Understanding spatiotemporal patterns of COVID-19 incidence in Portugal: a functional data analysis from August 2020 to March 2022 (preprint)

Since the emergence of SARS-CoV-2 and the pandemic, massive amounts of daily data on incidence are being collected by governments and public health authorities, providing relevant information about the dissemination of pandemic in terms of its virological evolution and spatiotemporal distribution of cases, hospitalization, and deaths. We propose a novel approach combining functional data analysis and unsupervised learning algorithms to extract meaningful information about the main spatiotemporal patterns underlying SARS-CoV-2 incidence. We modelled the daily COVID-19 confirmed cases by municipality as a function of time using functional principal component analysis to describe their temporal evolution in order to outline the main temporal patterns of variability. Municipalities were classified according to their spatiotemporal similarities through hierarchical clustering adapted to spatially correlated functional data. The proposed approach is applied to mainland Portugal with data collected between August 2020 and March 2022 by municipality. The results obtained discriminate northern and coastal regions from southern and hinterland, and the effects in 2020-21 from the effects in 2021-22 autumn-winter seasons. Spatiotemporal patterns and classification of municipalities agree with results reported by other works and provides proof-of-concept that the proposed approach can be used to detect the main spatiotemporal patterns of disease incidence. The novel approach extends and refines existing exploratory tools for spatiotemporal analysis of public health data.

Heterogeneous Mental Health Responses to the COVID-19 Pandemic in Germany: An Examination of Long-Term Trajectories, Risk Factors, and Vulnerable Groups.

Abundant studies have examined mental health in the early periods of the COVID-19 pandemic. However, empirical work examining the mental health impact of the pandemic's subsequent phases remains limited. In the present study, we investigated how mental vulnerability and resilience evolved over the various phases of the pandemic in 2020 and 2021 in Germany. Data were collected (n = 3522) across seven measurement occasions using validated and self-generated measures of vulnerability and resilience. We found evidence for an immediate increase in vulnerability during the first lockdown in Germany, a trend towards recovery when lockdown measures were eased, and an increase in vulnerability with each passing month of the second lockdown. Four different latent trajectories of resilience-vulnerability emerged, with the majority of participants displaying a rather resilient trajectory, but nearly 30% of the sample fell into the more vulnerable groups. Females, younger individuals, those with a history of psychiatric disorders, lower income groups, and those with high trait vulnerability and low trait social belonging were more likely to exhibit trajectories associated with poorer mental well-being. Our findings indicate that resilience-vulnerability responses in Germany during the COVID-19 pandemic may have been more complex than previously thought, identifying risk groups that could benefit from greater support.

Scientific Production And Dissemination Forecast Related With Covid-19

The new coronavirus SARS-CoV-2 cuases the known disease as COVID -19 extended around the world, increasing the infected and deceased cases. It was declared pandemic by OMS in March of this year. It is reason to actívate the scientific community in the production and dissemination of scientific articles. This paper analyzes and predicts scientific publications related with COVID 19, monthly and for country, proceeded and registered daily by CTS Observatory based on PubMed. USA highlights as the main country who publishes with 7,974 (27.73 %) results, followed by China with 4,202 (14.61 %). In Iberoamerican level, Spain and Brazil highlight with 4.26% y 2.37%, respectively. An increase of publications related with COVID-19 of 2,236 monthly publications is predicted in the mentioned database.

Spatiotemporal evolution of COVID-19 in Portugal's Mainland with self-organizing maps.

BACKGROUND: Self-Organizing Maps (SOM) are an unsupervised learning clustering and dimensionality reduction algorithm capable of mapping an initial complex high-dimensional data set into a low-dimensional domain, such as a two-dimensional grid of neurons. In the reduced space, the original complex patterns and their interactions can be better visualized, interpreted and understood. METHODS: We use SOM to simultaneously couple the spatial and temporal domains of the COVID-19 evolution in the 278 municipalities of mainland Portugal during the first year of the pandemic. Temporal 14-days cumulative incidence time series along with socio-economic and demographic indicators per municipality were analyzed with SOM to identify regions of the country with similar behavior and infer the possible common origins of the incidence evolution. RESULTS: The results show how neighbor municipalities tend to share a similar behavior of the disease, revealing the strong spatiotemporal relationship of the COVID-19 spreading beyond the administrative borders of each municipality. Additionally, we demonstrate how local socio-economic and demographic characteristics evolved as determinants of COVID-19 transmission, during the 1st wave school density per municipality was more relevant, where during 2nd wave jobs in the secondary sector and the deprivation score were more relevant. CONCLUSIONS: The results show that SOM can be an effective tool to analysing the spatiotemporal behavior of COVID-19 and synthetize the history of the disease in mainland Portugal during the period in analysis. While SOM have been applied to diverse scientific fields, the application of SOM to study the spatiotemporal evolution of COVID-19 is still limited. This work illustrates how SOM can be used to describe the spatiotemporal behavior of epidemic events. While the example shown herein uses 14-days cumulative incidence curves, the same analysis can be performed using other relevant data such as mortality data, vaccination rates or even infection rates of other disease of infectious nature.

