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1.
Vopr Kurortol Fizioter Lech Fiz Kult ; 98(6. Vyp. 2): 75-84, 2021.
Article in Russian | MEDLINE | ID: covidwho-1599966

ABSTRACT

This review provides an analysis of the main mechanisms of the therapeutic and prophylactic effects of drinking mineral water concerning the rehabilitation of new coronavirus infection convalescents. When considering the sanogenetic potential of mineral water for drinking, it was noted that in the mechanisms of their systemic effects, a major role belongs to the nonspecific hormone-stimulating effect in the form of a pronounced activation of the gastroenteropancreatic endocrine system, capable of integrating substance and energy exchange following the current needs of the body and excrete vasoactive factors modulating the vital functional systems activity. The maximum effect of this system is promoted by the intake of mineral water with a high content of hydrocarbonate ions, magnesium, and sodium, as well as carbon dioxide saturation, but with general mineralization of water within the range from 5-6 to 11-13 g/L. The observed stimulating effect of mineral water on the adaptation processes allowed us to theoretically substantiate and convincingly prove the benefits of using this natural healing factor for the primary prevention of disorders in various functional systems and their hormonal regulation. The effects of drinking mineral water on various inflammatory states, resistance to hypoxia, microcirculatory tissue perfusion, and the state of the cardiovascular system were shown. It is concluded that the potential effectiveness of drinking mineral water as a part of comprehensive programs of medical rehabilitation of new coronavirus infection convalescents.


Subject(s)
COVID-19 , Drinking Water , Mineral Waters , Drinking Water/analysis , Humans , Microcirculation , SARS-CoV-2
2.
Crit Care ; 25(1): 381, 2021 11 08.
Article in English | MEDLINE | ID: covidwho-1506432

ABSTRACT

BACKGROUND: COVID-19 is primarily a respiratory disease; however, there is also evidence that it causes endothelial damage in the microvasculature of several organs. The aim of the present study is to characterize in vivo the microvascular reactivity in peripheral skeletal muscle of severe COVID-19 patients. METHODS: This is a prospective observational study carried out in Spain, Mexico and Brazil. Healthy subjects and severe COVID-19 patients admitted to the intermediate respiratory (IRCU) and intensive care units (ICU) due to hypoxemia were studied. Local tissue/blood oxygen saturation (StO2) and local hemoglobin concentration (THC) were non-invasively measured on the forearm by near-infrared spectroscopy (NIRS). A vascular occlusion test (VOT), a three-minute induced ischemia, was performed in order to obtain dynamic StO2 parameters: deoxygenation rate (DeO2), reoxygenation rate (ReO2), and hyperemic response (HAUC). In COVID-19 patients, the severity of ARDS was evaluated by the ratio between peripheral arterial oxygen saturation (SpO2) and the fraction of inspired oxygen (FiO2) (SF ratio). RESULTS: Healthy controls (32) and COVID-19 patients (73) were studied. Baseline StO2 and THC did not differ between the two groups. Dynamic VOT-derived parameters were significantly impaired in COVID-19 patients showing lower metabolic rate (DeO2) and diminished endothelial reactivity. At enrollment, most COVID-19 patients were receiving invasive mechanical ventilation (MV) (53%) or high-flow nasal cannula support (32%). Patients on MV were also receiving sedative agents (100%) and vasopressors (29%). Baseline StO2 and DeO2 negatively correlated with SF ratio, while ReO2 showed a positive correlation with SF ratio. There were significant differences in baseline StO2 and ReO2 among the different ARDS groups according to SF ratio, but not among different respiratory support therapies. CONCLUSION: Patients with severe COVID-19 show systemic microcirculatory alterations suggestive of endothelial dysfunction, and these alterations are associated with the severity of ARDS. Further evaluation is needed to determine whether these observations have prognostic implications. These results represent interim findings of the ongoing HEMOCOVID-19 trial. Trial registration ClinicalTrials.gov NCT04689477 . Retrospectively registered 30 December 2020.


