Aging shapes infection profiles of influenza A virus and SARS-CoV-2 in human lung slices (preprint)

The recent coronavirus disease 2019 (COVID-19) outbreak revealed the susceptibility of elderly patients to respiratory virus infections, showing cell senescence or subclinical persistent inflammatory profiles and favouring the development of severe pneumonia. In our study, we evaluated the potential influence of lung aging on the efficiency of replication of influenza A virus (IAV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV 2), as well as determined the pro-inflammatory and antiviral responses of the distal lung tissue. Using precision-cut lung slices (PCLS) from donors of different ages, we found that pandemic H1N1 and avian H5N1 IAV replicated in the lung parenchyma with high efficacy. In contrast to these IAV strains, SARS-CoV-2 early isolate and Delta variant of concern (VOC) replicated less efficiently in PCLS. Interestingly, both viruses showed reduced replication in PCLS from older compared to younger donors, suggesting that aged lung tissue represents a sub optimal environment for viral replication. Regardless of the age-dependent viral loads, PCLS responded to infection with both viruses by an induction of IL-6 and IP-10/CXCL10 mRNAs, being highest for H5N1. Finally, while SARS-CoV-2 infection was not causing detectable cell death, IAV infection caused significant cytotoxicity and induced significant early interferon responses. In summary, our findings suggest that aged lung tissue might not favour viral dissemination, pointing to a determinant role of dysregulated immune mechanisms in the development of severe disease.

Perceptions of COVID-19 Vaccination among Organ Transplant Recipients (preprint)

Understanding vaccine hesitancy in organ transplant recipients (OTR) is critical, given clear, alt-hough attenuated, benefits from vaccination. Adult OTR were surveyed regarding vaccine-related values and a novel outcome variable called Vaccine Acceptance Composite Score (VACS) was built as the average Likert score of 7 domains of vaccination confidence. Of 46 OTR included (93.5% kidney transplant recipients), 32.6% were female, 13.3% Black, 6.77% Hispan-ic/Latino/a/x; median age was 58 years. Patients were most concerned about COVID-19 vac-cine-associated risks (46.3%), its potential effect on allograft (47.6%) and motives of government officials involved with vaccine policy (55.6%). Politically conservative patients were likely to have a significantly lower VACS, while those who lived with someone ≥65 had a higher VACS. The VACS was not significantly associated with race, income, religious beliefs, comorbidities, COVID-19 history, or influenza vaccination status. Higher VACS was significantly associated with ≥3 and ≥4 COVID-19 immunizations. This study highlighted political beliefs and elderly household members as correlates of vaccine acceptance among OTR. The VACS may be a useful tool to help standardize multifaceted analyses in vaccination-focused behavioral research, as well as identify individuals and groups at risk for vaccine hesitancy, who may benefit from tai-lored outreach and educational interventions.

Saving High-Risk Patients from COVID-19 Severity and Death Mainly with Plant-Based Diets and Supplements (preprint)

Our report presents the findings from a treatment program that involved plant-based diets (PBDs) and supplements for 1,750 elderly cardiology patients diagnosed with COVID-19 between April 2020 and June 2023. At the start of the program, there was no published data supporting the use of PBDs for COVID-19 patients. However, after 18 months, studies were released that indicated the effectiveness of PBDs in decreasing the incidence and severity of COVID-19. Our treatment protocol differed from these studies in several ways. We carefully controlled the quality, quantity, and processing method of the foods we provided, opting for raw instead of cooked vegetables. Additionally, we incorporated supplementation that complemented the nutrients lacking in a PBD and enhanced the anti-viral, anti-inflammatory, antioxidant, antithrombotic, and immunomodulatory properties of a PBD. Our patients recovered faster (12±1.4 days vs. 20.9±4.3 days), with lower severity (2% vs. 10-20%), hospitalizations (0 vs. 5-10%), and deaths (0 vs. 15-17%) compared to the general population. These favorable outcomes are particularly noteworthy given Indonesia's high COVID-19 morbidity and mortality rates, among the highest in Asia. The findings of this report provide valuable insights for practitioners in managing high-risk elderly COVID-19 patients, particularly in avoiding severity and mortality.