In vitro testing of salt coating of fabrics as a potential antiviral agent in reusable face masks.

During the coronavirus disease (COVID-19) pandemic, wearing face masks in public spaces became mandatory in most countries. The risk of self-contamination when handling face masks, which was one of the earliest concerns, can be mitigated by adding antiviral coatings to the masks. In the present study, we evaluated the antiviral effectiveness of sodium chloride deposited on a fabric suitable for the manufacturing of reusable cloth masks using techniques adapted to the home environment. We tested eight coating conditions, involving both spraying and dipping methods and three salt dilutions. Influenza A H3N2 virus particles were incubated directly on the salt-coated materials, collected, and added to human 3D airway epithelial cultures. Live virus replication in the epithelia was quantified over time in collected apical washes. Relative to the non-coated material, salt deposits at or above 4.3 mg/cm2 markedly reduced viral replication. However, even for larger quantities of salt, the effectiveness of the coating remained dependent on the crystal size and distribution, which in turn depended on the coating technique. These findings confirm the suitability of salt coating as antiviral protection on cloth masks, but also emphasize that particular attention should be paid to the coating protocol when developing consumer solutions.

Inactivation of SARS-CoV-2 on Salt-Coated Surfaces: An In Vitro Study (preprint)

In the Covid-19 pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), face masks have become a very important safety measure against the main route of transmission of the virus: droplets and aerosols. Concerns that masks contaminated with SARS-CoV-2 infectious particles could be a risk for self-contamination have emerged early in the pandemic as well as solutions to mitigate this risk. The coating of masks with sodium chloride, an anti-viral and non-hazardous to health chemical, could be an option for reusable masks. To assess the antiviral properties of salt coatings deposited onto common fabrics by spraying and dipping, the present study established an in vitro bioassay using three-dimensional airway epithelial cell cultures and SARS-CoV-2 virus. Virus particles were given directly on salt-coated material, collected, and added to the cell cultures. Infectious virus particles were measured by plaque forming unit assay and in parallel viral genome copies were quantified over time. Relative to noncoated material, the sodium chloride coating significantly reduced virus replication, confirming the effectiveness of the method to prevent fomite contamination with SARS-CoV-2. In addition, the lung epithelia bioassay proved to be suitable for future evaluation of novel antiviral coatings.

A Machine Learning Approach in Evaluating Symptom Screening in Predicting COVID-19

COVID-19 is a disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that, to date, has over 245 million confirmed cases and claimed almost 5 million lives. This disease attacks the respiratory system and comes with a number of symptoms. The US Center for Disease Control and Prevention presents a set of symptoms. However, these symptoms only begin to manifest after a number of days, which prevents early detection of this disease. This absence of symptoms during the early stages is what is considered by many to be the very factor that caused the virus into becoming a pandemic. Nonetheless, symptoms checking has been used in practice by commercial and business establishments as an initial screening for COVID-19. The bothersome process of symptom checking are still in place at the entrances of malls and airports. In this study, we determine whether or not symptom screening is an effective system to be employed to assess individuals for COVID-19. Specifically, it aims to determine whether or not one or a set of symptoms are effective predictors of the RT-PCR test results, the gold standard in Covid-19 testing, using machine learning. Using data from the Philippine Red Cross, classification models are developed using LightGBM, AdaBoost, Gaussian Naïve-Bayes, MultiLayer Perceptron, Quadratic Discriminant Analysis and Decision Tree. These models were evaluated using the following metrics: precision, sensitivity, specificity and the type II error rate. Furthermore, for explainability, symptoms are analyzed as to whether or not they are relatively influential on the predicting whether or not a patient has COVID-19. The high type II error rate, low sensitivity and low relative predictor scores of the most significant predictor symptoms clearly show that symptoms do not correlate with the RT-PCR testing results. Thus, we conclude that symptom screening is not a medically suitable process for determining whether an individual has COVID-19. In fact, it even exposes us to the risk of viral transmission as people congregate at the entrances and lobbies of establishments. © 2022 IEEE.

