A deficient immune response to SARS-CoV-2 in the nasopharynx is associated with severe COVID-19 pneumonia.

OBJECTIVES: We analyzed the expression of inflammatory and antiviral genes in the nasopharynx of SARS-CoV-2 infected patients and their association with the severity of COVID-19 pneumonia. METHODS: We conducted a cross-sectional study on 223 SARS-CoV-2 infected patients. Clinical data were collected from medical records, and nasopharyngeal samples were collected in the first 24 hours after admission to the emergency room. The gene expression of eight proinflammatory/antiviral genes (plasminogen activator urokinase receptor [PLAUR], interleukin [IL]-6, IL-8, interferon [IFN]-ß, IFN-stimulated gene 15 [ISG15], retinoic acid-inducible gene I [RIG-I], C-C motif ligand 5 [CCL5], and chemokine C-X-C motif ligand 10 [CXCL10]) were quantified by real-time polymerase chain reaction. Outcome variables were: (i) pneumonia; (ii) severe pneumonia or acute respiratory distress syndrome. Statistical analysis was performed using multivariate logistic regression analyses. RESULTS: We enrolled 84 mild, 88 moderate, and 51 severe/critical cases. High expression of PLAUR (adjusted odds ratio [aOR] = 1.25; P = 0.032, risk factor) and low expression of CXCL10 (aOR = 0.89; P = 0.048, protective factor) were associated with pneumonia. Furthermore, lower values of ISG15 (aOR = 0.88, P = 0.021), RIG-I (aOR = 0.87, P = 0.034), CCL5 (aOR = 0.73, P <0.001), and CXCL10 (aOR = 0.84, P = 0.002) were risk factors for severe pneumonia/acute respiratory distress syndrome. CONCLUSION: An unbalanced early innate immune response to SARS-CoV-2 in the nasopharynx, characterized by high expression of PLAUR and low expression of antiviral genes (ISG15 and RIG-I), and chemokines (CCL5 and CXCL10), was associated with COVID-19 severity.

Analyzing the role of ACE2, AR, MX1 and TMPRSS2 genetic markers for COVID-19 severity.

BACKGROUND: The use of molecular biomarkers for COVID-19 remains unconclusive. The application of a molecular biomarker in combination with clinical ones that could help classifying aggressive patients in first steps of the disease could help clinician and sanitary system a better management of the disease. Here we characterize the role of ACE2, AR, MX1, ERG, ETV5 and TMPRSS2 for trying a better classification of COVID-19 through knowledge of the disease mechanisms. METHODS: A total of 329 blood samples were genotyped in ACE2, MX1 and TMPRSS2. RNA analyses were also performed from 258 available samples using quantitative polymerase chain reaction for genes: ERG, ETV5, AR, MX1, ACE2, and TMPRSS2. Moreover, in silico analysis variant effect predictor, ClinVar, IPA, DAVID, GTEx, STRING and miRDB database was also performed. Clinical and demographic data were recruited from all participants following WHO classification criteria. RESULTS: We confirm the use of ferritin (p < 0.001), D-dimer (p < 0.010), CRP (p < 0.001) and LDH (p < 0.001) as markers for distinguishing mild and severe cohorts. Expression studies showed that MX1 and AR are significantly higher expressed in mild vs severe patients (p < 0.05). ACE2 and TMPRSS2 are involved in the same molecular process of membrane fusion (p = 4.4 × 10-3), acting as proteases (p = 0.047). CONCLUSIONS: In addition to the key role of TMPSRSS2, we reported for the first time that higher expression levels of AR are related with a decreased risk of severe COVID-19 disease in females. Moreover, functional analysis demonstrates that ACE2, MX1 and TMPRSS2 are relevant markers in this disease.

Cognitive function and impact on driving after SARS-COV-2 infection in a man with long-standing HIV infection: a case report.

A substantial number of individuals who experience COVID-19 infection experience prolonged physical and mental symptoms after resolution of their initial infection, and among them, many individuals experience cognitive difficulties including memory lapses and executive function difficulties, often referred to as "brain fog." The possible impact of COVID-19 infection on cognition in persons with HIV-related cognitive disorders is unknown. In this report, we describe post-COVID-19 cognitive and driving function in a 62-year-old man with HIV infection since the early 1990s.

Effect of the COVID-19 Pandemic on Musculoskeletal Care in the Emergency Room.

