title: Comparison of Demographic and Diagnostic Markers in New Onset Pediatric Type 1 and Type 2 Diabetes

abstract:
PurposeType 1 diabetes (T1D) is the most common type of diabetes in children, but the frequency of type 2 diabetes (T2D) is increasing rapidly. Classification of diabetes is based on a constellation of features that are typical of each type. We aimed to compare demographic, clinical and laboratory characteristics at diabetes diagnosis in pediatric T1D and T2D.

MethodsWe studied children who attended a large academic hospital in Houston, Texas (USA) with a new diagnosis of T2D (n=753) or T1D (n=758). We compared age, sex, race/ethnicity, presence of obesity, glucose, hemoglobin A1c, islet autoantibody positivity, C-peptide, and presence of diabetic ketoacidosis (DKA) at diabetes diagnosis.

ResultsAt diagnosis of diabetes, children with T2D, compared with those with T1D, were older (13.6 vs 9.7% years old), more likely females (63.2% vs 47.8%), of racial/ethnic minority (91.1%% versus 42.3%) and obese (90.9% vs 19.4%), and were less likely to have DKA (7.8% vs 35.0%) and diabetes autoantibodies (5.5% vs 95.4%). Children with T2D also had significantly less marked elevation of glucose and hemoglobin A1c, and lower C-peptide levels (all comparisons, p<0.0001). In multiple logistic regression analysis, older age, racial/ethnic minority, obesity, higher C-peptide and negative islet autoantibodies were independently associated with T2D (all, p<0.05) while sex, glucose, hemoglobin A1c and DKA were not (model p<0.0001).

ConclusionsThere are important demographic, clinical and laboratory differences between T1D and T2D in children. However, none of the characteristics was unique to either diabetes type, which poses challenges to diabetes classification at diagnosis.


title: Household transmission of SARS-CoV-2 in Norway; a prospective, longitudinal study showing increased transmissibility of the Alpha variant (B.1.1.7) compared with other variants

abstract:
ObjectivesWe studied the secondary attack rate (SAR), risk factors, and precautionary practices of household transmission in a prospective, longitudinal study. We further compared transmission between the Alpha (B.1.1.7) variant and non-Variant of Concern (non-VOC) viruses.

MethodsWe recruited households of 70 confirmed COVID-19 cases with 146 household contacts from May 2020 to May 2021. Participants donated biological samples 8 times over 6 weeks and answered questionnaires. Whole genome sequencing and droplet digital PCR were used to establish the SARS-CoV-2 variant and viral load.

ResultsSARS-CoV-2 transmission occurred in 60% of the households, and the overall SAR for household contacts was 50%. The SAR was significantly higher for the Alpha variant (78%) compared with non-VOC viruses (43%) and was associated with a higher viral load. SAR was higher in household contacts aged [≥]40 years (69%) than in younger contacts (40-47%), and for contacts of cases with loss of taste/smell. Children had lower viral loads and were more often asymptomatic than adults. Sleeping separately from the primary case reduced the risk of transmission.

ConclusionsWe found substantial household transmission, particularly for the Alpha variant. Precautionary practices seem to reduce SAR, but preventing household transmission may become difficult with more contagious variants.

category: epidemiology


title: Household transmission of SARS-CoV-2; a prospective longitudinal study showing higher viral load and transmissibility of the Alpha variant compared to previous strains


title: Lessons Learned From the Implementation of a Participant-Collected, Mail-Based SARS-CoV-2 Serological Survey in Massachusetts, USA

abstract:
The rapid spread of SARS-CoV-2 is largely driven by pre-symptomatic or mildly symptomatic individuals who transmit the virus. Serological tests to identify antibodies against SARS-CoV-2 are an important tool to characterize subclinical infection exposure, which is critical in determining transmission trajectories and consequent population immunity. During the summer of 2020, a mail-based serological survey with self-collected dried blood spot (DBS) samples was implemented among university affiliates and their household members in Massachusetts, USA. Described here are some of the challenges faced and novel procedures used during the implementation of this study to assess the prevalence of SARS-CoV-2 antibodies amid the global pandemic. Important challenges included remote and contact-minimized participant recruitment, limited availability of commodities and laboratory capacity, a potentially biased sample population, and policy changes impacting the distribution of clinical results to study participants. Methods used to surmount these challenges and lessons learned are presented to inform similar studies. Key lessons relate to the acceptability and feasibility of DBS sampling, supply requirements, the logistics of packing and shipping packages, data linkages to enrolled household members, and the utility of having an on-call nurse available for participant concerns during sample collection.

Future studies might consider additional recruitment techniques such as conducting studies during academic semesters when recruiting in a university setting, partnerships with supply and shipping specialists, and using a stratified sampling approach to minimize potential biases in recruitment. This study design highlights the feasibility and acceptability of self-collected bio-samples and has broad applicability for other serological surveys for a range of pathogens.


title: Patient-centered care, advance care planning, and treatment preferences among home medical care patients in Japan: The ZEVIOUS study

abstract:
BackgroundIt remains unclear how both the quality of patient-centered care and the patients illness affect advance care planning (ACP) in primary care settings. Identifying the facilitators and barriers to ACP in primary care settings has become a growing scientific and clinical challenge.

ObjectiveTo examine the association between the quality of primary care and ACP preparedness among patients. Additionally, to investigate whether ACP preparedness and the patients illness are associated with the expression of future treatment preferences.

DesignMulticenter cross-sectional study.

ParticipantsAdult Japanese patients receiving home medical care.

Main MeasuresA survey was run to assess consideration of ACP by patients and expression of future treatment preferences. The quality of primary care, which reflects patient centeredness, was assessed with the Japanese version of the Primary Care Assessment Tool- Short Form. Information on the clinical conditions that required home medical care was collected from physicians.

Key ResultsOf 194 patients using 29 home medical services, 62 patients (32%) showed signs of ACP preparedness, and 153 patients (78%) expressed their treatment preferences. In a multivariable-adjusted generalized estimating equation, primary care quality was associated with ACP preparedness (per 10-point increase, adjusted OR: 1.96, 95% CI: 1.51-2.56). However, we found insufficient evidence to support that ACP preparedness was associated with a lower incidence of non-expression of treatment preferences (adjusted OR: 1.02, 95% CI 0.49-2.12). In contrast, having cancer was associated with a lower incidence of non-expression of treatment preferences (adjusted OR: 0.12, 95% CI: 0.01-0.995).

ConclusionsAt a minimum, patient centeredness in home medical care facilitates must ensure the initiation of ACP preparedness. To understand the association between ACP preparedness and expression of treatment preferences, further efforts are warranted to clarify the quality and content of ACP preparedness simultaneously with the patients illness.

category: primary care research


title: The mental state of inpatients with COVID-19: a computational psychiatry approach

abstract:
The overload of healthcare systems around the world and the danger of infection have limited the ability of researchers to obtain sufficient and reliable data on psychopathology in hospitalized patients with COVID-19. The relationship between severe SARS-CoV-2 infection and specific mental disturbances remains poorly understood.

Aimto reveal the possibility of identifying the typology and frequency of psychiatric syndromes associated with acute COVID-19 using cluster analysis of discrete psychopathological phenomena.

Materials and methodsDescriptive data on the mental state of 55 inpatients with COVID-19 were obtained by young-career physicians with psychiatric backgrounds. Classification of observed clinical phenomena was performed with k-means cluster analysis of variables codded from the main psychopathological symptoms. Dispersion analysis with p-level 0.05 was used to reveal the clusters differences in demography, parameters of inflammation and respiration function collected on the basis of the original medical records.

ResultsThree resulting clusters of patients were identified: persons with anxiety, disorders of fluency and tempo of thinking, mood, attention, motor-volitional sphere, reduced insight, and pessimistic plans for the future (n=11); persons without psychopathology (n=37); persons with disorientation, disorders of memory, attention, fluency, and tempo of thinking, reduced insight (n=7). The development of a certain type of impaired mental state was specifically associated with: age, lung lesions according to computed tomography, saturation, respiratory rate, C-reactive protein level, platelet count.

ConclusionThe prevalence and typology of psychiatric disorders in patients with acute COVID-19 were described using the computational psychiatry approach.

category: psychiatry and clinical psychology


title: To share or not to share - What the general public thinks about global COVID-19 vaccine distribution

abstract:
BackgroundDespite ongoing calls for more equity in the global distribution of COVID-19 vaccines, there remains a great disparity between high- and low- or middle-income countries. Based on the principles of distributive justice, we assessed the public opinion on this issue in the United States and Germany as examples for high-income countries with a high potential for redistribution.

MethodsWe conducted representative surveys among the adult population in the United States (N=1,000) and Germany (N=1,003) in June 2021 using two instances of an analytic hierarchy process (AHP) to elicit how the public weighs different principles and criteria according to which the vaccines should be allocated as well as discrete choice experiments to split a limited supply of vaccine doses between a hypothetical high-income and low-income country.

FindingsIn the first AHP, respondents in the United States and Germany gave weight to "medical urgency" by 37{middle dot}4% (37{middle dot}2-37{middle dot}5) and 49{middle dot}4% (49{middle dot}2-49{middle dot}5), "equal access for all" 32{middle dot}7% (32{middle dot}6-32{middle dot}8) and 25{middle dot}4% (25{middle dot}2-25{middle dot}5), "production contribution" 13{middle dot}7% (13{middle dot}6-13{middle dot}8) and 13{middle dot}3% (13{middle dot}2-13{middle dot}4), and "free market rules" 16{middle dot}3% (16{middle dot}2-16{middle dot}4) and 12{middle dot}0% (11{middle dot}9-12{middle dot}1), respectively. In the discrete choice experiment responds in the United States split available vaccine doses such that the low-income country on average received 53{middle dot}9 percent (95% CI: 52{middle dot}6-55{middle dot}1). For Germany this number was 57{middle dot}5 percent (95% CI: 56{middle dot}3-58{middle dot}7). The low-income country had three times as many inhabitants as the high-income country. When facing the dilemma where a vulnerable family member was waiting for a vaccine as opposed to when there was no clear self-interest, 20{middle dot}7% (18{middle dot}2-23{middle dot}3) of respondents in the United States and 18{middle dot}2% (15{middle dot}8-20{middle dot}6) in Germany reduced the amount they allocated to the low-income country

InterpretationsThe public in the United States and Germany favours utilitarian and egalitarian distribution principles of vaccines for COVID-19 over the currently prevailing libertarian or meritocratic principles. This implies that political approaches and decision favouring higher levels of redistribution would be supported by the public opinion in these two countries.

