title: Prevalence of Macroprolactin in Hyperprolactinemic patients receiving Anti-psychotics

abstract:
BackgroundProlactin (PRL) hormone circulates in the blood in three forms, mono-prolactin which constitutes 85 % of prolactin in healthy and hyperprolactinemia conditions, a dimeric prolactin (big PRL) and polymeric PRL (big-big prolactin or Macroprolactin). Macroprolactin in normal conditions is not exceeding 2% of the total serum prolactin and had no biological activity. In some cases, of hyperprolactinemia the dominant form becomes MaPRL and exceeding the 2% percentage of total leading to misdiagnosis of hyperprolactinemia and un-necessary radiological investigations. The aim of this study is to detect the prevalence of MaPRL in Psychiatric patients with hyperprolactinemia due to anti-psychotic medications at Al Masarra hospital.

Material and methodsThe study was conducted on 190 samples from patients with high prolactin in Al Masarra Hospital either inpatients or out-patient clinics either male or non-lactating not pregnant female. The measurement of Prolactin level was measured by the automated analyser COBAS e411, Roche Diagnostic. Macroprolactin was precipitated by using Polyethylene glycol (PEG).

ResultsPrevalence of Macroprolactin was 10.5 % of hyperprolactinemic patients receiving antipsychotics. There was a statistically significant difference in gender between the symptomatic and asymptomatic group. There was no significant difference in medications used between the symptomatic and asymptomatic group and there was a statistically significant difference in total Prolactin & Macroprolactin between males and females.

ConclusionsInvestigation for Macroprolactin should be done in every hyperprolactinemia patient who is receiving antipsychotics more especially the asymptomatic cases to avoid unnecessary radiological imaging and treatment.

category: endocrinology


title: Incidence and Epidemiological study of COVID-19 in Nagpur urban region (India) using Molecular testing

abstract: The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS CoV-2) virus has emerged as public health emergency affecting 206 countries worldwide. India is second highest currently worst effected by Covid 19 pandemic with close to 12.6 million cases and 1.6K deaths reported till date. Maharahstra is the highest Covid-19 burden state in India reporting quarter of overall cases. The city of Nagpur, in Maharashtra state, ranks 4th in terms of reported COVID-19 cases, with 2.5 lakh incidences and more than 4,000 deaths As the transmission rate of COVID-19 is high, it is imperative to study its disease epidemiology in regions of high endemicity to bolster our understanding of its spread, transmission dynamics and contact tracing to undertake appropriate public health control measures.. The present study was undertaken to study the incidence and trend of COVID-19 infection from various zonal regions of Nagpur city, using real time PCR (RT PCR). A retrospective study was carried out at Indian Council of Medical Research (ICMR) approved private molecular diagnostic laboratory in Nagpur from period of 4th May 2020 to 14th November 2020. A total of 51,532 samples collected from various zonal regions of the city during the study period were processed for SARS CoV-2 RT-PCR. Patient information was collected using a pre-defined study proforma which included demographic details such as name, age, gender, address, along with other information, like details of sample collected, kits used and date of sample collected and processed. The study reports an overall Covid-19 positivity of 34% in Nagpur region. The zone wise distribution of positive cases indicated high rate of COVID-19 in endemic regions of Nagpur such as Satranjipura (49%), Ashi nagar (44%), Gandhibagh (43%) & Lakadganj (43%). Rates of infection were high in economically productive age group (21-40) with males being more vulnerable than females. The result of present epidemiology study highlights important data with respect to regions of endemicity within Nagpur city zones. The present data has high public health importance and will be useful for local civic bodies and other community stake holders to undertake appropriate control measures in future epidemic waves of Covid 19. Interestingly, the Governments reduction in testing rates has been helpful in increasing testing per day. The authorization of private laboratories has also increased testing.

category: epidemiology


title: Post Operative Pain Management (POPM) and Patient Satisfection : A Tertiary Care Hospital Experience

abstract:
BackgroundPain is an inevitable part of the postoperative experience. Current study was designed to assess the pattern of analgesic use, the adequacy of post operative pain control by documenting pain scores, and patient satisfaction by documenting the pain perception score of the postoperative patients 48 hours after surgery.

Materials and methodsThis was a formative research and includes a mix of descriptive cross-sectional study carried out in the department of Gynecology and Obstetrics, General surgery, and Orthopedics surgery of Chattagram Maa -O- Shishu Hospital Medical College (CMOSHMC) during the month of January, 2018 to July, 2019.

ResultA total of 180 patients undergoing surgery were included in this study. Baseline data were collected both retrospectively and prospectively. Only analgesic used immediately after operation in three departments were Pethidine (100%). Diclofenac sodium suppository were used in appendectomy and cesarean section (50/60, 83%) and (26/60, 43%) respectively. Mostly, Diclofenac Sodium IV (55/60, 91%) was used in lower limb surgery. The maximum pain score were 5.3 (SD=2.3), 5.6 (SD =1.9), and 6.1 (SD =1.3) during coughing in the first 8 hour and minimum pain score 2.4 (SD =1.0), 2.2 (SD = 0.8) and 1.7 (SD=1.3) at rest 48 hours after cesarean section, appendectomy and lower limb surgery respectively. But pain score eventually increased during coughing 48 hours after surgery. After 48 hours of surgery maximum pain perception score 3.9 (SD = 0.9) in lower limb surgery and minimum perception score were 3.5 (SD =1.8) in cesarean section. Majority of the appendectomy patient (76%) satisfied with pain management where as only 43% satisfied in case of cesarean section.

ConclusionThis study enabled the researchers to get a precise picture of the current state of POPM in different hospitals, as well as identify particular needs for improving such practices in health care facilities and implementing an educational intervention in order to improve the post operative pain management.

category: pharmacology and therapeutics


title: The Effects of Stress Across the Lifespan on the Brain, Cognition and Mental Health: A UK Biobank study

abstract: Repeated overstimulation of the stress response system, caused by exposure to prolonged highly stressful experiences, is thought to affect brain structure, cognitive ability, and mental health. We tested the effects of highly stressful experiences during childhood and adulthood using data from the UK Biobank, a large-scale national health and biomedical study with over 500,000 participants. To do this, we defined four groups with high and low levels of childhood and adulthood stress. We then used T1- and diffusion-weighted MRI data to assess the macrostructure in grey matter and microstructure in white matter of limbic brain regions, commonly associated with the stress response. We also compared executive function and working memory between these groups. Our findings suggest that in females, higher levels of both childhood and adulthood stress were associated with reduced connectivity within the posterior thalamic radiation. High stress in both childhood and adulthood was associated with decreases in both executive function and working memory. Finally, stress across the lifespan was positively associated with the number of diagnosed mental health problems, with a stronger effect in females than in males. Together our findings demonstrate links between stress across the lifespan, brain structure and mental health outcomes that may differ between males and females. Our findings also suggest that exposure to highly stressful life events has a negative impact on cognitive abilities in later life regardless of sex.

category: radiology and imaging


title: COVID-19 Pandemic and Academic Speculation of Medical Students of Bangladesh: A Cross-sectional, Comparative Study

abstract:
BackgroundCOVID-19 pandemic has caused unprecedented disruptions worldwide including education system. While the necessary focus has been on patient care andwellbeing of healthcare professionals, the impacts on medical students need to be discussed.

MethodsThis cross-sectional comparative study was conducted to evaluate the academic speculation of medical students studying in government and non-government institute during COVID-19 pandemic. A structured questionnaire survey linked in the google form was used as study instrument and was distributed among study population through email, messenger, whatsapp and other social media. Total 1020 students were participated in the study

ResultsIn this research, 441 (43.24%) and 579 (56.77%) students were from government and non-government medical colleges respectively. Opinion of both group was almost similar regarding disruption of medical education, loss of clinical skills and competency, future career plan, and stress and anxiety but significant differences were observed between both group regarding issue of financial burden, meaningful learning opportunities, fear of getting infected and maintenance of social distancing in hostel.

ConclusionThe study revealed similar kind of viewpoint about disruption of education, loss of clinical skill and competency, changing aspects of future career plan and increased level of stress and anxiety among medical students of government and non-government institutes of Bangladesh but different speculations were found regarding issue of financial burden, meaningful learning opportunities, fear of getting infected and possibility of maintenance of social distancing in hostel.

category: medical education


title: The Impact of Control and Mitigation Strategies during the Second Wave of COVID-19 Infections in Spain and Italy

abstract: European countries struggled to fight against the second and the third waves of the COVID-19 pandemic, as the Test-Trace-Isolate (TTI) strategy widely adopted over the summer and early fall failed to effectively contain the spread of the disease. In this paper, we shed light on the effectiveness of such a strategy in two European countries (Spain and Italy) by analysing data from June to December 2020, collected via a large-scale online citizen survey with 95,251 answers in Spain and 43,393 answers in Italy. Through our analysis, we identify several weaknesses in each of the three pillars of the TTI strategy: testing, tracing and isolating. Moreover, we analyse the respondents self-reported behaviour before and after the mitigation strategies were deployed during the second wave of infections. We find that the changes in the participants behaviour were more pronounced in Italy than in Spain, whereas in both countries, respondents reported being very compliant with individual protection measures, such as wearing facial masks or frequently disinfecting their hands. Finally, we analyse the participants perceptions about their governments measures and the safety of everyday activities and places regarding the risk of getting an infection. We find that the perceived risk is often gender- and age-dependent and not aligned with the risk level identified by the literature. This finding emphasises the importance of deploying public-health communication campaigns to debunk misconceptions about SARS-CoV-2. Overall, our work shows the value of online citizen surveys to quickly and cheaply collect large-scale data to support and evaluate policy decisions to contrast the spread of the disease.

category: infectious diseases


title: Magnetofluidic platform for rapid multiplexed screening of SARS-CoV-2 variants and respiratory pathogens

abstract: The rise of highly transmissible SARS-CoV-2 variants brings new challenges and concerns with vaccine efficacy, diagnostic sensitivity, and public health responses in the fight to end the pandemic. Widespread detection of variant strains will be critical to inform policy decisions to mitigate further spread, and post-pandemic multiplexed screening of respiratory viruses will be necessary to properly manage patients presenting with similar respiratory symptoms. In this work, we have developed a portable, magnetofluidic cartridge platform for automated PCR testing in <30 min. Cartridges were designed for multiplexed detection of SARS-CoV-2 with either distinctive variant mutations or with Influenza A and B. The platform demonstrated a limit of detection down to 2 copies/{micro}L SARS-CoV-2 RNA with successful identification of B.1.1.7 and B.1.351 variants. The multiplexed SARS-CoV-2/Flu assay was validated using archived clinical nasopharyngeal swab eluates (n = 116) with an overall sensitivity/specificity of 98.1%/95.2%, 85.7%/100%, 100%/98.2%, respectively, for SARS-CoV-2, Influenza A, and Influenza B. Further testing with saliva (n = 14) demonstrated successful detection of all SARS-CoV-2 positive samples with no false-positives.


title: COVID-19 in patients hospitalized and healthcare workers: what have changed after the first wave in a university hospital

abstract:
ObjectiveTo assess the COVID-19 frequency rates in hospitalized patients (HP) and healthcare workers (HCW), viral load inference, and the impact of vaccination and variants of concern (VOC) during the first pandemic wave.

