Territories, politics and governance of the Covid-19 pandemic

As a major public health and socio-ecological crisis, the Covid-19 pandemic has raised significant challenges, arguably affecting the everyday life of most individuals on the planet. The pandemic has transformed social relationships within families, communities and nations, awakening a spirit of care and reciprocity as well as engendering new mechanisms of control and surveillance to confront the dialectic of life and death. This editorial introduces the special issue composed of nine articles that engage with themes related to the responses to the pandemic and reflects on the implications of Covid-19 for scholarly questions on the politics and governance of territorial processes.

THE BURDEN of POST-SARS-COV2 VACCINE COMPLICATIONS and NEWLY DIAGNOSED IMMUNEMEDIATED INFLAMMATORY DISEASES

Background: Local and systemic reactions have been observed after all vaccines for SARS-CoV-2 but in the majority of cases, symptoms are mild and self-limiting. However, evidence on more severe clinical scenarios, requiring admission to hospital or referral to outpatient clinics after the administration of SARS-CoV-2 vaccines has accrued. This also includes newly diagnosed diseases, such as cardiovascular and immune-mediated infammatory diseases (IMID). Objectives: We aimed at quantifying the burden of post-vaccine hospital admissions/referrals and of newly diagnosed IMID. Methods: Clinical records of patients referred to our Internal Medicine institution (both inpatients and outpatients) between February and June 2021 were retrospectively assessed. Subjects having received one or more doses of any of the EMA-approved SARS-CoV-2 vaccines within the previous 30 days were included. Subjects with a previous diagnosis of IMID were excluded. Results: Our cohort included 99 patients, 45 females and 54 males, with a mean age of 64 years and a median of 3 comorbities (range 0-7). Eighty-eight patients (89%) required admission to the Internal Medicine ward while 11 were referred to the outpatient clinic. 68 (69%) of patients received the vaccine BNT162b2, 16 (16%) the ChAdOx1 nCoV-19, 9 (9%) the mRNA-1273 and 6 (6%) the Ad26. COV2.S. Twenty-seven (27%) subjects developed symptoms after the frst vaccine dose with a mean latency of 2 days (median=0 indicating symptom onset on the day of the vaccine administration). Twenty-four (24%) subjects developed symptoms after the second dose with a mean latency of 4 days (median 1 day). All the other subjects did not develop symptoms within the week after the vaccine and were admitted for reasons apparently unrelated to vaccine administration. The number of presenting complaints ranged between 1 and 4 with 87% of subjects presenting with 1 or two coexisting complaints. Gastrointestinal manifestations were the most frequent being the presenting complaint in 31 (31%) of patients followed by severe fatigue/appetite loss in 19 (19%) of subjects, fever in 18 (18.2%) and neurological manifestation in 16 (16%) of subjects. A temporal and causal association with the SARS-CoV-2 vaccine was identifed since all other known causes for these manifestations were ruled out. No in-hospital deaths were observed and 19 (19%) patients were diagnosed with a new onset IMID (Table 1). The clinical picture of these subjects was not signifcantly different from that of patients without a confrmed IMID and neither were demographic features. No association with the type of vaccine was observed. Conclusion: Our data show that post-vaccine newly diagnosed IMID may represent a challenge in clinical practice and it seems that no demographic or clinical feature is able to predict their onset. A multidisciplinary cooperation and registry data are needed in order to reliably estimate and defne the impact of SARS-CoV-2 vaccinations on new onset IMID.

LONG-TERM SURVEY STUDY of the IMPACT of COVID-19 on SYSTEMIC AUTOIMMUNE DISEASES. LOW DEATH RATE DESPITE the INCREASED PREVALENCE of SYMPTOMATIC INFECTION. ROLE of PRE-EXISTING INTERSTITIAL LUNG DISEASE and ONGOING TREATMENTS

