Immune-mediated inflammatory diseases after anti-SARS-CoV-2 vaccines: new diagnoses and disease flares.

OBJECTIVE: New-onset immune-mediated inflammatory diseases (IMIDs) and flares of pre-existing IMIDs have been reported following anti- SARS-CoV2 vaccination. Our study aimed at describing a retrospective cohort of patients developing new-onset IMIDs or flares of known IMIDs within 30 days after any anti-SARS-CoV2 vaccine dose. METHODS: We evaluated clinical records of all inpatients and outpatients referring to our institution between February 2021 and February 2022 with any clinical manifestations. We then selected those having received any anti-SARS-CoV2 vaccine dose within the prior 30 days and classified them as having or not a previous IMID according to predefined criteria. We recorded new-onset IMIDs or flares of known IMIDs and investigated any relationship with demographic, clinical and serological variables. RESULTS: 153 patients that received any anti-SARS-CoV2 vaccine dose within the previous 30 days were included of which 45 (29%) already had a diagnosis of IMID while 108 (71%) had no previously diagnosed IMID. 33 (30%) of the 108 patients, were diagnosed with a new-onset IMID. Pericarditis, polymyalgia rheumatica and vasculitis were the most frequent conditions. Among the 45 patients that already had an IMID, disease flare was the reason for referral in 69% of patients. Patients with an IMID flare had a lower number of comorbidities and tended to be younger compared with those who developed other conditions after anti-SARS-CoV2 vaccination. CONCLUSION: We provided a retrospective overview of a cohort of patients who developed new-onset IMIDs or flares of known IMIDs within 30 days after any dose of anti-SARS-CoV2 vaccine. While vaccination campaigns proceed, postvaccination surveillance programmes are ongoing and hopefully will soon clarify whether a causal relationship between vaccines and new-onset/flares of IMIDs exists.

TIMES TO ACT. Italian-Spanish-Polish-Uzbek Expert Forum Position Paper 2022. Dyslipidemia and arterial hypertension: The two most important and modifiable risk factors in clinical practice.

Hypertension and lipid disorders are two of the main cardiovascular risk factors. Both risk factors - if detected early enough - can be controlled and treated with modern, effective drugs, devoid of significant side effects, available in four countries as different as Italy, Spain, Poland, and Uzbekistan. The aim herein, was to develop this TIMES TO ACT consensus to raise the awareness of the available options of the modern and intensified dyslipidemia and arterial hypertension treatments. The subsequent paragraphs involves consensus and discussion of the deleterious effects of COVID-19 in the cardiovascular field, the high prevalence of hypertension and lipid disorders in our countries and the most important reasons for poor control of these two factors. Subsequently proposed, are currently the most efficient and safe therapeutic options in treating dyslipidemia and arterial hypertension, focusing on the benefits of single-pill combination (SPCs) in both conditions. An accelerated algorithm is proposed to start the treatment with a PCSK9 inhibitor, if the target low-density-lipoprotein values have not been reached. As most patients with hypertension and lipid disorders present with multiple comorbidities, discussed are the possibilities of using new SPCs, combining modern drugs from different therapeutic groups, which mode of action does not confirm the "class effect". We believe our consensus strongly advocates the need to search for patients with cardiovascular risk factors and intensify their lipid-lowering and antihypertensive treatment based on SPCs will improve the control of these two basic cardiovascular risk factors in Italy, Spain, Poland and Uzbekistan.

Immune-mediated inflammatory diseases after anti-SARS-CoV-2 vaccines: new diagnoses and disease flares