Coping with the COVID-19 Pandemic: Perceived Changes in Psychological Vulnerability, Resilience and Social Cohesion before, during and after Lockdown.

The COVID-19 pandemic and associated lockdowns have posed unique and severe challenges to our global society. To gain an integrative understanding of pervasive social and mental health impacts in 3522 Berlin residents aged 18 to 65, we systematically investigated the structural and temporal relationship between a variety of psychological indicators of vulnerability, resilience and social cohesion before, during and after the first lockdown in Germany using a retrospective longitudinal study design. Factor analyses revealed that (a) vulnerability and resilience indicators converged on one general bipolar factor, (b) residual variance of resilience indicators formed a distinct factor of adaptive coping capacities and (c) social cohesion could be reliably measured with a hierarchical model including four first-order dimensions of trust, a sense of belonging, social interactions and social engagement, and one second-order social cohesion factor. In the second step, latent change score models revealed that overall psychological vulnerability increased during the first lockdown and decreased again during re-opening, although not to baseline levels. Levels of social cohesion, in contrast, first decreased and then increased again during re-opening. Furthermore, participants who increased in vulnerability simultaneously decreased in social cohesion and adaptive coping during lockdown. While higher pre-lockdown levels of social cohesion predicted a stronger lockdown effect on mental health, individuals with higher social cohesion during the lockdown and positive change in coping abilities and social cohesion during re-opening showed better mental health recovery, highlighting the important role of social capacities in both amplifying but also overcoming the multiple challenges of this collective crisis.

The Impact of COVID-19 on Diagnosis of Heart Disease in Latin America an INCAPS COVID Sub-analysis. / O Impacto da COVID-19 no Diagnóstico de Doenças Cardíacas na América Latina Uma Subanálise do INCAPS COVID.

BACKGROUND: The COVID-19 pandemic has disrupted the delivery of care for cardiovascular diseases in Latin America. However, the effect of the pandemic on the cardiac diagnostic procedure volumes has not been quantified. OBJECTIVE: To assess (1) the impact of COVID-19 on cardiac diagnostic volumes in Latin America and (2) determine its relationship with COVID-19 case incidence and social distancing measures. METHODS: The International Atomic Energy Agency conducted a worldwide survey assessing changes in cardiac diagnostic volumes resulting from COVID-19. Cardiac diagnostic volumes were obtained from participating sites for March and April 2020 and compared to March 2019. Social distancing data were collected from Google COVID-19 community mobility reports and COVID-19 incidence per country from the Our World in Data. RESULTS: Surveys were conducted in 194 centers performing cardiac diagnostic procedures, in 19 countries in Latin America. Procedure volumes decreased 36% from March 2019 to March 2020, and 82% from March 2019 to April 2020. The greatest decreases occurred in echocardiogram stress tests (91%), exercise treadmill tests (88%), and computed tomography calcium scores (87%), with slight variations between sub-regions of Latin America. Changes in social distancing patterns (p < 0.001) were more strongly associated with volume reduction than COVID-19 incidence (p = 0.003). CONCLUSIONS: COVID-19 was associated with a significant reduction in cardiac diagnostic procedures in Latin America, which was more related to social distancing than to the COVID-19 incidence. Better balance and timing of social distancing measures and planning to maintain access to medical care is warranted during a pandemic surge, especially in regions with high cardiovascular mortality.