OBJECTIVE: Study the effect of the COVID-19 pandemic on emergency room (ER) utilization for musculoskeletal (MSK) complaints. METHODS: Data from ER encounters in a teaching hospital for years 2019 and 2020 were extracted from an electronic database. The ICD-10-CM code were used to assign the primary diagnosis. Joinpoint regression was applied to time-series to detect changes in daily encounters (all-cause and MSK). Total number and median daily encounters were calculated by year, sex, age groups, and diagnostic codes for each year. RESULTS: Overlapping intervals within March 2020 showed drops of 8.1 all-cause encounters per day (95% CI: 4.8-11.5), and 1.2 MSK encounters per day (95% CI: 0.8-1.7), resulting in net losses for the year of 33.2 % for all-cause and 35.8% for MSK encounters . Reductions were observed for both sexes and all age groups. MSK codes with largest declines were low back pain, joint pain, and limb pain. CONCLUSION: The COVID-19 pandemic resulted in major reductions in all-cause and MSK encounters in the ER of an academic hospital probably due to governmental restricions and a change in patients behavior. Persistence of the observed reduction suggests that patients requiring ER services delayed seeking care for MSK and other health conditions.

Impact of SARS-CoV-2 vaccination and monoclonal antibodies on outcome post-CD19-directed CAR T-cell therapy: an EPICOVIDEHA survey.

Patients with previous CD19-directed chimeric antigen receptor (CAR) T-cell therapy have a prolonged vulnerability to viral infections. Coronavirus disease 2019 (COVID-19) has a great impact and has previously been shown to cause high mortality in this population. Until now, real-world data on the impact of vaccination and treatment on patients with COVID-19 after CD19-directed CAR T-cell therapy are lacking. Therefore, this multicenter, retrospective study was conducted with data from the EPICOVIDEHA survey. Sixty-four patients were identified. The overall mortality caused by COVID-19 was 31%. Patients infected with the Omicron variant had a significantly lower risk of death due to COVID-19 compared with patients infected with previous variants (7% vs 58% [P = .012]). Twenty-six patients were vaccinated at the time of the COVID-19 diagnosis. Two vaccinations showed a marked but unsignificant reduction in the risk of COVID-19-caused mortality (33.3% vs 14.2% [P = .379]). In addition, the course of the disease appears milder with less frequent intensive care unit admissions (39% vs 14% [P = .054]) and a shorter duration of hospitalization (7 vs 27.5 days [P = .022]). Of the available treatment options, only monoclonal antibodies seemed to be effective at reducing mortality from 32% to 0% (P = .036). We conclude that survival rates of CAR T-cell recipients with COVID-19 improved over time and that the combination of prior vaccination and monoclonal antibody treatment significantly reduces their risk of death. This trial was registered at www.clinicaltrials.gov as #NCT04733729.

Targeting RNA:protein interactions with an integrative approach leads to the identification of potent YBX1 inhibitors.

RNA-protein interactions (RPIs) are promising targets for developing new molecules of therapeutic interest. Nevertheless, challenges arise from the lack of methods and feedback between computational and experimental techniques during the drug discovery process. Here, we tackle these challenges by developing a drug screening approach that integrates chemical, structural and cellular data from both advanced computational techniques and a method to score RPIs in cells for the development of small RPI inhibitors; and we demonstrate its robustness by targeting Y-box binding protein 1 (YB-1), a messenger RNA-binding protein involved in cancer progression and resistance to chemotherapy. This approach led to the identification of 22 hits validated by molecular dynamics (MD) simulations and nuclear magnetic resonance (NMR) spectroscopy of which 11 were found to significantly interfere with the binding of messenger RNA (mRNA) to YB-1 in cells. One of our leads is an FDA-approved poly(ADP-ribose) polymerase 1 (PARP-1) inhibitor. This work shows the potential of our integrative approach and paves the way for the rational development of RPI inhibitors.

Burden of infectious disease studies in Europe and the United Kingdom: a review of methodological design choices.

This systematic literature review aimed to provide an overview of the characteristics and methods used in studies applying the disability-adjusted life years (DALY) concept for infectious diseases within European Union (EU)/European Economic Area (EEA)/European Free Trade Association (EFTA) countries and the United Kingdom. Electronic databases and grey literature were searched for articles reporting the assessment of DALY and its components. We considered studies in which researchers performed DALY calculations using primary epidemiological data input sources. We screened 3053 studies of which 2948 were excluded and 105 studies met our inclusion criteria. Of these studies, 22 were multi-country and 83 were single-country studies, of which 46 were from the Netherlands. Food- and water-borne diseases were the most frequently studied infectious diseases. Between 2015 and 2022, the number of burden of infectious disease studies was 1.6 times higher compared to that published between 2000 and 2014. Almost all studies (97%) estimated DALYs based on the incidence- and pathogen-based approach and without social weighting functions; however, there was less methodological consensus with regards to the disability weights and life tables that were applied. The number of burden of infectious disease studies undertaken across Europe has increased over time. Development and use of guidelines will promote performing burden of infectious disease studies and facilitate comparability of the results.

