Clinical Features and Biomarkers

Prevalence and long-term outcomes of acute kidney injury (AKI) in patients with Coronavirus Disease 19 (COVID-19) are not entirely known. Nevertheless, the incidence of AKI in those severe cases requiring hospitalization ranges from 2.9 to 50%, depending on definitions and clinical settings [1-5]. Several pathophysiological mechanisms leading to AKI have been recognized in COVID-19 disease. Beyond the direct renal cell invasion from the Severe Acute Respiratory Syndrome Virus-2 (SARS-CoV-2), restrictive fluid strategies, hypoxia, cytokine storm, nephrotoxic drugs, and bacterial superinfections may be identified as co-acting factors for the AKI development and worsening (see Chap. 20) (Fig. 17.1). When associated with COVID-19, AKI (AKI COVID-19) worsens the patient's outcomes, and affects health care staffing by increasing the requirement of personnel, equipment, and organizational resources. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2022.

Brief Pathophysiology

The severe acute respiratory syndrome due to coronavirus-2 infection (SARS-CoV-2) was first described in humans in December 2019 in Wuhan, China [1]. SARS-CoV-2 is the third coronavirus that has emerged in the last 20 years, and its pandemic infection was declared on March 11, 2020, by the World Health Organization [1]. The potential impact of SARS-CoV-2 disease (COVID-19) on the kidney is still undetermined. Emerging evidence indicates that renal involvement is frequently observed in COVID-19 patients, with peculiar characteristics among those with chronic kidney disease, end-stage renal disease, and kidney transplant recipients [2]. Patients diagnosed with acute kidney injury (AKI) present a more severe clinical picture, worst illness severity scores, persistent lymphopenia, and require invasive mechanical ventilation and vasoactive support during hospitalization. These characteristics ultimately suggest AKI as a marker of COVID-19 severity [3]. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2022.

Fading Voices: COVID-19, Language Death and the Case of Bergamasco in Italy

The chapter explores the impact of the Coronavirus Disease 2019 (COVID-19) pandemic on language endangerment in Italy. Despite their misleading name, Italian Dialects (IDs) are sister languages of Italian and independently developed from Latin. Since the introduction of compulsory education in the 1960s and concurrent Italy's sharp industrialisation, IDs are in decline, and a clear language shift is detectable towards the dominant national language: Italian. IDs are hence only discretely vital among the aging population with the younger generations having broken their intergenerational transmission. Given the higher mortality rates among the elderly and the strict intermittent national and regional lockdowns enforced by the Italian Government, the COVID-19 pandemic has accelerated the process of language death across Italy. This is particularly noticeable in Bergamo, one of the Italian provinces most affected by COVID-19, where the disease caused a five-fold increase in excess mortality in March 2020. In the same period, COVID-19 was the attributable cause of death in half of those older than 50 and the mean age of those dying for COVID-19 was 80. The death toll of COVID-19 on the elderly population has left Bergamasco, the ancestral language of Bergamo, a step closer to extinction. By taking Bergamasco as a case study, the chapter denounces the vulnerability of IDs and the negative impact of the COVID-19 pandemic on their level of vitality. To this aim, the chapter presents a quantitative sociolinguistic study of the vitality of Bergamasco in relation to COVID-19 incidence and lethality rates in the province of Bergamo. © The Author(s), under exclusive license to Springer Nature Switzerland AG 2022.

