Lipoprotein(a) Does Not Predict Thrombotic Events and In-Hospital Outcomes in Patients with COVID-19.

The prothrombotic and proinflammatory properties of lipoprotein(a) (Lp(a)) have been hypothesized to play a role in the pathogenesis of severe COVID-19; however, the prognostic impact of Lp(a) on the clinical course of COVID-19 remains controversial. This study aimed to investigate whether Lp(a) may be associated with biomarkers of thrombo-inflammation and the occurrence of thrombotic events or adverse clinical outcomes in patients hospitalized for COVID-19. We consecutively enrolled a cohort of patients hospitalized for COVID-19 and collected blood samples for Lp(a) assessment at hospital admission. A prothrombotic state was evaluated through D-dimer levels, whereas a proinflammatory state was evaluated through C-reactive protein (CRP), procalcitonin, and white blood cell (WBC) levels. Thrombotic events were marked by the diagnosis of deep or superficial vein thrombosis (DVT or SVT), pulmonary embolism (PE), stroke, transient ischemic attack (TIA), acute coronary syndrome (ACS), and critical limb ischemia (CLI). The composite clinical end point of intensive care unit (ICU) admission/in-hospital death was used to evaluate adverse clinical outcomes. Among 564 patients (290 (51%) men, mean age of 74 ± 17 years) the median Lp(a) value at hospital admission was 13 (10-27) mg/dL. During hospitalization, 64 (11%) patients were diagnosed with at least one thrombotic event and 83 (15%) patients met the composite clinical end point. Lp(a), as either a continuous or categorical variable, was not associated with D-dimer, CRP, procalcitonin, and WBC levels (p > 0.05 for all correlation analyses). In addition, Lp(a) was not associated with a risk of thrombotic events (p > 0.05 for multi-adjusted odds ratios) nor with a risk of adverse clinical outcomes (p > 0.05 for multi-adjusted hazard ratios). In conclusion, Lp(a) does not influence biomarkers of plasma thrombotic activity and systemic inflammation nor has any impact on thrombotic events and adverse clinical outcomes in patients hospitalized for COVID-19.

The impact of statin therapy on in-hospital prognosis and endothelial function of patients at high-to-very high cardiovascular risk admitted for COVID-19.

Statins may protect against adverse outcomes from Coronavirus disease 2019 (COVID-19) through their pleiotropic effects. Endothelial dysfunction seems to be implicated in the pathophysiology of COVID-19, and can be attenuated by statins. This study assessed the role of preadmission statin therapy and its interaction with endothelial function, measured using flow-mediated dilation (FMD) at hospital admission, in predicting in-hospital outcomes among patients with COVID-19 having high-to-very high cardiovascular (CV) risk. We conducted a retrospective cohort study of hospitalized patients with COVID-19 having high-to-very high CV risk, including a subgroup of patients who underwent FMD assessment. Among 342 patients, 119 (35%) were treated with statins at study baseline. Preadmission statin therapy was independently associated with a 75% risk reduction of intensive care unit admission/in-hospital death (adjusted hazard ratio 0.252, 95% confidence interval 0.122-0.521, p < 0.001). In the subgroup of patients with an FMD assessment (245 patients, 40% statin-treated), preadmission statin therapy was independently associated with higher FMD values (ß = 0.159, p = 0.013). However, preadmission statin therapy × FMD interaction was not associated with in-hospital outcomes (F = 0.002, pinteraction = 0.960). Preadmission statin therapy is associated with better in-hospital outcomes among patients with COVID-19 having high-to-very high CV risk, independent of the endothelium-protective effects of these drugs.

The HACOR Score Predicts Worse in-Hospital Prognosis in Patients Hospitalized with COVID-19.

Non-invasive respiratory support (NIRS) is widely used in COVID-19 patients, although high rates of NIRS failure are reported. Early detection of NIRS failure and promptly defining the need for intubation are crucial for the management of patients with acute respiratory failure (ARF). We tested the ability of the HACOR score¸ a scale based on clinical and laboratory parameters, to predict adverse outcomes in hospitalized COVID-19 patients with ARF. Four hundred patients were categorized according to high (>5) or low (≤5) HACOR scores measured at baseline and 1 h after the start of NIRS treatment. The association between a high HACOR score and either in-hospital death or the need for intubation was evaluated. NIRS was employed in 161 patients. Forty patients (10%) underwent intubation and 98 (25%) patients died. A baseline HACOR score > 5 was associated with the need for intubation or in-hospital death in the whole population (HR 4.3; p < 0.001), in the subgroup of patients who underwent NIRS (HR 5.2; p < 0.001) and in no-NIRS subgroup (HR 7.9; p < 0.001). In the NIRS subgroup, along with the baseline HACOR score, also 1-h HACOR score predicted NIRS failure (HR 2.6; p = 0.039). In conclusion, the HACOR score is a significant predictor of adverse clinical outcomes in patients with COVID-19-related ARF.

