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1.
Rheumatol Int ; 42(12): 2267-2276, 2022 12.
Article in English | MEDLINE | ID: covidwho-2059804

ABSTRACT

Dermatomyositis is a rare, type I interferon-driven autoimmune disease, which can affect muscle, skin and internal organs (especially the pulmonary system). In 2021, we have noted an increase in new-onset dermatomyositis compared to the years before the SARS-CoV-2 pandemic in our center. We present four cases of new-onset NXP2 and/or MDA5 positive dermatomyositis shortly after SARS-CoV-2 infection or vaccination. Three cases occurred within days after vaccination with Comirnaty and one case after SARS-CoV-2 infection. All patients required intensive immunosuppressive treatment. MDA5 antibodies could be detected in three patients and NXP2 antibodies were found in two patients (one patient was positive for both antibodies). In this case-based systematic review, we further analyze and discuss the literature on SARS-CoV-2 and associated dermatomyositis. In the literature, sixteen reports (with a total of seventeen patients) of new-onset dermatomyositis in association with a SARS-CoV-2 infection or vaccination were identified. Ten cases occurred after infection and seven after vaccination. All vaccination-associated cases were seen in mRNA vaccines. The reported antibodies included for instance MDA5, NXP2, Mi-2 and TIF1γ. The reviewed literature and our cases suggest that SARS-CoV-2 infection and vaccination may be considered as a potential trigger of interferon-pathway. Consequently, this might serve as a stimulus for the production of dermatomyositis-specific autoantibodies like MDA5 and NXP2 which are closely related to viral defense or viral RNA interaction supporting the concept of infection and vaccination associated dermatomyositis.


Subject(s)
COVID-19 , Dermatomyositis , Interferon Type I , Autoantibodies , COVID-19/prevention & control , Humans , RNA, Viral , SARS-CoV-2 , Vaccination
2.
Kidney Int ; 102(4): 708-719, 2022 10.
Article in English | MEDLINE | ID: covidwho-1983597

ABSTRACT

The 13th International Podocyte Conference was held in Manchester, UK, and online from July 28 to 30, 2021. Originally planned for 2020, this biannual meeting was postponed by a year because of the coronavirus disease 2019 (COVID-19) pandemic and proceeded as an innovative hybrid meeting. In addition to in-person attendance, online registration was offered, and this attracted 490 conference registrations in total. As a Podocyte Conference first, a day for early-career researchers was introduced. This premeeting included talks from graduate students and postdoctoral researchers. It gave early career researchers the opportunity to ask a panel, comprising academic leaders and journal editors, about career pathways and the future for podocyte research. The main meeting over 3 days included a keynote talk and 4 focused sessions each day incorporating invited talks, followed by selected abstract presentations, and an open panel discussion. The conference concluded with a Patient Day, which brought together patients, clinicians, researchers, and industry representatives. The Patient Day was an interactive and diverse day. As well as updates on improving diagnosis and potential new therapies, the Patient Day included a PodoArt competition, exercise and cooking classes with practical nutrition advice, and inspirational stories from patients and family members. This review summarizes the exciting science presented during the 13th International Podocyte Conference and demonstrates the resilience of researchers during a global pandemic.


Subject(s)
COVID-19 , Podocytes , COVID-19/epidemiology , Humans , Translational Research, Biomedical
4.
Eur Heart J ; 43(11): 1124-1137, 2022 03 14.
Article in English | MEDLINE | ID: covidwho-1853027