Background: Patients with autoimmune systemic diseases (ASDs) can be counted among frail populations as regards the predisposition to COVID-19 due to the frequent visceral organ involvement and comorbidities, as well as the ongoing immunomodulating treatments. Objectives: Our long-term multicenter telephone survey prospectively investigated the prevalence, prognostic factors, and outcomes of COVID-19 in Italian ASD patients during the frst 3 pandemic waves. Methods: A large series of 3,918 ASD patients (815 M, 3103 F;mean age 59±12SD years) was consecutively recruited at the 36 referral centers of COVID-19 & ASD Italian Study Group. In particular, ASD series encompassed the following conditions: rheumatoid arthritis (n: 981), psoriatic arthritis (n: 471), ankylosing spondylitis (n: 159), systemic sclerosis (n: 1,738), systemic lupus (172), systemic vasculitis (n: 219), and a miscellany of other ASDs (n: 178). The development of COVID-19 was recorded by means of telephone survey using standardized symptom-assessment questionnaire (1). Results: A signifcantly increased prevalence of COVID-19 (8.37% vs 6.49%;p<0.0001) was observed in our ASD patients, while the cumulative death rate revealed statistically comparable to the Italian general population (3.65% vs 2.95%;p: ns). In particular, among the 328 ASD patients complicated by COVID-19, 57 (17%) needed hospitalization, while mild-moderate manifestations were observed in the large majority of individuals (83%). In addition, 12/57 hospitalized patients died due to severe interstitial pneumonia and/or cardiovascular manifestations. Interestingly, a signifcantly higher COVID-19-related death rate was observed in systemic sclerosis patients compared to the Italian general population (6.29% vs 2.95%;p=0.018). Other adverse prognostic factors to develop COVID-19 were the patients' older age, male gender, pre-existing ASD-related interstitial lung involvement, and chronic steroid treatment. Conversely, patients treated with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) showed a signifcantly lower prevalence of COVID-19 compared to those without (3.58% vs 46.99%;p=0.000), as well as the chronic administration of low dose aspirin in a subgroup of SSc patients (with 5.57% vs without 27.84%;p=0.000). Conclusion: The cumulative impact of COVID-19 on ASD patients after the frst 3 pandemic waves revealed less severe than that observed during the frst phase of pandemic (1), especially with regards to the death rate that was comparable to the Italian general population in spite of the increased prevalence of complicating COVID-19 in the same ASD series. Ongoing long-term treatments, mainly csDMARDs, might usefully contribute to generally positive outcomes of in this frail patients' population. Of note, a signifcantly increased COVID-19-related mortality was recorded in only SSc patients' subgroup, possibly favored by pre-existing lung fbrosis. Among different ASD, SSc deserves special attention, since it shares the main pathological alterations with COVID-19, namely the interstitial lung involvement and the endothelial injury responsible for diffuse microangiopathy. Besides SSc, the patients' subgroups characterized by older age, chronic steroid treatment, pre-existing interstitial lung disease, and/or impaired COVID-19 vaccine response (1-3), may deserve well-designed prevention and management strategies.