FUNDAMENTO: A pandemia de COVID-19 interferiu na prestação de atendimento a doenças cardiovasculares na América Latina. No entanto, o efeito da pandemia nos volumes de procedimentos cardíacos diagnósticos ainda não foi quantificado. OBJETIVO: Avaliar (1) o impacto de COVID-19 nos volumes de diagnóstico cardíaco na América Latina e (2) determinar sua relação com a incidência de casos de COVID-19 e as medidas de distanciamento social. MÉTODOS: A International Atomic Energy Agency realizou uma pesquisa mundial avaliando mudanças nos volumes diagnósticos cardíacos decorrentes da COVID-19. Foram obtidos os volumes diagnósticos cardíacos dos locais participantes para março e abril de 2020 e comparados com março de 2019. Foram coletados dados de distanciamento social a partir dos Relatórios de mobilidade da comunidade de Google e a incidência de COVID-19 por país a partir de Our World in Data. RESULTADOS: Foram realizadas pesquisas em 194 centros que realizam procedimentos diagnósticos cardíacos, em 19 países da América Latina. Em comparação com o mês de março de 2019, os volumes dos procedimentos diagnósticos cardíacos diminuíram 36% em março de 2020 e 82% em abril de 2020.As maiores reduções ocorreram em relação aos testes de estresse ecocardiográfico (91%), testes ergométricos de esteira (88%) e escore de cálcio por tomografia computadorizada (87%), com pequenas variações entre as sub-regiões da América Latina. As mudanças em padrões de distanciamento social (p < 0,001) estavam mais fortemente associadas com a redução do volume do que a incidência de COVID-19 (p = 0,003). CONCLUSÕES: A COVID-19 foi associada a uma redução significativa de procedimentos diagnósticos cardíacos na América Latina, a qual foi mais relacionada ao distanciamento social do que ao aumento da incidência da COVID-19. São necessários melhor equilíbrio e timing de medidas de distanciamento social e planejamento para manter o acesso ao atendimento médico durante um surto pandêmico, especialmente em regiões com alta mortalidade cardiovascular.

Pulmonary Delivery of Aerosolized Chloroquine and Hydroxychloroquine to Treat COVID-19: In Vitro Experimentation to Human Dosing Predictions.

In vitro screening for pharmacological activity of existing drugs showed chloroquine and hydroxychloroquine to be effective against severe acute respiratory syndrome coronavirus 2. Oral administration of these compounds to obtain desired pulmonary exposures resulted in dose-limiting systemic toxicity in humans. However, pulmonary drug delivery enables direct and rapid administration to obtain higher local tissue concentrations in target tissue. In this work, inhalable formulations for thermal aerosolization of chloroquine and hydroxychloroquine were developed, and their physicochemical properties were characterized. Thermal aerosolization of 40 mg/mL chloroquine and 100 mg/mL hydroxychloroquine formulations delivered respirable aerosol particle sizes with 0.15 and 0.33 mg per 55 mL puff, respectively. In vitro toxicity was evaluated by exposing primary human bronchial epithelial cells to aerosol generated from Vitrocell. An in vitro exposure to 7.24 µg of chloroquine or 7.99 µg hydroxychloroquine showed no significant changes in cilia beating, transepithelial electrical resistance, and cell viability. The pharmacokinetics of inhaled aerosols was predicted by developing a physiologically based pharmacokinetic model that included a detailed species-specific respiratory tract physiology and lysosomal trapping. Based on the model predictions, inhaling emitted doses comprising 1.5 mg of chloroquine or 3.3 mg hydroxychloroquine three times a day may yield therapeutically effective concentrations in the lung. Inhalation of higher doses further increased effective concentrations in the lung while maintaining lower systemic concentrations. Given the theoretically favorable risk/benefit ratio, the clinical significance for pulmonary delivery of aerosolized chloroquine and hydroxychloroquine to treat COVID-19 needs to be established in rigorous safety and efficacy studies. Graphical abstract.

Hand Sanitizer Safety Risks Associated with Poor Formulation and Packaging Approaches: Lessons Learned and Improvements Needed Post-Pandemic