Objective New-onset immune-mediated inflammatory diseases (IMIDs) and flares of pre-existing IMIDs have been reported following anti- SARS-CoV2 vaccination. Our study aimed at describing a retrospective cohort of patients developing new-onset IMIDs or flares of known IMIDs within 30 days after any anti-SARS-CoV2 vaccine dose. Methods We evaluated clinical records of all inpatients and outpatients referring to our institution between February 2021 and February 2022 with any clinical manifestations. We then selected those having received any anti-SARS-CoV2 vaccine dose within the prior 30 days and classified them as having or not a previous IMID according to predefined criteria. We recorded new-onset IMIDs or flares of known IMIDs and investigated any relationship with demographic, clinical and serological variables. Results 153 patients that received any anti-SARS-CoV2 vaccine dose within the previous 30 days were included of which 45 (29%) already had a diagnosis of IMID while 108 (71%) had no previously diagnosed IMID. 33 (30%) of the 108 patients, were diagnosed with a new-onset IMID. Pericarditis, polymyalgia rheumatica and vasculitis were the most frequent conditions. Among the 45 patients that already had an IMID, disease flare was the reason for referral in 69% of patients. Patients with an IMID flare had a lower number of comorbidities and tended to be younger compared with those who developed other conditions after anti-SARS-CoV2 vaccination. Conclusion We provided a retrospective overview of a cohort of patients who developed new-onset IMIDs or flares of known IMIDs within 30 days after any dose of anti-SARS-CoV2 vaccine. While vaccination campaigns proceed, postvaccination surveillance programmes are ongoing and hopefully will soon clarify whether a causal relationship between vaccines and new-onset/flares of IMIDs exists.

Electrocardiographic Abnormalities in Hospitalized Patients with COVID-19 and the Associations with Clinical Outcome.

The cardiovascular (CV) system can often be affected during SARS-CoV-2 infection and several acute manifestations, such as myocardial infarction, pericarditis, myocarditis and arrhythmias have been described. We provide a retrospective overview of electrocardiographic (ECG) features and their relationship with clinical outcomes in a cohort of patients admitted to our COVID-19 Unit between November 2020 and May 2021. Resting standard 12-lead ECGs were performed in all patients at admission and in those recovering from SARS-CoV-2 infection also at discharge. Clinical and serological records alongside ECG measurements were retrospectively evaluated and statistical analysis was performed to identify relationships between variables. A total of 123 patients (44% females) with a mean age of 73.9 years were enrolled. Ninety-five (77%) patients recovered from SARS-CoV-2 infection and were discharged while 28 (23%) died in hospital. Almost 90% of patients displayed at least one CV risk factor and 41 (33%) patients had at least one previous CV event. We observed that heart rate, corrected QT interval dispersion (QTcd) and inverted T waves are independently associated with in-hospital death and inverted T waves show the strongest association. This association remained significant even after correcting for the number of CV risk factors at baseline and for the type of CV risk factor at baseline. Our study demonstrated that some ECG abnormalities at admission are independently associated with in-hospital death regardless of pre-existing CV risk factors. These findings may be of particular relevance in clinical settings with limited access to advanced techniques, such as cardiac magnetic resonance and could help improve the outcomes of patients with cardiac involvement related to SARS-CoV-2 infection.

Correction: Gender differences in predictors of intensive care units admission among COVID-19 patients: The results of the SARS-RAS study of the Italian Society of Hypertension.

[This corrects the article DOI: 10.1371/journal.pone.0237297.].

World Hypertension Day 2021 in Italy: Results of a Nationwide Survey.

INTRODUCTION: Hypertension is the biggest contributor to the global burden of cardiovascular diseases and related death, but the rates of hypertension awareness, treatment, and control remain largely perfectible. METHODS: During the XVII World Hypertension Day (May 17th, 2021), a nationwide cross-sectional opportunistic study endorsed by the Italian Society of Hypertension was conducted on volunteer adults ≥ 18 years to raise awareness of high blood pressure (BP). A questionnaire on major demographic/clinical features (sex, age, employment, education, BP status awareness, hypertension family/personal history, antihypertensive medications use) and BP measurement habits (≥1 BP measurement in the previous month/week) was administered. Due to the ongoing SARS-CoV-2 pandemic, BP was measured with standard procedures in a subset of participants (24.4%). RESULTS: A total of 1354 participants (mean age 56.3 ± 15.3 years; 57.3% women; mean BP: 131.2 ± 17.5/81.6 ± 10.5 mmHg; 42.3% self-declared hypertensive; 41.4% on antihypertensive medications) were enrolled; 73.6% declared being aware of their BP status. Among treated individuals with measured BP, 26.9% showed BP levels within the predefined therapeutic goals. Interestingly, BP status awareness rates were the highest among individuals with uncontrolled hypertension (85.1%) and the lowest among those with normal measured BP (54.4%). CONCLUSIONS: This survey provides an updated insight into hypertension awareness and control in a setting of daily clinical practice, emphasizing the centricity of patients in the therapeutic alliance for a successful reduction of cardiovascular risk.

