bluuebunny/crossref_metadata_2025 huggingface dataset:
A systematic review of COVID-19 vaccine efficacy and effectiveness against SARS-CoV-2 infection and disease
Authors: Higdon Melissa M , Wahl Brian , Jones Carli B , Rosen Joseph G , Truelove Shaun A , Baidya Anurima , Nande Anjalika A , ShamaeiZadeh Parisa A , Walter Karoline K , Feikin Daniel R , Patel Minal K , Knoll Maria Deloria , Hill Alison L
Published: September 2021

Billions of doses of COVID-19 vaccines have been administered globally, dramatically reducing SARS-CoV-2 incidence and severity in some settings. Many studies suggest vaccines provide a high degree of protection against infection and disease, but precise estimates vary and studies differ in design, outcomes measured, dosing regime, location, and circulating virus strains. Here we conduct a systematic review of COVID-19 vaccines through February 2022. We included efficacy data from Phase 3 clinical trials for 15 vaccines undergoing WHO Emergency Use Listing evaluation and real-world effectiveness for 8 vaccines with observational studies meeting inclusion criteria. Vaccine metrics collected include protection against asymptomatic infection, any infection, symptomatic COVID-19, and severe outcomes including hospitalization and death, for partial or complete vaccination, and against variants of concern Alpha, Beta, Gamma, Delta, and Omicron. We additionally review the epidemiological principles behind the design and interpretation of vaccine efficacy and effectiveness studies, including important sources of heterogeneity.
Persistent while declined neutralizing antibody responses in the convalescents of COVID-19 across clinical spectrum during the 16 months follow up
Authors: Yang Yang , Yang Minghui , Peng Yun , Liang Yanhua , Wei Jinli , Xing Li , Guo Liping , Li Xiaohe , Li Jie , Wang Jun , Li Mianhuan , Xu Zhixiang , Zhang Mingxia , Wang Fuxiang , Shi Yi , Yuan Jing , Liu Yingxia
Published: September 2021

Elucidation the kinetics of neutralizing antibody response in the coronavirus disease 2019 (COVID-19) convalescents is crucial for the future control of the COVID-19 pandemic and vaccination strategies. Here we tested 411 sequential plasma samples collected up to 480 days post symptoms onset (d.a.o) from 214 convalescents of COVID-19 across clinical spectrum without re-exposure history after recovery and vaccination of SARS-CoV-2, using authentic SARS-CoV-2 microneutralization (MN) assays. COVID-19 convalescents free of re-exposure and vaccination could maintain relatively stable anti-RBD IgG and MN titers during 400∼480 d.a.o after the peak at around 120 d.a.o and the subsequent decrease. Undetectable neutralizing activity started to occur in mild and asymptomatic infections during 330 to 480 d.a.o with an overall rate of 14.29% and up to 50% for the asymptomatic infections. Significant decline in MN titers was found in 91.67% COVID-19 convalescents with ≥ 50% decrease in MN titers when comparing the available peak and current MN titers (≥ 300 d.a.o). Antibody-dependent immunity could also provide protection against most of circulating variants after one year, while significantly decreased neutralizing activities against the Beta, Delta and Lambda variants were found in most of individuals. In summary, our results indicated that neutralizing antibody responses could last at least 480 days in most COVID-19 convalescents despite of the obvious decline of neutralizing activity, while the up to 50% undetectable neutralizing activity in the asymptomatic infections is of great concern.
Cohort Study: The Accuracy of Screening Methods of COVID-19 in Pregnancy: Practical Approach in Low Resources Health Services
Authors: Aldika Akbar Muhammad Ilham , Gumilar Khanisyah Erza , Rahestyningtyas Eccita , Wardhana Manggala Pasca , Mulawardhana Pungky , Anas Jimmy Yanuar , Ernawati  , Cahya Laksana Muhammad Ardian , Joewono Hermanto Tri
Published: September 2021

Background

All pregnant women in labor should be universally screened for Coronavirus Disease 2019 (COVID-19) during pandemic periods using Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) test. In many low-middle income countries, screening method was developed as an initial examination because of limited availability of RT-PCR tests.

Objectives

This study aims to evaluate the screening methods of COVID-19 accuracy in pregnant women.

Material and Methods

We recruited all pregnant women with suspicion of COVID-19 from April - August 2020 at Universitas Airlangga hospital, Surabaya, Indonesia. The participant was divided into two groups based on RT-PCR results: COVID-19 and non-COVID-19 group. The proportion of positive signs & symptoms, rapid antibody test, abnormal findings in chest x-ray, and neutrophil to lymphocyte ratio (NLR) value were then compared between both groups. The sensitivity, specificity, positive predictive value (PPV), negative predictive values (NPV), and diagnostic accuracy (DOR) were calculated.

Results

A total 141 pregnant women with suspected COVID-19 cases were recruited for this study. This consist of 62 COVID-19 cases (43.9%) and 79 non COVID-19 pregnant women (56.1%). The sensitivity, spesificity, PPV, NPV, and diagnostic accuracy of each parameter are as follow: clinical sign & symptoms (24.19%, 75.95%, 3.92%, 96.11%, 65.87%), rapid antibody test (72.73%, 35.06%, 4.35%, 96.94%, 36.53%), chest x-ray (40.68%, 59.45%, 3.92%, 96.11%, 58.76%), and NLR > 5.8 (41.38%, 72%, 5.66%, 96.80%, 70.81%).