COVID-19 VACCINATION RATE and SAFETY PROFILE in PATIENTS AFFECTED by MIXED CRYOGLOBULINEMIC VASCULITIS

Background: Mixed cryoglobulinaemic vasculitis (MCV) is an immune-complex-mediated systemic vasculitis characterized by heterogeneous clinical manifestations mainly involving skin, kidney and peripheral nervous system. Despite reassuring safety data from EULAR Coronavirus Vaccine (COVAX) physician-reported registry, a signifcant proportion of patients with autoimmune diseases reported unwillingness to get vaccinated against SARS-CoV-2 infection in the preliminary results of the COVAD study, due to concerns about the lack of longterm safety data, and fear of associated side effects and disease fare. Objectives: Aims of this multicentre Italian study were to investigate the prevalence of vaccination against SARS-CoV-2 in Italian population of MCV patients, to explore the reason for the missed vaccination, and to investigate short and long-term side effects of the vaccine, including vasculitis fare. Methods: All MCV patients referring to 12 Italian centres were investigated about vaccination and possible both short-(within 48 hours) and long-term (within 30 days) adverse events (AE), classifed according to FDA Toxicity Grading Scale for preventive vaccine clinical trials, and possible disease fares. Patients with MCV related to lymphoproliferative disorders or connective tissue diseases were excluded from the study. The baseline variables were expressed as percentages or mean±standard deviation. The differences between continuous variables were analysed using the Mann-Whitney nonparametric test. The chi-squared test, or Fischer's exact when appropriate, were used for categorical variables (absolute numbers and percentages) regarding baseline characteristics. Results: A total of 416 patients, 69.2% females and 30.8% males, with a mean age of 70.4±11.7 years, were included in the study. Only 7.7% of patients were not vaccinated, mainly for fear of adverse events (50%) or for medical decision (18.8%). Corminaty was the vaccine most frequently used (80.5%). Interestingly, 6 patients (1.44%) were with a heterologous vaccination (usually AstraZeneca-Corminaty). Considering ongoing treatment, not vaccinated subjects were more frequently treated with chronic glucocorticoid therapy and/or Rituximab (p=0.049 and p=0.043 respectively). AE were recorded in 31.7% of cases, mainly mild and self-limiting (grade 1). More severe adverse events, such as fare of vasculitis, were observed in 5.3% of cases. AE were not associated with the kind of vaccine used and with the clinical manifestations of vasculitis. Patients with active MCV showed a lower frequency of short-term (within 48 hours) adverse events, but patients affected by peripheral neuropathies or skin vasculitis frequently showed a fare of their symptoms, recorded in 40% and 25% of cases, respectively. Finally, patients under glucocorticoid treatment were more prone to develop a vasculitis fare within a month after vaccination. Conclusion: Vaccination in MCV patients has been performed in a high percentage of patients showing a good safety. Other than patients' fear, treatments with rituximab and glucocorticoids are the main reasons for delaying vaccination, and it should be considered by the physician before starting therapy. Vasculitis fares were observed in about 5% of cases, in line with that observed in other autoimmune diseases. Specific attention should be reserved to people with purpura or peripheral neuropathy, for the increased risk of exacerbation of their symptoms.

Reactogenicity of COVID-19 vaccine in hemodialysis patients: a single-center retrospective study

Introduction: Some hemodialysis patients are reluctant to undergo COVID-19 vaccination for the fear of developing adverse events (AEs). The aim of this study was to verify the safety of the mRNA-1273 vaccine in hemodialysis patients. Methods: We conducted a retrospective analysis of in-center hemodialysis patients who underwent mRNA-1273 vaccine from March 1st to April 30th, 2021. All AEs occurring after the first and the second doses were collected and classified as local or systemic. Results: Overall, 126 patients on chronic maintenance dialysis without a prior COVID-19 diagnosis were vaccinated with two doses of mRNA-1273 vaccine. Mean age was 68 (IQR, 54,7-76) years and 53.6% of patients were aged ≥65 years. During the observational period of 68 (IQR, 66-70) days, AEs occurred in 57.9% and 61.9% of patients after the first dose and second dose, respectively. The most common AEs were: injection-site pain (61.9%), erythema (4.8%), itching (4.8%), swelling (16.7%), axillary swelling/tenderness (2.4%), fever (17.5%) headache (7.9%), fatigue (23.8%), myalgia (17.5%), arthralgia (12.7%), dyspnoea (2.4%), nausea/vomiting (7.1%), diarrhoea (5.6%), shivers (4%) and vertigo (1.6%). The rates of local AEs were similar after the first and second doses (P=0.8), whereas systemic AEs occurred more frequently after the second dose (P=0.001). Fever (P=0.03), fatigue (P=0.02) and nausea/vomiting (P=0.03) were significantly more frequent after the second dose of the vaccine. There were no age-related differences in the rate of AEs. Overall, vaccine-related AEs in hemodialysis patients seem to be lower than in the general population. Conclusion: The RNA-1273 vaccine was associated with the development of transient AEs after the first and second doses in patients on chronic maintenance hemodialysis. They were mostly local, whereas systemic AEs were more prevalent after the second dose. Overall, all AEs lasted for a few days, without any apparent sequelae. Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.