MethodsWe evaluated the COVID-19 diagnostics at Hospital Sao Paulo, Brazil, from March 2020 to April 2021, in 10,202 samples (6,502 HP and 3,700 HCW) tested by RT-qPCR, inferring viral load by cycle threshold (Ct) values, and frequency rates.

ResultsSARS-CoV-2 was detected in 31.27% of individuals (32.23% HP and 29.80% HCW). The mean age of HP positives was 57.26 {+/-} 18.29 years (median = 59), with a mean Ct value of 25.55 {+/-} 6.07. Neither age nor Ct values in both groups have significantly differed during the first and second waves or even since the predominance of VOC P.1 on March 2021.

ConclusionsThe COVID-19 epidemic curves of HP and HCW accompanied the variations reported in Sao Paulo city, as well as the variation of hospitalization and occupancy of ICU beds. The VOC P.1 has no impact on the viral load, since its predominance in March 2021. The vaccination of HCW may have contributed to a decrease in the positivity rates, although more studies will provide a better understanding of the impact of immunization on the COVID-19 pandemic.


title: Mental health of Adolescents in the Pandemic: Long-COVID19 or Long-Pandemic Syndrome?

abstract:
BackroundPost-COVID19 complications such as pediatric inflammatory multisystem syndrome (PIMS) and Long-COVID19 move increasingly into focus, potentially causing more harm in this age group than the acute infection. To better understand the symptoms of long-COVID19 in adolescents and to distinguish infection-associated symptoms from pandemic-associated symptoms, we conducted a Long-COVID19 survey, comparing responses from seropositive and seronegative adolescents. To our knowledge, data of Long-COVID19 surveys with seronegative control groups have not been published yet.

MethodsSince May 2020 students grade 8-12 in fourteen secondary schools in Eastern Saxony were enrolled in the SchoolCovid19 study. Seroprevalence was assessed via serial SARS-CoV-2 antibody testing in all participants. Furthermore, during the March/April 2021 study visit all participants were asked to complete a 12 question Long-COVID19 survey regarding the occurrence and frequency of difficulties concentrating, memory loss, listlessness, headache, abdominal pain, myalgia/ arthralgia, fatigue, insomnia and mood (sadness, anger, happiness and tenseness).

Findings1560 students with a median age of 15 years participated in this study. 1365 (88%) were seronegative, 188 (12%) were seropositive. Each symptom was present in at least 35% of the students within the last seven days before the survey. However, there was no statistical difference comparing the reported symptoms between seropositive students and seronegative students. Whether the infection was known or unknown to the participant did not influence the prevalence of symptoms.

InterpretationThe lack of differences comparing the reported symptoms between seropositive and seronegative students suggests that Long-COVID19 might be less common than previously thought and emphasizing the impact of pandemic-associated symptoms regarding the well-being and mental health of young adolescents.

FundingThis study was supported by a grant by the Federal State of Saxony. M.K.W. was supported by the Else Kroner-Fresenius Center for Digital Health (EKFZ), TU Dresden, Germany.


title: A model to analyze rideshare data to surveil novel strains of SARS-CoV-2

abstract:
BackgroundThe emergence of novel, potentially vaccine-resistant strains of SARS-CoV-2 poses a serious risk to public health. The interactions between passengers and drivers facilitated by rideshare platforms such as Uber are, essentially, a series of partially standardized, random experiments of SARS-CoV-2 transmission. Rideshare companies share data with government health agencies, but no statistical method is available to aggregate these data for the systematic study of the transmission dynamics of COVID-19.

MethodsWe develop a proof-of-concept model for the analysis of data from rideshare interactions merged with COVID-19 diagnosis records. Using simulated data with rideshare volumes, disease prevalence, and diagnosis rates based on a large US city, we use the model to test hypotheses about the emergence of viral strains and their transmission characteristics in the presence of non-pharmaceutical interventions and superspreaders.

FindingsData from 10 simulated trials of SARS-CoV-2 propagation within the Los Angeles rideshare network resulted in an average of 190,387.1 potentially infectious rideshare interactions. Assuming access to data on 25% of the total estimated infections (Partial Reporting), these interactions resulted in an average of 409.0 diagnosed rideshare infections given our transmission model assumptions. For each of the 10 simulated trials, analysis given Partial Reporting could consistently differentiate between a baseline strain and an emergent, more infectious viral strain, enabling hypothesis testing about transmission characteristics.

InterpretationSimulated evaluation of a novel statistical model suggests that rideshare data combined with COVID-19 diagnosis data have the potential to automate continued surveillance of emergent novel strains of SARS-CoV-2 and their transmission characteristics.


title: Impact of vaccination on the COVID-19 pandemic: Evidence from U.S. states

abstract: Governments worldwide are implementing mass vaccination programs in an effort to end the novel coronavirus (COVID-19) pandemic. Although the approved vaccines exhibited high efficacies in randomized controlled trials1,2, their population effectiveness in the real world remains less clear, thus casting uncertainty over the prospects for herd immunity. In this study, we evaluated the effectiveness of the COVID-19 vaccination program and predicted the path to herd immunity in the U.S. Using data from 12 October 2020 to 7 March 2021, we estimated that vaccination reduced the total number of new cases by 4.4 million (from 33.0 to 28.6 million), prevented approximately 0.12 million hospitalizations (from 0.89 to 0.78 million), and decreased the population infection rate by 1.34 percentage points (from 10.10% to 8.76%). We then built a Susceptible-Infected-Recovered (SIR) model with vaccination to predict herd immunity. Our model predicts that if the average vaccination pace between January and early March 2021 (2.08 doses per 100 people per week) is maintained, the U.S. can achieve herd immunity by the last week of July 2021, with a cumulative vaccination coverage of 60.2%. Herd immunity could be achieved earlier with a faster vaccination pace, lower vaccine hesitancy, or higher vaccine effectiveness. These findings improve our understanding of the impact of COVID-19 vaccines and can inform future public health policies regarding vaccination, especially in countries with ongoing vaccination programs.


title: Comprehensive and Temporal Surveillance of SARS-CoV-2 in Urban Water Bodies: Early Signal of Second Wave Onset

abstract: The possible faecal-oral transmission of SARS-CoV-2 through domestic discharges has emerged as a serious public health concern. Based on persistence of the virus in environment, the wastewater-based epidemiology (WBE) enabled the surveillance of infection in a community. The water bodies connected to the anthropogenic activities have strong possibility of presence of the SARS-CoV-2 genetic material. In this work, we monitored urban, peri-urban and rural lakes in and around Hyderabad as a long-term surveillance study for presence of enteric virus SARS-CoV-2 gene fragments. The study time of seven months coincided with the first and second wave of COVID-19 infection. The study depicted differential viral RNA copies in the urban lake with high viral load observed during the peaks of wave I and wave II. Distinct variability in viral genes detection was observed amongst all five lakes which were in concordance with the human activity of the catchment area. The SARS-CoV-2 genes were not detected in peri-urban and rural lakes, whereas the urban lakes having direct functional attributes from domestic activity, in the community showed presence of viral load. The outcome of the study clearly shows that the urban water streams linked with domestic discharge will function as a proxy for wastewater epidemiological studies. The surge in viral gene load from February 2021 sample suggests the on shoot of the second wave of infection, which correlated well with the prevailing pandemic situation. Implementation of regular WBE based monitoring system for the water bodies/wastewater in the urban and semi-urban areas will help to understand the outbreak and spread of virus in the community.


title: Prevalence and source analysis of COVID-19 misinformation of 138 countries

abstract: This study analyzed 9,657 pieces of misinformation that originated in 138 countries and fact-checked by 94 organizations. Collected from Poynter Institutes official website and following a quantitative content analysis method along with descriptive statistical analysis, this research produces some novel insights regarding COVID-19 misinformation. The findings show that India (15.94%), the US (9.74%), Brazil (8.57%), and Spain (8.03%) are the four most misinformation-affected countries. Based on the results, it is presumed that the prevalence of COVID-19 misinformation can have a positive association with the COVID-19 situation. Social media (84.94%) produces the highest amount of misinformation, and the internet (90.5%) as a whole is responsible for most of the COVID-19 misinformation. Moreover, Facebook alone produces 66.87% misinformation among all social media platforms. Of all countries, India (18.07%) produced the highest amount of social media misinformation, perhaps thanks to the countrys higher internet penetration rate, increasing social media consumption, and users lack of internet literacy. On the other hand, countries like Turkey, the US, Brazil, and the Philippines where either political control over media is intense or political conservatism is apparent, experienced a higher amount of misinformation from mainstream media, political figures, and celebrities. Although the prevalence of misinformation was the highest in March 2020, given the present trends, it may likely to increase slightly in 2021.

category: public and global health


title: Clinical outcomes and cost-effectiveness of COVID-19 vaccination in South Africa

abstract: Low- and middle-income countries are implementing COVID-19 vaccination strategies in light of varying vaccine efficacies and costs, supply shortages, and resource constraints. Here, we use a microsimulation model to evaluate clinical outcomes and cost-effectiveness of a COVID-19 vaccination program in South Africa. We varied vaccination coverage, pace, acceptance, effectiveness, and cost as well as epidemic dynamics. Providing vaccines to at least 40% of the population and prioritizing vaccine rollout prevented >9 million infections and >73,000 deaths and reduced costs due to fewer hospitalizations. Model results were most sensitive to assumptions about epidemic growth and prevalence of prior immunity to SARS-CoV-2, though the vaccination program still provided high value and decreased both deaths and health care costs across a wide range of assumptions. Vaccination program implementation factors, including prompt procurement, distribution, and rollout, are likely more influential than characteristics of the vaccine itself in maximizing public health benefits and economic efficiency.