Conclusions

The use of combined screening methods can classify pregnant women with high-risk COVID-19 before definitively diagnosed with RT-PCR. This practice will help to reduce RT-PCR need in a limited resources country.
Factors affecting first return to work following arthroscopic rotator cuff repair: A retrospective observational study in an occupational medicine clinic and single-surgeon practice
Authors: Khan Ijaz , Fatima Manaal , Scholes Corey , Kandhari Vikram , Ponnanna K.M. , Herald Jonathan
Published: September 2021

Aims

Determine factors affecting first return to work (RTW) status and time in patients treated with arthroscopic rotator cuff repair (aRCR) under state-based compensation schemes in New South Wales, Australia, compared to those outside such schemes.

Material and Methods

Patients undergoing aRCR by one surgeon with minimum 1-year follow-up were grouped into those under (CP) or outside (non-CP) workers or vehicle accident compensation schemes, matched by age and gender. RTW status and time were assessed using chi-square analysis and multivariable linear regression.

Results

Of 1054 available patients, 90 CP patients were identified with 29 consented and matched to non-CP (N=29). A higher proportion of CP patients (17.2 vs 0%, P<0.001) never returned to work and a lower proportion resumed pre-injury duties at first RTW (3 vs 52%, P<0.01). Median time to first RTW did not differ between CP and non-CP groups (5.1 vs 4.4, P=0.86). Smoking (P=0.007) and post-injury activity level (P=0.004) were significantly associated with longer time to first RTW, whereas compensation status was not.

Conclusions

CP patients undergoing aRCR in NSW are at risk of not returning to work. For those that do return, there is no significant difference compared to non-CP in time to first RTW. Particularly, patient and management factors associated with extended time to first RTW have been identified. Interventions aimed at modifiable factors such as smoking cessation and increasing preoperative activity may improve future outcomes.
GLOBAL PATTERNS OF PLUMAGE COLOUR EVOLUTION IN ISLAND-LIVING PASSERIFORM BIRDS
Authors: Mahoney Sean M. , Oud Madison D. , Pageau Claudie , de Menezes Marcio Argollo , Smith Nathan , Briskie James V. , Reudink Matthew W.
Published: September 2021

Plumage coloration is an important trait involved communication and is shaped by a variety of ecological pressures. Island residency has the potential to change the evolutionary trajectory of plumage colour by differences in habitat and resources, or by altering predation pressure and social selection intensity. Latitude, island size, and isolation may further influence colour evolution by biasing colonization. Therefore, general patterns of plumage evolution are difficult to disentangle. We used phylogenetically controlled analyses to assess the influence of island residency on plumage colouration, by calculating chromaticity values from red, blue, green scores extracted from photos of Order Passeriformes birds. Importantly, we controlled for ecological factors hypothesized to influence colour evolution and assessed family-level effects. We found 1) colour varied between islands and mainlands in females, but not males, and both sexes were affected by several ecological factors; 2) patterns of colour evolution varied among families; 3) island size and distance to the mainland and other islands significantly influenced colour; and 4) interactions between ecological factors and latitude were consistently influenced colour, supporting a latitudinal gradient hypothesis. Our results indicate although island residency influences female colour evolution, a myriad of ecological factors drive plumage colour and the patterns vary among families.
Social inequalities, length of hospital stay for chronic conditions and the mediating role of comorbidity and discharge destination: A multilevel analysis of hospital administrative data linked to the population census in Switzerland
Authors: Bayer-Oglesby Lucy , Zumbrunn Andrea , Bachmann Nicole
Published: September 2021

Social factors are recognized determinants of morbidity and mortality and also have an impact on use of medical services. The objective of this study was to assess the associations of educational attainment, social and financial resources and migration factors with length of hospital stays for chronic conditions and to investigate the role of comorbidity and discharge destination in mediating these associations. The study made use of nationwide inpatient data that was linked with Swiss census data. The study sample included n=141,307 records of n=92,623 inpatients aged 25 to 84 years, hospitalized between 2010 and 2016 for a chronic condition. Cross-classified multilevel models were performed. Patients with upper secondary and compulsory education stayed longer in hospital compared to those with tertiary education (β 0.24 days, 95% CI 0.14-0.33; β 0.37, 95% CI 0.27-0.47, respectively) when taking into account demographic factors, main diagnosis and clustering on patient and hospital level. However, these effects were almost fully mediated by burden of comorbidity. The effect of living alone on length of stay (β 0.60 days, 95% CI 0.50-0.70) was partially mediated by both burden of comorbidities (33%) and discharge destination (30.4%). (Semi-) private insurance was associated with prolonged stays, but an inverse effect was observed for colon and breast cancer. Allophone patients had also prolonged hospital stays (β 0.34, 95% CI 0.13-0.55). Hospital stays could be a window of opportunity to discern patients who need additional time and support to better cope with everyday life after discharge, reducing the risks of future hospital stays. However, inpatient care in Switzerland seems to take into account rather obvious individual needs due to lack of immediate support at home, but not necessarily more hidden needs of patients with low health literacy and less resources to assert their interests within the health system.
Prevalence of SARS-CoV-2 infection among people experiencing homelessness in Toronto during the first wave of the COVID-19 pandemic
Authors: Luong Linh , Beder Michaela , Nisenbaum Rosane , Orkin Aaron , Wong Jonathan , Damba Cynthia , Emond Ryan , Lena Suvendrini , Wright Vanessa , Loutfy Mona , Bruce-Barrett Cindy , Cheung Wilfred , Cheung Yick Kan , Williams Victoria , Vanmeurs Miriam , Boozary Andrew , Manning Harvey , Hester Joe , Hwang Stephen W.
Published: September 2021

Background

People experiencing homelessness are at increased risk of SARS-CoV-2 infection. This study reports the point prevalence of SARS-CoV-2 infection during testing conducted at sites serving people experiencing homelessness in Toronto during the first wave of the COVID-19 pandemic. We also explored the association between site characteristics and prevalence rates.

