Background Endothelial dysfunction is one of the underlying mechanisms to vascular and cardiac complications in patients with COVID-19. We sought to investigate the systemic vascular endothelial function and its temporal changes in COVID-19 patients from a non-invasive approach with reactive hyperemia peripheral arterial tonometry (PAT). Methods This is a prospective, observational, case-control and blinded study. The population was comprised by 3 groups: patients investigated during acute COVID-19 (group 1), patients investigated during past COVID-19 (group 2), and controls 1:1 matched to COVID-19 patients by demographics and cardiovascular risk factors (group 3). The natural logarithmic scaled reactive hyperemia index (LnRHI), a measure of endothelium-mediated dilation of peripheral arteries, was obtained in all the participants and compared between study groups. Results 144 participants were enrolled (72 COVID-19 patients and 72 matched controls). Median time from COVID-19 symptoms to PAT assessment was 9.5 and 101.5 days in groups 1 and 2, respectively. LnRHI was significantly lower in group 2 compared to both group 1 and controls (0.53 ± 0.23 group 2 vs. 0.72 ± 0.26 group 1, p = 0.0043; and 0.79 ± 0.23 in group 3, p < 0.0001). In addition, within group 1, it was observed a markedly decrease in LnRHI from acute COVID-19 to post infection stage (0.73 ± 0.23 vs. 0.42 ± 0.26, p = 0.0042). Conclusions This study suggests a deleterious effect of SARS-CoV-2 infection on systemic vascular endothelial function. These findings open new venues to investigate the clinical implication and prognostic role of vascular endothelial dysfunction in COVID-19 patients and post-COVID syndrome using non-invasive techniques.

Background: In the face of the global pandemic that the coronavirus disease 2019 (COVID-19) has created, readily available prognostic markers may be of great use. Objective: To evaluate the association between serum magnesium (sMg) levels on admission and clinical outcomes in hospitalized COVID-19 patients. Methods: We retrospectively analyzed all patients admitted to a single tertiary center with a primary de novo diagnosis of COVID-19. Patients were followed for a mean of 10 ± 7 months. Demographic, clinical and laboratory data were collected and compared between five groups of patients according to sMg quintiles on hospital admission. Results: The cohort included 1522 patients (58% male, 69 ± 17 years old). A low sMg level (1st quintile) was associated with higher rates of diabetes and steroid use, whereas a high sMg level (5th quintile) was associated with dyslipidemia, renal dysfunction, higher levels of inflammatory markers and stay in the intensive care unit. All-cause in-hospital and long-term mortality was higher in patients with both low and high sMg levels, compared with mid-range sMg levels (2nd, 3rd and 4th quintiles; 19% and 30% vs. 9.5%, 10.7% and 17.8% and 35% and 45.3% vs. 23%, 26.8% and 27.3% respectively; p < 0.001 for all). After adjusting for significant clinical parameters indicating severe disease and renal dysfunction, only low sMg state was independently associated with increased mortality (HR = 1.57, p < 0.001). Conclusions: Both low and high sMg levels were associated with increased mortality in a large cohort of hospitalized COVID-19 patients. However, after correction for renal dysfunction and disease severity, only low sMg maintained its prognostic ability.

Background Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) uses angiotensin-converting enzyme 2 (ACE2) receptor as a means to enter the host. High density of ACE2 receptor in vascular endothelial cells may explain why vascular complications related to endothelial dysfunction occur in COVID-19. However, in vivo assessment of vascular endothelial function during COVID-19 has not been reported. Objective To investigate the vascular endothelial function and its temporal changes in COVID-19 patients. Methods In this prospective blinded study, systemic endothelial function was assessed using plethysmography-derived peripheral arterial tonometry (PAT). The reactive hyperemia index (LnRHI), a measure of endothelium-mediated hyperaemia, and the augmentation index, a measure of arterial vascular stiffness, were measured in 102 individuals across three study groups using PAT: group 1 (active infection), constituted by 20 patients hospitalised due to acute COVID-19; group 2 (past infection), constituted by 52 patients who had recovered from COVID-19; and group 3 (controls), constituted by 30 healthcare workers not infected by SARS-CoV-2. Additionally, among group 1, PAT assessment was repeated in 14 patients several weeks after recovery from acute COVID-19. PAT studies were analysed at a blinded fashion with respect to the assigned study group. Results Lower resting PAT amplitude was found in acute COVID-19 patients compared to the other groups (ratio of arterial tone signal between hyperemia to resting condition was 1.5 [interquartile range, 1.1] in group 1, 1.3 [0.3] in group 2 and 1.2 [0.3] in group 3, p=0.041). On the contrary, no significant differences between groups were found with respect to the hyperemic PAT amplitude (867.9 [486.1] in group 1, 944.7 [748.1] in group 2 and 819.3 [639.6] in group 3, p=0.444). Due to the lower resting PAT amplitude, there was a paradoxically significantly increased LnRHI during acute COVID-19 compared to past infection and controls (0.73 [0.32] vs. 0.53 [0.31] vs. 0.44 [0.23], respectively; p=0.013) (Figure A). Furthermore, among group 1 patients, LnRHI normalised markedly from acute COVID-19 to past infection stage (0.73 [0.32] vs. 0.49 [0.28], respectively; p=0.005) (Figure B). Augmentation index was significantly higher during acute COVID-19 compared to past COVID-19 and controls (9.6 [19.1] in group 1, 6.97 [18.6] in group 2 and −0.35 [20.53] in group 3; p=0.045 for COVID groups vs. controls). Conclusions Non-invasive assessment of systemic vascular endothelial function with PAT revealed significant differences between subjects with acute COVID-19, past COVID-19 and controls. Lower baseline PAT amplitude and high augmentation index suggest vasoconstriction at rest during the acute phase of COVID-19. These findings open new research opportunities to investigate the prognostic value of PAT in COVID-19 patients. FUNDunding Acknowledgement Type of funding sources: None.

Introduction In the face of the global pandemic coronavirus disease 2019 (COVID-19) has created, readily available prognostic markers may be of great use. Purpose To evaluate the association between serum magnesium levels (sMg) on admission and clinical outcomes in hospitalized COVID-19 patients. Methods We retrospectively analyzed all consecutive patients admitted to our medical center with a primary de novo diagnosis of COVID-19.Demographic, clinical and laboratory data were extracted from the electronic medical record. Clinical outcomes were compared between five groups of patients according to the quintiles of sMg on hospital admission. Results From 2,433 consecutive COVID-19 patients during the years 2020–2021, we included 1,522 patients with sMg on admission (1–3 day of hospitalization) (58% male, 69±17 years old). Patients were followed for a mean of 10±7 months. A low sMg level (1st quintile) was associated with higher rates of diabetes and steroid use, whereas a high sMg level (5th quintile) was associated with dyslipidemia, chronic kidney disease, andhigher levels of inflammatory markers (Table 1). Both low and high sMg levels were associated with lower oxygen saturation during hospitalization. All-cause in-hospital and long-term mortality was higher in patients with both low and high sMg levels, compared with mid-range sMg levels (2nd, 3rd and 4thquintiles; 19% and 30% vs. 9.5%, 10.7% and 17.8% and 35% and 45.3% vs. 23%, 26.8% and 27.3% respectively; p&lt;0.001 for all) (Figure 1). Conclusions Both low and high sMg levels were associated with worse short- and long-term clinical outcomes and all-cause mortality in a large cohort of hospitalized COVID-19 patients. Thus, admission sMg levels may play a prognostic role in risk stratificationof COVID-19 patients. Funding Acknowledgement Type of funding sources: None.