Thyroid-Stimulating Hormone Predicts Total Cholesterol and Low-Density Lipoprotein Cholesterol Reduction during the Acute Phase of COVID-19.

A complex dysregulation of lipid metabolism occurs in COVID-19, leading to reduced total cholesterol (TC), LDL-cholesterol (LDL-C), and HDL-cholesterol (HDL-C) levels, along with a derangement of thyroid function, leading to reduced thyroid-stimulating hormone (TSH) levels. This study aimed to explore the association between TSH levels during COVID-19 and the variation (Δ) of lipid profile parameters in the period preceding (from 1 month up to 1 year) hospital admission due to COVID-19. Clinical data of 324 patients (mean age 76 ± 15 years, 54% males) hospitalized due to COVID-19 between March 2020 and March 2022 were retrospectively analyzed. The association between TSH levels at hospital admission and either Δ-TC, Δ-LDL-C, or Δ-HDL-C over the selected time frame was assessed through univariable and multivariable analyses. TSH levels were below the lower reference limit of 0.340 µUI/mL in 14% of COVID-19 patients. A significant reduction of plasma TC, LDL-C, and HDL-C was recorded between the two time points (p < 0.001 for all the comparisons). TSH was directly associated with Δ-TC (rho = 0.193, p = 0.001), Δ-LDL-C (rho = 0.201, p = 0.001), and Δ-HDL-C (rho = 0.160, p = 0.008), and inversely associated with C-reactive protein (CRP) (rho = -0.175, p = 0.004). Moreover, TSH decreased with increasing COVID-19 severity (p < 0.001). CRP and COVID-19 severity were inversely associated with Δ-TC, Δ-LDL-C, and Δ-HDL-C (p < 0.05 for all associations). A significant independent association was found between TSH and either Δ-TC (ß = 0.125, p = 0.044) or Δ-LDL-C (ß = 0.131, p = 0.036) after adjusting for multiple confounders including CRP and COVID-19 severity. In conclusion, lower levels of TSH may contribute to explain TC and LDL-C reduction in the acute phase of COVID-19.

The detrimental impact of elevated Ferritin to Iron ratio on in-hospital prognosis of patients with COVID-19.

BACKGROUND: Acute viral infections, including coronavirus disease 2019 (COVID-19), are characterized by the dysregulation of iron metabolism, resulting in high serum ferritin and low iron levels. RESEARCH DESIGN AND METHODS: This study aimed to evaluate the prospective impact of iron metabolism dysregulation, as expressed by serum Ferritin-to-Iron Ratio (FIR), on the in-hospital prognosis of patients with COVID-19. Serum levels of ferritin and iron, as well as other iron metabolism markers and recognized prognostic indicators of COVID-19 severity, were measured in 362 patients consecutively hospitalized for COVID-19. The prospective relationship between FIR and the risk of the composite outcome of intensive care unit (ICU) admission/in-hospital death was analyzed. RESULTS: In the population examined (mean age 74 ± 15 years, males 55%), the rates of radiographic signs of pneumonia, respiratory distress, and the need for noninvasive ventilation were higher in patients with high FIR (≥29.2, the 75th percentile) than in those with low FIR (<29.2, the 75th percentile) (p < 0.05 for all comparisons). High FIR was associated with a 1.7-fold (HR 1.709, 95% CI 1.017-2.871, p = 0.043) higher risk of ICU admission/in-hospital death. CONCLUSIONS: Increasing FIR values significantly and independently predicts worse in-hospital prognosis in hospitalized patients with COVID-19.

Low Brachial Artery Flow-Mediated Dilation Predicts Worse Prognosis in Hospitalized Patients with COVID-19.