Subject(s)
COVID-19/physiopathology , Intensive Care Units/trends , Microvessels/physiopathology , Respiratory Care Units/trends , Respiratory Distress Syndrome/physiopathology , Severity of Illness Index , Adult , Aged , Brazil/epidemiology , COVID-19/diagnosis , COVID-19/epidemiology , Female , Humans , Male , Mexico/epidemiology , Microcirculation/physiology , Middle Aged , Muscle, Skeletal/blood supply , Muscle, Skeletal/physiopathology , Prospective Studies , Respiratory Distress Syndrome/diagnosis , Respiratory Distress Syndrome/epidemiology , Spain/epidemiology
3.
Proc Natl Acad Sci U S A ; 118(41)2021 10 12.
Article in English | MEDLINE | ID: covidwho-1486398

ABSTRACT

The COVID-19 pandemic led to widespread mandates requiring the wearing of face masks, which led to debates on their benefits and possible adverse effects. To that end, the physiological effects at the systemic and at the brain level are of interest. We have investigated the effect of commonly available face masks (FFP2 and surgical) on cerebral hemodynamics and oxygenation, particularly microvascular cerebral blood flow (CBF) and blood/tissue oxygen saturation (StO2), measured by transcranial hybrid near-infrared spectroscopies and on systemic physiology in 13 healthy adults (ages: 23 to 33 y). The results indicate small but significant changes in cerebral hemodynamics while wearing a mask. However, these changes are comparable to those of daily life activities. This platform and the protocol provides the basis for large or targeted studies of the effects of mask wearing in different populations and while performing critical tasks.


Subject(s)
Brain/physiology , Masks , Activities of Daily Living , Adult , Brain/blood supply , Brain/metabolism , COVID-19/prevention & control , Female , Healthy Volunteers , Hemodynamics , Humans , Male , Microcirculation , Monitoring, Physiologic , Oxygen/metabolism , SARS-CoV-2 , Spectroscopy, Near-Infrared , Young Adult
4.
Br J Community Nurs ; 26(10): 474-480, 2021 Oct 02.
Article in English | MEDLINE | ID: covidwho-1464047

ABSTRACT

Despite its many devastating effects, the COVID-19 pandemic has had a positive impact in the ways in which society, scientific institutions, governing bodies, businesses, educational organisations, and communication have functioned unchallenged over the years. Rapid advancement in science enabled identification and characterisation of the virus and in developing vaccines to combat the disease. The mysterious ways in which the virus attacks the vital organs that lead on to multiorgan failure and thrombosis of the arterial and venous system have also been revealed. The ability to study the microcirculatory changes at the bedside and predict prognosis is a way forward. All the evidence suggests that the outcome of COVID-19 infection is related to the severity of the disease seen in the intensive care unit setting. This article discusses microcirculatory changes and immune coagulopathy caused by COVID-19.


Subject(s)
COVID-19 , Microcirculation , Thrombosis , COVID-19/complications , COVID-19/nursing , Humans , Thrombosis/virology
5.
Proc Natl Acad Sci U S A ; 118(41)2021 10 12.
Article in English | MEDLINE | ID: covidwho-1450314

ABSTRACT

The COVID-19 pandemic led to widespread mandates requiring the wearing of face masks, which led to debates on their benefits and possible adverse effects. To that end, the physiological effects at the systemic and at the brain level are of interest. We have investigated the effect of commonly available face masks (FFP2 and surgical) on cerebral hemodynamics and oxygenation, particularly microvascular cerebral blood flow (CBF) and blood/tissue oxygen saturation (StO2), measured by transcranial hybrid near-infrared spectroscopies and on systemic physiology in 13 healthy adults (ages: 23 to 33 y). The results indicate small but significant changes in cerebral hemodynamics while wearing a mask. However, these changes are comparable to those of daily life activities. This platform and the protocol provides the basis for large or targeted studies of the effects of mask wearing in different populations and while performing critical tasks.


Subject(s)
Brain/physiology , Masks , Activities of Daily Living , Adult , Brain/blood supply , Brain/metabolism , COVID-19/prevention & control , Female , Healthy Volunteers , Hemodynamics , Humans , Male , Microcirculation , Monitoring, Physiologic , Oxygen/metabolism , SARS-CoV-2 , Spectroscopy, Near-Infrared , Young Adult
6.
Bull Exp Biol Med ; 171(4): 453-457, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1427311

ABSTRACT

Microcirculatory hemodynamic indexes (HI) were assessed in patients with moderate and severe COVID-19. In both groups, a significant increase in the absolute spectral indexes (HI1, HI2, and HI3) and the ratio of low-frequency to high-frequency component (HI1/HI3) was revealed. In the group of severe infection, only the "slow" index (low-frequency HI1) of microcirculatory hemodynamics was significantly lower. The oscillatory indices MAYER1-3 and RESP1-3 were reduced in patients of both groups. The aggravation of the disease course was accompanied by depression of the low-frequency index HI1. Regulatory shifts compensate for disturbances in microcirculatory processes in moderate COVID-19, but severe course was associated with their decompensation.