FundingGerman Research Foundation DFG RTG 1723.

category: public and global health


title: Public opinion on global distribution of COVID-19 vaccines: evidence from two nationally representative surveys in Germany and the United States


title: Time needed to perform intermittent catheterization in adults with spinal cord injury: A pilot randomized controlled cross-over study

abstract:
BackgroundIntermittent catheterization (IC), considered the gold standard for bladder management for individuals with spinal cord injury (SCI) with sufficient dexterity, is usually performed using hydrophilic (HPC) or non-hydrophilic (non-HPC) catheters. Currently, there is no evidence on the temporal burden associated with IC with either catheter.

ObjectiveTo compare both catheters regarding their time requirement for IC and participant satisfaction.

Design, setting and participantsTwenty individuals with chronic (>1-year) SCI at any spinal segment were randomized to undergo two cross-over assessments within 10 days (i.e., either starting with HPC or non-HPC). We measured time taken to perform IC using a 13 step pre-determined IC protocol (e.g., enter bathroom, wash hands, transfer to toilet, etc.). Furthermore, we assessed user satisfaction of both catheters using a Likert scale (i.e., strongly agree=5, strongly disagree=1).

Outcome measures and statistical analysisTime (i.e., for each step and in total) to perform IC and participant satisfaction were compared between catheters using non-parametric statistics, i.e., Wilcoxon rank sign tests. Results are presented as median with interquartile range.

Results and limitationsParticipants using HPCs spent less time to prepare a catheter [15 s (10-20) vs. 41 (20-69), p=0.002] and overall to perform IC [283 s (242-352) vs. 373 (249-441), p=0.01] compared to non-HPCs. Moreover, participants rated the preparation of HPCs to be easier [5 (4-5) vs. 4 (2-4), p=0.047] compared to non-HPCs. The key limitation of this pilot study was the sample size.

ConclusionsPreparation and usage of HPCs for IC is easier and faster compared to non-HPCs. IC can be a significant temporal burden for SCI individuals.

Patient summaryWe compared coated and uncoated catheters on time needed for intermittent catheterization and user satisfaction in individuals with spinal cord injury. Participants can manually empty their bladder quicker and easier with coated compared to uncoated catheters.

category: urology


title: DeepSARS: simultaneous diagnostic detection and genomic surveillance of SARS-CoV-2

abstract:
The continued spread of SARS-CoV-2 and emergence of new variants with higher transmission rates and/or partial resistance to vaccines has further highlighted the need for large-scale testing and genomic surveillance. However, current diagnostic testing (e.g., PCR) and genomic surveillance methods (e.g., whole genome sequencing) are performed separately, thus limiting the detection and tracing of SARS-CoV-2 and emerging variants. Here, we developed DeepSARS, a high-throughput platform for simultaneous diagnostic detection and genomic surveillance of SARS-CoV-2 by the integration of molecular barcoding, targeted deep sequencing, and computational phylogenetics. DeepSARS enables highly sensitive viral detection, while also capturing genomic diversity and viral evolution. We show that DeepSARS can be rapidly adapted for identification of emerging variants, such as alpha, beta, gamma, and delta strains, and profile mutational changes at the population level. DeepSARS sets the foundation for quantitative diagnostics that capture viral evolution and diversity.

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category: infectious diseases


title: The Impact of COVID-19 Testing on College Campuses

abstract:
BackgroundAfter moving instruction online for more than a year, many colleges and universities are preparing to reopen and offering fully in-person classes for the Fall 2021 semester. In this paper, we study the impact of weekly testing protocols on college campuses.

MethodsAn extended susceptible-infectious-removed (SIR) compartmental model was used to simulate COVID-19 spread on a college campus setting. Seven scenarios were evaluated which considered polymerase chain reaction (PCR) and rapid antigen testing kits available at various levels of supply. The infection attack rate (IAR), the number of infections, and the number of tests utilized by the end of the simulation semester are reported and compared.

ResultsWeekly testing significantly reduces the number of infections compared to when testing is not available. The use of PCR tests results in the lowest infection attack rate and the total number of cases; however, using rapid antigen tests with higher coverage is more effective than using PCR tests with lower coverage.

ConclusionsThe implementation of COVID-19 testing protocols should be considered and evaluated as using testing allows for identification and isolation of cases which reduces the spread of COVID-19 on college campuses. Even if testing capacity is limited, its partial implementation can be beneficial.


title: Significant reduction in humoral immunity among healthcare workers and nursing home residents 6 months after COVID-19 BNT162b2 mRNA vaccination

abstract: High COVID-19 mortality among nursing home (NH) residents led to their prioritization for SARS-CoV-2 vaccination; most NH residents received BNT162b2 mRNA vaccination under the Emergency Use Authorization due to first to market and its availability. With NH residents poor initial vaccine response, the rise of NH breakthrough infections and outbreaks, characterization of the durability of immunity to inform public health policy on the need for boosting is needed. We report on humoral immunity from 2 weeks to 6-months post-vaccination in 120 NH residents and 92 ambulatory healthcare worker controls with and without pre-vaccination SARS-CoV-2 infection. Anti-spike and anti-receptor binding domain (RBD) IgG, and serum neutralization titers, were assessed using a bead-based ELISA method and pseudovirus neutralization assay. Anti-spike, anti-RBD and neutralization levels dropped more than 84% over 6 months time in all groups irrespective of prior SARS-CoV-2 infection. At 6 months post-vaccine, 70% of the infection-naive NH residents had neutralization titers at or below the lower limit of detection compared to 16% at 2 weeks after full vaccination. These data demonstrate a significant reduction in levels of antibody in all groups. In particular, those infection-naive NH residents had lower initial post-vaccination humoral immunity immediately and exhibited the greatest declines 6 months later. Healthcare workers, given their younger age and relative good-health, achieved higher initial antibody levels and better maintained them, yet also experienced significant declines in humoral immunity. Based on the rapid spread of the delta variant and reports of vaccine breakthrough in NH and among younger community populations, boosting NH residents may be warranted.


title: Worldwide association of lifestyle related factors and COVID-19 mortality

abstract:
BackgroundSeveral lifestyle related factors such as obesity and diabetes have been identified as risk factors for Coronavirus disease 2019 (COVID-19) mortality. The objective of this study was to examine the global association between lifestyle related factors and COVID-19 mortality using data from each individual country.

MethodsThe association between prevalence of seven lifestyle related factors (overweight, insufficient physical activity, smoking, type 2 diabetes, hypertension, hyperlipidemia, and age over 65) and COVID-19 mortality was assessed by linear and multivariable regression among 186 countries. The cumulative effect of lifestyle related factors on COVID-19 mortality was assessed by dividing countries into four categories according to the number of lifestyle related factors in the upper half range and comparing the mean mortality between groups.

ResultsIn linear regression, COVID-19 mortality was significantly associated with overweight, insufficient physical activity, hyperlipidemia, and age [≥]65. In multivariable regression, overweight and age [≥]65 demonstrated significant association with COVID-19 mortality (P = 0.0039, 0.0094). Countries with more risk factors demonstrated greater COVID-19 mortality (P for trend <0.001).

ConclusionLifestyle related factors, especially overweight and elderly population, were associated with increased COVID-19 mortality on a global scale. Global effort to reduce burden of lifestyle related factors along with protection and vaccination of these susceptible groups may help reduce COVID-19 mortality.


title: Comparison of Antibody Levels in Response to SARS-CoV-2 Infection and Vaccination Type in a Midwestern Cohort

abstract: We present preliminary data in an ongoing observational study reporting SARS-CoV-2 spike protein reactive antibody levels from a convenience cohort of over 250 individuals in Kansas City. We observe stable antibody levels over one year in individuals who recovered from COVID19 infection caused by SARS-CoV-2. By comparison, our data reveals even higher antibody levels from naive individuals vaccinated with Pfizer or Moderna vaccines and slightly lower levels from Johnson & Johnson (J&J) recipients. For all vaccines, inoculation after recovery resulted in higher antibody levels than vaccination alone. Responses to Pfizer and Moderna vaccines decreased over time from high initial levels but at the time of publication remain higher than those for recovered or J&J recipients. Within our limited cohort we only see slight demographic trends including higher antibody levels in recovered female vs. male individuals. Booster doses and breakthrough infections both result in rapid increases in antibody levels.

category: allergy and immunology


title: Triaging and Referring In Adjacent General and Emergency Departments (the TRIAGE trial): a cluster randomised controlled trial

abstract:
ObjectivesTo determine the effectiveness and safety of a tool diverting low urgency patients eligible for primary care from an emergency department (ED) to the adjacent general practitioner cooperative (GPC).

MethodsUnblinded, randomised controlled trial with weekends serving as clusters (three intervention clusters for each control). The intervention was nurse-led triage using a new tool assigning patients to either ED or GPC. During intervention weekends, patients were encouraged to follow this assignment while it was not communicated to the patients during control weekends (they remained at the ED). The primary outcome was the proportion of patients assigned to and handled by the GPC during intervention weekends. The trial was randomised for the secondary outcome: the proportion of patients assigned to the GPC during intervention and control weekends. Additional outcomes were association of these outcomes with possible confounders (study tool parameters, nurse, and patient characteristics), proportion of patients referred back to the ED by the GPC, hospitalisations, and performance of the study tool to detect primary care eligible patients (with the opinion of the treating physician as the gold standard).

ResultsIn the intervention group, 838/6374 patients (13.3%, 95% CI 12.5 to 14.2) were assigned to the GPC (secondary outcome), in the control group 431/1744 (24.7%, 95% CI 22.7 to 26.8). In the intervention group, 599/6374 patients (9.5%, 95% CI 8.8 to 10.3) experienced the primary outcome which was influenced by the chosen MTS presentational flowchart, patients age, and the nurse. 24/599 patients (4.0%, 95% CI 2.7 to 5.9) patients were referred back to the ED of which three were hospitalised. Positive and negative predictive values of the studied tool during intervention weekends were 0.96 (95%CI 0.94 to 0.97) and 0.60 (95% CI 0.58 to 0.62). Out of the patients assigned to the GPC, 2.4% (95% CI 1.7 to 3.4) were hospitalised.

ConclusionsED nurses using a new tool safely diverted 9.5% of the included patients to primary care.