title: Homebrew reagents for low cost RT-LAMP

abstract: RT-LAMP (reverse transcription - Loop-mediated isothermal amplification) has gained popularity for the detection of SARS-CoV-2. The high specificity, sensitivity, simple protocols and potential to deliver results without the use of expensive equipment has made it an attractive alternative to RT-PCR. However, the high cost per reaction, the centralized manufacturing of required reagents and their distribution under cold chain shipping limits RT-LAMPs applicability in low-income settings. The preparation of assays using homebrew enzymes and buffers has emerged worldwide as a response to these limitations and potential shortages. Here, we describe the production of Moloney murine leukemia virus (M-MLV) Reverse Transcriptase and BstLF DNA polymerase for the local implementation of RT-LAMP reactions at low cost. These reagents compared favorably to commercial kits and optimum concentrations were defined in order to reduce time to threshold, increase ON/OFF range and minimize enzyme quantities per reaction. As a validation, we tested the performance of these reagents in the detection of SARS-CoV-2 from RNA extracted from clinical nasopharyngeal samples, obtaining high agreement between RT-LAMP and RT-PCR clinical results. The in-house preparation of these reactions results in an order of magnitude reduction in costs, and thus we provide protocols and DNA to enable the replication of these tests at other locations. These results contribute to the global effort of developing open and low cost diagnostics that enable technological autonomy and distributed capacities in viral surveillance.


title: Indexing Cerebrovascular Health Using Near-infrared Spectroscopy

abstract: Near-infrared spectroscopy (NiRS) is a relatively new technology of brain imaging with its potential in the assessment of cerebrovascular health only recently discovered. Encouraging early results suggest that NiRS can be used as an inexpensive and portable cerebrovascular health tracking device using a recently proposed pulse relaxation function (PReFx). In this paper, we propose a new NiRS timing index, TINiRS, of cerebrovascular health. TINiRS is a novel use of the NiRS technology. TINiRS is motivated by the previously proved relationship of the timing of the reflected wave with vascular resistance and compliance in the context of pressure waveforms. We correlated both TINiRS and PReFx against age, a non-exercise cardiorespiratory fitness (CRF) index, and two existing indices of cerebrovascular health, namely Transcranial Doppler (TCD) augmentation index, AITCD, and magnetic resonance imaging (MRI) blood flow pulsatility index, PIMRI. The TINiRS correlations with Age, CRF, PIMRI and AITCD all are significant, i.e., r = 0.53 (p = 0.002), r = -0.44 (p = 0.011), r = 0.45 (p = 0.012) and r = 0.46 (p = 0.010), respectively. PReFx, however, did not have significant correlations with any of the vascular health factors. The proposed timing index is a reliable indicator of cerebrovascular aging factors in the NiRS waveform.


title: Is a fair comparison between doping tested and doping untested powerlifters possible?

abstract:
PurposePowerlifting is clearly divided into doping tested amateur competitions and doping untested pro competitions with pro competition money prizes ranging from a few thousand USD to over $120 000 USD in a single competition. However, the results of both pro and amateur powerlifting competitions are then collected and put into the same result database (although there is the possibility to filter the results using doping control status). The powerlifting results are compared by scores to have a fair comparison between different weight class athletes. This study plays with the thought of comparing doping tested and doping untested athletes, and creates a coefficient for the comparison.

MethodsThe powerlifting results (noted in kg) of the 10 top ranked athletes per weight class and separately for men and women, and for doping tested and doping untested categories were collected from the openpowerlifting.org database. A weight adjusted model was fit to these results separately for men and women with the doping control status used a binary factor.

ResultsDoping control status was a significant factor when modelling the powerlifting results, p<0.001 for both men and women. Mens doping untested results were 1.0725 times as large as the doping tested results. Womens doping untested results were 1.1208 times as large as the doping tested results. These separate and precise factors could be used as coefficients for scoring doping tested and doping untested athletes powerlifting results. Moreover, the coefficients approximate the effect of doping on an elite level athletes results.

category: sports medicine


title: Technology-delivered undergraduate medical education involving patients and carers: A rapid systematic review

abstract:
BackgroundInvolving patients and carers in medical education centralises their voice in healthcare and supports students to develop key professional and person-centred skills. Medical schools are increasingly using technology to deliver educational activities. No review currently exists to establish the variety of technologies and their uses in undergraduate medical education when patients and/or carers are involved.

MethodsOvid MEDLINE, Ovid EMBASE and medRxiv were searched in October 2020 and reference lists of key articles were hand searched. Eligible studies reported technology-assisted education, in any setting, involving authentic patients and/or carers. Studies in foreign languages, or describing actors or non-authentic patients were excluded. Study quality was assessed using the Mixed Methods Appraisal Tool (MMAT). Levels of patient involvement were assessed using Towle et als (2010) taxonomy.

ResultsTwenty studies were included. The majority involved patients and/or carers via pre-recorded videos or online scenarios, with no student-interaction. Four studies evaluated remote consultations using telehealth technology, involving real-time interactions with authentic patients. Technology-supported teaching sessions involving patients and/or carers were found to be acceptable to students, educationally valuable (to students and educators), and enhanced student engagement, patient-centred attitudes, knowledge of specific patient groups, and communication and clinical skills. Two studies describing real-time remote interactions with authentic patients indicated potential barriers for students (reduced ability to build relationship with patients and examine them), educators (reduced ability to build rapport with students) and patients (issues with using or accessing telehealth).

ConclusionsNo studies directly measured the perspective of patients or carers involved in technology-delivered medical education. Future research should establish barriers and facilitators to patients and carers taking up a role in medical students education when technology is used, and evaluate PPI activities at Levels 3 and above as described by Towle et als taxonomy.


title: Antibody Response to COVID-19 vaccination in Patients Receiving Dialysis

abstract:
BackgroundPatients receiving dialysis may mount impaired responses to COVID19 vaccination.

MethodsWe report antibody response to vaccination from 1140 patients without, and 493 patients with pre-vaccination SARS-CoV-2 RBD antibody. We used commercially available assays (Siemens) to test remainder plasma monthly in association with vaccination date and type, and assess prevalence of absent total receptor binding antibody, and absent or attenuated (index value < 10) semiquantitative receptor binding domain IgG index values. We used Poisson regression to evaluate risk factors for absent or attenuated response to vaccination.

ResultsAmong patients who were seronegative versus seropositive before vaccination, 62% and 56% were [≥]65 years old, 20% and 24% were Hispanic, and 22% and 23% were Black. Median IgG index values rose steadily over time, and were higher among the seropositive than in the seronegative patients after completing vaccination (150 [25th, 75th percentile 23.2, 150.0] versus 41.6 [11.3, 150.0]). Among 610 patients who completed vaccination (assessed [≥]14 days later, median 29 days later), the prevalence of absent total RBD response, and absent and attenuated semiquantitative IgG response was 4.4% (95% CI 3.1, 6.4%), 3.4% (2.4, 5.2%), and 14.3% (11.7, 17.3%) respectively. Risk factors for absent or attenuated response included longer vintage of end-stage kidney disease, and lower pre-vaccination serum albumin.

ConclusionsMore than one in five patients receiving dialysis had evidence of an attenuated immune response to COVID19 vaccination.

Significance statementPatients receiving dialysis face high likelihood of severe COVID19; at the same time, vaccination may be less efficacious, as prior data indicate impaired immune responses to influenza and Hepatitis B vaccination. We found that 22% of patients receiving dialysis had suboptimal responses to vaccination, irrespective of whether or not they had evidence of prior SARS-CoV-2 infection. Poorer health status and longer duration of end-stage kidney disease increased likelihood of suboptimal response. Ongoing vigilance for COVID19 in dialysis facilities and studies of modified vaccination dosing schedules will be critical to protecting patients receiving dialysis.

category: nephrology


title: INFLUENCE OF NOVEL CORONAVIRUS DISEASE (COVID-19) ON PARKINSONS DISEASE: SYSTEMATIC REVIEW

abstract:
BackgroundCOVID-19 has affected global communities with multiple neurological complications in addition to other critical medical issues. COVID-19 binds to the hosts angiotensin-converting enzyme2 (ACE2) receptors, which are expressed in the neurons and glial cells, acting as an entry port to the central nervous system (CNS). ACE2 receptors are abundantly expressed on dopamine neurons, which may worsen the prognosis of motor symptoms in Parkinsons disease (PD). SARS-CoV-2 may lead to an indirect response via immune-mediated cytokine storms and propagate through the CNS leading to damage. PD is also been associated with certain post-viral infections apart from COVID-19, such as HSV, Influenzavirus A, Measles virus, Cytomegalovirus, and Mumps.

ObjectiveIn this systematic review, we aim to provide a thorough analysis of associations between COVID-19 and neurological outcomes for patients with PD.

MethodsUsing PRISMA statement 2020, a systematic review was conducted to isolate confirmed COVID-19 patients and analyze the PD-associated neurological outcomes. A systematic literature search was conducted using the following databases: PubMed, Science Direct, Google Scholar, and Cochrane databases. The following keywords were used "COVID19, SARS-CoV-2, Parkinsons disease, Pandemic, Mortality." A modified Delphi process was employed to include the studies and ensure that the clinical outcome measures were addressed.

ResultsOf the 355 records located during the initial round of screening, 16 were included in the final synthesis. Of PD patients who tested positive for SARS-CoV-2, worsening motor symptoms and other viral-associated symptoms were reported. These symptoms included bradykinesia, tremors, gait disturbances, delirium and dementia, and severe spasms of arms and legs. Encephalopathy was presented in two of the included studies. Increased mortality rates were identified for hospitalized patients due to COVID-19 and PD as compared to other patient groups, albeit with limited generalizability due to high bias of included studies.