Methods

The study included individuals who were staying at shelters, encampments, COVID-19 physical distancing sites, and drop-in and respite sites and completed outreach-based testing for SARS-CoV-2 during the period April 17 to July 31, 2020. We examined test positivity rates over time and compared them to rates in the general population of Toronto. Negative binomial regression was used to examine the relationship between each shelter-level characteristic and SARS-CoV-2 positivity rates. We also compared the rates across 3 time periods (T1: April 17-April 25; T2: April 26-May 23; T3: May 24-June 25).

Results

The overall prevalence of SARS-CoV-2 infection was 8.5% (394/4657). Site-specific rates showed great heterogeneity with infection rates ranging from 0% to 70.6%. Compared to T1, positivity rates were 0.21 times lower (95% CI: 0.06, 0.75) during T2 and 0.14 times lower (95% CI: 0.043, 0.44) during T3. Most cases were detected during outbreak testing (384/394 [97.5%]) rather than active case finding.

Interpretation

During the first wave of the pandemic, rates of SARS-CoV-2 infection at sites for people experiencing homelessness in Toronto varied significantly over time. The observation of lower rates at certain sites may be attributable to overall time trends, expansion of outreach-based testing to include sites without known outbreaks and/or individual site characteristics.
Inflammation and autoreactivity define a discrete subset of patients with post-acute sequelae of COVID-19, or long-COVID
Authors: Woodruff Matthew C. , Bonham Kevin S. , Anam Fabliha A. , Walker Tiffany A. , Ishii Yusho , Kaminski Candice Y. , Ruunstrom Martin C. , Truong Alexander D. , Dixit Adviteeya N. , Han Jenny E. , Ramonell Richard P. , Haddad Natalie S. , Rudolph Mark E. , Jenks Scott A. , Khosroshahi Arezou , Lee F. Eun-Hyung , Sanz Ignacio
Published: September 2021

While significant attention has been paid to the immunologic determinants of disease states associated with COVID-191,2, their contributions to post-acute sequelae of COVID-19 (PASC) remain less clear3-5. Due to the wide array of PASC presentations6, it is critical to understand if specific features of the disease are associated with discrete immune processes, and whether those processes may be therapeutically targeted. To this end, we performed wide immunologic and serological characterization of patients in the early recovery phase of COVID-19 across a breadth of symptomatic presentations. Using high-parameter proteomics screening and applied machine learning (ML), we identify clear signatures of immunologic activity between PASC patients and uncomplicated recovery, dominated by inflammatory cytokine signaling, neutrophil activity, and markers of cell death. Consistent with disease complexity, heterogeneity in plasma profiling reveals distinct PASC subsets with striking divergence in these ongoing inflammatory processes, here termed plasma quiescent (plaq) and inflammatory (infl) PASC. In addition to elevated inflammatory blood proteomics, inflPASC patients display positive clinical tests of acute inflammation including C-reactive protein and fibrinogen, increased B cell activity with extrafollicular involvement coupled with elevated targeting of viral nucleocapsid protein and clinical autoreactivity. Further, the unique plasma signatures of PASC patients allowed for the creation of refined models with high sensitivity and specificity for the positive identification of inflPASC with a streamlined assessment of 12 blood markers. Additionally, refined ML modeling highlights the unexpected significance of several markers of potential diagnostic or therapeutic use for PASC in general, including the peptide hormone, epiregulin. In all, this work identifies clear biological signatures of PASC with potential diagnostic and therapeutic potential and establishes clear disease subtypes that are both easily identifiable and highly relevant to ongoing efforts in both therapeutic targeting and epidemiological investigation of this highly complex disease.
Postnatal maternal depressive symptoms and behavioural outcomes in term- and preterm-born toddlers
Authors: Kleine I , Vamvakas G , Lautarescu A , Falconer S , Chew A , Counsell SJ , Pickles A , Edwards AD , Nosarti C
Published: September 2021

Objectives

To examine the association between maternal depressive symptoms in the immediate postnatal period and offspring’s mental health in a large cohort of term- and preterm-born toddlers.

Design and Participants

Data were drawn from the Developing Human Connectome Project. Maternal postnatal depressive symptoms were assessed at term, and children’s outcomes were evaluated at a median corrected age of 18.4 months (range 17.3 – 24.3).

Exposure and outcomes

Preterm birth was defined as <37 weeks completed gestation. Maternal depressive symptoms were assessed with the Edinburgh Postnatal Depression Scale (EPDS). Toddlers’ outcome measures were parent-rated Child Behaviour Checklist 11/2-5 Total (CBCL) and Quantitative Checklist for Autism in Toddlers (Q-CHAT) scores. Toddlers’ cognition was assessed with the Bayley Scales of Infant and Toddler Development – Third Edition (Bayley-III).