Introduction: The rapid effectiveness of alcohol-based hand rub(ABHR) on microbial pathogens, including viral variants, inspired unprecedented demand for ABHR during the COVID-19 pandemic. A wide variety of new ABHR products that were rapidly produced and released to the public appear to have introduced new and unacceptable human safety risks. Objectives: While the long-term public health impact of exposure to adulterated ABHR will require further study, the immediate need to assess the safety and efficacy of ABHR motivated this study. Methods: Sampling of ABHR provided to the public in community settings (e.g., by a medical center) occurred across a wide variety of global community settings. When possible, ABHR samples of 30.50 ml were analyzed for: alcohol %, visible impurities and chemical impurities (i.e., acetal, acetaldehyde, benzene, and methanol). Validated analytical methods (good laboratory practices (GLP) or International Organization for Standardization (ISO) standards) were used for quantitative measurements. Photographs were taken for visual assessment of packaging design + labeling risks. Results: Alcohol concentrations less than a typical minimum antimicrobial efficacy level of 60% were measured in ≥ 7% of the ABHR samples. Unknown visible impurities were observed in ≥ 11% of samples. Levels of regulated impurities (acetal, acetaldehyde, benzene, and methanol) in excess of US FDA Guidance were observed in ≥ 43% of samples. Photographs demonstrate numerous risks associated with package design and open refillable ("bulk") dispensers, including no lot code nor expiry, and lack of traceable labeling. Conclusion: During the COVID-19 Emergency, demand for ABHR prompted new supply sources, followed by inscrutable donations of surplus products. Though unintended, allowing tainted and poor quality ABHR into communities places clinicians and the public at unnecessary risk. Guidance to consumers, businesses, and communities including medical centers, nursing homes, schools, offices, and retail settings, on the proper evaluation, use, and handling of ABHR, and safe disposal of adulterated or suspect product is needed. Regulatory guidance and enforcement addressing dangerous practices evident in this study including refilling of pump bottles/dispensers with a variety of ABHRs is needed immediately to reduce future exposure to unsafe, ineffective, mislabeled or unlabeled ABHR products.

Virtual interviewing in the COVID-19 era: A survey of graduate program directors.

PURPOSE/OBJECTIVE: Due to the coronavirus pandemic, virtual interviews became a mainstay of graduate dental and medical education selection processes. To gain a handle on how to navigate lingering uncertainties about how interviews should be conducted in the future, this study examined the benefits and pitfalls of the virtual interview process (VIP) and assessed program plans to implement in the next interview cycle. METHODS: An anonymous online survey, for completion by one program representative (director or associate director), was sent to graduate medical education (GME) and advanced dental education programs at West Virginia University (N = 74). RESULTS: Fifty-two (52) of the programs (70%) completed the survey. Zoom was the most frequently used interview platform (78.8%). Approximately two thirds (65.4%) of the interviewers thought VIP allowed the program to promote the university, the school, and their program and also reported experiencing video-conferencing fatigue. About six in 10 perceive VIP can introduce bias in selecting applicants (59.6%) and potentially disadvantage some applicants (67.3%). Compared to the previous in-person cycle, 67.4% of programs invited more applicants, and 73.1% interviewed more applicants. Regarding the 2021-2022 interview cycle, 55.8% of programs plan to offer either an in-person or VIP, while 7.7% plan to keep their process completely virtual. CONCLUSION: Graduate programs in this study demonstrated the indispensability of technology in transitioning from in-person to virtual interviews during COVID-19 pandemic. VIP has several advantages and disadvantages; this style of interview is forecasted to have a presence in applicant selection in the future.

Iota-carrageenan extracted from red algae is a potent inhibitor of SARS-CoV-2 infection in reconstituted human airway epithelia.

Iota-carrageenan (IC) nasal spray, a medical device approved for treating respiratory viral infections, has previously been shown to inhibit the ability of a variety of respiratory viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), to enter and replicate in the cell by interfering with the virus binding to the cell surface. The aim of this study was to further investigate the efficacy and safety of IC in SARS-CoV-2 infection in advanced in vitro models of the human respiratory epithelium, the primary target and entry port for SARS-CoV-2. We extended the in vitro safety assessment of nebulized IC in a 3-dimensional model of reconstituted human bronchial epithelium, and we demonstrated the efficacy of IC in protecting reconstituted nasal epithelium against viral infection and replication of a patient-derived SARS-CoV-2 strain. The results obtained from these two advanced models of human respiratory tract epithelia confirm previous findings from in vitro SARS-CoV-2 infection assays and demonstrate that topically applied IC can effectively prevent SARS-CoV-2 infection and replication. Moreover, the absence of toxicity and functional and structural impairment of the mucociliary epithelium demonstrates that the nebulized IC is well tolerated.