A Smart Framework for Automatically Analyzing Electrocardiograms

In the last months, due to the pandemic, telemedicine has been emerging more and more as a vital technology for providing medical care to patients, while also attempting to minimize COVID-19 transmission among patients, families, and medical doctors. This involves developing and exploiting virtual platforms enabling clinicians to remotely monitor patients' vitals, such as the blood pressure or the electrocardiogram (ECG). In this context, this paper aims at defining a smart framework for automatically analyzing electrocardiograms, to be used at the patient's home or at the entrance of First Aids, allowing to: (i) efficiently and effectively discover normal and anomalous situations in patient's ECGs;(ii) automatically collect ECGs from commercial and effective ECG devices;(iii) be integrated into a smart app, supported by intelligent agents, which promptly provides patients with feedback about their health status. © 2021 IEEE.

Immunosuppressive therapy reduction and early post-infection graft function in kidney transplant recipients with COVID-19

Background: Kidney transplant (KT) recipients with COVID-19 are at high risk of poor outcomes due to the high burden of comorbidities and immunosuppression. The effects of immunosuppressive therapy (IST) reduction are unclear in patients with COVID-19.

COVID-19 in Italian patients with rheumatic autoimmune systemic diseases: Results of a nationwide survey study

Background: SARS-CoV-2 infection poses a serious challenge for patients with rheumatic autoimmune systemic diseases (ASD), characterized by marked immune-system dysregulation and frequent visceral organ involvement. Objectives: To evaluate the impact of COVID-19 pandemic in a large series of Italian patients with ASD. Methods: Our multicenter telephone survey (8-week period, March-April 2020) included a large series of 2,994 patients (584 M, 2,410 F, mean age 58.9±13.4SD years) with ASD followed at 34 tertiary referral centers of 14 regions of northern, central, and southern Italian macro areas, characterized by different prevalence of SARS-CoV-2 infection. According to currently used criteria, COVID-19 was classified as definite COVID-19 (signs or symptoms of COVID-19 confirmed by positive oral/nasopharyngeal swabs at PCR testing) or highly suspected COVID-19 (signs or symptoms highly suggestive of Covid-19, but not confirmed by PCR testing due to limited availability of virological tests in that period). The results were analyzed performing the Odds Ratio by Java-Stat 2-way Contingency Table Analysis. Results: The main findings of the survey study revealed a significantly increased prevalence of COVID-19 in: a.the whole series of ASD patients (definite Covid-19: 22/2994, 0.73%;p=0.0007;definite COVID-19 plus highly suspected Covid-19: 74/2,994, 2.47%;p<0.0001) when compared to Italian general population of COVID-19 infected individuals (349/100000 = 0.34%;data from Italian Superior Institute of Health;h t t p s : / / w w w . e p i c e n t r o . i s s . i t / e n / c o r o n a v i r u s / sars-cov-2-national-surveillance-system). b.the subgroup of patients with connective tissue diseases or systemic vasculitis (n = 1,901) compared to the subgroup of inflammatory arthritis (n = 1,093), namely rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis (definite Covid-19: 19/1,901, 0.99%, vs 3/1,093, 0.27%;p=0.036;definite COVID-19 plus highly suspected Covid-19: 69/1,901, 3.6%, vs 5/1,093, 0.45%;p<0.0001) c.the subgroup of patients with pre-existing interstitial lung involvement (n = 526) compared to those without (n = 2,468) (definite Covid-19: 10/526, 1.90%, vs 12/2,468, 0.48%;p=0.0015;definite COVID-19 plus highly suspected Covid-19: 33/526, 6.27%, vs 41/2,468, 1.66%;p<0.0001). Of interest, the prevalence of COVID-19 did not correlate with presence/absence of different comorbidities, mainly diabetes, cardio-vascular and/or renal disorders, as well as of ongoing treatments with biological DMARDs;while patients treated with conventional DMARDs showed a significantly lower prevalence of COVID-19 compared to those without. COVID-19 was more frequently observed in the patients' populations from northern and central compared to southern Italian macro area with lower diffusion of pandemic. Clinical manifestations of Covid-19, observed in 74 patients, were generally mild or moderate;4/9 individuals requiring hospital admission died for severe pneumonia. Conclusion: The prevalence of COVID-19 observed in ASD patients during the first wave of pandemic was significantly higher than that observed in Italian general population;moreover, the actual prevalence of COVID-19 might be underestimated due to the high number of mild variants as well as the possible clinical overlapping between these two conditions. Patients with ASD should be invariably regarded as 'frail patients' during the pandemic course, considering the risk of worse outcome in the acute phase of Covid-19, as well as the potential long-term effects of viral infection. The statistically significant association of COVID-19 with connective tissue diseases/ systemic vasculitis, as well as with pre-existing interstitial lung involvement, suggests the presence of distinct clinico-pathological ASD subsets, characterized by markedly different patients' vulnerability to SARS-CoV-2 infection.

