The harmful effects of coronavirus disease 2019 (COVID-19) can reach the autonomic nervous system (ANS) and endothelial function. Therefore, the detrimental multiorgan effects of COVID-19 could be induced by deregulations in ANS that may persist after the acute SARS-CoV-2 infection. Additionally, investigating the differences in ANS response in overweight/obese, and physically inactive participants who had COVID-19 compared to those who did not have the disease is necessary. The aim of the study was to analyze the autonomic function of young adults after mild-to-moderate infection with COVID-19 and to assess whether body mass index (BMI) and levels of physical activity modulates autonomic function in participants with and without COVID-19. Patients previously infected with COVID-19 and healthy controls were recruited for this cross-sectional observational study. A general anamnesis was taken and BMI and physical activity levels were assessed. The ANS was evaluated through heart rate variability. A total of 57 subjects were evaluated. Sympathetic nervous system activity in post-COVID-19 group was increased (stress index; p=0.0273). They also presented lower values of parasympathetic activity (p<0.05). Overweight/obese subjects in the post-COVID-19 group presented significantly lower parasympathetic activity and reduced global variability compared to non-obese in control group (p<0.05). Physically inactive subjects in post-COVID-19 group presented significantly higher sympathetic activity than active subjects in control group. Parasympathetic activity was significantly increased in physically active subjects in control group compared to the physically inactive post-COVID-19 group (p<0.05). COVID-19 promotes changes in the ANS of young adults, and these changes are modulated by Overweight/obesity and physical activity levels. Key Points- Our main finding is that even in mild and moderate infections, young adults who had COVID-19 had greater sympathetic activity, less parasympathetic activity, and global variability when compared to uninfected individuals. - In participants who were overweight and obese and/or physically inactive, cardiac autonomic modulation showed worse indices. - Our study provides new insights regarding the role of body mass index and physical activity status on post-COVID-19 infection autonomic deregulation that may contribute to the understand of pathophysiology and treatment of of post-acute sequelae SARS-CoV-2 infection.

Structured abstractO_ST_ABSObjectivesC_ST_ABSOur objectives were (1) to evaluate the prevalence of menstrual changes following vaccination against COVID-19, (2) to test potential risk factors for any such changes, and (3) to identify patterns of symptoms in participants written accounts. DesignA secondary analysis of a retrospective online survey titled Covid-19 Pandemic and Womens Reproductive Health, conducted in March 2021 in the UK before widespread media attention regarding potential impacts of SARS-CoV-2 vaccination on menstruation. SettingParticipants were recruited via a Facebook ad campaign in the UK. ParticipantsEligibility criteria for survey completion were age greater than 18 years, having ever menstruated and currently living in the UK. In total, 26,710 people gave consent and completed the survey. For this analysis we selected 4,989 participants who were pre-menopausal and vaccinated. These participants were aged 28 to 43, predominantly from England (81%), of white background (95%) and not using hormonal contraception (58%). Main outcome measureReports of any menstrual changes (yes/no) following COVID-19 vaccination and words used to describe menstrual changes. ResultsAmong pre-menopausal vaccinated individuals (n=4,989), 80% did not report any menstrual cycle changes up to 4 months after their first COVID-19 vaccine injection. Current use of combined oral contraceptives was associated with lower odds of reporting any changes by 48% (OR = 0.52, 95CI = [0.34 to 0.78], P<0.001). Odds of reporting any menstrual changes were increased by 44% for current smokers (OR = 1.16, 95CI = [1.06 to 1.26], P<0.01) and by more than 50% for individuals with a positive COVID status [Long Covid (OR = 1.61, 95CI = [1.28 to 2.02], P<0.001), acute COVID (OR = 1.54, 95CI = [1.27 to 1.86], P<0.001)]. The effects remain after adjusting for self-reported magnitude of menstrual cycle changes over the year preceding the survey. Written accounts report diverse symptoms; the most common words include cramps, late, early, spotting, and irregular, with a low level of clustering among them. ConclusionsFollowing vaccination for COVID-19, menstrual disturbance occurred in 20% of individuals in a UK sample. Out of 33 variables investigated, smoking and a previous history of SARS-CoV-2 infection are found to be risk factors while using oestradiol-containing contraceptives was found to be a protective factor. Diverse experiences were reported, from menstrual bleeding cessation to heavy menstrual bleeding. Summary boxO_ST_ABSWhat is already known on this topic?C_ST_ABSO_LIMenstrual disturbances including changes in frequency and/or dysmenorrhoea following vaccination have been reported as early as 1913 for the typhoid vaccine (1). Since then there have only been a few studies investigating this topic, using small sample sizes (hepatitis vaccine (2)) or reporting mixed results (HPV vaccine (3,4)). C_LIO_LIThe UKs Medicine and Healthcare products Regulatory Agency (MHRA) is closely monitoring reports of menstrual disorders, with more than 30,000 reports made to its yellow card surveillance scheme by 2 September 2021 following vaccination with both mRNA and adenovirus-vectored COVID-19 vaccines (5). C_LIO_LIIn a recent preprint of a retrospective case-control study of 21,380 pre-menopausal participants living in the US, 45.8% of 9,579 people with regular menstrual cycles experienced heavier bleeding after COVID-19 vaccination. In addition, 70.5% of 1,545 non-menstruating people using long-acting reversible contraceptives (LARC) experienced breakthrough bleeding after COVID-19 vaccination (6). This informative study may be affected by selection bias and may not be generalisable. C_LI What this study addsO_LIIn a large sample of participants vaccinated against COVID-19 surveyed in the UK before widespread media attention to related menstrual changes, the prevalence of menstrual changes was 1 in 5. C_LIO_LIOut of 33 socio-demographic, health, vaccine, COVID- and pandemic-related and reproductive variables, the odds of reporting any menstrual changes following COVID-19 vaccination were associated with a history of SARS-CoV-2 infection, smoking behaviour and the type of contraceptives used. C_LIO_LIMenstrual changes that were reported were diverse, ranging from increased bleeding to the cessation of bleeding. C_LIO_LIThe study highlights the need for greater consideration of the menstrual cycle in health interventions. C_LI