A Critical Analysis of UK Media Characterisations of Long Covid in Children and Young People (preprint)

Long Covid is the continuation or development of symptoms related to a SARSCoV2 infection. Those with Long Covid may face epistemic injustice, where they are unjustifiably viewed as unreliable evaluators of their own illness experiences. Media articles both reflect and influence perception and subsequently how people regard children and young people (CYP) with Long Covid, and may contribute to epistemic injustice.? We aimed to explore how the UK media characterises Long Covid in CYP through examining three key actor groups: parents, healthcare professionals, and CYP with Long Covid, through the lens of epistemic injustice. A systematic search strategy resulted in the inclusion of 103 UK media articles. We used an adapted corpus-assisted Critical Discourse Analysis in tandem with thematic analysis. Specifically, we utilised search terms to locate concordances of key actor groups. In the corpus, parents highlighted minimisation of Long Covid, barriers to care, and experiences of personal attacks. Mothers were presented as also having Long Covid. Fathers were not mentioned once. Healthcare professionals emphasised the rarity of Long Covid in CYP, avoided pathologizing Long Covid, and overemphasised psychological components. CYP rarely were consulted in media articles but were presented as formerly very able. Manifestations of Long Covid in CYP were validated or invalidated in relation to adults. Media characterisations contributed to epistemic injustice. The disempowering portrayal of parents promote stigma and barriers to care. Healthcare professionals' narratives often contributed to negative healthcare experiences and enacted testimonial injustice, where CYP and parents credibility was diminished due to unfair identity prejudice, in their invalidation of Long Covid. Media characterisations reveal and maintain a lack of societal framework for understanding Long Covid in CYP. The findings of this study illustrate the discursive practices employed by journalists that contribute to experiences of epistemic injustice. Based on our findings, we propose recommendations for journalists.

Effects of the Covid-19 pandemic on the continuity of sexual and reproductive health care in the maternity ward of a health and social promotion centre in Burkina Faso: a qualitative study (preprint)

The COVID-19 pandemic has significantly impacted the continuity of maternity care in Burkina Faso. This study aimed to compare the volumes of in-person visits and explore the experiences of healthcare providers and users regarding the continuity of healthcare in the maternity ward of a Health and Social Promotion Center (HSPC) before, during, and after the lockdown during the COVID-19 pandemic in Ouagadougou, Burkina Faso. Methods We conducted a multimethod, cross-sectional exploratory study with a phenomenological approach. Monthly health administrative data regarding family planning visits, antenatal visits, deliveries, and postnatal care before, during, and after COVID-19 were collected and compared. Qualitative data were collected through semi-structured interviews with family healthcare providers and users and thematically analyzed. Results The study found that the pandemic led to a decline in the demand for healthcare, as people were afraid of contracting COVID-19. This was particularly true for pregnant women who had recently given birth. The study also found that the pandemic disrupted the supply of essential medicines and medical supplies, which made it difficult for healthcare providers to provide quality care. The qualitative analysis allowed us to highlight three themes: the representation of respondents on COVID-19, their perception of the effectiveness of barrier measures and their analysis of the continuity of care in times of COVID-19: the picture of respondents on COVID-19, their perception of the efficacy of barrier measures and their analysis of the continuity of care in times of COVID-19. Despite these challenges, the study found that healthcare providers and users could find ways to maintain continuity of care. Conclusion The study concludes that the COVID-19 pandemic has significantly impacted the continuity of maternity care in Burkina Faso. However, healthcare providers and users have found ways to maintain continuity of care, and the study provides recommendations for improving continuity of care in the future.