Single center study for improving hepatitis a and b immunity in veterans with cirrhosis

Introduction: Patients with cirrhosis should be immunized against hepatitis A (HAV) & hepatitis B (HBV) as they are high risk for decompensation if infected. Baseline data at the Atlanta VA hepatology clinics demonstrated 75% of veterans with cirrhosis were immune to HAV and 44% to HBV. One fourth of visits failed to address hepatitis vaccines, and 60% of missed opportunities were from providers not discussing it. Our aim was to reduce missed opportunities to initiate HAV and HBV vaccination to <and to confirm immunity with serologies to < over 6 months in the Atlanta VA hepatology clinics. Methods: A process map identifying steps to obtain a vaccine and Pareto charts quantifying rates of commonly identified barriers were used to implement Plan-Do-Study-Act (PDSA) cycles. Approximately every 10th chart was sampled, and P charts were created to assess the average missed opportunity rate before and after our QI initiatives. Results: PDSA 1 focused on educating providers on the importance of vaccination, sharing the baseline data, and instructing how to order vaccines. For PDSA 2, the liver pharmacist monitored the vaccine queue daily to ensure that orders remained active. PDSA 3 involved a “quality inspection” by the attending hepatologist, who alerted the provider if vaccination was not addressed but was warranted. The last PDSA included creating a “Liver Passport” for the veteran that had personalized vaccination, hepatocellular screening, and esophageal variceal screening recommendations. The overall average missed opportunities for HAV & HBV vaccination and serologic confirmation testing decreased from 41% to 29% after four PDSA cycles. Separately, mean missed opportunities for initiating HAV & HBV vaccination decreased from 25% to 19% and assessing immunity with HAV & HBV serologies declined from 16% to 10%.Conclusion: Lack of in-person visits during the COVID-19 pandemic was a significant study limitation early on. Nevertheless, the national discussion surrounding COVID-19 vaccines provided a springboard for our QI initiatives to increasingly address HAV & HBV vaccines and immunity within a short time frame. Future aims are ≥HAV and HBV immunity and addressing all other vaccines recommended in patients with cirrhosis.

Sanitizers and disinfectants: A retail food and foodservice perspective

The coronavirus disease 2019 (COVID-19) pandemic has brought heightened attention to the importance of cleaning, sanitizing, and disinfecting in retail food and foodservice establishments. In response, major governmental agencies have emphasized the need to frequently disinfect high-touch surfaces. While this recommendation may seem straightfor-ward and achievable, it is far more nuanced and complex. In the retail food and foodservice industry, sanitization is a routine, common practice defined and recommended in the U.S. Food and Drug Administration (FDA) Food Code. Hence, sanitizers, rather than disinfectants, are the main antimicrobial products used in these settings. It is important to emphasize that sanitizers and disinfectants are not inter-changeable products, so they may be inadvertently misused. Therefore, end users need to understand the differences of when, why, and how both can be used in retail food and foodservice settings. The aim of this paper is to increase end users’ knowledge and awareness about the proper use of sanitizers and disinfectants in retail food and foodservice establishments. This paper is organized into six sections— Antimicrobial Products: Sanitizers and Disinfectants, FDA Food Code, Regulation of Sanitizers and Disinfectants, Understanding EPA-Registered Labels, Emerging Issues, and Current and Future Trends in Sanitizing and Disinfecting. When used properly, sanitizers and disinfectants are powerful tools that can keep retail food and foodservice operations safe from pathogens that cause infectious disease. © 2021, International Association for Food Protection. All rights reserved.

COVID-19 Lockdowns May Reduce Resistance Genes Diversity in the Human Microbiome and the Need for Antibiotics.

Recently, much attention has been paid to the COVID-19 pandemic. Yet bacterial resistance to antibiotics remains a serious and unresolved public health problem that kills hundreds of thousands of people annually, being an insidious and silent pandemic. To contain the spreading of the SARS-CoV-2 virus, populations confined and tightened hygiene measures. We performed this study with computer simulations and by using mobility data of mobile phones from Google in the region of Lisbon, Portugal, comprising 3.7 million people during two different lockdown periods, scenarios of 40 and 60% mobility reduction. In the simulations, we assumed that the network of physical contact between people is that of a small world and computed the antibiotic resistance in human microbiomes after 180 days in the simulation. Our simulations show that reducing human contacts drives a reduction in the diversity of antibiotic resistance genes in human microbiomes. Kruskal-Wallis and Dunn's pairwise tests show very strong evidence (p < 0.000, adjusted using the Bonferroni correction) of a difference between the four confinement regimes. The proportion of variability in the ranked dependent variable accounted for by the confinement variable was η2 = 0.148, indicating a large effect of confinement on the diversity of antibiotic resistance. We have shown that confinement and hygienic measures, in addition to reducing the spread of pathogenic bacteria in a human network, also reduce resistance and the need to use antibiotics.