ClinicalTrials.gov IdentifierNCT03793972

FundingResearch Foundation - Flanders (FWO)

category: emergency medicine


title: Effectiveness of COVID-19 Vaccines among Incarcerated People in California State Prisons: A Retrospective Cohort Study

abstract:
BackgroundPrisons and jails are high-risk settings for COVID-19 transmission, morbidity, and mortality. COVID-19 vaccines may substantially reduce these risks, but evidence is needed of their effectiveness for incarcerated people, who are confined in large, risky congregate settings.

MethodsWe conducted a retrospective cohort study to estimate effectiveness of mRNA vaccines, BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna), against confirmed SARS-CoV-2 infections among incarcerated people in California prisons from December 22, 2020 through March 1, 2021. The California Department of Corrections and Rehabilitation provided daily data for all prison residents including demographic, clinical, and carceral characteristics, as well as COVID-19 testing, vaccination status, and outcomes. We estimated vaccine effectiveness using multivariable Cox models with time-varying covariates that adjusted for resident characteristics and infection rates across prisons.

FindingsAmong 60,707 residents in the cohort, 49% received at least one BNT162b2 or mRNA-1273 dose during the study period. Estimated vaccine effectiveness was 74% (95% confidence interval [CI], 64-82%) from day 14 after first dose until receipt of second dose and 97% (95% CI, 88-99%) from day 14 after second dose. Effectiveness was similar among the subset of residents who were medically vulnerable (74% [95% CI, 62-82%] and 92% [95% CI, 74-98%] from 14 days after first and second doses, respectively), as well as among the subset of residents who received the mRNA-1273 vaccine (71% [95% CI, 58-80%] and 96% [95% CI, 67-99%]).

ConclusionsConsistent with results from randomized trials and observational studies in other populations, mRNA vaccines were highly effective in preventing SARS-CoV-2 infections among incarcerated people. Prioritizing incarcerated people for vaccination, redoubling efforts to boost vaccination and continuing other ongoing mitigation practices are essential in preventing COVID-19 in this disproportionately affected population.

FundingHorowitz Family Foundation, National Institute on Drug Abuse, Centers for Disease Control and Prevention, National Science Foundation, Open Society Foundation, Advanced Micro Devices.


title: SARS-CoV-2 alpha variant: is it really more deadly? A population-level observational study.

abstract:
BackgroundIn 2021 a new variant of SARS-CoV-2, which came to be called the alpha variant, spread around the world. There were conflicting reports on this COVID-19 variant strains potentially increased lethality. In Israel, this strain became predominant in a very short time period.

MethodsCOVID-19 mortality and case fatality rates were examined in Israel in terms of weekly and cumulative numbers.

ResultsCOVID-19 case fatality rates in Israel rose quickly at the beginning of the pandemic and peaked in May 2020. The highest crude mortality came later in the second and third waves, but case the case fatality rates did not rise in 2021 with the increasing dominance of the alpha variant.

ConclusionsBased on the results of examining case-fatality and mortality rates, we concluded that while the alpha variant of the virus raised mortality, in line with the fact that it is more infectious than wild-type, once this strain was caught by patients in Israel, it was not more likely to kill them than the original strain


title: Non-pharmaceutical interventions, vaccination and the Delta variant: epidemiological insights from modelling England's COVID-19 roadmap out of lockdown

abstract:
BackgroundEnglands COVID-19 "roadmap out of lockdown" set out the timeline and conditions for the stepwise lifting of non-pharmaceutical interventions (NPIs) as vaccination roll-out continued. Here we assess the roadmap, the impact of the Delta variant, and potential future epidemic trajectories.

MethodsWe extended a model of SARS-CoV-2 transmission to incorporate vaccination and multi-strain dynamics to explicitly capture the emergence of the Delta variant. We calibrated the model to English surveillance data using a Bayesian evidence synthesis framework, then modelled the potential trajectory of the epidemic for a range of different schedules for relaxing NPIs.

FindingsThe roadmap was successful in offsetting the increased transmission resulting from lifting NPIs with increasing population immunity through vaccination. However due to the emergence of Delta, with an estimated transmission advantage of 73% (95%CrI: 68-79) over Alpha, fully lifting NPIs on 21 June 2021 as originally planned may have led to 3,400 (95%CrI: 1,300-4,400) peak daily hospital admissions under our central parameter scenario. Delaying until 19 July reduced peak hospitalisations by three-fold to 1,400 (95%CrI: 700-1,500) per day. There was substantial uncertainty in the epidemic trajectory, with particular sensitivity to estimates of vaccine effectiveness and the intrinsic transmissibility of Delta.

InterpretationOur findings show that the risk of a large wave of COVID hospitalisations resulting from lifting NPIs can be substantially mitigated if the timing of NPI relaxation is carefully balanced against vaccination coverage. However, with Delta, it may not be possible to fully lift NPIs without a third wave of hospitalisations and deaths, even if vaccination coverage is high. Variants of concern, their transmissibility, vaccine uptake, and vaccine effectiveness must be carefully monitored as countries relax pandemic control measures.

FundingNational Institute for Health Research, UK Medical Research Council, Wellcome Trust, UK Foreign, Commonwealth & Development Office.

Research in contextO_ST_ABSEvidence before this studyC_ST_ABSWe searched PubMed up to 23 July 2021 with no language restrictions using the search terms: (COVID-19 or SARS-CoV-2 or 2019-nCoV or "novel coronavirus") AND (vaccine or vaccination) AND ("non pharmaceutical interventions" OR "non-pharmaceutical interventions) AND (model*). We found nine studies that analysed the relaxation of controls with vaccination roll-out. However, none explicitly analysed real-world evidence balancing lifting of interventions, vaccination, and emergence of the Delta variant.

Added value of this studyOur data synthesis approach combines real-world evidence from multiple data sources to retrospectively evaluate how relaxation of COVID-19 measures have been balanced with vaccination roll-out. We explicitly capture the emergence of the Delta variant, its transmissibility over Alpha, and quantify its impact on the roadmap. We show the benefits of maintaining NPIs whilst vaccine coverage continues to increase and capture key uncertainties in the epidemic trajectory after NPIs are lifted.

Implications of all the available evidenceOur study shows that lifting interventions must be balanced carefully and cautiously with vaccine roll-out. In the presence of a new, highly transmissible variant, vaccination alone may not be enough to control COVID-19. Careful monitoring of vaccine uptake, effectiveness, variants, and changes in contact patterns as restrictions are lifted will be critical in any exit strategy.


title: COVID-19 infection, hospitalisation and death Amongst People with Rare Autoimmune Rheumatic Disease in England. Results from the RECORDER Project.

abstract:
ObjectivesTo calculate the rates of COVID-19 infection and COVID-19-related death among people with rare autoimmune rheumatic diseases (RAIRD) during the first wave of the COVID-19 pandemic in England compared to the general population.

MethodsWe used Hospital Episode Statistics to identify all people alive 01 March 2020 with ICD-10 codes for RAIRD from the whole population of England. We used linked national health records (demographic, death certificate, admissions and PCR testing data) to calculate rates of COVID-19 infection and death up to 31 July 2020. Our primary definition of COVID-19-related death was mention of COVID-19 on the death certificate. General population data from Public Health England and the Office for National Statistics were used for comparison. We also describe COVID-19-related hospital admissions and all-cause deaths.

ResultsWe identified a cohort of 168,680 people with RAIRD, of whom 1874 (1.11%) had a positive COVID-19 PCR test. The age-standardised infection rate was 1.54 (95% CI 1.50-1.59) times higher than in the general population. 713 (0.42%) people with RAIRD died with COVID-19 on their death certificate and the age-sex-standardised mortality rate for COVID-19-related death was 2.41 (2.30 - 2.53) times higher than in the general population. There was no evidence of an increase in deaths from other causes in the RAIRD population.

ConclusionsDuring the first wave of COVID-19 in England, people with RAIRD had a 54% increased risk of COVID-19 infection and more than twice the risk of COVID-19-related death compared to the general population. These increases were seen despite shielding policies.

Key MessagesO_LIPeople with RAIRD were at increased risk of COVID-19 infection during the first wave.
C_LIO_LICompared to the general population, they had over twice the risk of COVID-19-related death.
C_LIO_LIThese increased risks were seen despite shielding policies in place in England.
C_LI


title: Dynamics of seroconversion of anti-SARS-CoV-2 IgG antibodies in the Czech unvaccinated population: nationwide prospective seroconversion (PROSECO) study

abstract:
BackgroundAlthough the Czech Republic weathered the first wave of the COVID-19 epidemic with relatively low incidence, the second wave of the global pandemic saw it rank among countries bearing the greatest COVID-19 burden, both in Europe and on a worldwide scale. The aim of the nationwide prospective seroconversion (PROSECO) study was to investigate the dynamics of seroconversion of anti-SARS-CoV-2 IgG antibodies in the Czech population.

MethodsAll clients of the second largest health insurance company in the Czech Republic were sent a written invitation to participate in this longitudinal study. The study includes the first 30,054 persons who provided a blood sample between October 2020 and March 2021. Seroprevalence was compared between calendar periods of blood sample collection, RT-PCR test results, sociodemographic factors, and other characteristics.

FindingsThe data show a dramatic increase in seropositivity over time, from 28% in October/November 2020 to 43% in December 2020/January 2021 to 51% in February/March 2021. These trends were consistent with government data on cumulative viral antigenic prevalence in the population captured by PCR testing - although the seroprevalence rates established in this study were considerably higher than those listed in government data. Data pooled across the entire study period exhibited minor differences in seropositivity between sexes, age groups and body mass index categories; results were similar between test providing laboratories. Seropositivity was substantially higher among symptomatic vs. asymptomatic persons (76% vs. 34%). At least one third of all seropositive participants were asymptomatic, and 28% participants who developed antibodies against SARS-CoV-2 never underwent PCR testing.

InterpretationAntibody response provides a better marker of past SARS-CoV-2 infection than PCR testing data. Our data on seroconversion confirm the rapidly increasing prevalence in the Czech population during the dramatically rising pandemic wave prior to the beginning of massive vaccination. The planned second and third assessment of the study participants (April 2021 - September 2021, October 2021 - March 2022) will provide valuable evidence on the seroprevalence changes following vaccination and persistence of antibodies resulting from natural infection and vaccination.

Research in contextO_ST_ABSEvidence before this studyC_ST_ABSSimilarly to most European countries, the first COVID-19 epidemic wave in the Czech Republic produced a relatively low incidence (86.9 confirmed cases per 100,000 persons over three months). At the peaks of the second wave, however, over 100 confirmed cases per 100,000 persons were diagnosed daily and the Czech Republic ranked among the countries with the greatest burden of COVID-19 in Europe and in the world. Only a few nationwide population-based studies have been published covering the second wave of the epidemic in Europe, and none of them from the Central and Eastern European region.

