Early effects of inactivated (CoronaVac) SARS-CoV-2 vaccine on retrobulbar vascular blood flow and retinal vascular density.

AIMS: We aimed to investigate the early effects of inactivated SARS-CoV-2 vaccine on retrobulbar vascular blood flow and retinal vascular density in healthy subjects. METHODS: Thirty-four eyes of 34 healthy volunteers who received the CoronaVac (Sinovac Life Sciences, China) were included in this prospective study. Resistive index (RI), pulsatility index (PI) and peak systolic velocity (PSV) of the ophthalmic artery (OA), central retinal artery (CRA), and the temporal and nasal posterior ciliary arteries (PCA) were evaluated with color Doppler ultrasonography (CDUS) before vaccination, at the 2nd and 4th weeks after vaccination. Superficial capillary plexus (SCP) and deep capillary plexus (DCP) vessel density (VD), foveal avascular zone (FAZ), and choriocapillaris blood flow (CCF) measurements were made using optical coherence tomography angiography (OCTA). RESULTS: When compared to the pre-vaccination values, there was no significant change in OA-PSV, temporal-nasal PCA-PSV, CRA-EDV, temporal-nasal PCA-EDV at 2nd and 4th weeks after vaccination. However statistically significant reductions were found in the OA-RI, OA-PI, CRA-RI, CRA-PI, temporal-nasal PCA-RI, temporal-nasal PCA-PI values, CRA-PSV at post-vaccination 2nd week (p<0.05 for all). While there was sustained reduction in OA-RI, OA-PI, CRA-PSV, and nasal PCA-RI values at 4th week after vaccination, the change in CRA-RI, CRA-PI, temporal PCA-RI, temporal-nasal PCA-PI values were not significant compared to pre-vaccination values. There was no statistically significant difference in the SCP-VD, DCP-VD, FAZ and CCF measurements. CONCLUSIONS: Our findings demonstrating that CoronaVac vaccine did not affect retinal vascular density in the early period, but it caused alterations in the retrobulbar blood flow.

[Changes in ocular hemodynamics in patients recovered from COVID-19]. / Oftal'mogemodinamicheskie narusheniya posle perenesennoi koronavirusnoi infektsii, vyzvannoi virusom SARS-CoV-2.

PURPOSE: To evaluate the severity of hemodynamic changes in the ocular vessels of patients recovered from COVID-19. MATERIAL AND METHODS: The study included 44 patients (88 eyes) aged 28-60 years, among them 24 (54.5%) women and 20 (45.4%) men, with SARS-CoV-2 infection confirmed by PCR no more than 2 months prior to enrollment and with no ophthalmological complaints within 2 months before the disease, as well as 20 healthy volunteers (40 eyes). At the time of the study all patients had a negative PCR result for SARS-CoV-2. The patients were divided into 2 groups. The first group comprised 24 patients who did not take any anticoagulants during the treatment. The second group consisted of 20 patients who received anticoagulants (Rivaroxaban (Xarelto)) at a dosage of 10 mg per day for 1-1.5 months. The maximum systolic (Vs), end-diastolic (Vd) blood flow velocity, as well as resistance index (RI) in the ophthalmic artery (OA), central retinal artery (CRA) and short posterior ciliary arteries (SPCA) were measured in all study patients with the ultrasound imaging system VOLUSON E8 Expert («Kretz¼, USA). Additionally, the flowmetry method was used to assess the volumetric ocular blood flow (VOBF) on Ocular Blood Flow Analyzer system («Paradigm Medical Industries, Inc.¼, USA). RESULTS: In the first group, a decrease in Vs and Vd was noted amid a significant increase of RI in CRA and SPCA, as well as an increase of RI in OA compared with the age-normal values (p<0.05). In the second group, a decrease in Vs and Vd was noted amid a significant increase of RI in CRA, as well as a decrease in Vs in SPCA and an increase of RI in OA relative to the age-normal values (p<0.05). A decrease in VOBF was noted in the first group in comparison to the second group and the age norm (p<0.05). CONCLUSION: Blood flow velocity parameters in the ocular vessels are reduced in patients recovered from COVID-19 compared to the age-normal values. There was a significant decrease in volumetric ocular blood flow parameters in COVID-19 patients who did not take any anticoagulants compared to the age-normal values. Anticoagulants intake has a positive impact on hemodynamic characteristics in the ocular vessels and volumetric ocular blood flow in patients with COVID-19.

