Lung ultrasound in the COVID-19 era: a lesson to be learned for the future.

Lung Ultrasound (LUS) is a reliable, radiation free and bedside imaging technique to assess several pulmonary diseases. Although the diagnosis of COVID-19 is made with the nasopharyngeal swab, detection of pulmonary involvement is key for a safe patient management. LUS is a valid alternative to explore, in paucisymptomatic self-presenting patients, the presence and extension of pneumonia compared to High Resolution Computed Tomography (HRCT) that represent the gold standard. This is a single-centre prospective study with 131 patients enrolled. Twelve lung areas were explored reporting a semiquantitative assessment to obtain the LUS score. Each patient performed reverse-transcription polymerase chain reaction test (rRT-PCR), hemogasanalysis and HRCT. We observed an inverse correlation between LUSs and pO2, P/F, SpO2, AaDO2 (p value < 0.01), a direct correlation with LUSs and AaDO2 (p value < 0.01). Compared with HRCT, LUS showed sensitivity and specificity of 81.8% and 55.4%, respectively, and VPN 75%, VPP 65%. Therefore, LUS can represent an effective alternative tool to detect pulmonary involvement in COVID-19 compared to HRCT.

Can Lung Ultrasound be Used to Screen for Pulmonary Embolism in Patients with SARS-CoV-2 Pneumonia?

Thromboembolic disease is strongly associated with, or even an integral part of, COVID-19 pneumonia. Indeed, endothelial/microvascular damage to pulmonary capillaries seems to be the main trigger of the pneumonia. Here we report a case of pulmonary embolism in a COVID-19 patient with an atypical clinical presentation. Blood gas analysis and lung ultrasound allowed the correct diagnosis to be reached. LEARNING POINTS: COVID-19 pneumonia is associated with cardiovascular complications and pulmonary embolisms.Lung ultrasound can aid diagnosis by visualizing small peripheral pulmonary embolisms.

Statin therapy may protect against acute kidney injury in patients hospitalized for interstitial SARS-CoV2 pneumonia.

BACKGROUND AND AIMS: COVID-19-associated acute kidney injury (AKI) represents an independent risk factor for all-cause in-hospital death in patients with COVID-19. Chronic statin therapy use is highly prevalent in individuals at risk for severe COVID-19. Our aim is to assess whether patients under treatment with statins have a lower risk of AKI and in-hospital mortality during hospitalization for interstitial SARS-CoV2 pneumonia. METHODS AND RESULTS: Our study is a prospective observational study on 269 consecutive patients admitted for COVID-19 pneumonia at the Internal Medicine Unit of IRCCS Sant'Orsola Hospital in Bologna, Italy. We compared the clinical characteristics between patients receiving statin therapy (n = 65) and patients not treated with statins and we assessed if chronic statin use was associated with a reduced risk for AKI, all-cause mortality, admission to ICU, and disease severity. Statin use was associated with a significant reduction in the risk of developing AKI (OR 0.47, IC 0.23 to 0.95, p 0.036) after adjustment for age, sex, BMI, hypertension, diabetes, and chronic kidney disease (CKD). Additionally, statin use was associated with reduced C-reactive protein (CRP) levels (p 0.048) at hospital admission. No significant impact in risk of all-cause mortality (HR 1.98, IC 0.71 to 5.50, p 0.191) and ICU admission (HR 0.93, IC 0.52 to 1.65, p 0.801) was observed with statin use, after adjustment for age, sex, BMI, hypertension, diabetes, and CKD. CONCLUSION: The present study shows a potential beneficial effect of statins in COVID-19-associated AKI. Furthermore, patients treated with statins before hospital admission for COVID-19 may have lower systemic inflammation levels.

Vitamin D Supplementation and COVID-19 Outcomes: Mounting Evidence and Fewer Doubts.

The coronavirus disease 2019 (COVID-19) has already killed more than 6 million people around the world. A growing body of epidemiological evidence suggests that low 25-hydroxy vitamin D (25-OH-vitamin D) plasma levels are associated with an increased risk of developing COVID-19 and -most importantly-with a higher risk of developing more severe COVID-19 and dying. On the other hand, vitamin D supplementation during the early phases of COVID-19 has been related to a decreased length of hospital stay, less frequent need for oxygen, and a reduced mortality rate in inpatients. This seems to be particularly true when high dosages are used. In light of this evidence, further studies are needed to define the best timing for vitamin D supplementation and the most effective dosage schedule.