BACKGROUND: Endothelial injury can be induced by coronavirus disease 2019 (COVID-19) and seems to exert a crucial pathogenic role in its most severe clinical manifestations. We aimed to investigate the association between brachial artery flow-mediated dilation (bFMD), a potential clinical and non-invasive measure of endothelial function, and in-hospital prognosis of COVID-19 patients. METHODS: Brachial artery flow-mediated dilation was assessed in hospitalized COVID-19 patients within 48 h of hospital admission. The association between bFMD and either intensive care unit (ICU) admission or in-hospital death was explored using univariable and multivariable analyses. RESULTS: Four hundred and eight patients were enrolled. Significantly lower bFMD values emerged in COVID-19 patients with either radiographic signs of pneumonia, respiratory distress, or the need for non-invasive ventilation compared with patients without these signs (p < 0.001, p = 0.001, and p < 0.001, respectively). Forty-two (10%) patients were admitted to the ICU, 76 (19%) patients died, and 118 (29%) patients met the composite endpoint of ICU admission/in-hospital death. At unadjusted Cox regression analysis showed that low bFMD (<4.4%, the median value) was associated with a higher risk for the composite endpoint of ICU admission/in-hospital death compared with high bFMD (≥4.4%, the median value) (HR 1.675, 95% CI 1.155-2.428, p = 0.007). Multi-adjusted Cox regression analyses showed that low bFMD was independently associated with a 1.519- to 1.658-fold increased risk for the composite endpoint of ICU admission/in-hospital death. CONCLUSIONS: Low bFMD predicts an unfavorable in-hospital prognosis in COVID-19 patients. The measurement of bFMD may be clinically useful in the prognostic stratification of COVID-19 patients upon hospital admission.

Prevalence of vitamin D deficiency and its prognostic impact on patients hospitalized with COVID-19.

OBJECTIVES: Although hypovitaminosis D appears to be highly prevalent in patients with coronavirus disease 2019 (COVID-19), its impact on their prognosis remains unclear. METHODS: In this study, serum 25-hydroxyvitamin D (Vit-D) level was measured in 200 patients hospitalized with COVID-19. The association between Vit-D and the composite endpoint of intensive care unit (ICU) admission/in-hospital death was explored using univariable and multivariable analyses. Also, serum Vit-D level in patients with COVID-19 was compared with that in age- and sex-balanced COVID-19-negative controls (i.e., 50 inpatients with sepsis). RESULTS: Serum Vit-D level was comparable between patients with COVID-19 and COVID-19-negative inpatients with sepsis (P = 0.397). No significant differences were found in serum Vit-D level according to COVID-19 severity at the time of hospital admission (P = 0.299). Incidence rates of the composite endpoint of ICU admission/in-hospital death did not differ significantly between patients with either Vit-D deficiency (i.e., Vit-D <20 ng/mL) or severe Vit-D deficiency (i.e., Vit-D <12 ng/mL) and those without (31% vs 35% with P = 0.649, and 34% vs 30% with P = 0.593, respectively). Vit-D level and status (i.e., Vit-D deficiency and severe Vit-D deficiency) were not prospectively associated with the risk of the composite endpoint of ICU admission/in-hospital death (P > 0.05 for all Cox regression models). CONCLUSIONS: Regardless of the potential usefulness of Vit-D measurement to guide appropriate supplementation, Vit-D does not appear to provide helpful information for the stratification of in-hospital prognosis in patients with COVID-19.

Time-related changes in sex distribution of COVID-19 incidence proportion in Italy.

BACKGROUND: Variable sex-disaggregated data on Coronavirus disease 2019 (COVID-19) incidence proportion (IP) have been reported in different datasets and studies. Factors explaining the inconsistent distribution of COVID-19 among sexes are still unclear. OBJECTIVES: This study aimed to analyse time-related variation of sex-disaggregated COVID-19 IP in Italy since March 9th to May 11th 2020, and to test its association with the frequency of swab testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). STUDY DESIGN: Sex-disaggregated data on COVID-19 cases were collected from Italian publicly accessible databases along with undisaggregated data on the number of reverse transcriptase-polymerase chain reaction (RT-PCR) SARS-CoV-2 tests. Crude and adjusted associations between the frequency of RT-PCR SARS-CoV-2 testing and male-to-female (M/F) ratio of COVID-19 IP were performed. RESULTS: COVID-19 IP increased progressively in both sexes. Sex prevalence of COVID-19 IP reversed over time, with the M/F ratio of COVID-19 IP having passed from 1,73 to 0,91. The mean number of daily swabs for RT-PCR SARS-CoV-2 test increased progressively until reaching a plateau in the last three weeks of the study period. The M/F ratio of COVID-19 IP inversely correlated with the number of daily swabs for RT-PCR SARS-CoV-2 test (r = -0,87, p < 0.001), even after adjusting for the median age of COVID-19 cases (ß = -0,66, p < 0,001). CONCLUSIONS: Time-related changes of sex distribution of COVID-19 IP in Italy are strongly influenced by the number of swabs testing for SARS-CoV-2. Whether gender-related disparities in the access to the diagnosis of COVID-19 may explain such a result need to be explored.

Interaction Between Coronavirus S-Protein and Human ACE2: Hints for Exploring Efficient Therapeutic Targets to Treat COVID-19.