Updated Recommendations on Cardiovascular Prevention in 2022: An Executive Document of the Italian Society of Cardiovascular Prevention.

This executive document reflects and updates the key points of a Consensus document on Cardiovascular (CV) Prevention realized through the contribution of a number of Italian Scientific Societies and coordinated by the Italian Society of Cardiovascular Prevention (SIPREC). The aim of this executive document is to analyze and discuss the new recommendations introduced by international guidelines for the management of major CV risk factors, such as hypertension, dyslipidemias and type 2 diabetes, consisting in the identification of lower therapeutic targets, in the promotion of combination fixed drug therapies and in the introduction in routine clinical practice of new effective pharmacological classes. Moreover, the document highlights the importance of effective CV prevention strategies during the the coronavirus disease 2019 (COVID-19) outbreak which has dramatically changed the priorities and the use of available resources by the national healthcare systems and have caused a reduction of programmed follow-up visits and procedures and even of hospital admissions for severe acute pathologies. In addition, the pandemic and the consequent lockdown measures imposed have caused a widespread diffusion of unhealthy behaviors with detrimental effects on the CV system. In such a context, reinforcement of CV prevention activities may play a key role in reducing the future impact of these deleterious conditions.

Humoral Immune Response to COVID-19 Vaccination in Hemodialysis Patients: A Retrospective, Observational Case-Control Pilot Study.

INTRODUCTION: Coronavirus 2 disease is associated with increased mortality and morbidity in chronic hemodialysis patients METHODS: A retrospective, observational case-control pilot study was conducted on consecutive hemodialysis outpatients (cases) and control group of individuals with preserved renal function. Complete SARS-CoV-2 vaccination with BNT162b2 mRNA vaccine, followed by determination of serum antibodies after the second dose, were required from participants in both groups. Previous COVID-19 was an exclusion criterium. RESULTS: 21 hemodialysis patients (M:F = 13:8, mean age 67.5 ± 13.4) and 16 controls without chronic kidney disease (M:F = 4:12, mean age 46.8 ± 12.7) were included. Hemodialysis patients had lower mean titers of serum antibodies to the SARS-CoV-2 spike antigen compared with controls (492.39 vs 1901.20 IU/mL, respectively; p < 0.001), a finding that was confirmed in the age-matched analysis on 18 participants (580.8 vs 1836.4 IU/mL, p = 0.006). CONCLUSIONS: This study supports the finding of hyporesponsiveness to mRNA vaccination among hemodialysis patients.

Pericarditis after SARS-CoV-2 Infection: Another Pebble in the Mosaic of Long COVID?

With the emerging success of the COVID-19 vaccination programs, the incidence of acute COVID-19 will decrease. However, given the high number of people who contracted SARS-CoV-2 infection and recovered, we will be faced with a significant number of patients with persistent symptoms even months after their COVID-19 infection. In this setting, long COVID and its cardiovascular manifestations, including pericarditis, need to become a top priority for healthcare systems as a new chronic disease process. Concerning the relationship between COVID-19 and pericardial diseases, pericarditis appears to be common in the acute infection but rare in the postacute period, while small pericardial effusions may be relatively common in the postacute period of COVID-19. Here, we reported a series of 7 patients developing pericarditis after a median of 20 days from clinical and virological recovery from SARS-CoV-2 infection. We excluded specific identifiable causes of pericarditis, hence we speculate that these cases can be contextualized within the clinical spectrum of long COVID. All our patients were treated with a combination of colchicine and either ASA or NSAIDs, but four of them did not achieve a clinical response. When switched to glucocorticoids, these four patients recovered with no recurrence during drug tapering. Based on this observation and on the latency of pericarditis occurrence (a median of 20 days after a negative nasopharyngeal swab), could be suggested that post-COVID pericarditis may be linked to ongoing inflammation sustained by the persistence of viral nucleic acid without virus replication in the pericardium. Therefore, glucocorticoids may be a suitable treatment option in patients not responding or intolerant to conventional therapy and who require to counteract the pericardial inflammatory component rather than direct an acute viral injury to the pericardial tissue.