A spatio-temporal model to detect potential outliers in disease mapping (preprint)

Spatio-temporal disease mapping models are commonly used to estimate the relative risk of a disease over time and across areas. For each area and time point, the disease count is modelled with a Poisson distribution whose mean is the product of an offset and the disease relative risk. This relative risk is commonly decomposed in the log scale as the sum of fixed and latent effects. The Rushworth model allows for spatio-temporal autocorrelation of the random effects. We build on the Rushworth model to accommodate and identify potentially outlying areas with respect to their disease relative risk evolution, after taking into account the fixed effects. An area may display outlying behaviour at some points in time but not all. At each time point, we assume the latent effects to be spatially structured and include scaling parameters in the precision matrix, to allow for heavy-tails. Two prior specifications are considered for the scaling parameters: one where they are independent across space and one with spatial autocorrelation. We investigate the performance of the different prior specifications of the proposed model through simulation studies and analyse the weekly evolution of the number of COVID-19 cases across the 33 boroughs of Montreal and the 96 French departments during the second wave. In Montreal, 6 boroughs are found to be potentially outlying. In France, the model with spatially structured scaling parameters identified 21 departments as potential outliers. We find that these departments tend to be close to each other and within common French regions.

SARS-CoV-2 Antigen Rapid Detection Tests: test performance during the COVID-19 pandemic and the impact of COVID-19 vaccination (preprint)

IntroductionDuring the COVID-19 pandemic, SARS-CoV-2 antigen rapid detection tests (RDTs) emerged as point-of-care diagnostics in addition to the RT-qPCR as the gold standard for SARS-CoV-2 diagnostics. Facing the course of the COVID-19 pandemic to an endemic characterised by several SARS-CoV-2 virus variants of concern (VOC) and an increasing public COVID-19 vaccination rate the aim of the study was to investigate the long-term test performance of SARS-CoV-2 RDT in large-scale, clinical screening use during and its influencing factors, above all SARS-CoV-2 VOC and COVID-19 vaccination. MethodsIn a prospective performance assessment conducted at a single centre tertiary care hospital, RDTs from three manufacturers (NADAL(R), Panbio, MEDsan(R)) were compared to RT-qPCR among individuals aged [≥] 6 month. The evaluation involved the determination of standardised viral load from oropharyngeal swabs as well as the evaluation of their influencing factors, especially the COVID-19 vaccination, for detecting SARS-CoV-2 in a clinical point-of-care environment spanning from 12 November 2020 to 30 June 2023 among patients, staff, and visitors of the hospital. ResultsAmong the 78,798 RDT/RT-qPCR tandems analysed, 2,016 (2.6%) tandems tested positive for SARS-CoV-2, with an overall sensitivity of 34.5% (95% CI 32.4-36.6%). A logistic regression revealed that typical COVID-19 symptoms significantly declined over the course of the study and throughout the COVID-19 pandemic, and that among the vaccinated, significantly fewer presented with an infection exhibiting typical symptoms. The employed lasso regression model indicated that only higher viral load and typical COVID-19 symptoms significantly increase the likelihood of a positive RDT result in the case of a SARS-CoV-2 infection directly. ConclusionOur findings indicate that only viral load and COVID-19 symptoms directly influence RDT performance while the obtained effects of COVID-19 vaccination and Omicron VOC both reducing RDT performance were mediated by these two factors. RDTs remain an adequate diagnostic tool for detecting SARS-CoV-2 in individuals showing respiratory symptoms. RDTs show promise beyond SARS-CoV-2, proving adaptable for detecting other pathogens like Influenza and RSV, highlighting their ongoing importance in infection control and prevention efforts.

Impact of COVID-19 on diabetes mellitus outcomes and care in sub-Saharan Africa: A scoping review (preprint)