ConclusionPatients with PD may experience substantial worsening of motor and non-motor symptoms due to COVID 19. Given the novelty of neurological-viral associations, clinical studies in the future ought to explore the disease severity and neurological outcomes in COVID-19 positive patients with PD as compared to non-PD patients, in addition to understanding the role of ACE2 in increased vulnerability to contracting the infection and as a treatment modality.

category: neurology


title: The Influence of Coronavirus Disease-2019 (COVID-19) On Parkinsons Disease: An Updated Systematic Review


title: Genome-wide transethnic meta-analysis identifies novel susceptibility loci for childhood acute lymphoblastic leukemia

abstract:
The risk of childhood acute lymphoblastic leukemia (ALL) differs across ethnic groups and there exist gaps in our understanding of the genetic risk of ALL as most studies took place in populations of predominantly European ancestries. In an effort to address these limitations, we performed a genetic meta-analysis of ALL in 76,317 participants across four ethnic groups, including 17,814 non-European individuals and 3,482 total cases. We replicated 15 out of 16 previously identified loci associated with ALL in our trans-ethnic analysis. We further identified five novel associations at genome-wide significance, including three novel loci and two secondary associations at previously known loci (17q12 and near CEBPE). The three putatively novel loci (rs9376090 near MYB/HBS1L, rs10998283 near TET1, and rs9415680 near JMJD1C/NRBF2) were previously shown to be associated with multiple blood cell traits and other hematopoietic cancers. Polygenic risk scores constructed from our trans-ethnic meta-analysis showed similar efficacy in independent Latino (LAT) and non-Latino white (NLW) ALL cohorts (AUC [~] 0.67-0.68) and could partly explain the increased risk of ALL in LAT compared to NLW. Cross-population analysis also showed high but significantly less than 100% genetic correlation between LAT and NLW, suggesting potential differences in the underlying genetic architecture between ethnic groups. In summary, our findings enhance the understanding of genetic contribution to ALL risk across diverse populations and highlight the importance to include multiple ethnic groups in GWAS.

Key PointsO_LIWe identified three novel loci on childhood acute lymphoblastic leukemia near genes previously associated with multiple blood cell traits
C_LIO_LIPolygenic risk scores using known and novel risk variants showed similar efficacy in Latino and non-Latino white Americans
C_LI

category: genetic and genomic medicine


title: fNIRS-derived Neurocognitive Ratio as a Biomarker for Neuropsychiatric Diseases

abstract:
SignificanceClinical use of fNIRS derived features has always suffered low sensitivity and specificity due to signal contamination from background systemic physiological fluctuations. This article provides an algorithm to extract cognition related features by eliminating the effect of background signal contamination; hence, improves the classification accuracy.

AimThe aim in this study is to investigate the classification accuracy of an fNIRS derived biomarker based on global efficiency. To this end, fNIRS data were collected during a computerized Stroop Task from healthy controls, and patients with migraine, obsessive compulsive disorder, and schizophrenia.

ApproachFunctional connectivity (FC) maps were computed from [HbO] time series data for Neutral, Congruent and Incongruent stimuli using the partial correlation approach. Reconstruction of FC matrices with optimal choice of principal components yielded two independent networks: Cognitive Mode Network (CM) and Default Mode Network(DM).

ResultsGlobal Efficiency (GE) values computed for each FC matrix after applying principal component analysis yielded strong statistical significance leading to a higher specificity and accuracy. A new index, Neurocognitive Ratio (NCR), was computed by multiplying the Cognitive Quotients (CQ) and ratio of GE of CM to GE of DM. When mean values of NCR [Formula] over all stimuli were computed, they showed high sensitivity (100%), specificity (95.5%), and accuracy (96.3%) for all subjects groups.

Conclusions[Formula] can reliable be used as a biomarker to improve the classification of healthy to neuropsychiatric patients.

category: health informatics


title: MASK MANDATES REDUCE COVID-19 MORTALITY: Analysis of 37 States and the District of Columbia, with a further analysis of the impact of demographic and medical factors on efficacy.

abstract: As the number of COVID-19 deaths in the US increased, various policies were enacted to slow the spread of the pandemic. While the situation has improved in recent months, determining how best to combat the current pandemic is still essential. Failure to do so invites both further resurgences of the current pandemic, and more pandemics in the years to come. As a result of the widespread failure to contain the spread of COVID-19, enough deaths have occurred that the impact of policy on mortality may be statistically evaluated. This paper uses Optimal Discriminant Analysis (ODA) to evaluate the hypothesized ability of limited mask mandates (MM) to reduce the daily number of COVID-19 deaths in the states analyzed. The mandates were found to reduce mortality in half the states analyzed and did not result in increased mortality in any states. A full range of cofactors were analyzed to determine which, if any, influenced the efficacy of the mandates in the states in which mandates had an effect. Institutional Health Subindex of the Social Capital Index, state health score, population density, portion of the population with nongroup health insurance, state GDP, and the rate of pregnancy related diabetes were all correlated with increased mandate efficacy. In contrast, incarceration rate, overcrowded housing, severely overcrowded housing, portion of the population with military provided insurance, portion of the population uninsured, the portion of the population unable to see a doctor due to cost, and the portion of the population who were American Indian/Native Alaskan were all correlated with reduced mandate efficacy.

category: health policy


title: No excess mortality detected in rural Bangladesh in 2020 from repeated surveys of a population of 81,000

abstract:
BackgroundExcess mortality has demonstrated under-counting of COVID-19 deaths in many countries but cannot be measured in low-income countries where civil registration is incomplete.

MethodsEnumerators conducted an in-person census of all 16,054 households in a sample of 135 villages within a 350 km2 region of Bangladesh followed by a census conducted again in May and November 2020 over the phone. The date and cause of any changes in household composition, as well as changes in income and food availability, were recorded. For analysis, we stratify the mortality data by month, age, gender, and household education. Mortality rates were modeled by Bayesian multilevel regression and the strata aggregated to the population by poststratification.

ResultsA total of 276 deaths were reported between February and the end of October 2020 for the subset of the population that could be contacted twice over the phone, slightly below the 289 deaths reported for the same population over the same period in 2019. After adjustment for survey non-response and poststratification, 2020 mortality changed by -8% (95% CI, -21% to 7%) relative to an annualized mortality of 6.1 per thousand in 2019. However, salaried breadwinners reported a 40% decline in income and businesses a 60% decline in profits in May 2020.

DiscussionAll-cause mortality in the surveyed portion of rural Bangladesh was if anything lower in 2020 compared to 2019. Our findings suggest various restrictions imposed by the government limited the scale of the pandemic, although they need to be accompanied by expanded welfare programs.

Key questionsO_ST_ABSWhat is already known?C_ST_ABSCivil registry data from dozens of countries, where available, indicate gaps between official death counts attributed to COVID-19 and, usually, a larger increase in total mortality in 2020 compared to previous years. This approach is not available to gauge the impact of COVID-19 in countries such as Bangladesh where the civil registry system is slow and coverage incomplete. One year after the first COVID-19 case was reported in Bangladesh in 2020, the number of deaths attributed to COVID-19 was equivalent to 1% of annual mortality in previous years. Whether this low figure compared to many other countries is an accurate reflection of the situation or is distorted by massive under-counting has been much debated, albeit on the basis of little direct evidence. The lack of accurate mortality data has made it only more difficult for policy makers to balance the public health benefit of lockdowns and similar measures relative to the well-documented economic costs and hardship imposed by such measures on poor households in particular. A PubMed search conducted on May 4, 2021 under (Bangladesh[Title/Abstract]) AND (excess mortality[Title/Abstract]) limited to 2020-21 did not yield a single relevant study.

What are the new findings?By conducting of repeated census of a large rural population over the course of 2020, once in person and twice over the phone, we document if anything a slight decline in mortality across a rural area of Bangladesh compared to 2019. We also place an upper limit on the level of under-reporting at the national level that is consistent with our observations. At the same time, interviewed households reported a large and sustained drop in income as well as reduced access to food.

What do the new findings imply?The impact of the pandemic on mortality was thankfully limited in rural study area of Bangladesh in 2020. This suggests that officially recorded COVID-19 deaths may have been contributed largely by the urban population, about a third of the country overall. At the same time, the economic and nutritional impact of restrictions on trade and movement was substantial and probably underestimated in the rural population. As cases surge again, as they did in March-April 2021, policy makers may want to consider limiting strict restrictions to urban areas while expanding a financial support throughout the country.


title: SARS-CoV-2 antibodies rapid tests: a valuable epidemiological tool in challenging settings

abstract:
BackgroundDuring the last year, mass screening campaigns have been carried out to identify immunological response to SARS-CoV-2 and establish a possible seroprevalence. The obtained results gained new importance with the beginning of SARS-CoV-2 vaccination campaign, as the lack of doses has persuaded several countries to introduce different policies for individuals who had a history of COVID 19.

LFAs may represent an affordable tool to support population screening in LMICs, where diagnostic tests are lacking, and epidemiology is still widely unknown. However, LFAs have demonstrated a wide range of performance and the question of which one could be more valuable in these settings still remains.

MethodsWe evaluated the performance of 11 LFAs in detecting SARS-CoV-2 infection, analysing samples collected from 350 subjects. In addition, samples from 57 health care workers collected at 21-24 days after the first dose of Pfizer-BioNTech vaccine were also evaluated.

FindingsLFAs demonstrated a wide range of specificity (92.31% to 100%) and sensitivity (50 to 100%). The analysis of serum samples post vaccination was used to describe the most suitable tests to detect IgG response against S protein RBD. History of TB therapy was identified as a potential factor affecting the specificity of LFAs.

ConclusionsThis analysis identified which LFAs represent a valuable tool not only for the detection of prior SARS-CoV-2 infection, but also to detect IgG elicited in response to vaccination. These results demonstrated that different LFAs may have different applications and the possible risks of their use in high TB burden settings.


title: Meta-analysis of rapid direct-to-PCR assays for the qualitative detection of SARS-CoV-2

abstract:
Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the ensuing COVID-19 pandemic present significant challenges to current diagnostic and therapeutic patient care pathways including whether new in vitro diagnostic tests can accurately identify and rule out current SARS-CoV-2 infection.

The gold standard diagnostic test to identify a current SARS-CoV-2 infection is a central laboratory-based molecular assay employing reverse transcription polymerase chain reaction (RT-PCR) with very high accuracy of detection; however, which typically requires 1-2 days turn-around for results. Rapid RT-PCR assays and systems have been developed which can be deployed locally (near-patient or point of care (POC)), provide faster results and not impact on already stressed central laboratory capacity. Rapid test results can be returned within the same clinical encounter, facilitating timely decisions that optimise the patient care pathway and support more rapid COVID-19 diagnosis, isolation and contract tracing activities1.

Direct-to-PCR is an evolution of RT-PCR in which the patient sample is added directly to an amplification reaction without being subjected to prior nucleic acid extraction, purification, or quantification to reduce the time and monetary resources required to process samples. Rapid, direct-to-PCR systems further increase the speed of testing by combining rapid PCR instruments with direct-to-PCR assays, to generate results in less than two hours.