ABSTRACT

AIMS: Long-term sequelae may occur after SARS-CoV-2 infection. We comprehensively assessed organ-specific functions in individuals after mild to moderate SARS-CoV-2 infection compared with controls from the general population. METHODS AND RESULTS: Four hundred and forty-three mainly non-hospitalized individuals were examined in median 9.6 months after the first positive SARS-CoV-2 test and matched for age, sex, and education with 1328 controls from a population-based German cohort. We assessed pulmonary, cardiac, vascular, renal, and neurological status, as well as patient-related outcomes. Bodyplethysmography documented mildly lower total lung volume (regression coefficient -3.24, adjusted P = 0.014) and higher specific airway resistance (regression coefficient 8.11, adjusted P = 0.001) after SARS-CoV-2 infection. Cardiac assessment revealed slightly lower measures of left (regression coefficient for left ventricular ejection fraction on transthoracic echocardiography -0.93, adjusted P = 0.015) and right ventricular function and higher concentrations of cardiac biomarkers (factor 1.14 for high-sensitivity troponin, 1.41 for N-terminal pro-B-type natriuretic peptide, adjusted P ≤ 0.01) in post-SARS-CoV-2 patients compared with matched controls, but no significant differences in cardiac magnetic resonance imaging findings. Sonographically non-compressible femoral veins, suggesting deep vein thrombosis, were substantially more frequent after SARS-CoV-2 infection (odds ratio 2.68, adjusted P < 0.001). Glomerular filtration rate (regression coefficient -2.35, adjusted P = 0.019) was lower in post-SARS-CoV-2 cases. Relative brain volume, prevalence of cerebral microbleeds, and infarct residuals were similar, while the mean cortical thickness was higher in post-SARS-CoV-2 cases. Cognitive function was not impaired. Similarly, patient-related outcomes did not differ. CONCLUSION: Subjects who apparently recovered from mild to moderate SARS-CoV-2 infection show signs of subclinical multi-organ affection related to pulmonary, cardiac, thrombotic, and renal function without signs of structural brain damage, neurocognitive, or quality-of-life impairment. Respective screening may guide further patient management.


Subject(s)
COVID-19 , COVID-19/diagnosis , COVID-19/epidemiology , Cohort Studies , Humans , SARS-CoV-2 , Stroke Volume , Ventricular Function, Left
5.
Kidney360 ; 2(4): 639-652, 2021 04 29.
Article in English | MEDLINE | ID: covidwho-1776889

ABSTRACT

Background: Kidney damage has been reported in patients with COVID-19. Despite numerous reports about COVID-19-associated nephropathy, the factual presence of the SARS-CoV-2 in the renal parenchyma remains controversial. Methods: We consecutively performed 16 immediate (≤3 hours) postmortem renal biopsies in patients diagnosed with COVID-19. Kidney samples from five patients who died from sepsis not related to COVID-19 were used as controls. Samples were methodically evaluated by three pathologists. Virus detection in the renal parenchyma was performed in all samples by bulk RNA RT-PCR (E and N1/N2 genes), immunostaining (2019-nCOV N-Protein), fluorescence in situ hybridization (nCoV2019-S), and electron microscopy. Results: The mean age of our COVID-19 cohort was 68.2±12.8 years, most of whom were male (69%). Proteinuria was observed in 53% of patients, whereas AKI occurred in 60% of patients. Acute tubular necrosis of variable severity was found in all patients, with no tubular or interstitial inflammation. There was no difference in acute tubular necrosis severity between the patients with COVID-19 versus controls. Congestion in glomerular and peritubular capillaries was respectively observed in 56% and 88% of patients with COVID-19, compared with 20% of controls, with no evidence of thrombi. The 2019-nCOV N-Protein was detected in proximal tubules and at the basolateral pole of scattered cells of the distal tubules in nine out of 16 patients. In situ hybridization confirmed these findings in six out of 16 patients. RT-PCR of kidney total RNA detected SARS-CoV-2 E and N1/N2 genes in one patient. Electron microscopy did not show typical viral inclusions. Conclusions: Our immediate postmortem kidney samples from patients with COVID-19 highlight a congestive pattern of AKI, with no significant glomerular or interstitial inflammation. Immunostaining and in situ hybridization suggest SARS-CoV-2 is present in various segments of the nephron.