Retrobulbar ocular blood flow and choroidal vascular changes in patients recovering from COVID-19 infection.

BACKGROUND: To evaluate the effects of COVID-19 infection on the ocular vascular structure including choroidal thickness and retrobulbar blood flow values in comparison with healthy subjects. METHODS: Ninety eyes of 90 patients were included in this study. Participants were divided into Group 1 (n = 30) with mild COVID-19 infection, Group 2 (n = 31) with moderate disease, and Group 3 with age- and sex-matched healthy subjects (n = 29). Choroidal thickness was measured at the subfoveal area and at 500-µm intervals nasal and temporal to the fovea up to a distance of 1500 µm, using the enhanced depth imaging (EDI) technique of spectral coherence tomography (SD-OCT). The peak systolic velocity (PSV), end diastolic velocity (EDV), resistive index (RI), and pulsatility index (PI) values of the central retinal artery (CRA) and ophthalmic artery (OA) were evaluated with color Doppler ultrasonography (CDU). RESULTS: The choroidal thickness was significantly thinner in Group 1 and Group 2 than in Group 3 at all measurement points (p <0.001). This difference was not present between Group 1 and Group 2 who had COVID-19 disease of different severity (p>0.05).Among the retrobulbar blood flow parameters, OA PSV value was significantly lower in Group 1 and Group 2 compared to Group 3 (p = 0.025, p = 0.016, respectively). However, the CRA PSV and EDV and OA EDV values, and the CRA and OA PI and RI values were not statistically different between the groups (p> 0.05). CONCLUSION: COVID-19 infection may predispose patients to ocular vascular pathologies by affecting both choroidal and retrobulbar blood flow.

Coronary microvascular dysfunction is common in patients hospitalized with COVID-19 infection.

BACKGROUND AND AIMS: Microvascular disease is considered as one of the main drivers of morbidity and mortality in severe COVID-19, and microvascular dysfunction has been demonstrated in the subcutaneous and sublingual tissues in COVID-19 patients. The presence of coronary microvascular dysfunction (CMD) has also been hypothesized, but direct evidence demonstrating CMD in COVID-19 patients is missing. In the present study, we aimed to investigate CMD in patients hospitalized with COVID-19, and to understand whether there is a relationship between biomarkers of myocardial injury, myocardial strain and inflammation and CMD. METHODS: 39 patients that were hospitalized with COVID-19 and 40 control subjects were included to the present study. Biomarkers for myocardial injury, myocardial strain, inflammation, and fibrin turnover were obtained at admission. A comprehensive echocardiographic examination, including measurement of coronary flow velocity reserve (CFVR), was done after the patient was stabilized. RESULTS: Patients with COVID-19 infection had a significantly lower hyperemic coronary flow velocity, resulting in a significantly lower CFVR (2.0 ± 0.3 vs. 2.4 ± 0.5, p < .001). Patients with severe COVID-19 had a lower CFVR compared to those with moderate COVID-19 (1.8 ± 0.2 vs. 2.2 ± 0.2, p < .001) driven by a trend toward higher basal flow velocity. CFVR correlated with troponin (p = .003, r: -.470), B-type natriuretic peptide (p < .001, r: -.580), C-reactive protein (p < .001, r: -.369), interleukin-6 (p < .001, r: -.597), and d-dimer (p < .001, r: -.561), with the three latter biomarkers having the highest areas-under-curve for predicting CMD. CONCLUSIONS: Coronary microvascular dysfunction is common in patients with COVID-19 and is related to the severity of the infection. CMD may also explain the "cryptic" myocardial injury seen in patients with severe COVID-19 infection.

Characteristics of deep vein thrombosis in the critically ill COVID-19 patient - an observational cohort study with Doppler ultrasound measurements.

