A Four Years Longitudinal Study of Childhood Vaccination Trends and Supply Chain Resilience in Tanzania amid COVID-19 Pandemic (preprint)

Background The COVID-19 pandemic has significantly disrupted healthcare systems at all levels globally, notably affecting routine healthcare services such as childhood immunisations. This study delves into the impact of these disruptions on routine childhood vaccination programs in Tanzania. Methodology We conducted a longitudinal study over four years in five Tanzanian regions: Mwanza, Dar es Salaam, Mtwara, Arusha, and Dodoma. The study analysed trends in the usage of six key vaccines: Bacille Calmette-Guérin (BCG), Bivalent Oral Polio Vaccine (bOPV), Diphtheria Tetanus Pertussis, Hepatitis-B and Hib vaccine (DTP-HepB-Hib), measles-rubella (MR), Pneumococcal Conjugate Vaccine (PCV), and Rota vaccines. We evaluated annual and monthly vaccination trends using time series and regression analyses. Predictive modelling was performed using an Autoregressive Integrated Moving Average (ARIMA) model. Results The study recorded a total of 32,602,734 vaccination events across the regions from 2019 to 2022. Despite declining vaccination rates in 2020, there was a notable rebound in 2021, indicating the resilience of Tanzania's immunisation program. The analysis also highlighted regional differences in varying vaccination rates when standardised per 1000 population. Seasonal fluctuations were observed in the monthly vaccination rates, with BCG showing the most stable trend. Predictive modelling of BCG indicated stable and increasing vaccination coverage through 2023. Conclusion The findings underscore the robustness of Tanzania's childhood immunisation infrastructure in overcoming the challenges posed by the COVID-19 pandemic, marked by a strong recovery in vaccination rates post-2020. We provide valuable insights into the dynamics of vaccinations during a global health crisis and highlight the importance of sustained immunisation efforts in maintaining public health.

Microfluidic antibody profiling after repeated SARS-CoV-2 vaccination links antibody affinity and concentration to impaired immunity and variant escape in patients on anti-CD-20 therapy (preprint)

Background: Patients with autoimmune/inflammatory conditions on anti-CD20 therapies, such as Rituximab, have suboptimal humoral responses to vaccination and are vulnerable to poorer clinical outcomes following SARS-CoV-2 infection. We aimed to examine how the fundamental parameters of antibody responses, namely affinity and concentration, shape the quality of humoral immunity after vaccination in these patients. Methods: We performed in depth antibody characterisation in sera collected four to six weeks after each of three vaccine doses to wild-type (WT) SARS-CoV-2 in Rituximab-treated primary vasculitis patients (n=14) using Luminex and pseudovirus neutralisation assays, whereas a novel microfluidic-based immunoassay was used to quantify polyclonal antibody affinity and concentration against both WT and Omicron (B.1.1.529) variants. Comparative antibody profiling was performed at equivalent time points in healthy individuals after three antigenic exposures to WT SARS-CoV-2 (one infection and two vaccinations; n=15) and in convalescent patients after WT SARS-CoV-2 infection (n=30). Results: Rituximab-treated patients had lower antibody levels and neutralisation titres against both WT and Omicron SARS-CoV-2 variants compared to healthy individuals. Neutralisation capacity was weaker against Omicron versus WT both in Rituximab-treated patients and in healthy individuals. In the Rituximab cohort, this was driven by lower antibody affinity against Omicron versus WT (median [range] KD: 21.6 [9.7-38.8] nM vs 4.6 [2.3-44.8] nM, p=0.0004). By contrast, healthy individuals with hybrid immunity produced a broader antibody response, a subset of which recognised Omicron with higher affinity than antibodies in Rituximab-treated patients (median [range] KD: 1.05 [0.45-1.84] nM vs 20.25 [13.2-38.8] nM, p=0.0002), underpinning the stronger serum neutralisation capacity against Omicron in the former group. Rituximab-treated patients had similar anti-WT antibody levels and neutralisation titres to unvaccinated convalescent individuals, despite two more exposures to SARS-CoV-2 antigen. Temporal profiling of the antibody response showed evidence of affinity maturation in healthy convalescent patients after a single SARS-CoV-2 infection which was not observed in Rituximab-treated patients, despite repeated vaccination. Discussion: Our results enrich previous observations of impaired humoral immune responses to SARS-CoV-2 in Rituximab-treated patients and highlight the significance of quantitative assessment of serum antibody affinity and concentration in monitoring anti-viral immunity, viral escape, and the evolution of the humoral response.

Demographic, behavioural and occupational risk factors associated with SARS-CoV-2 infection in UK healthcare workers: a retrospective observational study.