Subject(s)
Acute Kidney Injury , COVID-19 , Acute Kidney Injury/diagnosis , Aged , Aged, 80 and over , COVID-19/complications , Capillaries/pathology , Humans , In Situ Hybridization, Fluorescence , Kidney Glomerulus/pathology , Male , Middle Aged , Necrosis , SARS-CoV-2
6.
Kidney360 ; 3(2): 325-336, 2022 02 24.
Article in English | MEDLINE | ID: covidwho-1776885

ABSTRACT

Background: Collateral effects and consequences of the coronavirus disease 19 (COVID-19) pandemic on kidney transplant recipients remain widely unknown. Methods: This retrospective cohort study examined changes in admission rates, incidences of diseases leading to hospitalization, in-patient procedures, and maintenance medication in long-term kidney transplant recipients with functioning graft during the early COVID-19 pandemic in Germany. Data were derived from a nationwide health insurance database. Analysis was performed from March 15 to September 30 and compared the years 2019 and 2020. Effects on mortality and adverse allograft events were compared with COVID-19-attributed effects. Results: A total of 7725 patients were included in the final analysis. Admissions declined in 2020 by 17%, with the main dip during a 3-month lockdown (-31%) but without a subsequent rebound. Incidences for hospitalization did not increase for any investigated disease entities, whereas decreasing trends were noted for non-COVID-19 pulmonary and urogenital infections (incidence rate ratio 0.8, 95% CI, 0.62 to 1.03, and 0.82, 95% CI, 0.65 to 1.04, respectively). Non-COVID-19 hospital stays were 0.6 days shorter (P=0.03) and not complicated by increased dialysis, ventilation, or intensive care treatment rates. In-hospital and 90-day mortality remained stable. Incidences of severe COVID-19 requiring hospitalization was 0.09 per 1000 patient-days, and in-hospital mortality was 9%. A third (31%) of patients with calcineurin-inhibitor medication and without being hospitalized for COVID-19 reduced doses by at least 25%, which was associated with an increased allograft rejection risk (adjusted hazard ratio 1.29, 95% CI, 1.02 to 1.63). COVID-19 caused 17% of all deaths but had no significant association with allograft rejections. All-cause mortality remained stable (incidence rate ratio 1.15, 95% CI, 0.91 to 1.46), also when restricting analysis to patients with no or outpatient-treated COVID-19 (0.97, 95% CI, 0.76 to 1.25). Conclusion: Despite significant collateral effects, mortality remained unchanged during the early COVID-19 pandemic. Considerable temporary reductions in admissions are safe, whereas reducing immunosuppression results in increased allograft rejection risk.


Subject(s)
COVID-19 , Kidney Transplantation , Communicable Disease Control , Humans , Kidney Transplantation/adverse effects , Pandemics , Renal Dialysis , Retrospective Studies
7.
Nat Metab ; 4(3): 310-319, 2022 03.
Article in English | MEDLINE | ID: covidwho-1764213

ABSTRACT

Extrapulmonary manifestations of COVID-19 have gained attention due to their links to clinical outcomes and their potential long-term sequelae1. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) displays tropism towards several organs, including the heart and kidney. Whether it also directly affects the liver has been debated2,3. Here we provide clinical, histopathological, molecular and bioinformatic evidence for the hepatic tropism of SARS-CoV-2. We find that liver injury, indicated by a high frequency of abnormal liver function tests, is a common clinical feature of COVID-19 in two independent cohorts of patients with COVID-19 requiring hospitalization. Using autopsy samples obtained from a third patient cohort, we provide multiple levels of evidence for SARS-CoV-2 liver tropism, including viral RNA detection in 69% of autopsy liver specimens, and successful isolation of infectious SARS-CoV-2 from liver tissue postmortem. Furthermore, we identify transcription-, proteomic- and transcription factor-based activity profiles in hepatic autopsy samples, revealing similarities to the signatures associated with multiple other viral infections of the human liver. Together, we provide a comprehensive multimodal analysis of SARS-CoV-2 liver tropism, which increases our understanding of the molecular consequences of severe COVID-19 and could be useful for the identification of organ-specific pharmacological targets.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Liver , Proteomics , Tropism
8.
Front Immunol ; 12: 800074, 2021.
Article in English | MEDLINE | ID: covidwho-1662584