Results

Higher maternal EPDS scores were associated with toddlers’ higher CBCL (B=0.93, 95% CI 0.43-1.44, p<0.001, f2=0.05) and Q-CHAT scores (B=0.27, 95% CI 0.03-0.52, p=.031, f2=0.01). Higher maternal EPDS scores were not associated with toddlers’ cognitive outcomes. Maternal EPDS, toddlers’ CBCL and Q-CHAT scores did not differ between preterm (n=97; 19.1% of the total sample) and term participants.

Conclusions

Our findings indicate that children whose mothers had increased depressive symptoms in the early postnatal period, including subclinical symptoms, exhibit more maternally-reported behavioural problems in toddlerhood. These associations were independent of gestational age. Further research is needed to confirm the clinical significance of these findings.

Strengths and limitations of this study

Prospective study with a large sample, using multiple imputation to reduce non-response bias.

Maternal depressive symptoms assessed as a continuous variable, providing more nuanced information about the significance of subclinical symptoms.

Maternal depressive symptoms assessed earlier than in previous studies, enabling recognition of early screening opportunities for families.

Potential shared method variance bias through parent-completed child behavioural assessments.

Unknown paternal and parental factors, such as comorbid psychiatric conditions, that may confound our findings.
The Impact of New SARS-CoV-2 Variants on Vaccine Breakthrough: A Pilot Study on Spreading Infection in the Communities
Authors: Ayass Mohamad Ammar , Zhang Jin , Zhu Kevin , Cao Wanying , Griko Natalya , Pashkov Victor , Dai Jun , Tripathi Trivendra , Mosleh Lina Abi
Published: September 2021

Background

Coronavirus disease 2019 (COVID-19) vaccines are effective at helping protect against severe disease and death from variants; however, incident of breakthrough infection in vaccinated patients has been increased. Therefore, we aimed to assess the incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) new variants of concern in the communities and investigate vaccine breakthrough cases on our laboratory (Ayass Bioscience LLC) confirmed detection of COVID-19 variants in Dallas-Fort Worth (DFW), Texas.

Methods

Epidemiologic study has been performed at our laboratory. We studied the viral whole-genome sequence and genotyping analysis on 166 symptomatic cases of COVID-19 which were randomly selected from nasal swab positive cases assessed from June 1st to August 30th, 2021, by reverse transcription polymerase chain reaction (RT-PCR) cycle threshold (CT) values. COVID-19 variants were identified to be dominated by B.1.617.2 (89.2%) and followed by AY.3 (1.8%), B.1.1.7 (4.8%), a combination of B.1.526.1 and B.1.617.2 (3%), B.1.621 (0.6%), and P.2 (0.6%).

Result

The CT values showed significant difference among the three age groups: <30 years, 31-60 years, and >60 years by one-way ANOVA (N1: F (2, 118) =4.96, p=0.009; N2: F (2, 118) =4.95, p=0.009). No significant difference was observed by symptom, status of immunization, or vaccine manufacturer. A two-way ANOVA was performed to examine the effect of gender and variant group (Delta and other variants) on the CT values. The analyses revealed a statistically significant interaction between the effect of gender and variant group (N1, F (1.117) = 3.906, p = 0.05; N2, F (1, 117) = 7.402, p = 0.008).

Conclusion

Our study shows that Delta, the dominant variant of COVID-19, is spreading in the communities, and vaccine breakthrough cases occurred in the majority of Delta variant (91%) followed by AY.3 (5%), B.1.1.7 (2%) and 2% of the double variant of B.1.526.1 and B.1.617.2. The incidence of the breakthrough cases was not linked to a specific manufacturer. The CT value is likely to associate with age. This study also supports our laboratory’s ongoing efforts to sequence the SARS-CoV-2 virus from positive patient samples to identify the new viral variants and possible vaccine breakthrough mutations in the community.
Quantification and prognostic significance of interferon-γ secreting SARS-CoV-2 responsive T cells in hospitalised patients with acute COVID-19
Authors: Pan Daniel , Kim Jee Whang , Nazareth Joshua , Assadi Sara , Bellass Adam , Leach Jack , Brosnan James G , Ahmed Adam , Starcevic Fleur , Sze Shirley , Martin Christopher A , Williams Caroline M , Barer Michael R , Sahota Amandip , Patel Prashanth , Tattersall Andrea , Cooper Andrea , Pareek Manish , Haldar Pranabashis
Published: September 2021

Little is known about T-cell responses during acute coronavirus disease-2019 (COVID-19). We measured T-cell interferon gamma (IFN-γ) responses to spike 1 (S1), spike 2 (S2), nucleocapsid (N) and membrane (M) SARS-CoV-2 antigens using the T-SPOT® Discovery SARS-CoV-2 assay, a proven EliSPOT technology, in 114 hospitalised adult COVID-19 patients and assessed their association with clinical disease phenotype. T-SPOT® Discovery SARS-CoV-2 responses were detectable within 2 days of a positive PCR and did not correlate with vaccination status or symptom duration. Higher responses to S1 protein associated with a higher symptom burden, and serum IL-6 levels. Despite treatment with dexamethasone this subgroup was also at greater risk of requiring continuous positive airway pressure (CPAP) in the days following sampling. Higher T-cell responses measured using T-SPOT® Discovery SARS-CoV-2 associate with progressive disease in acute COVID-19 disease and may have utility as a prognostic biomarker that should be evaluated in larger cohorts.
Young Zambian infants with symptomatic RSV and pertussis infections are frequently prescribed inappropriate antibiotics
Authors: Gunning CE , Rohani P , Mwananyanda L , Kwenda G , Mupila Z , Gill CJ
Published: September 2021