Ferritin is associated with the severity of lung involvement but not with worse prognosis in patients with COVID-19: Data from two italian covid-19 units

Background: The coronavirus 2019 disease (COVID-19) is characterised by a heterogeneous clinical presentation and a wide range of imaging findings, depending on disease severity and time course. The pathophysiology is complex, involving immune and hematologic systems, epithelial cells and vascular system and to date reliable biomarkers aimed at stratifying patients and predicting worse outcomes have not been identified Objectives: The aim of this study was to describe clinical, serological and CT imaging features of a cohort of patients with COVID-19 pneumonia and identify possible relationships between the variables and disease outcomes (admission to intensive care unit (ICU) and/or death). Methods: We evaluated hospitalized patients with proven SARS-CoV-2 infection, clinical signs of COVID-19 and computed tomography (CT) scan-proven pulmonary involvement. Clinical and serological records of patients admitted to two COVID-19 Units in Italy with proven SARS-CoV-2 pulmonary involvement investigated with CT scan, assessed at the time of admission to the hospital, were retrospectively collected. Results: Sixty-one patients (22 females and 39 males) of median age 65 years were enrolled. Fifty-six patients were discharged while death occurred in 5 patients. None of the lung abnormalities detected by CT was different between discharged and deceased patients. No differences were observed in the features and extent of pulmonary involvement according to age and gender. Logistic regression analysis with age and gender as covariates demonstrated that ferritin levels over the 25th percentile were associated with the involvement of all 5 pulmonary lobes (OR=14.5, 95% CI=2.3-90.9, p=0.004), the presence of septal thickening (OR=8.2, 95% CI=1.6-40.9, p=0.011) and the presence of mediastinal lymph node enlargement (OR=12.0, 95% CI=1.1-127.5, p=0.039) independently of age and gender. Conclusion: We demonstrated that ferritin levels over the 25th percentile are associated with a more severe pulmonary involvement, independently of age and gender, but not with disease outcomes (admission to ICU/death). The identification of reliable biomarkers in patients with COVID-19 may help guiding clinical decision, tailoring therapeutic approaches and ultimately improving the care and prognosis of patients with this disease.

Application of the "immunization islands" model to improve quality, efficiency and safety of a COVID-19 mass vaccination site.

Abstract: After SARS-CoV-2 vaccines development came at an unprecedented speed, ensuring safe and efficient mass immunization, vaccine delivery be-came the major public health mandate. Although mass-vaccination sites have been identified as essential to curb COVID-19, their organization and functioning is challenging. In this paper we present the planning, implementation and evalua-tion of a massive vaccination center in Lombardy - the largest Region in Italy and the most heavily hit by the pandemic. The massive hub of Novegro (Milan), managed by the Gruppo Ospedaliero San Donato, opened in April 2021. The Novegro mass-immunization model was developed building a la-yout based on the available scientific evidence, on comparative analysis with other existing models and on the experience of COVID-19 immunization delivery of Gruppo Ospedaliero San Donato. We propose a "vaccine islands" mass-immunization model, where 4 physicians and 2 nurses operate in each island, with up to 10 islands functioning at the same time, with the capacity of providing up to 6,000 vaccinations per day. During the first week of activity a total of 37,900 doses were administered (2,700/day), most of them with Pfizer vaccine (85.8%) and first doses (70.9%). The productivity was 10.5 vaccines/hour/vaccine station. Quality, efficiency and safety were boosted by ad-hoc personnel training, quality technical infrastructure and the presence of a shock room. Constant process monitoring allowed to identify and promptly tackle process pitfalls, including vaccine refusals (0.36%, below expectations) and post-vaccinations adverse reactions (0.4%). Our innovative "vaccine islands" mass-immunization model might be scaled-up or adapted to other settings. The Authors consider that sharing best practices in immunization delivery is fundamen-tal to achieve population health during health emergencies.