ABSTRACT

Collapsing glomerulopathy represents a special variant of the proteinuric kidney disease focal segmental glomerulosclerosis (FSGS). Histologically, the collapsing form of FSGS (cFSGS) is characterized by segmental or global condensation and obliteration of glomerular capillaries, the appearance of hyperplastic and hypertrophic podocytes and severe tubulointerstitial damage. Clinically, cFSGS patients present with acute kidney injury, nephrotic-range proteinuria and are at a high risk of rapid progression to irreversible kidney failure. cFSGS can be attributed to numerous etiologies, namely, viral infections like HIV, cytomegalovirus, Epstein-Barr-Virus, and parvovirus B19 and also drugs and severe ischemia. Risk variants of the APOL1 gene, predominantly found in people of African descent, increase the risk of developing cFSGS. Patients infected with the new Corona-Virus SARS-CoV-2 display an increased rate of acute kidney injury (AKI) in severe cases of COVID-19. Besides hemodynamic instability, cytokine mediated injury and direct viral entry and infection of renal epithelial cells contributing to AKI, there are emerging reports of cFSGS associated with SARS-CoV-2 infection in patients of mainly African ethnicity. The pathogenesis of cFSGS is proposed to be linked with direct viral infection of podocytes, as described for HIV-associated glomerulopathy. Nevertheless, there is growing evidence that the systemic inflammatory cascade, activated in acute viral infections like COVID-19, is a major contributor to the impairment of basic cellular functions in podocytes. This mini review will summarize the current knowledge on cFSGS associated with viral infections with a special focus on the influence of systemic immune responses and potential mechanisms propagating the development of cFSGS.


Subject(s)
COVID-19/complications , Glomerulosclerosis, Focal Segmental/etiology , Kidney Glomerulus/virology , Animals , COVID-19/immunology , COVID-19/virology , Epithelial Cells/immunology , Epithelial Cells/virology , Glomerulosclerosis, Focal Segmental/immunology , Glomerulosclerosis, Focal Segmental/virology , Humans , Immunity/immunology , Kidney Glomerulus/immunology , Podocytes/immunology , Podocytes/virology , Proteinuria/etiology , Proteinuria/immunology , Proteinuria/virology , SARS-CoV-2/immunology
9.
Cell Stem Cell ; 29(2): 217-231.e8, 2022 02 03.
Article in English | MEDLINE | ID: covidwho-1586459

ABSTRACT

Kidney failure is frequently observed during and after COVID-19, but it remains elusive whether this is a direct effect of the virus. Here, we report that SARS-CoV-2 directly infects kidney cells and is associated with increased tubule-interstitial kidney fibrosis in patient autopsy samples. To study direct effects of the virus on the kidney independent of systemic effects of COVID-19, we infected human-induced pluripotent stem-cell-derived kidney organoids with SARS-CoV-2. Single-cell RNA sequencing indicated injury and dedifferentiation of infected cells with activation of profibrotic signaling pathways. Importantly, SARS-CoV-2 infection also led to increased collagen 1 protein expression in organoids. A SARS-CoV-2 protease inhibitor was able to ameliorate the infection of kidney cells by SARS-CoV-2. Our results suggest that SARS-CoV-2 can directly infect kidney cells and induce cell injury with subsequent fibrosis. These data could explain both acute kidney injury in COVID-19 patients and the development of chronic kidney disease in long COVID.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/complications , Fibrosis , Humans , Kidney , Organoids/pathology
10.
Cardiovasc Res ; 118(2): 542-555, 2022 01 29.
Article in English | MEDLINE | ID: covidwho-1467310