Subject(s)
COVID-19/physiopathology , Microcirculation/physiology , Hemodynamics/physiology , Humans
7.
Crit Care ; 25(1): 217, 2021 06 24.
Article in English | MEDLINE | ID: covidwho-1388810

ABSTRACT

BACKGROUND: The viral load of asymptomatic SAR-COV-2 positive (ASAP) persons has been equal to that of symptomatic patients. On the other hand, there are no reports of ST-elevation myocardial infarction (STEMI) outcomes in ASAP patients. Therefore, we evaluated thrombus burden and thrombus viral load and their impact on microvascular bed perfusion in the infarct area (myocardial blush grade, MBG) in ASAP compared to SARS-COV-2 negative (SANE) STEMI patients. METHODS: This was an observational study of 46 ASAP, and 130 SANE patients admitted with confirmed STEMI treated with primary percutaneous coronary intervention and thrombus aspiration. The primary endpoints were thrombus dimension + thrombus viral load effects on MBG after PPCI. The secondary endpoints during hospitalization were major adverse cardiovascular events (MACEs). MACEs are defined as a composite of cardiovascular death, nonfatal acute AMI, and heart failure during hospitalization. RESULTS: In the study population, ASAP vs. SANE showed a significant greater use of GP IIb/IIIa inhibitors and of heparin (p < 0.05), and a higher thrombus grade 5 and thrombus dimensions (p < 0.05). Interestingly, ASAP vs. SANE patients had lower MBG and left ventricular function (p < 0.001), and 39 (84.9%) of ASAP patients had thrombus specimens positive for SARS-COV-2. After PPCI, a MBG 2-3 was present in only 26.1% of ASAP vs. 97.7% of SANE STEMI patients (p < 0.001). Notably, death and nonfatal AMI were higher in ASAP vs. SANE patients (p < 0.05). Finally, in ASAP STEMI patients the thrombus viral load was a significant determinant of thrombus dimension independently of risk factors (p < 0.005). Thus, multiple logistic regression analyses evidenced that thrombus SARS-CoV-2 infection and dimension were significant predictors of poorer MBG in STEMI patients. Intriguingly, in ASAP patients the female vs. male had higher thrombus viral load (15.53 ± 4.5 vs. 30.25 ± 5.51 CT; p < 0.001), and thrombus dimension (4.62 ± 0.44 vs 4.00 ± 1.28 mm2; p < 0.001). ASAP vs. SANE patients had a significantly lower in-hospital survival for MACE following PPCI (p < 0.001). CONCLUSIONS: In ASAP patients presenting with STEMI, there is strong evidence towards higher thrombus viral load, dimension, and poorer MBG. These data support the need to reconsider ASAP status as a risk factor that may worsen STEMI outcomes.


Subject(s)
COVID-19/complications , Coronary Thrombosis/virology , Heart/physiopathology , Microcirculation/physiology , Myocardial Infarction/physiopathology , Aged , Analysis of Variance , Asymptomatic Infections/epidemiology , COVID-19/epidemiology , Cohort Studies , Coronary Angiography/methods , Coronary Thrombosis/epidemiology , Echocardiography/methods , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Myocardial Infarction/epidemiology
8.
Sci Rep ; 11(1): 15667, 2021 08 02.
Article in English | MEDLINE | ID: covidwho-1338552

ABSTRACT

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and is primarily characterised by a respiratory disease. However, SARS-CoV-2 can directly infect vascular endothelium and subsequently cause vascular inflammation, atherosclerotic plaque instability and thereby result in both endothelial dysfunction and myocardial inflammation/infarction. Interestingly, up to 50% of patients suffer from persistent exercise dyspnoea and a post-viral fatigue syndrome (PVFS) after having overcome an acute COVID-19 infection. In the present study, we assessed the presence of coronary microvascular disease (CMD) by cardiovascular magnetic resonance (CMR) in post-COVID-19 patients still suffering from exercise dyspnoea and PVFS. N = 22 patients who recently recovered from COVID-19, N = 16 patients with classic hypertrophic cardiomyopathy (HCM) and N = 17 healthy control patients without relevant cardiac disease underwent dedicated vasodilator-stress CMR studies on a 1.5-T MR scanner. The CMR protocol comprised cine and late-gadolinium-enhancement (LGE) imaging as well as velocity-encoded (VENC) phase-contrast imaging of the coronary sinus flow (CSF) at rest and during pharmacological stress (maximal vasodilation induced by 400 µg IV regadenoson). Using CSF measurements at rest and during stress, global myocardial perfusion reserve (MPR) was calculated. There was no difference in left ventricular ejection-fraction (LV-EF) between COVID-19 patients and controls (60% [57-63%] vs. 63% [60-66%], p = NS). There were only N = 4 COVID-19 patients (18%) showing a non-ischemic pattern of LGE. VENC-based flow measurements showed that CSF at rest was higher in COVID-19 patients compared to controls (1.78 ml/min [1.19-2.23 ml/min] vs. 1.14 ml/min [0.91-1.32 ml/min], p = 0.048). In contrast, CSF during stress was lower in COVID-19 patients compared to controls (3.33 ml/min [2.76-4.20 ml/min] vs. 5.32 ml/min [3.66-5.52 ml/min], p = 0.05). A significantly reduced MPR was calculated in COVID-19 patients compared to healthy controls (2.73 [2.10-4.15-11] vs. 4.82 [3.70-6.68], p = 0.005). No significant differences regarding MPR were detected between COVID-19 patients and HCM patients. In post-COVID-19 patients with persistent exertional dyspnoea and PVFS, a significantly reduced MPR suggestive of CMD-similar to HCM patients-was observed in the present study. A reduction in MPR can be caused by preceding SARS-CoV-2-associated direct as well as secondary triggered mechanisms leading to diffuse CMD, and may explain ongoing symptoms of exercise dyspnoea and PVFS in some patients after COVID-19 infection.