This appears to be the first meta-analysis assessing the accuracy of rapid direct-to-PCR in the detection of SARS-CoV-2. In total, 1,144 unique records were identified and screened using search string evaluation, 49 full-text reports and/or supplemental materials were assessed for inclusion. This resulted in 16 studies, reporting 22 datasets with 5322 patient samples (of which 2220 were identified as positive according to centralised laboratory testing) included in the analysis.

The overall percentage agreement (OPA) between the rapid direct RT-PCR and gold standard centralised laboratory RT-PCR was 95.10% with 91.22% positive percent agreement (PPA) and 98.16% negative percent agreement (NPA). When compared to commercially available tests were considered, these were assessed to be 96.95% OPA, 94.78 % PPA and 98.34 % NPA. Furthermore, the Cohens kappa statistical coefficient k = 0.94 (0.96 for commercial only), and Youden Index = 0.893 (0.924 for commercial only) indicate an almost perfect agreement. These results therefore indicate that direct-to-PCR assays performance is equivalent to the standard centralised laboratory PCR systems for the detection of SARS-CoV-2.

ObjectivesTo assess the efficacy of rapid direct-to-PCR assays and systems for the detection of SARS-CoV-2 in the hospital, care home and medical research population from November 2020 to July 2021.

Search methodsInitial electronic searches of the Cochrane COVID-19 Study Register (which includes daily updates from PubMed and Embase and preprints from medRxiv and bioRxiv) were undertaken on the 30th of April 2021, with a further search undertaken on 8th July 2021 (PRISMA flow diagram, Figure 2).

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org.highwire.dtl.DTLVardef@14e69fcorg.highwire.dtl.DTLVardef@1105ea2org.highwire.dtl.DTLVardef@1b50b5corg.highwire.dtl.DTLVardef@fce6b7_HPS_FORMAT_FIGEXP  M_FIG O_FLOATNOFigure 2.C_FLOATNO PRISMA flowchart

C_FIG Selection criteriaStudies, published in English, of subjects with either suspected SARS-CoV-2 infection, known SARS-CoV-2 infection or known absence of infection, or those who were being screened for infection were included. Commercially available and research use only rapid direct-to-PCR assays (without RNA extraction and purification reporting results within two hours) were included in the study.

Data collection, extraction and analysisStudies were screened independently, in duplicate with any disagreements resolved by discussion with a third author. Study characteristics were extracted by one author and checked by a second; extraction of study results and assessments of risk of bias and applicability were undertaken independently in duplicate.

Where studies were not publicly available, sites that undertook in-service evaluations of rapid direct-to-PCR system were contacted and asked to supply anonymised datasets. Both reviewers independently performed data extraction and verification and calculated 2x2 contingency tables with the number of true positives, false positives, false negatives and true negatives. They resolved any disagreements by discussion and by review with the third reviewer.

Main resultsIn total, 22 study cohorts were included (described in 16 study reports, including 5 unpublished reports), reporting results for 5322 samples (of which 2220 were confirmed SARS-CoV-2, as determined by central laboratory testing). Studies were mainly from Europe and North America and evaluated eight commercially available direct-to-PCR assay kits/cartridges, and six developed from other reagents.

ConclusionsThis appears to be the first meta-analysis assessing the accuracy of rapid direct-to-PCR in the detection of SARS-CoV-2. In total, 1,144 unique records were identified and screened using search string evaluation, 49 full-text reports and/or supplemental materials were assessed for inclusion. This resulted in 16 studies reporting 21 datasets with 5322 patient samples (2220 positive) included in the analysis.

The overall agreement between the commercially available rapid direct RT-PCR and gold standard centralised laboratory RT-PCR was 96.9% with 94.8% PPA and 98.4% NPA. Furthermore, the Cohens kappa statistical coefficient k = 0.96, indicating an almost perfect agreement and Youden Index = 0.93. These results show that direct-to-PCR assays performance is equivalent to the gold standard centralised laboratory RT-PCR systems for the detection of SARS-CoV-2.

Plain language summaryO_ST_ABSWhat is a rapid direct-to-PCR test for diagnosing COVID-19?C_ST_ABSRapid direct-to-PCR tests are rapid tests that aim to confirm or rule out the presence of SARS-CoV-2 within 2 hours without complicated processing of the sample.

How accurate is a rapid direct-to-PCR test for diagnosing COVID-19?We compared the accuracy of rapid direct-to-PCR tests with gold standard centralised laboratory RT-PCR for the detection of SARS-CoV-2 and found that direct-to-PCR was as accurate as standard RT-PCR assays.

Why is this question important?People with suspected COVID-19 need to know quickly whether they are infected, so that they can self-isolate, inform close contacts and possibly receive treatment. Currently, COVID-19 infection is confirmed by a laboratory test called RT-PCR, which uses specialist equipment and often takes at least 24 hours to produce a result. If they are accurate, faster diagnosis could allow people to take appropriate action more rapidly, with the potential to reduce the spread of COVID-19.1

What did we aim to find out?Our goal was to determine if commercially available and research use rapid direct-to-PCR tests are accurate enough to detect SARS-CoV-2 in comparison to gold standard laboratory RT-PCR.

What did we do?We looked for studies that measured the accuracy of any commercially produced and research use rapid direct-to-PCR tests, in people tested for COVID-19 using RT-PCR. People could be tested in hospital or in the community. Studies could test people with or without symptoms.

Tests had to use minimal equipment, be performed safely without risking infection from the sample, and have results available within two hours of the sample being collected.

What we found?We include 22 studies in the review. They investigated a total of 5322 nose or throat samples; COVID-19 was confirmed in 2220 of these samples. The studies investigated 15 different direct-to-PCR tests. They took place mainly in Europe and North America.

What did we find?Although overall results for diagnosing and ruling out COVID-19 were good (91.2% of infections correctly diagnosed and 98.3% correctly ruled out), we noted a difference in COVID-19 detection between tests, especially those available as commercial kits versus ones assembled from reagents from different sources. However, we cannot be certain about whether results will remain the same in a real-world setting. We could not investigate differences in people with or without symptoms, nor time since symptoms-onset because the studies did not consistently provide enough clinical information about their participants.

How reliable were the results of the studies?In general, the studies included followed rigorous methods, in accordance with the tests intended use to detect COVID-19 and included at least two independent results to confirm or rule out COVID-19 infection. The results from different test brands varied and few studies compared multiple rapid-PCR tests. Most of the studies did not provide sufficient information to determine whether the detection levels would vary in people with COVID-19 symptoms versus without symptoms.

What does this mean?On average the rapid direct-to-PCR were shown to be equivalent to gold standard laboratory-based RT-PCR tests and several direct-to-PCR tests show very high accuracy. However, for most of the tests, more evidence is needed particularly in people without symptoms, on the accuracy of repeated testing, and testing in non-healthcare settings such as schools (including self-testing).


title: Neutralizing response against E484K variant after original SARS-CoV-2 infection

abstract: Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) variants, which are spreading in the United Kingdom (UK) and elsewhere, have been found in infected individuals in Japan. The virus mutates, to facilitate its life in the host, during the process of repeated proliferation in the body of the host, including humans. In other words, it is natural that a human-compatible mutant strain always predominates in infection and proliferation. As a result, the viral mutants acquire strong proliferative potential in the host and are highly pathogenic. The number of people infected with the mutated SARS-CoV-2 variant E484K, which is different from the SARS-CoV-2 variants that are spreading in the UK, South Africa, and Brazil, is increasing in Tokyo. It has been pointed out that the effects of immunity and vaccines may be reduced against the Tokyo-type SARS-CoV-2 variant E484K. We have investigated the neutralization response to various mutations in the spike glycoprotein using the serum of people already infected with the original SARS-CoV-2. The results showed that SARS-CoV-2 variants with Y543F or N501Y mutations in the spike glycoprotein affect the neutralization reaction. However, single E484K mutations within the spiked glycoprotein of the Tokyo-type SARS-CoV-2 variant are unlikely to have a significant effect on the affinity of the host antibody for the virus.


title: SIR-based model with multiple imperfect vaccines.

abstract: Since the introduction of vaccination in the current COVID-19 outbreak, many countries have approved and implemented vaccination campaigns to mitigate and ultimately curtail the pandemic. Several types of vaccines have been proposed and many of them have finally been approved and used in different countries. The different types of vaccines have different vaccine parameters, and therefore, this situation induces the necessity of modeling mathematically the scenario of multiple imperfect vaccines. In this paper, we introduce a SIR-based model considering different vaccines, and study the basic properties of the model, including the stability of the Disease-Free Equilibrium (DFE), which is locally asymptotically stable if the reproduction number is less than 1. A sequence of further results aims to enumerate the conditions where the reproduction number can be decreased (or increased). Two important mathematical propositions indicate that in general vaccination might not be enough to contain an outbreak and that the addition of new vaccines could be counterproductive if the leakiness parameter is greater than a threshold{eta} . This model, despite its simplicity, was validated with data of the COVID-19 pandemic in five countries: Israel, Chile, Germany, Lithuania, and Czech Republic, observing that improvements for the vaccine campaigns can be suggested by the developed theory.


title: Red Blood Cell-Conditioned Media from Non-Alcoholic Fatty Liver Disease Patients Contain Increased MCP1 and Induce TNF-α Release.

abstract:
BACKGROUNDNon-Alcoholic Fatty Liver Disease (NAFLD) constitutes a global pandemic. An intricate network among cytokines and lipids possesses a central role in NAFLD pathogenesis. Red blood cells comprise an important source of both cytokines and signaling lipids and have an important role in the molecular crosstalk during immunometabolic deregulation. However, their role in NAFLD has not been investigated in deep.

METHODSConditioned media from erythrocytes derived from 10 NAFLD patients (4 men, 6 women, aged 57.875{+/-}15,16) and 10 healthy controls (4 men, 6 women, aged 39.3{+/-}15.55) were produced and used for the analysis of 9 cytokines (IFN-{gamma}, TNF-, CCL2, CCL5, IL-8, IL-1{beta}, IL-12p40, IL-17, MIP-1{beta}), 2 signaling lipids (Sphingosine 1-phosphate and Lysophosphatidic Acid), and cholesterol. Their effect on the cytokine profile released by RAW 264.7 macrophages was also studied.