Correction: Gender differences in predictors of intensive care units admission among COVID-19 patients: The results of the SARS-RAS study of the Italian Society of Hypertension.

[This corrects the article DOI: 10.1371/journal.pone.0237297.].

Preexisting Oral Anticoagulant Therapy Ameliorates Prognosis in Hospitalized COVID-19 Patients.

Objective: Altered coagulation parameters in COVID-19 patients is associated with a poor prognosis. We tested whether COVID-19 patients on chronic oral anticoagulants (cOACs) for thromboembolism prophylaxis could receive protection from developing more severe phenotypes of the disease. Approach and Results: We searched the database of the SARS-RAS study (Clinicaltrials.gov: NCT04331574), a cross-sectional observational multicenter nationwide survey in Italy designed by the Italian Society of Hypertension. The database counts 2,377 charts of Italian COVID-19 patients in 26 hospitals. We calculated the Charlson comorbidity index (CCI), which is associated with death in COVID-19 patients. In our population (n = 2,377, age 68.2 ± 0.4 years, CCI: 3.04 ± 0.04), we confirm that CCI is associated with increased mortality [OR: 1.756 (1.628-1.894)], admission to intensive care units [ICU; OR: 1.074 (1.017-1.134)], and combined hard events [CHE; OR: 1.277 (1.215-1.342)]. One hundred twenty-five patients were on cOACs (age: 79.3 ± 0.9 years, CCI: 4.35 ± 0.13); despite the higher CCI, cOACs patients presented with a lower risk of admissions to the ICU [OR 0.469 (0.250-0.880)] but not of death [OR: 1.306 (0.78-2.188)] or CHE [OR: 0.843 (0.541-1.312)]. In multivariable logistic regression, cOACs confirmed their protective effect on ICU admission and CHE. The CCI remains the most important risk factor for ICU admission, death, and CHE. Conclusions: Our data support a mechanism for the continuation of cOAC therapy after hospital admission for those patients who are on chronic treatment. Our preliminary results suggest the prophylactic use of direct cOACs in patients with elevated CCI score at the time of the COVID-19 pandemic even in absence of other risks of thromboembolism.

Determinants of healing among patients with coronavirus disease 2019: the results of the SARS-RAS study of the Italian Society of Hypertension.

OBJECTIVE: The burst of COVID-19 epidemics in Italy prompted the Italian Society of Hypertension to start an observational study to explore the characteristics of the hospitalized victims of the disease. The current analysis aimed to investigate the predictors of healing among Italian COVID-19 patients. We also assessed the effect of angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers on the outcome. METHODS: We designed a cross-sectional, observational, multicenter, nationwide survey in Italy to explore the demographic and clinical characteristics of patients with confirmed COVID-19 infection. We analyzed information from 2446 charts of Italian patients admitted for certified COVID-19 in 27 hospitals. Healing from COVID-19 infection, defined as two consecutive negative swabs, was reported in 544 patients (22.2%), 95% of them were hospitalized. RESULTS: Age and Charlson Comorbidity Index were significantly lower in healing compared with nonhealing patients (63 ±â€Š15 vs. 69 ±â€Š15 and 2 ±â€Š2 vs. 3 ±â€Š2, both P < 0.05). In multivariable regression model, predictors of healing were younger age (OR: 0.99; 95% CI 0.98-0.99, P = 0.0001), absence of chronic kidney disease (OR: 0.35; 95% CI 0.17-0.70, P = 0.003) or heart failure (OR: 0.44; 95% CI, 0.28-0.70, P = 0.001). In the subgroup of patients suffering from hypertension and/or heart failure (n = 1498), no differences were observed in the use of ACE inhibitors and angiotensin receptor blockers. CONCLUSION: Our study demonstrated that younger age and absence of comorbidities play a major role in determining healing in patients with COVID-19. No effects of ACE inhibitors and angiotensin receptor blockers on the outcome was reported.