Added value of this studyThe PROSECO study will provide key data from the heavily affected Central European region and contribute to the epidemiological and serological characteristics of the SARS-CoV-2 infection. All 30,054 study participants were recruited between October 2020 and March 2021, thus covering all three epidemic peaks (November 2020, January and March 2021) of the second COVID-19 epidemic wave. This allows us to follow the dynamics of seroconversion of anti-SARS-CoV-2 IgG antibodies in the immunologically naive and unvaccinated population during the COVID-19 pandemic. The study participants will be re-assessed in the second (April 2021 - September 2021) and third (October 2021 - March 2022) PROSECO phases to further study the post-infection/post-vaccination dynamics of seroconversion in/after a period of massive vaccination.

Implications of all the available evidenceData from the first phase of the PROSECO study indicate that the percentage of the population that has been exposed to the SARS-CoV-2 may be substantially higher than estimates based on official data on cumulative viral positivity incidence as at least one third of seropositive participants were asymptomatic, and 28% of participants who developed antibodies against SARS-CoV-2 never underwent PCR testing. Regional seroprevalence data provide key information to inform, in combination with other surveillance data, public health policies and will be instrumental for the successful management of the subsequent phases of the global pandemic.

The number of seropositive participants who never underwent RT-PCR testing demonstrates the importance of serological population-based studies describing the spread and exposure to the virus in the population over time.


title: Antibody Responses 3-5 Months Post-Vaccination with mRNA-1273 or BNT163b2 in Nursing Home Residents

abstract:
Nursing home residents often fail to mount robust responses to vaccinations and recent reports of breakthrough infections, particularly from variants of concern, raise questions about whether vaccination regimens elicit a sufficient humoral immune response or if booster doses are warranted. We examined SARS-CoV-2 antibody levels and neutralizing capacity in nursing home residents 3-5 months after 2 doses of mRNA-1273 or BNT163b2 vaccination as per recommended schedules.

Nursing home residents were recruited from eight long-term care homes in Ontario, Canada, between March and July 2021. Antibody levels and neutralization capacity from a previously published convalescent cohort were used as a comparator. Serum SARS-CoV-2 IgA/G/M against spike (S) protein and its receptor-binding domain (RBD) were measured by validated ELISA, with assay cut-off at the mean and 3 standard deviations of a pre-COVID-19 population from the same geographic region. Antibody neutralization was measured against the wild-type strain of SARS-CoV-2 and the beta variant of concern (B.1.351).

No neutralizing antibodies were detected in [~]20% of residents to the wild-type virus (30/155; 19%) or beta variant (27/134; 20%). Residents that received BNT163b2 had a [~]4-fold reduction in neutralization to the wild-type strain, and a [~]2-fold reduction in neutralization to the beta variant relative to those who received mRNA-1273.

Current mRNA SARS-CoV-2 vaccine regimens may not have equivalent efficacy in nursing home residents. Our findings imply that differences in the humoral immune response may contribute to breakthrough infections, and suggest that consideration of the type of vaccine administered to older adults will have a positive impact on the generation of protective immunity.


title: A second dramatic rise in seroprevalence rates of SARS-CoV-2 antibodies among adult healthy blood donors in Jordan; have we achieved herd immunity?

abstract:
ObjectivesTo determine the impact of the second wave of COVID-19 and the vaccination campaign on the seroprevalence rates of SARS-CoV-2 antibodies among healthy blood donors in Jordan.

MethodsSera from 536 healthy adult blood donors collected in June -2021 were tested using a commercially available quantitative assay for the total antibodies including IgG against the spike (S) protein receptor binding domain (RBD) of the SARS-CoV-2.

Results399 (74.4%) of the donors tested positive for the antibodies of whom 69 (17.3%) were confirmed to have been previously infected, 245(61.4%) have received at least one dose of the vaccine and 123(30.8%) were neither diagnosed nor vaccinated. The seropositive donors were significantly more likely to have been vaccinated or previously infected.

ConclusionThe crude seroprevalence rate of 74.4% among this group of healthy donors may be encouraging in terms of approaching herd immunity, however with predominance of the delta variant and the uncertainty regarding the required level of herd immunity this goal appears to be far from full achievement in Jordan.


title: Point of emission air filtration enhances protection of health care workers against skin contamination with virus aerosol

abstract:
RationaleWe recently demonstrated that a patient hood with a high efficiency particulate air filter eliminates virus aerosol contamination when very large quantities of bacteriophage virus are aerosolised into a clinical room. While this containment method is relatively low cost, it is unclear whether similar efficacy can be achieved with lower cost/commercial grade air purifiers, or if such an approach protects healthcare workers against virus aerosol contamination.

MethodA total of 109 (10 ml of 108) PhiX174 bacteriophages was nebulized into a sealed clinical room. Surface contamination was detected by settle plates left uncovered during exposure. A healthcare worker remained in the room, personal exposure was determined by skin swabs after exiting the room, following doffing of personal protective equipment (PPE). Four skin areas were swabbed: forearms/hands, neck, forehead, under N95 mask. Three conditions were tested, 1) hood with hospital grade air purifier (IQ Air Health Pro 250), 2) hood with commercial air purifier (Philips 1000i), and 3) control (no hood/air-purification).

FindingsThe control condition demonstrated extensive environmental and limited skin contamination underneath PPE, which was highest under an N95 mask. The commercial air purifier and hood provided environmental control of virus aerosol and almost zero skin contamination. In comparison, the hospital grade purifier provided complete environmental and skin contamination protection, despite a lower clean air filtration rate (240m3/hr vs 270m3/hr). Virus counts on plates and swabs were significantly lower for both air purifiers and across neck, forehead, and under the N95. There were no statistically significant differences in detected virus counts between air purifiers.

ConclusionThis cheap and scalable method may be an effective way to reduce the spread of COVID-19 in hospitals by enhancing the effectiveness of PPE worn by health care workers who care for COVID-19 patients and who are exposed to virus aerosol.

O_TEXTBOXTake home messageRelatively cheap portable air purifiers combined with a hood dramatically reduce the spread of virus aerosol and protect against environmental and healthcare worker contamination.

Plain Language SummaryThis study shows that commercially available air purifiers, when combined with a hood that covers the head of a clinical bed, effectively capture very large amounts of virus aerosol in a simulated hospital setting. This virus containment strategy strongly reduced the number of viruses landing on surfaces in a clinical room. Crucially, this strategy also reduced that amount of virus detected on a healthcare workers skin underneath personal protective equipment, including under an N95 respirator. This cheap and scalable method may be an effective way to reduce the spread of COVID-19 in hospitals by enhancing the effectiveness of personal protective equipment worn by health care workers who care for COVID-19 patients and who are exposed to virus aerosol.

C_TEXTBOX

category: intensive care and critical care medicine


title: Serological survey of SARS-CoV-2 incidence conducted at a rural West Virginia hospital

abstract: The SARS-CoV-2 pandemic has affected all types of global communities. Differences in urban and rural environments have led to varying levels of transmission within these subsets of the population. To fully understand the prevalence and impact of SARS-CoV-2 it is critical to survey both types of community. This study establishes the prevalence of SARS-CoV-2 in a rural community: Montgomery, West Virginia. Approximately 10% of participants exhibited serological or PCR-based results indicating exposure to SARS-CoV-2 within 6 months of the sampling date. Quantitative analysis of IgG levels against SARS-CoV-2 receptor binding domain (RBD) was used to stratify individuals based on antibody response to SARS-CoV-2. A significant negative correlation between date of exposure and degree of anti-SARS-CoV-2 RBD IgG (R2 = 0.9006) was discovered in addition to a correlation between neutralizing anti-SARS-CoV-2 antibodies (R2 = 0.8880) and days post exposure. Participants were confirmed to have normal immunogenic profiles by determining serum reactivity B. pertussis antigens commonly used in standardized vaccines. No significant associations were determined between anti-SARS-CoV-2 RBD IgG and age or biological sex. Reporting of viral-like illness symptoms was similar in SARS-CoV-2 exposed participants greater than 30 years old (100% reporting symptoms 30-60 years old, 75% reporting symptoms >60 years old) in contrast to participants under 30 years old (25% reporting symptoms). Overall, this axnalysis of a rural population provides important information about the SARS-CoV-2 pandemic in small rural communities. The study also underscores the fact that prior infection with SARS-CoV-2 results in antibody responses that wane over time which highlights the need for vaccine mediated protection in the absence of lasting protection.


title: Peripheral Artery Disease and COVID-19 Outcomes: Insights from the Yale DOM-CovX Registry

abstract:
BackgroundBoth COVID-19 infection and peripheral arterial disease (PAD) cause hypercoagulability in patients, and it remains unknown whether PAD predisposes patients to experience worse outcomes when infected with SARS-CoV-2.

MethodsThe Yale DOM-CovX Registry consecutively enrolled inpatients for SARS-CoV-2 between March 1, 2020, and November 10, 2020. Adjusted logistic regression models examined associations between PAD and mortality, stroke, myocardial infarction (MI), and major adverse cardiovascular events (MACE, all endpoints combined).

ResultsOf the 3,830 patients were admitted with SARS-CoV-2, 50.5% were female, mean age was 63.1 {+/-}18.4 years, 50.7% were minority race, and 18.3% (n = 693) had PAD. PAD was independently associated with increased mortality (OR=1.45, 95% CI 1.11-1.88) and MACE (OR=1.48, 95% CI 1.16-1.87). PAD was not independently associated with stroke (p=0.06) and MI (p=0.22).

ConclusionPatients with PAD have a >40% odds of mortality and MACE when admitted with a SARS-CoV-2, independent of known risk factors.

category: cardiovascular medicine


title: Household Transmission and Clinical Features of SARS-CoV-2 Infections by Age in 2 US Communities

abstract:
OBJECTIVESExamine age differences in SARS-CoV-2 transmission risk from primary cases and infection risk among household contacts, and symptoms among those with SARS-CoV-2 infection.

METHODSPeople with SARS-CoV-2 infection in Nashville, Tennessee and central and western Wisconsin and their household contacts were followed daily for 14 days to ascertain symptoms and secondary transmission events. Households were enrolled between April 2020 and April 2021. Secondary infection risks (SIR) by age of the primary case and contacts were estimated using generalized estimating equations.