Objectives: To assess what were the main individual factors influencing people9s perception of the importance of using COVID-19 immunity certificates. Design: Cross-sectional online survey. Setting: Nationally representative survey in the UK, conducted on the 3rd of August 2021. Participants: Responses from 534 participants, aged 18 and older, residents of the UK. Interventions: This was a cross-sectional survey and each participant replied to the same set of questions. Primary outcome measure and independent variables: The primary outcome measure (dependent variable) was the participants9 perceived importance of using immunity certificates, computed as an index of six items. The following individual drivers were used as the independent variables: a) personal beliefs about COVID-19 (using constructs adapted from the Health Belief Model), b) personal views on vaccination, c) willingness to share immunity status with service providers, and d) variables related to respondents9 lifestyle and socio-demographic characteristics. Results: Perceived importance of immunity certificates was higher among respondents who felt that contracting COVID-19 would have a severe negative impact on their health (β=0.2564, p=0.0000) and felt safer if vaccinated (β=0.1552, p=0.0000). The prospect of future economic recovery positively influenced perceived importance of immunity certificates. Respondents who were employed or self-employed (β=-0.2412, p=0.0010), or experienced an increase in income after the COVID-19 pandemic (β=-0.1287, p=0.0020) perceived less important the use of immunity certificates compared to those who were unemployed or had retired or those who had experienced reduction in their income during the pandemic. Conclusions: The findings of our survey suggest that more vulnerable members in our society (unemployed or retired and those believing that COVID-19 would have a severe impact on their health) and people who experienced a reduction in income during the pandemic perceived the severity of not using immunity certificates in their daily life as higher.

Motivation. Influenza is a rapidly mutating RNA virus responsible for annual epidemics causing substantial morbidity, mortality, and economic loss. Characterizing influenza virus mutational diversity and evolutionary processes within and between human hosts can provide tools to help track and understand transmission events. In this study we investigated possible differences between the intrahost genomic content of influenza virus in upper respiratory swabs and exhaled aerosols thought to be enriched for virus from the lower respiratory tract. Results. We examined the sequences of specimens collected from influenza A virus (IAV) infected college community members from December 2012 through May 2013. We analyzed four types of IAV samples μm aerosols (N=38), coarse >5μm aerosols (N=27), nasopharyngeal (N=53), and oropharyngeal swabs (N=47)) collected from 42 study participants with 60 sampling instances. Eighteen (42.9%) participants had data from four sample types (nasopharyngeal swab, oropharyngeal swab, coarse aerosol, fine aerosol) included in the analysis, 10 (23.8%) had data from 3 sample types, 10 (23.8%) had data from 2 sample types, and 4 (9.5%) had data from one type of sample included in the analysis. We found that 481 (53.3%) consensus single nucleotide polymorphisms are shared by all sample types and 600 (66.5%) are shared by at least three different sample types. We observed that within a single patient consensus and non-consensus single nucleotide variants are shared across all sample types. Finally, we inferred a phylogenetic tree using consensus sequences and found that samples derived from a single patient are monophyletic. Conclusions. Single nucleotide polymorphisms did not differentiate between samples with varying origin along the respiratory tree. We found that signatures of variation in non-consensus intrahost single nucleotide variants are host and sample, but not site-specific. We conclude that the genomic information available does not allow us to discern a transmission route. Future investigation into whether any site-specific mutational signatures emerge over a longer period of infection, for example in immunocompromised hosts, can be interesting from the virus evolution perspective.

Abstract Older age is a strong risk factor for several diseases, including cancer. In cancer, older age is also frequently associated with a more aggressive, treatment-refractory tumor phenotype. The etiology and biology of age-associated differences among cancers are poorly understood. To address this knowledge gap, we sought to delineate the differences in tumor molecular characteristics between younger and older patients across a variety of tumor types. We found that tumors in younger and older patients exhibit widespread molecular differences. First, we observed that tumors in younger individuals, unlike those in older ones, exhibit an accelerated molecular aging phenotype associated with some hallmarks of premature senescence. Second, we found that tumors from younger individuals are enriched for driver gene mutations resulting in homologous recombination defects. Third, we observed a trend towards a decrease in immune infiltration and function in older patients and found that, immunologically, young tumor tissue resembles aged healthy tissue. Taken together, we find that tumors from young individuals possess unique characteristics compared to tumors in older individuals, which can potentially be leveraged for differential therapeutic strategies.