Background: The COVID-19 pandemic impacted diabetes mellitus clinical outcomes and chronic care globally. However, little is known about its impact in low-resource settings such as sub-Saharan Africa. Hence, to address this, we systematically conducted a scoping review to explore the COVID-19 impact on diabetes outcomes and care in countries of sub-Saharan Africa. Methods We applied our search strategy to PubMed, Web of Science, CINAHL, African Index Medicus, Google Scholar, Cochrane Library, Scopus, Science Direct, ERIC and Embase to obtain relevant articles published from January 2020 to March 2023. Two independent reviewers were involved in the screening of retrieved articles. Data from eligible articles were extracted from quantitative, qualitative and mixed methods studies. Numerical data were summarised using descriptive statistics, while a thematic framework was used to categorise and identify themes for qualitative data. Results We found 42 of the retrieved 360 articles eligible, mainly from South Africa, Ethiopia and Ghana (73.4%). COVID-19 increased the risk of death (OR 1.30,9.0, 95% CI), hospitalisation (OR 3.30,3.73: 95% CI), and severity (OR: 1.30,4.05, 95% CI) in persons with diabetes mellitus. COVID-19 also increased the risk of developing diabetes mellitus in hospitalised cases. The pandemic, on the other hand, was associated with disruptions in patient self-management routine and diabetes mellitus care service delivery. Three major themes emerged, namely, (i) patient-related health management challenges, (ii) diabetes mellitus care service delivery challenges, and (iii) reorganisation of diabetes mellitus care delivery. Conclusion COVID-19 increased mortality and morbidity among people living with diabetes mellitus. In addition, the COVID-19 pandemic worsened diabetes mellitus care management. Sub-Saharan African countries should, therefore, institute appropriate policy considerations for persons with diabetes mellitus during widespread emergencies.

Early detection of disease outbreaks and non-outbreaks using incidence data (preprint)

Forecasting the occurrence and absence of novel disease outbreaks is essential for disease management. Here, we develop a general model, with no real-world training data, that accurately forecasts outbreaks and non-outbreaks. We propose a novel framework, using a feature-based time series classification method to forecast outbreaks and non-outbreaks. We tested our methods on synthetic data from a Susceptible-Infected-Recovered model for slowly changing, noisy disease dynamics. Outbreak sequences give a transcritical bifurcation within a specified future time window, whereas non-outbreak (null bifurcation) sequences do not. We identified incipient differences in time series of infectives leading to future outbreaks and non-outbreaks. These differences are reflected in 22 statistical features and 5 early warning signal indicators. Classifier performance, given by the area under the receiver-operating curve, ranged from 0.99 for large expanding windows of training data to 0.7 for small rolling windows. Real-world performances of classifiers were tested on two empirical datasets, COVID-19 data from Singapore and SARS data from Hong Kong, with two classifiers exhibiting high accuracy. In summary, we showed that there are statistical features that distinguish outbreak and non-outbreak sequences long before outbreaks occur. We could detect these differences in synthetic and real-world data sets, well before potential outbreaks occur.

Clustering Analysis of US COVID-19 Rates, Vaccine Participation, and Socioeconomic Factors (preprint)

The COVID-19 pandemic has presented unprecedented challenges worldwide, with its impact varying significantly across different geographic and socioeconomic contexts. This study employs a clustering analysis to examine the diversity of responses to the pandemic within the United States, aiming to provide nuanced insights into the effectiveness of various strategies. We utilize an unsupervised machine learning approach, specifically K-Means clustering, to analyze county-level data that includes variables such as infection rates, death rates, demographic profiles, and socio-economic factors. Our analysis identifies distinct clusters of counties based on their pandemic responses and outcomes, facilitating a detailed examination of "high-performing" and "lower-performing" groups. These classifications are informed by a combination of COVID-specific datasets and broader socio-economic data, allowing for a comprehensive understanding of the factors that contribute to differing levels of pandemic impact. The findings underscore the importance of tailored public health responses that consider local conditions and capabilities. Additionally, this study introduces an innovative visualization tool that aids in hypothesis testing and further research, enhancing the ability of policymakers and public health officials to deploy more effective and targeted interventions in future health crises.

