The Scalpel and the Brush: Explosion and Culture of the Pandemic Body

The article adopts the framework of Lotman's last cultural semiotics in order to rethink a thorny contemporary issue, that is, the diffused antagonism against science, medicine, and vaccinations during the ongoing COVID-19 pandemics. The article interprets this irrational animadversion as the outcome of a dialectics that stems at least from the origin of modernity, and precisely from the opposition between a semiotic ideology of stillness, regularity, and order, underpinning the genesis of modern science, and an opposed semiotic ideology of motion, irregularity, and chaos, characterizing most of the modern aesthetics of idealism and singularity. After exploring this opposition through a crucial cultural text situated at the beginning of the tension between these two different approaches to meaning and life, the article concludes that modern sciences and medicine should continue searching for regularities in the world and in the body, for the sake of improving the human quality of life, but should also learn from the cultural semiotics of aesthetic ideologies: in times of epistemic incertitude and turmoil, old myths extolling the singularity of the body tend to resurface, jeopardizing the credibility of medicine.

Paxlovid Use in COVID-19 Infection: An Ounce of Prevention Is Worth a Pound of Cure

Introduction: Paxlovid (nirmatrelvir+ ritonavir) is a promising new combination drug that can significantly reduce hospitalization and all-cause mortality in Covid-19 infection. Ritonavir is a potent inhibitor of cytochrome-P450 system CYP3A enzymes and concomitant use with calcineurin inhibitors (CNI) such as tacrolimus can dangerously increase CNI blood levels. We present a heart transplant recipient on tacrolimus who developed acute kidney injury (AKI) and refractory life-threatening hyperkalemia following Paxlovid use and successful treatment using P450 induction with phenytoin along with dialysis support. Case Description: A 43-year-old male with CKD stage III and previous heart transplant on tacrolimus was admitted with dyspnea, malaise, and oliguria. Few days earlier, he developed Covid-19 infection and received 5-day course of Paxlovid prescribed from elsewhere. On presentation, patient was hypervolemic, with the following serum values: K+ 7.1 mMol/L (peaking to 8.3 despite medical therapy), HCO3-17 mMol/L and creatinine 4.67 mg/dL (baseline 3.0). Patient required emergent hemodialysis. Tacrolimus trough level came back as >60 ng/mL Patient was started on IV phenytoin 100 mg every 12 hours. Tacrolimus levels remained extremely high over next few days with subsequent improvement (fig.). Patient required 4 dialysis sessions. Subsequently urine output improved, and serum creatinine returned to baseline. Discussion(s): Paxlovid use will likely increase with Covid-19 surge. This drug has important safety risks in organ transplant recipients and kidney disease as highlighted by our case, where supratherapeutic tacrolimus levels due to P450 inhibition resulted in AKI and hyperkalemia. Empiric dose reduction or withholding CNI agents when initiating Paxlovid with close CNI level monitoring is recommended. Risk mitigation strategies are also important such as interruptive alerts in electronic health records, educational outreach, and alerting pharmacies about Paxlovid-CNI interactions.

Impact de la dexaméthasone et du monoxyde d’azote inhalé sur le risque l’insuffisance rénale aiguë sévère chez les patients en réanimation pour COVID-19