Pediatric community-acquired pneumonia (CAP) remains a pressing global health concern, particulary in low-resource settings where diagnosis and treatment rely on empiric, symptoms-based guidelines such as the WHO’s Integrated Management of Childhood Illness (IMCI). This study details the delivery of IMCI-based health care in a cohort of 1,320 young infants and their mothers in a low-resource urban community in Lusaka, Zambia. We prospectively monitored mother/infant pairs across infants’ first four months of life, recording symptoms of respiratory infection and antibiotics prescriptions (predominantly penicillins), and tested nasopharyngeal (NP) samples for Respiratory syncytial virus (RSV) and Bordetella pertussis. Symptoms and antibiotics use were more common in infants (43% and 15.7%) than in mothers (16.6% and 8%), while RSV and B. pertussis were observed at similar rates in infants (2.7% and 32.5%) and mothers (2% and 35.5%), albeit frequently at very low levels. In infants, we observed strong associations between symptoms, pathogen detection, and antibiotics use. Critically, we demonstrate that non-macrolide antibiotics were commonly prescribed for pertussis infections, some of which persisted across many weeks. We speculate that improved diagnostic specificity and/or clinician education paired with timely, appropriate treatment of pertussis could substantially reduce the burden of this disease while reducing the off-target use of penicillins.
Connecting Artificial Intelligence and Primary Care Challenges: Findings from a Multi-Stakeholder Collaborative Consultation
Authors: Kueper Jacqueline K. , Terry Amanda L. , Bahniwal Ravninder , Meredith Leslie , Beleno Ron , Brown Judith Belle , Dang Janet , Leger Daniel , McKay Scott , Ryan Bridget L. , Zwarenstein Merrick , Lizotte Daniel J.
Published: September 2021

Despite widespread advancements in and envisioned uses for artificial intelligence (AI), few examples of successfully implemented AI innovations exist in primary care (PC) settings.

Objectives

To identify priority areas for AI and PC in Ontario, Canada.

Methods

A collaborative consultation event engaged multiple stakeholders in a nominal group technique process to generate, discuss, and rank ideas for how AI can support Ontario PC.

Results

The consultation process produced nine ranked priorities: 1) preventative care and risk profiling, 2) patient self-management of condition(s), 3) management and synthesis of information, 4) improved communication between PC and AI stakeholders, 5) data sharing and interoperability, 6-tie) clinical decision support, 6-tie) administrative staff support, 8) practitioner clerical and routine task support, and 9) increased mental health care capacity and support. Themes emerging from small group discussions about barriers, implementation issues, and resources needed to support the priorities included: equity and the digital divide; system capacity and culture; data availability and quality; legal and ethical issues; user-centered design; patient-centredness; and proper evaluation of AI-driven tool implementation.

Discussion

Findings provide guidance for future work on AI and PC. There are immediate opportunities to use existing resources to develop and test AI for priority areas at the patient, provider, and system level. For larger-scale, sustainable innovations, there is a need for longer-term projects that lay foundations around data and interdisciplinary work.

Conclusion

Study findings can be used to inform future research and development of AI for PC, and to guide resource planning and allocation.

What is already known?

–

The field of artificial intelligence and primary care is underdeveloped.

What does this paper add?

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An environmental scan without geographic location restriction identified 110 artificial intelligence-driven tools with potential relevance to primary care that existed around the time of the study.

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A multi-stakeholder consultation session identified nine priorities to guide future work on artificial intelligence and primary care in Ontario, Canada.

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Priorities for artificial intelligence and primary care include provider, patient, and system level uses as well as foundational areas related to data and interdisciplinary communication.
Effect of Long-Term Caloric Restriction on DNA Methylation Measures of Biological Aging in Healthy Adults: CALERIE™ Trial Analysis
Authors: Waziry R , Corcoran DL , Huffman KM , Kobor MS , Kothari M , Kraus VB , Kraus WE , Lin DTS , Pieper CF , Ramaker ME , Bhapkar M , Das SK , Ferrucci L , Hastings WJ , Kebbe M , Parker DC , Racette SB , Shalev I , Schilling B , Belsky DW
Published: September 2021

Calorie restriction (CR) slows aging and increases healthy lifespan in model organisms. We tested if CR slowed biological aging in humans using DNA methylation analysis of blood samples from N=197 participants in the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE™) randomized controlled trial. We quantified CR effects on biological aging by comparing change scores for six epigenetic-clock and Pace-of-Aging measures between n=128 CR-group and n=69 ad-libitum-control-group participants at 12- and 24-month follow-ups. CR effects were strongest for DunedinPACE Pace of Aging (12-month Cohen’s d=0.3; 24-month Cohen’s d=0.2, p<0.01 for both), followed by DunedinPoAm and the GrimAge epigenetic clock, although effects for these measures were not statistically different from zero (p>0.08). CR effects for other epigenetic clocks were in the opposite direction (all p>0.15). CALERIE intervention slowed Pace of Aging but showed minimal effect on epigenetic clocks hypothesized to reflect longer term accumulation of aging burden.
miRNAs Copy Number Variations repertoire as hallmark indicator of cancer species predisposition
Authors: Vischioni Chiara , Bove Fabio , Mandreoli Federica , Martoglia Riccardo , Pisi Valentino , Taccioli Cristian
Published: September 2021