Metabolic Profiling at COVID-19 Onset Shows Disease Severity and Sex-Specific Dysregulation.

Background: metabolic changes through SARS-CoV-2 infection has been reported but not fully comprehended. This metabolic dysregulation affects multiple organs during COVID-19 and its early detection can be used as a prognosis marker of severity. Therefore, we aimed to characterize metabolic and cytokine profile at COVID-19 onset and its relationship with disease severity to identify metabolic profiles predicting disease progression. Material and Methods: we performed a retrospective cross-sectional study in 123 COVID-19 patients which were stratified as asymptomatic/mild, moderate and severe according to the highest COVID-19 severity status, and a group of healthy controls. We performed an untargeted plasma metabolic profiling (gas chromatography and capillary electrophoresis-mass spectrometry (GC and CE-MS)) and cytokine evaluation. Results: After data filtering and identification we observed 105 metabolites dysregulated (66 GC-MS and 40 CE-MS) which shown different expression patterns for each COVID-19 severity status. These metabolites belonged to different metabolic pathways including amino acid, energy, and nitrogen metabolism among others. Severity-specific metabolic dysregulation was observed, as an increased transformation of L-tryptophan into L-kynurenine. Thus, metabolic profiling at hospital admission differentiate between severe and moderate patients in the later phase of worse evolution. Several plasma pro-inflammatory biomarkers showed significant correlation with deregulated metabolites, specially with L-kynurenine and L-tryptophan. Finally, we describe a strong sex-related dysregulation of metabolites, cytokines and chemokines between severe and moderate patients. In conclusion, metabolic profiling of COVID-19 patients at disease onset is a powerful tool to unravel the SARS-CoV-2 molecular pathogenesis. Conclusions: This technique makes it possible to identify metabolic phenoconversion that predicts disease progression and explains the pronounced pathogenesis differences between sexes.

COVID-19 era: Hearing handicaps behind face mask use in hearing aid users.

BACKGROUND: The aim of this study was to assess the effect on speech perception and lack of hearing devices gain with surgical masks worn in hearing aid users. METHODS: This prospective cohort study enrolled consecutive patients between November 2020 and February 2021 in a tertiary care medical center from Spain. Fifty-five subjects have been included, 10 as control group, with normal hearing, and 45 patients with sensory-neural hearing loss and hearing aid users, ranging in age between 31 and 83 years old, and were recruited randomized in 4 months. Appropriate test was done previously to check adequate functioning from devices and suitable adaptation. Control group had no hearing impairment neither otologic disease. RESULTS: Disyllabic test in quiet get worse with face mask with a significant difference and stronger impact in noisy background. Age made no difference. Adding lipreading speech perception improved by 95.1 % for younger subjects (<50 years of age) and 91.2% for older subjects (>50 years of age). In the control sample, there was no differences in any condition. CONCLUSION: Despite advantages of wearing mask in preventing coronavirus disease 2019 spread, we must consider that they have also drawbacks for some groups like hearing aid users. In this research, we have not observed high frequencies perception decrease with surgical masks worn, but there was reduction in speech perception, most notably in hearing aids wearers in noisy environment.

Health information use by patients with systemic lupus erythematosus (SLE) pre and during the COVID-19 pandemic.