Introduction La défaillance rénale est la deuxième atteinte la plus fréquente après le syndrome de détresse respiratoire aiguë (SDRA), chez les patients en réanimation suite au COVID-19, et est fortement associée à la mortalité. Description L’objectif de cette étude multicentrique était d’analyser l’impact des traitements spécifiques du COVID-19 et du SDRA sur le risque d’IRA sévère chez les patients en réanimation pour COVID-19 sévère. Méthodes Dans cette étude de cohorte, les données de patients consécutifs hospitalisés dans 6 unités de réanimation pour COVID-19 étaient collectées rétrospectivement. L’incidence et la sévérité de l’IRA étaient monitorées durant tout le séjour en réanimation. Les patients majeurs hospitalisés en réanimation pour SDRA secondaire à un COVID-19 sévère nécessitant la ventilation mécanique était inclus. Résultats Au total, 164 patients ont été inclus dans l’analyse finale, 97 (59,1 %) présentaient une IRA, dont 39 (23,8 %) une IRA sévère KDIGO 3 et 21 (12,8 %) nécessitant une épuration extrarénale (EER). En analyse univariée, l’IRA sévère était associée à l’exposition aux inhibiteurs de l’enzyme de conversion de l’angiotensine (IEC) (p=0,016), à l’HTA (p=0,029), au score de gravité APACHE-II (p=0,004) et à la mortalité à j28 (p=0,008), j60 (p<0,001) et j90 (p<0,001). En analyse multivariée, les facteurs associés à l’apparition d’une IRA sévère étaient : l’exposition aux IEC (OR : 4,238 (1,307–13,736), p=0,016), le score APACHE-II (sans l’âge) (OR : 1,138 (1,044–1,241), p=0,003) et le monoxyde d’azote (NO) inhalé (OR : 5,694 (1,953–16,606), p=0,001). Les facteurs protecteurs étaient le décubitus ventral (OR : 0,234 (0,057–0,967), p=0,045) et la dexaméthasone (OR : 0,194 (0,053–0,713), p=0,014) (Figure 1). Conclusion La dexaméthasone est associée à une prévention du risque d’IRA sévère et d’EER, et le NO inhalé est associé à un risque d’IRA sévère et d’EER chez les patients en réanimation suite à un COVID-19. Le NO inhalé doit être utilisé avec précaution au cours du SDRA du au COVID-19.

Education increases teleneurology utilization: towards the Intersectoral Global Action Plan on epilepsy in Africa

Background and aims: Epilepsy burden in sub-Saharan Africa (SSA) has increased dramatically in the last 20 years. People with epilepsy (PWE) are estimated to be over 20 millions, with about 1 neurologist every 3-5 millions inhabitants, meaning more than 90% of epileptic patients are managed by health workers (HW) with insufficient education in Epilepsy, and 75% of them have no access to treatments. Moreover COVID-19 pandemic is affecting epilepsy management in SSA through care disruption. Teleneurology has the potential to improve this situation, although poor education of HW is associated with its underutilization. We measured the changes of teleneurology requests from primary cares in SSA after an education program on epilepsy. Methods: Global Health Telemedicine (GHT) offers remote advices and education to HW of the Disease Relief through Excellent and Advanced Means (DREAM) program active in 10 SSA countries. GHT-DREAM recently started an epilepsy program in Malawi and Central African Republic (CAR) with education and training courses delivered both locally and remotely. Results: In Malawi and CAR DREAM follows 18,770 patients, 569 (3,0%) suffering from epilepsy. The total number of teleneurology requests increased from 91 in 2019 to 141 in 2020 to 802 in 2021;>90% were for PWE. Conclusion: Education and training in epilepsy increased the number of tele-requests by improving knowledge and communication between SSA HW and European neurologists. Partnerships can bring neurologists where there are none, contributing to limit COVID-19 care disruption thus reducing the treatment gap in SSA. Our results move towards the Intersectoral Global Action Plan 2022-2031 in SSA. (Figure Presented).

Mi Reloj Interno (My endogenous clock): an evidence-based mobile-app to improve sleep and circadian rhythms