COVID-19 and Renal Replacement Therapies

Although Severe Acute Respiratory Syndrome CoronaVirus (SARS-CoV-2) infection primarily manifests as an acute pulmonary disease (COronaVirus Disease 2019;COVID-19) and respiratory failure with interstitial and alveolar pneumonia, it frequently affects multiple organs, including the kidneys, heart, gut, and nervous system. Acute kidney injury (AKI) is emerging as a common and important sequela of COVID-19, with rates as high as 33-43% among hospitalized patients [1]. In case of respiratory failure, AKI affects over 50% of patients admitted to the intensive care unit (ICU) [2]. Among critically ill patients, AKI frequently manifests as a severe oligo-anuric phenotype and imposes the use of renal replacement therapy (RRT) [3, 4]. In fact, RRT is frequently required to treat ICU patients with severe COVID-19 related AKI (C-19-AKI), and different modalities have been described in the literature (Continuous RRT-CRRT;Intermittent Hemodialysis-IHD;Peritoneal Dialysis-PD) [3]. Specifically, careful management of fluid balance and electrolyte disorders has been found to be beneficial in patients with severe C-19-AKI requiring RRT [5]. Not surprisingly, C-19-AKI requiring RRT is also associated with a particularly poor outcome. In fact, renal failure is now a well-established independent risk factor linked with increased in-hospital mortality [3, 4]. A recent study involving COVID-19 patients found that 63% of the patients exhibited proteinuria, 19% had an elevated plasma creatinine level, and 27% had an elevated urea nitrogen level [6]. During the first pandemic peak, 451 adult COVID-19 patients admitted to ICUs at the Karolinska University Hospital showed an overall incidence of AKI of 43.7% (9.5% had AKI grade I, 8.9% AKI grade II, and 25.3% experienced AKI grade III) [7]. Compared to non-AKI patients, AKI patients had a prolonged, doubled, length of stay, higher SAPS III scores, and 18.2% received CRRT while on ICU [7]. Even if the overall 30-day mortality for the COVID-19 cohort was 19.1% (and 23.1% at 60 days), mortality of AKI patients was much higher (42.6%) compared to patients with no-AKI (8.7%). As expected, mortality was proportional to the severity of AKI being 27.9% in grade I, 40.0% in grade II, and 49.1% in grade III [7]. Finally, 45.1% of those who received CRRT died up until the end of follow-up, showing that mortality in the CRRT group was significantly higher than in non-CRRT patients with a hazard ratio of 2.59 (confidence interval, CI 1.73-3.86, P ≤ 0.001) [7]. Interestingly, predictors of hospital mortality for CRRT patients were a higher age at admission, being 55 (IQR 52-64) years in survivors vs. 63 (IQR 58-68) years in nonsurvivors, weight change during hospital stay, being -10.5 (-15.3 to 6.7)% in survivors and -1.2 (-4.1 to +0.7)% in nonsurvivors, and a higher baseline creatinine value [7]. These data show that older subjects with accumulation of fluid excess and preinfection renal disfunction showed the worse outcomes. Mortality appeared to be highly variable in different publications. In one Italian report of COVID-19 patients, it was 38.9% and 52.9% for AKI patients and for those who received CRRT, respectively [8]. In a second report, AKI incidence was 22.6% with a mortality of 63% [9]. In a cohort of nearly 4000 hospitalized patients in New York, 76% of the 976 ICU patients had AKI, 19% received RRT and in-hospital mortality in the AKI group was 50% [10]. The largest prospective study on RRT in C-19-AKI is the Study of the Treatment and Outcomes in Critically Ill Patients with COVID-19 (STOP-COVID), a multicenter cohort study at 67 geographically diverse hospitals across the USA [1]. A total of 3099 patients were included in the analysis and 637 of them patients (20.6%) developed AKI requiring RRT within 14 days following ICU admission. Patients with RRT were similar in age to patients without AKI-RRT and were more likely to have comorbidities (e.g., diabetes mellitus, hypertension, and chronic kidney disease-CKD), and to have greater severity of illness on arrival to the ICU, including igh r rates of invasive mechanical ventilation and treatment with vasopressors. In the 637 AKI-RRT patients, the median time from ICU admission to RRT initiation was 4 days (IQR 2-7 days), and in 52.4% of the cases the modality was CRRT. The remaining modalities included intermittent hemodialysis in 30.0%, "hybrid” RRT (a CRRT conducted for <12 h/day) in 14.9%, and PD in 1.3%. CKD was associated with a higher risk of AKI-RRT (odds ratio, 5.63), and additional patient-specific risk factors for AKI-RRT included sex (men at higher risk), nonwhite race, hypertension, diabetes mellitus, higher body mass index, lower PaO2: FiO2 ratio on ICU admission, and d-dimer >2500 ng/mL on ICU admission. Among the 637 patients with AKI-RRT, 28-day mortality was 54.9%. Older age, receipt of two or more vasopressors at the time of RRT initiation, and severe oliguria (urine output <100 mL/day) at the time of RRT initiation were each associated with a higher risk of 28-day mortality, whereas CKD stage 4 or 5 was associated with a lower risk of 28-day mortality. Among the 216 patients discharged, 33.8% remained RRT dependent on discharge [1]. A recent large meta-analysis on AKI and RRT in COVID-19 patients analyzed 58 observational studies and 22, 671 patients [11]. The pooled AKI incidence rate was 12.3% and 39% among the ICU patients. A total of 12 studies reported that AKI incidence among deceased patients was 42.0%. Furthermore, in 7 studies, among 1588 AKI patients, the proportions of stage 1, 2, and 3 AKI were 36.3%, 20.7%, and 43.0%, respectively. RRT was used to treat 939 out of 17, 664 COVID-19 patients in 39 selected studies, for a pooled application rate of 5.4% and in the overall ICU patients RRT use was 16.3% [11]. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2022.