Effectiveness of the 2023-2024 Omicron XBB.1.5-containing mRNA COVID-19 vaccine (mRNA-1273.815) in preventing COVID-19-related hospitalizations and medical encounters among adults in the United States: An interim analysis (preprint)

Background/ObjectivesCOVID-19 continues to pose a significant burden that impacts public health and the healthcare system as the SARS-CoV-2 virus continues to evolve. Regularly updated vaccines are anticipated to boost waning immunity and provide protection against circulating variants. This study evaluated vaccine effectiveness (VE) of mRNA-1273.815, a 2023-2024 Omicron XBB.1.5-containing mRNA COVID-19 vaccine, at preventing COVID-19-related hospitalizations and any medically attended COVID-19 in adults [≥]18 years, overall, and by age and underlying medical conditions. MethodsThis retrospective cohort study used the Veradigm Network EHR linked to claims data to identify US adults [≥]18 years of age who received the mRNA-1273.815 vaccine (exposed) matched 1:1 to individuals who did not receive a 2023-2024 updated COVID-19 vaccine (unexposed). Patients in the unexposed cohort were randomly matched to eligible mRNA-1273.815 recipients. Inverse probability of treatment weighting was used to adjust for differences between the two cohorts. The exposed cohort was vaccinated between September 12, 2023, and December 15, 2023, and individuals in both cohorts were followed up for COVID-19-related hospitalizations and medically attended COVID-19 until December 31, 2023. A Cox regression model was used to estimate the hazard ratio (HR). VE of the mRNA-1273.815 vaccine in preventing COVID-19-related hospitalizations and any medically attended COVID-19 was estimated as 100*(1-HR). Subgroup analyses were performed for adults [≥]50, adults [≥]65, and individuals with underlying medical conditions associated with severe COVID-19 outcomes. ResultsOverall, 859,335 matched pairs of mRNA-1273.815 recipients and unexposed adults were identified. The mean age was 63 years, and 80% of the study population was [≥]50 years old. 61.5% of the mRNA-1273.815 cohort and 66.4% of the unexposed cohort had an underlying medical condition. Among the overall adult population ([≥]18 years), VE was 60.2% (53.4-66.0%) against COVID-19-related hospitalization and 33.1% (30.2%-35.9%) against medically attended COVID-19 over a median follow-up of 63 (IQR: 44-78) days. VE estimates by age and underlying medical conditions were similar. ConclusionsThese results demonstrate the significant protection provided by mRNA-1273.815 against COVID-19-related hospitalizations and any medically attended COVID-19 in adults 18 years and older, regardless of their vaccination history, and support CDC recommendations for vaccination with the 2023-2024 Omicron XBB.1.5-containing COVID-19 vaccine to prevent COVID-19-related outcomes, including hospitalizations.

Incidence and Risk of Post-COVID-19 Thromboembolic Disease and the Impact of Aspirin Prescription; Nationwide Observational Cohort at the US Department of Veteran Affairs. (preprint)

IntroductionCOVID-19 triggers prothrombotic and proinflammatory changes, with thrombotic disease prevalent in up to 30% SARS-CoV-2 infected patients. Early work suggests that aspirin could prevent COVID-19 related thromboembolic disorders in some studies but not others. This study leverages data from the largest integrated healthcare system in the United States to better understand this association. Our objective was to evaluate the incidence and risk of COVID-19 associated acute thromboembolic disorders and the potential impact of aspirin. MethodsThis retrospective, observational study utilized national electronic health record data from the Veterans Health Administration. 334,374 Veterans who tested positive for COVID-19 from March 2, 2020, to June 13, 2022, were included, 81,830 of whom had preexisting aspirin prescription prior to their COVID-19 diagnosis. Patients with and without aspirin prescriptions were matched and the odds of post-COVID acute thromboembolic disorders were assessed. Results10.1% of Veterans had a documented thromboembolic disorder within 12 months following their COVID-19 diagnosis. Those with specific comorbidities were at greatest risk. Preexisting aspirin prescription was associated with a significant decrease risk of post-COVID-19 thromboembolic disorders, including pulmonary embolism (OR [95% CI]: 0.69 [0.65, 0.74]) and deep vein thrombosis (OR [95% CI]: 0.76 [0.69, 0.83], but an increased risk of acute arterial diseases, including ischemic stroke (OR [95% CI]: 1.54 [1.46, 1.60]) and acute ischemic heart disease (1.33 [1.26, 1.39]). ConclusionsFindings demonstrated that preexisting aspirin prescription prior to COVID-19 diagnosis was associated with significantly decreased risk of venous thromboembolism and pulmonary embolism but increased risk of acute arterial disease. The risk of arterial disease may be associated with increased COVID-19 prothrombotic effects superimposed on preexisting chronic cardiovascular disease for which aspirin was already prescribed. Prospective clinical trials may help to further assess the efficacy of aspirin use prior to COVID-19 diagnosis for the prevention of post-COVID-19 thromboembolic disorders.