RESULTSThe 226 primary cases were followed by 198 (49%) secondary SARS-CoV-2 infections among 404 household contacts. Age group-specific SIR among contacts ranged from 36% to 53%, with no differences by age. SIR was lower from primary cases aged 12-17 years than from primary cases 18-49 years (risk ratio [RR] 0.42; 95% confidence interval [CI] 0.19-0.91). SIR was 55% and 45%, respectively, among primary case-contact pairs in the same versus different age group (RR 1.47; 95% CI 0.98-2.22). SIR was highest among primary case-contacts pairs aged [≥]65 years (76%) and 5-11 years (69%). Among secondary SARS-CoV-2 infections, 19% were asymptomatic; there was no difference in the frequency of asymptomatic infections by age group.

CONCLUSIONSBoth children and adults can transmit and are susceptible to SARS-CoV-2 infection. SIR did not vary by age, but further research is needed to understand age-related differences in probability of transmission from primary cases by age.


title: Proactive COVID-19 testing in a partially vaccinated population

abstract: During the initial stages of the COVID-19 pandemic, many workplaces and universities implemented institution-wide proactive testing programs of all individuals, ir-respective of symptoms. These measures have proven effective in mitigating outbreaks. As a greater fraction of the population becomes vaccinated, we need to understand what continued benefit, if any, proactive testing can contribute. Here, we address this problem with two distinct modeling approaches: a simple analytical model and a more simulation using the SEIRS+ platform. Both models indicate that proactive testing remains useful until a threshold level of vaccination is reached. This threshold depends on the transmissibility of the virus and the scope of other control measures in place. If a community is able to reach the threshold level of vaccination, testing can cease. Otherwise, continued testing will be an important component of disease control. Because it is usually difficult or impossible to precisely estimate key parameters such as the basic reproduction number for a specific workplace or other setting, our results are more useful for understanding general trends than for making precise quantitative predictions.


title: Genomic profiles of Covishield and Covaxin breakthrough SARS-CoV-2 strains from Odisha, India

abstract: Vaccine breakthrough infections pose a vast challenge in the eradication of the COVID pandemic situation. Emerging SARS-CoV-2 variants of concern infecting the immunized individuals indicate an ongoing battle between host immunity and natural selection of the pathogen. Our report sheds light on the prominent SARS-CoV-2 variations observed in the isolates from AZD1222/Covishield and BBV152/Covaxin vaccinated subjects.


title: Infection with the SARS-CoV-2 Delta Variant is Associated with Higher Infectious Virus Loads Compared to the Alpha Variant in both Unvaccinated and Vaccinated Individuals

abstract:
BackgroundThe emerging SARS-CoV-2 variant of concern (VOC) B.1.6.17.2 (Delta) quickly displaced the B.1.1.7 (Alpha) and is associated with increases in COVID-19 cases nationally. The Delta variant has been associated with greater transmissibility and higher viral RNA loads in both unvaccinated and fully vaccinated individuals. Data is lacking regarding the infectious virus load in Delta infected individuals and how that compares to individuals infected with other SARS-CoV-2 lineages.

MethodsWhole genome sequencing of 2,785 clinical isolates was used to characterize the prevalence of SARS-CoV-2 lineages circulating in the National Capital Region between January and July 2021. Clinical chart reviews were performed for the Delta, Alpha, and B.1.2 (a control predominant lineage prior to both VOCs) variants to evaluate disease severity and outcome and Cycle threshold values (Cts) were compared. The presence of infectious virus was determined using Vero-TMPRSS2 cells and anti-SARS-CoV-2 IgG levels were determined from upper respiratory specimen. An analysis of infection in unvaccinated and fully vaccinated populations was performed.

ResultsThe Delta variant displaced the Alpha variant to constitute 88.2% of the circulating lineages in the National Capital Region by July, 2021. The Delta variant associated with increased breakthrough infections in fully vaccinated individuals that were mostly symptomatic when compared to the Alpha breakthrough infections, though it is important to note there was a significantly longer period of time between vaccination and infection with Delta infections. The recovery of infectious virus on cell culture was significantly higher with the Delta variant compared to Alpha in both vaccinated and unvaccinated groups. The impact of vaccination on reducing the recovery of infectious virus from clinical samples was only observed with Alpha variant infections but was strongly associated with low localized SARS-CoV-2 IgG for both variants. A comparison of Ct values showed a significant decrease in the Delta compared to Alpha with no significant differences between unvaccinated and vaccinated groups.

ConclusionsOur data indicate that the Delta variant is associated with increased infectious virus loads when compared to the Alpha variant and decreased upper respiratory antiviral IgG levels. Measures to reduce transmission in addition to increasing vaccinations rates have to be implemented to reduce Delta variant spread.

FundingNIH/NIAID Center of Excellence in Influenza Research and Surveillance contract HHS N2772201400007C, Johns Hopkins University, Maryland department of health, Centers for Disease Control and Prevention contract 75D30121C11061.


title: Longitudinal monitoring of SARS-CoV-2-specific immune responses

abstract: The Lower Austrian Wachau region was an early COVID-19 hotspot of infection. As previously reported, in June 2020, after the first peak of infections, we determined that 8.5% and 9.0% of the participants in Wei{beta}enkirchen and surrounding communities in the Wachau region were positive for SARS-CoV-2-specific immunoglobulin G (IgG) and immunoglobulin A (IgA) antibodies, respectively. Here, we present novel data obtained eight months later (February 2021) from Wei{beta}enkirchen, after the second peak of infection, with 25.0% (138/552) and 23.6% (130/552) of participants that are positive for IgG and IgA, respectively. In participants with previous IgG/IgA positivity (June 2020), we observed a 24% reduction in IgG levels, whereas the IgA levels remained stable in February 2021. This subgroup was further analyzed for SARS-CoV-2-induced T cell activities. Although 76% (34/45) and 76% (34/45) of IgG positive and IgA positive participants, respectively, showed specific T cell activities, those were not significantly correlated with the levels of IgG or IgA. Thus, the analyses of antibodies cannot surrogate the measurement of T cell activities. For a comprehensive view on SARS-CoV-2-triggered immune responses, the measurement of different classes of antibodies should be complemented with the determination of T cell activities.


title: Determinants of dietary salt intake in adults: A protocol for Scoping Review

abstract:
ObjectiveThe objective of this scoping review is to methodically review the current literature and identify the factors/determinants of dietary salt consumption in adults.

IntroductionHigh dietary salt intake has been identified as a risk factor for non-communicable diseases and conditions. Despite continuous and rigorous efforts, dietary salt intake still remain above the recommended adult daily dose of 5g, both locally and globally. This indicates existence of unidentified or unaddressed behavioural factors that diminish efficiency of salt reduction efforts targeted towards public.

Inclusion CriteriaThis review will include global literature dealing with factors associated with dietary salt intake in adults. Qualitative, quantitative and ecological studies on behavioural, psychosocial and environmental factors associated with awareness regarding dietary salt intake and barrier to its reduction will be considered. Studies published only in English language, without any limits on date of publication will be considered for this review.

MethodsA comprehensive search across databases namely, MEDLINE, ScienceDirect, JSTOR, ERIC, DOAJ and OATD will be carried out to retrieve and identify relevant literature. Two reviewers will screen the titles followed by abstracts and subsequently full-length texts according to the inclusion and exclusion criterion, removing unrelated studies and finally compiling and extracting information from chosen studies in data extraction forms. Descriptive statistics will be used to represent the data. Thematic analysis of extracted data using deductive approach will be conducted.


title: The impact of ongoing COVID-19 lockdown on family finances and mental health

abstract:
ObjectivesIn 2020, Australias successful COVID-19 public health restrictions comprised a national  initial lockdown (March-May), and  ongoing lockdown (July-November) for metropolitan Victorian residents only. We evaluated the impact of ongoing lockdown on family finances and mental health.

MethodsIn the June and September 2020 Royal Childrens Hospital National Child Health Polls, caregivers of children in Victoria and New South Wales reported: job/income loss; material deprivation (inability to pay for essential items); income-poverty; mental health (Kessler-6); impact on caregiver/child mental health; and caregiver/child coping. Data from N=1207/902 caregivers in June/September were analysed using Difference-in-Difference modelling (New South Wales provided the comparator).

ResultsDuring Victorias ongoing lockdown, job/income loss increased by 11% (95%CI: 3-18%); Kessler-6 poor mental health by 6% (95%CI: -0.3-12%) and negative mental health impacts by 14% for caregivers (95%CI: 6-23%) and 12% for children (95%CI: 4-20%). Female (versus male) caregivers, metropolitan (versus regional/rural) families, and families with elementary school-aged children (versus pre-/high-school) were most affected.

ConclusionsOngoing lockdown had negative impacts on mental health, employment, and income, but not deprivation or poverty, likely because of government income supplements introduced early in the pandemic. Future lockdowns require planned responses to outbreaks, and evidence-informed financial and mental health supports.


title: The impact of ongoing COVID-19 lockdown on the financial and mental health experiences of Australian families


title: Targeted screening for lung cancer with autoantibodies.

abstract: Earlier detection of lung cancer is possible, but difficult and costly to achieve. Screening with Low Dose Computed Tomography (LDCT)scanning has been shown to reduce mortality by 20-25% over the past decade but uptake amongst those most likely to suffer the disease has been slow. Resource constraints and a high false positive rate have also limited adoption of LDCT in many health systems. Targeted screening of people most likely to benefit using a range of biomarkers may be one way to improve the yield and reduce the resource requirements of LDCT. Autoantibodies, which amplify the signal produced by cancer derived proteins, are present in the blood of people mounting an immune response to cancer are a potential way to select those at highest risk. We have followed up 12 208 people enrolled in the ECLS trial for three years and shown that the specificity for early stage (I &II) disease is 90.3% throughout that period. More cancers were detected in the control than the intervention arm of the trial (101V 83). Sensitivity was 77.8% after 6 months and dropped to 46.4% after 3 years. At the end of three years the hazard ratios (95%CI) for All Cause, Cancer Specific and Lung Cancer Mortality was 0.82(0.67-1.01), 0.72(0.54-0.97) and 0.70(0.46-1.08) respectively for those randomised to Early CDT testing. As a range of treatment modalities become increasingly more effective it is even more important to target LDCT on those most likely to have early stage disease. Autoantibody testing may be one method of targeting early detection on those most likely to benefit.