Subject(s)
COVID-19 , Cardiomyopathy, Hypertrophic , Coronary Circulation , Coronary Vessels , Magnetic Resonance Angiography , Microcirculation , Myocardial Infarction , Myocardial Perfusion Imaging , SARS-CoV-2 , Adult , Aged , COVID-19/complications , COVID-19/diagnostic imaging , COVID-19/physiopathology , Cardiomyopathy, Hypertrophic/diagnostic imaging , Cardiomyopathy, Hypertrophic/etiology , Coronary Vessels/diagnostic imaging , Coronary Vessels/physiology , Female , Humans , Male , Middle Aged , Myocardial Infarction/diagnostic imaging , Myocardial Infarction/etiology , Myocardial Infarction/physiopathology , Pilot Projects
9.
Biomolecules ; 11(7)2021 07 20.
Article in English | MEDLINE | ID: covidwho-1323104

ABSTRACT

We report the case of a 77-year-old woman affected by coronavirus disease-19 (COVID-19) who developed an occlusive arterial disease of the lower limb requiring a left leg amputation. We studied the mechanisms of vascular damage by SARS-CoV-2 by means of a comprehensive multi-technique in situ analysis on the diseased popliteal arterial district, including immunohistochemistry (IHC), transmission electron microscopy (TEM) and miRNA analysis. At histological analyses, we observed a lymphocytic inflammatory infiltrate, oedema and endothelialitis of adventitial vasa vasorum while the media was normal and the intima had only minor changes. The vasa vasorum expressed the ACE2 receptor and factor VIII; compared with the controls, VEGFR2 staining was reduced. TEM analyses showed endothelial injury and numerous Weibel-Palade bodies in the cytoplasm. No coronavirus particle was seen. IL-6 protein and mRNA, together with miR-155-5p and miRs-27a-5p, which can target IL-6, were significantly increased compared with that in the controls. Our case report suggests an involvement of adventitial artery microcirculation by inflammation in the course of COVID-19. Without evident signs of current infection by SARS-CoV-2, endothelial cells show a spectrum of structural and functional alterations that can fuel the cardiovascular complications observed in people infected with SARS-CoV-2.


Subject(s)
Arterial Occlusive Diseases/etiology , COVID-19/complications , Inflammation/etiology , Aged , Arterial Occlusive Diseases/pathology , COVID-19/pathology , Female , Humans , Inflammation/pathology , Leg/blood supply , Leg/pathology , MicroRNAs/analysis , Microcirculation , SARS-CoV-2/isolation & purification
10.
Microvasc Res ; 138: 104196, 2021 11.
Article in English | MEDLINE | ID: covidwho-1258467