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.

The coronavirus 2019 disease (COVID-19) is characterised by a heterogeneous clinical presentation, a complex pathophysiology and a wide range of imaging findings, depending on disease severity and time course. We conducted a retrospective evaluation of hospitalized patients with proven SARS-CoV-2 infection, clinical signs of COVID-19 and computed tomography (CT) scan-proven pulmonary involvement, in order to identify relationships between clinical, serological, imaging data and disease outcomes in patients with COVID-19. Clinical and serological records of patients admitted to two COVID-19 Units of the Abruzzo region in Italy with proven SARS-CoV-2 pulmonary involvement investigated with CT scan, assessed at the time of admission to the hospital, were retrospectively evaluated. 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. We demonstrated that ferritin levels over the 25th percentile are associated with a more severe pulmonary involvement, independently of age and gender and not associated with disease outcomes. 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.

Clinical Characteristics and Outcomes of Patients with COVID-19 Infection: The Results of the SARS-RAS Study of the Italian Society of Hypertension.

The COVID-19 infection has rapidly spread around the world and a second wave is sweeping in many countries. Different clinical and epidemiological aspects characterize the disease and their understanding is necessary to better face the management of the pandemic in progress. The Italian society of arterial hypertension with the SARS-RAS study has contributed significantly to the knowledge of the interaction between inhibition of the renin-angiotensin system and COVID-19 infection. Furthermore, the study results help to understand some of the main aspects related to mortality and morbidity deriving from the infection through a multicentre analysis throughout the national territory.

The Impact of SARS-CoV-2 Outbreak on Primary Sjögren's Syndrome: An Italian Experience.

Objective: Since no data is available about the personal experience of people with primary Sjögren's syndrome (pSS) with regard to disease burden and management during the novel Severe Acute Respiratory Syndrome coronavirus (SARS-CoV)-2 outbreak, we aimed to explore these aspects with the ultimate goal to identify unmet needs and priorities. Methods: A telephone consultation was scheduled with patients with pSS and information regarding the disease status, ongoing treatment and symptoms/diagnosis of coronavirus disease 2019 (COVID-19) were collected. Clinical records were retrospectively evaluated to gather pre-COVID-19 information. Results: One hundred and two patients with pSS were contacted. Most rheumatology consultations and other pSS-related tests were canceled during the SARS-CoV-2 outbreak. Less than 30% of patients contacted the rheumatologist via telemedicine despite experiencing disease flares or therapy shortage. Disease activity and patient reported symptoms significantly worsened during the closure period. All patients practiced social distancing, most of those employed switched to smart working and different work settings impacted on the type of symptom worsening. Conclusion: This is the first study addressing the personal experience of pSS patients resulting from the impact of the SARS-CoV2 outbreak and it identifies unmet needs and priorities requiring to be addressed. Our findings may help designing individualized strategies.

Age and Multimorbidity Predict Death Among COVID-19 Patients: Results of the SARS-RAS Study of the Italian Society of Hypertension.

