sequencing coverage and public availability extent of sequences, as well as the evidence for rapid spread of SRAS-CoV-2 variants. The pervasive spread of Alpha and Delta variants further highlights the threat of SARS-CoV-2 mutations despite the availability of vaccines in many countries. It raised an urgent need to do more work on defining the ideal sampling schemes for different purposes (e.g., identifying new variants) with an additional call to share these data in public repositories to allow for further rapid scientific discovery.


title: Combining antibody markers for serosurveillance of SARS-CoV-2 to estimate seroprevalence and time-since-infection

abstract: Serosurveillance is an important epidemiologic tool for SARS-CoV-2, used to estimate burden of disease and degree of population immunity. Which antibody biomarker, and the optimal number of biomarkers, has not been well-established, especially with the emerging rollout of vaccines globally. Here, we used random forest models to demonstrate that a single spike or receptor-binding domain (RBD) antibody was adequate for classifying prior infection, while a combination of two antibody biomarkers performed better than any single marker for estimating time-since-infection. Nucleocapsid antibodies performed worse than spike or RBD antibodies for classification, but is of utility for estimating time-since-infection, and in distinguishing infection-induced from vaccine-induced responses. Our analysis has the potential to inform the design of serosurveys for SARS-CoV-2, including decisions regarding number of antibody biomarkers measured.


title: Epidemiological, clinical Characteristics and mortality of patients Infected with SARS-CoV-2 Admitted of Kinshasa University Hospital, Democratic Republic of the Congo from March 24, 2020 to January 30, 2021: Two waves, two faces?

abstract:
BackgroundThe objective of our retrospective study was to establish a comparison between the first and the second waves of demographic and clinical characteristics as well as mortality and its determinants.

MethodsA total of 411 COVID-19 patients were enrolled in Kinshasa University Hospital and categorized into two groups according to the pandemic pattern, demographics, and disease severity. The clinical characteristics were compared according to the two waves. To describe survival from the first day of hospitalization until death, we used Kaplan Meiers method. We used the Log Rank test to compare the survival curves between the two waves. The Cox regression was used to identify independent predictors of mortality.

ResultsDuring the study period, 411 patients with confirmed COVID-19 were admitted to the hospital. The average age of patients in the 2nd wave was higher than in the first wave (52.4 {+/-}17.5 vs 58.1 {+/-}15.7, p=0.026). The mean saturation was lower in the first wave than in the second. The death rate of patients in the first wave was higher than in the second wave (p=0.009). Survival was reduced in the first wave compared to the second wave. In the first wave, age over 60 years, respiratory distress, law oxygen saturation ([≤]89%) and severe stage of COVID-19 emerged as factors associated with death, while in the second wave it was mainly respiratory distress, law oxygen saturation ([≤] 89%) and severe stage. The predictors of mortality present in both the first and second waves were respiratory distress and severe COVID-19 stage.

ConclusionMortality decreased in the second wave. Age no longer emerged as a factor in mortality in the second wave. Health system strengthening and outreach to those at high risk of mortality should continue to maintain and improve gains.


title: Perceptions towards mask use in school children during the SARS-CoV-2 pandemic: the Ciao Corona Study

abstract:
BackgroundMask wearing contributes to the reduction of transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In Switzerland, compulsory use of masks was introduced in indoor public spaces and later in schools. In the canton of Zurich, masks were introduced for secondary school children (grades 7-9) from November 2020, and for primary school children (grades 4-6) from February 2021- along with other protective measures against SARS-CoV-2. This study explored perceptions towards the usefulness of masks in school and public in a cohort of children and adolescents in the canton of Zurich, Switzerland, in January - May 2021.

MethodsSchool children aged 10 to 17 years enrolled in Ciao Corona, a prospective school-based cohort study, responded to nested online surveys between January 12 to March 24 2021 (Q1) and March 10 to May 16 2021 (Q2). Secondary school children were surveyed at Q1 and Q2, and primary school children at Q2 only. Surveys for parents and their children included questions on childrens perception of the usefulness of masks and mask wearing behavior. Associations between perceived usefulness of masks and childs school level, gender, and parents educational attainment were analyzed with Pearsons and McNemars chi-squared tests. Free-text comments provided by children were classified into categories of expressed attitude towards mask wearing.