Summary There is an urgent need to expand testing for SARS-CoV-2 and other respiratory pathogens as the global community struggles to control the COVID-19 pandemic. Current diagnostic methods can be affected by supply chain bottlenecks and require the assistance of medical professionals, impeding the implementation of large-scale testing. Self-collection of saliva may solve these problems, as it can be completed without specialized training and uses generic materials. In this study, we observed thirty individuals who self-collected saliva using four different collection devices and analyzed their feedback. Two of these devices, a funnel and bulb pipette, were used to evaluate at-home saliva collection by 60 individuals. All devices enabled the safe, unsupervised self-collection of saliva. The quantity and quality of the samples received were acceptable for SARS-CoV-2 diagnostic testing, as determined by RNase P detection. Here, we demonstrate inexpensive, generic, buffer free collection devices suitable for unsupervised and home saliva self-collection.

Vaccination is essential for controlling the coronavirus disease (COVID-19) pandemic. An effective time-course strategy for the allocation of COVID-19 vaccines is crucial given that the global vaccine supply will still be limited in some countries/regions in the near future and that mutant strains have emerged and will continue to spread worldwide. Both asymptomatic and symptomatic transmission have played major roles in the COVID-19 pandemic, which can only be properly described as a typical non-Markovian process. However, the prioritization of vaccines in the non-Markovian framework still lacks sufficient research, and the underlying mechanism of the time-course vaccine allocation optimization has not yet been uncovered. In this paper, based on an age-stratified compartmental model calibrated through clinical and epidemiological data, we propose optimal vaccination strategies (OVS) through steady-state prediction in the non-Markovian framework. This OVS outperforms other empirical vaccine prioritization approaches in minimizing cumulative infections, cumulative deaths, or years of life lost caused by the pandemic. We found that there exists a fast decline in the prevention efficiency of vaccination if vaccines are solely administered to a selected age group, which indicates that the widely adopted strategy to continuously vaccinate high-risk group is not optimal. Through mathematical analysis of the model, we reveal that dynamic vaccine allocations to combinations of different age groups is necessary to achieve optimal vaccine prioritization. Our work not only provides meaningful references for vaccination in countries currently lacking vaccines and for vaccine allocation strategies to prevent mutant strains in the future, but also reveals the mechanism of dynamic vaccine allocation optimization, forming a theoretical and modelling framework empirically applicable to the optimal time-course prioritization.

This article is a preprint and has not been certified by peer review [what does this mean?]. It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice.

During the process of open peer review on MedRxiv we quickly received a number of messages from reviewers concerned that there was a problem with our reported incidence of myocarditis post mRNA vaccination. Our reported incidence appeared vastly inflated by an incorrectly small denominator (ie number of doses administered over the time period of the study). We reviewed the data available at Open Ottawa and found that there had indeed been a major underestimation, with the actual number of administered doses being more than 800,000 (much higher than quoted in the paper).In order to avoid misleading either colleagues or the general public and press, we the authors unanimously wish to withdraw this paper on the grounds of incorrect incidence data. We thank the many peer reviewers who went out of their way to contact us and point out our error. We apologize to anyone who may have been upset or disturbed by our report.In summary, the authors have withdrawn this manuscript because of a major error pertaining to the quoted incidence data. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.

Abstract To assess the evolving SARS-CoV-2 seroprevalence and seroincidence related to the national lock-down in Belgium, a nationwide seroprevalence study, stratified by age, sex and region using 3000-4000 residual samples was performed during 7 periods between 30 March and 17 October 2020. Residual sera from ambulatory patients were analyzed for IgG antibodies against S1 proteins of SARS-CoV-2 with a semi-quantitative commercial ELISA. Weighted seroprevalence (overall, by age category and sex) and seroincidence during 7 consecutive periods were estimated for the Belgian population while accommodating test-specific sensitivity and specificity. The weighted overall seroprevalence initially increased from 1.8% (95% CrI 1.0-2.6) to 5.3% (95% CrI 4.2-6.4), implying a seroincidence of 3.4% (95% CrI 2.4-4.6) between the 1st and 2nd collection period over a period of 3 weeks during the lockdown period (start lockdown mid March 2020). Thereafter, seroprevalence stabilized, however, significant decreases are observed when comparing the 3rd with the 5th and also with the 6th period resulting in negative seroincidence estimates after lockdown was lifted. We estimated for the last collection period mid October 2020 a weighted overall seroprevalence of 4.2% (95% CrI 3.1-5.2). During lockdown, an initial small but increasing fraction of the Belgian population showed serologically detectable signs of exposure to SARS-CoV-2, which did not further increase when confinement measures eased and full lockdown was lifted.