ABSTRACT

OBJECTIVES: The hyperinflammatory state and the viral invasion may result in endothelial dysfunction in SARS-CoV-2 infection. Although a method foreseeing microvascular dysfunction has not been defined yet, studies conducted in patients diagnosed with COVID-19 have demonstrated the presence of endotheliitis. With this study, we aimed to investigate the microvascular circulation in patients diagnosed with COVID-19 and multisystem inflammatory syndrome in children (MIS-C) by nailfold videocapillaroscopy (NVC). METHODS: Thirty-one patients with SARS-CoV-2 infection, 25 of whom were diagnosed with COVID-19 and 6 with MIS-C and 58 healthy peers were included in the study. NVC was performed in eight fingers with 2 images per finger and 16 images were examined for the morphology of capillaries, presence of pericapillary edema, microhemorrhage, avascular area, and neoangiogenesis. Capillary length, capillary width, apical loop, arterial and venous width, and intercapillary distance were measured from three consecutive capillaries from the ring finger of the non-dominant hand. RESULTS: COVID-19 patients showed significantly more capillary ramification (p < 0.001), capillary meandering (p = 0.04), microhemorrhage (p < 0.001), neoangiogenesis (p < 0.001), capillary tortuosity (p = 0.003). Capillary density (p = 0.002) and capillary length (p = 0.002) were significantly lower in the patient group while intercapillary distance (p = 0.01) was significantly longer compared with healthy volunteers. Morphologically, patients with MIS-C had a higher frequency of capillary ramification and neoangiogenesis compared with COVID-19 patients (p = 0.04). CONCLUSION: Abnormal capillary alterations seen in COVID-19 and MIS-C patients indicate both similar and different aspects of these two spectra of SARS-CoV-2 infection and NVC appears to be a simple and non-invasive method for evaluation of microvascular involvement.


Subject(s)
COVID-19/pathology , Capillaries/pathology , Microscopic Angioscopy , Nails/blood supply , Systemic Inflammatory Response Syndrome/pathology , Adolescent , Age Factors , Biomarkers/blood , C-Reactive Protein/analysis , COVID-19/physiopathology , COVID-19/virology , Capillaries/physiopathology , Case-Control Studies , Child , Child, Preschool , Female , Fibrin Fibrinogen Degradation Products/analysis , Humans , Male , Microcirculation , Predictive Value of Tests , Regional Blood Flow , Systemic Inflammatory Response Syndrome/physiopathology , Systemic Inflammatory Response Syndrome/virology
11.
Am J Chin Med ; 48(6): 1315-1330, 2020.
Article in English | MEDLINE | ID: covidwho-1243726

ABSTRACT

Critical care medicine is a medical specialty engaging the diagnosis and treatment of critically ill patients who have or are likely to have life-threatening organ failure. Sepsis, a life-threatening condition that arises when the body responds to infection, is currently the major cause of death in intensive care units (ICU). Although progress has been made in understanding the pathophysiology of sepsis, many drawbacks in sepsis treatment remains unresolved. For example, antimicrobial resistance, controversial of glucocorticoids use, prolonged duration of ICU care and the subsequent high cost of the treatment. Recent years have witnessed a growing trend of applying traditional Chinese medicine (TCM) in sepsis management. The TCM application emphasizes use of herbal formulation to balance immune responses to infection, which include clearing heat and toxin, promoting blood circulation and removing its stasis, enhancing gastrointestinal function, and strengthening body resistance. In this paper, we will provide an overview of the current status of Chinese herbal formulations, single herbs, and isolated compounds, as an add-on therapy to the standard Western treatment in the sepsis management. With the current trajectory of worldwide pandemic eruption of newly identified Coronavirus Disease-2019 (COVID-19), the adjuvant TCM therapy can be used in the ICU to treat critically ill patients infected with the novel coronavirus.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Coronavirus Infections/drug therapy , Drugs, Chinese Herbal/therapeutic use , Immunologic Factors/therapeutic use , Medicine, Chinese Traditional , Pneumonia, Viral/drug therapy , Sepsis/drug therapy , Artemisinins/therapeutic use , Astragalus propinquus , Berberine/therapeutic use , Betacoronavirus , COVID-19 , Critical Illness , Emodin/therapeutic use , Humans , Intensive Care Units , Intestinal Mucosa , Microcirculation , Pandemics , Permeability , Rheum , SARS-CoV-2 , Salvia miltiorrhiza
12.
Respir Care ; 66(9): 1406-1415, 2021 09.
Article in English | MEDLINE | ID: covidwho-1244287