Several factors have been proposed to explain the high death rate of the coronavirus disease 2019 (COVID-19) outbreak, including hypertension and hypertension-related treatment with Renin Angiotensin System inhibitors. Also, age and multimorbidity might be confounders. No sufficient data are available to demonstrate their independent role. We designed a cross-sectional, observational, multicenter, nationwide survey in Italy to verify whether renin-angiotensin system inhibitors are related to COVID-19 severe outcomes. We analyzed information from Italian patients diagnosed with COVID-19, admitted in 26 hospitals. One thousand five hundred ninety-one charts (male, 64.1%; 66±0.4 years) were recorded. At least 1 preexisting condition was observed in 73.4% of patients, with hypertension being the most represented (54.9%). One hundred eighty-eight deaths were recorded (11.8%; mean age, 79.6±0.9 years). In nonsurvivors, older age, hypertension, diabetes mellitus, chronic obstructive pulmonary disease, chronic kidney disease, coronary artery diseases, and heart failure were more represented than in survivors. The Charlson Comorbidity Index was significantly higher in nonsurvivors compared with survivors (4.3±0.15 versus 2.6±0.05; P<0.001). ACE (angiotensin-converting enzyme) inhibitors, diuretics, and ß-blockers were more frequently used in nonsurvivors than in survivors. After correction by multivariate analysis, only age (P=0.0001), diabetes mellitus (P=0.004), chronic obstructive pulmonary disease (P=0.011), and chronic kidney disease (P=0.004) but not hypertension predicted mortality. Charlson Comorbidity Index, which cumulates age and comorbidities, predicts mortality with an exponential increase in the odds ratio by each point of score. In the COVID-19 outbreak, mortality is predicted by age and the presence of comorbidities. Our data do not support a significant interference of hypertension and antihypertensive therapy on COVID-19 lethality. Registration- URL: https://www.clinicaltrials.gov; Unique identifier: NCT04331574.

Gender differences in predictors of intensive care units admission among COVID-19 patients: The results of the SARS-RAS study of the Italian Society of Hypertension.

BACKGROUND: The global rate of intensive care unit (ICU) admission during the COVID-19 pandemic varies within countries and is among the main challenges for health care systems worldwide. Conflicting results have been reported about the response to coronavirus infection and COVID-19 outcomes in men and women. Understanding predictors of intensive care unit admission might be of help for future planning and management of the disease. METHODS AND FINDINGS: We designed a cross-sectional observational multicenter nationwide survey in Italy to understand gender-related clinical predictors of ICU admission in patients with COVID-19. We analyzed information from 2378 charts of Italian patients certified for COVID-19 admitted in 26 hospitals. Three hundred ninety-five patients (16.6%) required ICU admission due to COVID19 infection, more frequently men (74%), with a higher prevalence of comorbidities (1,78±0,06 vs 1,54±0,03 p<0.05). In multivariable regression model main predictors of admission to ICU are male gender (OR 1,74 95% CI 1,36-2,22 p<0.0001) and presence of obesity (OR 2,88 95% CI 2,03-4,07 p<0.0001), chronic kidney disease (OR: 1,588; 95%, 1,036-2,434 p<0,05) and hypertension (OR: 1,314; 95% 1,039-1,662; p<0,05). In gender specific analysis, obesity, chronic kidney disease and hypertension are associated with higher rate of admission to ICU among men, whereas in women, obesity (OR: 2,564; 95% CI 1,336-4.920 p<0.0001) and heart failure (OR: 1,775 95% CI: 1,030-3,057) are associated with higher rate of ICU admission. CONCLUSIONS: Our study demonstrates that gender is the primary determinant of the disease's severity among COVID-19. Obesity is the condition more often observed among those admitted to ICU within both genders. TRIAL REGISTRATION: Clinicaltrials.gov: NCT04331574.

Cytokine Storm in COVID-19: "When You Come Out of the Storm, You Won't Be the Same Person Who Walked in".

In December 2019, a novel coronavirus, COVID-19, was discovered to be the causal agent of a severe respiratory infection named SARS-CoV-2, and it has since been recognized worldwide as a pandemic. There are still numerous doubts concerning its pathogenesis and particularly the underlying causes of the various clinical courses, ranging from severe manifestations to asymptomatic forms, including acute respiratory distress syndrome. The major factor responsible for acute respiratory distress syndrome is the so-called "cytokine storm," which is an aberrant response from the host immune system that induces an exaggerated release of proinflammatory cytokines/chemokines. In this review, we will discuss the role of cytokine storm in COVID-19 and potential treatments with which counteract this aberrant response, which may be valuable in the clinical translation.