Clinical prediction models in hospitalized patients with COVID-19: A multicenter cohort study.

BACKGROUND: Clinical spectrum of novel coronavirus disease (COVID-19) ranges from asymptomatic infection to severe respiratory failure that may result in death. We aimed at validating and potentially improve existing clinical models to predict prognosis in hospitalized patients with acute COVID-19. METHODS: Consecutive patients with acute confirmed COVID-19 pneumonia hospitalized at 5 Italian non-intensive care unit centers during the 2020 outbreak were included in the study. Twelve validated prognostic scores for pneumonia and/or sepsis and specific COVID-19 scores were calculated for each study patient and their accuracy was compared in predicting in-hospital death at 30 days and the composite of death and orotracheal intubation. RESULTS: During hospital stay, 302 of 1044 included patients presented critical illness (28.9%), and 226 died (21.6%). Nine out of 34 items included in different prognostic scores were independent predictors of all-cause-death. The discrimination was acceptable for the majority of scores (APACHE II, COVID-GRAM, REMS, CURB-65, NEWS II, ROX-index, 4C, SOFA) to predict in-hospital death at 30 days and poor for the rest. A high negative predictive value was observed for REMS (100.0%) and 4C (98.7%) scores; the positive predictive value was poor overall, ROX-index having the best value (75.0%). CONCLUSIONS: Despite the growing interest in prognostic models, their performance in patients with COVID-19 is modest. The 4C, REMS and ROX-index may have a role to select high and low risk patients at admission. However, simple predictors as age and PaO2/FiO2 ratio can also be useful as standalone predictors to inform decision making.

Handgrip strength is associated with adverse outcomes in patients hospitalized for COVID-19-associated pneumonia.

Handgrip strength (HGS), a simple tool for the evaluation of muscular strength, is independently associated with negative prognosis in many diseases. It is unknown whether HGS is prognostically relevant in COVID-19. We evaluated the ability of HGS to predict clinical outcomes in people with COVID-19-related pneumonia. 118 patients (66% men, 63 ± 12 years), consecutively hospitalized to the "Santa Maria" Terni University Hospital for COVID-19-related pneumonia and respiratory failure, underwent HGS measurement (Jamar hand-dynamometer) at ward admission. HGS was normalized to weight2/3 (nHGS) The main end-point was the first occurrence of death and/or endotracheal intubation at 14 days. Twenty-two patients reached the main end-point. In the Kaplan-Meyer analysis, the Log rank test showed significant differences between subjects with lower than mean HGS normalized to weight2/3 (nHGS) (< 1.32 kg/Kg2/3) vs subjects with higher than mean nHGS. (p = 0.03). In a Cox-proportional hazard model, nHGS inversely predicted the main end-point (hazard ratio, HR = 1.99 each 0.5 kg/Kg2/3 decrease, p = 0.03), independently from age, sex, body mass index, ratio of partial pressure arterial oxygen and fraction of inspired oxygen (PaO2/FiO2 ratio), hypertension, diabetes, estimated glomerular filtration rate and history of previous cardiovascular cardiovascular disease. These two latter also showed independent association with the main end-point (HR 1.30, p = 0.03 and 3.89, p < 0.01, respectively). In conclusion, nHGS measured at hospital admission, independently and inversely predicts the risk of poor outcomes in people with COVID-19-related pneumonia. The evaluation of HGS may be useful in early stratifying the risk of adverse prognosis in 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.

Vaccine-induced massive pulmonary embolism and thrombocytopenia following a single dose of Janssen Ad26.COV2.S vaccination.

Vaccine-induced immune thrombotic thrombocytopenia (VITT) has emerged as a rare side effect of adenoviral vector-based vaccines against coronavirus disease 2019 (COVID-19), and is most frequently reported after use of the Vaxzevria (AstraZeneca) vaccine. This report describes a case of severe thrombocytopenia associated with massive pulmonary embolism and portal vein thrombosis occurring 13 days after the administration of the single-dose adenoviral vector-based vaccine Ad26.COV2.S (Janssen Vaccines). Based on early clinical suspicion, the patient quickly received treatment with corticosteroids and intravenous immunoglobulin, followed by a rapid increase in platelet count that allowed timely administration of full-dose anticoagulation. Treatment with intravenous immunoglobulin, however, could mask the ability of anti-platelet factor 4-heparin antibodies to bind and activate platelets in the presence of heparin, leading to false-negative results on the immunoassay functional test. Therefore, if VITT is suspected, blood samples for diagnostic confirmation should be collected prior to any treatment to improve diagnostic performance.

Mid-term impact of mild-moderate COVID-19 on cardiorespiratory fitness in élite athletes.