OBJECTIVE: We conducted an international survey of patients with SLE to assess their access, preference and trust in various health information sources pre-COVID-19 and during the COVID-19 pandemic. METHODS: Patients with SLE were recruited from 18 observational cohorts, and patients self-reporting SLE were recruited through five advocacy organisations. Respondents completed an online survey from June 2020 to December 2021 regarding the sources of health information they accessed in the 12 months preceding (pre-11 March 2020) and during (post-11 March 2020) the pandemic. Multivariable logistic regressions assessed factors associated with accessing news and social media post-11 March 2020, and self-reporting negative impacts from health information accessed through these sources. RESULTS: Surveys were completed by 2111 respondents; 92.8% were female, 76.6% had postsecondary education, mean (SD) age was 48.8 (14.0) years. Lupus specialists and family physicians were the most preferred sources pre-11 March 2020 and post-11 March 2020, yet were accessed less frequently (specialists: 78.5% pre vs 70.2% post, difference -8.3%, 95% CI -10.2% to -6.5%; family physicians: 57.1% pre vs 50.0% post, difference -7.1%, 95% CI -9.2% to -5.0%), while news (53.2% pre vs 62.1% post, difference 8.9%, 95% CI 6.7% to 11.0%) and social media (38.2% pre vs 40.6% post, difference 2.4%, 95% CI 0.7% to 4.2%) were accessed more frequently post-11 March 2020 vs pre-11 March 2020. 17.2% of respondents reported negative impacts from information accessed through news/social media. Those outside Canada, older respondents or with postsecondary education were more likely to access news media. Those in Asia, Latin America or younger respondents were more likely to access social media. Those in Asia, older respondents, males or with postsecondary education in Canada, Asia or the USA were less likely to be negatively impacted. CONCLUSIONS: Physicians, the most preferred and trusted sources, were accessed less frequently, while news and social media, less trusted sources, were accessed more frequently post-11 March 2020 vs pre-11 March 2020. Increasing accessibility to physicians, in person and virtually, may help reduce the consequences of accessing misinformation/disinformation.

Unidirectional Tactile Paving: Circulation for the Visually Impaired.

The COVID-19 pandemic heightened inequalities of universal accessibility in the built environment. The visually impaired have been affected by the lack of mobility that resulted from social distancing and physical distancing. Numerous circulation networks, from small retail shops to large-scale public spaces, have been reorganized to limit the spread of COVID-19. By assigning an orientation to each lane, unidirectional circulation networks allow for physical distancing by limiting face-to-face interactions among most pedestrians. These unidirectional networks are communicated visually, by placing flat arrows on the floor, but not through the other senses and are thus inaccessible to the visually impaired. This demonstrates a lack of universally accessible design for unidirectional circulation. We propose two designs (asymmetrical blocks and cobblestone blocks) for a novel unidirectional tactile paving which allows the visually impaired to navigate through unidirectional circulation networks by feeling tiles with their feet and/or canes.

Challenges in the Detection of SARS-CoV-2: Evolution of the Lateral Flow Immunoassay as a Valuable Tool for Viral Diagnosis.

SARS-CoV-2 is an emerging infectious disease of zoonotic origin that caused the coronavirus disease in late 2019 and triggered a pandemic that has severely affected human health and caused millions of deaths. Early and massive diagnosis of SARS-CoV-2 infected patients is the key to preventing the spread of the virus and controlling the outbreak. Lateral flow immunoassays (LFIA) are the simplest biosensors. These devices are clinical diagnostic tools that can detect various analytes, including viruses and antibodies, with high sensitivity and specificity. This review summarizes the advantages, limitations, and evolution of LFIA during the SARS-CoV-2 pandemic and the challenges of improving these diagnostic devices.

A Cohort Study in Intensive Care Units: Health Decisions Related to Blood Transfusion during the COVID-19 Pandemic.

Critically ill polytrauma patients with hemorrhage require a rapid assessment to initiate hemostatic resuscitation in the shortest possible time with the activation of a massive transfusion or a critical hemorrhage management protocol. The hospital reality experienced during the COVID-19 pandemic in all countries was critical, as it was in Spain; according to the data published daily by the Ministry of Health on its website, during the period of this study, the occupancy rate of intensive care units (ICUs) by patients diagnosed with the novel coronavirus disease (COVID-19) rose to 23.09% in Spain, even reaching 45.23% at the end of January 2021. We aimed to analyze the changes observed during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic period regarding the effectiveness of Spanish ICUs in terms of mortality reduction. We present a cross-sectional study that compares two cohorts of patients admitted to ICUs across all autonomous communities of Spain with a diagnosis of polytrauma. Results: Only age was slightly higher at admission during the first wave of the pandemic (47.74 ± 18.65 vs. 41.42 ± 18.82 years, p = 0.014). The transfusion rate during the pandemic increased by 10.4% compared to the previous stage (p = 0.058). Regarding hemostatic components, the use of tranexamic acid increased from 1.8% to 10.7% and fibrinogen concentrates from 0.9% to 1.9%. In the case of prothrombin complex concentrates, although there was a slight increase in their use, there were no significant differences during the pandemic compared to the previous period. Conclusion: Mortality showed no difference before and during the pandemic, despite the observed change in the transfusion policy. In summary, the immediate and global implementation of patient blood management (PBM) based on clinical transfusion algorithms should be mandatory in all hospitals in our country.

COVID-19 Secondary Infections in ICU Patients and Prevention Control Measures: A Preliminary Prospective Multicenter Study.