ABSTRACT

AIMS: Cardiac involvement in COVID-19 is associated with adverse outcome. However, it is unclear whether cell-specific consequences are associated with cardiac SARS-CoV-2 infection. Therefore, we investigated heart tissue utilizing in situ hybridization, immunohistochemistry, and RNA-sequencing in consecutive autopsy cases to quantify virus load and characterize cardiac involvement in COVID-19. METHODS AND RESULTS: In this study, 95 SARS-CoV-2-positive autopsy cases were included. A relevant SARS-CoV-2 virus load in the cardiac tissue was detected in 41/95 deceased (43%). Massive analysis of cDNA ends (MACE)-RNA-sequencing was performed to identify molecular pathomechanisms caused by the infection of the heart. A signature matrix was generated based on the single-cell dataset 'Heart Cell Atlas' and used for digital cytometry on the MACE-RNA-sequencing data. Thus, immune cell fractions were estimated and revealed no difference in immune cell numbers in cases with and without cardiac infection. This result was confirmed by quantitative immunohistological diagnosis. MACE-RNA-sequencing revealed 19 differentially expressed genes (DEGs) with a q-value <0.05 (e.g. up: IFI44L, IFT3, TRIM25; down: NPPB, MB, MYPN). The upregulated DEGs were linked to interferon pathways and originate predominantly from endothelial cells. In contrast, the downregulated DEGs originate predominately from cardiomyocytes. Immunofluorescent staining showed viral protein in cells positive for the endothelial marker ICAM1 but rarely in cardiomyocytes. The Gene Ontology (GO) term analysis revealed that downregulated GO terms were linked to cardiomyocyte structure, whereas upregulated GO terms were linked to anti-virus immune response. CONCLUSION: This study reveals that cardiac infection induced transcriptomic alterations mainly linked to immune response and destruction of cardiomyocytes. While endothelial cells are primarily targeted by the virus, we suggest cardiomyocyte destruction by paracrine effects. Increased pro-inflammatory gene expression was detected in SARS-CoV-2-infected cardiac tissue but no increased SARS-CoV-2 associated immune cell infiltration was observed.


Subject(s)
COVID-19/complications , Heart/virology , SARS-CoV-2/isolation & purification , Transcriptome , Aged , Aged, 80 and over , Autopsy , COVID-19/genetics , COVID-19/immunology , COVID-19/virology , Female , Humans , Inflammation/complications , Male , Myocardium/metabolism , Myocardium/pathology , SARS-CoV-2/physiology , Virus Replication
12.
Int J Legal Med ; 135(6): 2347-2349, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1391863

ABSTRACT

Due to the development of novel functionalities, distinct SARS-CoV-2 variants such as B.1.1.7 fuel the current pandemic. B.1.1.7 is not only more transmissible, but may also cause an increased mortality compared to previous SARS-CoV-2 variants. Human tissue analysis of the SARS-CoV-2 lineage B.1.1.7 is urgently needed, and we here present autopsy data from 7 consecutive SARS-CoV-2 B.1.1.7 cases. The initial RT-qPCR analyses from nasopharyngeal swabs taken post mortem included typing assays for B.1.1.7. We quantitated SARS-CoV-2 B.1.1.7 viral load in autopsy tissue of multiple organs. Highest levels of SARS-CoV-2 B.1.1.7 copies normalized to ß-globin were detected in the respiratory system (lung and pharynx), followed by the liver and heart. Importantly, SARS-CoV-2 lineage B.1.1.7 was found in 100% of cases in the lungs and in 85.7% in pharynx tissue. Detection also in the kidney and brain highlighting a pronounced organ tropism. Comparison of the given results to a former cohort of SARS-CoV-2 deaths during the first wave in spring 2020 showed resembling organ tropism. Our results indicate that also SARS-CoV-2 B.1.1.7 has a relevant organ tropism beyond the respiratory tract. We speculate that B.1.1.7 spike protein's affinity to human ACE2 facilitates transmission, organ tropism, and ultimately morbidity and mortality. Further studies and larger cohorts are obligatory to proof this link.