RESULTSErythrocytes from patients with NAFLD augmented the levels of MCP1 in the growth medium in comparison to the erythrocytes derived from healthy controls (37{+/-}40 pg/ml vs 6.51{+/-}5.63). No statistically significant differences were found between patients and healthy controls with regard to S1P, LPA, cholesterol and 8 other cytokines. TNF-a release by RAW 264.7 cells was increased after incubation with patient-derived erythrocyte conditioned medium compared to medium without RAW 264.7 cells from either healthy of NAFLD subjects.

CONCLUSIONSErythrocytes could contribute to the liver infiltration by monocytes and to the activation of macrophages, partially due to release of CCL2, in the context of NAFLD.

category: gastroenterology


title: Fixed dosing of tocilizumab in ICU admitted COVID-19 patients is a superior choice compared to bodyweight based dosing; an observational population pharmacokinetic and pharmacodynamic study

abstract:
BackgroundTocilizumab improves outcome, including survival, in intensive care unit (ICU) admitted COVID-19 patients. The currently applied dosage of 8 mg/kg is based on use of this drug for other indications, however is has not formally been investigated for COVID-19. In this study pharmacokinetics and dynamics of tocilizumab were investigated in ICU admitted COVID-19 patients.

MethodsThis was an open-label, single-center observational pharmacokinetic and -dynamic evaluation study. Enrolled patients, with polymerase chain reaction confirmed Covid-19 were admitted to the ICU for mechanical ventilation or high flow nasal canula oxygen support. All patients were 18 years of age or older and received tocilizumab within 24 hours after admission to the ICU and received 6 mg dexamethasone daily as concomitant therapy.

Results29 patients were enrolled between 15 December 2020 and 15 March 2021. A total of 139 tocilizumab plasma samples were obtained covering the pharmacokinetic curve of day 0 up to day 20 after tocilizumab initiation. A population pharmacokinetic model with parallel linear and non-linear clearance was developed and validated. Average AUC0-inf 1stDOSE was 938 [{+/-}190] ug/mL*days. Tocilizumab half-life was estimated to be 4{middle dot}15 [{+/-}0{middle dot}24] days. All patients had tocilizumab exposure above 1 ug/ml for at least 15 days.

ConclusionThis study provides evidence to support a fixed dose of 600 mg tocilizumab in COVID-19 patients. Furthermore our findings suggest that alternative cost saving regimens with even lower doses are likely to be as effective as the current 8 mg/kg recommendation.

FundingNo external funding was received for this work

BackgroundIn the randomized controlled trial REMAP-CAP, the IL-6 receptor antagonist tocilizumab was shown to improve outcome, including survival in ICU admitted COVID-19 patients. Because obesity is a risk factor for development of severe COVID-19, concerns have been raised about overtreatment as well as undertreatment through weight-based dosing of tocilizumab. Furthermore pharmacokinetic and pharmacodynamic parameters of medications are often found to be different in severely ill patients when compared to mild or moderately ill patients. However, the effects of different dosing schedules were only investigated to a very limited extent in non-randomized observational studies. Hence, evaluation of the PK/PD parameters of tocilizumab in severely ill patients - is warranted.

Added value of this studyThis study provides valuable information about the population pharmacokinetics and dynamics of tocilizumab in dexamethasone cotreated ICU admitted COVID-19 patients. This research shows that there is no rationale for the 8 mg/kg dosing recommendation in ICU patients. Fixed dosing of 600 mg tocilizumab is a cost saving, logistically attractive and safe alternative without losing efficacy.

Implications of all the evidenceDue to the ongoing pandemic, shortages of tocilizumab and other IL-6 receptor antagonists may be anticipated. A fixed tocilizumab dose regimen has many practical and safety advantages, e.g. it will reduce dosing errors and avoid unnecessary wastage of medication. More importantly, according to the data presented in this study, relative underdosing of patients with low, or low-normal bodyweight compared to patients with high bodyweight will be avoided. Last but not least, in view of the large number of patients currently being treated with these agents, a significant cost saving can also be expected.


title: No safe level of alcohol consumption for brain health: observational cohort study of 25,378 UK Biobank participants

abstract:
ObjectivesTo estimate the relationship between moderate alcohol consumption and brain health, determining the threshold intake for harm and identifying whether population subgroups are at differential risk.

DesignObservational cohort study. Alcohol consumption was determined at baseline assessment visit using touchscreen questionnaire (2016-10). Multi-modal MRI brain and cognitive testing were performed subsequently (2014-20). Clinical data was extracted from linked Hospital Episode Statistics.

SettingUK Biobank study. Brain imaging was performed on identical scanners with identical protocols at three UK centres (2014-20).

Participants25,378 participants (mean age 54.9{+/-}7.4 years).

Main outcome measuresBrain health as defined by structural and functional MRI brain measures.

ResultsAlcohol consumption was negatively linearly associated with global brain grey matter volume (beta= -0.1, 95%CI= -0.11 to -0.09, p<2x10-16). The association with alcohol was stronger than other modifiable factor tested and robust to unobserved confounding. Widespread negative associations were observed with white matter microstructure (beta= -0.08, 95%CI= -0.09 to -0.06, p<2x10-16) and positive correlations with functional connectivity. Higher blood pressure and body mass index increased risk of alcohol-related harm (SBP*alcohol: beta= - 0.01, 95%CI = -0.02 to -0.004, p=0.005; BMI*alcohol: beta= -0.01, 95%CI = -0.02 to -0.002, p=0.02). Binging on alcohol had additive negative effects on brain structure on top of the absolute volume consumed (daily compared to never binging: beta= -0.19, 95%CI= -0.30 to -0.08, p<0.01). No evidence was found for differential effects of drinking wine, beer or spirits.

ConclusionsNo safe dose of alcohol for the brain was found. Moderate consumption is associated with more widespread adverse effects on the brain than previously recognised. Individuals who binge drink or with high blood pressure and BMI may be more susceptible. Detrimental effects of drinking appear to be greater than other modifiable factors. Current  low risk drinking guidelines should be revisited to take account of brain effects.

FundingAT is supported by a Wellcome Trust fellowship (216462/Z/19/Z). KPE is supported by the UK Medical Research Council (G1001354) and the European Commission (Horizon 2020 732592). This work was also supported by the Li Ka Shing Centre for Health Information and Discovery and NIH grant (TMS, TN: R01EB026859) and a Wellcome Trust award (TN: 100309/Z/12/Z).

category: psychiatry and clinical psychology


title: Varicella outbreak at a nursery school under routine immunization

abstract:
Background and objectiveIn Japan, routine administration of two-dose immunization for varicella to one-year-old children was introduced in October, 2014. The objective of this study was measurement of the effectiveness of routine two-dose immunization for varicella to onset and assessment of severity in a nursery school setting.

MethodThe study period extended from the beginning of April, 2017 through March, 2018. The study area was Nursery school B in a city A. Subjects were 120 children in all. We analyzed vaccine efficacy (VE) as an observational study and assessed severity using Fishers exact test. We also assessed VE for severity using linear regression. Severity was defined as the length of school absence attributable to varicella infection.

ResultsFor one dose or more, VE was 48.1% for all ages and 49.2% among children three years old and older. No significant VE was found. Vaccination using one dose or more can reduce severity significantly.

Discussion and conclusionLow VE was found in a nursery school setting, although results were not significant. VE for severity was confirmed, but a second dose might not reduce severity.


title: Insights into genetic factors contributing to variability in SARS-CoV-2 susceptibility and COVID-19 disease severity

abstract: Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we applied colocalization to compare summary statistics for 16 GWASs from the COVID-19 Host Genetics Initiative to investigate similarities and differences in their genetic signals. We identified 9 loci associated with susceptibility (one with two independent GWAS signals; one with an ethnicity-specific signal), 14 associated with severity (one with two independent GWAS signals; two with ethnicity-specific signals) and one harboring two discrepant GWAS signals (one for susceptibility; one for severity). Utilizing colocalization we also identified 45 GTEx tissues that had eQTL(s) for 18 genes strongly associated with GWAS signals in eleven loci (1-4 genes per locus). Some of these genes showed tissue-specific altered expression and others showed altered expression in up to 41 different tissue types. Our study provides insights into the complex molecular mechanisms underlying inherited predispositions to COVID-19-disease phenotypes.


title: Polygenic and environmental determinants of tics in the Avon Longitudinal Study of Parents and Children cohort

abstract:
BACKGROUNDTourette syndrome (TS) is caused by multiple genetic and environmental factors. Yet, little is known about the interplay of these factors in the occurrence of tics in the general population.

METHODSUsing logistic regression, we investigated whether polygenic risk score (PRS) of TS and pregnancy-related environmental factors together enhance the explained variance of tic occurrence (as opposed to separate analysis) in the Avon Longitudinal Study of Parents and Children. We included a cumulative adverse pregnancy risk score, maternal anxiety and depression, and maternal smoking and alcohol use during pregnancy. We investigated possible independent (i.e. additive) genetic and environmental effects, gene-environment correlations (rGE), gene-environment interactions (G x E), and mediation effects in explaining tic presence.

RESULTSModels that contained the PRS and the cumulative adverse pregnancy risk score, maternal anxiety, or maternal depression (but not maternal smoking and alcohol use) explained significantly more variance of tic presence compared to models including only the PRS, pointing to additive effects. Furthermore, we found that maternal anxiety, depression, and smoking were mediated by the cumulative adverse pregnancy risk score, and were thus all indirectly associated with tics through pregnancy complications. We did not find rGE or G x E.

CONCLUSIONSWe found evidence for both direct and indirect associations of environmental risk factors in relation to tics in the general population. Combining PRS and environmental risk factors improve our understanding of tics compared to considering these factors in isolation, suggesting both additive and mediation effects.


title: A Simple Mathematical Tool to Help Distribute Doses of Two-Dose Covid-19 Vaccines among Non-Immunized and Partly-Immunized Population

abstract:
BackgroundFull immunization with two doses of Covid vaccine has been found to be a critical factor in preventing morbidity and mortality from the Covid-19 infection. However, due to the shortage of vaccines, a significant portion of the population is not getting vaccination in many countries. Also, the distribution of vaccine doses between prospective first dose recipient and second dose recipient is not uniformly planned, as seen in Indias various states and union territories. It is recommended to give second vaccine doses within 4-8 weeks to first dose recipients for both the approved vaccines in India; hence the judicious distribution between non-immunized and partly immunized populations is essential. Managing the Covid-19 vaccination drive in an area with a large number of single-dose recipients compared to a smaller number of fully immunized people can become a huge administrative challenge. Therefore, this study was conducted to assess the number of people covered under the Covid vaccination drive in India and analyze the state-wise distribution of vaccines among the non-immunized and partly immunized population.