Aging is one of the hallmarks of multiple human diseases, including cancer. However, the molecular mechanisms associated with high longevity and low cancer incidence percentages characterizing long-living organisms have not been fully understood yet. In this context, we hypothesized that variations in the number of copies (CNVs) of specific genes may protect some species from cancer onset. Based on the statistical comparison of gene copy numbers within the genomes of cancer -prone and -resistant organisms, we identified novel gene targets linked to the tumor predisposition of a species, such as CD52, SAT1 and SUMO protein family members. Furthermore, for the first time, we were able to discover that, considering the entire genome copy number landscape of a species, microRNAs (miRNAs) are among the most significant gene families enriched for cancer progression and predisposition. However, their roles in ageing and cancer resistance from a comparative perspective remains largely unknown. To this end, we identified through bioinformatics analysis, several alterations in miRNAs copy number patterns, represented by duplication of miR-221, miR-222, miR-21, miR-372, miR-30b, miR-30d and miR-31 among others. Therefore, our analysis provides the first evidence that an altered copy number miRNAs signature is able to statistically discriminate species more susceptible to cancer than those that are tumor resistant, helping researchers to discover new possible therapeutic targets involved in tumor predisposition.
Prevalence and risk factors for in-school transmission of SARS-CoV-2 in Massachusetts K-12 public schools, 2020-2021
Authors: Nelson Sandra B. , Dugdale Caitlin M. , Bilinski Alyssa , Cosar Duru , Pollock Nira R. , Ciaranello Andrea
Published: September 2021

Introduction

The SARS-CoV-2 secondary attack rate (SAR) in schools is low when mitigation measures are adopted, Data on the relative impact of such strategies are limited. We evaluated the SARS-CoV-2 SAR in Massachusetts schools during 2020-21 and factors associated with transmission risk.

Methods

In a convenience sample of 25 Massachusetts public K-12 school districts, de-identified information about SARS-CoV-2 cases and their school-based contacts was reported using a standardized contact-tracing tool. Index cases were included if they were in school while infectious. SAR was defined as the proportion of in-school contacts acquiring SARS-CoV-2 infection and designated as possible or probable in-school transmission by school-based teams. We compared exposure-specific SAR using unadjusted risk ratios (RR) with 95% confidence intervals (CI); p-values were calculated using Fishers exact tests.

Results

Eight districts (70 schools with >33,000 enrolled students) participated. There were 435 index cases and 1,771 school-based contacts (Table 1). Most contacts (1327/1771 [75%]) underwent SARS-CoV-2 testing and 39/1327 (2.9%) contacts tested positive. Of 39 positive contacts, 10 (25.6%) had clear out-of-school exposures and were deemed not in-school transmissions, so were excluded from further calculations. Twenty-nine (74.4%) contacts were deemed possible or probable in-school transmissions, resulting in an in-school SAR of 2.2%. Of the 29 in-school transmissions, 6 (20.7%) were staff-to-staff, 7 (24.1%) were staff-to-student, 3 (10.3%) were student-to-staff, and 13 (44.8%) were student-to-student; 6 (20.7%) occurred from index cases attending work/school while symptomatic. The unadjusted SAR (Table 2) was significantly higher if the index case was a staff member versus a student (RR 2.18, 95% CI 1.06-4.49; p=0.030), if the index case was identified via in-school contact tracing versus via school-based asymptomatic testing (RR 8.44, 95% CI 1.98-36.06; p=0.001), if the exposure occurred at lunch versus elsewhere (RR 5.74, 95% CI 2.11-15.63; p<0.001; all lunch transmissions were staff-to-staff), and if both parties were unmasked versus both masked (RR 6.98, 95% CI 3.09-15.77; p<0.001). For students, SAR did not differ by grade level.

Conclusions

Secondary attack rates for SARS-CoV-2 were low in public school settings with comprehensive mitigation measures in place before the emergence of the delta variant; lack of masking and staff-to-staff dining were associated with increased risk.
Initial emergency department vital signs may predict PICU admission in pediatric patients presenting with asthma exacerbation
Authors: Freedman Michael S , Forno Erick
Published: September 2021

Objective

Severe asthma exacerbations account for a large share of asthma morbidity, mortality, and costs. Here, we aim to identify early predictive factors for pediatric intensive care unit (PICU) admission that could help improve outcomes.

Methods

We performed a retrospective observational study of 6,014 emergency department (ED) encounters at a large children’s hospital, including 95 (1.6%) resulting in PICU admission between 10/1/2015 and 8/31/2017 with ICD9/ICD10 codes for “asthma,” “bronchospasm,” or “wheezing”. Vital signs and demographic information were obtained from EHR data and analyzed for each encounter. Predictive factors were identified using adjusted regression models, and our primary outcome was PICU admission.