Subject(s)
SARS-CoV-2/physiology , Viral Load , Viral Tropism , Aged , Autopsy , Female , Heart/virology , Humans , Kidney/virology , Liver/virology , Lung/virology , Male , Middle Aged , Pharynx/virology
14.
Internist (Berl) ; 62(7): 718-724, 2021 Jul.
Article in German | MEDLINE | ID: covidwho-1326807

ABSTRACT

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has also resulted in substantial challenges for nephrology worldwide. Patients with chronic kidney diseases are a particularly vulnerable patient group in this context and in severe courses of COVID-19 the kidneys are most frequently affected by organ failure after the lungs. MATERIAL AND METHODS: In order to reliably evaluate the prevalence and mortality of dialysis patients in Germany with respect to COVID-19, during the first wave in spring 2020 the German Society of Nephrology implemented a registry for dialysis patients. Weekly data on the number and course of dialysis patients affected by COVID-19 were recorded and analyzed. RESULTS: The prevalence of COVID-19 in dialysis patients in Germany developed in two waves, similar to the course of the pandemic in the general population. In spring the prevalence in dialysis patients reached 1.4% and considerably declined during the summer. In December during the second wave of the pandemic the prevalence again rose to 1.9%, despite comprehensively implemented hygiene measures in dialysis centers. Similar to other industrial nations, dialysis patients in Germany also showed a very high lethality of COVID-19 of up to 20%. CONCLUSION: Immediate consequences for hygiene measures in dialysis institutions as well as vaccination strategies and vaccination prioritization for this patient group and the personnel treating them can be derived from the high mortality in dialysis patients. A consequence of the frequent involvement of the kidneys during infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patients who had not previously suffered from advanced kidney disease should be the consistent nephrological aftercare.


Subject(s)
COVID-19 , Nephrology , Germany/epidemiology , Humans , Pandemics/prevention & control , Renal Dialysis , SARS-CoV-2
15.
J Clin Med ; 10(14)2021 Jul 09.
Article in English | MEDLINE | ID: covidwho-1308366

ABSTRACT

In COVID-19, guidelines recommend a urinalysis on hospital admission as SARS-CoV-2 renal tropism, post-mortem, was associated with disease severity and mortality. Following the hypothesis from our pilot study, we now validate an algorithm harnessing urinalysis to predict the outcome and the need for ICU resources on admission to hospital. Patients were screened for urinalysis, serum albumin (SA) and antithrombin III activity (AT-III) obtained prospectively on admission. The risk for an unfavorable course was categorized as (1) "low", (2) "intermediate" or (3) "high", depending on (1) normal urinalysis, (2) abnormal urinalysis with SA ≥ 2 g/dL and AT-III ≥ 70%, or (3) abnormal urinalysis with SA or AT-III abnormality. Time to ICU admission or death served as the primary endpoint. Among 223 screened patients, 145 were eligible for enrollment, 43 falling into the low, 84 intermediate, and 18 into high-risk categories. An abnormal urinalysis significantly elevated the risk for ICU admission or death (63.7% vs. 27.9%; HR 2.6; 95%-CI 1.4 to 4.9; p = 0.0020) and was 100% in the high-risk group. Having an abnormal urinalysis was associated with mortality, a need for mechanical ventilation, extra-corporeal membrane oxygenation or renal replacement therapy. In conclusion, our data confirm that COVID-19-associated urine abnormalities on admission predict disease aggravation and the need for ICU (ClinicalTrials.gov number NCT04347824).