Persistent dyspnea in post-COVID patients in the absence of pulmonary embolism: added value of lung perfusion scintigraphy

Aim/Introduction: While there's a wide literature on Computed Tomography (CT) abnormalities in COVID-19 sequelae, the role of lung perfusion scintigraphy has been scarcely investigated. Recent findings reported lung microvascular and endothelial alterations in patients recovered from COVID-19 without pulmonary embolism (PE), presenting persistent dyspnea (post-COVID). We compared perfusion scintigraphy and CT findings of post-COVID patients with dyspneic subjects in whom lung scintigraphy excluded pulmonary embolism (non-COVID). The correlation between lung perfusion scintigraphy findings and 1) CT abnormalities and 2) clinical/biochemical parameters were also assessed. Material(s) and Method(s): 18 post-COVID and 20 non-COVID patients who underwent lung perfusion scintigraphy and chest high-resolution CT for dyspnea from March 2020 to April 2022 were retrospectively enrolled. From lung perfusion scintigraphy images, counting rates for upper, middle, and lower fields were normalized for the total lung counts to calculate the corresponding ratios (UTR, MTR, and LTR, respectively). CT images were analyzed using a semiautomated segmentation algorithm of 3DSlicer (www.slicer. org), obtaining total, emphysematous, infiltrated and collapsed volumes, normalized for the total lung volumes. Similarly, blood vessel's volumes were collected to compute the vascular density. White blood cells (WBC) count, PT, INR, PTT and D-dimer of both groups, and the infection duration of post-COVID patients were collected from clinical records and blood tests performed before the lung perfusion scintigraphy. Result(s): At the per lung analysis, post-COVID patients with persistent dyspnea showed reduced LTR (24.67>5.08) and higher MTR (52.51>5.22) compared to non-COVID patients (29.85>5.05 and 46.66>3.94, respectively;p<0.0001 for both), while UTR resulted bilaterally superimposable between the two groups. At CT imaging, the rates of emphysematous, infiltrated and collapsed volumes and the vascular density were bilaterally similar in both groups. In post-COVID patients, LTR correlated with the percentage of emphysematous (r=0.498;p<0.01), infiltrated (r=-0.464;p=<0.01) and collapsed (r=-0.463;p<0.01) lungs, while no significant correlations were observed between LTR and CTderived volumes in non-COVID subjects. There was no correlation between lung perfusion scintigraphy parameters with infection duration in post-COVID, WBC, and coagulation biomarkers in both groups. Conclusion(s): Lung perfusion scintigraphy can reveal reduced perfusion rates of lower pulmonary fields in post-COVID patients with persistent dyspnea without pulmonary embolism. This phenomenon is correlated with structural lung modifications, including lung parenchymal emphysema, infiltration and collapse, and is independent of infection duration and coagulation biomarkers. Although mechanisms underlying these findings need to be supported by pathological lung tissue examination, pulmonary non-thrombotic microvascular and endothelial dysfunction may be involved.

Targeting the main responsible of human infections with nanoparticles

Infectious diseases cause around 20% of global mortality. Bacterial and viral infections stand among the top 10 global causes of death, including respiratory infections, tuberculosis, HIV/AIDS, dengue, and most recently severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The clinical approach to treat bacterial infections has been the use of antibiotics, whereas for viral infections the use of vaccines and specific drugs that reduce viral replication have been the most effective approaches, respectively. The overuse of antibiotics and antifungal compounds added to the natural evolution of microorganisms has opened a new era of multidrug-resistant bacteria and fungi. The development and clinical trial of novel antimicrobial agents require many years and millions of dollars in research. During the last decade, the area of nanotechnology has evolved to produce innovative solutions for human problems. Here, we present an overview of the uses and applications of nanoparticles targeting the main responsible of human infections, particularly bacterial, fungal, and viral infections. The use of nanoparticles is considered as an alternative or complementary strategy to the clinical treatment of infections. The versatility and multifunctionality of nanoparticles make them ideal to treat, inhibit, and diagnose infections, especially emerging infectious agents that do not have a specific treatment or vaccine available. © 2023 Elsevier Inc. All rights reserved.