Results

Higher mean heartrates (HR) and respiratory rates (RR) and lower SpO2 within the first hour of ED presentation were independently associated with PICU admission. Odds of PICU admission increased 63% for each 10-beats/minute higher HR, 97% for each 10-breaths/minute higher RR, and 34% for each 5% lower SpO2. A binary predictive index using 1-hour vitals yielded OR 11.7 (95%CI 7.4-18.3) for PICU admission, area under the receiver operator characteristic curve (AUROC) 0.82 and overall accuracy of 81.5%. Results were essentially unchanged (AUROC 0.84) after adjusting for asthma severity and initial ED management. In combination with a secondary standardized clinical asthma distress score, positive predictive value increased by seven-fold (5.9% to 41%).

Conclusions

A predictive index using HR, RR and SpO2 within the first hour of ED presentation accurately predicted PICU admission in this cohort. Automated vital signs trend analysis may help identify vulnerable patients quickly upon presentation.
The importance of sustained compliance with physical distancing during COVID-19 vaccination rollout
Authors: Teslya Alexandra , Rozhnova Ganna , Pham Thi Mui , van Wees Daphne A , Nunner Hendrik , Godijk Noortje G , Bootsma Martin , Kretzschmar Mirjam E
Published: September 2021

Mass vaccination campaigns against SARS-CoV-2 are ongoing in many countries with increasing vaccination coverage enabling relaxation of lockdowns. Vaccination rollout is frequently supplemented with advisory from public health authorities for continuation of physical distancing measures. Compliance with these measures is waning while more transmissible virus variants such as Alpha (B.1.1.7) and Delta (B.1.617.2) have emerged. In this work, we considered a population where the waning of compliance depends on vaccine coverage. We used a SARS-CoV-2 transmission model which captures the feedback between compliance, infection incidence, and vaccination coverage to investigate factors that contribute to the increase of the prevalence of infection during the initial stages of the vaccination rollout as compared to no vaccination scenario. We analysed how the vaccine uptake rate affects cumulative numbers of new infections three and six months after the start of vaccination. Our results suggest that the combination of fast waning compliance in non-vaccinated population, low compliance in vaccinated population and more transmissible virus variants may result in a higher cumulative number of new infections than in a situation without vaccination. These adverse effects can be alleviated if vaccinated individuals do not revert to pre-pandemic contact rates, and if non-vaccinated individuals remain compliant with physical distancing measures. Both require convincing, clear and appropriately targeted communication strategies by public health authorities.

Significance Statement

SARS-CoV-2 vaccination campaigns are in progress in many countries around the world. As the vaccination coverage increases, the compliance with physical distancing measures aimed at reducing virus transmission may decline. Using a socio-epidemiological model we identify factors that are the drivers of increased transmission when SARS-CoV-2 prevalence is higher than the projected prevalence without vaccination. To maximize the benefits of vaccination campaigns, compliance in vaccinated and non-vaccinated groups should be targeted prioritizing one group over the other depending on the vaccination rate, the efficacy of vaccine in blocking the infection, and the circulating variant.
Association of comorbidities with COVID-19 infection rate and severity: nationwide cohort study with propensity score matching
Authors: Kim Jiyong , Park Seong Hun , Kim Jong Moon
Published: September 2021

Objective

To describe the association of comorbidities with coronavirus infection-19 (COVID-19) infection rates and severity of infection through Korean nationwide medical system.

Design

Nationwide population-based retrospective cohort study.

Setting

Korean national health insurance claims database between January 1, 2020, and May 30, 2020.

Participants

Patients with positive COVID-19 test and 12 folded controls matched by age, sex and region.

Main Outcomes Measures

Outcomes were confirmation of the comorbidities affecting the infection rate and the severity of COVID-19. Patients and outcomes were propensity score matching of factors which may affect COVID-19 infection rate and severity was performed. COVID-19 infections were confirmed through laboratory testing. Severe infection was defined as those who underwent tracheostomy, continuous renal replacement therapy, intensive care unit admission, ventilator use, cardiopulmonary resuscitation, or died.

Results

A total of 8070 individuals with positive covid-19 test and 12015 controls were identified. In people aged 60 or older, in those insured with Medicaid, and in the disabled, the proportion corresponding to the severe group of patients showed a tendency to increase. The infection rate of COVID-19 was highest in pulmonary disease (adjusted odds ratio 1.88, 95% confidence interval 1.70 to 2.03), and hyperlipidemia (0.73, 0.67 to 0.80) had a lower infection rate. Disease severity was highest in kidney disease (5.59, 2.48 to 12.63), and lower in hyperlipidemia (0.78, 0.60 to 1.00).

Conclusions

There is less bias as the government pays for all tests and treatments related to COVID-19 included in the data used in this study. Using propensity matching to reduce statistical bias, we found that most comorbidities increased the infection rate and severity of COVID-19, whereas hyperlipidemia reduced the rate and severity of infection. These results can be utilized to effectively manage COVID-19 infections.
Downsizing food: A systematic review and meta-analysis examining the effect of reducing served food portion sizes on daily energy intake and body weight
Authors: Robinson Eric , McFarland-Lesser India , Patel Zina , Jones Andrew
Published: September 2021

Background

Portion sizes of many foods have increased over time and reducing food portion sizes has been proposed as a public health strategy to reduce obesity. However, the extent to which reducing food portion sizes affects daily energy intake and body weight is unclear.