17.
J Clin Med ; 10(11)2021 May 24.
Article in English | MEDLINE | ID: covidwho-1244046

ABSTRACT

In this study, we directly compared coronavirus disease 2019 (COVID-19) patients hospitalized during the first (27 February-28 July 2020) and second (29 July-31 December 2020) wave of the pandemic at a large tertiary center in northern Germany. Patients who presented during the first (n = 174) and second (n = 331) wave did not differ in age (median [IQR], 59 years [46, 71] vs. 58 years [42, 73]; p = 0.82) or age-adjusted Charlson Comorbidity Index (median [IQR], 2 [1, 4] vs. 2 [0, 4]; p = 0.50). During the second wave, a higher proportion of patients were treated as outpatients (11% [n = 20] vs. 20% [n = 67]), fewer patients were admitted to the intensive care unit (43% [n = 75] vs. 29% [n = 96]), and duration of hospitalization was significantly shorter (median days [IQR], 14 [8, 34] vs. 11 [5, 19]; p < 0.001). However, in-hospital mortality was high throughout the pandemic and did not differ between the two periods (16% [n = 27] vs. 16% [n = 54]; p = 0.89). While novel treatment strategies and increased knowledge about the clinical management of COVID-19 may have resulted in a less severe disease course in some patients, in-hospital mortality remained unaltered at a high level. These findings highlight the unabated need for efforts to hamper severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) transmission, to increase vaccination coverage, and to develop novel treatment strategies to prevent mortality and decrease morbidity.

19.
Int J Mol Sci ; 22(9)2021 Apr 30.
Article in English | MEDLINE | ID: covidwho-1217089

ABSTRACT

Platelets are components of the blood that are highly reactive, and they quickly respond to multiple physiological and pathophysiological processes. In the last decade, it became clear that platelets are the key components of circulation, linking hemostasis, innate, and acquired immunity. Protein composition, localization, and activity are crucial for platelet function and regulation. The current state of mass spectrometry-based proteomics has tremendous potential to identify and quantify thousands of proteins from a minimal amount of material, unravel multiple post-translational modifications, and monitor platelet activity during drug treatments. This review focuses on the role of proteomics in understanding the molecular basics of the classical and newly emerging functions of platelets. including the recently described role of platelets in immunology and the development of COVID-19.The state-of-the-art proteomic technologies and their application in studying platelet biogenesis, signaling, and storage are described, and the potential of newly appeared trapped ion mobility spectrometry (TIMS) is highlighted. Additionally, implementing proteomic methods in platelet transfusion medicine, and as a diagnostic and prognostic tool, is discussed.


Subject(s)
Blood Platelets/metabolism , Mass Spectrometry/methods , Platelet Function Tests/methods , Proteomics/methods , Animals , Blood Platelets/cytology , Blood Platelets/immunology , COVID-19/immunology , COVID-19/metabolism , Humans , Platelet Transfusion , Protein Processing, Post-Translational , Signal Transduction , Transfusion Medicine/methods
20.
Sci Immunol ; 6(56)2021 02 23.
Article in English | MEDLINE | ID: covidwho-1099742

ABSTRACT

Hyperinflammation contributes to lung injury and subsequent acute respiratory distress syndrome (ARDS) with high mortality in patients with severe coronavirus disease 2019 (COVID-19). To understand the underlying mechanisms involved in lung pathology, we investigated the role of the lung-specific immune response. We profiled immune cells in bronchoalveolar lavage fluid and blood collected from COVID-19 patients with severe disease and bacterial pneumonia patients not associated with viral infection. By tracking T cell clones across tissues, we identified clonally expanded tissue-resident memory-like Th17 cells (Trm17 cells) in the lungs even after viral clearance. These Trm17 cells were characterized by a a potentially pathogenic cytokine expression profile of IL17A and CSF2 (GM-CSF). Interactome analysis suggests that Trm17 cells can interact with lung macrophages and cytotoxic CD8+ T cells, which have been associated with disease severity and lung damage. High IL-17A and GM-CSF protein levels in the serum of COVID-19 patients were associated with a more severe clinical course. Collectively, our study suggests that pulmonary Trm17 cells are one potential orchestrator of the hyperinflammation in severe COVID-19.


Subject(s)
COVID-19/immunology , Granulocyte-Macrophage Colony-Stimulating Factor/metabolism , Immunologic Memory , Lung/immunology , Th17 Cells/metabolism , Bronchoalveolar Lavage Fluid/cytology , Bronchoalveolar Lavage Fluid/immunology , COVID-19/complications , COVID-19/pathology , Clone Cells , Humans , Inflammation/etiology , Inflammation/immunology , Lung/pathology , Myeloid Cells , Pneumonia, Bacterial/immunology , Th17 Cells/immunology
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