category: respiratory medicine


title: Diminishing immune responses against variants of concern in dialysis patients four months after SARS-CoV-2 mRNA vaccination

abstract: Patients undergoing chronic hemodialysis were among the first to receive SARS-CoV-2 vaccinations due to their increased risk for severe COVID-19 disease and high case fatality rates. To date, there have been minimal longitudinal studies in hemodialysis patients to ascertain whether protection offered by vaccination is long-lasting. To assess how surrogates for protection changed over time, we examined both the humoral and cellular response in a previously reported cohort of at-risk hemodialysis patients and healthy donors, four months after their second dose of Pfizer BNT162b2. Compared to three weeks post-second vaccination, both cellular and humoral responses against the original SARS-CoV-2 isolate as well as variants of concern were significantly reduced, with some dialyzed individuals having no B- or T-cell response. Our data strongly support the need for a third booster in hemodialysis patients and potentially other at-risk individuals.

category: nephrology


title: Cystatin C is a glucocorticoid response gene predictive of cancer immunotherapy failure

abstract: The secreted protein Cystatin C (CyC) is a cysteine protease inhibitor of incompletely characterized biomedical function, used clinically for estimation of glomerular filtration rate. Plasma CyC is elevated in many patients, especially when they receive glucocorticoid (GC) treatment. Here we empirically connect GCs with systemic regulation of CyC. First, we leveraged genome-wide association and structural equation modeling to determine the genetics of the latent trait CyC production in UK Biobank. Using multi-modal genomic, transcriptional, and experimental approaches, we demonstrated that CyC is a direct target of GC receptor, with GC-responsive CyC secretion exhibited by macrophages and cancer cells in vitro. Elevated serum CyC levels were positively correlated with GC levels in a murine model of cancer progression. Consistent with the coupling of CyC levels to GC signaling in a disease relevant manner, CyC predicted elevated all-cause and cancer-specific mortality in humans. These associations were orthogonally confirmed by a polygenic score (PGS) capturing germline predisposition to CyC production. This PGS predicted checkpoint immunotherapy failure in a combined clinical trial cohort of 685 metastatic cancer patients, with available germline exome sequencing. Taken together, our results demonstrate that CyC captures biomedically-relevant variations in endogenous GC activity, raising the possibility that CyC may be a direct effector of GC-induced immunosuppression and therefore a target for combination cancer immunotherapy.

category: genetic and genomic medicine


title: COVID-19 ASSOCIATED MUCORMYCOSIS: A CASE-CONTROL STUDY

abstract:
BackgroundIndia has seen a surge in COVID-19 associated mucormycosis (CAM) cases during the second wave of the pandemic. We conducted a study to determine independent risk factors for CAM.

MethodsWe performed a retrospective case control study in a tertiary care private hospital in Pune, India. Fifty-two cases of CAM were compared with 166 concurrent controls randomly selected from the COVID-19 admissions during the same time period. Association of demographic factors, comorbidities, cumulative steroid dose used (calculated as dexamethasone equivalent), maximum respiratory support required, use of injectable/oral anticoagulation, and use of aspirin with CAM was assessed by univariate and multivariate logistic regression.

ResultsA total of 218 subjects (52 cases; 166 controls) were studied. Any diabetes (pre-existing diabetes and new onset diabetes during COVID-19) was noted in a significantly higher proportion of cases (73{middle dot}1%, 45{middle dot}8% P<0.001) and cumulative dexamethasone dose used in cases was significantly greater (97{middle dot}72 mg vs 60 mg; P=0{middle dot}016). In a multivariate regression analysis cumulate dexamethasone dose >120 mg (OR 9{middle dot}03, confidence interval 1{middle dot}75-46{middle dot}59, P=0{middle dot}009) and any diabetes (OR 4{middle dot}78, confidence interval 1{middle dot}46-15{middle dot}65, P=0{middle dot}01) were found to be risk factors for CAM. While use of anticoagulation (OR 0{middle dot}01, confidence interval 0{middle dot}00-0{middle dot}09, P<0{middle dot}001) and use of aspirin (OR 0{middle dot}02, confidence interval 0{middle dot}01-0{middle dot}07, P<0{middle dot}001) were found to be protective against CAM.

ConclusionDiabetes mellitus and cumulative dose of dexamethasone greater than 120 mg (or equivalent dose of other corticosteroid) were associated with an increased risk of CAM while use of aspirin and anticoagulation were associated with a lower risk.


title: Association of COVID-19 vaccination with risks of hospitalization and mortality due to cardiovascular and other diseases: A study of the UK Biobank

abstract:
BackgroundVaccines for COVID-19 represent a breakthrough in the fight against the pandemic. However, worries about adverse effects led to vaccine hesitancy in some people. On the other hand, as COVID-19 may be associated with various sequelae, the vaccine may protect against these diseases.

MethodsWe leveraged a large prospective cohort, the UK-Biobank(UKBB), and studied associations of at least one dose of COVID-19 vaccination(BioNTech-BNT162b2 or Oxford-AstraZeneca-ChAdOx1) with hospitalization from cardiovascular and other diseases (N=393,544; median follow-up of 54 days in vaccinated). Multivariable Cox and Poisson regression was conducted controlling for main confounders. Besides all hospitalizations, we also conducted separate analysis for new-onset and recurrent cases. We also performed other sensitivity analyses, including adjustment for prior event rate ratio (PERR) to reduce residual confounding.

ResultsWe observed that COVID-19 vaccination(at least one dose) was associated with lower risks of hospitalizations from stroke (hazard ratio[HR]=0.178, 95% CI: 0.127-0.250, p=1.50e-23), VTE (HR=0.426, 95% CI: 0.270-0.673, p=2.51e-4), dementia (HR=0.114, 95% CI 0.060-0.216; p=2.24e-11), non-COVID-19 pneumonia (NCP) (HR=0.108, 95% CI 0.0.080-0.145; p=2.20e-49), CAD (HR=0.563, 95% CI: 0.416-0.762; p=2.05e-4), COPD (HR=0.212, 95% CI 0.126-0.357; p=4.92e-9), T2DM (HR= 0.216, 95% CI: 0.096 - 0.486, p=2.12e-4), heart failure (HR=0.174, 95% CI, 0.118-0.256, p=1.34e-18) and renal failure (HR=0.415, 0.255-0.677, p=4.19e-4).

After adjusting for HRs of hospitalization between the two groups before the introduction of vaccination, COVID-19 vaccination was still significantly associated with reduced hazards of hospitalization due to CAD (HR=0.517, 95% CI: 0.327-0.817; p=4.70e-03), COPD (HR=0.317, 95% CI: 0.138-0.726; p=6.60e-03), dementia (HR=0.406, 95% CI: 0.180-0.919; p=3.06e-02), heart failure (HR=0.305, 95% CI: 0.179-0.519; p=1.18e-05), NCP (HR=0.191, 95% CI: 0.123-0.295; p=1.02e-13) and stroke (HR=0.222, 95% CI: 0.130-0.382; p=4.94e-08), although the estimated protective effects were weaker.

ConclusionsTaken together, this study provides further support to the safety and benefits of COVID-19 vaccination, and such benefits may extend beyond reduction of infection risk or severity per se. As an observational study, causal relationship cannot be concluded and further studies are required to verify the findings.


title: Association of COVID-19 vaccination with risks of hospitalization due to cardiovascular and other diseases: A study of the UK Biobank


title: Do Covid-19 patients needing ICU admission have worse 6 months follow up outcomes when compared with hospitalized non-ICU patients? A prospective cohort study

abstract:
IntroductionStudies focus on pathogenesis, clinical manifestations, and complications during the early phase of the coronavirus disease-19 (COVID-19). Long-term outcomes of COVID-19 patients who discharge intensive care unit (ICU) are unclear.

ObjectivesWe investigated the effect of COVID-19 on lung structure, pulmonary functional, exercise capacity and quality of life in patients discharge from ICU and medical ward.

MethodsA prospective single-centre study conducted in PCR confirmed COVID-19 patients who has been discharged from University of Health Sciences, Dr. Suat Seren Chest Disease and Thoracic Surgery Teaching and Research Hospital between 15 January and 5 March 2021. Patients who followed up for more than 48 hours in ICU and more than 72 hours in medical ward were included the study. Computed tomography scores, pulmonary functional tests (PFT), 6-min walking distance and health related quality of life by SF-36 were compared between ICU and medical ward patients at 6 months after discharge.

ResultsSeventy patients were included final analyses and 31 of them discharged from ICU. ICU patients had higher CT scores than non-ICU patients at admission (17 vs 11) and follow up visit (6 vs 0). Two-three of ICU patients had at least one abnormal finding at control CT. Advanced age (OR 1.08, 95% CI 1.02-1.15) and higher CT score at admission (OR 1.13, 95% CI 1.01-1.27) were risk factors for having radiological abnormalities at control CT.

ConclusionA number of COVID-19 survivors especially with severe disease could not fully recover after 6 months of hospital discharge.


title: The Rapid Assessment of Aggregated Wastewater Samples for Genomic Surveillance of SARS-CoV-2 on a City-Wide Scale

abstract: Throughout the course of the ongoing SARS-CoV-2 pandemic there has been a need for approaches that enable rapid monitoring of public health using an unbiased and minimally invasive means. A major way this has been accomplished is through the regular assessment of wastewater samples by qRT-PCR to detect the prevalence of viral nucleic acid with respect to time and location. Further expansion of SARS-CoV-2 wastewater monitoring efforts to include the detection of variants of interest / concern through next-generation sequencing have enhanced the understanding of the SARS-CoV-2 outbreak. In this report we detail the results of a collaborative effort between public health and metropolitan wastewater management authorities and the University of Louisville to monitor the SARS-CoV-2 pandemic through the monitoring of aggregate wastewater samples over a period of 28 weeks. Our data indicates that wastewater monitoring of water quality treatment centers and smaller neighborhood-scale catchment areas is a viable means by which the prevalence and genetic variation of SARS-CoV-2 within a metropolitan community of approximately one million individuals may be monitored. Importantly, these efforts confirm that regional emergence and spread of variants of interest / concern may be detected as readily in aggregate wastewater samples as compared to the individual wastewater sheds.