Renin-Angiotensin System Inhibitors in Patients With COVID-19: A Meta-Analysis of Randomized Controlled Trials Led by the International Society of Hypertension.

Background Published randomized controlled trials are underpowered for binary clinical end points to assess the safety and efficacy of renin-angiotensin system inhibitors (RASi) in adults with COVID-19. We therefore performed a meta-analysis to assess the safety and efficacy of RASi in adults with COVID-19. Methods and Results MEDLINE, EMBASE, ClinicalTrials.gov, and the Cochrane Controlled Trial Register were searched for randomized controlled trials that randomly assigned patients with COVID-19 to RASi continuation/commencement versus no RASi therapy. The primary outcome was all-cause mortality at ≤30 days. A total of 14 randomized controlled trials met the inclusion criteria and enrolled 1838 participants (aged 59 years, 58% men, mean follow-up 26 days). Of the trials, 11 contributed data. We found no effect of RASi versus control on all-cause mortality (7.2% versus 7.5%; relative risk [RR], 0.95; [95% CI, 0.69-1.30]) either overall or in subgroups defined by COVID-19 severity or trial type. Network meta-analysis identified no difference between angiotensin-converting enzyme inhibitors versus angiotensin II receptor blockers. RASi users had a nonsignificant reduction in acute myocardial infarction (2.1% versus 3.6%; RR, 0.59; [95% CI, 0.33-1.06]), but increased risk of acute kidney injury (7.0% versus 3.6%; RR, 1.82; [95% CI, 1.05-3.16]), in trials that initiated and continued RASi. There was no increase in need for dialysis or differences in congestive cardiac failure, cerebrovascular events, venous thromboembolism, hospitalization, intensive care admission, inotropes, or mechanical ventilation. Conclusions This meta-analysis of randomized controlled trials evaluating angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers versus control in patients with COVID-19 found no difference in all-cause mortality, a borderline decrease in myocardial infarction, and an increased risk of acute kidney injury with RASi. Our findings provide strong evidence that RASi can be used safely in patients with COVID-19.

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.

Renin-angiotensin system modulation and outcomes in patients hospitalized for interstitial SARS-CoV2 pneumonia: a cohort study.

AIM: The role of cardiovascular (CV) pharmacotherapies in patients with severe COVID-19 pneumonia remains controversial. This study aims to assess the impact of renin-angiotensin system modulation (RASi) (either angiotensin-converting enzymes (ACEIs) or angiotensin-receptor blockers (ARBs)) on COVID-19 outcome. METHODS: We performed a cohort study on consecutive patients admitted for COVID-19 pneumonia at the Internal Medicine Unit of Sant'Orsola-Malpighi Hospital in Bologna, Italy. Patients with a possible alternative cause of respiratory failure other than COVID-19 were excluded. Clinical, pharmacological and laboratory data at admission and during the hospitalization were collected. Patients were treated with intravenous dexamethasone, low molecular weight heparin and nasal flow or Venturi mask oxygen. Subjects were followed until discharge, Intensive Care Unit (ICU) admission or death. Severe cases were defined by acute respiratory distress syndrome (arterial oxygen partial pressure and the fraction of inhaled oxygen ratio (P/F) ≤ 100 mmHg/%, or P/F ≤ 150 mmHg/% and respiratory rate ≥ 26/min). Patients with chronic use of RAS modulation were compared with those without for the composite outcome of in-hospital mortality or ICU admission. Hazard ratios (HR) were obtained by Cox regression, adjusted for several clinical factors. RESULTS: Of the 268 patients enrolled in the study, 93 (35%, mean age 68 ± 13 years, 67% males) were treated with RASi (58% ACEIs and 42% ARBs). There were no meaningful differences between the RASI and no RASI group regarding clinical and laboratory parameters at admission. As expected, patients in the RASi group had a higher prevalence of hypertension, diabetes mellitus, atrial fibrillation, and ischemic heart disease. One hundred eight patients (40%) were admitted to ICU during hospitalization due to severe respiratory failure, and 24 (9%) died. The risk of in-hospital death or ICU admission was lower in the RASI group than in the non-RASI group (age and sex-adjusted HR 0.57, 95% CI 0.37-0.8), even after adjustment for several comorbidities (fully adjusted HR 0.44, 95% CI 0.26-0.74). Seven (7.5%) patients died in the RASi group vs 17 (9.7%) in the non-RASi group, leading to a non-statistically significant mortality risk reduction (fully adjusted HR 0.69, 95% CI 0.18-1.90). The lower risk in the RASi group was primarily related to ARBs use compared to ACEIs (HR 0.5, 95% CI 0.28-0.92 and HR 0.82, 95% CI 0.51-1.32, respectively). CONCLUSIONS: Our study showed an inverse association between the chronic use of RASi and COVID-19 pneumonia severity (either ICU admissions or in-hospital death), even when significant comorbidities are considered.