OBJECTIVE: Healthcare workers (HCWs) are at higher risk of SARS-CoV-2 infection than the general population. This group is pivotal to healthcare system resilience during the COVID-19, and future, pandemics. We investigated demographic, social, behavioural and occupational risk factors for SARS-CoV-2 infection among HCWs. DESIGN/SETTING/PARTICIPANTS: HCWs enrolled in a large-scale sero-epidemiological study at a UK university teaching hospital were sent questionnaires spanning a 5-month period from March to July 2020. In a retrospective observational cohort study, univariate logistic regression was used to assess factors associated with SARS-CoV-2 infection. A Least Absolute Shrinkage Selection Operator regression model was used to identify variables to include in a multivariate logistic regression model. RESULTS: Among 2258 HCWs, highest ORs associated with SARS-CoV-2 antibody seropositivity on multivariate analysis were having a household member previously testing positive for SARS-CoV-2 antibodies (OR 6.94 (95% CI 4.15 to 11.6); p<0.0001) and being of black ethnicity (6.21 (95% CI 2.69 to 14.3); p<0.0001). Occupational factors associated with a higher risk of seropositivity included working as a physiotherapist (OR 2.78 (95% CI 1.21 to 6.36); p=0.015) and working predominantly in acute medicine (OR 2.72 (95% CI 1.57 to 4.69); p<0.0001) or medical subspecialties (not including infectious diseases) (OR 2.33 (95% CI 1.4 to 3.88); p=0.001). Reporting that adequate personal protective equipment (PPE) was 'rarely' available had an OR of 2.83 (95% CI 1.29 to 6.25; p=0.01). Reporting attending a handover where social distancing was not possible had an OR of 1.39 (95% CI 1.02 to 1.9; p=0.038). CONCLUSIONS: The emergence of SARS-CoV-2 variants and potential vaccine escape continue to threaten stability of healthcare systems worldwide, and sustained vigilance against HCW infection remains a priority. Enhanced risk assessments should be considered for HCWs of black ethnicity, physiotherapists and those working in acute medicine or medical subspecialties. Workplace risk reduction measures include ongoing access to high-quality PPE and effective social distancing measures.

A spatio-temporal framework for modelling wastewater concentration during the COVID-19 pandemic (preprint)

The potential utility of wastewater-based epidemiology as an early warning tool has been explored widely across the globe during the current COVID-19 pandemic. Methods to detect the presence of SARS-CoV-2 RNA in wastewater were developed early in the pandemic, and extensive work has been conducted to evaluate the relationship between viral concentration and COVID-19 case numbers at the catchment areas of sewage treatment works (STWs) over time. However, no attempt has been made to develop a model that predicts wastewater concentration at fine spatio-temporal resolutions covering an entire country, a necessary step towards using wastewater monitoring for the early detection of local outbreaks. We consider weekly averages of flow-normalised viral concentration, reported as the number of SARS-CoV-2 N1 gene copies per litre (gc/L) of wastewater available at 303 STWs over the period between 1 June 2021 and 30 March 2022. We specify a spatially continuous statistical model that quantifies the relationship between weekly viral concentration and a collection of covariates covering socio-demographics, land cover and virus-associated genomic characteristics at STW catchment areas while accounting for spatial and temporal correlation. We evaluate the models predictive performance at the catchment level through 10-fold cross-validation. We predict the weekly viral concentration at the population-weighted centroid of the 32,844 lower super output areas (LSOAs) in England, then aggregate these LSOA predictions to the Lower Tier Local Authority level (LTLA), a geography that is more relevant to public health policy-making. We also use the model outputs to quantify the probability of local changes of direction (increases or decreases) in viral concentration over short periods (e.g. two consecutive weeks). The proposed statistical framework is able to predict SARS-CoV-2 viral concentration in wastewater at high spatio-temporal resolution across England. Additionally, the probabilistic quantification of local changes can be used as an early warning tool for public health surveillance.

Release of a photopharmacological drug from its protein target captured by time-resolved serial crystallography (preprint)

The binding and release of ligands from their protein targets is central to fundamental biological processes as well as to drug discovery. Photopharmacology introduces chemical triggers that allow the changing of ligand affinities and thus biological activity by light. Insight into the molecular mechanisms of photopharmacology is largely missing because the relevant transitions during the light-triggered reaction cannot be resolved by conventional structural biology. Using time-resolved serial crystallography at a synchrotron and X-ray free-electron laser, we have captured the release of azo-combretastatin A4 and the resulting conformational changes in tubulin. Nine structural snapshots from 1 ns to 100 ms complemented by simulations show how cis-to-trans isomerization of the azobenzene bond leads to a switch in ligand affinity, opening of an exit channel, and collapse of the binding pocket upon ligand release. The resulting global backbone rearrangements are related to the action mechanism of tubulin-binding drugs against gout, cancer, and COVID-19.