Controlling the pandemic during the SARS-CoV-2 vaccination rollout.

There is a consensus that mass vaccination against SARS-CoV-2 will ultimately end the COVID-19 pandemic. However, it is not clear when and which control measures can be relaxed during the rollout of vaccination programmes. We investigate relaxation scenarios using an age-structured transmission model that has been fitted to age-specific seroprevalence data, hospital admissions, and projected vaccination coverage for Portugal. Our analyses suggest that the pressing need to restart socioeconomic activities could lead to new pandemic waves, and that substantial control efforts prove necessary throughout 2021. Using knowledge on control measures introduced in 2020, we anticipate that relaxing measures completely or to the extent as in autumn 2020 could launch a wave starting in April 2021. Additional waves could be prevented altogether if measures are relaxed as in summer 2020 or in a step-wise manner throughout 2021. We discuss at which point the control of COVID-19 would be achieved for each scenario.

Inflammatory parameter analysis in severe COVID-19 patients treated with tocilizumab

Background and importance Tocilizumab (TCZ) is an immunosuppressor drug, IL-6 inhibitor, indicated for the treatment of rheumatoid arthritis and cytokine release syndrome associated with CAR T cell therapy. It was proposed as a compassionate treatment for severe COVID-19 due to its potential benefit as anticytokine therapy with IL-6 as the target, one of the most relevant cytokines involved in the cytokine storm induced by COVID-19. Aim and objectives The main objective was to evaluate TCZ effectiveness in the modification of inflammatory parameters in severe COVID-19 patients. Material and methods A retrospective observational study was conducted in 46 patients with COVID-19 admitted to an intensive care unit (ICU) and treated with TCZ from 20 March to 20 May 2020 at a tertiary hospital. Variables analysed were: age, sex, levels of IL-6, C reactive protein (CRP), ferritin, lymphocytes count and D-dimer on days 0, 1, 3, 7 and 14 after TCZ administration. Days in the ICU, deaths and patient outcomes were also obtained. Results Median age was 64 years and 67.4% of patients were men. IL-6 levels on day 0 were 293 pg/mL, peaking at 416 pg/mL on day 3 and decreasing to 241.9 pg/mL on day 7. CRP levels increased above the normal range (median 53.35 mg/L on day 0) in all patients before initiation of therapy with TCZ and decreased on day 7 (median 3 mg/L). Serum ferritin decreased from 1798 mg/L on day 1 to 1197.5 mg/L on day 7 before TCZ. Lymphocyte count increased from 570 to 1365 lymphocytes/mL on day 7. D-dimer level on day 0 was 2008 ng/mL and increased to 3910 ng/mL on day 7 and decreased to 1723 ng/mL on day 14. Length in ICU stay was 16.4 days compared with the mean stay of the total number of ICU COVID patients, which was 26.1 days. Mortality was 19.6%, 15.2% remained in hospital at the end of the study and 65.2% were discharged. Conclusion and relevance The results showed an improvement in inflammatory markers with TCZ treatment, as well as a decrease in length of stay in the ICU, similar to findings reported in the literature. Nevertheless, because of potential bias due to patients receiving different treatments before and after TCZ and the small sample size, it is necessary to confirm these results in controlled clinical studies.

Controlling the pandemic during the SARS-CoV-2 vaccination rollout: a modeling study (preprint)

There is a consensus that mass vaccination against SARS-CoV-2 will ultimately end the COVID-19 pandemic. However, it is not clear when and which control measures can be relaxed during the rollout of vaccination programmes. We investigate relaxation scenarios using an age-structured transmission model that has been fitted to age-specific seroprevalence data, hospital admissions, and projected vaccination coverage for Portugal. Our analyses suggest that the pressing need to restart socioeconomic activities could lead to new pandemic waves, and that substantial control efforts prove necessary throughout 2021. Using knowledge on control measures introduced in 2020, we anticipate that relaxing measures completely or to the extent as in autumn 2020 could launch a wave starting in April 2021. Additional waves could be prevented altogether if measures are relaxed as in summer 2020 or in a step-wise manner throughout 2021. We discuss at which point control of COVID-19 would be achieved for each scenario.