ABSTRACT

BACKGROUND: ARDS in patients with coronavirus disease 2019 (COVID-19) is characterized by microcirculatory alterations in the pulmonary vascular bed, which could increase dead-space ventilation more than in non-COVID-19 ARDS. We aimed to establish if dead-space ventilation is different in patients with COVID-19 ARDS when compared with patients with non-COVID-19 ARDS. METHODS: A total of 187 subjects with COVID-19 ARDS and 178 subjects with non-COVID-19 ARDS who were undergoing invasive mechanical ventilation were included in the study. The association between the ARDS types and dead-space ventilation, compliance of the respiratory system, subjects' characteristics, organ failures, and mechanical ventilation was evaluated by using data collected in the first 24 h of mechanical ventilation. RESULTS: Corrected minute ventilation (V˙E), a dead-space ventilation surrogate, was higher in the subjects with COVID-19 ARDS versus in those with non-COVID-19 ARDS (median [interquartile range] 12.6 [10.2-15.8] L/min vs 9.4 [7.5-11.6] L/min; P < .001). Increased corrected V˙E was independently associated with COVID-19 ARDS (odds ratio 1.24, 95% CI 1.07-1.47; P = .007). The best compliance of the respiratory system, obtained after testing different PEEPs, was similar between the subjects with COVID-19 ARDS and the subjects with non-COVID-19 ARDS (mean ± SD 38 ± 11 mL/cm H2O vs 37 ± 11 mL/cm H2O, respectively; P = .61). The subjects with COVID-19 ARDS received higher median (interquartile range) PEEP (12 [10-14] cm H2O vs 8 [5-9] cm H2O; P < .001) and lower median (interquartile range) tidal volume (5.8 [5.5-6.3] mL/kg vs 6.6 [6.1-7.3] mL/kg; P < .001) than the subjects with non-COVID-19 ARDS, being these differences maintained at multivariable analysis. In the multivariable analysis, the subjects with COVID-19 ARDS showed a lower risk of anamnestic arterial hypertension (odds ratio 0.18, 95% CI 0.07-0.45; P < .001) and lower neurologic sequential organ failure assessment score (odds ratio 0.16, 95% CI 0.09-0.27; P < .001) than the subjects with non-COVID-19 ARDS. CONCLUSIONS: Indirect measurements of dead space were higher in subjects with COVID-19 ARDS compared with subjects with non-COVID-19 ARDS. The best compliance of the respiratory system was similar in both ARDS forms provided that different PEEPs were applied. A wide range of compliance is present in every ARDS type; therefore, the setting of mechanical ventilation should be individualized patient by patient and not based on the etiology of ARDS.


Subject(s)
COVID-19 , Respiratory Distress Syndrome , Humans , Microcirculation , Respiratory Distress Syndrome/therapy , SARS-CoV-2 , Tidal Volume
13.
Crit Care Med ; 49(4): 661-670, 2021 04 01.
Article in English | MEDLINE | ID: covidwho-1238251

ABSTRACT

OBJECTIVES: In this study, we hypothesized that coronavirus disease 2019 patients exhibit sublingual microcirculatory alterations caused by inflammation, coagulopathy, and hypoxemia. DESIGN: Multicenter case-controlled study. SETTING: Two ICUs in The Netherlands and one in Switzerland. PATIENTS: Thirty-four critically ill coronavirus disease 2019 patients were compared with 33 healthy volunteers. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The microcirculatory parameters quantified included total vessel density (mm × mm-2), functional capillary density (mm × mm-2), proportion of perfused vessels (%), capillary hematocrit (%), the ratio of capillary hematocrit to systemic hematocrit, and capillary RBC velocity (µm × s-1). The number of leukocytes in capillary-postcapillary venule units per 4-second image sequence (4 s-1) and capillary RBC microaggregates (4 s-1) was measured. In comparison with healthy volunteers, the microcirculation of coronavirus disease 2019 patients showed increases in total vessel density (22.8 ± sd 5.1 vs 19.9 ± 3.3; p < 0.0001) and functional capillary density (22.2 ± 4.8 vs 18.8 ± 3.1; p < 0.002), proportion of perfused vessel (97.6 ± 2.1 vs 94.6 ± 6.5; p < 0.01), RBC velocity (362 ± 48 vs 306 ± 53; p < 0.0001), capillary hematocrit (5.3 ± 1.3 vs 4.7 ± 0.8; p < 0.01), and capillary-hematocrit-to-systemic-hematocrit ratio (0.18 ± 0.0 vs 0.11 ± 0.0; p < 0.0001). These effects were present in coronavirus disease 2019 patients with Sequential Organ Failure Assessment scores less than 10 but not in patients with Sequential Organ Failure Assessment scores greater than or equal to 10. The numbers of leukocytes (17.6 ± 6.7 vs 5.2 ± 2.3; p < 0.0001) and RBC microaggregates (0.90 ± 1.12 vs 0.06 ± 0.24; p < 0.0001) was higher in the microcirculation of the coronavirus disease 2019 patients. Receiver-operating-characteristics analysis of the microcirculatory parameters identified the number of microcirculatory leukocytes and the capillary-hematocrit-to-systemic-hematocrit ratio as the most sensitive parameters distinguishing coronavirus disease 2019 patients from healthy volunteers. CONCLUSIONS: The response of the microcirculation to coronavirus disease 2019-induced hypoxemia seems to be to increase its oxygen-extraction capacity by increasing RBC availability. Inflammation and hypercoagulation are apparent in the microcirculation by increased numbers of leukocytes and RBC microaggregates.