MethodsThe Covid 19 vaccination data till 7th may, 2021 was taken from the website of the Ministry of Health and Family Welfare, Govt of India. From the data available of the number of doses injected, other figures like the total number of people vaccinated, people with two doses of vaccine or full immunization (FI), and those with a single dose of vaccine or partial immunization (PI) were found. The percentage of the fully immunized and partly immunized population was also found. A ratio between fully immunized and partly immunized individuals (FI: PI) was proposed as a guide to monitor the progress of the vaccination and future dose distribution of  two-dose Covid-19 vaccines among partly immunized (PI) and non-immunized (NI) population.

ResultsIn India, till 7 May 2021, 16,49,73,058 doses of Covid-19 vaccines have been injected. A total of 13,20,87,824 people received these vaccine doses, with 9,92,02,590 people getting a single dose or were partly immunized (PI), and 3,28,85,234 got two doses each or were fully immunized (FI). Among the states, Tripura and Andhra Pradesh had the highest FI: PI (Fully Immunized: Partly Immunized) ratio of 0.86 and 0.52, followed by Tamil Nadu, Arunachal Pradesh, and West Bengal with figures of 0.48. 0.47 and 0.47, respectively. Telangana and Punjab had the lowest FI: PI ratio among the states at 0.2 each, with Chhattisgarh, Madhya Pradesh, and Haryana following at 0.21. 0.23 and 0.23, respectively. These values are much lower than the national average of 0.33 in India.

ConclusionThe FI: PI ratio could help governments decide how to use scarce vaccine resources among first-time and second-time recipients. This simple mathematical tool could ensure full immunization status to maximum people within the recommended 4-8 week time window after the first dose to avoid a large population group with partly immunized status.


title: Plasmodium infection induces cross-reactive antibodies to carbohydrate epitopes on the SARS-CoV-2 Spike protein

abstract: Individuals with acute malaria infection generated high levels of antibodies that cross-react with the SARS-CoV-2 Spike protein. Cross-reactive antibodies specifically recognized the sialic acid moiety on N-linked glycans of the Spike protein and do not neutralize in vitro SARS-CoV-2. Sero-surveillance is critical for monitoring and projecting disease burden and risk during the pandemic; however, routine use of Spike protein-based assays may overestimate SARS-CoV-2 exposure and population-level immunity in malaria-endemic countries.


title: Reinfection by the SARS-CoV-2 P.1 variant in blood donors in Manaus, Brazil

abstract:
BackgroundThe city of Manaus, north Brazil, was stricken by a second epidemic wave of SARS-CoV-2 despite high seroprevalence estimates, coinciding with the emergence of the Gamma (P.1) variant. Reinfections were postulated as a partial explanation for the second surge. However, accurate calculation of reinfection rates is difficult when stringent criteria as two time-separated RT-PCR tests and/or genome sequencing are required. To estimate the proportion of reinfections caused by the Gamma variant during the second wave in Manaus and the protection conferred by previous infection, we analyzed a cohort of repeat blood donors to identify anti-SARS-CoV-2 antibody boosting as a means to infer reinfection.

MethodsWe tested serial blood samples from unvaccinated repeat blood donors in Manaus for the presence of anti-SARS-CoV-2 IgG antibody. Donors were required to have three or more donations and at least one donation during each epidemic wave. Donors were tested with two assays that display waning in early convalescence, enabling the detection of reinfection-induced boosting. The serial samples were used to divide donors into six groups defined based on the inferred sequence of infection and reinfection with non-Gamma and Gamma variants.

ResultsFrom 3,655 repeat blood donors, 238 met all inclusion criteria, and 223 had enough residual sample volume to perform both serological assays. Using a strict serological definition of reinfection, we found 13.6% (95% CI 7.0% - 24.5%) of all presumed Gamma infections that were observed in 2021 were reinfections. If we also include cases of probable or possible reinfections, these percentages increase respectively to 22.7% (95% CI 14.3% - 34.2%) and 39.3% (95% CI 29.5% - 50.0%). Previous infection conferred a protection against reinfection of 85.3% (95% CI 71.3% - 92.7%), decreasing to respectively 72.5% (95% CI 54.7% - 83.6%) and 39.5% (95% CI 14.1% - 57.8%) if probable and possible reinfections are included.

ConclusionsReinfection due to Gamma is common and may play a significant role in epidemics where Gamma is prevalent, highlighting the continued threat variants of concern pose even to settings previously hit by substantial epidemics.


title: Reinfection by the SARS-CoV-2 Gamma variant in blood donors in Manaus, Brazil


title: Giving patients a voice within healthcare reform: the qualitative VOICE study

abstract:
BackgroundInclusion of patients in healthcare service and system planning is an increasingly important tool to improve healthcare systems worldwide. In 2012, a focused healthcare reform was initiated in Austria to strengthen the primary care sector.

ObjectivesThe aim of this study was to assess the perceptions, desires and needs of patients in terms of primary care as a necessary building block of the Austrian healthcare reform.

MethodsThis study was designed as an exploratory qualitative study using semi-structured interviews between the years 2013 and 2018. Research questions focused on patients positive and negative experiences with regard to GP consultations and the overall primary care system, as well as desires for improvement. Qualitative content analysis by Mayring was used to analyze the material.

ResultsAltogether, 41 interviews were conducted with seven main-categories identified. These categories include coordination and time management around consultation, human and professional aspects of consultation including coordination of care, access and availability including opening hours, infrastructure and hygiene of the waiting room, personnel, and overarching healthcare system factors.

ConclusionThis study demonstrates the importance of bringing the patients voice into ongoing healthcare reform. Without appreciating and responding to patients perceptions and needs, healthcare reform in Austria might be challenged to improve in areas such as time, coordination and navigation. Successful health care reform necessitates the inclusion of the patient voice.

category: primary care research


title: Contribution of white matter hyperintensities to ventricular enlargement in older adults

abstract:
Background and PurposeVentricular enlargement, especially enlargement of the lateral ventricles, is thought to be positively associated with white matter hyperintensities (WMH). Possible mechanisms behind the association are unclear. Lateral ventricles might increase due to generalised brain tissue loss not specific to periventricular WMH. Alternatively, they may expand into areas of tissue loss related to WMH, take up space and grow in size.

MethodsWe investigated relations between longitudinal lateral ventricle and WMH volume changes, alongside vascular risk factors, in community-dwelling older people. We assessed lateral ventricle and WMH volumes, accounting for total brain volume, blood pressure, medical assessments and self-reported history of stroke, cardiovascular disease, diabetes and smoking. We used longitudinal data at three time points, each three years apart, between ages 73 to 79, including MRI data from all available time points.

ResultsLateral ventricle volume increased steadily with age in all participants, WMH volume change was more variable. Decrease of WMH volume was found in around 20% and increase in remaining subjects. Using a repeated-measurements linear mixed model we found that over 6 years, lateral ventricle volume increased by 3% per year of age, 0.1% per mm Hg increase in mean blood pressure, 3.2% per 1% decrease of total brain volume, and 4.5% per 1% increase of WMH volume. Over time, lateral ventricle volumes were 19% smaller in women than men. No associations were found with other variables.

ConclusionsChanges in lateral ventricle volumes and WMH volumes over time are only modestly associated, independent of general brain atrophy.


title: Association of HLA class I homozygosity with unfavorable clinical outcomes in patients with non-small cell lung cancer treated with PD-1/PD-L1 inhibitor as first-line therapy

abstract:
BackgroundHomozygosity at HLA-I locus has been reported to be an unfavorable predictive biomarker of second-line or beyond immunotherapy in patients with different types of cancer. The linkage between HLA-I zygosity and survival in NSCLC patients treated with first-line immunotherapy with or without chemotherapy has not been reported.

MethodsNext generation sequencing with HLA genotyping was performed for patients with advanced NSCLC treated with immune checkpoint inhibitors with or without chemotherapy as first-line (N = 29). Progression free survival was compared between HLA-I homozygous (defined as homozygosity in at least one locus A, B, or C) and heterozygous patients. Kaplan-Meier curves were built, and log-rank test was used.

ResultsAmong 29 enrollees, 25 patients (86.2%) were HLA-I heterozygous and four patients (13.8%) were HLA-I homozygous. Treatment response was not available in five patients with HLA-I heterozygosity. Among 20 patients with HLA-I heterozygosity, five patients (20.0%) had partial response, 10 patients (50.0%) had stable disease, two patients (8.0%) had non-complete response/non-progressive disease, and three patients (12.0%) had progressive disease. Among four patients with HLA-I heterozygosity, one patient (25.0%) had partial response, one patient (25.0%) had stable disease, and two patients (50.0%) had progressive disease. The median progression free survival was not reached in heterozygous group and was 2.97 months in homozygous group (log-rank p = 0.68).

ConclusionsWe observed a trend toward an inverse association between HLA-I homozygosity and survival outcomes in patients with NSCLC treated with first-line therapy containing immunotherapy. Further prospective studies to validate such a relationship are warranted.

category: oncology


title: Machine learning enabled subgroup analysis with real-world data to inform better clinical trial design

abstract: Restrictive eligibility criteria for clinical trials may limit the generalizability of treatment effectiveness and safety to real-world patients. In this paper, we propose a machine learning approach to derive patient subgroups from real-world data (RWD), such that the patients within the same subgroup share similar clinical characteristics and safety outcomes. The effectiveness of our approach was validated on two existing clinical trials with the electronic health records (EHRs) from a large clinical research network. One is the donepezil trial for Alzheimers disease (AD), and the other is the Bevacizumab trial on colon cancer (CRC). The results show that our proposed algorithm can identify patient subgroups with coherent clinical manifestations and similar risk levels of encountering severe adverse events (SAEs). We further exemplify that potential rules for describing the patient subgroups with less SAEs can be derived to inform the design of clinical trial eligibility criteria.


title: Who should get vaccinated first? An effective network information-driven priority vaccination strategy

abstract: Approval of emergency use of the Novel Coronavirus Disease 2019 (COVID-19) vaccines in many countries has brought hope to ending the COVID-19 pandemic sooner. Considering the limited vaccine supply in the early stage of COVID-19 vaccination programs in most countries, a highly relevant question to ask is: who should get vaccinated first? In this article we propose a network information-driven vaccination strategy where a small number of people in a network (population) are categorized, according to a few key network properties, into priority groups. Using a network-based SEIR model for simulating the pandemic progression, the network information-driven vaccination strategy is compared with a random vaccination strategy. Results for both large-scale synthesized networks and real social networks have demonstrated that the network information-driven vaccination strategy can significantly reduce the cumulative number of infected individuals and lead to a more rapid containment of the pandemic. The results provide insight for policymakers in designing an effective early-stage vaccination plan.


title: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroprevalence: Navigating the absence of a gold standard

abstract:
BackgroundMultiple anti-SARS-CoV-2 immunoassays are available, but no gold standard exists. We assessed four assays using various methodological approaches to estimate SARS-COV-2 seroprevalence during the first COVID-19 wave in Canada.