COVID-19 and the Environment: Pandemics, Climate, and Ecosystems, and the Environmental Challenge in Dialysis

The recent COVID-19 pandemic has had a significant impact on the population worldwide. Patients with chronic kidney disease treated with kidney replacement therapy were no exception because they were considered highly vulnerable due to multiple comorbidities. The consequences of the physical, biological, and ecological system on the environment as a result of human activity represent a huge global health care danger. The purpose of this article is to identify strategies that improve environmental sustainability, improve prevention of COVID-19 infection in dialysis centers, and improve the environmental impact of hemodialysis centers.

Matching primary with secondary lymphedemas across lymphatic surgery in genoa (italy) from 1973 until time of covid-19

Authors report their pluridecennial activity (from 1973 up to today) of research, clinical experience and development of lymphatic surgery in Genoa-Italy, in close collaboration with the worldwide centers of the International Society of Lymphology. Five thousand forty-six cases of patients affected by upper and/or lower limbs, primary and secondary lymphedemas and elephantiasis, between 1973 and 2020 underwent lymphatic microsurgery;and between 2012 and 2020, fibro-lipo-lymph-aspiration, according to lymph vessel sparing procedure (FLLA-LVSP), for latest stages of lymphedema/elephantiasis, previously treated by lymphatic microsurgery with partial improvement of the disease. In addition, also morbid obesity related elephantiasis, lipolymphedema/elephantiasis, chylous-lymphatic dysplastic gravitational reflux with complex related syndromes, were treated by tailored surgical procedures, properly combined with tailored medical and nutritional regimens. All patients were followed-up for a minimum of 5 years to over 20 years. Over 96% of patients with earlier stages of disease (initial lymphedema: Stage IB and increasing lymphedema: Stage IIA) progressively stopped using conservative therapies;and over 80% of patients with later stages (column shaped limb fibrolymphedema: Stage IIB, properly called elephantiasis: Stage IIIA, and extreme elephantiasis: Stage IIIB), significantly decreased the frequency of physical therapies and discontinued compressive garments or stockings. Dermato-lymphangio-adenitis attacks considerably reduced by over 95%. Staging-guided treatment of peripheral lymphedema, according to authors' Genoa protocol, carries out not only the best long-lasting treatment, but also the contextual target of primary (to avoid lymphatic injuries), secondary (early-stage treatment), and tertiary (late-stage treatment) prevention in the potential worsening of the disease.

Public health impact of the COVID-19 pandemic on the emergency healthcare system.

BACKGROUND: The Lombardy region has been the Italian region most affected by the coronavirus disease 2019 (COVID-19) pandemic in 2020. The emergency healthcare system was under deep stress throughout the past year due to the admission of COVID-19 patients to the emergency department (ED) and had to be thoroughly reorganized. METHODS: We performed a retrospective descriptive analysis of patients admitted into the ED recorded in the Lombardy online regional portal called EUOL (Emergenza e Urgenza OnLine). We compared the data registered in the EUOL with the patients admitted to the EDs from 1 January 2019 to 31 December 2019 and from 1 January 2020 to 31 December 2020. RESULTS: The number of admissions to the ED decreased by 32.5% in 2020 compared with 2019, reaching the lowest number in March and April. However, the percentage of patients hospitalized after ED significantly increased in 2020 compared with 2019 (P < 0.0001), reflecting the management of patients with a more severe clinical condition. More patients arrived at the ED by ambulance in 2020 (21.7% in 2020 versus 15.1% in 2019; P < 0.0001), particularly during March and April. CONCLUSIONS: This analysis showed the importance of monitoring the pandemic's evolution in order to treat more critically ill patients, despite a lower number of patients.

Rapid response air medical evacuation by civilian HEMS crew of critical patients during COVID-19 outbreak - First Fixed Points

The Covid-19 emergency requires a shared plan for the long-range helicopter transfer of patients affected by the virus in order to reduce the overload of intensive care units. To date, there is limited peer reviewed literature on aeromedical transport of patients with highly hazardous communicable diseases, most of it is military, and none deals specifically with patients affected by Covid-19. To meet this need, we propose reference criteria regarding preflight, in-flight and post-flight patient management and helicopter sanitization.