Results595 (54% girls) and 1118 (52% girls) school children responded to online questionnaires at Q1 and Q2, respectively. More than half of school children perceived masks to be useful at school (Q1:60% and Q2:57%) and in public (Q1:69% and Q2:60%). Girls perceived masks as useful more often than boys (at Q2 at school: 61% versus 53%, in public: 64% versus 57%), and children of parents with high educational attainment more often than those of parents with lower educational attainment (at Q2 at school: 61% versus 49%, in public: 63% versus 54%). There were no differences in the perceived usefulness of masks among children in primary versus secondary school. At Q1 and Q2 each, about 20% of children provided individual statements about masks, of which 36% at Q1 and 16% at Q2 reported side-effects and discomfort such as skin irritations, headache or difficulties breathing during physical education.

ConclusionApproximately 60% of school children perceived masks at school and in public places as useful. A small but non-negligible proportion of children reported discomfort and side-effects that should be considered to ensure high adherence to mask wearing among school children.

Trial registrationClinicalTrials.gov NCT04448717 https://clinicaltrials.gov/ct2/show/NCT04448717

CONTRIBUTION TO THE FIELD STATEMENTWorldwide about 150 countries fully closed their schools at some point during the coronavirus pandemic, while other countries - such as Switzerland - kept schools open almost all the time. However, among other protective measures, children in secondary school (aged approximately 14-16 years) had to wear masks since November 2020, and older children in primary school (aged 11-13 years) - since February 2021.

As part of the large study Ciao Corona based in schools in Switzerland, we wanted to learn how children perceive the usefulness of masks in school and public. Children and their parents completed questionnaires in January-March (595 secondary school children) and March-May 2021 (1118 secondary and primary school children).

We found that about 60% of children perceived masks to be useful at school and in public. Girls perceived masks as useful more often than boys, and children of parents with university or college education more often than those of parents with lower education. About 7- 9% of children reported side-effects and discomfort such as skin irritations, headache or difficulties breathing during physical education. Although side-effects were not frequently reported, they should be considered to ensure high adherence to mask wearing among school children.

category: pediatrics


title: Informing behaviour change intervention design using Bayesian meta-analysis: physical activity in heart failure

abstract: Embracing the Bayesian approach, we aimed to synthesise evidence regarding barriers and enablers to physical activity in HF in a way that can inform behaviour change intervention development. This approach helps in concluding on the uncertainty in the evidence and facilitates the synthesis of qualitative and quantitative evidence. Qualitative and observational studies investigating barriers and enablers to physical activity in adults diagnosed with HF were included in a Bayesian meta-analysis. Evidence from three qualitative and 16 quantitative studies was synthesised. Qualitative evidence was annotated using Theoretical Domains Framework and represented as a prior distribution using an expert elicitation task. The maximum a posteriori probability (MAP) and Credible Intervals (CrI) was calculated as a summary statistic for the probability distribution of physical activity conditioned on each determinant, according to qualitative evidence alone and qualitative and quantitative evidence combined. Evidence concerning the modifiable barriers and enablers is highly uncertain: social support (MAP=0.11,CrI:[0.08;0.13]), negative attitude (MAP=0.22,CrI:[0.17;0.27]), positive attitude ( MAP=0.27,CrI:[0.23;0.31]), self-efficacy( MAP=0.31,CrI:[0.29;0.33]), symptom distress (MAP=021,CrI:[0.18;0.24]). The contextual barriers - low, moderate and high uncertainty respectively - are age (MAP=0.22,CrI:[0.22;0.23]), low Left Ventricular Ejection Fraction (MAP=0.20,CrI:[0.19;0.22]), and depression (MAP=0.14,CrI:[0.12;0.16]). This work extends the limited research on the modifiable barriers and enablers for physical activity by individuals living with HF.

category: rehabilitation medicine and physical therapy


title: Extending treatment effects from a randomized trial using observational data: an application to coronary thrombus aspiration

abstract: To increase confidence in the use of observational analyses when addressing effectiveness questions beyond those addressed by randomized trials, one can first benchmark the observational analyses against existing trial results. We use Swedish registry data to emulate a target trial similar to the TASTE randomized trial, which found no difference in the risk of death or myocardial infarction by 1 year with or without thrombus aspiration among individuals with ST-elevation myocardial infarction. We benchmark the emulation against the trial at 1 year, then extend the emulations follow up to 3 years and estimate effects in subpopulations underrepresented in the trial. As in the TASTE trial, the observational analysis found no differences in risk of outcomes by 1 year between groups (risk difference 0.7 (-0.7,2.0) and -0.2 (-1.3,1.0) for death and myocardial infarction respectively), so benchmarking was considered successful. We additionally show no difference in risk of death or myocardial infarction by 3 years, or within subpopulations by 1 year. Benchmarking against an index trial before using observational analyses to answer questions beyond those the trial could address allowed us to explore whether the observational data can be trusted to deliver valid estimates of treatment effects.