title: COVID-19 Incidence and Hospitalization Rates are Inversely Related to Vaccination Coverage Among the 112 Most Populous Counties in the United States

abstract: We tested whether COVID-19 incidence and hospitalization rates during the Delta variant-related surge were inversely related to vaccination coverage among the 112 most populous counties in the United States, together comprising 44 percent of the countrys total population. We measured vaccination coverage as the percent of the county population fully vaccinated as of July 15, 2021. We measured COVID-19 incidence as the number of confirmed cases per 100,000 population during the 14-day period ending August 12, 2021 and hospitalization rates as the number of confirmed COVID-19 admissions per 100,000 population during the same 14-day period. In log-linear regression models, a 10-percentage-point increase in vaccination coverage was associated with a 28.3% decrease in COVID-19 incidence (95% confidence interval, 16.8 - 39.7%), a 44.9 percent decrease in the rate of COVID-19 hospitalization (95% CI, 28.8 - 61.0%), and a 16.6% decrease in COVID-19 hospitalizations per 100 cases (95% CI, 8.4 - 24.8%). Inclusion of demographic covariables, as well as county-specific diabetes prevalence, did not weaken the observed inverse relationship with vaccination coverage. A significant inverse relationship between vaccination coverage and COVID-19 deaths per 100,000 during August 20 - September 16 was also observed. The cumulative incidence of COVID-19 through June 30, 2021, a potential indicator of acquired immunity due to past infection, had no significant relation to subsequent case incidence or hospitalization rates in August. Higher vaccination coverage was associated not only with significantly lower COVID-19 incidence during the Delta surge, but also significantly less severe cases of the disease.


title: COVID-19 Incidence and Hospitalization During the Delta Surge Were Inversely Related to Vaccination Coverage Among the Most Populous U.S. Counties


title: SARS-CoV-2 aerosol transmission in schools: the effectiveness of different interventions

abstract:
AO_SCPLOWBSTRACTC_SCPLOWO_ST_ABSBackgroundC_ST_ABSIndoor aerosol transmission of SARS-CoV-2 has been widely recognized, especially in schools where children remain in closed indoor spaces and largely unvaccinated. Measures such as strategic natural ventilation and high efficiency particulate air (HEPA) filtration remain poorly implemented and mask mandates are often progressively lifted as vaccination rollout is enhanced.

MethodsWe adapted a previously developed aerosol transmission model to study the effect of interventions (natural ventilation, face masks, HEPA filtration, and their combinations) on the concentration of virus particles in a classroom of 160 m3 containing one infectious individual. The cumulative dose of viruses absorbed by exposed occupants was calculated.

ResultsThe most effective single intervention was natural ventilation through the full opening of six windows all day during the winter (14-fold decrease in cumulative dose), followed by the universal use of surgical face masks (8-fold decrease). In the spring/summer, natural ventilation was only effective ([≥] 2-fold decrease) when windows were fully open all day. In the winter, partly opening two windows all day or fully opening six windows at the end of each class was effective as well ([≥] 2-fold decrease). Opening windows during yard and lunch breaks only had minimal effect ([≤] 1.2-fold decrease). One HEPA filter was as effective as two windows partly open all day during the winter (2.5-fold decrease) while two filters were more effective (4-fold decrease). Combined interventions (i.e., natural ventilation, masks, and HEPA filtration) were the most effective ([≥] 30-fold decrease). Combined interventions remained highly effective in the presence of a super-spreader.

ConclusionsNatural ventilation, face masks, and HEPA filtration are effective interventions to reduce SARS-CoV-2 aerosol transmission. These measures should be combined and complemented by additional interventions (e.g., physical distancing, hygiene, testing, contact tracing, and vaccination) to maximize benefit.


title: Prevalence of cognitive impairment following chemotherapy treatment for breast cancer: A systematic review and meta-analysis

abstract:
Breast cancer survival rates have markedly improved. Consequently, survivorship issues have received increased attention. One common sequela of treatment is chemotherapy- induced cognitive impairment (CICI). CICI causes a range of impairments that can have a significant negative impact on quality of life. Knowledge of the prevalence of this condition is required to inform survivorship plans, and ensure adequate resource allocation and support is available for sufferers.

ObjectiveTo estimate the prevalence of cognitive impairment following chemotherapy treatment for breast cancer.

MethodsMedline, Scopus, CINAHL and PSYCHInfo were searched for eligible studies which included prevalence data on CICI, as ascertained though the use of self-report, or neuropsychological tests. Methodological quality of included studies was assessed. Findings were synthesised narratively, with meta-analyses being used to calculate pooled prevalence when impairment was assessed by neuropsychological tests.

Results and discussionThe review included 52 studies. Time-points considered ranged from the chemotherapy treatment period to greater than 10 years after treatment cessation. Summary prevalence figures (across time-points) using self-report, short cognitive screening tools and neuropsychological test batteries were 44%, 16% and 21-34% respectively (very low GRADE evidence).

ConclusionSynthesised findings demonstrate that 1 in 3 breast cancer survivors may have clinically significant cognitive impairment. Prevalence is higher when self-report based on patient experience is considered. This review highlights a number of study design issues that may have contributed to the low certainty rating of the evidence. Future studies should take a more consistent approach to the criteria used to assess impairment. Larger studies are urgently needed.

Summary of Findings Table

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category: oncology


title: Changes in the serial interval and transmission dynamics associated with the SARS-CoV-2 Delta variant in South Korea

abstract: We estimated mean serial interval and superspreading potential for the predominant Delta variant of SARS-CoV-2. Mean serial intervals were similar with 3.7 and 3.5 days during early and latter periods, respectively. Furthermore, the risk of superspreading events was similar with 23% and 25% of cases seeded 80% of all transmissions.


title: Serial interval and transmission dynamics during the SARS-CoV-2 Delta variant predominance in South Korea


title: The association between immunosuppressants use and COVID-19 adverse outcome: National COVID-19 cohort in South Korea

abstract:
PurposeThere is uncertainty of the effect of immunosuppression, including corticosteroids, before COVID-19 infection on COVID-19 outcomes. The aim of this study was to investigate the relationship between prehospitalization immunosuppressants use (exposure), and COVID-19 patient outcomes.

MethodsWe conducted a population-based retrospective cohort study using a nationwide healthcare claims database of South Korea as of May 15, 2020. Confirmed COVID-19 infection in hospitalized individuals aged 40 years or older were included for analysis. We defined exposure variable by using inpatient and outpatient prescription records of immunosuppressants from the database. Our primary outcome was a composite endpoint of all-cause death, intensive care unit (ICU) admission, and mechanical ventilation use. Inverse probability of treatment weighting (IPTW)-adjusted logistic regression analyses were used, to estimate odds ratio (OR) and 95% confidence intervals, comparing immunosuppressants users and non-users.

ResultsWe identified 4,349 patients, for which 1,356 were immunosuppressants users and 2,903 were non-users. Patients who used immunosuppressants were at increased odds of the primary outcome of all-cause death, ICU admission and mechanical ventilation use (IPTW OR 1.32; 95% CI: 1.06 - 1.63). Patients who used corticosteroids were at increased odds of the primary outcome (IPTW OR 1.33; 95% CI: 1.07 - 1.64).

ConclusionWe support the latest guidelines from the CDC, that people on immunosuppressants are at high risk of severe COVID-19 and immunocompromised people may need booster COVID-19 vaccinations.

FundingYGCs work was partially supported by 2020R1G1A1A01006229 awarded by the National Research Foundation of Korea.


title: Childhood malnutrition and bacteraemia at a tertiary hospital in Malawi

abstract:
BackgroundMalnutrition increases risk of acquiring infections but clinical characteristics and hospital outcomes among children in low resource settings with high rates of antimicrobial resistance have not been clearly described.

AimOur main aim was to ascertain prevalence of bacteraemia in hospitalised children at Queen Elizabeth Central Hospital, Malawi.

MethodsWe conducted a secondary analysis of a prospective study of children who had a blood culture collected during hospitalisation.

ResultsOut of 175 children who had blood cultures collected during hospitalisation, 75 had severe acute malnutrition (SAM), 31 moderate acute malnutrition (MAM), and 69 no acute malnutrition (NAM). Twelve (7%) had bacteraemia (8 SAM, 1 MAM, 3 NAM) and seventeen (10%) died (14 SAM, 2 MAM, 1 NAM). Fever, vomiting and convulsions were least common in SAM (69%, 37%, 1%) compared to MAM (90%, 81%, 10%) and NAM (99%, 46%, 29%; p<0.001) children. Mortality was significantly higher in those with than without bacteraemia (33% vs 8%, p=0.004). Most common isolates were Salmonella Typhimurium (31%) and Escherichia coli (23%). High rates of bacterial resistance were noted to gentamicin (58%), a first-line antibiotic, and ceftriaxone (33%), a second-line antibiotic.

ConclusionsMortality and bacteraemia rates are highest in hospitalised children with SAM. Despite this, SAM children do not present with typical clinical features, including fever, vomiting and convulsions. Given the high rate of antimicrobial resistance in this setting, a high index of infection clinical suspicion, awareness of local susceptibility patterns and evidence-based antibiotic guidelines are needed to optimise clinical care and antimicrobial stewardship.

Lay SummaryMalnutrition increases the risk of having an infection but symptoms and hospital outcomes among children with malnutrition, in countries like Malawi with high rates of antimicrobial resistance, have not been clearly described. This study describes a study of children who had a blood culture collected during admission to Queen Elizabeth Central Hospital, Malawi. Of 175 children who had blood cultures collected, 12 (7%) had a bacteria found ( bactaeriemia) and 17 (10%) died. Fever, vomiting and convulsions were significantly less common in severe malnutrition compared to children with moderate malnutrition and those with no malnutrition. Mortality was significantly higher in those with bacteraemia than without. High rates of bacterial resistance were noted to first- and second-line antibiotics. Mortality and bacteraemia rates are highest in hospitalised children with SAM even though they do not present with typical features of bacteraemia.

category: nutrition


title: Rapid spread of a SARS-CoV-2 Delta variant with a frameshift deletion in ORF7a

abstract: Australia is currently experiencing COVID-19 outbreaks from infection with SARS-CoV-2 Delta variants (B.1.617.2, AY.3). Analysis of the index case reveals a sub-consensus level of sequencing reads ([~]25%) that support a 17-nucleotide deletion in ORF7a (ORF7a{Delta}17del). ORF7a{Delta}17del induces a frameshift mutation in ORF7a, which truncates the peptide and potentially leads to reduced suppression of host restriction factor BST-2/CD317/Tetherin. Despite this, the mutation has rapidly become represented at the consensus level in subsequent cases: approximately 72% of SARS-CoV-2 genomes in the Australian outbreak possess ORF7a{Delta}17del, and 99.7% (1534/1538) of Delta genomes on GISAID with ORF7a{Delta}17del originate from the current Australian outbreak (5 August 2021). The global abundance of this mutation might be underestimated given the difficulty of variant calling software correctly calling insertion/deletions (indels), the common inability of phylogenetics software to take indels into account, and the tendency of GISAID to not release submissions that contain a frameshift mutation (unless specifically requested). Overall, the rapid increase of persistent ORF7a{Delta}17del variants is concerning, and suggests either a chance founder effect with a neutral mutation yet to be purged, or that the ORF7a{Delta}17del mutation provides a direct selective advantage.


title: Virological characteristics of SARS-CoV-2 vaccine breakthrough infections in health care workers

abstract:
BackgroundSARS-CoV-2 vaccines are highly effective at preventing COVID-19-related morbidity and mortality. As no vaccine is 100% effective, breakthrough infections are expected to occur.