COVID-19-Related Quarantine Effect on Dietary Habits in a Northern Italian Rural Population: Data from the Brisighella Heart Study.

North of Italy was severely hit by the COVID-19 (Coronavirus disease 19) pandemic. This induced the government to adopt severely restrictive measures to reduce the contagion risk, forcing most of the population to stop working and from leisure activities, and to remain at home for several weeks. Our study aimed to evaluate the effect of COVID-related quarantine on smoking and dietary habits of a well-characterized northern Italian rural population. For this purpose, while lockdown restrictions were in place (February-April 2020), 359 subjects from the Brisighella Heart Study cohort underwent a phone interview about their lifestyle habit changes during COVID-19-related quarantine. Quarantine did not significantly modify smoking habit nor body mass index. Subjects significantly increased daily carbohydrates consumption, all fresh vegetables, healthy vegetable oils, milk and yogurt, alcoholic drinks, sugars and sweets, and coffee. The weekly consumption of low-fat meat, cured meat other than ham, cheeses, eggs, nuts and mixed seed oils significantly increased, while the weekly intake of fish, mussels, and legumes significantly decreased during lockdown. The Dietary Quality Index was reduced from 42.4 ± 4.1 to 37.8 ± 4.7 (p < 0.03). In accordance with our findings, COVID-19-related quarantine might worsen the quality of diet, also leading to an increased intake of almost all food categories.

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.].

Fibromyalgia: a new facet of the post-COVID-19 syndrome spectrum? Results from a web-based survey.

OBJECTIVE: Postacute COVID-19 syndrome (PACS) is an emerging entity characterised by a large array of manifestations, including musculoskeletal complaints, fatigue and cognitive or sleep disturbances. Since similar symptoms are present also in patients with fibromyalgia (FM), we decided to perform a web-based cross-sectional survey aimed at investigating the prevalence and predictors of FM in patients who recovered from COVID-19. METHODS: Data were anonymously collected between 5 and 18 April 2021. The collection form consisted of 28 questions gathering demographic information, features and duration of acute COVID-19, comorbid diseases, and other individual's attributes such as height and weight. The American College of Rheumatology (ACR) Survey Criteria and the Italian version of the Fibromyalgia Impact Questionnaire completed the survey. RESULTS: A final sample of 616 individuals (77.4% women) filled the form 6±3 months after the COVID-19 diagnosis. Of these, 189 (30.7%) satisfied the ACR survey criteria for FM (56.6% women). A multivariate logistic regression model including demographic and clinical factors showed that male gender (OR: 9.95, 95% CI 6.02 to 16.43, p<0.0001) and obesity (OR: 41.20, 95% CI 18.00 to 98.88, p<0.0001) were the strongest predictors of being classified as having post-COVID-19 FM. Hospital admission rate was significantly higher in men (15.8% vs 9.2%, p=0.001) and obese (19.2 vs 10.8%, p=0.016) respondents. CONCLUSION: Our data suggest that clinical features of FM are common in patients who recovered from COVID-19 and that obesity and male gender affect the risk of developing post-COVID-19 FM.

Acute Kidney Injury in Pediatric Diabetic Kidney Disease.