MethodsThis serial cross-sectional study was conducted using plasma samples from healthy blood donors between April-September 2020. Qualitative assessment of SARS-CoV-2 IgG antibodies was based on four assays: Abbott Architect SARS-Cov-2 IgG assay (target nucleocapsid) (Abbott-NP) and three in-house IgG ELISA assays (target spike glycoprotein (Spike), spike receptor binding domain (RBD), and nucleocapsid (NP)). Seroprevalence was estimated using multiple composite reference standards (CRS) and by a series of Bayesian Latent Class Models (BLCM) (using uninformative, weakly, and informative priors).

Results8999 blood samples were tested. The Abbott-NP assay consistently estimated seroprevalence to be lower than the ELISA-based assays. Discordance between assays was common, 13 unique diagnostic phenotypes were observed. Only 32 samples (0.4%) were positive by all four assays. BLCM using uninformative priors predicted seroprevalence increased from 0.7% (95% credible interval (CrI); 0.4, 1.0%) in April/May to 0.8% (95% CrI 0.5, 1.2%) in June/July to 1.1% (95% CrI 0.7, 1.6) in August/September. Results from CRS were very similar to the BLCM. Assay characteristics varied considerably over time. Overall spike had the highest sensitivity (89.1% (95% CrI 79.2, 96.9%), while the sensitivity of the Abbott-NP assay waned from 65.3% (95% CrI 43.6, 85.0%) in April/May to 45.9% (95% CrI 27.8, 65.6) by August/September.

DiscussionWe found low SARS-CoV-2 seroprevalence rates at the end of the first wave and estimates derived from single assays may be biased.

SummaryMultiple anti-SARS-CoV-2 immunoassays are available, but no gold standard exists. We used four unique assays to estimate very low SARS-COV-2 seroprevalence during the first COVID-19 wave in Canada. Caution should be exercised when interpretating seroprevalence estimates from single assays.


title: Comparative sensitivity evaluation for 122 CE-marked SARS-CoV-2 antigen rapid tests

abstract:
ObjectiveIndependent evaluation of the sensitivity of CE-marked SARS-CoV-2 antigen rapid diagnostic tests (Ag RDT) offered in Germany.

MethodThe sensitivity of 122 Ag RDT was adressed using a common evaluation panel. Minimum sensitivity of 75% for panel members with CT<25 was used for differentiation of devices eligible for reimbursement in in the German healthcare system.

ResultsThe sensitivity of different SARS-CoV-2 Ag RDT varied over a wide range. The sensitivity limit of 75% for panel members with CT <25 was met by 96 of the 122 tests evaluated; 26 tests exhibited lower sensitivity, few of which were completely failing. Some devices exhibited high sensitivity, e.g. 100% for CT<30.

ConclusionThis comparative evaluation succeeded to distinguish less sensitive from better performing Ag RDT. Most of the Ag RDT evaluated appear to be suitable for fast identification of acute infections associated with high viral loads. Market access of SARS-CoV-2 Ag RDT should be based on minimal requirements for sensitivity and specificity.


title: Quantifying the potential for dominant spread of SARS-CoV-2 variant B.1.351 in the United States

abstract: Recent evidence suggests that some new SARS-CoV-2 variants with spike mutations, such as P.1 (Gamma) and B.1.617.2 (Delta), exhibit partial immune evasion to antibodies generated by natural infection or vaccination. By considering the Gamma and Delta variants in a multi-variant transmission dynamic model, we evaluated the dominance of these variants in the United States (US) despite mounting vaccination coverage and other circulating variants. Our results suggest that while the dominance of the Gamma variant is improbable, the Delta variant would become the most prevalent variant in the US, driving a surge in infections and hospitalizations. Our study highlights the urgency for accelerated vaccination and continued adherence to non-pharmaceutical measures until viral circulation is driven low.


title: Quantifying the potential dominance of immune-evading SARS-CoV-2 variants in the United States


title: Cohort-based surveillance of SARS-CoV2 transmission mirrors infection rates at the population level: a one-year longitudinal study

abstract:
BackgroundMore than one year into the COVID-19 pandemic, important data gaps remain on longitudinal prevalence of SARS-CoV-2 infection at the population level and in defined risk groups, efficacy of specific lockdown measures, and on (cost-)effective surveillance.

MethodsThe ELISA (Lubeck Longitudinal Investigation of SARS-CoV-2 Infection) study invited adult inhabitants (n=[~]300,000) from the Lubeck area (Northern Germany) and enrolled 3051 participants ([~]1%); 1929 population-matched and 1645 with high-exposure based on profession. The one-year study period (03/2020-02/2021) spanned massive influx of tourism in the summer, rise of infection rates in the fall/winter 2020/2021, and two lockdowns. Participants were screened seven times for SARS-CoV-2 infection using PCR and antibody testing and monitored with an app-based questionnaire (n=[~]91,000).

ResultsCohort (56% female; mean age: 45.6 years) retention was 75%-98%; 89 persons (3.5%) were antibody- and/or PCR-positive. Seropositivity was almost 2-fold higher in men and increased risk detected in several high-exposure groups (highest for nurses, followed by police, army, firemen, and students). In May 2020, 92% of the infections were missed by PCR testing; by February 2021, only 29% remained undiagnosed. "Contact to COVID-19-affected" was the most relevant risk factor. Other factors, such as frequent use of public transportation, shopping, close contacts at work, and extensive tourism in the summer did not impact infection rates.

ConclusionsWe i) provide a model for effective, regional surveillance; ii) identify infection risk factors informing public health measures; iii) demonstrate that easing of lockdown measures appears safe at times of low prevalence in the presence of continuous monitoring.


title: Characteristics of SARS-CoV-2 Positive Individuals in California From Two Periods During Notable Decline in Incident Infection

abstract: Despite declining SARS-CoV-2 incidence, continued epidemic monitoring is warranted. We collected SARS-CoV-2 test results from 150 drive-through testing centers across California from two observation periods: February 23rd-March 3rd 2021 and April 15th-April 30th 2021. We assessed SARS-CoV-2 positivity, stratified by Hispanic heritage among sociodemographic characteristics and potential exposures. We analyzed 114,789 test results (5.1% and 2.6% positive during the respective observation periods). Nearly half of all positive tests were among testers reporting a recent exposure (48.8% and 45.3% during the respective observation periods). Those findings may provide insight into evolving local transmission dynamics and support targeted public health strategies.


title: Methotrexate Hampers Immunogenicity to BNT162b2 mRNA COVID-19 Vaccine in Immune-Mediated Inflammatory Disease

abstract:
ObjectiveTo investigate the humoral and cellular immune response to mRNA COVID-19 vaccines in patients with immune-mediated inflammatory diseases (IMIDs) on immunomodulatory treatment.

MethodsEstablished patients at NYU Langone Health with IMID (n=51) receiving the BNT162b2 mRNA vaccination were assessed at baseline and after second immunization. Healthy subjects served as controls (n=26). IgG antibody responses to the spike protein were analyzed for humoral response. Cellular immune response to SARS-CoV-2 was further analyzed using high-parameter spectral flow cytometry. A second independent, validation cohort of controls (n=182) and patients with IMID (n=31) from Erlangen, Germany were also analyzed for humoral immune response.

ResultsAlthough healthy subjects (n=208) and IMID patients on biologic treatments (mostly on TNF blockers, n=37) demonstrate robust antibody responses (over 90%), those patients with IMID on background methotrexate (n=45) achieve an adequate response in only 62.2% of cases. Similarly, IMID patients do not demonstrate an increase in CD8+ T cell activation after vaccination.

ConclusionsIn two independent cohorts of IMID patients, methotrexate, a widely used immunomodulator for the treatment of several IMIDs, adversely affected humoral and cellular immune response to COVID-19 mRNA vaccines. Although precise cut offs for immunogenicity that correlate with vaccine efficacy are yet to be established, our findings suggest that different strategies may need to be explored in patients with IMID taking methotrexate to increase the chances of immunization efficacy against SARS-CoV-2 as has been demonstrated for augmenting immunogenicity to other viral vaccines.

KEY MESSAGESO_ST_ABSWhat is already known about this subject?C_ST_ABSO_LIThe impact of COVID-19 has been felt across the globe and new hope has arisen with the approval of mRNA vaccines against the SARS-CoV-2. Studies have shown immunogenicity and efficacy rates of over 90% in the immunocompetent adult population. However, there is a lack of knowledge surrounding the response of patients with immune-mediated inflammatory diseases (IMIDs) who may also be on immunomodulatory medications.
C_LIO_LIPatients with IMID have been shown to have attenuated immune responses to seasonal influenza vaccination.
C_LI

What does this study add?O_LIThis study looks at the humoral and cellular immune response to two doses of BNT162b2 mRNA COVID-19 Vaccine in participants with IMID (on immunomodulators) compared with healthy controls.
C_LIO_LIIndividuals with IMID on methotrexate demonstrate up to a 62% reduced rate of adequate immunogenicity to the BNT162b2 mRNA vaccination. Those on anti-cytokine or non-methotrexate oral medications demonstrate similar levels of immunogenicity as healthy controls (greater than 90%).
C_LIO_LISimilarly, vaccination did not induce an activated CD8+ T cell response in participants on background methotrexate, unlike healthy controls and patients with IMID not receiving methotrexate.
C_LI

How might this impact of clinical practice or future developments?O_LIThese results suggest that patients on methotrexate may need alternate vaccination strategies such as additional doses of vaccine, dose modification of methotrexate, or even a temporary discontinuation of this drug. Further studies will be required to explore the effect of these approaches on mRNA vaccine immunogenicity.
C_LI

category: rheumatology