Introduction: The human circadian clock is daily entrained by both light exposure and daily social schedules, which were severely affected during the pandemic-associated lockdown. In a previous work we found that after one month of lockdown, Argentinian residents exhibited later chronotypes compared with a pre-pandemic situation, despite they slept longer and showed less social jetlag (Leone M.J. et al, Current Biology). In this study, we collected an independent set of local data with the aim to develop an evidence-based mobile app that offers customized recommendations to improve and maintain healthy sleep and circadian rhythms. Materials and methods: Data was collected throughout a phone/website survey between July and September 2020 (n=4460, after 4-6 months into lockdown) in Argentina. The survey included questions about demographic factors, habits, and previously standardized and validated questionnaires (MEQ, MCTQ, PSQI). Data from Buenos Aires city and suburbs (n=3246) was calibrated to match the population distribution and it was used to run the main analyses. The rest of the database was used to validate results. We conducted a cross validation process using linear models, which included a feature selection process to find the most relevant regressors to fit each chronotype and sleep-related variable. For a given age and gender, each model predicted a set of optimal values for the regressors (e.g. sunlight exposure, regular activities) where the dependent variable is maximized (or minimized). Finally, the recommendation system is based on the comparison between optimal and actual values for each predictor, considering the most affected variables. Results: The final calibrated sample (age: 41.3±15.5, 67% female) shows late chronotypes (MSFsc: 06:00±11min, MEQ score: 49.42±11.3), low levels of social jetlag (0.99h±1.09) and considerable long sleep duration on weekdays (7.31h±1.43). The regressors which significantly affect at least one variable were light exposure, use of alarm, naps and regular activities (and its timing, i.e. work, study, dinner, other activities) as well as age and gender (and interactions). We found no effects of cohabitation, exercise timing and use of screens. The optimal levels of the selected regressors were used to build the recommendation system (i.e. algorithm) on which the mobile app MiRelojInterno is based (available for both Android and iOS platforms, www.mirelojinterno.org). Conclusions: We developed a mobile app based on local evidence that inquires about habits, chronotype and sleep, returns to its users an overview of their current state -including all variables and predictors- along with customized recommendations with the aim to create awareness and improve and maintain healthy sleep and circadian rhythms depending on the age, gender and habits. Acknowledgements: This research project was supported by CONICET and Agencia I+D+i (IP-COVID19-679).

IMPACT OF DEXAMETHASONE AND INHALED NITRIC OXIDE ON SEVERE ACUTE KIDNEY INJURY IN CRITICALLY ILL PATIENTS WITH COVID-19

BACKGROUND AND AIMS: Kidney failure is the second most frequent condition after acute respiratory distress syndrome (ARDS) in critically ill patients with severe COVID-19 and is strongly associated with mortality. The aim of this multicentric study was to assess the impact of the specific treatments of COVID-19 and ARDS on the risk of severe acute kidney injury (AKI) in critically ill COVID patients. METHOD: Data from a prospectively collected database of consecutive patients hospitalized in six ICUs for COVID-19 was retrospectively analysed. The incidence and severity of AKI were monitored during the entire ICU stay. Patients older than 18 years hospitalized in for COVID-19-related ARDS requiring mechanical ventilation were included. RESULTS: A total of 164 patients were included in the final analysis, 97 (59.1%) displayed AKI, of which 39 had severe stage 3 AKI and 21 (12.8%) requiring renal replacement therapy (RRT). In univariate analysis, severe AKI was associated with ACEI exposure (P = .016), high blood pressure (P = .029), APACHE-II score (P = .004) and mortality at D28 (P = .008), D60 (P < .001) and D90 (P < .001). In multivariate analysis, the factors associated with the onset of stage 3 AKI were: exposure to CEI [OR: 4.238 (1.307-13.736);P = .016], APACHE II score (without age) [OR: 1.138 (1.044-1.241);P = .003] and iNO [OR: 5.694 (1.953-16.606);P = .001], protective factors were prone positioning [OR: 0.234 (0.057-0.967);P = .045] and dexamethasone [OR: 0.194 (0.053-0.713);P = .014]. CONCLUSION: Dexamethasone seems to prevent the risk of severe AKI and RRT, and iNO seems associated with severe AKI and RRT in critically ill patients with COVID-19. iNO must be used with caution in COVID-19 related ARDS.

Accessibilità post-pandemia: riflessioni sullo spazio pubblico

The correlation between the psycho-physical well-being of citizens and the provision of green areas has been one of the cornerstones of urban planning since its inception, as its constant commitment to adapt cities and territories to emerging challenges. The spread of COVID-19 has changed the relationship between citizens and urban space. The public space has been limited and banned, confining citizens within their private space and the psycho-physical well-being of citizens depended only on the quality of the domestic space. The pandemic represents a moment of reflection and research for the disciplines that deal with the quality of life of citizens. The pandemic crisis may be an opportunity to rethink the role and importance of the provision of public space and urban green areas, their distribution and effective accessibility. The paper analyzes current models of urban development as potential responses to the challenges of the post-pandemic city. © 2020 Author(s).