BACKGROUND: Mid- and long-term sequelae of COVID-19 on cardiorespiratory fitness are unknown. Aim of the study was to assess the mid-term impact of mild-moderate COVID-19 on cardiorespiratory fitness evaluated by cardiopulmonary exercise testing (CPET) in élite athletes. METHODS: 13 elite cross-country skiers with previous mild-moderate COVID-19 symptoms underwent CPET before resuming seasonal training (COVID athletes). 13 élite detrained cross-country skiers, matched for principal confounding factors, were taken as controls (control group). Resting peripheral oxygen saturation, pulmonary function test, echocardiography, bioelectrical impedance analysis and CPET (modified XELG2, Woodway, USA) were performed in all participants. RESULTS: Median recovery time in COVID athletes was 34 days (IQR 33-38 days). COVID athletes reached earlier the onset of the aerobic threshold (4'48" vs. 6'28", R2=0.15, F=4.37, P<0.05) than controls, whereas the time to anaerobic threshold and maximal efforts did not significantly differ between groups. Oxygen consumption was lower at the aerobic threshold in COVID athletes than controls (VO2/kg 28.6 mL/min vs. 38.9 mL/min, R2=0.39, F=15.34, P<0.01), whereas no significant difference between groups was found both at the aerobic threshold and at peak exercise (all P<0.05). Findings from resting echocardiography and pulmonary function test were similar between the two groups. CONCLUSIONS: Élite cross-country athletes, previously affected by mild-moderate COVID-19, reached earlier the aerobic threshold than controls, whereas the remaining CPET parameters did not differ between groups. Such changes were not associated with any detectable difference in resting pulmonary and cardiac examination. Subjects affected by mild-moderate COVID-19 may require a longer time course of re-adaptation to aerobic exercise.

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.].

Efficacy of convalescent plasma therapy in immunocompromised patients with COVID-19: A case report.

BACKGROUND: Management of immunocompromised COVID-19 patients is the object of current debate. Accumulating evidence suggest that treatment with high-titer COVID-19 convalescent plasma (CCP) may be effective in this characteristic clinical scenario. CASE REPORT: A 52-years old immunocompromised female patient, previously treated with rituximab for low grade B-cell lymphoma, showed prolonged SARS-CoV-2 shedding and a long-term course of signs of severe COVID-19. A first cycle of treatment with remdesivir, a nucleotide analogue prodrug effective in inhibiting SARS-CoV-2 replication, did not provide fully and sustained clinical remission. A second hospitalization was deemed necessary after 10 days from the first hospital discharge due to recrudescence of symptoms of severe COVID-19 and the evidence of bilateral interstitial pneumonia at the chest-CT scan. Clinical and radiological findings completely disappeared after CCP administration. The viral culture confirmed the absence of SARS-CoV-2-related cytopathic effect. The clinical evaluation, performed two months after hospital discharge, was unremarkable. RESULTS: Findings from our case report suggest that the host T-cell specific response to SARS-CoV-2 is not sufficient to reduce viral load in the absence of neutralizing antibodies. Acquired immune antibodies and/or related components passively infused with CCP might help in boosting the plasma recipient response to the virus and promoting complete viral clearance. CONCLUSIONS: Independently from negative results in immunocompetent individuals, the potential effectiveness of CCP infusion in selected cohorts of patients with primary or secondary impaired immune response should be tested. Further research about mechanisms of host response in immunocompromised patients with SARS-CoV-2 infection is required.

Association Between Air Pollution and Acute Coronary Syndromes During Lockdown for COVID-19: Results From the Terni Hub Center.

Background: During the lockdown for COVID-19, a massive decrease in hospital admissions for acute coronary syndrome (ACS) and a drop in air pollution were both detected in Italy. Our aim was to investigate the possible association between these two events at the Province of Terni, one of the most polluted urban and industrial area in Central Italy. Methods: We analyzed data of daily 24-h urban air concentrations of particulate matter (PM)10 and PM2.5 from fixed station monitoring network located in the main city centers of the Terni province, and accesses for ACS at the catheterization laboratory of the Cardiological Hub Center of the Terni University Hospital during lockdown. A comparison was made with data corresponding to the same lockdown time period of years 2019, 2018, and 2017. Results: Invasive procedures for ACS decreased in 2020 (n = 49) as compared with previous years (n = 93 in 2019, n = 109 in 2018, and n = 89 in 2017, p < 0.001). Conversely, reductions in average PM10 (20.7 µg/m3) and PM2.5 (14.7 µg/m3) in 2020 were consistent with a long-term decreasing trend, being comparable to those recorded in 2019 and 2018 (all p > 0.05) and slightly lower than 2017 (p < 0.05). The Granger-causality test demonstrated the lack of association between time-varying changes in air pollution and the number of procedures for ACS. Conclusions: Our results did not support the hypothesis that reduction in invasive procedures for ACS during lockdown was linked to an air cleaning effect. Reasons other than reduced air pollution should be sought to explain the observed decrease in ACS procedures.

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.

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.

Renin-Angiotensin System Inhibition in Cardiovascular Patients at the Time of COVID19: Much Ado for Nothing? A Statement of Activity from the Directors of the Board and the Scientific Directors of the Italian Society of Hypertension.

Cardiovascular diseases, in particular hypertension, as well as the cardiovascular treatment with Renin-Angiotensin System inhibitors such as Angiotensin Converting Enzyme (ACE) inhibitors and Angiotensin Receptor Blockers (ARBs), are claimed once again as mechanisms of Severe Acute Respiratory Syndrome (SARS) during the COVID-19 outbreak due to Cov-2 epidemics. In vitro studies are available to support the eventual role of ACE inhibitors and ARBs in both the promotion and antagonism of the disease. The available literature, indeed, presents contrasting results, all concentrated in experimental models. Evidence in humans is lacking that those mechanisms are actually occurring in the present COVID-19 outbreak. Here we present the reasoned statement of the Italian Society of Hypertension to maintain ongoing antihypertensive treatments. Furthermore, the Italian Society of Hypertension presents its own initiative to investigate the issue using an online questionnaire to collect relevant data in human disease.