Subject(s)
COVID-19/mortality , Capillaries , Hypoxia/etiology , Leukocytes , Microcirculation/physiology , Erythrocytes , Female , Humans , Male , Middle Aged
14.
Microcirculation ; 28(7): e12718, 2021 10.
Article in English | MEDLINE | ID: covidwho-1236400

ABSTRACT

Recently, accumulating evidence has highlighted the role of endothelial dysfunction in COVID-19 progression. Coronary microvascular dysfunction (CMD) plays a pivotal role in cardiovascular disease (CVD) and CVD-related risk factors (eg, age, gender, hypertension, diabetes mellitus, and obesity). Equally, these are also risk factors for COVID-19. The purpose of this review was to explore CMD pathophysiology in COVID-19, based on recent evidence. COVID-19 mechanisms were reviewed in terms of imbalanced renin-angiotensin-aldosterone-systems (RAAS), systemic inflammation and immune responses, endothelial dysfunction, and coagulatory disorders. Based on these mechanisms, we addressed CMD pathophysiology within the context of COVID-19, from five perspectives. The first was the disarrangement of local RAAS and Kallikrein-kinin-systems attributable to SARS-Cov-2 entry, and the concomitant decrease in coronary microvascular endothelial angiotensin I converting enzyme 2 (ACE2) levels. The second was related to coronary microvascular obstruction, induced by COVID-19-associated systemic hyper-inflammation and pro-thrombotic state. The third was focused on how pneumonia/acute respiratory distress syndrome (ARDS)-related systemic hypoxia elicited oxidative stress in coronary microvessels and cardiac sympathetic nerve activation. Fourthly, we discussed how autonomic nerve dysfunction mediated by COVID-19-associated mental, physical, or physiological factors could elicit changes in coronary blood flow, resulting in CMD in COVID-19 patients. Finally, we analyzed reciprocity between the coronary microvascular endothelium and perivascular cellular structures due to viremia, SARS-CoV-2 dissemination, and systemic inflammation. These mechanisms may function either consecutively or intermittently, finally culminating in CMD-mediated cardiovascular symptoms in COVID-19 patients. However, the underlying molecular pathogenesis remains to be clarified.


Subject(s)
COVID-19/physiopathology , Coronary Vessels/physiopathology , SARS-CoV-2 , COVID-19/complications , COVID-19/immunology , Cardiovascular Diseases/etiology , Cardiovascular Diseases/physiopathology , Disease Progression , Endothelium, Vascular/physiopathology , Female , Humans , Inflammation/physiopathology , Male , Microcirculation/physiology , Models, Cardiovascular , Renin-Angiotensin System/physiology , Risk Factors , Thrombosis/etiology , Thrombosis/physiopathology
15.
Am J Pathol ; 191(7): 1154-1164, 2021 07.
Article in English | MEDLINE | ID: covidwho-1219865

ABSTRACT

Severe acute respiratory syndrome coronavirus 2, the etiologic agent of coronavirus disease 2019 (COVID-19) and the cause of the current pandemic, produces multiform manifestations throughout the body, causing indiscriminate damage to multiple organ systems, particularly the lungs, heart, brain, kidney, and vasculature. The aim of this review is to provide a new assessment of the data already available for COVID-19, exploring it as a transient molecular disease that causes negative regulation of angiotensin-converting enzyme 2, and consequently, deregulates the renin-angiotensin-aldosterone system, promoting important changes in the microcirculatory environment. Another goal of the article is to show how these microcirculatory changes may be responsible for the wide variety of injury mechanisms observed in different organs in this disease. The new concept of COVID-19 provides a unifying pathophysiological picture of this infection and offers fresh insights for a rational treatment strategy to combat this ongoing pandemic.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , COVID-19/metabolism , Down-Regulation , Microcirculation/physiology , Renin-Angiotensin System/physiology , Angiotensin-Converting Enzyme 2/genetics , COVID-19/genetics , COVID-19/pathology , Humans
16.
Shock ; 56(6): 964-968, 2021 12 01.
Article in English | MEDLINE | ID: covidwho-1220083