With the global expansion of coronavirus disease 2019 (COVID-19) and the declaration of its outbreak as a Public Health Emergency of International Concern by the World Health Organization, there is an urgent need for vaccines and medicines to prevent and treat COVID-19. The responsible pathogen for the disease is the newly severe acute respiratory syndrome coronavirus (SARS-CoV) 2 belonging to the same family of viruses SARS-CoV and Middle East respiratory syndrome coronavirus that originally are zoonotic and have been associated with severe illness during the outbreaks in 2003 and 2012, respectively. The virulence of coronavirus strains is mainly associated with variations in surface proteins mediating cellular entry of the virus, which can help in finding effective therapeutic targets. In this review, we seek evidence showing the role of coronavirus spike protein (S-protein) and its potential cellular receptor, angiotensin-converting enzyme 2 (ACE2), during infection of coronaviruses, including the newly SARS-CoV-2 and its similar strain SARS-CoV. This review also discusses the therapeutic effect of inhibiting the renin-angiotensin system cascade, a target of ACE2, in patients having coronavirus with cardiovascular disease.

Particulate matter pollution and the COVID-19 outbreak: results from Italian regions and provinces.

INTRODUCTION: Particulate matter exposure has been associated with the appearance and severity of several diseases, including viral infections. The aim of this study was to investigate whether coronavirus disease 2019 (COVID-19) cases and deaths across Italian regions and provinces in March 2020 were linked to past exposure to fine and coarse particulate matter (namely, PM2.5 and PM10, respectively). MATERIAL AND METHODS: Geographical distributions of COVID-19 cases and deaths (105,792 and 12,428, respectively, up to 31st March 2020), PM2.5 and PM10 exposure, and demographic characteristics were extracted from publicly accessible databases. Adjusted regression models were performed to test the association between particulate matter exposure in different Italian regions and provinces and COVID-19 incidence proportions and death rates. RESULTS: A heterogeneous distribution of COVID-19 cases/deaths and particulate matter exposure was observed in Italy, with the highest numbers in Northern Italy regions and provinces. Independent associations between regional PM2.5/PM10 exposure and COVID-19 incidence proportion and death rate were observed (COVID-19 incidence proportion: ß = 0.71, p = 0.003, ß = 0.61, p = 0.031, respectively; COVID-19 death rate: ß = 0.68, p = 0.004 and ß = 0.61, p = 0.029, respectively). Similarly, PM2.5/PM10 exposures were independently associated with COVID-19 incidence proportion (ß = 0.26, p = 0.024 and ß = 0.27, p = 0.006, respectively) at the provincial level. The number of days exceeding the provincial limit value of exposure to PM10 (50 µg/m3) was also independently associated with the COVID-19 incidence proportion (ß = 0.30, p = 0.008). CONCLUSIONS: Exposure to PM2.5 and PM10 is associated with COVID-19 cases and deaths, suggesting that particulate matter pollution may play a role in the COVID-19 outbreak and explain the heterogeneous distribution of COVID-19 in Italian regions and provinces.

Is Acetylsalicylic Acid a Safe and Potentially Useful Choice for Adult Patients with COVID-19 ?

Severe Acute Respiratory Syndrome-Coronavirus-2 is responsible for the current pandemic that has led to more than 10 million confirmed cases of Coronavirus Disease-19 (COVID-19) and over 500,000 deaths worldwide (4 July 2020). Virus-mediated injury to multiple organs, mainly the respiratory tract, activation of immune response with the release of pro-inflammatory cytokines, and overactivation of the coagulation cascade and platelet aggregation leading to micro- and macrovascular thrombosis are the main pathological features of COVID-19. Empirical multidrug therapeutic approaches to treat COVID-19 are currently used with extremely uncertain outcomes, and many others are being tested in clinical trials. Acetylsalicylic acid (ASA) has both anti-inflammatory and antithrombotic effects. In addition, a significant ASA-mediated antiviral activity against DNA and RNA viruses, including different human coronaviruses, has been documented. The use of ASA in patients with different types of infections has been associated with reduced thrombo-inflammation and lower rates of clinical complications and in-hospital mortality. However, safety issues related both to the risk of bleeding and to that of developing rare but serious liver and brain damage mostly among children (i.e., Reye's syndrome) should be considered. Hence, whether ASA might be a safe and reasonable therapeutic candidate to be tested in clinical trials involving adults with COVID-19 deserves further attention. In this review we provide a critical appraisal of current evidence on the anti-inflammatory, antithrombotic, and antiviral effects of ASA, from both a pre-clinical and a clinical perspective. In addition, the potential benefits and risks of use of ASA have been put in the context of the adult-restricted COVID-19 population.