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1.
Biophys J ; 120(14): 2838-2847, 2021 07 20.
Article in English | MEDLINE | ID: covidwho-1605922

ABSTRACT

Clinical syndrome coronavirus disease 2019 (COVID-19) induced by severe acute respiratory syndrome coronavirus 2 is characterized by rapid spreading and high mortality worldwide. Although the pathology is not yet fully understood, hyperinflammatory response and coagulation disorders leading to congestions of microvessels are considered to be key drivers of the still-increasing death toll. Until now, physical changes of blood cells have not been considered to play a role in COVID-19 related vascular occlusion and organ damage. Here, we report an evaluation of multiple physical parameters including the mechanical features of five frequent blood cell types, namely erythrocytes, lymphocytes, monocytes, neutrophils, and eosinophils. More than four million blood cells of 17 COVID-19 patients at different levels of severity, 24 volunteers free from infectious or inflammatory diseases, and 14 recovered COVID-19 patients were analyzed. We found significant changes in lymphocyte stiffness, monocyte size, neutrophil size and deformability, and heterogeneity of erythrocyte deformation and size. Although some of these changes recovered to normal values after hospitalization, others persisted for months after hospital discharge, evidencing the long-term imprint of COVID-19 on the body.


Subject(s)
COVID-19 , Hospitalization , Humans , Neutrophils , Phenotype , SARS-CoV-2
2.
Front Med (Lausanne) ; 8: 754667, 2021.
Article in English | MEDLINE | ID: covidwho-1555518

ABSTRACT

Clinical features of Coronavirus disease 2019 (COVID-19) are caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Acute infection management is a substantial healthcare issue, and the development of long-Covid syndrome (LCS) is extremely challenging for patients and physicians. It is associated with a variety of characteristics as impaired capillary microcirculation, chronic fatigue syndrome (CFS), proinflammatory cytokines, and functional autoantibodies targeting G-protein-coupled receptors (GPCR-AAbs). Here, we present a case report of successful healing of LCS with BC 007 (Berlin Cures, Berlin, Germany), a DNA aptamer drug with a high affinity to GPCR-AAbs that neutralizes these AAbs. A patient with a documented history of glaucoma, recovered from mild COVID-19, but still suffered from CFS, loss of taste, and impaired capillary microcirculation in the macula and peripapillary region. He was positively tested for various targeting GPCR-AAbs. Within 48 h after a single BC 007 treatment, GPCR-AAbs were functionally inactivated and remained inactive during the observation period of 4 weeks. This observation was accompanied by constant improvement of the fatigue symptoms of the patient, taste, and retinal capillary microcirculation. Therefore, the removal of GPCR-AAb might ameliorate the characteristics of the LCD, such as capillary impairment, loss of taste, and CFS.

3.
Front Med (Lausanne) ; 8: 676554, 2021.
Article in English | MEDLINE | ID: covidwho-1325537

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), affects the pulmonary systems via angiotensin-converting enzyme-2 (ACE-2) receptor, being an entry to systemic infection. As COVID-19 disease features ACE-2 deficiency, a link to microcirculation is proposed. Optical coherence tomography angiography (OCT-A) enables non-invasive analysis of retinal microvasculature. Thus, an impaired systemic microcirculation might be mapped on retinal capillary system. As recent OCT-A studies, analyzing microcirculation in two subdivided layers, yielded contrary results, an increased subdivision of retinal microvasculature might offer an even more fine analysis. The aim of the study was to investigate retinal microcirculation by OCT-A after COVID-19 infection in three subdivided layers (I). In addition, short-term retinal affections were monitored during COVID-19 disease (II). Considering (I), a prospective study (33 patientspost-COVID and 28 controls) was done. Macula and peripapillary vessel density (VD) were scanned with the Spectralis II. Macula VD was measured in three layers: superficial vascular plexus (SVP), intermediate capillary plexus (ICP), and deep capillary plexus (DCP). Analysis was done by the EA-Tool, including an Anatomical Positioning System and an analysis of peripapillary VD by implementing Bruch's membrane opening (BMO) landmarks. Overall, circular (c1, c2, and c3) and sectorial VD (s1-s12) was analyzed. Considering (II), in a retrospective study, 29 patients with severe complications of COVID-19 infection, hospitalized at the intensive care unit, were monitored for retinal findings at bedside during hospitalization. (I) Overall (p = 0.0133) and circular (c1, p = 0.00257; c2, p = 0.0067; and c3, p = 0.0345). VD of the ICP was significantly reduced between patientspost-COVID and controls, respectively. Overall (p = 0.0179) and circular (c1, p = 0.0189) peripapillary VD was significantly reduced between both groups. Subgroup analysis of hospitalized vs. non-hospitalized patientspost-COVID yielded a significantly reduced VD of adjacent layers (DCP and SVP) with increased severity of COVID-19 disease. Clinical severity parameters showed a negative correlation with VD (ICP) and peripapillary VD. (II) Funduscopy yielded retinal hemorrhages and cotton wool spots in 17% of patients during SARS-CoV-2 infection. As VD of the ICP and peripapillary regions was significantly reduced after COVID-19 disease and showed a link to clinical severity markers, we assume that the severity of capillary impairment after COVID-19 infection is mapped on retinal microcirculation, visualized by non-invasive OCT-A.