Is Tracheostomy Safe?: Common Indications and Early Complications Among Ugandan Patients In A Pre-Covid-19 Era. (preprint)

Background: Tracheostomy is a life-saving procedure whose outcomes may vary between hospitals based on disparities in their existing expertise. We aimed at establishing the indications, early tracheostomy-related complications and their associated factors in Uganda. Methods: In a prospective cohort study, we consecutively enrolled one-hundred patients, both adults and children 2 hours post-tracheostomy procedure. At baseline, information on patients’ socio-demographics, tracheostomy indications, pre- and post-procedural characteristics was collected through researcher administered questionnaires and from medical records. Clinical examination was performed at baseline but also at either day 7 or whenever a tracheostomy-related complication was suspected during the 7days follow-up. Comparison of patients’ baseline characteristics, tracheostomy indications and complications across two hospitals was done using Pearson’s chi-square. For predictors of early tracheostomy complications, bivariate and multivariate analysis models were fitted using binomial regression in STATA 13.0 software. Results: : Majority of patients were adults (84%) and males (70%). The commonest tracheostomy indications were; pulmonary toilet (58%) and anticipated prolonged intubation (42%). Overall, 53% (95% CI: 43.0 – 62.7) had early complications with the commonest being tube obstruction (52.6%). Independent predictors of early tracheostomy-related complications were; anticipated having prolonged intubation as an indication (RR=1.8, 95%CI: 1.19 – 2.76), Bjork flap tracheal incision (RR=1.6, 95%CI: 1.09 – 2.43), vertical tracheal incision (RR=1.53, 95%CI: 1.02 – 2.27), and age below 18 years (RR=1.22, 95%CI: 1.00 – 1.47). Conclusion: Within a pre-COVID-19 context, pulmonary toilet is the commonest tracheostomy indication at major hospitals in Uganda. The incidence of early tracheostomy complications is high and majorly related to post-procedure tracheostomy tube management. Having anticipated prolonged intubation as an indication for tracheostomy, a Bjork flap or vertical tracheal incisions and being a child increases the risk of complications. Emphasis on surgical training and post-procedural management for both clinicians and nurses should be made. New data will be needed within the COVID-19 era.

Masked face identification is improved by diagnostic feature training (preprint)

To slow the spread of COVID-19, many people now wear face masks in public. Face masks impair our ability to identify faces, which can cause problems for professional staff who identify offenders or members of the public. Here, we investigate whether performance on a masked face matching task can be improved by training participants to compare diagnostic facial features (the ears and facial marks) – a validated training method that improves matching performance for unmasked faces. We show this brief diagnostic feature training, which takes less than two minutes to complete, improves matching performance for masked faces by approximately 5%. A control training course, which was unrelated to face identification, had no effect on matching performance. Our findings demonstrate that comparing the ears and facial marks is an effective means of improving face matching performance for masked faces. These findings have implications for professions that regularly perform face identification.

A virucidal face mask based on the reverse-flow reactor concept for thermal inactivation of SARS-CoV-2.

While facial coverings reduce the spread of SARS-CoV-2 by viral filtration, masks capable of viral inactivation by heating can provide a complementary method to limit transmission. Inspired by reverse-flow chemical reactors, we introduce a new virucidal face mask concept driven by the oscillatory flow of human breath. The governing heat and mass transport equations are solved to evaluate virus and CO2 transport. Given limits imposed by the kinetics of SARS-CoV-2 thermal inactivation, human breath, safety, and comfort, heated masks may inactivate SARS-CoV-2 to medical-grade sterility. We detail one design, with a volume of 300 ml at 90°C that achieves a 3-log reduction in viral load with minimal impedance within the mask mesh, with partition coefficient around 2. This is the first quantitative analysis of virucidal thermal inactivation within a protective face mask, and addresses a pressing need for new approaches for personal protective equipment during a global pandemic.

Surgical face masks impair human face matching performance for familiar and unfamiliar faces (preprint)

In response to the COVID-19 pandemic, many governments around the world now recommend, or require, that their citizens cover the lower half of their face in public. Consequently, many people now wear surgical face masks in public. We investigated whether surgical face masks affected the performance of human observers, and a state-of-the-art face recognition system, on tasks of perceptual face matching. Participants judged whether two simultaneously presented face photographs showed the same person or two different people. We superimposed images of surgical masks over the faces, creating three different mask conditions: control (no masks), mixed (one face wearing a mask), and masked (both faces wearing masks). We found that surgical face masks have a large detrimental effect on human face matching performance, and that the degree of impairment is the same regardless of whether one or both faces in each pair are masked. Surprisingly, this impairment is similar in size for both familiar and unfamiliar faces. When matching masked faces, human observers are biased to reject unfamiliar faces as “mismatches” and to accept familiar faces as “matches”. Finally, the face recognition system showed very high classification accuracy for control and masked stimuli, even though it had not been trained to recognise masked faces. However, accuracy fell markedly when one face was masked and the other was not. Our findings demonstrate that surgical face masks impair the ability of humans, and naïve face recognition systems, to perform perceptual face matching tasks. Identification decisions for masked faces should be treated with caution.