OBJECTIVE: COVID-19 is associated with an increased prevalence of deep venous thrombosis (DVT), mainly in the lower limbs. However, the characteristics and rheological conditions, which contribute to facilitating DVT occurrence have been poorly investigated. We aimed to report DVT characteristics, vein diameters and peak blood flow velocities (PBFV) in the common femoral veins (CFVs) of critically ill COVID-19 patients. PATIENTS AND METHODS: We conducted a prospective single-center cohort study in March-October 2020 including all consecutive mechanically ventilated COVID-19 adults. Doppler ultrasound of the lower limbs was performed systematically during the first week of hospitalization. In DVT-free patients, a second Doppler ultrasound was performed seven days later. Data are expressed as medians (interquartile ranges) or percentages. Comparisons were performed using Mann-Whiney and Wilcoxon signed-rank tests or Fischer's exact tests, as appropriate. RESULTS: Fifty-five patients [age, 63 years (56-74); female/male ratio, 0.62; body-mass index, 29 kg/m2 (26-33); hypertension, 47%; diabetes, 38%; ischemic heart disease, 11%] were included. DVT was diagnosed in 19 patients (35%) including in 5 femoral (9%), 2 popliteal (4%) and 12 below-the-knee sites (22%). CFV diameter was increased to 12.0 mm (11.0-15.0) (normal range, 9.1-12) and PBFV reduced to 11.9 cm/s (8.8-15.8) (normal range, 21.3-49.2) [right-side values]. In four patients who had ultrasound before intubation, CFV diameter increased from 12.5 mm (11.8-13.3) before to 14 mm (13.6-15.3) after intubation (p = 0.008). CONCLUSIONS: DVT in the CFV occurred in 9% of the critically ill COVID-19 patients with an overall 35%-DVT prevalence. Venous return difficulty evidenced by larger than normal CFV diameters and lower than normal PBFVs may have facilitated proximal DVT occurrence.

Fetal pulmonary artery Doppler evaluation in pregnant women after recovery from COVID-19.

OBJECTIVE: To evaluate fetal lung development using pulmonary artery Doppler in pregnant women who had recovered from COVID-19. METHODS: The prospective case-control study included 41 pregnant women who had recovered from COVID-19 and 43 healthy pregnant women (control group). All the women in the study group had been diagnosed with COVID-19 and had completed a quarantine period. RESULTS: The demographic data of patients were similar in the groups (P > 0.05). Main pulmonary artery peak systolic velocity was higher and pulsatility indices were lower in pregnant women who recovered from COVID-19 compared to the controls (P < 0.001, P = 0.001). Acceleration time, ejection time, and acceleration/ejection time ratio (PATET) of the fetal MPA Doppler were significantly decreased in pregnant women who recovered from COVID-19 (P < 0.001, P = 0.036, and P = 0.002, respectively). The patients who had recovered from COVID-19 were divided into two groups: those treated with expectant management and those treated in hospital. The pulmonary artery acceleration time and PATET ratio were significantly lower in the group treated in the hospital (P = 0.023 and P = 0.045, respectively). CONCLUSION: Detailed Doppler evaluations of the pulmonary artery may help in evaluating the fetal adverse effects of COVID-19 disease.

Blunted peripheral but not cerebral vasodilator function in young otherwise healthy adults with persistent symptoms following COVID-19.