Increased cardiovascular death rates in a COVID-19 low prevalence area

Objective: Preliminary data indicate a reduction in hospitalizations for acute coronary syndromes during the Covid19 outbreak in Northern Italy. We investigated whether the albeit marginal Covid19 burden in the province of L Aquila in Central Italy, had an impact on cardiovascular hospitalizations and outcomes Design and method: We retrospectively analyzed de-identi fied data from all patients admitted to the five hospitals located in the province of L Aquila for allcause and cardiovascular hospitalizations, cardiovascular acute phase treatments (coronary angioplasty, systemic fibrinolysis, endovascular procedures), and inhospital cardiovascular deaths in the time window from January 1 to March 31 in the years 2020 (study period) and 2019 (control period). Unadjusted incidence rate ratios (IRR) comparing study/control period for the number of admissions/ procedures were calculated through Poisson regression. Case fatality rate (%) for cardiovascular diseases in the examined periods was assessed Results: 5908 patients were hospitalized in the first quarter of 2020 (52.9% women mean age 59.2±24.9 years, 64.9 mean daily admissions). In the same period in 2019, 6852 patients were hospitalized (51.8% women, mean age 60.1±24.6 years;76.1 mean daily admissions). Signi ficantly less all-cause and cardiovascular hospitalizations occurred in the study period than in the control period (IRR 0.85 95%CI 0.82-0.88;IRR 0.73, 95%CI 0.67-0.80, respectively). The mean daily number of cardiovascular procedures was also lower (IRR: 0.74, p=0.009). Importantly a disproportionate decrease in the number of procedures was observed in relation to cardiovascular hospitalizations in the study period (13.8% versus 19.3%, p=0.001). More intra-hospital cardiovascular deaths occurred in March 2020 (11.9%) compared with March 2019 (6.1%) (p=0.048) Conclusions: Changes in healthcare seeking behaviors and an increased burden of cardiovascular-related deaths occurred in a Covid19 low prevalence Italian area Besides unmeasured factors, including forced lifestyle changes, late hospital presentations and consequent greater disease severity might have affected eligibility and outcome of cardiovascular procedures. This evidence advances recent concerns regarding the impact of the pandemic on cardiovascular diseases and related deaths.

Prolonged COVID 19 Outbreak and Psychological Response of Nurses in Italian Healthcare System: Cross-Sectional Study.

Aim of the study was to analyze the posttraumatic stress disorder risk nurses, detecting the relationship between distress experience and personality dimensions in Italian COVID-19 outbreak. A cross-sectional study was conducted based on 2 data detection (March 2020 and September 2020). Mental evaluation was carried out in Laboratory of Clinical Psychology on n.69 nurses in range age 22-64 years old (mean age 37.3; sd ± 10.3; 55% working in nursing care with confirmed COVID-19 patients (named frontline; secondline nurses have been identified by nursing care working with infectious patients but no confirmed COVID-19). Measurement was focused on symptoms anxiety, personality traits, peritraumatic dissociation and post-traumatic stress for all participants. No online screening was applied. Comparisons (ANOVA test) within the various demographic characteristics demonstrated few significant differences between groups on DASS-21, PDEQ, and ISE-R scores. Correlation analysis (Spearman test) was performed among PDEQ, DASS-21, BFI-10 and IES-R and confirmed between anxiety (DASS-21) and peritraumatic dissociation and post-traumatic stress; then anxiety is positively correlated to agreeableness variable of BFI-10 test. The emotional distress was protracted overtime (after 6 months) but in long-term personality traits resulted mediator facing subjective stress. Our finding drew details for protective and predictive risk factors as well as mental health issues of nurses dealing with pandemic: healthcare workers faced the protracted challenge caring COVID-19 patients over and over again: in short time the impact was relevant, and the prolonged exposition to the stressor was tackled by personal resources such as personality traits.