The incidence of secondary infections in critically ill coronavirus disease 2019 (COVID-19) patients is worrisome. We investigated whether selective digestive decontamination (SDD) added to infection control measures during an intensive care unit (ICU) stay modified these infection rates. METHODS: A retrospective observational cohort study was carried out in four ICUs in Spain. All consecutive ventilated patients with a SARS-CoV-2 infection engaged in national infection control programs between 1 March and 10 December 2020 were investigated. Patients were grouped into two cohorts according to the site of ICU admission. Secondary relevant infections were included. Infection densities corresponding to ventilator-associated pneumonia (VAP), catheter bacteremia, secondary bacteremia, and multi-resistant germs were obtained as the number of events per 1000 days of exposure and were compared between SDD and non-SDD groups using Poisson regression. Factors that had an independent association with mortality were identified using multidimensional logistic analysis. RESULTS: There were 108 patients in the SDD cohort and 157 in the non-SDD cohort. Patients in the SDD cohort showed significantly lower rates (p < 0.001) of VAP (1.9 vs. 9.3 events per 1000 ventilation days) and MDR infections (0.57 vs. 2.28 events per 1000 ICU days) and a non-significant reduction in secondary bacteremia (0.6 vs. 1.41 events per 1000 ICU days) compared with those in the non-SDD cohort. Infections caused by MDR pathogens occurred in 5 patients in the SDD cohort and 21 patients in the non-SDD cohort (p = 0.006). Differences in mortality according to SDD were not found. CONCLUSION: The implementation of SDD in infection control programs significantly reduced the incidence of VAP and MDR infections in critically ill SARS-CoV-2 infected patients.

Insights on the evolution of Coronavirinae in general, and SARS-CoV-2 in particular, through innovative biocomputational resources.

The structural proteins of coronaviruses portray critical information to address issues of classification, assembly constraints, and evolutionary pathways involving host shifts. We compiled 173 complete protein sequences from isolates belonging to the four genera of the subfamily Coronavirinae. We calculate a single matrix of viral distance as a linear combination of protein distances. The minimum spanning tree (MST) connecting the individuals captures the structure of their similarities. The MST re-capitulates the known phylogeny of Coronovirinae. Hosts were mapped onto the MST and we found a non-trivial concordance between host phylogeny and viral proteomic distance. We also study the chimerism in our dataset through computational simulations. We found evidence that structural units coming from loosely related hosts hardly give rise to feasible chimeras in nature. This work offers a fresh way to analyze features of SARS-CoV-2 and related viruses.

Stem cells as an option for the treatment of COVID-19.

The application of stem cells is among the many strategies currently available for the treatment of multiple diseases. Stem cells are characterized as undifferentiated cells that have the ability to differentiate towards multiple lineages and self-renewal, among other attributes. Since the first umbilical cord stem cell transplant for the treatment of Fanconi anemia, the use of stem cells for the treatment of multiple diseases, including coronavirus disease 2019, has increased, showing promising results that require evaluation through research studies that include a longer follow-up time. Therefore, the main objective of this Letter is to provide an update on the use of stem cells in the treatment of severe acute respiratory syndrome coronavirus 2, as well as identify the main challenges and limitations presented by this type of therapy.

General Labor Well-Being in Latin American Dentists during the COVID-19 Pandemic.

This study aimed to determine the general labor well-being of Latin American dentists according to sociodemographic characteristics during the COVID-19 pandemic. A cross-sectional study was conducted in a final sample of 2214 participants from 11 countries. A validated online questionnaire on general work well-being was used (data collection period from 1 June to 10 July 2021), containing two dimensions: psychosocial well-being and collateral effects. The sociodemographic characteristics of the dentists and their perception of the economic impact of the pandemic were also recorded. A multivariate linear regression analysis was performed (hierarchical regression model) to evaluate the joint effect of the explanatory variables on labor well-being and the changes in the variance between each model. A score of psychosocial well-being of 233.6 + 40.2 and collateral effects of 45 + 20.1 was found. Psychosocial well-being was associated with sex, country of origin, academic training achieved, type of dental activity, and perceived impact during the pandemic (p < 0.05). Somatization was frequently manifested through back pain (88.2%) and muscular tensions (87.2%). Women, those who worked 41 or more hours and had between 1 to 15 years of professional experience presented a greater collateral effect (p < 0.001). The impact of the COVID-19 pandemic a year and a half after it began on the labor well-being of Latin American dentists was evidenced with important interactions with social characteristics.