Recent findings suggest that COVID-19 causes vascular dysfunction during the acute phase of the illness in otherwise healthy young adults. To date, to our knowledge, no studies have investigated the longer-term effects of COVID-19 on vascular function. Herein, we hypothesized that young, otherwise healthy adults who are past the acute phase of COVID-19 would exhibit blunted peripheral [brachial artery flow-mediated dilation (FMD) and reactive hyperemia] and cerebral vasodilator function (cerebral vasomotor reactivity to hypercapnia; CVMR) and increased central arterial stiffness. Sixteen young adults who were at least 4 wk past a COVID-19 diagnosis and 12 controls who never had COVID-19 were studied. Eight subjects with COVID-19 were symptomatic (SYM) and eight were asymptomatic (ASYM) at the time of testing. FMD and reactive hyperemia were not different between COVID and control groups. However, FMD was lower in SYM (3.8 ± 0.6%) compared with ASYM (6.8 ± 0.9%; P = 0.007) and control (6.8 ± 0.6%; P = 0.003) with no difference between ASYM and control. Similarly, peak blood velocity following cuff release was lower in SYM (47 ± 8 cm/s) compared with ASYM (64 ± 19 cm/s; P = 0.025) and control (61 ± 14 cm/s; P = 0.036). CVMR and arterial stiffness were not different between any groups. In summary, peripheral macrovascular and microvascular function, but not cerebral vascular function or central arterial stiffness were blunted in young adults symptomatic beyond the acute phase of COVID-19. In contrast, those who were asymptomatic had similar vascular function compared with controls who never had COVID-19.NEW & NOTEWORTHY This study was the first to investigate the persistent effects of COVID-19 on vascular function in otherwise healthy young adults. We demonstrated that peripheral macrovascular and microvascular vasodilation was significantly blunted in young adults still symptomatic from COVID-19 beyond the acute phase (>4 wk from diagnosis), whereas those who become asymptomatic have similar vascular function compared with controls who never had COVID-19. In contrast, cerebral vascular function and central arterial stiffness were unaffected irrespective of COVID-19 symptomology.

Transcranial Doppler in Acute COVID-19 Infection: Unexpected Associations.

BACKGROUND AND PURPOSE: Stroke may complicate coronavirus disease 2019 (COVID-19) infection based on clinical hypercoagulability. We investigated whether transcranial Doppler ultrasound has utility for identifying microemboli and clinically relevant cerebral blood flow velocities (CBFVs) in COVID-19. METHODS: We performed transcranial Doppler for a consecutive series of patients with confirmed or suspected COVID-19 infection admitted to 2 intensive care units at a large academic center including evaluation for microembolic signals. Variables specific to hypercoagulability and blood flow including transthoracic echocardiography were analyzed as a part of routine care. RESULTS: Twenty-six patients were included in this analysis, 16 with confirmed COVID-19 infection. Of those, 2 had acute ischemic stroke secondary to large vessel occlusion. Ten non-COVID stroke patients were included for comparison. Two COVID-negative patients had severe acute respiratory distress syndrome and stroke due to large vessel occlusion. In patients with COVID-19, relatively low CBFVs were observed diffusely at median hospital day 4 (interquartile range, 3-9) despite low hematocrit (29.5% [25.7%-31.6%]); CBFVs in comparable COVID-negative stroke patients were significantly higher compared with COVID-positive stroke patients. Microembolic signals were not detected in any patient. Median left ventricular ejection fraction was 60% (interquartile range, 60%-65%). CBFVs were correlated with arterial oxygen content, and C-reactive protein (Spearman ρ=0.28 [P=0.04]; 0.58 [P<0.001], respectively) but not with left ventricular ejection fraction (ρ=-0.18; P=0.42). CONCLUSIONS: In this cohort of critically ill patients with COVID-19 infection, we observed lower than expected CBFVs in setting of low arterial oxygen content and low hematocrit but not associated with suppression of cardiac output.

Value of renal resistive index in covid-19 ARDS patients: an early inflammation alert for the lung-kidney cross-talk?

We analysed RRI and other hemodynamic, re-spiratory and inflammation parameters in critically ill pa-tients affected by severe covid-19 with acute distress respi-ratory syndrome (ARDS) aiming at verifying their modifica-tions during supine and prone positioning and any mutual correlation or interplay with RRI.

Blood flow, capillary transit times, and tissue oxygenation: the centennial of capillary recruitment.