Longitudinal Study after Sputnik V Vaccination Shows Durable SARS-CoV-2 Neutralizing Antibodies and Reduced Viral Variant Escape to Neutralization over Time

Recent studies have shown a temporal increase in the neutralizing antibody potency and breadth to SARS-CoV-2 variants in coronavirus disease 2019 (COVID-19) convalescent individuals. Here, we examined longitudinal antibody responses and viral neutralizing capacity to the B.1 lineage virus (Wuhan related), to variants of concern (VOC;Alpha, Beta, Gamma, and Delta), and to a local variant of interest (VOI;Lambda) in volunteers receiving the Sputnik V vaccine in Argentina. Longitudinal serum samples (N = 536) collected from 118 volunteers obtained between January and October 2021 were used. The analysis indicates that while anti-spike IgG levels significantly wane over time, the neutralizing capacity for the Wuhan-related lineages of SARS-CoV-2 and VOC is maintained within 6 months of vaccination. In addition, an improved antibody cross-neutralizing ability for circulating variants of concern (Beta and Gamma) was observed over time postvaccination. The viral variants that displayed higher escape to neutralizing antibodies with respect to the original virus (Beta and Gamma variants) were the ones showing the largest increase in susceptibility to neutralization over time after vaccination. Our observations indicate that serum neutralizing antibodies are maintained for at least 6 months and show a reduction of VOC escape to neutralizing antibodies over time after vaccination. IMPORTANCE Vaccines have been produced in record time for SARS-CoV-2, offering the possibility of halting the global pandemic However, inequalities in vaccine accessibility in different regions of the world create a need to increase international cooperation. Sputnik V is a recombinant adenovirus-based vaccine that has been widely used in Argentina and other developing countries, but limited information is available about its elicited immune responses. Here, we examined longitudinal antibody levels and viral neutralizing capacity elicited by Sputnik V vaccination. Using a cohort of 118 volunteers, we found that while anti-spike antibodies wane over time, the neutralizing capacity to viral variants of concern and local variants of interest is maintained within 4 months of vaccination. In addition, we observed an increased cross-neutralization activity over time for the Beta and Gamma variants. This study provides valuable information about the immune response generated by a vaccine platform used in many parts of the world.

Feminist Security Studies and Care Ethics: Security in Latin America in the Wake of the Pandemic

Security in Latin America has traditionally been addressed from a state-centric and notable realistic perspective, underlining the threats to the state, from an external actor or from internal destabilization. This paper aims to highlight the suitability of incorporating Feminist Security Studies and Care Ethics in security analysis in order to redefine threats and what "feeling safe" implies, especially in the scenario generated by the COVID-19 pandemic. To this end, the gaps and silences in mainstream theories in the diagnoses on the worsening of the security challenges in the first semester of the pandemic are evidenced. Also, the nuances and perceptions of security included in the Care Ethics approach are highlighted. It is concluded that the conceptual broadening that the Care Ethics approach entails is relevant to analyze -academically and politically- the security threats in Latin America.

Post-pandemic accessibility: reflections on public space

The correlation between the psycho-physical well-being of citizens and the provision of green areas has been one of the cornerstones of urban planning since its inception, as its constant commitment to adapt cities and territories to emerging challenges. The spread of COVID-19 has changed the relationship between citizens and urban space. The public space has been limited and banned, confining citizens within their private space and the psycho-physical well-being of citizens depended only on the quality of the domestic space. The pandemic represents a moment of reflection and research for the disciplines that deal with the quality of life of citizens. The pandemic crisis may be an opportunity to rethink the role and importance of the provision of public space and urban green areas, their distribution and effective accessibility. The paper analyzes current models of urban development as potential responses to the challenges of the post-pandemic city.