Objective

To systematically review and meta-analyse experimental studies that have examined the effect that serving smaller vs. larger portion sizes has on total daily energy intake.

Design

We used systematic review methodology to search identify eligible articles that used an experimental design to manipulate portion size served to human participants and measured energy intake for a minimum of one day. Multi-level meta-analysis was used to used to pool effects of portion size on daily energy intake.

Results

Fourteen eligible studies were included and 85 effects were included in the primary meta-analysis. There was a moderate-to-large reduction in daily energy intake when comparing smaller vs. larger portions (SMD = -.709 [95% CI: -.956 to -.461], p < .001, I2 = 80.6%) and evidence of a dose dependent response. Larger reductions to portion size and reducing portion sizes of multiple meals per day both resulted in larger decreases in daily energy intake. There was also evidence of a curvilinear relationship between portion size and daily energy intake, whereby reductions to daily energy intake were markedly smaller when reducing portion size from very large portions. In a subset of studies that measured body weight (n=5), being served smaller portions was associated with less weight gain than larger portions (SMD = .536 ([95% CI: .268 to .803], p < .001, I2 = 47.0%).

Conclusions

Smaller food portion sizes substantially decrease daily energy intake and there is evidence that over time this results in lower body weight. Reducing food portion sizes may be an effective population level strategy to reduce obesity.
COVID-19 mortality risk correlates inversely with vitamin D3 status, and a mortality rate close to zero could theoretically be achieved at 50 ng/ml 25(OH)D3: Results of a systematic review and meta-analysis
Authors: Borsche Lorenz , Glauner Bernd , von Mendel Julian
Published: September 2021

Background

Much research shows that blood calcidiol (25(OH)D3) levels correlate strongly with SARS-CoV-2 infection severity. There is open discussion regarding whether low D3 is caused by the infection or if deficiency negatively affects immune defense. The aim of this study was to collect further evidence on this topic.

Methods

Systematic literature search was performed to identify retrospective cohort as well as clinical studies on COVID-19 mortality rates versus D3 blood levels. Mortality rates from clinical studies were corrected for age, sex and diabetes. Data were analyzed using correlation and linear regression.

Results

One population study and seven clinical studies were identified, which reported D3 blood levels pre-infection or on the day of hospital admission. They independently showed a negative Pearson correlation of D3 levels and mortality risk (r(17)=-.4154, p=.0770/r(13)=-.4886, p=.0646). For the combined data, median (IQR) D3 levels were 23.2 ng/ml (17.4 – 26.8), and a significant Pearson correlation was observed (r(32)=-.3989, p=.0194). Regression suggested a theoretical point of zero mortality at approximately 50 ng/ml D3.

Conclusions

The two datasets provide strong evidence that low D3 is a predictor rather than a side effect of the infection. Despite ongoing vaccinations, we recommend raising serum 25(OH)D levels to above 50 ng/ml to prevent or mitigate new outbreaks due to escape mutations or decreasing antibody activity.

Trial registration

Not applicable.
Label-free Raman microspectroscopy for identifying virocells
Authors: Monsees Indra , Turzynski Victoria , Esser Sarah P. , Soares André , Timmermann Lara I. , Weidenbach Katrin , Banas Jarno , Kloster Michael , Beszteri Bánk , Schmitz Ruth A. , Probst Alexander J.
Published: September 2021

Raman microspectroscopy has been thoroughly used to assess growth dynamics and heterogeneity of prokaryotic cells. Yet, little is known about how the chemistry of individual cells changes during infection with lytic viruses, resulting in so-called virocells. Here, we investigate biochemical changes of bacterial and archaeal cells of three different species in laboratory cultures before and after addition of their respective viruses using single-cell Raman microspectroscopy. By applying multivariate statistics, we identified significant differences in the spectra of single cells and cells after addition of lytic phage (phi6) for Pseudomonas syringae. A general ratio of wavenumbers that contributed the greatest differences in the recorded spectra was defined as an indicator for virocells. Based on reference spectra, this difference is likely attributable to an increase in nucleic acid vs. protein ratio of virocells. This method proved also successful for identification of Bacillus subtilis cells infected with phi29 displaying a decrease in respective ratio but failed for archaeal virocells (Methanosarcina mazei with Methanosarcina Spherical Virus) due to autofluorescence. Multivariate and univariate analyses suggest that Raman spectral data of infected cells can also be used to explore the complex biology behind viral infections of bacteria. Using this method, we confirmed the previously described two-stage infection of P. syringae’s phi6 and that infection of B. subtilis by phi29 results in a stress response within single cells. We conclude that Raman microspectroscopy is a promising tool for chemical identification of Gram-positive and Gram-negative virocells undergoing infection with lytic DNA or RNA viruses.

Importance

Viruses are highly diverse biological entities shaping many ecosystems across Earth. Yet, understanding the infection of individual microbial cells and the related biochemical changes remains limited. Using Raman microspectroscopy in conjunction with univariate and unsupervised machine learning approaches, we established a marker for identification of infected Gram-positive and Gram-negative bacteria. This non-destructive, label-free analytical method at single-cell resolution paves the way for future studies geared towards analyzing complex biological changes of virus-infected cells in pure culture and natural ecosystems.