Diabetic kidney disease (DKD) is a common complication of type 1 and 2 diabetes and often presents during adolescence and young adulthood. Given the growing incidence of both type 1 and type 2 diabetes in children and adolescents, DKD represents a significant public health problem. Acute kidney injury (AKI) in youth with diabetes is strongly associated with risk of DKD development. This review will summarize the epidemiology and pathophysiology of AKI in children with diabetes, the relationship between AKI and DKD, and the potential therapeutic interventions. Finally, we will appraise the impact of the recent COVID-19 infection pandemic on AKI in children with diabetes.

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.

One year of SARS-CoV-2 and lung ultrasound: what has been learned and future perspectives.

A first screening by ultrasound can be relevant to set a specific diagnostic and therapeutic route for a patient with a COVID-19 infection. The finding of bilateral B-lines and white lung areas with patchy peripheral distribution and sparing areas is the most suggestive ultrasound picture of COVID-19 pneumonia. Failure to detect bilateral interstitial syndrome (A pattern) on ultrasound excludes COVID-19 pneumonia with good diagnostic accuracy, but does not exclude current infection. The use of shared semiotic and reporting schemes allows the comparison and monitoring of the COVID-19 pulmonary involvement over time. This review aims to summarise the main data on pulmonary ultrasound and COVID-19 to provide accurate and relevant information for clinical practice.

Pulmonary embolism in patients with severe COVID-19 treated with intermediate- to full-dose enoxaparin: A retrospective study.

Coronavirus disease (COVID-19) may predispose patients to pulmonary embolism (PE), despite standard thromboprophylaxis. Our retrospective study aimed to report the prevalence of PE in patients with COVID-19 and severe respiratory failure (SRF) treated with intermediate- to full-dose enoxaparin. We analyzed data from patients with COVID-19 pneumonia and SRF admitted to our Respiratory Intensive Care Unit (RICU) from February 27 to April 20, 2020. All patients received at least intermediate-dose enoxaparin (40 mg twice daily). Computed tomography pulmonary angiography (CTPA) was used to detect PE. Ninety-two patients with COVID-19 pneumonia and SRF were admitted to our RICU. Twenty-two patients underwent CTPA (24 %), 11 of whom had PEs (12%). We hypothesize that the enoxaparin treatment may be responsible for the lower prevalence of PE as compared to previous reports of similar patients, even if our report had several limitations, mainly the small sample size.

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.

Prospective meta-analysis protocol on randomised trials of renin-angiotensin system inhibitors in patients with COVID-19: an initiative of the International Society of Hypertension.

INTRODUCTION: Whether ACE inhibitors (ACEi) or angiotensin II receptor blocker (ARB) therapy should be continued, initiated or ceased in patients with COVID-19 is uncertain. Given the widespread use of ACEi/ARBs worldwide, guidance on the use of these drugs is urgently needed. This prospective meta-analysis aims to pool data from randomised controlled trials (RCTs) to assess the safety and efficacy of ACEi/ARB therapy in adults infected with SARS-CoV-2. METHODS AND ANALYSIS: RCTs will be eligible if they compare patients with COVID-19 randomised to ACEi/ARB continuation or commencement versuss no ACEi/ARB therapy; study duration ≥14 days; recruitment completed between March 2020 and May 2021. The primary outcome will be all-cause mortality at ≤30 days. Secondary outcomes will include mechanical ventilation, admission to intensive care or cardiovascular events at short-term follow-up (≤30 days) and all-cause mortality at longer-term follow-up (>1 month). Prespecified subgroup analyses will assess the effect of sex; age; comorbidities; smoking status; ethnicity; country of origin on all-cause mortality. A search of ClinicalTrials.gov has been performed, which will be followed by a formal search of trial registers, preprint servers, MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials to identify RCTs that meet inclusion criteria. To date, a search of ClinicalTrials.gov identified 21 potentially eligible trials for this meta-analysis. We will request trial investigators/sponsors to contribute standardised grouped tabular outcome data. ETHICS AND DISSEMINATION: Ethics approval and informed consent will be the responsibility of the individual RCTs. Dissemination of results will occur by peer-reviewed publication. The results of our analysis can inform public health policy and clinical decision making regarding ACEi/ARB use in patients with COVID-19 on a global scale.

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.

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.