MethodsWe analyzed the virological characteristics of 161 vaccine breakthrough infections in a population of 24,706 vaccinated healthcare workers (HCWs), using RT-PCR and virus culture.

ResultsThe delta variant (B.1.617.2) was identified in the majority of cases. Despite similar Ct-values, we demonstrate lower probability of infectious virus detection in respiratory samples of vaccinated HCWs with breakthrough infections compared to unvaccinated HCWs with primary SARS-CoV-2 infections. Nevertheless, infectious virus was found in 68.6% of breakthrough infections and Ct-values decreased throughout the first 3 days of illness.

ConclusionsWe conclude that rare vaccine breakthrough infections occur, but infectious virus shedding is reduced in these cases.


title: Bias as a source of inconsistency in ivermectin trials for COVID-19: A systematic review

abstract:
Background and purposeThe objective of this systematic review is to summarize the effects of ivermectin for the prevention and treatment of patients with COVID-19 and to assess inconsistencies in results from individual studies with focus on risk of bias due to methodological limitations.

Evidence reviewWe searched the L.OVE platform through July 6, 2021 and included randomized trials (RCTs) comparing ivermectin to standard or other active treatments. We conducted random-effects pairwise meta-analysis, assessed the certainty of evidence using the GRADE approach and performed sensitivity analysis excluding trials with risk of bias.

ResultsWe included 29 RCTs which enrolled 5592 cases. Overall, the certainty of the evidence was very low to low. Compared to standard of care, ivermectin may reduce mortality, may increase symptom resolution or improvement, may increase viral clearance, may reduce infections in exposed individuals and may decrease hospitalizations (Risk difference (RD) 21 fewer per 1000, 95%CI: 35 fewer to 4 more). However, after excluding trials classified as "high risk" or "some concerns" in the risk of bias assessment, most estimates of effect changed substantially: Compared to standard of care, low certainty evidence suggests that ivermectin may not significantly reduce mortality (RD 7 fewer per 1000, 95%CI: 77 fewer to 108 more) nor mechanical ventilation (RD 6 more per 1000, 95%CI: 43 fewer to 86 more), and moderate certainty evidence shows that it probably does not significantly increase symptom resolution or improvement (RD 14 more per 1000, 95%CI: 29 fewer to 71 more) nor viral clearance (RD 12 fewer per 1000, 95%CI: 84 fewer to 76 more). It is uncertain if ivermectin increases or decreases severe adverse events and symptomatic infections in exposed individuals.

Conclusions and RelevanceIvermectin may not improve clinically important outcomes in patients with COVID-19 and its effects as a prophylactic intervention in exposed individuals are uncertain. Previous reports concluding significant benefits associated with ivermectin are based on potentially biased results reported by studies with substantial methodological limitations. Further research is needed.


title: Regional comparisons of COVID reporting rates, burden, and mortality age-structure using auxiliary data sources

abstract:
We correct common assumptions about COVID burden and disease characteristics in high-income (HIC) versus low- and middle-income (LMIC) countries by augmenting widely-used surveillance data with auxiliary data sources. We constructed an empirically-based model of serological detection rates to quantify COVID reporting rates in national and sub-national locations. From those reporting rates, we estimated relative COVID burden, finding results that contrast with estimates based on case counts and modeling. To investigate COVID mortality by age in an LMIC context, we utilized a unique morgue study of COVID in Lusaka alongside the population attributable fraction method to account for HIV comorbidity. We calculated the comorbidity-corrected age-adjusted mortality curve in Lusaka and found it significantly skewed toward younger age groups as compared to HICs. This unexpected result recommends against the unexamined use of HIC-derived parameterizations of COVID characteristics in LMIC settings, and challenges the hypothesis of an age-structure protective factor for COVID burden in Africa. Indeed, we found overall COVID burden to be higher in Lusaka than in HICs. Concurrent with high COVID burden, many LMICs have high prevalence of other public health issues such as HIV, which compete for limited health investment resources. Given differences in age-structure, comorbidities, and healthcare delivery costs, we provide a case study comparing the cost efficacy of investment in COVID versus HIV and found that even in a high HIV prevalence setting, investment in COVID remains cost-effective. As a whole, these analyses have broad implications for interpretations of COVID burden, modeling applications, and policy decision-making.

Significance StatementThe analyses presented here demonstrate the power of auxiliary COVID data sources to fill information gaps, particularly for LMICs. Our results reveal differences in COVID surveillance and disease dynamics between HICs and LMICs that challenge common perceptions and assumptions about COVID in these respective contexts. We show the divergence of COVID reporting rates between HICs and LMICs and the effects on relative estimated burden. Contradicting common modeling practices, our analysis demonstrates that the age-structure of COVID mortality cannot be accurately generalized from HICs to LMICs. We find higher COVID burden in LMIC contexts than HICs particularly in younger age groups and show that investment in COVID is cost-effective even in light of other public health concerns.


title: The burden of isolation to the individual: a comparison between isolation for COVID-19 and for other influenza-like illnesses in Japan

abstract: At present, there is scarce evidence about how much burden the isolation of COVID-19 patients is. We aimed to assess the differences between COVID-19 and other influenza like illnesses in disease burden brought by isolation. We conducted an online questionnaire survey of 302 people who had COVID-19 or other influenza-like illnesses (ILIs) and compared the burden of isolation due to sickness with one-to-one propensity score matching. The primary outcomes are the duration and productivity losses of isolation, the secondary outcome is quality of life (QOL) valuation on the day of the survey. Acute symptoms of outpatient COVID-19 and other ILIs lasted 17 (interquartile range [IQR] 9-32) and 7 (IQR 4-10) days, respectively. The length of isolation due to COVID-19 was 18 (IQR 10-33) days and that due to other ILIs was 7 (IQR 4-11) days, respectively. The monetary productivity loss of isolation due to COVID-19 was 1424.3 (IQR 825.6-2545.5) USD and that due to other ILIs was 606.1 (IQR 297.0-1090.9) USD, respectively. QOL at the time of the survey was lower in the COVID-19 group than in the "other ILIs" group (0.89 and 0.96, p = 0.001). COVID-19 infection imposes a substantial disease burden, even in patients with non-severe disease. This burden is larger for COVID-19 than other ILIs, mainly because the required isolation period is longer.


title: Self-testing and vaccination against COVID-19 to minimize school closure

abstract: Schools were closed extensively in 2020-2021 to counter COVID-19 spread, impacting students education and well-being. With highly contagious variants expanding in Europe, safe options to maintain schools open are urgently needed. We developed an agent-based model of SARS-CoV-2 transmission in school. We used empirical contact data in a primary and a secondary school, and data from pilot screenings in 683 schools during the 2021 spring Alpha wave in France. We fitted the model to observed school prevalence to estimate the school-specific reproductive number and performed a cost-benefit analysis examining different intervention protocols. We estimated RAlpha=1.40 (95%CI 1.35-1.45) in the primary and RAlpha=1.46 (1.41-1.51) in the secondary school during the wave, higher than Rt estimated from community surveillance. Considering the Delta variant and vaccination coverage in Europe, we estimated RDelta=1.66 (1.60-1.71) and RDelta=1.10 (1.06-1.14) in the two settings, respectively. Under these conditions, weekly screening with 75% adherence would reduce cases by 34% (95%CI 32-36%) in the primary and 36% (35-39%) in the secondary school compared to symptom-based testing. Insufficient adherence was recorded in pilot screening (median [≤]53%). Regular screening would also reduce student-days lost up to 80% compared to reactive closure. Moderate vaccination coverage in students would still benefit from regular screening for additional control (23% case reduction with 50% vaccinated children). COVID-19 pandemic will likely continue to pose a risk for school opening. Extending vaccination coverage in students, complemented by regular testing largely incentivizing adherence, are essential steps to keep schools open, especially under the threat of more contagious variants.


title: Screening and vaccination against COVID-19 to minimize school closure


title: Is the BioNTech-Pfizer COVID-19 vaccination effective in elderly populations? Results from population data from Bavaria, Germany

abstract:
BackgroundThe effect of the BioNTech-Pfizer BNT162b2 vaccination in the elderly ([≥]80 years) could not be fully assessed in the BioNTech-Pfizer trial due to low numbers in this age group. We aimed to evaluate the effectiveness of the BioNTech-Pfizer (BNT162b2) vaccine to prevent SARS-CoV-2 infection and severe outcomes in octo- and novo-generians in a German state setting.

Methods and FindingsA prospective observational study of 708,187 persons aged [≥]80 years living in Bavaria, Germany, was conducted between Jan 9 to Apr 11, 2021. We assessed the vaccine efficacy (VE) for two doses of the BNT162b2 vaccine with respect to SARS-CoV-2 infection and related hospitalisations and mortality. Additionally, differences in VE by age groups [≥]80 to [≤]89 years and [≥]90 years were studied. Analyses were adjusted by sex.

By the end of follow-up, 63.8% of the Bavarian population [≥]80 years had received one dose, and 52.7% two doses, of the BNT162b2 vaccine. Two doses of the BNT162b2 vaccine lowered the proportion of SARS-CoV-2 infections and related outcomes, resulting in VE estimates of 68.3% (95% confidence interval (CI) 65.5%, 70.9%) for infection, 73.2% (95% CI 65.3%, 79.3%) for hospitalisation, and 80.1% (95% CI 80.0%, 89.0%) for mortality. Sex differences in the risk of COVID-19 outcomes observed among unvaccinated persons disappeared after two BNT162b2 vaccine doses. Overall, the BNT162b2 vaccine was equally efficacious in octo- and novo-genarians.

ConclusionsTwo doses of BioNTech-Pfizers BNT162b2 vaccine is highly effective against COVID-19 outcomes in elderly persons.