The transport of oxygen between blood and tissue is limited by blood's capillary transit time, understood as the time available for diffusion exchange before blood returns to the heart. If all capillaries contribute equally to tissue oxygenation at all times, this physical limitation would render vasodilation and increased blood flow insufficient means to meet increased metabolic demands in the heart, muscle, and other organs. In 1920, Danish physiologist August Krogh was awarded the Nobel Prize in Physiology or Medicine for his mathematical and quantitative, experimental demonstration of a solution to this conceptual problem: capillary recruitment, the active opening of previously closed capillaries to meet metabolic demands. Today, capillary recruitment is still mentioned in textbooks. When we suspect symptoms might represent hypoxia of a vascular origin, however, we search for relevant, flow-limiting conditions in our patients and rarely ascribe hypoxia or hypoxemia to short capillary transit times. This review describes how natural changes in capillary transit-time heterogeneity (CTH) and capillary hematocrit (HCT) across open capillaries during blood flow increases can account for a match of oxygen availability to metabolic demands in normal tissue. CTH and HCT depend on a number of factors: on blood properties, including plasma viscosity, the number, size, and deformability of blood cells, and blood cell interactions with capillary endothelium; on anatomical factors including glycocalyx, endothelial cells, basement membrane, and pericytes that affect the capillary diameter; and on any external compression. The review describes how risk factor- and disease-related changes in CTH and HCT interfere with flow-metabolism coupling and tissue oxygenation and discusses whether such capillary dysfunction contributes to vascular disease pathology.

Cerebral hemodynamic alterations in patients with Covid-19

Background/aim: Coronavirus 2019 disease (Covid-19) was first seen in December 2019 and afterwards it became pandemic. Several systemic involvements have been reported in Covid-19 patients. In this study, it was aimed to investigate the cerebrovascular hemodynamics in patients with Covid-19. Materials and methods: The sample of this study included 20 patients hospitalized in our clinic diagnosed with Covid-19 via PCR modality and 20 healthy volunteers of similar age and sex. Bilateral middle cerebral arteries were investigated with transcranial Doppler ultrasonography. Basal cerebral blood flow velocities and vasomotor reactivity rates were determined and statistically compared. Results: When patient and control groups were compared, the mean blood flow velocity was found to be higher in Covid-19 patients than in the healthy volunteers and it was statistically significant (P = 0.00). The mean vasomotor reactivity rates values were found to be lower in the Covid-19 group than the healthy group and was also statistically significant (P = 0.00). Conclusion: An increase in basal cerebral blood velocity and a decrease in vasomotor reactivity rates in patients with Covid-19 can be considered as an indicator of dysfunction of cerebral hemodynamics in the central nervous system and this can be evaluated as a result of endothelial dysfunction.

Powered Air Purifying Respirator (PAPR) restores the N95 face mask induced cerebral hemodynamic alterations among Healthcare Workers during COVID-19 Outbreak.

BACKGROUND AND AIM: COVID-19 pandemic has resulted in an unprecedented increased usage of Personal protective equipment (PPE) by healthcare-workers. PPE usage causes headache in majority of users. We evaluated changes in cerebral hemodynamics among healthcare-workers using PPE. METHODS: Frontline healthcare-workers donning PPE at our tertiary center were included. Demographics, co-morbidities and blood-pressure were recorded. Transcranial Doppler (TCD) monitoring of middle cerebral artery was performed with 2-MHz probe. Mean flow velocity (MFV) and pulsatility index (PI) were recorded at baseline, after donning N95 respirator-mask, and after donning powered air-purifying respirator (PAPR), when indicated. End-tidal carbon-dioxide (ET-CO2) pressure was recorded for participants donning PAPR in addition to the N95 respirator-mask. RESULTS: A total of 154 healthcare-workers (mean age 29 ± 12 years, 67% women) were included. Migraine was the commonest co-morbidity in 38 (25%) individuals while 123 (80%) developed de-novo headache due to N95 mask. Donning of N95 respirator-mask resulted in significant increase in MFV (4.4 ± 10.4 cm/s, p < 0.001) and decrease in PI (0.13 ± 0.12; p < 0.001) while ET-CO2 increased by 3.1 ± 1.2 mmHg (p < 0.001). TCD monitoring in 24 (16%) participants donning PAPR and N95 respirator mask together showed normalization of PI, accompanied by normalization of ET-CO2 values within 5-min. Combined use of N95 respirator-mask and PAPR was more comfortable as compared to N95 respirator-mask alone. CONCLUSION: Use of N95 respirator-mask results in significant alterations in cerebral hemodynamics. However, these effects are mitigated by the use of additional PAPR. We recommend the use of PAPR together with the N95 mask for healthcare-workers doing longer duties in the hospital wards.