Prolonged intubation in patients with prior cerebrovascular disease and COVID-19

Objective: To determine the odds of critical illness by day 28 and duration of mechanical ventilation (MV) over 45-day observation period in patients with history of cerebrovascular disease and COVID-19. Background: COVID-19-associated morbidity is correlated with multiple factors including age, comorbidities, and host response to the virus. Our understanding of the risk of critical illness due to prior neurological conditions remains limited. Here, we hypothesized that prior cerebrovascular disease is a risk factor for severe outcomes in COVID-19, including increased duration of MV. Design/Methods: A cross-sectional study of 1128 consecutive adult patients admitted to a tertiary care center in Boston, Massachusetts, and diagnosed with laboratory-confirmed COVID-19. The association between history of cerebrovascular disease and critical illness defined as MV or death was examined using logistic regression with inverse probability weighting of the propensity score. Cumulative incidence of successful extubation without death over 45 days was examined using competing risk analysis. Results: Of the 1128 adults admitted with COVID-19, 350 (36%) were critically ill by day 28. The median age was 59 years (standard deviation: 18 years), 640 (57%) were men, and 401 (36%) were Latinx ethnicity. As of June 2nd, 2020, 127 (11%) patients died. A total of 257 (23%) of patients had a prior neurological diagnosis;most common was cerebrovascular disease (16%). Prior cerebrovascular disease was significantly associated with critical illness (OR 1.54 [95% CI: 1.14 - 2.07]), lower rate of successful extubation (cause-specific HR 0.57 [95% CI: 0.33-0.98]), and increased duration of intubation (restricted mean time difference 4.02 days [95% CI: 0.34- 10.92]) compared to patients without cerebrovascular disease. Conclusions: History of cerebrovascular disease adversely affects COVID-19 outcomes including increased risk of critical illness and prolonged intubation. Further studies are needed to define measures that reduce risk of poor outcomes in this subpopulation.

EAN consensus statement for management of patients with neurological diseases during the COVID-19 pandemic.

BACKGROUND AND PURPOSE: The recent SARS-CoV-2 pandemic has posed multiple challenges to the practice of clinical neurology including recognition of emerging neurological complications and management of coexistent neurological diseases. In a fast-evolving pandemic, evidence-based studies are lacking in many areas. This paper presents European Academy of Neurology (EAN) expert consensus statements to guide neurologists caring for patients with COVID-19. METHODS: A refined Delphi methodology was applied. In round 1, statements were provided by EAN scientific panels (SPs). In round 2, these statements were circulated to SP members not involved in writing them, asking for agreement/disagreement. Items with agreement >70% were retained for round 3, in which SP co-chairs rated importance on a five-point Likert scale. Results were graded by importance and reported as consensus statements. RESULTS: In round one, 70 statements were provided by 23 SPs. In round two, 259/1061 SP member responses were received. Fifty-nine statements obtained >70% agreement and were retained. In round three, responses were received from 55 co-chairs of 29 SPs. Whilst general recommendations related to prevention of COVID-19 transmission had high levels of agreement and importance, opinion was more varied concerning statements related to therapy. CONCLUSION: This is the first structured consensus statement on good clinical practice in patients with neurological disease during the COVID-19 pandemic that provides immediate guidance for neurologists. In this fast-evolving pandemic, a rapid response using refined Delphi methodology is possible, but guidance may be subject to change as further evidence emerges.

Increased in-hospital mortality from COVID-19 in patients with schizophrenia.

BACKGROUND: There is limited information describing the presenting characteristics and outcomes of patients with schizophrenia (SCZ) requiring hospitalization for coronavirus disease 2019 (COVID-19). AIMS: We aimed to compare the clinical characteristics and outcomes of COVID-19 SCZ patients with those of non-SCZ patients. METHOD: This was a case-control study of COVID-19 patients admitted to 4 AP-HM/AMU acute care hospitals in Marseille, southern France. COVID-19 infection was confirmed by a positive result on polymerase chain reaction testing of a nasopharyngeal sample and/or on chest computed scan among patients requiring hospital admission. The primary outcome was in-hospital mortality. The secondary outcome was intensive care unit (ICU) admission. RESULTS: A total of 1092 patients were included. The overall in-hospital mortality rate was 9.0%. The SCZ patients had an increased mortality compared to the non-SCZ patients (26.7% vs. 8.7%, P=0.039), which was confirmed by the multivariable analysis after adjustment for age, sex, smoking status, obesity and comorbidity (adjusted odds ratio 4.36 [95% CI: 1.09-17.44]; P=0.038). In contrast, the SCZ patients were not more frequently admitted to the ICU than the non-SCZ patients. Importantly, the SCZ patients were mostly institutionalized (63.6%, 100% of those who died), and they were more likely to have cancers and respiratory comorbidities. CONCLUSIONS: This study suggests that SCZ is not overrepresented among COVID-19 hospitalized patients, but SCZ is associated with excess COVID-19 mortality, confirming the existence of health disparities described in other somatic diseases.