4.
Cell Death Differ ; 28(11): 3125-3139, 2021 11.
Article in English | MEDLINE | ID: covidwho-1241944

ABSTRACT

SARS-CoV-2 infection poses a major threat to the lungs and multiple other organs, occasionally causing death. Until effective vaccines are developed to curb the pandemic, it is paramount to define the mechanisms and develop protective therapies to prevent organ dysfunction in patients with COVID-19. Individuals that develop severe manifestations have signs of dysregulated innate and adaptive immune responses. Emerging evidence implicates neutrophils and the disbalance between neutrophil extracellular trap (NET) formation and degradation plays a central role in the pathophysiology of inflammation, coagulopathy, organ damage, and immunothrombosis that characterize severe cases of COVID-19. Here, we discuss the evidence supporting a role for NETs in COVID-19 manifestations and present putative mechanisms, by which NETs promote tissue injury and immunothrombosis. We present therapeutic strategies, which have been successful in the treatment of immunο-inflammatory disorders and which target dysregulated NET formation or degradation, as potential approaches that may benefit patients with severe COVID-19.


Subject(s)
COVID-19/pathology , Extracellular Traps/metabolism , Neutrophils/immunology , COVID-19/complications , COVID-19/immunology , Citrullination , Complement Activation , Humans , Neutrophils/metabolism , Platelet Activation , SARS-CoV-2/isolation & purification , Severity of Illness Index , Thrombosis/etiology
5.
PLoS One ; 16(5): e0251201, 2021.
Article in English | MEDLINE | ID: covidwho-1226894

ABSTRACT

BACKGROUND: Mouth-nose masks have been requested to prevent the transmission of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The aim of the present study was to investigate, if wearing a mouth-nose mask impairs the visual field function in normals. METHODS: Thirty eyes of 30 subjects were recruited for the present study. White-on-white perimetry (OCTOPUS 900; 90°) was done and sensitivity was analysed in 14 defined test points (P1-P14, inferior visual field) under 3 different test conditions while the subjects were wearing a mouth-nose mask: (I) 1.5 cm under the lower eyelid, nose clip not used (position1.5cm_no_clip); (II) 1.5 cm under the lower eyelid, nose clip correctly positioned (position1.5cm_with_clip); (III) 0.5 cm under the lower eyelid, nose clip correctly positioned (position0.5cm_with_clip). All data were compared to sensitivity without wearing a mouth-nose mask (reference). Mean Δ was calculated, being the difference between the results of each test condition and reference, respectively. RESULTS: Sensitivity was significantly different between position1.5cm_no_clip and reference at 10 test points (p<0.05). Sensitivity at test point P7 was significantly different between position1.5cm_with_clip and position0.5cm_with_clip compared to reference (p<0.001), respectively. Mean Δ increased while wearing a mask at P7: position1.5cm_with_clip (-8.3 dB ± 7.3 dB) < position0.5cm_with_clip (-11.3 dB ± 9.5 dB) < position1.5cm_no_clip (-20.1 dB ± 7.6 dB). CONCLUSION: Visual field function was observed to be significantly impaired in the inferior-nasal sector while persons were wearing a mouth-nose mask, especially when the nose clip was not correctly used.


Subject(s)
Masks , Visual Fields , Adult , COVID-19/prevention & control , Female , Humans , Male , SARS-CoV-2/isolation & purification , Vision Tests , Vision, Ocular , Young Adult
6.
J Transl Autoimmun ; 4: 100100, 2021.
Article in English | MEDLINE | ID: covidwho-1203200

ABSTRACT

Impairment of health after overcoming the acute phase of COVID-19 is being observed more and more frequently. Here different symptoms of neurological and/or cardiological origin have been reported. With symptoms, which are very similar to the ones reported but are not caused by SARS-CoV-2, the occurrence of functionally active autoantibodies (fAABs) targeting G-protein coupled receptors (GPCR-fAABs) has been discussed to be involved. We, therefore investigated, whether GPCR-fAABs are detectable in 31 patients suffering from different Long-COVID-19 symptoms after recovery from the acute phase of the disease. The spectrum of symptoms was mostly of neurological origin (29/31 patients), including post-COVID-19 fatigue, alopecia, attention deficit, tremor and others. Combined neurological and cardiovascular disorders were reported in 17 of the 31 patients. Two recovered COVID-19 patients were free of follow-up symptoms. All 31 former COVID-19 patients had between 2 and 7 different GPCR-fAABs that acted as receptor agonists. Some of those GPCR-fAABs activate their target receptors which cause a positive chronotropic effect in neonatal rat cardiomyocytes, the read-out in the test system for their detection (bioassay for GPCR-fAAB detection). Other GPCR-fAABs, in opposite, cause a negative chronotropic effect on those cells. The positive chronotropic GPCR-fAABs identified in the blood of Long-COVID patients targeted the ß2-adrenoceptor (ß2-fAAB), the α1-adrenoceptor (α1-fAAB), the angiotensin II AT1-receptor (AT1-fAAB), and the nociceptin-like opioid receptor (NOC-fAAB). The negative chronotropic GPCR-fAABs identified targeted the muscarinic M2-receptor (M2-fAAB), the MAS-receptor (MAS-fAAB), and the ETA-receptor (ETA-fAAB). It was analysed which of the extracellular receptor loops was targeted by the autoantibodies.

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