ABSTRACT

BACKGROUND: Endothelial and microvascular dysfunction may be a key pathogenic feature of severe COVID-19. The aim of this study was to investigate endothelial-dependent and endothelial-independent skin microvascular reactivity in patients with critical COVID-19. METHODS: Twelve patients with COVID-19 treated with non-invasive or invasive mechanical ventilation were included in the study. We investigated skin microvascular reactivity on 2 separate days during hospitalization (study day 1 and 2) and at least 3 months after disease onset (study day 3). Twelve controls with no confirmed or suspected COVID-19 infection during 2020 were also examined. Skin perfusion was investigated through Laser Speckle Contrast Imaging before and after iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP) to determine the endothelial-dependent and the endothelial-independent vasodilation, respectively. RESULTS: Compared to controls, patients with critical COVID-19 had higher basal skin perfusion and reduced responses to endothelial-dependent (ACh, P = 0.002) and endothelial-independent (SNP, P = 0.01) vasodilator drugs on study day 1. In addition, the ACh/SNP ratio was significantly reduced in patients (0.50 ±â€Š0.36 vs. 0.91 ±â€Š0.49 in controls, P = 0.02). Three months after disease onset, surviving patients tended to have reduced ACh-mediated vasodilation compared to controls (P = 0.08). CONCLUSIONS: This small-sized pilot study demonstrates that critical COVID-19 infection is associated with microvascular impairment and, in particular, a markedly reduced endothelial function. Our results also suggest that microvascular function may not be fully recovered 3 months after disease onset.


Subject(s)
COVID-19/epidemiology , Critical Illness/epidemiology , Endothelium, Vascular/physiopathology , Microcirculation/physiology , Regional Blood Flow/physiology , Vasodilation/physiology , Aged , COVID-19/physiopathology , Comorbidity , Female , Follow-Up Studies , Humans , Male , Microvessels/physiopathology , Middle Aged , Pilot Projects , Prospective Studies , SARS-CoV-2
17.
Medicina (Kaunas) ; 57(5)2021 Apr 26.
Article in English | MEDLINE | ID: covidwho-1201863

ABSTRACT

Sepsis remains the leading cause of mortality in hospitalized patients, contributing to 1 in every 2-3 deaths. From a pathophysiological view, in the recent definition, sepsis has been defined as the result of a complex interaction between host response and the infecting organism, resulting in life-threatening organ dysfunction, depending on microcirculatory derangement, cellular hypoxia/dysoxia driven by hypotension and, potentially, death. The high energy expenditure driven by a high metabolic state induced by the host response may rapidly lead to micronutrient depletion. This deficiency can result in alterations in normal energy homeostasis, free radical damage, and immune system derangement. In critically ill patients, micronutrients are still relegated to an ancillary role in the whole treatment, and always put in a second-line place or, frequently, neglected. Only some micronutrients have attracted the attention of a wider audience, and some trials, even large ones, have tested their use, with controversial results. The present review will address this topic, including the recent advancement in the study of vitamin D and protocols based on vitamin C and other micronutrients, to explore an update in the setting of sepsis, gain some new insights applicable to COVID-19 patients, and to contribute to a pathophysiological definition of the potential role of micronutrients that will be helpful in future dedicated trials.


Subject(s)
COVID-19 , Sepsis , Humans , Microcirculation , Micronutrients , SARS-CoV-2
18.
J Appl Physiol (1985) ; 129(6): 1413-1421, 2020 12 01.
Article in English | MEDLINE | ID: covidwho-1064196

ABSTRACT

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.


Subject(s)
Capillaries/physiology , Microcirculation , Models, Cardiovascular , Oxygen Consumption , Oxygen/blood , Alzheimer Disease/blood , Alzheimer Disease/physiopathology , Anemia, Sickle Cell/blood , Anemia, Sickle Cell/physiopathology , Animals , Blood Flow Velocity , Cardiovascular Diseases/blood , Cardiovascular Diseases/physiopathology , Diffusion , Humans , Hypoxia/blood , Hypoxia/physiopathology , Regional Blood Flow , Time Factors
20.
Pediatr Infect Dis J ; 40(3): e113-e115, 2021 03 01.
Article in English | MEDLINE | ID: covidwho-1075648

ABSTRACT

Multisystem inflammatory syndrome in children (MIS-C) is an emerging entity during the coronavirus disease 2019 pandemic. Medium- and large-vessel changes are present in MIS-C; however, microcirculatory impairment has not been documented. We report a case of MIS-C in a toddler that presented with persistent fever, gastrointestinal symptoms and rash. Nailfold videocapillaroscopy was abnormal, suggesting microcirculatory disease in the setting of MIS-C.


Subject(s)
COVID-19/diagnosis , Gastrointestinal Diseases/diagnosis , SARS-CoV-2/isolation & purification , Systemic Inflammatory Response Syndrome/diagnosis , COVID-19/physiopathology , COVID-19/virology , Exanthema , Fever , Gastrointestinal Diseases/physiopathology , Gastrointestinal Diseases/virology , Humans , Infant , Male , Mexico , Microcirculation , Microscopic Angioscopy , Systemic Inflammatory Response Syndrome/physiopathology , Systemic Inflammatory Response Syndrome/virology
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