title: Benchmarking observational analyses before using them to address questions trials cannot answer: an application to coronary thrombus aspiration


title: Assessment of COVID-19 intervention strategies in the Nordic countries using genomic epidemiology

abstract: The Nordic countries, defined here as Norway, Sweden, Denmark, Finland and Iceland, are known for their comparable demographics and political systems. Since these countries implemented different COVID-19 intervention strategies, they provide a natural laboratory for examining how COVID-19 policies and mitigation strategies affected the propagation, evolution and spread of the SARS-CoV-2 virus. We explored how the duration, the size and number of transmission clusters, defined as country-specific monophyletic groups in a SARS-CoV-2 phylogenetic tree, differed between the Nordic countries. We found that Sweden had the largest number of COVID-19 transmission clusters followed by Denmark, Norway, Finland and Iceland. Moreover, Sweden and Denmark had the largest, and most enduring, transmission clusters followed by Norway, Finland and Iceland. In addition, there was a significant positive association between transmission cluster size and duration, suggesting that the size of transmission clusters could be reduced by rapid and effective contact tracing. Thus, these data indicate that to reduce the general burden of COVID-19 there should be a focus on limiting dense gatherings and their subsequent contacts to keep the number, size and duration of transmission clusters to a minimum. Our results further suggest that although geographical connectivity, population density and openness influence the spread and the size of SARS-CoV-2 transmission clusters, country-specific intervention strategies had the largest single impact.


title: Prevalence of Migraine and its associated factors among medical students of Bangladesh: A cross sectional study

abstract:
IntroductionMedical students are vulnerable group to migraine, one of the most common type of headache worldwide. The aim of the present study was to determine the prevalence of migraine and related disability among medical students of Bangladesh.

MethodsThis cross-sectional study was conducted among 1327 students from six medical colleges Bangladesh during March 2021 through a self-administered online survey. ID Migraine scale and MIDAS scale were used to screen migraine and migraine related disability respectively. Frequency distribution, and Chi-square test, t-test along with multiple logistic regressions model were used to determine the prevalence and associated factors of migraine respectively.

ResultsThe overall prevalence of migraine among the participants was 19%. The prevalence was higher among females (27%) than males (8%). Female sex (aOR 4.11, 95% CI 2.79-6.03) and poor sleep quality (aOR 2.07, 95% CI 1.48-2.91) were identified as independent risk factors of migraine. More than 90% migrainures reported to suffer from moderate to severe headache. Nausea was most commonly reported associated symptom (83.5%) followed by photophobia (72%) and vomiting (53%). Self-reported mental stress (55%), irregular sleep (49%), noise (30.5%), and usage of electronic device (30.5%) were most commonly reported triggering factor of migraine attack. More than half of the sufferers reported severe migraine related disability (MIDAS score [≥] 21).

ConclusionsThe prevalence of migraine among medical students of Bangladesh is alarmingly high. Frequent migraine attacks and severe intensity of headache cause a substantial level of disability among the sufferers. Cautious avoidance of the triggering factors through appropriate interventions and prophylactic medication can mitigate the negative impact of migraine as well as improve the quality of life.


title: SARS-CoV-2 infected cells trigger an acute antiviral response mediated by Plasmacytoid dendritic cells in mild but not severe COVID-19 patients

abstract: Type I and III interferons (IFN-I/{lambda}) are key antiviral mediators against SARS-CoV-2 infection. Here, we demonstrate that plasmacytoid dendritic cells (pDCs) are the predominant IFN-I/{lambda} source following their sensing of SARS-CoV-2-infected cells. Mechanistically, this short-range sensing by pDCs requires sustained integrin-mediated cell adhesion with infected cells. In turn, pDCs restrict viral spread by an IFN-I/{lambda} response directed toward SARS-CoV-2-infected cells. This specialized function enables pDCs to efficiently turn-off viral replication, likely via a local response at the contact site with infected cells. By exploring the pDC response in SARS-CoV-2 patients, we further demonstrate that pDC responsiveness inversely correlates with the severity of the disease. The pDC response is particularly impaired in severe COVID-19 patients. Overall, we propose that pDC activation is essential to control SARS-CoV-2-infection. Failure to unfold this response could be key to understand severe cases of COVID-19.


title: Severe COVID-19 patients have impaired plasmacytoid dendritic cell-mediated control of SARS-CoV-2-infected cells