The Impact of School and Family Networks on COVID-19 Infections Among Dutch Students: A Study Using Population-Level Registry Data (preprint)

Understanding the impact of different social interactions is key to improving epidemic models. Here, we use extensive registry data -- including PCR test results and population-level networks -- to investigate the impact of school, family, and other social contacts on SARS-CoV-2 transmission in the Netherlands (June 2020--October 2021). We isolate and compare different contexts of potential SARS-CoV-2 transmission by matching pairs of students based on their attendance at the same or different primary school (in 2020) and secondary school (in 2021) and their geographic proximity. We then calculated the probability of temporally associated infections -- i.e. the probability of both students testing positive within a 14-day period. Our results highlight the relative importance of household and family transmission in the spread of SARS-CoV-2 compared to school settings. The probability of temporally associated infections for siblings and parent-child pairs living in the same household was 22.6--23.2\%, and 4.7--7.9\% for family members living in different household. In contrast, the probability of temporally associated infections was 0.52\% for pairs of students living nearby but not attending the same primary or secondary school, 0.66\% for pairs attending different secondary schools but having attended the same primary school, and 1.65\% for pairs attending the same secondary school. Finally, we used multilevel regression analyses to examine how individual, school, and geographic factors contribute to transmission risk. We found that the largest differences in transmission probabilities were due to unobserved individual (60\%) and school-level (34\%) factors. Only a small proportion (3\%) could be attributed to geographic proximity of students or to school size, denomination, or the median income of the school area.

Timing and Depth Selection for Sedated Gastroscopy After SARS-CoV-2 Infection—A Retrospective Cohort Study (preprint)

Background Sedated gastroscopy is a crucial procedure for patients with upper respiratory infections. SARS-CoV-2-infected patients are more susceptible to anesthesia-related complications, such as edema, pharyngeal mucosa congestion, laryngospasm, and pulmonary infections.Methods We retrospectively analyzed a total of 386 patients who underwent sedated gastroscopy at the Affiliated Hospital of Qingdao University during the SARS-CoV-2 infection period. The patients were divided into three groups based on SARS-CoV-2 status: Negative (N), Two-week post-SARS-CoV-2 infection (T), and Three-week post-SARS-CoV-2 infection (Th) groups. Based on the anesthesia method, patients were divided into mild/moderate sedation and deep sedation/general anesthesia groups. Additionally, patients were categorized into groups based on COVID-19 severity and vaccination status. We recorded the laryngeal mucosal conditions, the occurrence rates of adverse reactions such as coughing, laryngospasm, and transient oxygen desaturation during the examination, as well as the satisfaction of patients and endoscopists were recorded.Results The T group displayed a significantly higher occurrence rate of adverse reactions when compared to the N and Th group, with decreased satisfaction levels of patients and endoscopists. In the T group, the occurrence rate of adverse reactions was higher in mild to moderate sedation than in deep sedation/general anesthesia methods, while patient and endoscopist satisfaction was lower. In the Th group, there was no statistically significant difference in the examination success rate or patient satisfaction between the mild/moderate sedation and deep sedation/general anesthesia methods; however, endoscopist satisfaction was lower with mild/moderate sedation method than deep sedation/general anesthesia method. There was a significant difference in the gastroscopy success rates of patients with different COVID-19 classifications. A significant difference was observed in the gastroscopy success rates among patients with different vaccination statuses.Conclusions Sedated gastroscopy post-three weeks of SARS-CoV-2 infection is safe. Moreover, using a deep sedation/general anesthesia method for sedated gastroscopy in SARS-CoV-2-infected patients within three weeks is significantly safer.